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ABSTRACT BOOK
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Dear Participants,
With all my respect, I welcome you to the 4th International Meeting on Pharmacy &
Pharmaceutical Sciences (IMPPS-4) which will take place between 18th September 2014.
I would like to thank you so much on behalf of our faculty for honoring us with your
grace.
We are very glad to be hosting this event in our historical building representing the history
of our faculty that goes back half a century in Istanbul, which is a Metropolitan city, with
historical and cultural richness beginning with about 330 AD and coming up to day.
As Marmara University Faculty of Pharmacy we have realized the first three of the series of the International
Pharmaceutical Congresses in 1994, 1998 and 2010. Today we gathered here for the fourth time for exchanging
research, sharing ideas and networking.
The broad content of the congress offers opportunity for discussion of the recent developments in pharmaceutical
sciences with international experts from all disciplines of pharmaceutical sciences as well as sharing the
experience with pharmacy professionals.
I sincerely thank you to Marmara University Rectorate for the valuable supports on holding the congress at this
historical location and publication of the congress booklets; to all my friends who contributed to the organization
of the congress; Flap Tour Company’s valuable team; our sponsors who support us and to my colleagues from
Turkey and from abroad for participating in the congress.
I wish all an efficient and successful congress, and a pleasant time in Istanbul.
Prof. Dr. Gülden Zehra OMURTAG
President of Congress
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Honorary President of the meeting
M. Emin Arat, Prof. Dr.
Rector of Marmara University
COMMITTEES
President
Gulden Z. Omurtag Prof. Dr.
Secretary
Mesut Sancar, Assoc. Prof. Dr.
Treasurer
H. Kubra Elcioglu, Assoc. Prof. Dr.
Organizing Committee
Feyza Arıcıoglu, Prof. Dr.
Sinem Gokturk, Prof. Dr.
Guniz Kucukguzel, Prof. Dr.
Betul Okuyan, Assist. Prof. Dr.
Ali Demir Sezer, Assoc. Prof. Dr.
Semra Sardas, Prof. Dr.
Esra Tatar, Assist. Prof. Dr.
Timucin Ugurlu, Assoc. Prof. Dr.
Fikriye Uras, Prof. Dr.
Scientific Committee
A.Seza Bastug
Adile Cevikbas
Afife Mat
Ahmet Araman
Akgul Yesilada
Azize Sener
Barry P. Rosen
Bedia Kaymakcıoglu
Bernd Kaina
Betul Dortunc
Buket Alpertunga
Ebrahim F. Razzazi
Fikret Vehbi İzzettin
George J. Christ
Goksel Sener
Gulactı Topcu
Guler Yalcın
Gulgun Tınaz
Hulya Akgun
Ilkay Kucukguzel
Imer Okar
Jawed Fareed
Julide Akbuga
Kadir Turan
Levent Kabasakal
Leyla Bitis
Mert Ulgen
Social Committee
Ahmet Dogan
Ayfer Beceren
Bahar Goker
Ceren Sahin
Emine Alarcin
Filiz Arıoz-Ozdemir
Gizem Bulut
Necla Kulabas
Rabia Oba
Seher Karslı-Ceppioglu
Sevgi Karakus
Sevda Suzgec-Selcuk
Suna Ozbas-Turan
Sule Apikoglu-Rabus
Turgut Taskın
Yusuf Kemal Demir
Yesim Canturk-Talman
Local Sub-Committee
Ahmet Ozer Sehirli
Ali Sen
Aslı Demirci
Aylin Sancar
Aysen Cucu
Beyza Betül Koçak
Burcak Gurbuz
Caglar Demirbag
Deniz Cıkla-Yılmaz
Derya Ozsavcı
Dilek Bilgic Alkaya
Morando Soffritti
Myron A. Mehlman
Mursit Pekin
Osman Ziya Sayhan
Sarfraz Ahmad
Sena F. Sezen
Sidney J. Stohs
Seref Demirayak
Sermin Tetik
Turkan Yurdun
Umran Soyoglu-Gurer
Yıldız Ozsoy
William W. Au
Elif Calıskan-Salihi
Erkan Rayaman
Esra Dalkılıc
Fatma Ozaydın
Gokcen Yasayan
Gulbin Erdogan
Halil Aksoy
Ismail Senkardes
Nese Erdinc
Nuray Yuktas
Oya Kerimoglu
Ozlem Bingol-Ozakpınar
Pelin Suzgun-Cıkla
Pervin Rayaman
Serap Ayaz-Seyhan
Serap Karaderi
Sevcan Gül Akgün
Sevil Aydın
Sevinc Sahbaz
Tugce Yesil
Turgut Şekerler
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SCIENTIFIC PROGRAM
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THURSDAY, 18.09.2014
9.00-13.00
SYMPOSIUM ON BIOSIMILARS
15.00-15.30
OPENING
SEMAZEN CEREMONY
15.30-16.10
Chairman: Semra ŞARDAŞ
Medicinal plants and microorganisms in drug development
Professor Doctor Her Royal Highness Princess Chulabhorn
(Chulabhorn Research Institute – THAILAND)
16.10-16.30
COFFEE BREAK
16.30-17.50
Chairman: Betul DORTUNC
Role of Nanotechnology in Drug Delivery
Hayat ONYUKSEL
Safety considerations when designing oral solid dosage forms
Ali Rajabi SIAHBOOMI
18.00
WELCOME RECEPTION
Bulent HalvaSi Trio
FRIDAY, 19.09.2014
HALL A
9.00-10.40Biosimilars
Chairman: Timucin UGURLU
9.00-9.30 Biopharmaceuticals: status, trends and future
Gary WALSH
9.30-10.00 Production of Biopharmaceuticals from Transgenic Animals
Sema BIRLER
10.00-10.40 Biosimilars, “To be or not to be”
Haleh HAMEDIFAR
10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40Psycotherapy
Chairman: Feyza ARICIOGLU
11.00-11.30 Pharmacoenhancement of endocannabinoid signalling: new avenues of anxiety therapy?
Carsten WOTJAK
11.30-12.00 Where do we stand in the era of psychotherapy?
Feyza ARICIOGLU
12.40-13.30 LUNCH, POSTER VIEWING EXHIBITION
13.30-15.10
Recent Advances in Pharmacotherapy I
Chairman: Turay YARDIMCI
13.30-14.00 The role played by the HLA complex in adverse drug reactions
Mehmet Tevfik DORAK
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14.00-14.30 Growth Arrest Specific-6 (Gas6)/Axl Pathway: Potential new strategy for drug development
Fikriye URAS
15.10-15.30 COFFEE BREAK - POSTER VIEWING
15.30-17.40 Drug Safety and Personalized Medicine
Chairman: Ahmet AYDIN
15.30-16.00 Disease Caused by Benzene
Myron MEHLMAN
16.00-16.30 New Translation Models to Link OMICS to Health Innovation: Micro-grants for Big Data
Vural OZDEMIR
HALL B
9.00-10.40 Phytotherapy
Chairman: Leyla BITIS
9.00-9.30 Phytotherapy in Turkey and the plants of Turkey as source of herbal medicinal products
Filiz MERICLI
9.30-10.00 Disclosure of the activity mechanism of a Turkish folk remedy to combat rheumatic complaints
Erdem YESILADA
10.00-10.40 Potential anti-Alzheimer Agents from Lamiaceae Family Plants
Gulactı TOPCU
10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40
Drug Design I
Chairman: Ilkay KUCUKGUZEL
11.00-11.30
New cyclin dependent kinase inhibitors. Elucidation of their molecular mechanism of action.
Hervé GALONS
11.30-12.00 Recent developments in enantioseparation of chiral drugs
Bezhan CHANKVETADZE
12.40-13.30 LUNCH, POSTER VIEWING EXHIBITION
13.30-15.10 Pharmaceutical Analysis
Chairman: Sinem GOKTURK
13.30-14.00 Application of mass spectrometry based proteomics for production and characterization of biopharmaceuti cals
E. RAZZAZI-FAZELI
14.00-14.30
Cuprac Methods Of Antıoxidant Capacity/Activity Measurement Applicable To Food, Pharmaceuticals And Biological Fluids
Resat APAK
14.30-15.10 New Trends in Analytical Chemistry
Guler YALCIN
15.10-15.30 COFFEE BREAK - POSTER VIEWING
15.30-17.40
Oxidative Stress and Antioxidants
Chairman: Goksel SENER
15.30-16.00 Drug-Induced Oxidative Stress and Toxicity
Sibel OZDEN
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16.00-16.30 ROS Diagnostics and Biomarkers
A. Suha YALCIN
16.30-17.00
Bio-image-informatics: a new tool to monitor cell organelle dynamics
Birol COTUK
HALL C
9.00-10.40
Oral Presentations
Chairman: Esra TATAR
9.00-09.15 GPCR-interacting proteins and their individual functional roles
Livia BASILE
9.15-9.30
Pros and Cons of Pilus: A target for antivirulence therapeutics and an unlikely player in the fight against cancer
Ender VOLKAN
9.30-9.45
Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase
Gizem CAKIR
9.45-10.00
Synthesis, characterization, phosphate buffer stability, and antiproliferative effects of a novel modified male
ic anhydride containing Copolymer/Anticancer Drug conjugates
Gulderen KARAKUS
10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40
Oral Presentation
Chairman: Emine ALARCIN
11.00-11.15 Novel nanoparticles for gene delivery: preparation, optimization, cell uptake and cytotoxicity investigation
Sanam ARAMI
11.15-11.30 Preparatıon And In Vıtro- In Vıvo Evaluatıon Of Transdermal Formulatıons Of Betahıstıne
Sevinc SAHBAZ
11.30-11.45 Characterization studies of well-defined block co-polymer assemblies
Gokcen YASAYAN
11.45-12.00 Degradative Activities of Antibiotic-resistant Staphylococcus saprophyticus, Bacillus pumilus, Gracilibacillus dipsosauri and Idiomarina loihiensis
Pınar CAGLAYAN
12.15-12.40 Effect of Using Antibacterial Agent, Direct and Alternating Electric Currents to Kill Bacteria in Hide Curing and Pre-Soaking Liquors
Meral BIRBIR
12.40-13.30 LUNCH, POSTER VIEWING EXHIBITION
13.30-15.10
Pharmacoeconomics and Pharmacoepidemiology
Chairman: Levent KABASAKAL
13.30-14.00 Evidence Based Medicine: Critical appraisal of epidemiological studies
Pınar AY
14.00-14.30 Health Economics in Turkey
Deniz GURANLIOGLU
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15.10-15.30 COFFEE BREAK - POSTER VIEWING
15.30-17.40
Cosmetics
Chairman: Oya KERIMOGLU
15.30-16.00 Challenging Materials for Cosmetic Use
Yasemin YAZAN
SATURDAY, 20.09.2014
HALL A
9.00-10.50Ethnobotany
Chairman: Sevda SUZGEC SELCUK
09.00-09.30 Quality control of herbal medicine
Rudolf BAUER
09.30-09.30 A summary and comparison of folk medicinal plant uses in Catalonia
Joan Valles XIRAU
09.30-10.00 A review on ethnobotany in Turkey
Kerim ALPINAR
10.00-10.20 An ethnobotanical study in Marmara Islands (Balıkesir-Turkey
Gizem BULUT
10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40
Recent Advances in Pharmacotherapy III
Chairman: Fikriye URAS
11.00-11.30 Mechanism of INPP4B tumor suppression
Irina AGOULNIK
11.30-12.00 Use of mechanism-based evidence for the development of therapy for human cancers William W. AU
12.00-12.40 Ticks, Crimean-Congo Haemoragic Fever and pharmacological prospects
Aysen GARGILI
12.40-13.30 LUNCH, POSTER VIEWING EXHIBITION
13.30-15.10
Clinical Pharmacy and Pharmaceutical Care
Chairman: Fikret Vehbi IZZETTIN
13.30-14.00 Pharmacists and pharmaceutical care
Foppe van MIL
14.00-14.30 Clinical Pharmacist Counseling in Cardio- Metabolic Diseases
Sule APIKOGLU RABUS
14.30-15.10 Medication Related Problems in Geriatric Patients: The Role of Pharmacist
Betul OKUYAN
15.10-15.30 COFFEE BREAK - POSTER VIEWING
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15.30-17.30
Drug Design II
Chairman: Guniz KUCUKGUZEL
15.30-16.00 3D Analysis of the Binding Site Images for Predicting Binding Affinities in Drug Design
Erdem BUYUKBINGOL
16.00-16.30 Better understanding of the monoamine oxidases – associated I2 binding site : Combining molecular modelling and enzymology
Salvatore GUCCIONE
20.00 GALA DINNER
HALL B
9.00-10.40
Recent Advances in Pharmacotherapy II
Chairman: Kubra ELCIOGLU
9.00-9.30 Recent Advances in Pharmacotherapy
Gul BAKTIR
9.30-10.00 New treatment strategies in peripheral neuropathies
Sena SEZEN
10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40
Drug Development
11.00-11.30 Jamming bacterial communication (“Quorum Sensing”): A new approach to the control of bacterial infections
Gulgun TINAZ
Chairman: Bedia KAYMAKCIOGLU
11.30-12.00 Interference with bacterial cell-to-cell communication - a novel strategy to combat infections
Rolf W. HARTMANN
12.00-12.40 Chaperone-Usher Pilus Assembly Mechanisms and Antivirulence Therapeutics
Ender VOLKAN
12.40-13.30
LUNCH, POSTER VIEWING EXHIBITION
13.30-15.10
Industrial Pharmacy
Chairman: Julide AKBUGA
13.30-14.00 Biotechnological Industry in Turkey and The Biosimilars As The New Driving Force
Cem KOCAK
14.00-14.30 New Trends in Quality of Pharmaceuticals
Buket AKSU
14.30-15.10 Innovative Developments In Turkish Pharmaceutical Industry
Seyfullah DAGISTANLI
15.10-15.30 COFFEE BREAK - POSTER VIEWING
15.30-17.30
Industrial Pharmacy
Chairman: Yıldız OZSOY
15.30-16.00 Evaluation of Hexagonal Boron Nitride as a new tablet lubricant
Timucin UGURLU
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16.00-16.30 Product Development, Clinical Trials; From Laboratory to Pharmacy
Asligul KENDİRCİ
HALL C
9.00-10.40
Social and Administrative Pharmacy
Chairman: Sule APIKOGLU RABUS
09.00-09.30 The Impact of Health Literacy on Drug Use of the Community
Haydar SUR
09.30-10.00 Pharmacy Management: Today and Tomorrow
Nazlı SENCAN
10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40
Pharmaceutical Waste and Environment
Chairman: Turkan YURDUN
11.00-11.30 Drug content of waters. Is it important for human health?
Ahmet AYDIN
12.40-13.30
LUNCH, POSTER VIEWING EXHIBITION
13.30-15.10 Stem Cell
Chairman: Gulgun TINAZ
13.30-14.15 Stem cells in Medical Training
Tunc AKKOC
14.15 - 15.10 WORKSHOP by
BAB Microscope and Image Analysis Systems Comet Assay Solution with Mathematical Modeling
Babacan UGUZ & OGulcan Berk UGUZ
15.10-15.30 COFFEE BREAK - POSTER VIEWING
15.30-17.30 Oral Presentation
Chairman: Derya OZSAVCI & Ozlem BINGOL OZAKPINAR
15.30-15.45 Life Span Effect Dıffernt Infusions of Verbascum Trıchostylum on Caenorhabdıtıs Elegans Exposed to Chronic Heat Stress
Hasan KILICGUN
15.45-16.00 Effect of taurine on chemotherapy induced nausea and vomiting in acute lymphoblastic leukemia.
Mina ISLAMBULCHILAR
16.00-16.15 Investigation of histone lysine trimethylation or acetylation in sporadic breast tumors and matched normal tissues
Seher KARSLI-CEPPIOGLU
16.15-16.30 Cytokine Levels and Platelet Functions in Preeclampsia
Fikriye URAS
16.30-16.45 Plasma Growth Arrrest Specific (GAS6) levels in B-cell chronic lymphocytic leukemia patients
Dilvin GUNEY
16.45-17.00 The Role of GAS6/TAM Signalling in Differentiation of Mesenchymal Stem Cells
Nese ERIZ
17.00-17.15 The Plasma Levels of GAS6 in Recurrent Pregnancy Losses
Fikriye URAS
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SUNDAY, 21.09.2014
HALL A
9.00-10.40 Recent Advances in Pharmacotherapy IV
Chairman: Sermin TETIK
9.00-9.30 Hypercoagulability in Ovarian Cancer: Laboratory and Clinical Perspectives
Sarfraz AHMAD
9.30-10.00 Gene silencing molecules and using in therapy
Emine SALVA
10.00-10.40 Chemotherapy resistance: Cancer genetics on behalf of clinical therapy
Betul KARADEMIR
10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40
Drug Delivery
Chairman: Ahmet ARAMAN & Yusuf Kemal DEMIR
11.00-11.30 Nanocarriers as vaccine and gene delivery
Oya ALPAR
11.30-12.00 Nanoscale drug delivery systems and the blood-brain barrier
Yılmaz CAPAN
12.00-12.40 Poly( Lactic-co-Glycolic Acid) Based Drug Delivery Devices For Tissue Engineering and Regenerative Medicine
Oya KERIMOGLU
12.40-13.30
LUNCH, POSTER VIEWING EXHIBITION
13.30-15.10 Pharmacy Education
13.30-14.00 Major Changes in Clinical Pharmacy Education and Practice
Sid STOHS
Chairman: Mesut SANCAR - Gul BAKTIR
14.00-14.30 Professional Practice and Competency Standarts in Pharmacy
Levent USTUNES
14.30-15.00 Importance of Clinical Rounds in Pharmacy Education and Practice
Fikret Vehbi IZZETTIN
15.00-15.40 Patient –Centered Pharmacy Education: Do we really need it or not?
Akgul YESILADA
15.45-16.00 COFFEE BREAK - POSTER VIEWING
16.00-16.30 CLOSING & AWARDS CEREMONY
HALL B
9.00-10.40
Pharmacy Practices
9.00-9.30 Role of Community Pharmacies in Promoting Rational Use of Drugs In Developing Countries-A Way Forward
Azhar HUSSAIN
Chairman: Betul OKUYAN
9.30-10.00 Role of Dietary Supplements in Disease Prevention and Management
Sid STOHS
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10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40 Food and Drug
Chairman: Gulden Z. OMURTAG
11.00-11.30 The carcinogenic risks of artificial sweeteners: the cases of aspartame and sucralose
Morando SOFFRITTI
11.30-12.00 Prebiotics and probiotics
Dilek HEPERKAN
12.00-12.30 Risk factors and assessment of bacterial pathogens in food
Irem Omurtag KORKMAZ
12.40-13.30
LUNCH, POSTER VIEWING EXHIBITION
13.30-15.10 Recent Advances in Pharmacotherapy V
Chairman: Buket ALPERTUNGA & Ayfer BECEREN
13.30-14.00 Drug transporters: Circadian rhythms and therapeutic implications
Alper OKYAR
14.00-14.30 Blast injury induced functional and structural changes in brain
Nihal TUMER
14.30-15.10
Leptin Resistance: Perdisposing Factor in Obesity
Philip J. SCARPACE
15.10-16.00 COFFEE BREAK - POSTER VIEWING
HALL C
9.00-10.40
Therapeutic Drug Monitoring & ADME
Chairman: Guler YALCIN
9.00-9.30 Metabolites. Friends or Enemies? for Drug Development
Mert ULGEN
9.30-10.00 Twenty-four Years of Experience in Therapeutic Drug Monitoring: Past,Present, and Future
Goncagul HAKLAR
10.00-10.40 Ensuring Bioanalytical Principles on BA/BE studies
Seda UNSALAN
10.40-11.00 COFFEE BREAK - POSTER VIEWING
11.00-12.40 Miscellaneous Topics in Pharmaceutical Sciences
Chairman: Gulbin ERDOGAN
11.00-11.30 History of Haydarpasa Campus
Emre DOLEN
11.30-12.30 Oral Presentation
Chairman: Erkan RAYAMAN
11.30-11.45 Health Professional Students Knowledge on Pharmacovigilance (PV)
Meri KOLUACIK
11.45-12.00 Clinical Pharmacotherapy Education by Problem Based Learning in Clinical Pharmacy Courses
Sule APIKOGLU-RABUS
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12.00-12.15 An example of a workshop about the use of creative drama in pharmacy education for development of communication skills of pharmacy students
Filiz Arıoz OZDEMIR, Goknil Pelin COSKUN
12.40-13.30 LUNCH, POSTER VIEWING EXHIBITION
13.30-15.30 Oral Presentation
Chairman: Gizem BULUT & Hulya AKGUN
13.45-14.00 Sustainable Collection and Characterization of Colchicum L. Species in the Flora of Turkey for Etnobotanical Purposes
Ahu ALTINKUT UNCUOGLU
14.00-14.15 The investigation of antidiabetic and in vivo antioxidant capacity of fruits, barks and leaves of Cornus mas L.
Aylin SEPICI DINCEL
14.15-14.30 Validated Methods in Bioalalysis
Somaieh SOLTANI
14.30-14.45 Sequential injection technique as a tool for sample pre-treatment in pharmaceutical analysis
Ivana ŠRÁMKOVÁ
14.45-15.00 Determination and Pharmacokinetics of Olanzapine in Human Plasma by LC/MS Method
Mehmet Emrah YAMAN
15.30-16.00 COFFEE BREAK - POSTER VIEWING
16.00-16.30 CLOSING & AWARDS CEREMONY
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PLENARY LECTURES
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PL 1 MEDICINAL PLANTS AND MICROORGANISMS IN DRUG DEVELOPMENT
PROFESSOR DOCTOR HER ROYAL HIGHNESS PRINCESS CHULABHORN
CHULABHORN RESEARCH INSTITUTE AND CHULABHORN GRADUATE INSTITUTE
Natural products constitute a significant repertoire of chemicals, many of which have been used as drugs and they may
be used as indispensable tools in biomedical research. Many local folk medıcınes contain natural products of plant origin,
which remain a largely untapped reservoir of natural compounds with novel chemical structures and biological activities. One
common objective of practicing research in the field of natural products is to study plants and other bioresources including
microorganism and marine organisms for chemicals that may serve as lead compounds for further development into new drugs
for various diseases.
We have recently investigated some Thai medicinal plants as well as some microorganisms, particularly fungi for new bioactive
natural products. The identification of these compounds by various spectroscopic techniques will be presented. In some
special cases, the unique chemistry as well as the biosynthesis and biological activities exhibited by some of these compounds
will be presented.
PL 2 ROLE OF NANOTECHNOLOGY IN DRUG DELIVERY
HAYAT ONYUKSEL
UNIVERSITY OF ILLINOIS AT CHICAGO, COLLEGE OF PHARMACY, DEPARTMENT OF BIOPHARMACEUTICAL SCIENCES, US
Local delivery of drugs to target tissues after systemic (mostly intravenous) application is relatively new approach to achieve
higher drug efficacy with low toxicity. Drug targeting can be achieved by multiple mechanisms and one of them is the passive
targeting using nanotechnology. This type of targeting involves drug carriers or drug particles that are big enough (> 10nm) not
to escape out of the normal vasculature (with pores <4nm) and not subject to renal clearance (pores <10nm), but can easily
extravasate at diseased sites with leaky vasculatures (pores <100nm), such as cancer or inflamed tissues. Nanotechnology
based targeted drug delivery significantly changes the biodistribution, pharmacokinetics, and pharmacodynamics of the drug
compared to the conventional delivery of the free drug, resulting with high efficacy and hardly any drug toxicity to healthy
tissues. Therefore, nanotechnology may play an important role in the future drug therapy of some diseases making cure a
realistic possibility.
PL 3 BIOPHARMACEUTICALS, STATUS, TRENDS AND FUTURE
GARY WALSH
CHAIR, INDUSTRIAL BIOTECHNOLOGY, CES DEPT AND MSSI, UNIVERSITY OF LIMERICK, IRELAND
To date 246 biopharmaceuticals containing 166 distinct active biopharmaceutical ingredients have been approved in the EU
and/or the US, generating sales of US $140 billion in 2013. Since January 2010, 54 such biopharmaceutical products have been
approved in the US and/or EU. Highlights include the approval of the first glycoengineered monoclonal antibody (mAb), the
first biosimilar mAb, as well as the first gene therapy-based product. Ongoing technical trends include the increasing relative
importance of mAbs, and mammalian cell-based expression systems, and the European biosimilar market is finally taking hold.
Approvals over the next several years will continue to be dominated by mAb-based products, by products synthesized using
conventional expression systems and administered via conventional parenteral delivery.
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PL 4 PRODUCTION OF BIOPHARMACEUTICALS FROM TRANSGENIC ANIMALS
SEMA BIRLER
ISTANBUL UNIVERSITY, FACULTY OF VETERINARY MEDICINE, DEPARTMENT OF REPRODUCTION AND ARTIFICIAL INSEMINATION
Biopharmaceuticals are important products synthesized only from living biological sources rather than other pharmaceuticals
synthesized chemically. Despite of some restrictions or hazards, there are several sources to obtain biopharmaceuticals from
living organisms, humans or animals. After the development of recombinant DNA technologies there are new sources to
produce biopharmaceuticals such as bacterial and mammalian cell culture, transgenic plants and transgenic animals.
Transgenic animals offer an inexpensive and easy way for the production of biopharmaceuticals. Especially after the approval
of the products obtained from transgenic animals by European medıcınes Agency (EMA), generation of transgenic animals
which produce pharmaceutically important proteins in their milk has received increased interest. The first product approved
by EMA in 2006 is Atryn, human antithrombin, produced in transgenic goats’ milk by the company GTC Biotherapeutics. The
second product Rhucin, human C1 esterase inhibitor, manufactured from rabbits’ milk by the company Pharming was approved
in 2009.
Although methods still reqire improvement, recent advances in transgenic technology can allow reliable and efficient
production of transgenic animals. There are different methods for generating transgenic animals. Injection of gene consruct
into the pronucleus of an early embryo is the best method for the production of transgenic mice. Somatic cell cloning by using
transfected somatic cells is another method, particularly used for the production of transgenic livestock animals. Viral vectors
are important tools for the efficiency of transgenic production. Hyperactive plasmids are also promising in the respects of
efficiency and reliability. In Turkey, the first transgenic rabbits and lamb were generated in Istanbul UNIVERSITY in 2013 by using
hyperactive plasmids in collaboration with Hawaii unıversıty.
PL 5 BIOSIMILARS, TO BE OR NOT TO BE
HALEH HAMEDIFAR
CINNAGEN CO. TEHRAN IRAN
Patent Cliff of blockbuster brands in biopharmaceutical market by early 2000 brought a new approach for manufacturing theirs
generics which later named as biosimilars.
The world market for biopharmaceuticals is now about >$190 billion; growing at ~15% annually.
The biopharmaceutical market now constitutes ≥15%, approaching 20%, of the World’s total pharmaceutical market, which is
now essentially at $1 trillion/year.
While biosimilars are finally starting to substantially penetrate the market, it is crucial to know how to survive in this complicated
environment and how to take more share from this attractive market.
Biosimilars due to their lower price and same quality are attractive enough for payers and policy makers to be seriously
considered.
During last decade several biosimilar products came to the market, but their market share were quite different in each case.
Based on quality, nature of the market, and type of disease the approach and the success rate become different. Biosimilar role
in health care budget becomes more and more significant and payers all over the world find them a promising way to skip crisis
due to new expensive medicines come to the market day by day. However the way, time, and manner for entering to the market
is the key factor to have a portion of this complicated biopharmaceutical market.
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PL 6 DISCLOSURE OF THE ACTIVITY MECHANISM OF A TURKISH FOLK REMEDY TO COMBAT RHEUMATIC COMPLAINTS
ERDEM YESILADA
YEDITEPE UNIVERSITY FACULTY OF PHARMACY
The leaves of Sambucus ebulus L. (Adoxaceae) (SE) have been used in Turkish folk medıcıne against a battery of diseases from
peptic ulcer to hyperglycaemia and to rheumatic complaints. The methanolic and aqueous extracts of SE showed potent in
vivo anti-inflammatory activity against carrageenan-induced hind paw edema as well as adjuvant-induced chronic arthritis
models (1). Chlorogenic acid was isolated as one of the active metabolite from methanol extract. Hexane subextract produced
statistically significant inhibition on edema induced by carrageenan comparable to diclofenac. The methanol extract also exerted
significant inhibitory activity against IL-1α and IL-1β, while hexane subextract showed the highest inhibitory activity on TNFα
(2). Ursolic acid from the diethyl ether subextract of ethanol extract of the leaves was the active principle against TNFα-induced
expression of VCAM-1 and ICAM-1 on the surface of HUVECs as monitoring tool (3). Recently through in vitro activity-guided
isolation processing several nuclear factor kappa-B inhibitory constituents have been isolated. Their chemical structures were
identified; a mixture of two flavonoids [1] (quercetin-3-O-β-D-glucopyranoside and quercetin-3-O-β-D-galactopyranoside), two
flavonoids (isorhamnetin-3-O-β-D-glucopyranoside [2] and isorhamnetin-3-O-β-rutinoside [3]) and two iridoids (Sambulin A [4]
and Sambulin B [5]). Among these [2] inhibited NO, iNOS, TNFα, while [3] inhibited PGE2/COX2 while both exerted their effects
through p38/IκBα. Iridoids [3, 4] suppressed iNOS/COX2 levels, NO/PGE2 and TNFα, as well as JNK and IκBα phosphorylations.
Additionally [5] inhibited IL-6 and [4] also inhibited p38 phosphorylation. Consequently, in vitro/in vivo experimental data have
provided molecular and mechanistic evidences supporting the traditional use of this remedy. 1. Yeşilada E. Antiinflammatory
Activity of the Aerial Parts of Sambucus ebulus; Isolation of an Antiinflammatory Principle. Doğa Turkish Journal of Pharmacy
1992; 2: 111-123. 2. Yeşilada E, Üstün O, Sezik E, et al.. Inhibitory Effects of Turkish Folk Remedies on Inflammatory Cytokines;
Interleukin-1α , Interleukin-1β , and Tumor Necrosis Factor α. Journal of Ethnopharmacology 1997; 58: 59-73. 3. Schwaiger S,
Zeller I, Pölzelbauer P, et al. Identification and pharmacological characterization of the anti-inflammatory principal of the leaves
of dwarf elder (Sambucus ebulus L.). J. Ethnopharmacol. 2010; 133: 704-9.
PL 7 RECENT DEVELOPMENTS IN ENANTIOSEPARATION OF CHIRAL DRUGS
BEZHAN CHANKVETADZE
INSTITUTE OF PHYSICAL AND ANALYTICAL CHEMISTRY, SCHOOL OF EXACT AND NATURAL SCIENCE, TBILISISTATE UNİVERSITY,
CHAVCHAVADZE AVE, GEORGIA
The first part of this presentation shortly summarizes recent developments in liquid phase enantioseparation techniques such as
high-performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC), nano-liquid chromatography (nanoLC), capillary electrochromatography (CEC) and capillary electrophoresis (CE). In HPLC, novel chiral selectors, mobile phases,
mobile phase additives and inert carriers, as well as some unusual effects and approaches for a better understanding of the
chiral recognition mechanisms are summarized. In the SFC part of the presentation, the emphasis will be made on uncommon
additives of the mobile phases and chemometric-based efforts for classification of the available stationary phases as well
as getting some information about the chiral recognition mechanisms. The nano-LC and CEC parts of the presentation will
discuss the application of novel materials (chiral molecular frameworks) and inert carriers (core-shell silica) while the CE part
focuses on chiral recognition mechanisms with cyclodextrin-type chiral selectors in aqueous and non-aqueous CE. The second
part of the presentation will highlight the efforts of our group with regard to separations of enantiomers in the liquid phase
with the highest possible coverage of analytes, separation selectivity, plate numbers and shortest analysis time. In order to
achieve this goal, the systematic optimization of the composition of polysaccharide-based chiral selectors, the structures of the
studied analytes (chiral sulphoxides), composition of the mobile phases, mobile phase additives and separation temperature
have been performed. In a parallel project, the particle size of the silica, its morphology (porosity and pore size), the nature
of the chiral selector and its content in the chiral stationary phase were optimized in order to reach the highest possible
column performance. Chiral analytes studied involved chiral drugs such as dihydropyridine and arylpropionic acid derivatives,
b-blockers, imidazole derivatives and sulphoxides.
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PL 8 SYNTHETIC CANNABINOIDS: THE NEW TSUNAMI THAT HITS THE NATION
İLHAN YARGIÇ
İSTANBUL UNIVERSITY ISTANBUL MEDICAL FACULTY PSYCHIATRY DEPARTMENT
Natural cannabis (Δ9-THC, tetrahidrokanabinol) is derived from the plant called Cannabis Sativa. Acute effects of cannabis
include euphoria, relaxation, subjective slowing in time perception, dizziness, analgesia, difficulties in memory and problem
solving, ataxia, tachycardia, systolic hypertension, postural hypotension, increased apatite, anxiety, paranoid thoughts and
depression. Cannabis can cause dependence and withdrawal. DSM-5 lists withdrawal symptoms as: anger, irritability or feelings
of aggression; depressed mood; feelings of restlessness; loss of appetite; insomnia; feelings of anxiety or nervousness; physical
symptoms of withdrawal, such as headache, stomach pains, increased sweating, fever, chills or shakiness.
Cannabis is also known to have some therapeutic effects such as antiemetic in cancer patients, spasmolytic in multiple sclerosis
(MS), appetizer in AIDS, anti-inflammatory in rheumatoid arthritis, antidiarrheic in Chrone’s disease and also useful in neuropathic
pain, glaucoma and movement disorders. Cannabis acts on cannabinoid receptors (CB1 and CB2). Main endogen cannabinoids
are anandamide and arachidonilglyserol. Marijuana contains approximately 60 cannabinoids. Δ9-tetrahydrocannabinol which is
the most effective one activates mesolimbic dopaminergic system so that it affects reward and reinforcement mechanism.Today
there are a few medications containing cannabinoids used for medical purposes: Dronabinol (Marinol®), Nabilone (Cesamet
®), Nabiximols (Sativex®) and medical marijuana. Nabiximols (Sativex® oral spray) was approved for decreasing stress, muscle
rigidity and pain in MS. It can be used in moderate to severe cases that are refractory to other spasmolytic medications. Good
results have also been reported with neuropathic pain, overactive bladder, cancer pain and Tourette syndrome. Medical uses
of cannabis have led investigators to search for synthetic cannabinoids (SC). These compounds which were initially used for
analgesia have THC like effects. They were not marketed as medicine due to their psychoactive properties, however, their
abuse spread rapidly. These compounds are marketed on the street with names such as Spice, K2, Genie in Europe and USA. In
Turkey they have street names such as Bonzai, Jamaica and Jamaican Gold. Their chemical structure is quite different than THC.
They are designated with chemical formulas like JWH-018, JWH-073, HU-210, CP-47, CP-497, JWH-018 and a new one is added
every day. They were officially registered as illegal substances on 13.02.2011 in Turkey. Their cannabinoid receptor (CB1R)
affinity and activity is higher than those of THC. They have a larger effect size and more frequent and more severe adverse
effects compared to THC (1). Their effect starts more rapidly but lasts shorter. There is risk of intoxication depending on amount
and degree of purity. Their adverse effects which are not seen or less frequently seen with natural THC include convulsions,
anxiety, aggressiveness, muscle rigidity and confusion. Their abuse has been popular rapidly due to their easy access and being
undetectable in routine urine screens. SC’s have been reported to cause dependence and
physiological withdrawal (2).
Poison Control Center data in USA report agitation, confusion, hallucination, hypertension, myocardial ischemia, heart attack
linked to the use of SC. Toxic effects usually resolve in 3-4 hours (3). There are many case reports of convulsions due to SC.
They are generalized tonic clonic (GTC), usually multiple and don’t leave sequel (4). Emergency department physicians should
suspect from SC abuse in young males who apply with first time GTC seizure (5). In cases of new and sudden onset psychosis
who are on urine drug screen follow-up or in cases who demonstrate signs of cannabis abuse but give negative urine test, SC
abuse should be suspected (6). SC have also been reported to cause some other serious medical adverse effects like acute
kidney failure, acute loss of vision and Wernike Syndrome. Although in the international literature intoxication of synthetic
cannabinoids has been reported to resolve without sequel, our country has been shocked by the increasing number of Bonzai
related deaths recently. Until now, exact mechanism of causality underlying these cases has not been resolved.
References:
1. Brents LK, Reichard EE, Zimmerman SM, Moran JH, Fantegrossi WE, Prather PL.
Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor
affinity and activity. PLoS One. 2011; 6(7):e21917.
2. Castellanos D, Thornton G. Synthetic cannabinoid use: recognition and management. J Psychiatr Pract. 2012;18(2):86-93.
3. Wells DL, Ott CA. The “new” marijuana. Ann Pharmacother. 2011; 45(3):414-417.
4. Tofighi B, Lee JD. Internet highs--seizures after consumption of synthetic cannabinoids purchased online. J Addict Med. 2012;
6(3):240-241
5. de Havenon A, Chin B, Thomas KC, Afra P. The secret “spice”: an undetectable toxic cause of seizure. Neurohospitalist. 2011;
1(4):182-186.
6. Cohen J, Morrison S, Greenberg J, Saidinejad M. Clinical presentation of intoxication due to synthetic cannabinoids. Pediatrics.
2012; 129(4):e1064-1067
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PL 9 PHARMACOENHANCEMENT OF ENDOCANNABINOID SIGNALING: NEW AVENUES OF ANXIETY THERAPY
CARSTEN T. WOTJAK
MAX PLANCK INSTITUTE OF PSYCHIATRY, DEPARTMENT OF STRESS NEUROBIOLOGY AND NEUROGENETICS, RESEARCH GROUP
“NEURONAL PLASTICITY” KRAEPELINSTR MUNICH, GERMANY
Anxiety disorders such as specific and social phobias, panic disorder and posttraumatic stress disorder belong to the most
frequent psychiatric disorders in our societies. They bear enormous personal and economic burdens. With benzodiazepines,
we have a class of drugs in our hands which successfully ameliorates anxiety symptoms. However, benzodiazepines cannot
be applied in combination with exposure-based therapies due to state dependency and amnesic effects. This illustrates the
interest of preclinical and clinical research in developing novel therapeutic interventions. The endocannabinoid system of the
brain represents one of the new promising targets. This system is comprised by a distinct set of synthesizing and degrading
enzyme, uptake mechanisms and selective binding sites. Remarkably, endocannabinoids are synthesized and released on
demand in postsynaptic nerve terminals. As retrograde messengers, they travel to primarily presynaptically localized receptors.
Receptor binding leads to reduced (in case of cannabinoid receptor type 1, CB1) or enhanced (in case transient receptor
potential vanilloid receptors 1, TRPV1) of neurotransmitter signaling. The complexity of the endocannabinoid system is further
increased by the existence of different endocannabinoids (e.g. anandamide or 2-AG). Preclinical studies illustrate the potential
of enhanced endocannabinoid signaling (e.g. by blocking re-uptake or degradation) in reducing fear expression and facilitating
safety learning. The efficacy of this intervention critically depends on the players targeted (i.e. anandamide vs. 2-AG, CB1 vs.
TRPV1). Preclinical studies hold the promise of future application in anxiety patients.
PL10 WHERE DO WE STAND IN THE ERA OF PSYCHOTHERAPY?
FEYZA ARICIOGLU
MARMARA UNIVERSITY, SCHOOL OF PHARMACY, DEPARTMENT OF PHARMACOLOGY AND PSYCHOPHARMACOLOGY RESEARCH
UNİT, HAYDARPASA, ISTANBUL, TURKEY
Rapidly accumulating evidence suggests that the glutamatergic system plays an important role in the neuropathology and
treatment of major depressive disorder, bipolar disorder (BD) and schizophrenia. Recently it has been shown that ketamine has
a rapid and long lasting antidepressant activity after a single dose, which acts on the human brain by blocking the N-methyl-Daspartate (NMDAR) receptors. In studies with rats, basic researchers demonstrated that ketamine rapidly activates the so called
“mammalian target of rapamycin” (mTOR) pathway, one of many such pathways that perform signal transduction in neurons.
This new approach may be a revolutionary break-through in the treatment of depression and it might lead to novel therapeutic
targets for antidepressant drug development.
BD is one of the common psychiatric diseases that leads to certain corrupted certain brain abilities. Today a growing body
of evidence has directed much attention to the hyperactivation of glycogen synthase kinase-3 (GSK-3) in several psychiatric
disorders including BD. GSK-3 is widely expressed in many tissues with the highest levels in the brain and the importance
of regulatory mechanisms on GSK-3 is highlighted through the aspect of Akt-GSK-3 engagement by possibly bringing novel
aspects to the treatment of BD. The involvement of GSK-3 in BD is also supported by the fact that GSK-3 is also regulated by
neuromodulators such as brain-derived neurotrophic factor (BDNF), a well-known neurotrophin that regulates differentiation,
survival and development of neurons and synaptic plasticity. When binding to TrkB, BDNF is responsible for activating the PI3K/
AKT pathway and consecutively phosphorylating GSK-3 finally resulting in its inhibition. In fact, targeting Toll like receptors as
initiator molecular mechanisms of cytokine-mediated inflammatory responses, namely Nod-like receptor protein 3 (NLRP3)
inflammasome, is now holding huge promise. GSK-3 has been shown to play a regulatory role in immune responses through
cytokine production namely as TNF-α and IL-6. NLRP3 inflammasome, a multiprotein complex that is formed by the activation
of NLRP3 and is responsible for initiating IL-1β and IL-18-mediated inflammatory responses, has become an important topic
which may add novel aspects to the cytokine hypothesis of depression. High plasma levels of pro-inflammatory cytokines
such as IL-1β, IL-6 and TNF-α have been reported by several clinical studies in patients with depression. In addition, plasma
levels of these pro-inflammatory cytokines are shown to be decreased with antidepressant therapies. Thus, great effort has
been made to discover novel therapeutic implications targeting immune mechanisms that would replace currently available
drugs.
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PL 11 THE ROLE PLAYED BY THE HLA COMPLEX IN ADVERSE DRUG REACTIONS
MEHMET TEVFIK DORAK
HEALTH SCIENCES LIVERPOOL HOPE UNIVERSITY, UK
The human leukocyte antigen (HLA) complex located in chromosome 6p21.3 is the most gene dense region in the human
genome. HLA genes encode cell proteins whose main function is presentation of peptide antigens. HLA molecules are the most
polymorphic proteins and show a very high number of disease associations mainly with autoimmune and infectious diseases.
Most polymorphisms concentrate in antigen-binding clefts. Over the past decade, HLA molecules are also recognised as being
modulators of hypersensitivity against drugs. Of these, HLA- B*57:01 (abacavir) and B*15:02 (carbamazepin) associations are
best studied. Variuos HLA mediated adverse drug reactions for allopurinol, aspirin, D-penicillamine, fluoxacilline, levamisole,
phenytoin, sulfonamides and other drugs are recognised. Such adverse reactions are mediated by different classes of HLA
molecules (A,B,C,DR) and more than one mechanism may be involved. Potential mechanisms involving haptens, super
antigens and pharmacologic interference with immune receptors have been ruled out. Recent molecular studies identified
the mechanism for adverse reaction to abacavir as alteration in HLA-B*57:01 peptide binding motif by occupying sites within
the cleft leading to presentation of novel peptides to T-cells causing polyclonal activation similar to what happens in HLA mismatched transplantation. Besides providing clinical testing opportunities for drug safety, these developments may also
provide insight into immunopathogenesis of disorders also mediated by HLA molecules.
PL 12 GROWTH ARREST SPECİFİC-6 (GAS6)/AXL PATHWAY: POTENTİAL NEW STRATEGY FOR DRUG DEVELOPMENT
FIKRIYE URAS
MARMARA UNIVERSITY, TURKEY
Growth arrest-specific 6 protein, GAS6, is expressed in several kinds of cells and tissues, such as hematopoietic cells,
endothelial and vascular smooth muscle cells, and brain tissue. It is evident that GAS6 is related to certain physiological and
physiopathological conditions including cell migration, adhesion, and cell growth and survival, but its precise physiological role
has not yet been clarified.
GAS6 has been implicated in inflammation, autoimmune, vascular and kidney diseases. It is the ligand for Tyro 3, Axl and Mer
(TAM receptors) of the tyrosine kinase family. GAS6/TAM pathway controls various cellular functions, including macrophage
clearance of apoptotic cells and natural killer cell differentiation. GAS6 is overexpressed in various cancers including glioblastoma,
lung, gastric, breast, colon, and ovarian cancer. Whereas increased GAS6/Axl interaction indicated a poor prognosis in patients
with glioblastoma and ovarian carcinoma, low tumor Axl mRNA levels was independently correlated with improved survival in
patients with renal cell carcinoma, demonstrating the complexity of the system.
There is also evidence in some cancer types that GAS6 may have a role in resistance to chemotherapy. The GAS6/Axl pathway
may provide a focus for new strategies for treatment of certain types of cancer. Treatment of AXL-transfected U937 acute
myeloid leukaemia cells with recombinant GAS6 resulted in resistance to some drugs such as doxorubicin, VP16, and cisplatin.
The cancer-restricted action of GAS6, together with its passivity on stroma cells and its therapeutic inhibition may help target
cancer-related inflammation.
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PL 13 PHYTOTHERAPY IN TURKEY AND THE PLANTS OF TURKEY AS SOURCE OF HERBAL MEDICINAL PRODUCTS
FILIZ MERICLI
DEPARMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, NEAR EAST UNIVERSITY, NICOSIA, TURKISH REPUBLIC OF
NORTHERN CYPRUS
Turkey is the point of the encounter of 3 different eco-systems and it is very rich in plant diversity. Flora of Turkey is represented
with more than 10000 plants and about one-third of them are endemic. Besides a rich plant diversity, Turkey is also very rich
in cultural varieties. The plant and cultural diversities in Turkey, provide very rich traditional treatments and folk medıcınes.
Folk remedies and medicinal plants of Turkey are investigated by Turkish scientists working in Faculties of Pharmacy and nearby
professions. More than 1000 new compounds have been isolated from Turkish plants and published by the researchers from
pharmacognosy departments in Turkey(1). The biological activities of Turkish medicinal plants are also investigated by our
colleagues.
Today Phytotherapy applications in Turkey can be evaluated in 2 groups.
A. Traditional folk medicines: The usage of herbs with advices of people or media, such as TV and newspapers. Herbal materials
are provided from markets called “aktar”.
B. Rational Phytotherapy: According to the prescriptions of the physicians and/or pharmacists’ suggestions. The herbal products
(medicinal teas and phytomedicines) are provided from pharmacies. Example: Hedera helix, Pelargonium sidoides (2).
As the results of our investigations, there are a lot of plants like Silybum marianum, Crataegus, Thymus ,Origanum, species that
can be used as sources of herbal medicinal products(3).
References
1. Meriçli F, Meriçli AH, Seyhan GV et al. Willipelletierine, a New Diterpenoid Alkaloid from Consolida scleroclada. Pharmazie
2002; 57, 761-762.
2. Meriçli F, Alp İ. Bronşit ve Öksürükte Doğal ve Etkin Çözüm Duvar Sarmaşığı Hedera helix. Fitomed 2010,18,42-50.
3. Topal G, Koç, Meriçli AH et al. Effects of Crataegus microphylla on Vascular Dysfunction in Streptozotocin-induced Diabetic
Rats. Phythother. Res. 2013; 27, 330-337.
PL 14 POTENTIAL ANTI-ALZHEIMER AGENTS FROM LAMIACEAE FAMILY PLANTS
GULACTI TOPCU
DEPARTMENT OF PHARMACOGNOSY & PHYTOCHEMİSTRY, FACULTY OF PHARMACY BEZMIÂLEM VAKİF UNIVERSITY, ISTANBUL,
TURKEY
Alzheimer’s disease (AD) is one of the most common and progressive neurodegenerative disorders with dementia in the world.
Current AD treatment is symptomatic and is mainly focused on the inhibition of cholinesterases. However, none of them
provides a satisfactory treatment for AD, and studies are still going on to find new potential drugs from both synthetic chemicals
and natural sources (1).
In this study, investigation of new cholinesterase inhibitors from Lamiaceae family plants were evaluated and a number of
terpenoids and phenolics/flavonoids isolated will be presented as potential drugs in the treatment of AD. For this purpose,
Lavandula, Leonurus, Melissa, Micromeria, Nepeta, Origanum, Rosmarinus, Salvia, Satureja, Scutellaria, Sideritis, Stachys and
Thymus species from Lamiaceae family plants were investigated (2).
As terpenoids, triterpenoids, especially oleanane, ursane, and lupane triterpenoids, have high potential in the treatment of AD in
the future (3). Diterpenes, especially phenolic ring-containing diterpenes, such as abietanes, were tested for anticholinesterase
activity, and most abietanes have been found to be active against BChE rather than AChE (2). Ferruginol and taxodione are
fairly common abietanes isolated from a number of Salvia species (2) that exhibited high BChE inhibition activity and moderate
AChE inhibition activity, indicating their dual inhibition properties. Some kaurane diterpenes of Sideritis species were also
found to be active (4). As a conclusion, a number of Lamiaceae plants that have been investigated should be considered as
anticholinesterase agents in the potential treatment of AD with dual inhibition on AChE and BChE, or selective inhibition against
only one of them (2-5).
References
1. Murray AP, Faraoni MB, Castro MJ, Alza NP and Cavallaro V. Natural AChE Inhibitors from Plants and Their Contribution to
Alzheimer’s Disease Therapy. Curr Neuropharm 2013; 11: 388-413.
2. Topcu G, Kusman T. Lamiaceae Family Plants as a Potential Anticholinesterase Source in the Treatment of Alzheimer’s Disease,
Bezmiâlem Science 2014; 2: 1-25
3. Culhaoglu B, Yapar G, Dirmenci T, Topcu G. Bioactive Constituents of Salvia chrysophylla Stapf. Nat Prod Res 2013; 27: 438-47.
4. Ertas A, Ozturk M, Boga, M, Topcu G. Antioxidant and Anticholinesterase Activity Evaluation of ent-Kaurane Diterpenoids
from Sideritis arguta. J Nat Prod 2009; 72: 500-502.
5. Ozturk M, Kolak U, Topcu G, Oksuz S, Choudhary MI. Antioxidant and Anticholinesterase Active Constituents from Micromeria
cilicica by Radical-Scavenging Activity-Guided Fractionation. Food Chem 2011; 126: 31-38.
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PL 15 APPLICATION OF MASS SPECTROMETRY BASED PROTEOMICS FOR PRODUCTION AND CHARACTERIZATION OF
BIOPHARMACEUTICALS
EBRAHIM RAZZAZI-FAZELI
VETCORE FACILITY FOR RESEARCH / PROTEOMICS UNIT, VETERINARY MEDICINE UNIVERSITY VIENNA / AUSTRIA
Proteomics has become one of the most growing discipline within the systems biology nowadays and plays an important role in
characterization of biological processes. An essential part of modern proteomics is the biological mass spectrometry. There are
exactly 100 years, when Joseph John Thomson has developed the first “mass spectroscope” in 1913 for separation and analysis
of isotopes. Now a day mass spectrometry has become the most ubiquitous tool in analytical chemistry and biochemistry. It has
definitively revolutionized the field of biosciences with regard to protein analysis. Particularly, the biological mass spectrometry
has been shown to be the method of choice for characterization and evaluation of therapeutic proteins. Mass spectrometry
can provide detail information on not only amino acid sequence but also their alteration and post translational modifications.
In recombinant protein technology the study of host cell proteome such as Chinese Hamster Ovary cells or Escherichia coli (E.
coli) provide valuable information for optimizing the fermentation process. The achieved knowledge can help to enhance the
product yield and reduce degradation or aggregates of recombinant proteins [1]. Another example is the use of proteomics
in characterization of biological medicinal products such as therapeutic human polyclonal immunoglobulin concentrates [1].
In this paper an overview of different strategies used in proteomics and biological mass spectrometry for characterization of
therapeutic immunoglobulin as well as recombinant proteins and their host cell proteome will be given and its potential will
be discussed.
References
1. K. Marisch et al. A comparative analysis of industrial Escherichia coli K-12 and B strains in high-glucose batch cultivations on
process-, transcriptome- and proteome level (2013), PLoS One Volume 8 / Issue 8
2. F. Lackner et al. Contamination of therapeutic human immunoglobulin preparations with apolipoprotein H (2014)
Electrophoresis 2014, 35, 515–521
PL 16 CUPRAC METHODS OF ANTIOXIDANT CAPACITY/ACTIVITY MEASUREMENT APPLICABLE TO FOOD, PHARMACEUTICALS
AND BIOLOGICAL FLUIDS
RESAT APAK, KUBILAY GUCLU, MUSTAFA OZYUREK, S. ESIN CELIK, BURCU BEKTASOGLU, SEMA DEMIRCI CEKIC AND MUSTAFA
BENER
ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMISTRY, DIVISION OF ANALYTICAL CHEMISTRY, AVCILAR
ISTANBUL
Measuring the antioxidant activity/capacity levels of biological fluids and foods is carried out for the diagnosis and treatment of
oxidative stress−associated diseases in clinical biochemistry, for meaningful comparison of foods in regard to their antioxidant
content, and for controlling variations within or between products. Some drugs owe their activity totally to their antioxidative
activity, e.g., improvement of genetic stability in lymphocytes from Fanconi anemia patients originates from the combined effect
of α-lipoic acid and N-acetylcysteine. Various antioxidant activity/capacity methods have been used to monitor and compare
the antioxidant activity of food and drug. Complementary to existing methods in literature, novel approaches have recently
been developed such as CUPRAC (CUPric Reducing Antioxidant Capacity) total antioxidant capacity (TAC) assay (introduced by
our research group to world literature in 2004), its modified ROS scavenging assays and other modifications (e.g., antioxidant
sensor, post-column online HPLC technology). Antioxidants react with the CUPRAC reagent (cupric neocuproine) to produce
the Cu(I)-neocuproine (Nc) chromophore measured spectrophotometrically [1]. The method was successfully applied in our
laboratory to various food extracts (i.e., apricot, apple, hazelnut, herby cheese and vegetables) and human serum. Hydrophilic
antioxidants in serum were measured in aqueous phase after precipitation of proteins, while lipophilics were determined
in dichloromethane [2]. Main and modified CUPRAC assays have recently been compiled in a comprehensive review [3]. A
salicylate probe was converted to its CUPRAC−reactive hydroxylation products (dihydroxybenzoates) in a Fenton system, and
the hydroxyl radical scavenging rate constants of the tested antioxidants were determined by competition kinetics. Lipophilic
and hydrophilic antioxidants could be simultaneously assayed in acetone-water as their inclusion complexes with methyl-βcyclodextrin. Xanthine oxidase scavenging activity of polyphenolics was determined by urate measurement with CUPRAC.
Cupric neocuproine reagent in urea buffer also responded to thiol-containing proteins in food. Hydrogen peroxide scavenging
activity of polyphenolics was measured in the presence of Cu(II) catalyst with a modified CUPRAC method. A low-cost optical
antioxidant sensor (CUPRAC sensor) was developed by immobilizing the Cu(II)-Nc reagent onto a perfluorosulfonate cationexchange polymer membrane (Nafion®). A novel on-line HPLC-CUPRAC method was developed for the selective determination
of polyphenols in complex plant matrices. This type of pharmaceutical profiling may also be useful to identify, classify and
compare the antioxidant-active ingredients of drugs. Another modified CUPRAC method for measuring the superoxide (SO)
anion radical scavenging activity of plasma antioxidants (including thiols) utilized a tert-butylhydroquinone (TBHQ) probe with
PMS-NADH non-enzymic SO generation system [4]. The current direction of CUPRAC methodology can be best described as a selfsufficient and integrated train of measurements providing a useful “antioxidant and antiradical assay package”in biochemistry
and food chemistry comprising many assays, and the results are in accordance with those of independent reference methods,
having distinct advantages over certain established methods.
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References
[1] R. Apak, K. Güçlü, M. Özyürek, S. E. Karademir, J. Agric. Food Chem., 2004, 52, 7970.
[2] R. Apak, K. Güçlü, M. Özyürek, S. E. Karademir, M. Altun, Free Radical Res., 2005, 39, 949
[3] M. Özyürek, K. Güçlü, R. Apak, Trends Anal. Chem., 2011, 30, 652-664.
[4] B. Bekdeşer, M. Özyürek, K. Güçlü, R. Apak, Anal. Chem., 2011, 83, 5652-5660
PL 17 NEW TRENDS IN CHROMATOGRAPHY
GULER YALCIN
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTICAL CHEMISTRY, HAYDARPASA CAMPUS,
HAYDARPASA ISTANBUL
“The first thing the chemist must do is to isolate the substances he is interested in from the material and prepare them in a
pure state. The next step is, if possible, to identify these substances and find out what they consist of and how they are built
up from simple constituents.” These words are from the Presentation Speech of Prof. Arne Tíselius in the Ceremony of A.J.P.
Martin, R.L.M. Synge awarded with The Nobel Prize in 1952, on chromatography. However, chromatography gained progress
since 1952, the needs are still remain the same. Separating, purifying, identifying, quantifying of the substances in the complex
natural/artificial matrixes. Eventually “find out how they are built up from simple constituents”.
On the other hand, there are some environmental issues that require attention to make the ecology friendly.
Chromatographic separations needs to take some measures. These can be summarized in 10 points: 1. Improving resolution and
selectivity; 2. Having cost effective analysis. 3. Shortening the analysis time. 4. Obtaining the reproducible and the repeatable
results. 5. Lowering the detection limits. 6. Using the column packings resistant to heat and pH. 7. Using less organic solvent, 8.
Alternatively to organic solvents, using pressurized hot water (PHW-LC) 9. Compatibility with some detectors, like NMR, Mass,
flame ionization. 10. Increased confidence on analyte identification.
New trends meets the above mentioned essential points in chromatography are being summarized in this study. The columns for
increasing the resolution and selectivity and resistant the heat, pH are being produced: Nanostructured thin films for ultrathin
layer chromatography (1), diamond based adsorbents (2), metal organic frameworks (3), monolithic columns (4). Along with the
column technology, the instrument technology is getting improved. Ultra High Performance Liquid Chromatography (UHPLC),
Ultra Thin Layer Chromatography (UTLC) (1), Nanoflow Liquid Chromatography (5), Nano Chromatography, Termal Gradient
Liquid Chromatography, Pressurized Hot Water Liquid Chromatography (PHW-LC) (6) are some of these newly designed
instruments.
The most interesting progress in chromatography is the minimization and contingently lowering the amount of detectable
analyte. It probably would be helpful to find out that how “substances are built up from simple constituents” as Prof. Tiselius
told us.
References
1 Ultrathin-layer chromatography on SiO2, Al2O3, TiO2, and ZrO2nanostructured thin films, Julia Wannenmacher, Steven R. Jim,
Michael T. Taschuk, Michael J. Brett, GertrudE. Morlock, J. of Chromatogr. A, 1318 (2013) 234– 243.
2 Diamond based adsorbents and their application in chromatography Review Anton A. Peristyya, Olga N. Fedyaninab, Brett
Paulla, Pavel N. Nesterenkoa, J. of Chromatogr. A, 1357 (2014) 68–86.
3 Applications of metal-organic frameworks as stationary phases in chromatography, Yuebo Yu, Yuqian Ren, Wei Shen, Huimin
Deng, Zhiqiang Gao, Trends in Analytical Chemistry, 50 (2013) 33–41.
4 Monolithic columns in high-performance liquid chromatography, Guiochon G., J Chromatogr A. 2007 Oct 19;1168(1-2):101-68;
discussion 100. Epub 2007, Jun 3.
5 A direct nanoflow liquid chromatography-tandem mass spectrometry system for interaction proteomics. Natsume T, Yamauchi
6 Y, Nakayama H, Shinkawa T, Yanagida M, Takahashi N, Isobe T, Anal Chem. 2002 Sep 15;74(18):4725-33.
Liquid chromatography at elevated temperatures with pure water as the mobile phase, Kari Hartonen, Marja-Liisa Riekkola,
TrAC Trends in Analytical Chemistry, 01/2008; 27(1):1-14.
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PL 18 DRUG-INDUCED OXIDATIVE STRESS AND TOXICITY
SIBEL OZDEN
ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, ISTANBUL, TURKEY
Reactive oxygen species (ROS), can be generated from a variety of sources both endogenous and exogenous. ROS at low or
moderate concentration can play important physiological roles. However, excessive production of ROS can occur in response
to such stressors as toxicant exposure, radiation damage, and disease resulting in oxidative stress. ROS are generated due to
induction of various cytochrome P450 isoenzymes during detoxification of xenobiotics, lipid peroxidation and other intracellular
processes and involved in regulation of numerous factors, such as transcription factors kappa B, NFkB and AP-1, and PPARg
(Kakehashi et al., 2013). ROS have effects on key cellular components including DNA, protein and lipid macromolecules. Druginduced oxidative stress is implicated as a mechanism of toxicity in numerous tissues and organ systems. For example, cisplatin,
an antineoplastic agent, has been shown to increase oxidative stress by increasing levels of superoxide anion, H2O2, and
hydroxyl radical, resulting in nephrotoxicity. Acetaminophen caused hepatotoxicity due to the formation of reactive metabolites
and depletion of glutathione (Deavall et al., 2012). The aim of this review is to provide a comprehensive overview of the role
of oxidative stress in drug induced-toxicity. Furthermore, this review also provides an overview of current in vitro and in vivo
methods that measure oxidative stress biomarkers throughout the drug discovery process.
References:
1-Deavall DG, Martin EA, Horner JM, Roberts R. J Toxicol. 2012;2012:645460
2-Kakehashi A, Wei M, Fukushima S, Wanibuchi H. Cancers. 2013;5(4):1332-54
PL 19 ROS DIAGNOSTICS AND BIOMARKERS
A. SUHA YALCIN
DEPARTMENT OF MEDICAL BIOCHEMİSTRY, SCHOOL OF MEDICINE, MARMARA UNIVERSITY, MALTEPE-ISTANBUL, TURKEY
Free radicals are involved in different pathological conditions including atherosclerosis, cardiac disease, cancer, cerebrovascular
diseases, neurodegenerative diseases, diabetes, acute renal failure, emphysema, lung disease, bronchitis and alcoholic liver
diseases almost all of which are age-dependent conditions. Free radicals and reactive oxygen species (ROS) are continuously
formed during conversion of foods to energy using oxygen. These molecules can easily damage major components of the cell
such as proteins, lipids and DNA. An antioxidant defense system exists in aerobic organisms in order to control free radical
production and to prevent their harmful effects. However, in most cases the antioxidant defense system can not completely
protect against damaging effects of free radicals. This results in a conditon that is called oxidative stress. In this presentation
different methods used to assess the level of ROS and oxidative stress status will be discussed. Additionally, methods that
measure oxidative stress related effects such as antioxidant capacity, lipid peroxidation, protein oxidation and DNA damage will
be presented.
PL 20 BIO-IMAGE-INFORMATICS: A NEW TOOL TO MONITOR CELL ORGANELLE DYNAMICS
H. BIROL COTUK, A. DENIZ DURU
MARMARA UNIVERSITY DEPARTMENT OF SPORT HEALTH SCIENCES
With the advent of super-resolution imaging techniques such as PALM (photo-activation localization microscopy, STORM
(stochastic optical reconstruction microscopy) and STED (stimulated emission depletion) it became possible to visualize cell
structures beyond the optical diffraction limit. Together with advances in biological tissue labeling (e.g. enhanced green
fluorescent proteins, EGFP), multi-color images which pinpoint to the location of individual proteins or sub-organelle structures
in the several nanometer dimension can be collected digitally. By implementing the time domain during live cell imaging
experiments, the dynamics of these complex biological images warrants specialized time series analysis based on various image
data extraction and informatics techniques. Recent studies highlight the potential of this new approach, which can be termed
bio-image-informatics, to produce new insights into cellular and sub-cellular processes.
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PL 21 BETTER UNDERSTANDING OF THE MONOAMINE OXIDASES -ASSOCIATED I2 BINDING SITE COMBINING MOLECULAR
MODELLING AND ENZYMOLOGY
SALVATORE GUCCIONE
DIPARTIMENTO DI SCIENZE DEL FARMACO -UNIVERSITÀ DEGLI STUDI DI CATANIA- VIALE A.DORIA 6 ED. 2 CITTÀ UNIVERSITARIA,
ITALY
Since the demonstration of the existence of non-adrenoceptor imidazoline binding sites, numerous studies have focused on the
functional role of imidazoline receptors in the central nervous system.
The roles of imidazoline receptors, first identified by the non-selective agonist clonidine, are beginning to emerge as selective
agonists and antagonists are designed and synthesised to enable investigation. Selective I-1 ligands are used as antihypertensive
drugs; selective I-2 ligands which are only now being properly understood because the ligands lacked specificity induce
hypothermia and have emerging roles in attenuation of withdrawal anxiety and pain; and I-3 ligands influence insulin secretion
in the pancreas.
Selective I-2 receptor ligands modulate monoamines in the brain, making it possible that they have potential for modulating
behavior (and so use for anti-depressant, anti-anxiety, or in drug withdrawal) and for use in degenerative diseases, for example,
in preventing amyloid beta-induced neuronal apoptosis.
One protein known to bind imidazoline ligands is monoamine oxidase (MAO).
High-affinity I2 binding sites were convincingly localized to MAO in 1995 when expression of human MAO A and MAO B in yeast
resulted in a gain of previously nonexistent I2 ligand binding with nanomolar affinity.
The next step in medicinal chemistry is to investigate structure−activity correlations using molecular dynamics and enzymology
so that clear links between these studies and the pharmacology of these elusive sites can be determined.
Docking and molecular dynamics were used to explore how 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI) binds to
MAO A and to explain why tranylcypromine increases tight binding to MAO B.
PL 22 EVIDENCE BASED MEDICINE; CRITICAL APPRAISAL OF EPIDEMIOLOGICAL STUDIES
PINAR AY
MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PUBLIC HEALTH, ISTANBUL / TURKEY
Clinicians, public health practitioners and health-care policy makers come across to new queries during their practice every
day. A clinician might be questioning the efficacy and a safety of a new treatment regimen and whether it has superiority to the
conventional approach or not. A public health practitioner might be trying to understand the effectiveness of a school based
obesity prevention program whereas a policy maker might be interested in the cost effectiveness of adapting such a program
for the community. The decision making process is not easy since answers for such questions are not usually accessible through
textbooks. This necessitates the practice of Evidence Based medicine for all health-care workers in their daily practice.
David L. Sackett defines Evidence Based medicine as “the conscientious, explicit, and judicious use of current best evidence in
making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual
clinical expertise with the best available external clinical evidence from systematic research.” Today it is accepted that the use
of Evidence Based medicine is not limited to clinical questions, but encompasses all issues related to health and health-care.
The practice of Evidence Based medicine starts with formulating the well-built research question. The second step is searching
the best available evidence relevant to the formulated question. Evidence refers to scientifically sound research and the main
focus is the critical appraisal of the retrieved study. At this stage, the validity of the study and its applicability to practice
are discussed. This involves three major questions; “Are the results of the study valid?” “What are the results and are they
important?” and “Will the results be applicable to my problem?”. If the evidence is valid then it is integrated with the expertise
and evaluated within the socio-cultural context e.g. the preferences and values of the patient or the community in making a
decision.
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PL 23 HEALTH ECONOMICS IN TURKEY
DENIZ GURANLIOGLU
ASTRA ZENECA – TURKEY
Since 2003, Turkey has been implementing its Health Transformation Program (HTP) with the goal of realizing universal health
coverage. HTP emphasized the need for better quality information to make sound health system policies and administrative
decisions. With 95% of the country’s population now receiving of public health coverage for which the government has had to
make a significant financial commitment. The problem is how to meet rising health spending of Turkey and how to most effectively
use available limited resources for the benefit of the human health. Budgetary constraints have already led the government to
implement cost-containment measures in the short-term in the pharmaceutical field. Health economics has become increasingly
important throughout the world for long-term vertical and horizontal efficiency, as spending on health witnessed substantial
increases. In the light of all of the preceding, it will be important to make adequate use of health economics at all the areas of
healthcare for Turkey in the next years.
PL 24 CHALLENGING MATERIALS for COSMETIC USE
YASEMIN YAZAN
ANADOLU UNIVERSITY, DEPARTMENT OF PHARMACEUTICAL AND COSMETIC TECHNOLOGY
Scientific evidence about safety of natural/chemical cosmetic ingredients are reported in CIR (Cosmetic Ingredient Review), EEC
Cosmetic Directives, FDA Monographs of sunscreens, antiperspirants and skin protectants treated as OTC, IFRA (International
Fragrance Association) and the Journal of the American College of Toxicology. Safety of cosmetics are reviewed by technical
experts in those organizations and are the only reliable results.Cosmetic industry is generally guided and motivated by the
consumers. Concerns of consumers are the principal challenges of the cosmetic industry. Scientific acceptability of complete
safety but adequate efficacy related to cosmetics is not thoroughly understood by the consumers and therefore the cosmetic
industry is under commercial pressure for some issues. Environmental Working Group (EWG) considering the user-friendly
resources is among the organizations affecting the consumers. Several materials which are with limited use (eg alpha hydroxy
acids, formaldehyde), fragrances and parabens challenging for the cosmetic industry will be discussed scientifically in this
presentation. It can be concluded that there is little scientific evidence to leading short and long-term health risks under normal
use conditions for cosmetic ingredients. More research is needed to better define any possible risks.
PL 25 A SUMMARY AND COMPARISON OF FOLK MEDICINAL PLANT USES IN CATALONIA (IBERIAN PENINSULA)
JOAN VALLÈS, AIRY GRAS, MONTSE PARADA, MONTSE RIGAT, GINESTA SERRASOLSES, TERESA GARNATJE
LABORATORIDE BOTÀNICA – UNITAT ASSOCİADA CSIC, FACULTAT DE FARMÀCIA, UNIVERSITAT DE BARCELONA, CATALONIA,
SPAIN
Catalonia occupies the north-eastern corner of the Iberian Peninsula, with an extension of ca. 30,000 km2 and ca. 7 million
inhabitants. Extended from the Pyrenees to the Mediterranean Sea and the Iberian arid plains, with altitudes going from sea
level to 3,144 m, this country holds a huge variety of landscapes, its vascular flora being constituted by approx. 2,500 taxa. The
own language, Catalan (co-official with Spanish), is shared with other areas of the Spanish, French, Italian and Andorran states. Its
location in a biodiversity hotspot and its cultural identity make this territory attractive for ethnobiological studies. From the end
of 1980ies, extensive ethnobotanical research is performed in this area, having led to numerous PhD theses and other academic
works, from which a high number of books and scientific papers have derived (see 1 and 2, and references therein for an idea).
In the late years, the research team on ethnobotany of the UNIVERSITY of Barcelona and the Botanical Institute of Barcelona
(www.etnobiofic.cat) is coordinating this research and is compiling the results in a database (to date internal for the group, with
a perspective of becoming of public access), some of which are starting to become accessible in the Catalonia’s Biodiversity
Database (http://biodiver.bio.ub.es/biocat). From ethnobotanical interviews to more than 900 informants, data have been
obtained of more than 1,000 vascular plant taxa with folk uses in the field of health, mostly medicinal and food ones, including
those in the interface of both activities. In this communication we present a summary of the state-of-the-art of pharmaceutical
ethnobotany in Catalonia, stressing the most used plants and the most addressed troubles, we analyse these data and compare
them with those of other territories, and we depict the perspectives for further research in this field.
References
1. Parada M, Carrió E, Bonet MÀ, Vallès J. Ethnobotany of the Alt Empordà region (Catalonia, Iberian Peninsula). Plants used in
human traditional medicine. J Ethnopharmacol 2009;124:609–618. 2. Rigat M, Vallès J, Iglésias J, Garnatje T. Traditional and
alternative natural therapeutic products used in the treatment of respiratory tract infectious diseases in the eastern Catalan
Pyrenees (Iberian Peninsula). J Ethnopharmacol 2013;148:411–422.
*This abstract has been orally presented in the Fourth International Meeting on Pharmacy & Pharmaceutical Sciences, Istanbul,
Turkey on 18-21 September 2014.
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PL 26 A REVIEW ON ETHNOBOTANY IN TURKEY
KERIM ALPINAR 1 GIZEM BULUT 2
1
KEMERBURGAZ UNIVERSITY, ISTANBUL, TURKEY
2
MARMARA UNIVERSITY, ISTANBUL, TURKEY
While the ethnobotanical research reveals some part of the cultural wealth, it is also possible to benefit from the conclusions
thereof. For instance, researches comprising the plants used in folk medicine can be of help to health issues in respect of their
results. Gathering the written information and recording the verbal transfer without them being lost enable us to comprehend
the place of the plants in our life and to benefit from them in various fields in the future. Richness in the plant diversity of Turkey,
which is a land for their settlement for thousands of years, has brought a big fund of knowledge about making use of the plants
along. There is an increase in the number of publications regarding this knowledge. Believing in the requirement of assessing
the information on the plants mentioned in the publications, part of which has the title of folk culture of a certain region, folk
medicine, folk medicines, regional folklore, the identity tags; all serious publications comprising the use of plants are being
worked up into a bibliography in order to give support to the researchers who will be using such knowledge in their further
researches. In order to make the aforementioned researchers save time and help in providing resources, information on 1200
publications is present in the bibliography which has been prepared by reviewing various references since 1993. Furthermore,
information about the attempts which were materialized as paper, data base and publication also exists in this paper. Based
on approximately 1200 researches existing in the references in the form of books, congress papers, and periodicals since 1928
-when the Latin characters were accepted- until the first half of 2014, the evaluation of Turkey with regard to these publications
involving ethnobotany has been made. Meanwhile, we think that it is not possible to carry out a reliable evaluation unless these
publications are gathered as an archive; however, the bibliography will serve the purpose, even if limited, as we could not find
a study in which the publications on ethnobotany in our country are been presented collectively up to the present.
PL 27 AN ETHNOBOTANICAL STUDY IN MARMARA ISLAND (BALIKESIR-TURKEY)
GIZEM BULUT
MARMARA UNIVERSITY
Marmara ısland is situated on the Marmara Sea and it covers an area of 117 km2 and its higest point is 700 m. There is no
previous ethnobotanical research on Marmara island. According to our ethnobotanical studies in 2009 and 2014, 50 vascular
plant taxa are used in the island. The usage of the plants are as follows: traditional folk medicine (13 taxa), food (22 taxa), fuel
(6 taxa), toys (5 taxa), herbal tea (4 taxa), and others (23 taxa). The results are compared with those of other ethnobotanical
researches perfomed in neghboring areas.
PL 28 USE OF MECHANISM-BASED EVIDENCE FOR THE DEVELOPMENT OF THERAPY FOR HUMAN CANCERS
WILLIAM W. AU
MPH EDUCATION CENTER AND FACULTY OF PREVENTIVE MEDICINE, SHANTOU UNIVERSITY MEDICAL COLLEGE, SHANTOU,
CHINA
Improved therapeutic protocols can be developed based on better knowledge of mechanisms for causation of cancers. For
cervical cancer, it is the second leading cause of cancer mortality among females in the world. Current therapeutic protocols
require surgery, and radiation and chemotherapy which rendered most patients infertile. We have investigated the possibility
of using gene therapy for treatment of cervical cancer. Specifically, we used a dominant-negative gene against estrogen and
transfected it into cervical cancer cells in vitro, using adenovirus as the delivery agent. Upon transfection of the gene into two
cancer cell lines, cells showed cell cycle arrest within 12 hours and the arrest occurred at the G1/S border. Other observed
changes were: inhibition of cyclin D1 expression, blockage of human papilloma virus E6 and E7 gene expression, activation
of caspase 3 and expression of apoptosis. Therefore, the transfected gene blocked estrogen activities leading to a cascade
of events towards apoptosis. The observed mechanism needs to be validated in vivo and then in patients. If successful, the
approach can be used as a new gene therapy protocol for cervical cancer.
Breast cancer incidence and mortality have been increasing rapidly in China recently. We have investigated the involvement
of risk factors and the mechanisms for the increase. From our survey of patients, we observed that both endogenous and
externally introduced life-style factors were involved. The former involved cooking with lard instead of vegetable oil. The latter
involved exposure to cigarette smoke and having sedated life style. Using our challenge assay, we observed that inherent and
functional DNA repair deficiency was the broad-based and important risk factor. The repair deficiency was independent of
the BRCA1 and 2 mutations. In addition, the repair deficiency was significantly associated with poor prognosis: lymph node
metastasis, negative expression of estrogen receptor, increased Ki-7 expression, having diabetes, and increased mortality. The
mechanism can be used to develop improved therapeutic protocol for breast cancer, e.g. personalized therapy.
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PL 29 TICKS, CRIMEAN-CONGO HAEMORAGIC FEVER AND PHARMACOLOGICAL PROSPECTS
AYSEN GARGILI
MARMARA UNIVERSITY, FACULTY OF HEALTH SCIENCES, ISTANBUL, TURKEY
Crimean-Congo hemorrhagic fever is a severe, often fatal zoonosis, caused by Crimean-Congo hemorrhagic fever virus (CCHFv;
family Bunyaviridae, genus Nairovirus). Among the tick-borne viruses, CCHFv is the most important cause of severe and fatal
human hemorrhagic disease, with mortality rates ranging from 5% to more than 70%. Disease is widely distributed in African
continent, Russia, Southern European and Middle Eastern countries. Since it has first been diagnosed in 2003, Crimean-Congo
haemorrhagic fever (CCHF) is an endemic disease in Turkey. Number of annual cases and death rates were around 800 and 5%
respectively, between 2004 and 2013. Farmers, people dealing with animal husbandry and health workers were determined as
risk groups in epidemiologic studies.
CCHF viruses are mainly transmitted by the bite of ticks of the genus Hyalomma. The virus has been repeatedly isolated and/
or detected in these ticks since 1960, when the virus was first detected in arthropods. The virus has also been detected in
species from other tick genera such as Rhipicephalus, Dermacentor, Ixodes and Ornithodororos. Nevertheless, it is unclear
what vector status each has and what role each plays in the maintenance of the virus. The ecology and epidemiology of CCHFV
is complex and largely depends on the tick vector species and the geographic area. CCHFV is maintained in a silent vertical
and horizontal transmission cycle involving ticks as vectors and reservoirs, and a variety of small feral and large domestic
mammals as vertebrate hosts. Small mammals, such as hares, hedgehogs, and rodents, and domestic ruminants, such as goats,
sheep, and cattle serve as viral amplifying hosts. With the exception of ostriches in South Africa, Aves are not considered to be
amplifying host for CCHFV. However, migrating birds serve as a source of blood meals for ticks, and therefore provide a mode of
dispersal of uninfected and infected ticks, which contribute to the spread and subsequent emergence of foci. Also, long distance
movement of livestock may contribute to the dispersal of CCHFV infected ticks.
Current studies showed that Hyalomma marginatum is the main (if not only) vector in Turkey. Some studies have addressed
the question of the distribution of ticks involved in the viral transmission in different regions of Turkey and pointed out the
importance of sylvatic cycles of virus amplification under natural conditions. In the last years, clusters of cases of CCHF in Russia,
Bulgaria, Albania and Greece have been also reported. However, the viral strain recorded in Greece (Europe 2 strain) is different
from other viral isolates in that region. Such an isolate was made from Rhipicephalus bursa ticks collected from goats in and
near Thessaloniki in 1975. Interestingly, this strain is the most divergent of all the CCHFv strains, including those isolated in the
neighboring Balkan countries of Albania, Kosovo, and Bulgaria.
Treatment regimes for CCHF infection are mainly supportive practices such as plasma and fresh platelet replacements. Only
known etiologic treatment option, Ribavirin, was reported to be highly effective at early stage (first 3 days) of infection. Along
with the vaccine studies there is a substantial need for the development of effective anti viral agents. Considering that the ticks
are the major transmitting factor, control of the tick population is also important for the fight against the endemic infections.
Although there are numerous acaricides commercially available for treatment of the tick infestations of domestic animals,
most of them have residual effects. There is still a need for the development of anti-tick agents with long term efficacy but not
residual in meat or milk. Another important issue is the protection of humans from tick-bites. For this aim, repellents seem to
be practical for protection and studies are needed for the development of harmless and long-term effective substances.
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PL 30 PHARMACISTS AND PHARMACEUTICAL CARE
J.W.FOPPE VAN MIL
COMMUNITY PHARMACIST & PROFESSIONAL SECRETARY OF THE PHARMACEUTICAL CARE NETWORK EUROPE
Pharmacy is part of healthcare, and pharmacists are health care professionals. Society has given pharmacists a mandate to care
for the medicine-related aspects of the population.
The profession is characterized by the fact that it links two areas of expertise: the provision of a medicine, the product, and
care for the patient. The pharmacist brings these two areas together and classes it as his domain. Within this domain, the
pharmacist makes his own independent assessments. This means that every pharmacist is a pharmaceutical care provider
with a typical identity, knowledge and specific core values. This in turn demands an autonomous definition of the knowledge
domain and, at the same time, establishing the core values. The basis for the knowledge domain of a pharmacist is (1) the
medicine, (2) the human body, and (3) the human behavior. Core values of pharmacists are (1) Commitment to the patient’s
well-being, (2) Pharmaceutical expertise, (3) Social responsibility, (4) Reliability and care and (5) Professional autonomy. As
a professional, pharmacists are independent, and maintain their own standards in their field of expertise. As health care
professionals, pharmacists should do no harm. The practice of pharmacy can be divided in three levels: a basic level of
production and distribution, a clinical level of issues relating to patients and pharmacotherapy in a broader sense, and a care
level (pharmaceutical care) of the care for the individual patient. The newer elements of the tasks of pharmacists, such as
counselling, medication reconciliation and review and therapeutic outcome monitoring are all part of ‘pharmaceutical care’.
In most countries, pharmaceutical care is now the new paradigm for the work of the pharmacist, certainly in community but
increasingly also in hospital.
With the increasing industrialization of the preparation and compounding of medicines, the modern community and hospital
pharmacists have more time to care for the individual patient, and thus to implement pharmaceutical care. In many studies it
has now been proven that the implementation of pharmaceutical care improves patient outcomes, on clinical, humanistic and
economic level.
PL 31 CLINICAL PHARMACIST COUNSELING IN CARDIOMETABOLIC DISEASE
SULE APIKOGLU-RABUŞ
MARMARA UNIVERSITY FACULTY OF PHARMACY - CLINICAL PHARMACY DEPARTMENT, ISTANBUL – TURKEY
Cardiometabolic disease, also known as the metabolic syndrome consists of interrelated risk factors which may lead to atherosclerotic cardiovascular disease and type 2 diabetes. The most frequently occurring risk factors include abdominal obesity,
hypertension, hyperglycemia and dyslipidemia. Also, some patients may display characteristics of prothrombotic and proinflammatory states. Patients with metabolic syndrome are more likely to develop some other conditions, such as polycystic
ovary syndrome, gallstones, asthma and sleep apnea. The main goal of the treatment is to mitigate or modify the risk factors
in order to prevent or delay the development of cardiovascular disease. The primary treatment modality is the establishment
and adoption of a healthy life-style. In circumstances where lifestyle changes are insufficient and for those at high risk of
cardiovascular diseases, drug treatment may be required. All components of the cardiometabolic disease are needed to be
treated to improve metabolic and cardiovascular consequences. Yet, this cannot be managed by a single drug. Patients would
be prescribed one or more of the drug classes of cholesterol-lowering, antihypertensive, antidiabetic and antiaggregant drugs.
Adherence is a growing problem with many drugs including the statins, antihypertensives and antidiabetics. Experts agree that
successful intervention requires more comprehensive patient education, with interdisciplinary coordination among healthcare
providers. Therefore, pharmacists have an essential role in the management of the cardiometabolic disease. They can assess
patient risk communicating cardiometabolic disease risk factors, plan and suggest patient-specific interventions, and identify
barriers to lifestyle modifications. They can help patients with adherence to health lifestyle and drug therapy as well as guide
them through cardiometabolic disease self-care process.
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PL 32 MEDICATION RELATED PROBLEMS IN GERIATRIC PATIENTS: THE ROLE OF PHARMACIST
BETUL OKUYAN
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY, FACULTY OF PHARMACY - TURKEY
The identification of inappropriate medication usage in elderly patients; which would tend to predispose medication related
problems resulting in adverse drug reaction, medication induced hospitalization and economic burden, presents significant
challenges for pharmacists when considering polypharmacy frequency in geriatric patients. Pharmacists should evaluate risks
and benefits of current medications by predicting possible medication related problems and defining individual requirements of
elderly patients towards their medications in order to optimize patient safety and enhance the benefits of therapy. Pharmacists
should comprehensively evaluate suitability of the present pharmacotherapy in geriatric patients with the means of well
defined and commonly used tools for elderly patients such as Beers’ Criteria. The STOPP and START criteria which have been
recently developed to identify potentially inappropriate medications and potential prescribing omissions respectively in elderly
patients can be used. Medication reconciliation program could be performed in transmission between different health care
settings and would give opportunities to pharmacists to provide accurate medication lists in geriatric patients. Individualization
is an important component, which improves the overall quality of pharmaceutical care. During the pharmaceutical care process
in geriatric patients, tailoring medication therapy to individual requires would optimize therapy outcomes and lower drug
related problem. As a result of physiological changes related to age in the normal aging process, alterations in pharmacokinetics
and pharmacodynamics should be also considered by pharmacists while using medications in geriatric patients. Patients with
Alzheimer’s disease and dementia are more likely to be non-adherence to their medications and also it is more difficult to
evaluate patient reported health outcomes in these patients. Pharmacists should provide individualized patient education in
geriatric patients especially ones with Alzheimer’s disease. To minimize unintentional non-adherence to medications in geriatric
patients, their physical ability especially manual dexterity and visual impairment and cognitive capacity should be assessed in
order to determine the appropriate medication dosage forms and simplify dose regimen complexity. Some medications (eg.
Alzheimer therapy) may cause undesirable effects which can impact on daily activities such as: falling down, constipation,
urinary incontinence, and cognitive impairment. Exposure to anticholinergic effects and sedative agents in elderly patients
should be also evaluated considering these medications are more likely to induce adverse outcomes especially on physical and
cognitive functions. The lack of knowledge regarding medication would also cause drug related problems, thus pharmacists
should periodically assess elderly patients’ knowledge and attitude towards their medications. A geriatric self-care plan should
be generated by the pharmacist especially for common conditions such as constipation, urinary incontinence and insomnia.
Pharmacist should consult about over counter medicines and dietary supplements, which are commonly used by geriatric
patients, in order to provide geriatric patients’ tolerability and safety.
PL 33 3D ANALYSIS OF THE BINDING SITE IMAGES FOR PREDICTING BINDING AFFINITIES IN DRUG DESIGN
ALI OSMAN ATAC 1 OZLEM ERDAS 1 FERDA NUR ALPASLAN 1 ERDEM BUYUKBINGOL 2
1- DEPARTMENT OF COMPUTER ENGINEERING, INSTITUTE OF NATURAL SCIENCES, MIDDLE EAST TECHNICAL UNIVERSITY,
ANKARA, TURKEY
2- DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY, ANKARA, TURKEY
Understanding the interaction between drug molecules and proteins is one of the main challenges in drug design. Several tools
have been developed recently to decrease the complexity of the process. Artificial intelligence and machine learning methods
have promising results in predicting the affinities. Recently, accurate estimations (CIFAP) have been performed by extracting the
electrostatic potentials from images of the drug-protein binding sites which were generated by autodocking simulator (1). In
this study, a new algorithm, which is a modified version of CIFAP, has been implemented to predict binding affinities of Caspase3
inhibitors.
Reference
1. Erdas O, Andac CA, Gurkan-Alp AS, Alpaslan FN, Buyukbingol E. Compressed images for affinity prediction (CIFAP): a study on
predicting binding affinities for checkpoint kinase 1 protein inhibitors. Journal of Chemometrics. 2013;27(6):155-164
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PL 34 RECENT ADVANCES IN PHARMACOTHERAPY
GUL BAKTIR
YENI YUZYIL UNIVERSITY, HEAD OF PHARMACOLOGY DEPARTMENT
The number of people living with severe chronic diseases is growing and as almost all chronic disorders develop gradually
over a certain period of time, changes are often irreversible until a level is reached where it could be diagnosed and treated
properly. For many acute and chronic disorders, current treatment outcomes are considered as being inadequate and severe
chronic conditions such as cardiovascular disorders, diabetes and cancer are treated after onset of the disease, frequently at
near end-stages. Predictive, preventive and personalized medicine (PPPM) is a new integrative concept in the healthcare system
that provides prediction of individual predisposition to a disease before its onset, to take targeted preventive measures and
offer personalised treatment principles tailored to the person. Identification of a person’s risk of developing a particular medical
condition, detection of the disease at a subclinical stage, when it is easier and less expensive to treat effectively, determination
of how individual patients react differently to diseases and to their treatments, stratification of patients for the optimal therapy
planning, prediction and reduction of adverse drug-drug or drug-disease interactions by more effective early assessment of
individual drug responses and to improve pharmacotherapeutic outcomes in acute and chronic diseases are among targets as
well as benefits of PPPM.
This presentation includes examples of novel personalized therapies providing important new treatments for patients in various
disease areas.
PL 35 NEW TREATMENT STRATEGIES IN PERIPHERAL NEUROPATHIES
SENA F. SEZEN1,2
1
KARADENIZ TECHNICAL UNIVERSITY SCHOOL OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, TRABZON, TR
2
JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE, BRADY UROLOGICAL INSTITUTE, BALTIMORE, MD, USA
Peripheral neuropathy (PN) refers to damage of the peripheral somatic or autonomic nerves. Although a variety of factors and
diseases cause PN, it commonly occurs due to traumatic injury, chemotherapy, and metabolic disorders. This presentation will
discuss the pathophysiology and treatment approaches of PN with an emphasis on diabetes-induced autonomic neuropathy
(DPN). DPN is a common complication of diabetes that leads to significant mortality and morbidity. It
is associated with axonal damage, blunted neuroregenerative capacity, and the loss of nerve function that control the
cardiovascular, gastrointestinal and urogenital systems. Hyperglycemia plays a major role in the development and progression
of DPN but is also affected by insulin deficiency, hyperlipidemia and numerous biochemical mechanisms including increased
oxidative/nitrosative stress, mitochondrial dysfunction and distrupted intracellular signalling pathways. Despite advances in
understanding the etiology, DPN treatment remains a challange with current therapeutics still having suboptimal outcomes.
Therefore, identifying novel therapeutic strategies remains a paramount and also an intense area of research. This presentation
aimed to review the current literature about the etiology of DPN, summarize the new advancements in experimental
therapeutics and briefly present new findings from our laboratory, which contribute toward understanding the mechanisms of
DPN and development of potential new treatments.
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PL 36 JAMMING BACTERIAL COMMUNICATION (“QUORUMSENSING”): A NEWAPPROACH TO THE CONTROL OF BACTERIAL
INFECTIONS
GULGUN TINAZ
DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Antibiotics, which act either by killing or inhibiting the growth of bacteria, are commonly used for the treatment of bacterial
infections. The inappropriate and indiscriminate application of antibiotics in pharmacotherapy has led to the development
of widespread bacterial resistance to these agents (1). The harsh selection for resistant bacteria, coupled with the lack of
investment in antibacterial research and development, has resulted in a steady decline in the efficacy of existing therapies.
Today, a global concern has emerged that we are heading a post-antibiotic era with a reduced capability to fight bacteria and
there is an urgent need for the discovery of novel antibacterial drug targets and treatment strategies. One such new target is
quorum sensing (QS). QS is a cell-to-cell communication system employed by a variety of Gram (-) and Gram (+) bacteria to
co-ordinate group behaviors as function of cell-density (2). The discovery that many pathogenic bacteria employ QS to regulate
their pathogenicity and virulence factor production makes the QS system an attractive target for antimicrobial therapy (3).The
disruption of QS systems of pathogenic bacteria may offer an avenue of alternative therapy.
Therefore, compounds with QS inhibitory activity hold great expectations for the treatment of infectious diseases in an era
where availability of effective antibiotics is no longer guaranteed. Furthermore, such compounds could potentially be used in
combination with conventional antibiotics to increase the efficiency of disease control and to extend the life span of current
antimicrobials. Additionally, inhibition of bacterial QS, rather than bactericidal or bacteriostatic strategies, offers a promising
way to overcome the bacterial resistance problem. It is assumed that targeting the pathogenesis instead of killing the organism
will apply a gentler selective pressure for the development of bacterial resistance.
References
1 Livermore DM. The need for new antibiotics. Clin Microbiol Infect. 2004; 10(Suppl 4):1-9.
2 Hentzer M, Givskov M. Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin
Invest. 2003;112: 1300-1307.
3 Rasmussen TB, Givskov M. Quorum-sensing inhibitors as antipathogenic drugs.Int J Med Microbiol.2006; 296:149-161.
PL 37 INTERFERENCE WITH BACTERIAL CELL-TO-CELL COMMUNICATION – A NOVEL STRATEGY TO COMBAT INFECTIONS
HARTMANN R. W.1,2
1
HELMHOLTZ-INSTITUTE FOR PHARMACEUTICAL RESEARCH SAARLAND (HIPS), CAMPUS C2.3, SAARBRUCKEN, GERMANY
2
PHARMACEUTICAL AND MEDICINAL CHEMISTRY, SAARLAND UNIVERSITY, CAMPUS C2.3, SAARBRUCKEN, GERMANY
The emergence and spread of bacteria resistant to current antibiotics are a serious and growing health problem worldwide.
In pursuing our objective to develop new strategies to combat resistance in bacterial infections, we have focused our interest
on the bacterial cell-to-cell communication. Among other infections, Pseudomonas aeruginosa causes severe pneumonia in
patients suffering from cystic fibrosis. It is difficult to be eradicated, especially when present in biofilms. Biofilm formation and
virulence factor production are regulated by intercellular signal molecules. A selective blockade of this so called quorum sensing
system is a novel therapeutic strategy to limit pathogenicity and is considered to delay resistance development. Two proteins
are targeted, PqsD, a key enzyme in the biosynthesis of the signal molecules PQS and HHQ and their receptor PqsR. Following
different approaches, structure-based1 and ligand-based2-4 via transition states analogs of the enzymatic reaction3-4, the first
PqsD inhibitors described so far were obtained. The nitrophenylmethanols were able to permeate the gram-negative bacterial
cell wall and inhibited signal molecule production and biofilm formation. Regarding PqsR, SPR biosensor experiments led to the
discovery of highly efficient binders with low molecular weights including antagonists5. Site-directed mutagenesis combined
with isothermal titration calorimetry led to insights into the binding mode. The first highly potent antagonists have been
developed by structural modification of the natural ligand6. After an unexpected functional inversion of these antagonists in
P. aeruginosa had been revealed, second generation PqsR antagonists were rationally developed and able to efficiently reduce
virulence factor formation7. One of these antagonists showed a strong reduction of P. aeruginosa pathogenicity in vivo.
References
1 Sahner et al, J. Med.Chem. 2013, 8656-8664
2 Weidel et al, J. Med. Chem. 2013, 6146−6155
3 Storz et al, J. Am. Chem. Soc. 2012, 16143-16146
4 Storz et al, ACS Chem. Biol. 2013, 2794-801
5 Zender et al, J. Med. Chem. 2013, 6761−6774
6 Lu et al, Chem. Biol. 2012, 381-390
7 Lu et al, Angewandte, 2014, 53, 1109 –1112
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PL 38 CHAPERONE-USHER PILUS ASSEMBLY MECHANISMS AND ANTIVIRULENCE THERAPEUTICS
ENDER VOLKAN 1 SCOTT HULTGREN 2
CYPRUS INTERNATIONAL UNIVERSITY
1
WASHINGTON UNIVERSITY IN ST. LOUIS, SCHOOL OF MEDICINE
2
Chaperone-usher pili are adhesive, filamentous, rigid, polymeric protein appendages assembled on surfaces of pathogenic
bacteria. P- pili, assembled by uropathogenic Escherichia coli are virulence factors in urinary tract infections (UTIs). In Gramnegative bacteria, assembly of P-pili requires the crossing of subunits through the inner membrane, the periplasmic space
(with the help of the chaperone PapD to fold correctly) and assembly into an ordered structure at the outer membrane.
These appendages are required to bind host surfaces and establish infection; so their inhibition is a way to prevent infection.
Antivirulence therapeutics named ‘pilicides’ are bicyclic 2-pyridones designed to inhibit P-pilus biogenesis by binding the
chaperone protein (PapD) in uropathogenic Escherichia coli. Using coomassie blue stained SDS-PAGE gels and Western blotting,
our studies indicate that upon in vitro incubation of purified pilus subunits with certain pilicides at 2x or 100x molar excess
concentrations, the polymerization of P-pilus subunits (PapE) that form the tip section of the pilus is disrupted. These pilicides
likely induce non-productive aggregation of PapDE subunits as demonstrated by smears on Western blotting analysis. Electron
microscopic examination of PapDE incubated plus or minus pilicide revealed that the non-productive PapE aggregates induced
by pilicide were altered morphologically compared to PapE tip polymers. Some high molecular weight bands were consistent
with a PapD dimer, suggesting that disruption of PapE polymerization may be via formation of unproductive PapD dimers. These
findings indicate that studies on chaperone-usher pili can help improve our approaches of designing antivirulence therapeutics
for treatment of infections, while steering clear from antimicrobial resistance.
PL 39 NEW TRENDS IN QUALITY OF PHARMACEUTICALS
N. BUKET AKSU
CORPORATE RELATIONS DIRECTOR AT SANTA FARMA PHARMACEUTICALS, TURKEY
Pharmaceutical product development knowledge is intensive, and the product development process is quite complex. Recently,
the drug industry has experienced major developments in production information, quality management systems and risk
management and has developed modern production tools that can assist in ensuring the production quality. Since decades,
adoption of systematic approaches for developing products with robust quality, enhanced resource economics and improved
process capability has yielded high fruition in several technology-driven industries. The pharma industry, however, was quite
late in adopting the systematic approaches. Despite continuous innovations in the pharma industry for developing futuristic
new drugs and drug products, there has been a repeated set back owing their poor quality and manufacturing standards. With
the consequent growing concern and criticism, in this regard, the ICH instituted a series of quality guidances like Q8, Q9, Q10
and Q11, all emphasizing the adoption of systematic principles of Quality by Design (QbD) and Process Analytical Techniques
(PAT).
ICH aims to produce a single set of technical requirements for the registration of drug products and hence the development
process. Its objective is to improve efficiency of new drug development and registration process It is accomplished through
the development and implementation of harmonized guidelines and standards. Thanks to ICH for leading us to the discussion
regarding all the guidelines and Q8 (Pharmaceutical Development), Q9 (Quality Risk Management), Q10 (Quality System).
The new guidelines help industry professionals and regulators improve efficiency and flexibility while maintaining high quality
standards. ICH Q8 is related to design a quality product and manufacturing process and deliver consistent performance. It is
collation of knowledge establishing the rationale for type of dosage form, formulation proposed is suitable for the intended
use, proces and product understanding. ICH Q8 is an opportunity to present the knowledge gained through the aplication of
scientific approaches to product and process development (scientific understanding). ICH Q8 guideline supports knowledge
gained through the lifecycle of a product and using scientific approaches and quality risk management principles. Within
the scope of ICH Q8, an important step in the QbD approach to the development of drug products requires a distinction
between critical and non-critical product attributes and process parameters. ICH Q9 is a systematic process for the assesment,
control, communation and review of risks to the quality of the drug product across the product lifecycle. A process which
includes assessment, control, comunication and review of risk consisting of well defined steps which, when taken is sequence,
support better decision making by contributing to a greater insight into risks and their impacts. ICH Q10 guideline describes
a comprehensive approach to an effective pharmaceutical quality system based on ISO concepts, includes applicable current
GMP regulations including GAMP (Good Automated Manufacturing Practices), and complements ICH Q8 and ICH Q9. If the
principles described in the ICH Q8, Q9 and Q10 guidance documents are implemented together in a holistic manner, then an
effective system that emphasizes a harmonized science and risk-based approach to product development and maintenance is
in place. This provides an even greater (quality) assurance that the patient will receive product that meets the critical quality
attributes (CQA)
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As QbD approach embarks upon science and risk-based understanding, it helps in developing quality products rather than
building quality into the products, with minimal investment of time, money and resources, eventually leading to cost reduction
and faster market access. Various guidelines like ICH Q8- Q11, in this regard, are highly helpful for guiding the product
development scientists. Quality risk management (QRM) and science-based knowledge management are the two key elements
of QbD. QRM primarily focuses on the systematic and structured planning of reviews and inspections. QRM must be an integral
element of the pharmaceutical quality system to meet the predefined quality of the drug products as per the regulators and
consumers point of view. On the other hand, the science-based knowledge management system relies on decision making
regarding review and inspections, and for accomplishing desired cGMP compliance to the manufacturer. It provides thorough
and thought-through analysis of the concept by sharing of data and information to develop the products and processes
understanding. Target Product Profile (TPP) describes the general objective of the product development program and provides
information about the development works. TPP includes concepts that are required on the label of the pharmaceutical product.
TPP is a patient and labeling based concept and can be considered as the “user interface” of the ready-made pharmaceutical
product. Therefore, TPP is expected to be the same for a generic and the reference product. A generic product may use a
different formulation or design for applying the TPP. Many features of TPP are restricting or determining works of formulation
and process development researchers. Among them there are route of administration, form and amount of dosage, maximum
and minimum doses, presentation of pharmaceutical product and target patient population. Quality Target Product Profile
(QTPP) is a summary of product quality and relevant features and characteristics and thus aims to guarantee product efficacy
and safety. QTPP constitutes the basis of product development and begins by “design in the mind”. QTPP is a sub-branch of
the TPP published by the FDA and is focused on the chemistry, production and control phases of development. QTPP, defines
quantitative targets for features of a pharmaceutical product (such as dissolution, potency, impurity and stability). Also, it
includes specifications such as drug delivery dosage form, route of administration, packaging, appearance and diagnosis.
Critical Quality Attributes (CQAs) are the physical, chemical, biological and microbiological characteristics that should be directly
or indirectly controlled in order to meet the QTPP and ensure product quality. CQA is generally related to active substance
and excipients, intermediate products and finished products. The performance of CQAs depends on the independent product
and process variables called as material attributes and process parameters. Critical Process Parameters (CPPs) are process
parameters with variability effective on critical quality feature(s), therefore they should be monitored and controlled in order
to achieve required quality. The parameter expresses a characteristic of a system or process that is measurable or countable.
These parameters are usually considered as features related to processes such as temperature, mixing speed, mixing time,
type of stirrer, etc. Separating characteristics or parameters as critical or non-critical is an important result of the development
process. Among the several process parameters, the non-critical and critical process parameters are classified which actually
affect the product quality. If the real change in a parameter does not meet QTPP of the product, then that parameter is critical.
Accordingly, whether a parameter is critical or not depends on the extent of the considered change. In the development of
a design space, the important point in activity is proving or determining that uncategorized parameters left outside Design
of Experiments (DoE) are really non-critical process parameters and that this is the reason for their non-interaction. Before
starting to generate a design space, effort must be shown to reduce the number of unclassified process parameters. A screening
DoE can be carried out on this, to exclude meaningful interactions among process parameters. Single variable ranges are
appropriate for non-critical parameters and they can be added to the design space without any extra works, when there are no
interactions among them. Selection of correct instruments for developing design space can depend on various factors such as
complexity of the evaluated system, precision, relevant scientific information and company preference. There is no single tool
or approach that is ideal for all cases. Very valuable information can be obtained from all of them, there are certain reasons to
aid in determining which tool is to be used. Realizing the restricting features of today’s pharmaceutical product development
approaches, the FDA, together with the ICH has supported the concept of “Quality by Design”. Accordingly design space has
started to gain an important place in the pharmaceutical industry. Design space is defined as “multi-dimensional combinations
and interactions of input material variables (i.e. material features) and process parameters with proven assured quality”. Design
space is specific to a single unit operation, multiple unit operation or a single manufacturing process and defines operational
process parameters that are known to affect product quality. Design spaces can be considered as the link between CQAs
and CPPs. Design space (DS) is a production space provided by the control of critical parameters that are determined by the
formulation and manufacturing process. In addition, as stated in the ICH Q8 guidelines, working within this DS is not considered
a change. Process Analytical Technology (PAT) is a system for designing, analyzing, and controlling manufacturing through timely
measurements of critical quality and performance attributes of raw and in-process materials and processes with the goal of
ensuring final product quality. PAT brings a systems perspective to the design and control of manufacturing processes. Scientists
from Development, Manufacturing, Quality and Engineering will be able to engage with regulators to turn Q8, Q9, and the
imminent Q10 into a cross-functional and practical reality, helping to shape the future thinking of the industry. Regulators will
be present to listen to audience views and to provide their perspective.
As an example for QbD; in order to evaluate the QbD principles, Ramipril was used as a model drug and produced tablets
were designed with the application of INForm v.4 ANN which is a program using neural networks. The Program covers not only
neural networks with different backwards distributing algorithms, but also genetic algorithm, fuzzy logic, statistic methods and
graphical visualization. The results of the tablets manufactured by direct compression containing respectively MgSt and SSF
were evaluated by the program. The program provided the model properties for each tablet property. With reference to the
data obtained, all required measurements and evaluations were performed and the CQAs (tablet hardness, dissolution in 30
minutes, assay, impurity C and impurity D) were determined upon risk control.
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The results of the tablets manufactured by direct compression containing respectively MgSt and SSF were evaluated by the
program. The program provided the model properties for each tablet property. With reference to the data obtained, all required
measurements and evaluations were performed and the critical quality attributes (tablet hardness, dissolution in 30 minutes,
assay, impurity C and impurity D) were determined upon risk control. The objective of the study was to optimize ramipril
tablet formulation manufacturing by direct compression method, that complying with predefined specifications, by using
ANN program and QbD principles. Tablets prepared as optimized formulation analyzed and as a conclusion all the parameters
defined as critical quality attributes were in the range of specification limits. This study showed that a huge amount of detailed
data for QbD studies could be gained from ANN programs, that could not obtained with the routin R&D experiments QbD
applications allows for understanding critical and non-critical parameters in developing design space, provides opportunity for
focusing on important parameters in product quality in validation works. As the control range where product and process are
not affected, are better understood than a range generated only empirically, a wider validation acceptance criteria is achieved.
Product quality cannot be tested at the end of manufacturing process using QbD approach, but quality is designed at product
design phase and quality is embedded in the product. Rather than controlling quality, quality assurance is ensured, which is
more superior. Development and innovation are hindered because of processes and systems that are not changed. However,
with the design space brought by QbD, flexibilities such as real time release have become a part of the process. Because of
these changes, operability of the processes has been proven and reliance on the system has increased.
Testing of quality in process begins as the process is halted and testing is removed. Controls have been carried out based on
critical features in the process and changes made in relation to these have been managed and the process has been continuously
advanced. As continuous process improvement has become possible, an approach implementation has come where process
performance intended for process validation is continuously monitored, evaluated and adjusted.
Most importantly, other than these, this new approach has allowed for acting and decision making with scientific and risk based
information.
PL 40 EVALUATION OF HEXAGONAL BORON NITRIDE (HBN) AS A NEW TABLET LUBRICANT
TIMUCIN UGURLU
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, ISTANBUL, TURKEY
It is rare to find a solid oral dosage product consisting of drug alone. To produce a final product that is not only practical and
convenient to handle but also facilitates patient compliance, the drug substance needs to be processed with other excipients.
The drug “fillers” or “excipients” serve many purposes in the formulation. One class of functional excipients that is essential
in the most tablet formulations is “lubricants”. Lubricants are pharmaceutical excipients that decrease friction at the interface
between a tablet surface and the die wall during ejection and reduce wear on punches and dies, prevent sticking to punch
faces, improve the fluidity and filling properties and manufacturing efficiency of solid preparations. However, since most of
the lubricants have hydrophobic characters, they have deteriorating effects on tablet properties. The deteriorating effects are
due to formation of a hydrophobic layer on particles of powder during mixing process. If the concentration of a lubricant is too
high, or the mixing time is too long, the potential problem will be decrease in tablet hardness, inability to compress into tablets,
increase in tablet disintegration time and a decrease in dissolution rate. To get rid of negative effects of lubricants an alternative
lubricant was used in our study.
The objective of our study was to investigate the lubrication properties of hexagonal boron nitride (HBN) as a new tablet
lubricant and compare it with conventional lubricants such as magnesium stearate (MGST), stearic acid (STAC), and glyceryl
behenate (COMP). Tablets were manufactured on an instrumented single-station tablet press to monitor lower punch ejection
force (LPEF) containing varied lubricants in different ratio (0.5, 1, 2%). Tablet crushing strength, disintegration time and thickness
were measured. Tensile strength of compacted tablets were measured by applying a diametrical load across the edge of tablets
to determine mechanical strength. The deformation mechanism of tablets was studied during compression from the Heckel
plots with or without lubricants. MGST was found to be the most effective lubricant based on LPEF—lubrication concentration
profile and LPEF of HBN was found very close to that of MGST. HBN was better than both STAC and COMP. A good lubrication
was obtained at 0.5% for MGST and HBN. Where COMP and STAC showed 35% more LPEF compare to that of MGST. Even at the
concentration of 2% COMP and STAC did not decrease LPEF as much as 0.5% of MGST and HBN. Like all conventional lubricants
the higher the concentration of HBN the lower the mechanical properties of tablets because of its hydrophobic character.
However, this deterioration was not as pronounced as MGST. HBN had no significant effect on tablet properties. Based on the
Heckel plots, it was observed that after the addition of 1% lubricant granules showed less plastic deformation. As a result our
studies showed HBN can be used as a new lubricant in tabletting technology
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PL 41 CLINICAL TRIALS; FROM LABORATORY TO PHARMACY
ASLIGUL KENDIRCI
MENA & TURKEY CLINICAL OPERATIONS HEAD ROCHE ISTANBUL, TURKEY
A clinical trial is a research study conducted in human beings with the goal of answering specific questions about new therapies,
vaccines or diagnostic procedures, or new ways of using known treatments. Clinical trials are used to determine whether new
drugs, diagnostics or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way
to find treatments that help people.
After researchers test investigational new therapies or procedures in the laboratory and in animal studies, those with the most
promising possibilities are moved into human clinical trials. Clinical trials are broken down into different phases. During a trial,
more and more information is gained about the potential treatment, its risks and how well it may or may not work, along with
aspects related to quality of life.
Clinical trials are categorized as Phase I to IV trials. They are generally described as follows:
Phase I (small number of participants, normally between 6-10 healthy volunteers, or very sick patients for whom treatment
options are lacking)
Phase I studies are designed to allow scientists and medical doctors to understand what effects an investigational compound
has in human subjects.
Phase II (once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger
groups of patients, generally 20-300 depending on the type of disease)
Phase II studies are designed to begin to evaluate the safety and efficacy of an investigational medicine in patients, and often
used to determine if different dosages of the treatment have different effects
Phase III (carried out on large patient groups, 300–3,000 or more depending upon the disease being studied)
Phase III studies are designed to confirm the safety and efficacy of an investigational medicine. Large numbers of patients are
generally involved in order to adequately confirm benefit and safety.
Phase IV (also known as Post-Marketing Surveillance Trials)
Phase IV studies take place after the medicine has received regulatory approval (market authorization) and are designed to
provide broader efficacy and safety information about the new medicine in large numbers of patients, subpopulations of
patients, and to compare and/or combine it with other available treatments.
Clinical trials are an integral part of the drug and diagnostics discovery and development process. Before a new medicine
or diagnostic test can be made available, evidence of its safety and effectiveness must be provided by well-designed, wellcontrolled, and carefully monitored clinical studies in patients consenting to participate.
To develop a product from laboratory to Pharmacy takes 12-15 years and costs about 1.3 Billion dollars.
PL 42 DRUG AND PERSONAL CARE PRODUCT CONTENT OF WATER. IS IT IMPORTANT FOR HUMAN HEALTH?
AHMET AYDIN
YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF TOXICOLOGY
The contamination of water resources with chemicals due to pharmaceuticals and personel care products attracts attention
recently. US Environmental Protection Agency handled this case as Pharmaceuticals and Personal Care Products (PPCP) in water.
All drugs prescribed for a special disease in human and VETERINARY purposes and cosmetic ingridients including the fragrances
(musks) in toiletory products and the ultraviolet filters in sunscreens are covered by PPCP explanation. The contribution of
these products to chemical burden of surface and underground water is due to excretion from the body as parent molecule
or metabolite and bathing. Improper disposal of expired pharmaceuticals like draining into sewage is another threat for our
water resources. Drug factories are another potential source for the contamination of water with pharmaceuticals. Available
water treatment systems are not effective to eliminate PPCPs. Some ecological toxic effects are caused by PPCPs in water
system, but human health risks are not known properly. Most pronounced health effects of PPCPs are antibiotic resistance and
endocrin function impairment. Many other PPCPs have unknown consequences. Following drug classes have a great concern
for their potential unwanted health effects exposure via water resources: Antimicrobials, estrogenic steroids, antidepressants,
calcium-channel blockers, antiepileptic drugs, multi-drug transporters (efflux pumps), musk fragrances. Even if the level of
these pharmaceuticals in drinking water is low, special attention for vulnerable individuals is taken account.
Stem cells are undifferentiated cells with the high capacity to undergo self-renewal by asymmetric mitotic division. The main
characteristics of stem cells that make them extremely appealing for cell therapy are their capacity for self-renewal. By this
way, stem cells keep their ability to multiply while remaining undifferentiated and thus enabling constant. Further wit their
differential capacity they are important tool for active replacement of cell population in tissue, and differentiate into variety of
distinct cell type.
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PL 43 STEM CELLS IN MEDICAL TRAINING
TUNC AKKOC
MARMARA UNIVERSITY FACULTY OF MEDICINE, DEPARTMENT OF PEDIATRIC ALLERGY-IMMUNOLOGY, TURKEY
Stem cells can be divided into two main groups by site of origin as embryonic stem cell (ESCs), which are derived from inner
mass of blastocytes, and adult stem cells (ASCs), which are obtained from umblical cord blood, bone marrow, peripheral
blood, adipose tissue, dental and present specific tissue and organs throughout the adult body.
There are special terms which shows the capability of stem cells in differentiation. Most potent one is Totipotent stem cells which
capable of originating an entire organism, as they are able to generate extraembriyonic tissue such as placenta. Pluripotent
stem cells, in turn, able to differentiate into cells from any of three primary germ layers (ectoderm, endoderm and mesoderm,
primordial tissue formed in the early stages of embriyonic development that will later originate all other tissues in the body).
Unlike totipotent cells, pluripotent cells cannot grow an entire organism, as they are incapable of generating extraembryonic
tissues.
Bone marrow hematopoietic stem cells (HSCs) were the first ASCs to be studied and, consequently, are the best characterized.
These cell are capable of differentiation into the myeloid and lymphoid components of blood, and their transplantation has
long has long been used to great effect in the treatment of bone marrow failure and cancer. Another type of ASC present in
the bone marrow, but distinct properties from those of HCSs, was later isolated: mesenchymal stem cells (MSCs), also known
as stromal cells. As reported at the time of their discovery by friedenstein in the 1970s, MSCs are highly plastic adherentand
are similar to fibroblasts. As multipotent stem cells, MSCs can differentiate into cells derived from the mesoderm germ layer,
namely chondroblasts, adipocytes and osteocytes. As they inhibit proliferation and cytotoxic action of immune cells, MSCs have
been employed in the clinical treatment of several diseases, including graft versus host disease (GVHD) in its acute form. In
ClinicalTrials.gov database 31 studies were designed to test MSCs in the treatment of GVHD.
PL 44 HYPERCOAGULABILITY IN OVARIAN CANCER: LABORATORY AND CLINICAL PERSPECTIVES
SARFRAZ AHMAD
FLORIDA HOSPITAL CANCER INSTITUTE, DEPARTMENT OF GYNECOLOGIC ONCOLOGY, UNIVERSITY OF CENTRAL FLORIDA AND
FLORIDA STATE UNIVERSITY, COLLEGES OF MEDICINE,USA
Cancer represents a major cause of overall mortality, second only to cardiovascular events. Coagulation abnormalities are often
encountered in cancer patients, which are typically manifested by a low-grade form of disseminated intravascular coagulation
(heightened clotting activation, and therefore considered as “hypercoagulable”). Factors that contribute to the activation of
coagulation in cancer primarily include non-specific mechanisms such as tissue damage and inflammatory responses, and
prolonged immobilization, especially during hospital stay. Furthermore, coagulation may be induced by such treatments as
chemo- and/or radio-therapy. A significant number of cancer patients encounter complications of thromboembolic and/or
bleeding disorders. Among others, ovarian cancer is a leading cause of death from gynecologic malignancies in women. Unlike
breast cancer in which a significant progress has been made for early detection thereby saving lives, a majority of women
with advanced-stage ovarian cancer die because early-stages have no obvious symptoms. Furthermore, in the recent past no
affordable screening test has been approved that could have proven to be effective in the early diagnosis of the disease. Ovarian
cancer patients are significantly more likely to develop a blood clot and associated thromboembolic episodes. One would
expect that patients with this devastating disease to have a significantly higher level of clotting and platelet activation than the
subjects with benign tumors and healthy volunteers. There are several crucial laboratory markers/tests that can potentially
predict the hypercoagulability in a given subject/specimen. The hypercoagulability may be best correlated with the highest
levels of the activation markers in patients with advanced-stage and recurrent disease. Lower levels of clotting activation can be
expected in patients with ovarian cancer that are treated with polypharmocologic low-molecular weight heparins (LMWH) and
designer heparinomimetics, thereby minimizing the potential of hypercoagulable state. These understandings may improve
the rationale for novel anticoagulant therapy in select patients, and point the way to more targeted use of LMWH in studies
designed to prolong survival and delay/prevent the disease progression in women with ovarian cancer. This presentation will
provide an objective account of the laboratory and clinical perspectives that appropriate pre-operative coagulation and platelet
activation markers’ analysis in patients with ovarian cancer may be helpful towards the assessments of the relative risk of
thromboembolic events.
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PL 45 GENE SILENCING MOLECULES AND USING IN THERAPY
EMINE SALVA
DEPARTMENT OF PHARMACEUTICAL BIOTECHNOLOGY, FACULTY OF PHARMACY, INONU UNIVERSITY, MALATYA, TURKEY
The knockdown of genes is an important research area in pharmaceutical biotechnology. The down-regulation of genes can be
achieved either at the transcriptional or post-transcriptional levels. The sequence-specific gene silencing effect is known as RNA
interference (RNAi). RNAi is a highly promising technology using in the gene therapy applications to inhibit the expression of
pathologically relevant genes and can be very useful for the development of new drugs based on a gene inhibition expression
effect. There are four major anti-mRNA strategies; firstly single-stranded oligodeoxynucleotides (ODNs) with 18-20 bases in
length that inhibit the translation of mRNA into protein through Watson-Crick hybridization to targeted mRNAs; secondly
ribozymes with around 30 nt as RNA cleaving pharmaceuticals; thirdly microRNAs, naturally occuring small non-coding RNA
molecules with 20-24 nt that function post-transcriptional regulation of gene expression by binding to the 3’ untranslated
regions of their target mRNAs and finally the siRNAs that able to recognize the target mRNA with a high specificity through a
base pairing complementary sequence process resulting in the degradation of the target mRNA by intracellular nucleases.
The therapeutic applications of antisense molecules are as antiviral and anticancer agents, in central nervous system
therapeutics, in inflammation or cardiovascular therapeutics. Compared to the conventional drugs (e.g., low molecular weight
inhibitors, therapeutic antibodies), gene silencing molecules can be specifically targeted and inhibited in protein expression
in cell and also, the synthesis of these molecules does not require cellular expression system, complex protein purification or
refolding and is relatively uncomplicated. Therefore nucleic acid-based strategies may offer novel therapeutic approaches in
various pathologies including viral diseases and cancer. The efficient gene delivery becomes a primary prerequisite for gene
silencing in mammalian systems but there are some challenges which restrict its application. First challenge is the potential for
an ‘’off-target’’ effect. Second challenge is ‘’immune stimulation’’ during antisense therapy. Delivery of antisense molecules
during the therapy is also an important challenge in therapy. To overcome of these challenges, an appropriate delivery systems
are needed.
Viral and non-viral delivery systems protect antisense molecules from degradation and facilitate uptake by target cells. The
development of suitable carrier systems for delivery of antisense molecules raise considerable hope to bring into clinics novel
tharapeutic RNAi-based concepts in human.
PL 46 CHEMOTHERAPY RESISTANCE: CANCER GENETICS ON BEHALF OF CLINICAL THERAPY
BETUL KARADEMIR
DEPARTMENT OF BIOCHEMISTRY, MEDICINE FACULTY / GENETIC AND METABOLIC DISEASES RESEARCH AND INVESTIGATION
CENTER, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Proteasomal degradation is crucial to prevent the accumulation of cellular damage. The removal of the damage is a required
process for healthy organisms to keep the integrity while in cancer cells this situation may induce drug resistance. Regarding
chemotherapy for the cancer treatment, degradation mechanisms such as proteasomal system and autophagy have been
focused recently and proteasomal inhibition in cancer cells have been shown to induce autophagy. This induced pathway
may prevent the cancer cells from death or can cause autophagic cell death which is an important reason for chemotherapy
resistance. There are many preclinic studies to improve the results and on the other hand heat shock proteins are accepted
to be protective which may bring new approach. In our laboratory, several cancer cell lines have been tested from different
aspects of proteasomal activity. HCT116 colon cancer cell line was used to test the role of HSP70 and proteasome inhibition
on autophagic cell death. In this direction, heat shock treatment has been applied to the cells which is also an applied process
for cancer patients. Cell viability, proteasome activity, degradation of long-lived proteins, and the expressions of HSP70, LC3,
beclin1, caspase 9 and PARP have been analysed. Additionally, mouse hippocampal cell line is used to test the proteasomal
activity in relation to heat shock proteins which highlighted another important point for the chemothrapy resistance with
antioxidant gene expressions. Different breast cancer cell lines have also confirmed the role of proteasomal degradation in the
failure of chemotherapy.
Supported by TUBITAK COST-CM1001-110S281
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PL 47 NANOSCALE DRUG DELİVERY SYSTEMS AND THE BLOOD-BRAIN BARRIER
YILMAZ CAPAN
HACETTEPE UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, TURKEY
Drug delivery to the brain poses a major challenge due to the blood brain barrier (BBB). Thus, several strategies have been
developed to overcome the BBB and to achieve successful brain drug delivery. Certain endogenous molecules, such as insulin or
transferrin, do cross the blood-brain barrier via a process of receptor-mediated transcytosis (RMT). Our approach is to describe
the development of a chitosan nanoparticle carrier system, functionalized with poly(ethylene glycol) (PEG) and monoclonal
antibody targeted to the brain for the delivery of a caspase-3 inhibitor and basic fibroblast growth factor (bFGF). The inhibition
of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. On the other hand, growth
factors (e.g. bFGF) suppress cell death by acting at several points on death pathways and, additionally, promote regeneration.
These features make them promising agents for treatment of the neurodegenerative diseases. However, these large peptides
also cannot penetrate the brain tissue when systemically administrated. Thus, the development of an effective delivery system
is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (SA)-biotin (BIO)
technology, we describe here the design of chitosan (CS) nanospheres conjugated with PEG bearing the CD 71 monoclonal
antibody whose affinity for the transferrin receptor (TfR) may trigger receptor-mediated transport across the BBB. These
functionalized CS-PEG-BIO-SA/CD71 nanoparticles (NPs) were characterized for their particle size, zeta potential, drug loading
capacity, and release properties. Fluorescently labeled CS-PEG-BIOSA/CD 71 nanoparticles were administered systemically to
mice in order to evaluate their efficacy for brain translocation. The results showed that an important amount of nanoparticles
were located in the brain, outside of the intravascular compartment. These findings, which were also confirmed by electron
microscopic examination of the brain tissue, indicate that this novel targeted nanoparticulate drug delivery system was able to
translocate into the brain tissue after i.v. administration. Consequently, these novel nanoparticles are promising carriers for the
transport of the anticaspase peptide Z-DEVD-FMK and bFGF into the brain.
PL 48 POLY(LACTIC-CO-GLYCOLIC ACID) BASED DRUG DELIVERY DEVICES FOR TISSUE ENGINEERING AND REGENERATIVE
MEDICINE
OYA KERIMOGLU
MARMARA UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY HAYDARPAŞA ISTANBUL,
TURKEY
Poly(D,L-lactide-co-glycolide) (PLGA) is the most frequently used biodegradable polymer for developing nano/microparticles
encapsulating therapeutic drugs in controlled release (CR) applications. PLGA based drug delivery devices have several
advantages over the conventional devices. One of the advantage is the extended release rates of drugs up to days, weeks or
months. Other reasons for the widespread use of PLGA are its biodegradability, its biocompatibility, and the fact that PLGA has
been approved by FDA (Food and Drug Administration). PLGAs are commercially available with very different phys¬ico-chemical
properties, and that the drug release profile can be tailored by selecting PLGAs with the appropriate properties, such as
molecular weight (Mw) and the lactide: gycolide ratio. Numerous active pharmaceutical ingredients such as anti-cancer drugs,
analgesics, antibiotics and macromolecular drugs such as proteins, peptides, genes, vaccines, antigens, human growth factors,
vascular endothelial growth factors etc., are successfully incorporated into PLGA or PLGA based drug delivery devices. PLGA has
been used by several research¬ers in tissue engineering, vascular engineering, nerve regeneration, cartilage tissue engineering
and bone tissue engineering. According to various research, PLGA has been shown to be a successful biode¬gradable polymer
as a controlled release system and a drug delivery device for tissue engineer¬ing and regenerative medicine.
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PL 49 MAJOR CHANGES IN CLINICAL PHARMACY EDUCATION AND PRACTICE
SIDNEY J. STOHS
FACN, CNS, ATS, FAPHA, DEAN EMERITUS, CREIGHTON UNIVERSITY, OMAHA, USA
Major changes have occurred in pharmacy education and practice over the past 60 years. Major changes and advancements
have occurred with respect to the kinds and complexities of drugs available. Furthermore, pharmacy has evolved from a
practice devoted to compounding and patient care, to dispensing, to clinical pharmacy and drug information management, to
pharmaceutical care, and most recently to medication therapy management. Each of these terms and phases will be addressed.
Pharmacy education has similarly evolved from an educational system with a heavy focus on laboratory and dispensing skills to
a greater focus on drug information, patient care, and disease state and medication therapy management skills. The changes
that have occurred in pharmacy education with respect to courses and laboratories now taught will be reviewed. The role of
billing for clinical services to a third party payer and its importance to the future of pharmacy will also be considered.
PL 50 THE IMPORTANCE OF CLINICAL ROUNDS IN CLINICAL PHARMACY EDUCATION
FIKRET VEHBI IZZETTIN
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY, FACULTY OF PHARMACY, TURKEY
Clinical pharmacy is defined as that area of pharmacy concerned with the science and practice of rational medication use
(1). Pharmaceutical care is the responsible provision of drug therapy for the purpose of achieving definite outcomes that
improve a patient’s quality of life (2). Clinical rotation (round) and practice-based education is important to increase the level
of knowledge.By increasing the exposure of pharmacist or pharmacy students to patients and medical team in their education,
it will help for better understanding of patients, their diseases and drug therapy and will enhance communication skills. In
clinical rotation, pharmacy students will gain a knowledge about: general information about disease, sign and symptom,
drug therapy, non-pharmacological alternatives, side effect, administration, prevention and treatment of adverse reactions,
monitoring, drug-related problems. Introducing clinical rotation to pharmacy education needs reducing the laboratory hours
from traditional pharmacy education program. Because the knowledge gains form the laboratories are more product oriented
and not used in future pharmacy practice. And this leads to waste of time and energy. The important of clinical rotation will be
discussed through case presentation. Clinical rounds are an ideal opportunities for the students to learn and apply these patient
oriented services.
References
1-
The Definition of Clinical Pharmacy. Pharmacotherapy 2008;28(6):816-817
2-
Hepler C.D. Strand L.M. Opportunities and responsibilities in pharmaceutical care. American Journal of Hospital
Pharmacy, 1990 vol 47.
PL 51 PATIENT-CENTERED PHARMACY EDUCATION DO WE REALLY NEED IT OR NOT?
AKGUL YESILADA
ISTANBUL KEMRBURGAZ UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY
The rapid development in the pharmaceutical industry has given rise to the introduction of a vast number of ready-made
medicinal products to to market, and has diminished the need for compounding of medicines in the pharmacies and restricted
the role of pharmacists mostly to the borders of dispensing medicinal products, which resulted the underuse of pharmacy
workforce in the health service. In the developed countries this workforce was sucessfully channelized into clinical medication
management where pharmacists were educated to be the effective providers of critical information to other health care teams
on the benefits, risks and potential adverse reactions between therapeutic agents, with the application of so- called patientcentered education system. Thus, in the last two decades the pharmacists role in the health care service has gained a new
formation globally : experts on medicines. By this way the pharmacy profession has emerged as an important contributor for
implementing responsible use of drugs in the developed countries. In spite of all these developments, there is still a debate for
or against the need for patient –centered education in some countries including Turkey. In this presentation the various aspects
of transition to patient-centered pharmacy education in Turkey will be discussed with emphasis to FIP,WHO and UNESCO
commentary, reports initiatives and action plans.
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PL 52 ROLE OF COMMUNITY PHARMACIES IN PROMOTING RATIONAL USE OF DRUGS IN DEVELOPING COUNTRIES. A WAY
FORWARD
AZHAR HUSSAIN
DEAN/DIRECTOR (PHARMACY DEPARTMENT), HAMDARD INSTITUTE OF PHARMACEUTICAL SCIENCES, HAMDARD UNIVERSITY,
ISLAMABAD, PAKISTAN
The use of medicines for prevention, cure or reducing symptoms for illness is widespread in many societies, around the world.
In order for health consumers to achieve optimum health outcomes through the quality use of medicines (QUM), it is vital that
they have access to safe and effective medicines which are also affordable. Besides that, access to independent and reliable
information about medicines and their alternatives is also essential to enable safe and appropriate use. Distribution of medicines
relies heavily on community pharmacies and according to an estimate, 80% of the medicines in developing countries are being
distributed through this channel due to their easy accessibility. Thus, majority of the population relies on community pharmacies
for their health care needs. Community pharmacies in developed world have been extensively utilized in managing chronic
diseases and minor ailments successfully. On the other hand, the role of community pharmacies has been ignored in developing
countries. These pharmacies often lack adequate facilities, staffing and equipments. Besides this, the dispensers working at
these pharmacies are not trained, and yet, are involved in making diagnoses and recommending therapy to the patients along
with dispensing of medicines. Thus it becomes important to critically evaluate and design effective pharmacy practice models
to be implemented at these community pharmacies which are required to guide researchers and policy makers to look into the
situation from a broader perspective to improve current pharmacy practices and provision of pharmaceutical care. Innovative
approaches are required to design appropriate interventions, policies and ways for their effective implementation, to utilize
the maximum potential of community pharmacies in promoting rational use of drugs. In this presentation role of community
pharmacies and effective pharmacy practice models for promoting rational use of drugs will be discussed
PL 53 ROLE OF DIETARY SUPPLEMENTS IN DISEASE PREVENTION AND MANAGEMENT
SIDNEY J. STOHS
FACN, CNS, ATS, FAPHA, DEAN EMERITUS, CREIGHTON UNIVERSTY OMAHA, USA
For optimal health optimal nutrition is required, and health and metabolism are limited by nutrients that are deficient and
therefore rate limiting. Widespread deficiencies are common for vitamins D, E, A, K, B6, B12 and folic acid as well as for minerals
including magnesium, calcium, iodine, zinc, selenium, and iron. Dietary supplements are products taken by mouth intended
to supplement the diet. In the USA they are classified as foods and not drugs. Recent studies have clearly shown that the
use of dietary supplements is cost effective, resulting in significant health care cost savings. Examples regarding healthcare
cost savings will be provided, and the amounts of vitamins, minerals, and other supplements that should be consumed to
enhance and optimize health will be discussed. In addition, information will be provided regarding the use, safety and efficacy
of nutritive sweeteners as sugars and FDA approved non-nutritive (non-caloric) sweeteners as sucralose.
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PL 54 THE CARCINOGENIC RISKS OF ARTIFICIAL SWEETENERS: THE CASES OF ASPARTAME AND SUCRALOSE
MORANDO SOFFRITTI, MICHELA PADOVANI
CESARE MALTONI CANCER RESEARCH CENTRE, RAMAZZINI INSTITUTE, BOLOGNA, ITALY
Nowadays, after saccharine, aspartame (APM) is the most used artificial sweetener in the world. APM is used on more than
6,000 products and, among them, in over 500 drugs. The major consumers are children and women in childbearing age. Their
daily consumption has been estimated to be 2.5-5 mg/kg b.w.
APM is metabolized both in humans and rodents, by intestinal tract into phenilalanin, aspartic acid and methanol. APM is not
considered genotoxic based on in vitro and in vivo tests. Epidemiological studies did not show an increased carcinogenic risk,
except in one study which showed an association of increased risk of non-Hodgkin’s lymphoma and multiple myeloma in man
who consumed diet soda containing APM. Experimental carcinogenicity studies performed on rats and mice in early ’70 by the
industry producing APM, and on transgenic mice by the US National Toxicology Program did not show any carcinogenic effect.
Overall we believed that the safety of APM concerning the potential long-term toxic effects, in particular the carcinogenic ones,
was not been demonstrated by these studies. For these reasons we started a project encompassing several experiments on rats
and mice in which APM was administered in feed at various doses, to a large number of rats or mice per group per sex, starting
the treatment at different ages and keeping the animals under observation until spontaneous death.
In the first experiment we demonstrated that APM, administered from 8 weeks of age for the life-span to Sprague-Dawley
rats, induced a significant increased incidence of lymphomas/leukemias and of neoplastic lesions of the renal pelvis and
ureter in females, and a significant increased incidence of malignant schwannomas of the peripheral nerves in males. In a
second experiment we demonstrated that APM, administered from fetal life until spontaneous death, induced a significant
increased incidence of lymphomas/leukemias in males and females, and of mammary cancer in females. Furthermore this
study demonstrated an increase of the carcinogenic effects. The oncological results of a third study, performed on Swiss mice
treated with APM from fetal life until spontaneous death, demonstrated a significant increased incidence of hepatocellular
carcinomas and alveolar/bronchiolar carcinomas in males.
Concurrently with the APM mice study, we performed an experiment on mice to test the potential carcinogenic effects of
Sucralose, a widely used artificial sweetener in Europe and USA. Preliminary results of this study will be presented during the
conference.
PL 55 PROBIOTICS: IS FOOD A GOOD CARRIER
DILEK HEPERKAN
ISTANBUL TECHNICAL UNIVERSITY, FACULTY OF CHEMICAL AND METALLURGICAL ENGINEERING FACULTY, DEPARTMENT OF
FOOD ENGINEERING
Microorganisms especially bacteria can be used for a number of beneficial purposes. Among them, some are more prominent
like Lactobacilli and Bifidobacteria as health promoting to the host. Probiotics are living microorganisms which have several
beneficial properties such as improving intestinal tract health, producing antimicrobial substances, enhancing the immune
response, reducing symptoms of lactose intolerance, enhancing the bioavailability of nutrients, and decreasing the prevalence
of allergy in susceptible individuals. Prebiotics are substances that pass through the gastrointestinal tract without being digested
such as inulin, other fructo-oligosaccharides and even almonds. They serve as substrates for the probiotic organisms to enhance
their activity and survivability in the colon. A variety of food products containing probiotics, prebiotics and synbiotics are
considered as functional foods and have increasing interest in the public. In this presentation the importance of probiotics, the
role of prebiotics, factors affecting the growth and activity of probiotic organisms, their beneficial role on the host, potential
foods which carry probiotic microorganisms will be discussed in detail.
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PL 56 RISK FACTORS AND ASSESSMENT OF BACTERIAL PATHOGENS IN FOOD
B. IREM OMURTAG KORKMAZ
DEPARTMENT OF NUTRITION AND DIETETICS, FACULTY OF HEALTH SCIENCES, MARMARA UNIVERSITY
Consumers’ exposure to bacterial pathogens and their food consumption habits are strictly related to each other. Risk factors
contributing to foodborne illnesses show also similarities in-between countries. Due to the growing food sector and increased
health concerns, priority of food security issues became more important since last decades. In this concept most critical
contamination routes to be considered are; carefully handling of food, differences of consumers’ habits in rural and urban
regions, meat species used for a food, prevalence and concentration of a pathogen in raw meat, sufficient heat treatment,
amount of meat and other raw components per portion, and frequency of consumption of a food item. These factors can be
evaluated principally on the basis of the risks posed by a pathogen and thus potential problems might be predicted by ranking
of food. Accordingly a previous risk assessment model of Omurtag et al. (2013) was indicated that amount of contaminated
meat at serving stage and also foods with high frequency of consumption was presumed to support possible transmission ways
of contaminated food to consumer. Hence it is clear that risks associated with foodborne pathogens have to be assessed by
considering several risk factors and therefore providing scientific data on the concentration of pathogens in different food items
are considered to be useful.
Reference:
Omurtag I., Paulsen P., Hilbert F. & Smulders F.J.M. (2013). The risk of transfer of foodborne bacterial hazards in Turkey through
the consumption of meat; risk ranking of muscle foods with the potential to transfer Campylobacter spp., Food security, 5(1):117127.
PL 57 DRUG TRANSPORTERS: CIRCADIAN RHYTHMS AND THERAPEUTIC IMPLICATIONS
ALPER OKYAR
ISTANBUL UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL
Circadian rhythms (~24h period) have been shown for most biological variables in living organisms and are generated by
molecular clocks involving clock genes. The molecular clocks are coordinated by the suprachiasmatic nuclei along the ~24h
and orchestrates the circadian timing system (CTS). The CTS generates daily rhythms in cellular and organism physiology and
adjusts them to environmental cycles (1). The main function of the CTS is to coordinate bodily and cellular functions, drug
pharmacodynamics (PD) and pharmacokinetics (PK) over the 24h. Circadian changes modulate phase I, II and III drug metabolism,
detoxification and disposition processes. Some drugs are not only metabolized, but also transported via carriers, e.g., for
exsorptive transport through ATP-binding cassette (ABC) transporters in particular P-glycoprotein (P-gp), is the most outstanding
one among ABC transporters, as it confers the strongest resistance (MDR) to the variety of antineoplastics. Furthermore, P-gp
is expressed in many tissues and is responsible for absorption, distribution and excretion of various compounds. Recently, it
was reported that circadian rhythms may influence the PK of drugs and play a role in the pharmacokinetic processes when
affected by ABC carriers–mediated efflux. This is particularly relevant for anticancer drugs, with a narrow therapeutic index (2,
3). Indeed, circadian timing modifies the toxic effects of 40 anticancer medications in rodents and in patients. The mechanisms
of drug detoxification involve the cellular efflux of medications and/or their metabolites via transporters. This detoxification
rhythm can importantly contribute to host tolerability for some anticancer drugs such as irinotecan, docetaxel, doxorubicin and
methotrexate whose efflux involves ABC’s. However, we should consider also that several mechanisms jointly account for the
chronopharmacology of antineoplastics. The challenge is to identify the theoretically optimal chronotherapeutic schedules that
will best spare healthy tissues from toxic insults in an individual patient (2, 3).
References:
1-
Lévi F, Schibler U. Annu Rev Pharmacol Toxicol 2007; 47: 593-628.
2-
Lévi F, Okyar A. Expert Opin Drug Deliv 2011; 8: 1535-1541.
3-
Lévi F, Okyar A et al. Annu Rev Pharmacol Toxicol 2010; 50: 377-421
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PL 58 BLAST INJURY INDUCED FUNCTIONAL AND STRUCTURAL CHANGES IN BRAIN
NIHAL TUMER
PHARMACOLOGY & THERAPEUTICS UNIVERSITY OF FLORIDA AND
GERIATRIC RESEARCH EDUCATION & CLINICAL CENTER, VETERANS AFFAIRS MEDICAL CENTER, USA
Background: Overpressure blast-induced brain injury (OBI) is a common problem for military population. It leads to progressive
pathophysiological changes in brain. Therefore, we investigated the structure and function of the basilar artery (BA) following
OBI. Methods: Male Sprague Dawley rats (250-300 g) were divided into Control (Naive), single OBI [30 psi peak pressure, 1-2
ms duration], and repeated (every three days) OBI (r-OBI). Rats were sacrificed 24 h post injury; brain tissues were taken. BA
was cannulised in the pressurized system and vascular responses to KCl, acetylcholine (ACh) and diethylamine (DEA)-NONO-ate
evaluated. Cortex and cerebellum were used for immunohistochemistry and assessment of oxidative stress and inflammatory
markers. Results: The neurological status was impaired in OBI and r-OBI groups (4.16±1.5, 3.71±1.4 respectively vs 0.66±0.5
in control). A significant increase was detected in malondialdehide (MDA), an index for lipid peroxidation levels in OBI and
r-OBI groups compared with control in cortex (p<0.05, p<0.05, respectively) and cerebellum (p<0.01, p<0.001, respectively). A
significant decrease was detected in glutathione (GSH) levels in r-OBI groups compared with control group in cortex (p<0.01)
and cerebellum (p<0.05). Myeloperoxidase (MPO) activity-an index for neutrophil infiltration was significantly (p<0.01-0.05)
elevated in r-OBI. Additionally, tissue thromboplastic activity, a marker for coagulation, was significantly increased in both
regions, indicating a tendency for bleeding. Edema and protein levels of nerve growth factor (NGF) and nuclear factor kappa
B (NFKB) were significantly (p<0.01) increased in cortex after r-OBI. Furthermore, the glial fibrillary acidic protein (GFAP)
and ionized calcium-binding adapter molecule 1 (Iba1) immunoreactivity also demonstrated injury in the cortex. Endothelin
contractility was increased and ACh relaxation was decreased in BA in both injury groups. However, impaired DEA-induced
dilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. Conclusion: These findings indicate
that single OBI causes endothelium-dependent and -independent alterations in BA function and additionally, r-OBI induced
structural changes in the artery wall. The mechanism may be a result of the increased oxidative stress and concomitant decrease
in antioxidant levels in cortex and cerebellum.
PL 59 METABOLITES – FRIENDS OR ENEMIES FOR DRUG DEVELOPMENT ?
MERT ULGEN
ACIBADEM UNIVERSITY INSTITUTE OF HEALTH SCIENCES,ISTANBUL, TURKEY
Drug metabolism is an important process in establishing the safety and efficacy of a new drug molecule. Therefore, metabolism
studies are carried out in the drug development stage to evaluate a series of compounds in terms of their metabolic stability
and reactive toxic intermediates. The aim is to provide data for registration of the drug to be marketed. The identification
of metabolites plays important roles in various phases of drug development. In some cases, active metabolites are found to
have superior pharmacological properties than the parent molecules thereof and they may be candidates of new commercial
products. Again, most of the pro-drugs having active metabolites were incidentally explored at the end of the drug development
stage. If a toxic metabolite is identified, the protection of the functional groups involved is essential which requires re-design
of the parent molecule. Many drugs can be metabolised to reactive products and these intermediates may react with cellular
components ie DNA, nucleic acids, proteins and sugars in the body to form potential toxic products and they produce metabolite
related toxicity. In the present lecture, the beneficial and detrimental aspects of drug metabolism will be discussed with specific
examples in terms of drug development strategies and the functional groups of potantial toxic properties will be evaluated.
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PL 60 TWENTY-FOUR YEARS OF EXPERIENCE IN THERAPEUTIC DRUG MONITORING:PAST, PRESENT, AND FUTURE
GONCAGUL HAKLAR
DEPARTMENT OF BIOCHEMISTRY, SCHOOL OF MEDICINE, MARMARA UNIVERSITY ANDMARMARA UNIVERSITY PENDİK
RESEARCH AND EDUCATION HOSPITAL, BIOCHEMISTRY LABORATORY, ISTANBUL, TURKEY
Therapeutic drug monitoring is an important field in clinical biochemistry as blood levels of many of the therapeutic drugs
administered to patients must be frequently determined, both because of the possible toxic side effects of many of these
medications and because, often, lack of patient compliance results in subtherapeutic levels of the drug, requiring intervention.
Additionally, it is important for the physician, when initiating drug therapy, to ascertain when the blood levels of the drug have
achieved a stable therapeutic level. It becomes important, therefore, to understand the pharmacokinetics, on which drug
therapy is based. The techniques involved in detecting the presence and/or the level of particular drugs, whether they are
drugs of abuse or therapeutic drugs, are of two basic types: immunochemical and chromatographic. Much drug testing today is
performed using immunoassays, namely the enzyme-mediated (or multiplied) immunologic technique (EMIT) and fluorescence
polarization immunoassay (FPIA). The major methods for chromatographic techniques are thin-layer chromatography (TLC), highperformance liquid chromatography (HPLC), and gas chromatography–mass spectroscopy (GC-MS) and liquid chromatography–
mass spectroscopy (LC-MS). We measure the concentration of cardiac glycosides, anticonvulsants, immunosuppressives, drugs
used in the treatment of mania and depression, and chemotherapeutic agents for therapeutic drug monitoring in serum or
whole blood. Furthermore, blood or urine level of the major drugs of abuse including cocaine, the opiates, amphetamines,
benzodiazepines, barbiturates, and cannabinoids are also measured.
PL 61 ENSURING BIOANALYTICAL PRINCIPLES ON BA/BE STUDIES
SEDA UNSALAN
NOBEL ILAC– TURKEY
The global generics drug market has grown substantially in recent years. Given the rapid progress of the sector, organisations
must critically manage and assess bioequivalence studies (BE) that are mandatory when bringing new generic drugs to market.
Bioavailability (BA) and BE studies play a major role in the drug development phase for both new drug products and their
generic equivalents.
Bioanalytical part is the most important part of the BA/BE studies. Bioanalytical method validation employed for the quantitative
determination of drugs in biological fluids play a significant role in the evaluation and interpretation of BA, BE, pharmacokinetic
and toxicokinetic study data. The quality of these studies is directly related to the quality of the underlying bioanalytical data.
It is therefore important that guiding principles for the validation of these analytical methods be established and disseminated
to the pharmaceutical community.
A series of conferences and workshops on bioanalytical method validation and study sample analysis was started in early 1990s,
initiated by several scientific associations and supported by the US Food and Drug Administration. This approach resulted in
the current document “FDA Guidance for Industry Bioanalytical Method Validation”, published in May 2001 (FDA, 2001). This
document has been widely adopted as the standard reference for validation and routine drug analysis by the global bioanalytical
community. In following years, several workshops and conferences were held with the aim of clarification of specific parts
of the established Guidance and subsequent improvements in method validation. This included discussion of topics such as
calibration curves and QC ranges, determination of metabolites, incurred sample re-analysis, and documentation. The need
for a Guideline on validation of bioanalytical methods specifically applicable for studies in the European Unionis obvious. As a
consequence, a concept paper on the “Need of a Guideline for the Validation of Bioanalytical Methods” was released in 2008
by the Committee for Medicinal Products for HumanUse (CHMP) that came into effect in 2011.
References:
1 Viswanathan CT et al ., (2007). Workshop/Conference Report — Quantitative Bioanalytical Methods Validation and
Implementation: Best Practices for Chromatographic and Ligand Binding Assays. The AAPS Journal 9 (1) Article 4 (http://www.
aapsj.org).
2 Shah VP and Bansal S (2011). Historical perspective on the development and evolution of bioanalytical guidance and technology.
Bioanalysis 3(8), 823–827.
3 FDA- Guidance for industry: bioanalytical method validation. US Department of Health and Human Services FDA, Center for
Drug Evaluation and Research (2001).
4 EMA- Guideline on bioanalytical method validation. 21 July 2011 EMEA/CHMP/EWP/192217/2009 Committee for Medicinal
Products for Human Use (CHMP)
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PL 62 PHARMACY MANAEGEMENT: TODAY AND TOMORROW
NAZLI SENCAN
YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, PHARMACY MANAGEMENT AND SOCIAL PHARMACY DEPARTMENT, ISTANBUL,
TURKEY
There are countless books, presantations and works on both management and pharmacy, although the works on “pharmacy
management” is still improving in all around the world. Some cultures are dedicated and some are learning the importance
of pharmacy management on pharmacutical care and pharmaceutical services.Pharmacy management focuses on factors,
processes and outcome of pharmacy practice. Time, human resourse, financial, marketing, personal, innovation, risk,
environmental, decision making, education and etc. management are some of the main topics of pharmacy management. Also
social, ethical and lgal issues like inter and multicultural patient management, influence of culture on adharence, understanding
geriatric patients, management of waste pharmaceuticals are some of the research concepts of pharmacy management. In this
presantation, the researches done and published through out the world and Turkey will be summerised and future needs and
works will be proposed. The main subjects are common priorities of health care givers like ; pharmacovigilance management
and knowledge, smoking habbits, internships, drug advertisements, rational drug use, pharmacoeconomics, polypharmacy,
geriatric patient care, compliance, dental care, pharmaceutical waste, patient satisfaction, pharmacists commitment to work,
gender and pharmaceutical services, disabeled patients, financial loss of pharmacies and etc. It is obvious that pharmacy
management perspective leads pharmacists to add value to public health.
PL 63 THE IMPACT OF HEALTH LITERACY ON DRUG USE OF THE COMMUNITY
HAYDAR SUR
MD, PHD, PROFESSOR, BIRUNI UNIVERSITY FACULTY OF HEALTH SCIENCES
Irrational use of medicines is a major problem worldwide. WHO estimates that more than half of all medicines are prescribed,
dispensed or sold inappropriately, and that half of all patients fail to take them correctly. The overuse, underuse or misuse of
medicines results in wastage of scarce resources and widespread health hazards.
WHO defines rational use of drug as “Rational use of drugs requires that patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements for an adequate period of time, and the lowest cost to them and
their community.” (WHO, 1985) and advocates 12 key interventions to promote more rational use:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Establishment of a multidisciplinary national body to coordinate policies on medicine use
Use of clinical guidelines
Development and use of national essential medicines list
Establishment of drug and therapeutics committees in districts and hospitals
Inclusion of problem-based pharmacotherapy training in undergraduate curricula
Continuing in-service medical education as a licensure requirement
Supervision, audit and feedback
Use of independent information on medicines
Public education about medicines
Avoidance of perverse financial incentives
Use of appropriate and enforced regulation
Sufficient government expenditure to ensure availability of medicines and staff (1).
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The dimensions of the problem include both service providing and utilizing sides as well as health system managers and policy
makers. WHO recommends public education as a major solution options (1,2).Especially low level of health literacy among
health service utilizers is one of the most important reasons of irrational use of medicines (2).
Health literacy has been defined in many different ways since it was first introduced as a term and concept. A broad and inclusive definition developed in 2012 by the European Health Literacy Consortium:
“Health literacy is linked to literacy and entails people’s knowledge, motivation and competences to access, understand, appraise and apply health information in order to make judgements and take decisions in every- day life concerning health care,
disease prevention and health promotion to maintain or improve quality of life during the life course” (3).
Health literacy is a key determinant of health. Literacy is a stronger predictor of an individual’s health status than income, employment status, education level and racial or ethnic group (3).Low level of health literacy causes difficulties in the diagnosis
and treatment stages of service use and sometimes it makes the treatment impossible. One of the most important results of
this obstacle is related with use of prescribed drugs. Low ability to perceive the potential of treatment, misunderstanding and
misinterpretation of progresses about disease are all outcomes of low health literacy. Despite the compatibility of health literacy to literacy level in general, it is not uncommon to have difficulties with literate people in terms of health services and use
of drugs (4).
Development of new strategies and policies aimed to increase the health literacy level in community will certainly provide great
contribution to control irrational drug use. This success will give benefits to both health of the community and decrease the
overall drug expenditures.
References:
1.
http://www.who.int/medicines/areas/rational_use/en/ (date of access: 29.08.2014)
2.
Ambwani S., Mathur AK. Ratıonal Drug Use, Health Administrator Vol : XIX Number 1: 5-7.
3.
Health literacy The solid facts, Editors: Ilona Kickbusch, Jürgen M. Pelikan, Franklin Apfel & Agis D. Tsouros, WHO European Regional Office Publication, Copenhagen, 2013.
4.
Sur H. Gene Bir Moda: Sağlık Okuryazarlığı. SD Platform Sayı: 31.
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PL 64 BENZENE, A MULTIPOTENTIAL CARCINOGEN
MYRON A. MEHLMAN
MT. SINAI SCHOOL OF MEDICINE, NEW YORK, NY
Benzene is the most widely studied chemical in the world. Benzene is present in many household products and in occupational
settings using paint, organic solvents, printing, and in gasoline stations, petrochemical plants, and in shoe manufacture. Workers
and all these fields are exposed to benzene. Over 6,000 products and chemicals were analyzed for benzene content. Benzene
is extremely toxic and causes all types hematopoietic and lymphoreticular tumors. Toxicity of benzene has been known since
the 17th century. Benzene poisoning in humans is a product of degree of individual susceptibility, duration of exposure, and
concentration, which has a relative but not an absolute importance. The only safe concentration is zero (Hunter, F. 1939).
Professor Mustafa Aksoy from Turkey and his coworkers are world-recognized scientists in the studies of the carcinogenicity
of benzene. In addition to all types of leukemias and lymphomas, benzene has also been shown to cause lung, liver, stomach,
colon, kidney, urothelial, esophageal, nasopharyngeal and lymphosarcomatous tumors. Benzene biomarkers of exposure and
intermediate effects are dose-dependent. MDS is found in excess in less than 10 ppm of exposure, and peripheral blood cell
counts can be decreased at less than 1 ppm. Genetically defined subgroups with greater sensitivity to benzene are present in
the population.
PL 65 MUCOSAL NANOVACCINOLOGY
H. OYA ALPAR
KEMERBURGAZ UNIVERSITY ISTANBUL & UCL LONDON
Conventional vaccine delivery presents problems that are related both to patient compliance and to the adjuvants employed. A new
generation of vaccine antigens are being identified and produced in the form of subunits and synthetic peptides, which although
offering the advantage of safety, are in many cases weakly immunogenic. Therefore, there is an urgent need for pharmaceutically
acceptable delivery systems and adjuvants for these antigens and non-parenteral administration for immunological, practical
and economic reasons. To this end, biodegradable particles show particular promise. Particulate polymeric carriers made from
biodegradable synthetic polymers such as polyesters offer advantages in uniformity and flexibility. During our earlier studies,
we have demonstrated that microsphere-associated (adsorbed or encapsulated) vaccine antigens and plasmid DNA can lead
to significant immune responses, not only through parenteral delivery, but also through mucosal surfaces, especially through
the nasal route and also through the skin and that the responses induced can be optimised through formulation. These studies
illustrated the importance of particle characteristics such as hydrophobicity, size and surface charge, as well as polymer type,
molecular mass and crystallinity, on the modulation of immune response obtained. In addition, these responses may also be
increased by the addition of bioadhesives. We have also conducted an extensive investigation into the uptake and trafficking of
radio / fluorescent dye labelled microspheres following intranasal application. These studies showed that, in addition to particle
transference into mucosal inductive sites, such as NALT, we also have observed immunologically significant translocation of
micro-nano particulate material into systemic inductive sites, such as the spleen which is a prerequisite for the induction
of protective immunity. Early publications from our group show the ability of mucosally administered microencapsulated
recombinant subunit antigens derived from Y. pestis, to completely protect experimental animals from challenge with virulent
Plague causing bacteria. For the same microsphere preparation, when delivered intra-tracheally in a comparative study, which
also investigated i.m. and i.n. routes of delivery, mucosal routes gave equivalent or better immune responses than the parenteral
route. However, our work has not been restricted to just one clinically relevant vaccine but many others. For example as well as
particles containing a recombinant fusion protein, toxin F heavy chain (MBP- FHc) and subsequently with anthrax vaccine (using
different types on rPA protective antigen)-microsphere formulations, following protection studies engendered solid protection
in mice immunised i.n or i.m or both (combined) against a lethal challenge with the toxin and the organism respectively. In the
case of B.anthracis the protection level was both formulation and adsorbtion - method dependent. Again, in the context of
clinically relevant antigens, I will also discuss the formulation of PLA, PCL nanoparticules, surface modified with enhancers and
adhesive polymers carrying encapsulated or adsorbed S.equi antigens (extract vs. recombinant SeM protein) as a new strategy,
to control “strangles”. Also HepB hybrid cationic PLA-PEG nanoparticles to elicit strong humoral and cellular immunity after only
a single mucosal or parenteral administration to replace conventional Alum-HBsAg vaccine to develop improved vaccines with
a reduced dosing schedule, effective via a non-evasive route, and therapeutic vaccines for chronic hepatitis B virus carriers. In
testing various chitosan based nanocarriers both for immunisation and DNA transfection studies the low MR chitosan/DNA
polyplexes gave the highest and most reproducible transfection efficiencies. The low MR chitosan polyplexes/gWIZ were also
successful in eliciting an immune response, suggesting that they hold promise in the field and warrant further investigation.
These data will be discussed in the context of particle engineering and mucosal administration of nanoparticulate vaccine
carrier systems.
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PL 66 BIOTECHNOLOGICAL INDUSTRY IN TURKEY AND THE BIOSMILARS AS THE NEW DRIVING FORCE
CEM KOÇAK
KOÇAK FARMA
Biotechnological products present the fastest growing segment in the pharmaceutical industry. The terms biotechnology and
biopharmaceutical describe many complex and important products, technologies, R&D, and industries.
In this presentation the current status of Biotechnological and Biosimilar products in Turkey are summarized as well as the
opportunities in this area in Turkey. The consumption of biotechnological and biosimilar products increase constantly.
Since the approval of first biosimilar in 2006 in EU, biosimilar present the greatest opportunity of growth for the pharmaceutical
companies worlwide.
Turkish government is supporting local manufacturing of biotechnological products with several incentives.
PL 67 LEPTIN RESISTANCE: PREDISPOSING FACTOR IN OBESITY AND INFLUENCE WITH AGE:
PHILIP J. SCARPACE
UNIVERSITY OF FLORIDA, GAINESVILLE, FL.
Obesity is occurring at epidemic rates with frightful health consequences. Our hypothesis is that leptin resistance is an important causative factor in both diet-induced and age-related obesity. We demonstrated that both types of obesity are associated
with leptin resistance and this resistance resides within the first order hypothalamic neurons that contain leptin receptors, and
provided strong evidence that the leptin receptor-signaling cascade is impaired. Leptin is produced in white adipose tissue in
proportion to amount of fat tissue, and it was generally believed that the elevated leptin associated with obesity was simply
a consequence of the increased adiposity. Our data indicate that the elevated leptin with obesity, whether diet-induced or
age-related, is not just a consequence of obesity, but also one independent factor that predisposes animal to exacerbated highfat induced obesity. Moreover, we demonstrated that chronic treatment with leptin worsen rather than lessens the obesity.
Thus, an increase in obesity elevates leptin levels inducing leptin resistance, which in turn, exacerbates the obesity, leading to
ever-escalating cycle of increasing obesity
Aged rats with adult onset obesity are leptin resistance, and aged rats with leptin resistance gain more weight on a high fat
diet than younger leptin responsive rats. Consumption of high-fat diet in young rats leads to weight gain that is a mixture of
an increase in both lean and fat mass. In contrast, high-fat feeding in aged rats not only results in greater absolute increase in
weight gain, but the entire increase in weight is due to an increase in fat mass. The availability of highly palatable food is just as
alluring to adults as to younger individuals, but our findings suggest that the consequences of consumption this high-fat food
may be more dire in the aged population.
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PL 68 MECHANISM OF ACTION OF INPP4B TUMOR SUPPRESSOR IN ENDOCRINE CANCERS
AGOULNIK IU, DERYUGINA EI, LIN D, LOPEZ SM, SUAREZ E, HODGSON MC, BINGOL-OZAKPINAR O, URAS F, WANG Y
FIU HERBERT WERTHEIM COLLEGE OF MEDICINE, DEPARTMENT OF CELLULAR BIOLOGY AND PHARMACOLOGY, USA
Dysregulation of phosphatidyl inositol signaling occurs in many cancers. Phosphoinositides are produced by a large number of
phosphatidylinositol kinases and dephosphorylated by lipid phosphatases, such as tumor suppressors Inositol Polyphosphate
4-phosphatase type II (INPP4B) and PTEN. INPP4B has recently emerged as a potential tumor suppressor in prostate, breast,
ovarian, and other cancers. We and other groups have shown loss of INPP4B protein and mRNA with cancer progression to metastasis. Efforts are underway to characterize INPP4B catalytic activity and determine signaling pathways regulated by this tumor suppressor. INPP4B contains an N-terminal C2-lipid binding domain and a C-terminal phosphatase domain, which contains
a dual specificity phosphatase motif. We show that INPP4B can dephosphorylate both lipid and phospho-tyrosine substrates.
Both of these activities are potentially important for INPP4B tumor suppressor function. Using cell based assays we discovered
that loss of INPP4B leads to activation of several oncogenic signaling pathways that regulate proliferation and invasion. Our data
suggests that INPP4B and PTEN tumor suppressors perform distinct functions in epithelial cells and loss of INPP4B has different
consequences on tumor progression compared to loss of PTEN. PL 69 PROFESSIONAL PRACTICE AND COMPETENCY STANDARTS IN PHARMACY
LEVENT ÜSTÜNES
EGE UNIVERSITYFACULTY OF PHARMACY DEPARTMENT OF PHARMACOLOGY, BORNOVA, İZMİR
The primary responsibility of a pharmacist is to ensure safe and effective use of medicines through the provision of pharmaceutical care in the scope of clinical pharmacy.
Competencies refer to the knowledge, skills, attitudes and behaviours that an individual develops through education, training
and work experience. Taken together, these professional acquirements form a framework which provides a pattern to describe
the required competencies and appropriate code of conduct for a pharmacist’s daily practice. Competency standards focus on
key aspects of performance and express how a competent professional would act, in terms of attitudes, behaviors and observable results. Therefore the competency standards are embedded in every aspect of a pharmacist’s professional life.
On the other hand, complementing the compentency standards, professional practice standards relate to the systems, procedures and information used by pharmacists to achieve a level of conformity and uniformity in their practice. Professional
standards allow the pharmacy profession to qualitatively and quantitatively measure the extent to which a pharmacist complies
with his/her ethical and legal commitment to the community to ensure safe and effective delivery of pharmacy services, irrespective of the setting in which he/she practices.
As health-care professionals, pharmacists play an important role in improving access to health care and in closing the gap between the potential benefit of medicines and the actual value realized. This makes pharmacists an indispensable part of any
comprehensive health system. In addition, the increasingly complex and diverse nature of pharmacists’ roles in the health-care
system demands an unceasing observance of the competence of pharmacists as health-care professionals who need to have
up-to-date skills and expertise.
In this sense, professional practice and competency standards in pharmacy are vital to provide guidelines for the pharmacists
to improve access to health care, assist health promotion and ensure effective use of medicines for their patients. Fulfilling
these standards is a requisition for every pharmacist to be fully capable of performing their profession in the most effective and
beneficial manner, both for the patients they serve and for the society overall.
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PL 70 NEW TRANSLATİON MODELS TO LİNK OMICS TO HEALTH INNOVATİON: MİCRO-GRANTS FOR BİG DATA
VURAL ÖZDEMİR
FACULTY OF COMMUNICATIONS AND THE OFFICE OF THE RECTOR, INTERNATIONAL TECHNOLOGY AND INNOVATION POLICY,
GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
Translation of data-intensive OMICS technologies such as genomics, proteomics and metabolomics to concrete health innovations is at the epicentre of the research and development agenda. Yet the current translational research paradigms are based
on the traditional ‘science push’ model of translation, and rarely consider the ‘science pull’ model of translation whereby the
user communities and other societal stakeholders are included early on in the design stage of science and knowledge-based
innovations. We often under-appreciate the important contributions made by citizen scholars and lead users of innovations to
design innovative products and co-create new knowledge. We believe there are a large number of users waiting to be mobilized
so as to engage with Big Data-driven pharmacy research and practice as citizen scientists-only if some funding were available.
Yet many of these scholars may not meet the meta-criteria used to judge expertise, such as a track record in obtaining large research grants or a traditional academic curriculum vitae. We propose a novel idea and action framework to link OMICS to truly
novel (disruptive) health innovations: micro-grants, each worth $1000, for genomics and Big Data. Though a relatively small
amount at first glance, this far exceeds the annual income of the “bottom one billion”-the 1.4 billion people living below the
extreme poverty level defined by the World Bank ($1.25/day). We describe two types of micro-grants. Type 1 micro-grants can
be awarded through established funding agencies and philanthropies that create micro-granting programs to fund a broad and
highly diverse array of small artisan labs and citizen scholars to connect genomics and Big Data with new models of discovery
such as open user innovation. Type 2 micro-grants can be funded by existing or new science observatories and citizen think
tanks through crowd-funding mechanisms described herein. Type 2 micro-grants would also facilitate global health diplomacy
by co-creating crowd-funded micro-granting programs across nation-states in regions facing political and financial instability,
while sharing similar disease burdens, therapeutics, and diagnostic needs. Our hope is that the micro-grants will spur novel
forms of disruptive innovation and genomics translation by artisan scientists and citizen scholars alike.
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ORAL PRESENTATIONS
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OP 1 DEGRADATIVE ACTIVITIES OF ANTIBIOTIC-RESISTANT STAPHYLOCOCCUS SAPROPHYTICUS, BACILLUS PUMILUS,
GRACILIBACILLUS DIPSOSAURI AND IDIOMARINA LOIHIENSIS
PINAR CAGLAYAN 1, MERAL BIRBIR 1, AYSE OGAN 2, CRISTINA SáNCHEZ-PORRO 3, ANTONIO VENTOSA3
DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA
UNIVERSITY, GOZTEPE, ISTANBUL, TURKEY
2
DIVISION OF BIOCHEMISTRY, DEPARTMENT OF CHEMISTRY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY,
GOZTEPE, ISTANBUL, TURKEY
3
DEPARTMENT OF MICROBIOLOGY AND PARASITOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF SEVILLA,SPAIN
1
Proteolytic and lipolytic activities of five moderately halophilic bacteria isolated from salted skins were screened on media
containing 2% (w/v) gelatin and 1% (v/v) Tween 80, respectively. Then, these isolates were characterized using partial 16S rRNA
sequence analysis. Antibiotic susceptibilities of these isolates to gentamicin (10 µg), kanamycin (30 µg) and nalidixic acid (30 µg)
were examined. Protease and lipase activities of the isolates and their mix culture were determined by the casein digestion assay
at 280 nm and measuring the hydrolysis of p-NPB to p-nitrophenol at 405 nm, respectively. All isolates showed both positive
protease and lipase activities. According to phylogenetic analysis based on 16S rRNA gene sequence comparison, moderately
halophilic bacterial strains isolated from the skins were identified as Staphylococcus saprophyticus, Bacillus pumilus, Bacillus
licheniformis, Gracilibacillus dipsosauri and Idiomarina loihiensis. Protease activities of Gracilibacillus dipsosauri, Staphylococcus
saprophyticus, Bacillus pumilus, Idiomarina loihiensis and Bacillus licheniformis, and the mixed culture were found respectively
as 2.6, 2.0, 1.2, 3.0, 2.6 and 3.5 u/min. Lipase activities of Gracilibacillus dipsosauri, Staphylococcus saprophyticus, Bacillus
pumilus, Idiomarina loihiensis and Bacillus licheniformis and the mix culture were found as 64, 93, 87, 77, 55 and 93 µM/
mL, respectively. While Idiomarina loihiensis exhibited the highest protease activity, Staphylococcus saprophyticus displayed
the highest lipase activity. All isolates exhibited resistance against gentamicin (10 µg) kanamycin (30 µg) and nalidixic acid (30
µg). Due to destructive effects of these isolates on the preserved skins, effective treatment procedures should be applied to
preservation salt to exterminate these destructive antibiotic-resistant microorganisms.
OP 2 EFFECT OF USING ANTIBACTERIAL AGENT, DIRECT AND ALTERNATING ELECTRIC CURRENTS TO KILL BACTERIA IN HIDE
CURING AND PRE-SOAKING LIQUORS
EMINE VURAL GENC 1, YASAR BIRBIR 2, MERAL BIRBIR 3
INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF ELECTRIC AND ELECTRONIC ENGINEERING, FACULTY OF TECHNOLOGY, MARMARA UNIVERSITY, ISTANBUL,
TURKEY
3
DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA
UNIVERSITY, ISTANBUL, TURKEY
1
2
Prevention of bacterial activity during brine curing and pre-soaking processes on hides is very important to improve leather
quality. In this study, efficacy of different concentrations of potassium dimethyldithiocarbamete on the mixed culture of
bacteria at different exposure times were investigated. In addition, the effect of combined electric current treatment using
both 1.5 A direct and 2 A alternating electric currents, followed by 2240 mg/200 ml of test antibacterial agent treatment on
the mixed bacterial culture was examined. Mixed culture of bacteria containing proteolytic Bacillus mycoides and Aerococcus
viridans, lipolytic Staphylococcus xylosus and Enterobacter sakazakii were used. 700 ppm of the test agent was inadequate
to kill the bacteria in the mixed culture with a period of 6 hours. However, 1400 ppm, 2800 ppm and 5600 ppm completely
inactivated the bacteria in the same period of 6 hours, while 11200 ppm and 22400 ppm inactivated these microorganisms in 4
hours and 44800 ppm in 3 hours, respectively. The bacteria in the mixed culture treated with electric current were completely
exterminated after 2 hours of exposure to 11200 ppm test agent. Bacterial cell count of the mixed culture was reduced to a
low level via 12 min electric current treatment and the remaining microorganisms were then killed easily by the test agent. In
conclusion, this treatment system may be applied in hide brine curing and pre-soaking processes to more efficiently kill the
microorganisms in these liquors.
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OP 3 PROS AND CONS OF PILUS: A TARGET FOR ANTIVIRULENCE THERAPEUTICS AND AN UNLIKELY PLAYER IN THE FIGHT
AGAINST CANCER
MERVE SUZAN ZEDEN 1, SCOTT HULTGREN 2, ENDER VOLKAN 1
1
2
CYPRUS INTERNATIONAL UNIVERSITY, CYPRUS
WASHINGTON UNIVERSITY IN ST. LOUIS, SCHOOL OF MEDICINEN ,ABD
Pili are filamentous, polymeric protein appendages assembled by bacteria. P- and type-1 pili, assembled by uropathogenic
Escherichia coli via the chaperone-usher pathway, are virulence factors in urinary tract infections (UTIs). These appendages
are required to bind host surfaces and establish infection; so their inhibition is a way to prevent infection. Antivirulence
therapeutics named ‘pilicides’ are bicyclic 2-pyridones designed to inhibit P-pilus biogenesis. Using SDS-PAGE and Western
blotting, our studies indicate that certain pilicides are involved in blocking the polymerization of P-pilus subunits (PapE) that
form the tip section of the pilus. These pilicides likely induce non-productive aggregation of PapDE subunits as demonstrated
by Western blotting analysis. Type-1 pili are also involved in UTIs by binding to mannose moieties on bladder surface and
invading host tissues. In addition to binding mannose, type-1 pili were shown to mediate binding with β1 and α3 integrins
that are highly expressed on MDA-MD-231, highly metastatic human breast cancer cells. Upon co-culturing Type-1 piliated or
unpiliated Escherichia coli with MDA-MD-231 cells and carrying out toxicity assays, we have observed a significant increase in
cancer cell death when MDA-MD-231 cells were incubated with piliated bacteria rather than unpiliated bacteria. Interestingly,
this significant pili-mediated toxicity was specific to highly metastatic MDA-MD-231 cells as lowly metastatic MCF7 cells did not
experience significantly increased killing, suggesting that pili may have a role in targeting metastatic tumor cells. These findings
indicate that studies on chaperone-usher pili can help improve our approaches of designing therapeutics for treatment of both
infection and cancer.
OP 4 LIFE SPAN EFFECT DIFFERNT INFUSIONS OF VERBASCUM TRICHOSTYLUM ON CAENORHABDITIS ELEGANS EXPOSED TO
CHRONIC HEAT STRESS
HASAN KILICGUN
FACULTY OF PHARMACY ERZINCAN UNIVERSITY, ERZINCAN, TURKEY
Aging is commonly defined as the accumulation of diverse deleterious changes occurring in cells and tissues with advancing
age that are responsible for the increased risk of disease and death (1). Extracts of plant adaptogens such as Eleutherococcus
senticosus and Rhodiola rosea can increase stress resistance and life span in several model systems. In this study it was aimed
to investigate whether Verbascum trichostylum, which is endemic to Eastern Anatolia of Turkey, has any effect on lifespan of
the nematode C. elegans in a dose-dependent way under chronic heat treatment at 26°C or not. For this purpose 0.01mg/mL
0.1mg/mL, 1mg/mL, 10 mg/ml Verbascum concentrations were prepared and mixed with Escherichia coli OP50 bacteria which
is only feding source of Caenorhabditis elegans. Differnt concentrations of Verbascum trichostylum were able to increase stress
resistance in C. elegans against chronic heat stress treatment at 26°C. The most promising increase against chronic oxidative
stress conditions and lifespan were observed at the concentrations of 1mg/mL. Whereas, at 10 mg/ml concentrations tested a
lifespan shortening effect was observed. Based on these observations, this study indicates that Verbascum trichostylum can be
thought as an adaptogen. Because it was experienced as mild stressors at the lifespan-enhancing concentrations and thereby
induce increased stress resistance and a longer lifespan.The obtained findings are thought that verbascum has a significant
potential for aging as well as the treatment of aging related diseases.
1.Harman. D. The free radical theory of aging. Antioxid Redox Signal. 2003;5:557-561.
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OP 5 VALIDATED METHODS IN BIOALALYSIS
SOMAIEH SOLTANI , AFSANEH FARJAMI
PHARMACY FACULTY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, IRAN
Bioanalytical method(s) development is of great importance during the process of drug discovery, development, marketing
approval and clinical application and has significant impact in the pharmacokinetic and pharmacodynamic interpretations and
decision makings. In the present study the application of approved guidelines (i.e. ICH, FDA and USP) in bioanalytical method
development during the past decade has reviewed. The frequency of non-validated methods or partially validated ones versus
full validated methods are studied and guidelines application trend is discussed. According to the results miss application of
the guidelines and non validated methods are among the most challenging issues of the bioanalytical method development.
It seems that these methods should be reviewed according to the proper validation aspects more carefully before publication.
OP 6 THE ROLE OF GAS6/TAM SIGNALLING IN DIFFERENTIATION OF MESENCHYMAL STEM CELLS
NESE ERIZ , OZLEM BINGOL OZAKPINAR , NAZIYE OZKAN , FIKRIYE URAS
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
GAS6 (Growth arrest-specific 6) is a protein vitamin K-dependent protein and is expressed in certain tissues. GAS6 is a ligand
of Tyro3, Axl and Mer (TAM receptors). In this study, we aim to investigate the effects of GAS6 during differentiation of the
mesenchymal stem cells. Adipose tissue removed during a liposuction procedure was used as starting material. Mesenchymal
stem cells isolated from adipose tissue were analyzed by flow cytometry. Then adipogenic, chondrogenic or osteogenic
differentiation was achieved using the appropriate differentiation mediums. In parallel with these experiments, the cells were
incubated with varying doses of GAS6 added to the medium. RNAs of TAM receptors were subjected to Real-time-PCR analyses.
In addition, cells were checked morphologically by staining with suitable dyes to determine the possible effects of GAS6. During
chondrogenic differentiation, TAM receptors are expressed in high amounts and these increases were statistically significant
(p <0.001, 0.01 and 0.001, respectively). On the other hand, only the Mer receptor was found to be expressed highly during
adipogenic differentiation (p<0.001). It was found that osteogenic differentiation was inhibited by addition of GAS6; whereas
adipogenic differentiation was increased. Chondrogenic differentiation was decreased significantly, according to the dosage
of GAS6 (p<0.001). The findings obtained in this study revealed that GAS6/TAM system has a role on mesenchymal stem cell
differentiation in terms of the three differentiation modes: adipogenic, osteogenic and chondrogenic.
OP 7 THE PLASMA LEVELS OF GAS6 IN RECURRENT PREGNANCY LOSSES
MUSTAFA EROGLU 1, OZLEM BINGOL OZAKPINAR 2, LALE TURKGELDI 1, SADIK SAHIN 1, DILSAD HERKILOGLU 1, FIKRIYE URAS 2
1
2
ZEYNEP KAMIL GYNECOLOGIC AND PEDIATRIC TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, İSTANBUL, TURKEY
During the implantation period, a significant portion of embryos are lost and eventually less than half of clinically established
pregnancies end as full-term pregnancies without obstetrical complications. Recurrent pregnancy losses (RPL) are thought to have
multiple etiologies including autoimmune and cellular immune abnormalities and maternal thrombophilic disorders. Growth
arrest-specific 6 (GAS6) is a novel vitamin K dependent protein and has a role in inflammation. The aim of the current study is to
investigate the association of plasma GAS6 levels with RPL. We collected blood samples from 81 women with RPL. Also blood
samples of 66 women having had at least one live birth were collected as the control group. Patient and control groups’ plasma
GAS6 levels were measured with an ELISA kit (R&D), which were optimized by us in our own laboratory. We used Unpaired T test
for GAS6 levels. P<0.05 was taken as statistically significant. The plasma levels of gas6 were significantly higher in patients with
RPL than those of the control group (12.26±4.24 ng/mL and 10.57±3.72 respectively, p<0.01). The preliminary results show that
there is a relation between RPL and plasma GAS6 levels. Inhibition of GAS6 would be an appropriate therapeutic target to slow
down the progression of RPL.
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OP 8 CYTOKINE LEVELS AND PLATELET FUNCTIONS IN PREECLAMPSIA
SADIK SAHIN 1, OZLEM BINGOL OZAKPINAR 2, AYSIN TULUNAY 3, MUSTAFA EROGLU 1, ENVER CIRACI 2, FIKRIYE URAS 1, SERMIN
TETIK 2
ZEYNEP KAMIL GYNECOLOGIC AND PEDIATRIC TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, İSTANBUL, TURKEY
3
MARMARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF HEMATOLOGY AND IMMUNOLOGY, ISTANBUL, TURKEY
1
2
The aim of this study is to evaluate the hypothesis that preeclampsia is associated with increased systemic inflammatory
responses. We also determine whether there was a correlation between these markers with severity of preeclampsia and
platelet functions. Forty-one patients diagnosed with preeclampsia were recruited into our study. Preeclamptic patients
were grouped as severe (n=23) and mild (n=18). All patients were in the third trimester of the pregnancy and the values
obtained were compared to controls (N=30) who were in the third trimester of uncomplicated normal pregnancy and not
affected by either preeclampsia or gestational hypertension. Cytokine levels of interleukin-8 (IL-8) and IL-10 in plasma from
women with preeclampsia or from healthy pregnant women were analyzed with ELISA. Aggregation and activation response
of platelets to agonist adenosine-5-difosphate (ADP) was determined. Plasma IL-8 levels were significantly higher in severe
preeclamptics (p<0.05). There was no significant difference between mild preeclampsia and the controls (p>0.05). IL-10 levels
were significantly lower in severe preeclamptic patients compared to normal pregnants and mild preeclamptics (p<0.001 and
p<0.05), respectively. Platelet aggregation response to ADP was less in preeclamptics than normal pregnants (p<0.001). Also,
CD 62P levels, a marker of platelet activation, were elevated in preeclamptic patients (p<0.05). Negative correlation between
the regulatory cytokine IL-10 and pro-inflammatory cytokine IL-8 levels suggests cytokine network disturbance in severely
preeclamptic women. This might cause increase in platelet activation, thus decrease in platelet aggregation response to ADP in
preeclamptic patients due to exhaustation and turnover of platelets.
OP 9 SYNTHESIS, CHARACTERIZATION, PHOSPHATE BUFFER STABILITY, AND ANTIPROLIFERATIVE EFFECTS OF A NOVEL
MODIFIED MALEIC ANHYDRIDE CONTAINING COPOLYMER/ANTICANCER DRUG CONJUGATES
GULDEREN KARAKUS
FACULTY OF PHARMACY CUMHURIYET UNIVERSITY, TURKEY
Maleic anhydride (MA) copolymers also known as polyanhydrides, having highly reactive anhydride units, consists of MA and
vinyl-based monomers. In our research laboratories poly(maleic anhydride-co-styrene), poly(maleic anhydride-co-vinyl acetate),
poly(maleic anhydride-co-methyl methacrylate) and poly(maleic anhydride-co-allyl phenyl ether) were synthesized. Through
modification/derivatization/conjugation of these copolymers anhydride ring can be bound, by the ring opening reaction, to
amino (-NH2) or hydroxyl groups (-OH) of nucleophilic reagents resulted in either ester/carboxylic acid or amide/carboxylic
acid (1,2). Here MAVA was selected as the macromolecular drug carrier for modification through its reactive anhydride group
by the systematic addition of biologically active molecules such as noradrenaline, doxorubicin hydrochloride, hydroxyurea,
procainamide hydrochloride, cytarabine (3). Structural characterization of the MAVA copolymer and the modified products was
carried out by Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (1H-NMR and 13C-NMR). Their molecular
weights were also determined by size-exclusion-chromatography (SEC). All measurements confirmed that anticancer/other
agents was successfully covalently bound to the MAVA copolymer backbone. A mechanism was then also suggested for the
conjugation reaction. UV-Spectrophotometric measurements, for stability, indicated that conjugates kept its molecular integrity
in physiological-body-fluid, PBS (physiological pH 7.40 at 37 ºC). Antiproliferative activities of conjugates were also determined
by the BrdU cell proliferation ELISA assay, using C6 and HeLa cell lines. Two anti-cancer drugs, cisplatin and 5-fluorouracil, were
included as positive controls. By comparing with cisplatin, 5-florouracil and also free drug, results showed that conjugates have
significant activity against C6 (5-100 µg/ml) and HeLa (75 and 100 µg/ml). Furthermore antiproliferative activities of conjugates
were shown to increase depending on the concentration.
1. Saad GR, Morsi RE, Mohammady SZ, Elsabee MZ. Dielectric relaxation of monoesters based poly(styrene-co-maleic anhydride)
copolymer. J Polym Res. 2008;15:115-123. 2. Atıcı OG, Akar A, Rahimian R. Modification of poly(maleic anhydride-co- styrene)
with hydroxyl containing compounds. Turk J Chem. 2001;25:259-266. 3. Karakus G, Akin Polat Z, Yenidunya AF, Zengin HB, Karakus
CB Synthesis, characterization and cytotoxicity of novel modified poly[(maleic anhydride)-co-(vinyl acetate)]/noradrenaline
conjugate. Polym Int. 2013;62:492-500.
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OP 10 GPCR-INTERACTING PROTEINS AND THEIR INDIVIDUAL FUNCTIONAL ROLES
LIVIA BASILE 1, SALVATORE GUCCIONE 2, GISELLA ALFONSINO 3, DANILO MILARDI 4, MATTEO PAPPALARDO 5
ETNALEAD S.R.L. VIA SAN NULLO 5/I, CATANIA (ITALY)
ETNALEAD S.R.L. VIA SAN NULLO 5/I, CATANIA (ITALY); UNIVERSITY OF DEPARTMENT OF DRUG SCIENCES, CATANIA (ITALY)
3
UNIVERSITY OF CATANIA, DEPARTMENT OF DRUG SCIENCES, V.LE A.DORIA 6, I-95125 CATANIA (ITALY)
4
INSTITUTE OF BIOIMAGING AND BIOSTRUCTURES-NATIONAL COUNCIL OF RESEARCH CATANIA, (ITALY)
5
UNIVERSITY OF CATANIA, DEPARTMENT OF CHEMICAL SCIENCES,CATANIA (ITALY)
1
2
Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter and a vasoactive hormone synthesized from the amino acid
tryptophan mainly in the enterochromaffin cells of the intestine and in the brain. Based on biochemical and pharmacological
criteria, serotonin receptors are classified into seven main subtypes, 5-HT1-7, all of which are G-protein-coupled (GPCR),
whereas the 5-HT3 subtype represents a ligand-gated ion channel. GPCRs represent the most notable family of validated drug
target. The GPCRs structure contains an extracellular N-terminal and intracellular C-terminal, seven transmembrane helices
(7TMH) joined by intracellular and extracellular loops. 5-HT-7 receptor is involved in the regulation of important physiological
and pathological processes, such as emotions, thermoregulation, circadian rhythmicity, memory processes and smooth muscle
relaxation and depression (1). Comprising α, β, and γ subunits, the G protein binds to an agonist-activated receptor, and this
interaction triggers exchange of GDP for GTP in the GTPase domain of the G protein’s α subunit (2). Large Scale Molecular
Dynamic simulations using an experimentally (in vitro mutagenesis) validated homology model and a Gs-GTP complex were
performed to study the preferential interaction between 5-HT-7 and the Gs or G12 proteins, which probably differs in different
pathologies (3). Implicit in the search for the functional relevance of these interactions is the expectation that could serve to
address highly selective therapeutic opportunities.
1. Rosenbaum DM., et al. The structure and function of G-protein-coupled-receptors. NATURE. 2009; 459(7245):356-63. 2.
Wess J. G-protein-coupled: Molecular mechanisms involved in receptor activation and selectivity of G-protein recognition; The
FASEB Journal. 1997; 11(5):346-54. 3. Kvachnina El, et al. 5-HT-7 receptor is coupled to G alpha subunits of heterotrimeric G12protein to regulate gene transcription and neuronal morphology. J Neurosci. 2005;25(34):7821-30.
OP 11 NOVEL NANOPARTICLES FOR GENE DELIVERY: PREPARATION, OPTIMIZATION, CELL UPTAKE AND CYTOTOXICITY
INVESTIGATION
SANAM ARAMI 1, MOHAMMAD REZA RASHIDI 2, MAJID MAHDAVI 3, MOHAMMAD SAEID HEJAZI 4
PHARMACEUTICAL BIOTECHNOLOGY DEPARTMENT AND STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ
UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
2
PHARMACEUTICAL CHEMISTERY DEPARTMENT, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ,
IRAN
3
BIOCHEMISTRY DEPARTMENT, FACULTY OF SCIENCE, TABRIZ UNIVERSITY, TABRIZ, IRAN
4
PHARMACEUTICAL BIOTECHNOLOGY DEPARTMENT, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
1
Cancer is one of the most life threatening diseases worldwide and the breast cancer is the top cancer among women. siRNA
(small interferring RNA) is a single stranded RNA that interferes with the expression of specific genes with complementary
nucleotide sequences. siRNA functions by causing mRNA to be broken down after transcription, resulting in no translation .
The porpuse of this study was to prepare novel nanoparticles carrying the siRNA strands to cancerous cells. The nanoparticles
designed and syntethised as below: The desired nanoparticles should be biocampatible and have positive charge to be safe
and can form complexes with siRNA. They were syntethised encapsulating a ferricoxide core with polyethyleneglycol-lactide
polymer, chitosan and polyethylene imine respectively. The structure had been checked after each step via spectroscopic
methods. Size, zeta potential and their ability of comlexation to siRNA have been assessed by particle size analyzer, zetasizer
and gel retardation assay on agarose gel, respectively . Their toxicity has been avaluated towards MCF-7 , human breast cancer
cells, using MTT assay in 3 time intervals (24, 48, 72 hours). The results showed that the nanoparticles size was 37.43± 1.45
nanometers in diameter, and the electric charge was measured +49.2 mV .The cytotoxicity results didnt show significant
cytotoxicity toward the cells, although the survival percent has been reduced while increasing the particle concentration. So,
the mentioned particles can be carriers for gene delivery in MCF-7 cells. Detailed tests will be done on their cellular uptake and
gene silencing.
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OP 12 PREPARATION AND IN VITRO- IN VIVO EVALUATION OF TRANSDERMAL FORMULATIONS OF BETAHISTINE
SEVINC SAHBAZ 1, BETUL DORTUNC 1, MEHMET ZAFER GOREN 2
FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, MARMARA UNIVERSITY, AYDARPASA, ISTANBUL,
TURKEY
2
FACULTY OF MEDICINE, DEPARTMENT OF MEDİCAL PHARMACOLOGY, MARMARA UNIVERSITY, 34854 BAŞIBÜYÜK, ISTANBUL,
TURKEY
1
Betahistin has been used in the treatment of diseases accompanied by impaired peripheral circulation, e.g. Méniѐre’s syndrome,
to reduce the frequency of episodes of vertigo and tinnitus (1). The drug has a short half-life and should be taken three times
daily due to the rapid elimination. Contraindication in patients with peptic ulcer history and the difficulty of frequently dosing
requires administration ways other than the oral route. In the study, matrix transdermal system formulations of betahistine
were prepared. When the drug is given as controlled release system, dosing time interval will be extended, so the patient
compliance will be improved. As the dose amount given to the patient is reduced, adverse effects will be seen less and high
amount dose loading will be prevented. Besides, the patient can remove the patch easily in case of an adverse effect or
whenever he wants (2). To prepare the formulations, Eudragit RL 100 and Eudragit RS 100 polymers were preferred which are
widely used in controlled release dosage forms. Formulations were prepared using different ratios of these two polymers and a
suitable plasticizer and its ratios were optimized. Drug release tests and then, ex-vivo penetration studies from excised human
skin were evaluated. In-vivo studies were carried out with Wistar rats in three groups. The blood concentrations of the drug
were evaluated and as a conclusion, with transdermal formulations betahistine could be seen at least for 12 hours in the blood.
1. Weiser M, Strösser W, Klein P. Homeopatic vs Conventional Treatment of Vertigo. Arch Otolaryngol Head and Neck Surg.
1998; 124:879-885.
2. Hadgraft J. Dermal and Transdermal Delivery. In: Rathbone MJ, Hadgraft J, Roberts MS editors. Modified Release Drug Delivery
Technology. New York: Marcel Dekker Inc., 2003; p. 471-480.
OP 13 CHARACTERIZATION STUDIES OF WELL-DEFINED BLOCK CO-POLYMER ASSEMBLIES
GOKCEN YASAYAN 1, FRANCISCO FERNANDEZ TRILLO 2, STEPHANIE ALLEN 2, MARTYN C. DAVIES 2, CAMERON ALEXANDER 2
1
2
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
SCHOOL OF PHARMACY, UNIVERSITY OF NOTTİNGHAM, NOTTİNGHAM, UK
In recent years, synthetic chemistry has expanded the number of amphiphiles that can form vesicular aggregates, with some
examples showing improved stabilities when compared to phospholipid vesicles or liposomes.(1) Among these amphiphiles,
polymers offer great potential in the preparation of vesicles, as the correct choice of polymerisation techniques, allows for a
wide range of physical, chemical and mechanical properties. In addition, factors such as polymer architecture and molecular
weight can be controlled in order to enhance overall properties.(2) In this study, six types of amphiphilic block copolymer
structures derived from poly(phenylacrylamide)-block-poly(4-acrylamidobutanoic acid) with various chain lengths have been
characterised. To investigate the ability of amphiphilic block copolymers to self-assemble and the properties of the formed
assemblies, firstly a solvent exchange method was used to obtain vesicles and a dye inclusion/release assay was performed
using a fluorescence spectrometer. Secondly, these polymeric assemblies were characterised by atomic force microscopy,
transmission electron microscopy, dynamic light scattering and zeta potential measurements. Afterwards, the responses of the
assemblies to pH changes were investigated; the behaviour of the assemblies at pH 10, pH 7.4, pH 4 and pH 2 was studied by
atomic force microscopy, dynamic light scattering and zeta potential measurements. Finally, the effect of adding a polycation,
branched polyethylene imine on assemblies was examined by coating assemblies with this polycation; and the properties
were investigated by dye inclusion/release assay, atomic force microscopy, dynamic light scattering, and zeta potential studies.
1School of Pharmacy, UNIVERSITY of Nottingham, Nottingham, UK. 2Department of Pharmaceutical Technology, Faculty of
Pharmacy, Marmara UNIVERSITY, Istanbul, Turkey.
References
1. Discher BM, Won YY, Ege DS, Lee JCM, Bates FS, Discher DE, et al. Polymersomes: Tough vesicles made from diblock
copolymers. Science. 1999;284(5417).
2. Smart T, Lomas H, Massignani M, Flores-Merino MV, Perez LR, Battaglia G. Block copolymer nanostructures. Nano Today.
2008;3(3-4):38-46.
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OP 14 EFFECT OF TAURINE ON CHEMOTHERAPY INDUCED NAUSEA AND VOMITING IN ACUTE LYMPHOBLASTIC LEUKEMIA
MINA ISLAMBULCHILAR 1, MOHAMMADREZA SATTARI 2, IRAJ ASVADI 3, ZOHREH SANAAT 3, ALI ESFAHANI3
STUDENT RESEARCH COMMITTEE AND FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN.
HEMATOLOGY AND ONCOLOGY RESEARCH CENTER & DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY, FACULTY OF
PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
3
HEMATOLOGY AND ONCOLOGY RESEARCH CENTER, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
1
2
The purpose of this study was to evaluate the effect of oral taurine supplementation on the incidence of chemotherapy induced
nausea and vomiting in young adults with acute lymphoblastic leukemia. Forty young adults (aged over 16 years) with acute
lymphoblastic leukemia were recruited to the study at the beginning of maintenance course of their chemotherapy. The study
population was randomized in a double blind manner to receive either taurine or placebo. Life quality and adverse effects were
assessed using a questionnaire. Data were analyzed using SPSS software. Of total participants, 43.8% were female and 56.3
% were male. The median age was 19.16±1.95 years (ranges: 16-23 years). The results indicated that taurine supplemented
patients reported a significant (P<0.05) improvement in chemotherapy induced nausea and/or vomiting after taking taurine
during whole study period. Taurine administration significantly improved chemotherapy associated taste and smell alterations
compared to the control patients (P<0.05). Moreover, taurine significantly reduced weariness compared to placebo group
(P<0.05). In conclusion this study showed that taurine co-administration decreased the chemotherapy associated nausea and
vomiting during the maintenance period of treatment in young adults with acute lymphoblastic leukemia.
OP 15 INVESTIGATION OF HISTONE LYSINE TRIMETHYLATION OR ACETYLATION IN SPORADIC BREAST TUMORS AND
MATCHED NORMAL TISSUES
SEHER KARSLI-CEPPIOGLU 1, GAëLLE JUDES 2, ASLİHAN DAGDEMIR 2, MARJOLAINE NGOLLO 2, FRéDéRIQUE PENAULT-LLORCA 2,
ANDRé LEBERT 3, YVES-JEAN BIGNON 2, DOMINIQUE BERNARD-GALLON 2
DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF ONCOGENETICS, CENTRE JEAN PERRIN, PLACE HENRI DUNANT, CLERMONT-FERRAND, FRANCE.
3
UNIVERSITY BLAISE PASCAL, INSTITUT PASCAL UMR AUBIèRE, FRANCE
1
2
Epigenetic alterations are important key factors for cancer development and prognosis. Breast cancer is induced by the
accumulation of altered gene regulation. Therefore, we aimed to assess chromatin immunoprecipitation (ChIP) of three
modified histones including H3K27me3, H3K9ac, and H3K4ac in breast tumors compared with the normal tissue. In order to
identify the regulation of gene expression in 150 tumors and normal tissues, we proposed to follow ChIP with Q-PCR of 7 genes
(ERα, ERβ, PGR, BRCA1, EZH2, P300 and SRC3). In addition, we have evaluated protein levels by western blot. RT-qPCR was
used for the quantification of mRNA levels. Our results demonstrated that H3K27me3 histone mark has an important role in
controlling the gene expression. Gene expression levels of studied H3K27me3-enriched genes were significantly low in breast
cancer tumors when compared with normal tissue (p<0.05). Expression levels of ERβ and PGR genes were decreased on H3K4ac
mark-enriched sites in tumors (p<0.05). ERβ and PGR genes play a crucial role in determining breast cancer aggressiveness,
thus a modified H3K4ac mark would be substantial transcriptional expression of these genes. ERα protein levels in luminal-like
tumors were higher than in control tissue samples. We found that EZH2 protein levels in basal-like tumors were increased. In
addition, mRNA levels of EZH2 were higher in tumors than in normal tissue samples. Protein levels of PGR were also increased in
tumors and these results were consisted with mRNA levels of PGR. We aimed to provide an insight into epigenetic mechanisms
of breast cancer with this project. In conclusion, further investigations would reveal new aspects in biomarkers to predict breast
cancer aggressiveness and potential epigenetic therapies.
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OP 16 NOVEL 4-THIAZOLIDINONES AS NON-NUCLEOSIDE INHIBITORS OF HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA
POLYMERASE
GIZEM CAKIR 1, ILKAY KUCUKGUZEL 1, RUPA GUHAMAZUMDER 2, DINESH MANVAR 2, ESRA TATAR 1, AMARTYA BASU 2,
BHARGAV A. PATEL 3, TANAJI T. TALELE 3, NEERJA KAUSHIK-BASU 2
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, HAYDARPAŞA 34668
İSTANBUL, TURKEY
2
THE STATE UNIVERSITY OF NEW JERSEY, NEW JERSEY MEDICAL SCHOOL, DEPARTMENT OF BIOCHEMISTRY & MOLECULAR
BIOLOGY, USA
3
ST. JOHN’S UNIVERSITY, DEPARTMENT OF PHARMACEUTICAL SCIENCES, COLLEGE OF PHARMACY AND HEALTH SCIENCES,
QUEENS, USA
1
Hepatitis C virus (HCV) is an important human pathogen of global public health significance with an estimated prevalence of 180
million people world-wide and a predicted 100,000 new-cases each year. The HCV NS5B RNA dependent RNA polymerase (RdRp)
is a validated and attractive target for drug discovery. In this study, we report the therapeutic potential of the thiazolidinone
scaffold against HCV NS5B RdRp employing 5-(substituted benzylidene)-2-[[5-aryl-1,3,4-thiadiazol-2-yl]imino]-1,3-thiazolidine4-ones. We synthesized 21 derivatives of this scaffold (22-42) and investigated their anti-HCV potency and anti-HCV NS5B RdRp
activity. Of these, compounds 22-28 bearing 1,3-thiazolidine-4-one moiety displayed 6-31% anti-NS5B RdRp activity whereas
their corresponding arylidene derivatives 29-42, with the exception of compounds 32 and 34 exhibited ≥70% NS5B inhibition
at 50 µM. Among the arylidene derivatives, compound 33 was the most active with an IC50 value of 25.3 µM, whereas the
other derivatives of this series displayed between 25-55 µM IC50 values. In antiviral cell based assay, an inverse correlation
between the effect of the compounds on cellular viability and their antiviral efficacy emerged with the 1,3-thiazolidine-4one moiety bearing compounds 22-28 exhibiting ≥68% cellular viability but ≤35% anti-HCV activty, while the corresponding
arylidene derivatives 29-42 displayed ≤45% cellular viability but ≥70% anti-HCV activty. We further present a binding interaction
analysis of compound 33 within thumb pocket-II (TP-II) of NS5B with the objective of gaining insight into the compound binding
contacts for better inhibitor derivatization.
OP 17 IN VITRO SCAVENGING ACTIVITY AND CYTOTOXICITY EFFECT OF GREEN TEA (CAMELLIA SINENSIS) EXTRACTS AGAIN
PROSTATE CANCER CELL LINES.
SOUMIA LASSED , CLAUDIA DEUS , DJAMILA ZAMA , PAULO OLIVEIRA , FADILA BENAYACHE , SAMIR BENAYACHE
UNITé DE RECHERCHE VALORISATION DES RESSOURCES NATURELLES, MOLéCULES BIOACTIVES ET ANALYSES
PHYSICOCHIMIQUES ET BIOLOGIQUES (VARENBIOMOL), DéPARTEMENT DE CHIMIE, FACULTé DES SCIENCES EXACTES,
UNIVERSITé CONSTANTINE 1, 25000 CONSTANTINE, ALGéRIE.
Prostate cancer has been one of the most frequently diagnosed neoplasis in western countries. Numerous experimental
suggest that both dietary and lifestyle factor can act by promoting inflammation and oxidative stress leading to proteins, lipids,
DNA damage, associated with prostate cancer initiation and development. Prostate cancer is a suitable target for primary
chemopreventive intervention because is a unique malignancy that grows very slowly before symptoms arise. Green tea
obtained from the dried leaves of Camellia sinensis plant has been studied extensively for their effect in cancer prevention.
It can through their polyphenols antioxidant activity quench ROS and chelae transition metals produced during all the
carcinogenesis; however it can also be a source of ROS generation inducing stress and activating apoptotic pathways in cancer
cells. In this study, we evaluate the OH. Scavenging capacity of the different green tea extracts (ether, chloroform, ethyl acetate,
n-butanol) and their cytotoxicity effect again human prostate cancer cell line, PC-3 and human fibroblasts cell line, BJ using the
Sulforhodamine B (SRB) assay. The ether and chloroform extracts showed no scavenging activity on OH., however the butanolic
and ethyl acetate extracts observed to have a strong scavenging activity, with IC50 values of 16.72 and 20.57 µg/ml respectively
compared to ascorbic acid (positive control), and the half inhibition concentration was 10.32 µg/ml. The SRB assay results of
24 hours treatment obtained showed that the ether extract induce the cell death for both cancer and noncancerous cells at a
concentration ≥ 50 µg/ml, while the chloroform extract have no effect. The butanolic and ethyl acetate extracts revealed a dose
dependent effect in cancer cells. They can inhibit the proliferation of PC-3 cell line with IC50 values of 37.74 and 36.37µg/ml
respectively when the effect was not significant in BJ cell line. The results obtained in the present study suggest that the green
tea consumption may prevent from prostate cancer or reduce its development after onset.
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OP 18 PLASMA GROWTH ARRREST SPECIFIC (GAS6) LEVELS IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
DILVIN GUNEY 1, AYSIN TULUNAY 2, FUNDA PEPEDIL 2, ISIK KAYGUSUZ 2, CAFER ADIGÜZEL 3, TULIN TUGLULAR 2, EMEL
EKSIOGLU-DEMIRALP 4, FIKRIYE URAS 1
MARMARA UNIVERSITY SCHOOL OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENTS OF HEMATOLOGY, ISTANBUL, TURKEY
3
MEDIKAL PARK HOSPITAL GOZTEPE, DEPARTMENT OF HEMATOLOGY, ISTANBUL ,TURKEY
4
MEMORIAL HOSPITAL ,TISSUE TYPING AND IMMUNOLGY , ISTANBUL TURKEY
1
2
GAS6 (growth arrest-specific gene 6) is a vitamin K-dependent protein. Gas6 binds to Tyro3, Axl and Mer tyrosine kinase receptors
(TAM receptors). GAS6 is over expressed in various cancers including glioblastoma, lung, gastric, breast, colon, gastric, and
ovarian cancer. The objective of this study is to investigate the plasma level of GAS6 in patients with B-Cell chronic lymphocytic
leukemia (B-Cell-CLL). B-Cell-CLL patients (grade 0-1, according to the classification of RAI), who were not on a drug treatment,
were recruited in this study (n= 24, 11 female, 13 male). Their ages were 39 to 79 years (mean= 60.7), and the control group
consisted of 24 healthy volunteers (8 female, 16 male), whose age range was 51-78 years (mean= 63.5). EDTA-plasma (platelet
poor) was isolated by centrifugation (3100 x g) and then human GAS6 ELISA Kit (R&D, Minneapolis, MN, US) was used to assay
GAS6 concentration. The concentration of plasma GAS6 in the patient group was 4.11-26.44 ng/ml (mean= 14.85 ± 5.77). In the
control group, the range of total plasma GAS6 was between 9.57-31,28 ng/ml (mean= 16.8±6.18). The concentration of plasma
GAS6 in the B-Cell-CLL group was not significantly different than those of the control group (p=0.265). This is a preliminary study
with a small group. Future studies will show us whether plasma GAS6 concentrations in patients with CLL are different from the
control group or not. Further studies focusing on the molecular mechanism are required to elucidate the actual role of Gas6/
TAM signaling in B-Cell-CLL
OP19 THE INVESTIGATION OF ANTIDIABETIC AND IN VIVO ANTIOXIDANT CAPACITY OF FRUITS, BARKS AND LEAVES OF
CORNUS MAS L.
AYLIN SEPICI DINCEL 1, ENGIN CELEP 2, MERAL YUKSEL 3, ERDEM YESILADA 2
FACULTY OF MEDICINE, GAZİ UNIVERSITY, ANKARA
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, UNİVESİTY OF YEDİTEPE, ISTANBUL
3
DEPARTMENT OF MEDİCAL LABORATORY TECHNİCİANS, VOCATİONAL SCHOOL OF HEALTH RELATED SCİENCES, MARMARA
UNIVERSITY, ISTANBUL
1
2
In our country, during our field survey we observed that cornelian cherry (Cornus mas L., Cornaceae), fruits, leaves and bark
of branches have been used against diabetes among the country people. In order to evaluate the role of cornelian cherry in
the treatment of type-2 DM, this work had the following aims; to determine the hypoglycaemic effect of cornelian cherry in
streptozocin induced diabetes mellitus in rats and to elucidate the mechanism of action of cornelian cherry through evaluating
the effects on the serum insulin (ng/mL) concentrations in normal and diabetic animals and as well as on various routine
biochemical parameters, AGE (microg/mL), sRAGE (ng/mL) and brain, kidney, liver, heart, tissues of luminol and lusigenin
values (rlu/mg tissue) besides serum total antioxidant status (mM). Our study had 9 groups; normoglyceamic control, diabetes,
diabetes+reference group, diabetes groups treated with 100 and 200 mg/kg of methanol extraction of fruits, barks and leaves.
Another set of study groups were performed for oral glucose tolerance test. Our results revealed that especially leaves (100 mg/
kg) and the fruits (200 mg/kg) have a glucose lowering effects; increasing insulin and total antioxidant status, decreasing AGEs
products and could effect the tissue levels of luminol and lusigenin except liver tissue. As conclusion, the above observations
have clearly demonstrated that cornelian cherry (Cornus mas L.,Cornaceae) as a folk remedy, exerts effectual hypoglycaemic
activity in diabetic animals without inducing apparent toxicity, which confirms the folkloric utilisation.
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OP 20 SEQUENTIAL INJECTION TECHNIQUE AS A TOOL FOR SAMPLE PRE-TREATMENT IN PHARMACEUTICAL ANALYSIS
IVANA ŠRáMKOVá , LUKáš ZAHáLKA , DALIBOR ŠATíNSKý , BURKHARD HORSTKOTTE , HANA SKLENářOVá , PETR SOLICH
DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, CHARLES UNIVERSITY, , HRADEC KRáLOVé CZECH
REPUBLIC
Sequential injection analysis (SIA) is a flow technique based on programmable, bidirectional discontinuous flow. A typical
SIA system consists of a multiposition valve, peristaltic or syringe pump, holding coil and a detector, all computer controlled.
Solutions of a sample and reagents are aspirated by means of the pump into the connecting holding coil via a specific port of
the multiposition valve. After flow reversal towards a detection flow cell, the solutions merge and the signal of the formed
reaction product is recorded. The feasibility of SIA makes it an advantageous tool for sample pre-treatment since this step is
often tedious and time consuming. Different microextraction methods, both into liquid and onto solid phase, can be performed
within a SIA system, as demonstrated here by following novel applications: A. Dispersive liquid-liquid microextraction (DLLME)
e.g. in analysis of thiocyanates in human saliva samples (1); B. Head-space single-drop microextraction (HS-SDME) for analysis
of ethanol in wine (2); C. Microextraction by packed sorbent (MEPS) carried out as a sample cleaning procedure prior to HPLC
analysis of propranolol in urine. In this work, the benefits and potential of employing SIA in sample pre-treatment, especially
regarding the analysis time, reagents, sample and solvents consumption, waste production, automation and simplification,
are presented. Acknowledgements The authors gratefully acknowledge the financial support of Zentiva a.s and the Charles
UNIVERSITY in Prague – project GAUK 140/50/35003. The work is co-financed by the European Social Fund and the state budget
of the Czech Republic. TEAB, project no. CZ.1.07/2.3.00/20.0235.
1. Acebal C C, Sklenářová H, Škrlíková J, Šrámková I, Andruch V, Balogh J S, Solich P. Application of DV-SIA manifold for
determination of thiocyanate ions in human saliva samples. Talanta 2012; 96: 107-112 2. Šrámková I, Horstkotte B, Solich P,
Sklenářová H. Automated in-syringe single-drop head-space micro-extraction applied to the determination of ethanol in wine
samples. Anal Chim Acta 2014; http://dx.doi.org/10.1016/j.aca.2014.04.031
OP 21 DETERMINATION AND PHARMACOKINETICS OF OLANZAPINE IN HUMAN PLASMA BY LC/MS METHOD
MEVLUT ALBAYRAK , MEHMET EMRAH YAMAN , ONUR ŞENOL , YUCEL KADIOGLU
ATATURK UNIVERSITY FACULTY OF PHARMACY, ERZURUM, TURKEY
Olanzapine ( 2 - Methyl-4- ( 4 – methyl – 1 - piperazinyl ) – 10 H – thienol [ 2,3 – b ] [ 1,5 ] benzodiazepine ), is an atypical
antipsychotic drug which is used for the treatment of schizophrenia and bipolar disorder. Several analytical methods in order to
determine olanzapine concentration in human plasma samples at therapeutic range could be found in literature. In the present
study, a simple, sensitive and rapid liquid chromatography mass spectrometry (LC/MS) method was developed and validated
to determine olanzapine in human plasma using irbesartan as internal standard. The validated and proposed method was
applied to healthy volunteers for pharmacokinetic study. Extraction of olanzapine from plasma sample was accomplished by a
simple liquid-liquid extraction method and the separation of analytes were carried out on a reserved phase C18 column using
an isocratic mobile phase mixture and analyzed by MS using positive ion atmospheric pressure chemical ionization and multiple
reaction monitoring. The linear concentration range was found as 2-300 ng/ml. The limit of detection (LOD) and the limit of
quantitation (LOQ) were found as 0.8 ng/ml and 2 ng/ml with an acceptable precision, respectively. Inter-day accuracy (relative
error) and precision (relative standard deviation) were ranged from 2.94 to 3.33%, and from 1.51 to 6.70 %, respectively.
The average recovery values of extraction from spiked plasma samples were 94.8 ± 3.1%. The validated method has been
successfully used to analyze human plasma samples and can be applied to routine clinical studies and pharmacokinetic studies.
1. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT: Radioreceptor binding profile of
the atypical antipsychotic olanzapine. Neuropsychopharmacology 1996; 14:87–96 2. Cao, J, Zhang, ZJ, Tian, Y, Li, YY, Rui, JZ;
Liquid Chromatography-Mass Spectrometry Method for the Determination of Olanzapine in Human Plasma and Application to
a Bioequivalence Study. Current Pharmaceutical Analysis 2012; 8:247-254
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OP 22 CLINICAL PHARMACOTHERAPY EDUCATION BY PROBLEM-BASED LEARNING IN CLINICAL PHARMACY COURSES
SULE APIKOGLU-RABUS
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY, FACULTY OF PHARMACY, TURKEY
In our institution, problem based learning (PBL) has been being performed since 2000 at the ‘pharmacy skills laboratory’ practices
of the Clinical Pharmacy course at the 4th year of the education. The students practice basic pharmaceutical care principles
through case-based identification and solution of pharmaceutical care issues and therapy monitoring. Surveys questioning
the impact of PBL on the students and their attitudes towards the PBL sessions were administered after the whole practice
to all of the 4th year students who attended to the full course of the PBL practice. Follow-up surveys questioning the benefits
of the PBL sessions while practicing during the Pharmacy Practice courses that took place at the hospital wards, community
pharmacies and/or drug industry throughout the 5th year were handled out at the end of the 5th year to the same students.
All of the students strongly agreed or agreed that their clinical knowledge improved after PBL sessions. Of the students, 90-97%
strongly agreed or agreed that PBL is better than the classical practical and theoretical courses. On the follow-up questionnaires
administered at the 5th year 86% of the students strongly agreed or agreed that they used the knowledge, skills and the
approach to problem-solving that they earned during the PBL sessions while practicing at the hospital wards; while this rate was
83% for the community pharmacy. The students showed positive attitudes towards PBL that were still present after one-year.
OP 23 THE IMPORTANCE AND THE USE OF CREATIVE DRAMA IN PHARMACY EDUCATION, COMMUNICATION SKILLS IN
PROFFECIONAL LIFE
FILIZ ARIÖZ ÖZDEMIR1, GÖKNIL PELIN COŞKUN2
1
DEPARTMENT OF ANALYTİCAL CHEMİSTRY, FACULTY OF PHARMACY, MARMARA UNİVERSİTY, ISTANBUL, TÜRKİYE
DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, FACULTY OF PHARMACY, MARMARA UNİVERSİTY, ISTANBUL, TURKEY
2
Communication skills and its use is far more important in pharmaceutical profession and these skills can be given to pharmacy
students during their education. In recent years, in the field of education and personal development; ‘Creative Drama Method’
is widely used. This method is based on group work and the individuals of the group, ‘act’ with a game flow which is a lifestyle,
behaviour, concept or an event by using improvization, role playing, theatre and drama technics. The content of this work covers the results of a group work that was done in EPSA (European Pharmaceutical Students’ Association) Twinnet Project with 15
Serbian and 10 Turkish pharmacy students, a 3 hours of workshop. The first goal of this workshop was to motivate participants
to like eachother, increase the group dynamic, preapare the body and the participants for the next stage. In this first stage,
games are widely used and this workshop’s second stage was the ‘acting’ stage. The problem or the subject were acted by the
participants and creative solutions were expected. In this workshop, the participants were given 4 different subjects and were
asked to act them with 5 different groups. Every participant evaluated every groups’ acts and their feedback were asked. The
last stage of this workshop was the evaluation of the whole exercise and the participants were asked to summarize the whole
event in few words anonymously. The feedbacks from the participants led us conclude that; 1-Group individuals’ friendship,
2-Learning and comparison of two different country’s pharmacy education models and the use of pharmaceutical profession in
different areas, 3-Every individual gained experience and creative solutions and they can use these in their further professional
life.
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OP 24 HEALTH PROFESSIONAL STUDENTS KNOWLEDGE ON PHARMACOVIGILANCE (PV)
MERI KOLUACIK 1 , ASLI CULDUZ 2 , HANDE SIPAHI 3 , CIGDEM KASPAR 4 , NAZLI SENCAN 2
1
YEDITEPE UNIVERSITY FACULTY OF PHARMACY
2
DEPARTMENT OF PHARMACY MANAGEMENT AND SOCIAL PHARMACY, FACULTY OF PHARMACY, YEDITEPE UNIVERSITY
3
DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, YEDITEPE UNIVERSITY
4
DEPARTMENT OF BIOSTATISTICS, FACULTY OF MEDICINE, YEDITEPE UNIVERSITY
Spontaneous reporting of adverse drug reactions (ADRs) has a critical role on public health. Pharmacovigilance (PV) system
tries to minimize the potential health risks , outcomes of medicine consumption for public. The aim the study is to raise
the knowledge and awareness of the health care professional students on PV. An education presentaion is prepared by the
researchers and approvels and appointments are done via faculty professors. Between February 2014 and April 2014 trainings
have been conducted. The 3rd and 4th class students of the pharmacy, nursing, nutrition and dietetics, physiotherapy and
rehabilitation departments have participated. 8 different conference each took 20 minutes and 234 students have participated.
A survey was applied, awareness and opinions of the PV before and after the education was measured. The knowledge of
PV, reasons for not reporting, appreciated to the education were evaluated. According to results, 50% of students declared
that they have never heard PV system. After the training section, 91% of the students reported that PV system/spontaneous
reporting is helpful for detection and protection from ADRs. Academic resarchers should not only conduct scientific study but
also inform and involve in social interactions so as to promote public health. The results suggest that PV training and education
sessions for health care professional students are needed to be increased for the knowledge of PV and to foster positive
attitudes toward adverse effects of drugs.
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POSTER PRESENTATIONS
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PP 1 EFFECT OF COSOLVENTS ON MICELLE FORMATION OF AMPHIPHILIC DRUG AMITRIPTYLINE HYDROCHLORIDE
HASAN TOLGA ÖZÇAM , SINEM GÖKTÜRK
DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, GENERAL CHEMISTRY DIVISION, FACULTY OF PHARMACY, MARMARA
UNIVERSITY, ISTANBUL, TURKEY
Several drug molecules such as phenothiazine and benzodiazepine tranquilizers, analgesics, tricyclic antidepressants and nonsteroidal anti-inflammatory drugs display surface activity i.e. amphiphilic behavior (1-3). Amitriptyline hydrochloride (AMT)
is a pharmacologically active compound and is amphiphilic in nature. It belongs to the family of tricyclic antidepressants and
possesses a rigid, almost planar tricyclic ring system and a short hydrocarbon chain carrying a terminal nitrogen atom. In the
present study micellization of the amphiphilic drug AMT in the absence and presence of cosolvents have been reported by
using conductometric measurements at 298 K. Conductometric measurements were successfully used in determination of
critical micelle concentration (CMC) of AMT in aqueous media. The effect of various concentrations of organic solvents such
as methanol and ethanol (v/v) on micelle formation of AMP in aqueous solutions has been also studied. From conductivity
data the ionization degree (α) and counterion binding parameter (β) have been obtained. It was observed that the presence
of cosolvents, diminished the micelle formation of AMT i.e. increased the CMC. Micellization of AMT totally inhibited when
cosolvent concentration reached a certain value. 1. Schreier S, Malheiros S.V.P, de Paula E. Surface active drugs: self-association
and interaction with membranes and surfactants. Physicochemical and biological aspects. Biochimica et Biophysica Acta 2000;
1508: 210–234. 2. Erdinc N, Gokturk S, Tunçay M. A study on the adsorption characteristics of an amphiphilic phenothiazine
drug on activated charcoal in the presence of surfactants. Colloids and Surfaces B: Biointerfaces 2010; 75: 194–203 3. Göktürk
S, Var Ü. Effect of pharmaceutically important cosolvents on the interaction of promethazine and trifluopromazine HCl with
sodium dodecyl sulfate micelles. Journal of Dispersion Science and Technology 2012; 33:527–535. Acknowlodgements: This
study was financially supported by Research Fund of Marmara UNIVERSITY with the project numbers of SAG-CYLP-280214-0041.
PP 2 CHEMICAL COMPOSITION AND ANTIMICROBIAL ACTIVITY OF THE ESSENTIAL OIL FROM CULTIVATED SATUREJA
HORVATII SILIć (LAMIACEAE)
MARINA MILENKOVIC1, MIHAILO RISTIC2, DMITAR LAKUSIC3, VIOLETA SLAVKOVSKA4, BRANISLAVA LAKUSIC4
DEPARTMENT OF MICROBIOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF BELGRADE, VOJVODE STEPE BELGRADE, SERBIA
1
INSTITUTE FOR MEDICINAL PLANT RESEARCH “JOSIF PANCIC“, SERBIA
2
INSTITUTE OF BOTANY AND BOTANICAL GARDEN, SERBIA
3
DEPARTMENT OF BOTANY, FACULTY OF PHARMACY, UNIVERSITY OF BELGRADE, SERBIA
4
In this study the chemical composition and antimicrobial activity of the essential oils of Satureja horvatii cultivated plants
(Belgrade, Serbia) were characterized. S. horvatii is an endemo-relict species of Montenegro. The essential oils were isolated,
from the aerial parts of the plants at different phenological stages, by hydrodistillation and analyzed by GC and GC/MS.
Chemical compositions of the S. horvatii oils showed differences between the plants at different phenological stages. The main
compounds of the essential oil from plants at the flowering stage were linalool (53.5%), thymol (17.9%), and α-terpineol (8.5%).
At the stage of full fruiting the percentage of linalool (58.4–59.5%) and α-terpineol (11.8-12.3%) increased, while those of
thymol (4.6–7.6%) significantly decreased. The antimicrobial activity of tested oils was evaluated against ten standard strains of
microorganisms.The working solutions of essential oils (40 μL/mL) were prepared by dissolving the essential oils (EOs) in DMSO
and subsequent mixing with Müller–Hinton or Sabouraud dextrose broth. The EOs were tested in the final concetration range
of 0.313 - 20.000 μL/mL. All analyzed oils showed the greatest and uniform antimicrobial activity against the yeast (Candida
albicans). The essential oil isolated from plant in the flowering stage showed the maximum activity against Staphylococcus
epidermidis and Staphylococcus aureus. This oil exhibited moderate activity against the Enterococcus faecalis and weak activity
against the other microorganisms. Oils isolated from plants at fruiting stage showed moderate activity against Staphylococcus
epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa and weak activity against the other microorganisms.
Acknowledgement: The authors are grateful to the Serbian Ministry of Science and Technological Development (Project No.
173021 and 173030 ) for financial support. *This abstract has been presented as poster in Fourth International Meeting on
Pharmacy & Pharmaceutical Sciences, Istanbul, Turkey on 18-21 September 2014.
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PP 3 THE EFFECTS OF DNA METHYLTRANSFERASE ENZYMES ON AGING-RELATED HUMAN KLOTHO GENE EXPRESSION*
ELIF ÇAĞLAYAN , KADIR TURAN
DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL-TURKEY
There are both environmental and genetic factors affecting the aging process. One of the important genetic factors associated
with aging is klotho gene. It was shown that Klotho protein encoded by klotho gene has the positive or negative regulatory effects
on many metabolic pathways. However, much information about the regulation of klotho gene is not available. In a recently
published study, it was reported the results suggesting that the promoter region of human klotho gene could be epigenetically
controlled by DNA methylation. Therefore, in this work, it was aimed to reveal the effects of DNMT3A and DNMT3B enzymes
on the expression of klotho gene. For this purpose, it was artificially changed the expression level of DNMT3A and DNMT3B
in human originated HEK293 cells with siRNA transfection or overexpression and investigated by using reporter luciferase
gene how klotho gene promoter activity was affected. The results obtained in this research showed that DNMT enzymes have
negative regulatory effects on klotho gene promoter organized as a chromatin structure, whereas they are enhancing effect
on promoter activity when it was located on plasmid DNA. These results have a great importance to elucidate the functional
mechanism of human klotho gene.
*This work was supported by a grant from scientific research foundation of Marmara UNIVERSITY (grant number: SAG-CYLP-130313-02064, 2013).
PP 4 INVESTIGATION OF THE AFFINITY OF RECOMBINANT SOLUBLE FORM OF HUMAN GLUCAGON RECEPTOR PROTEIN
WITH GLUCAGON*
ŞULE İBIŞOĞLU , KADIR TURAN
DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL-TURKEY
The maintenance of the blood glucose level in a narrow range has a vital importance. The human bodies desire blood glucose
to be maintained between 70 mg/dl and 110 mg/dl. The significant deviations from these values can cause massive damages in
the body. Therefore, the blood glucose level is mainly controlled by particularly insulin and glucagon. Some other factors such
as GLP-1, GIP, cortisol and growth hormone are also involve in this control. More or less synthesis of glucagon and/or insulin
than normal levels in the body or disorders in interactions of these hormones with their receptors lead to a deterioration
in blood glucose and ultimately causes type I or II diabetes. The high level of blood glucagon is also important as much as
insulin deficiency to diabetes. Therefore, extensive studies are being carried out on glucagon receptor antagonists to block
the function of glucagon receptor, having a potential usage in the treatment of diabetes. In this work, we aimed to produce
a recombinant soluble form of human glucagon receptor and to reveal the affinity of this protein to glucagon. Therefore, we
cloned extracellular domain of human glucagon receptor into the mammalian expression vectors (pCAGGS and pCHA) and
monitored the expression and cellular localization of this proteins in mammalian cells. Immunofluorescence assays showed
that, extracellular domain of glucagon receptor is being efficiently expressed in the cells and localized in cytoplasm. The research
to reveal the affinity of soluble extracellular domain of glucagon receptor to glucagon by using co-immunoprecipitation and
co-localization experiments is going on.
*This work was supported by a grant from scientific research foundation of Marmara UNIVERSITY (grant number: SAG-CYLP-131113-0426, 2013).
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PP 5 INVESTIGATION OF THE RELATIONSHIP BETWEEN INFLUENZA VIRUS NS1 PROTEIN AND CELLULAR FACTORS WITH
YEAST TWO-HYBRID ASSAY*
AYŞEGÜL PRINÇAL , KADIR TURAN
DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL-TURKEY
Influenza A viruses are enveloped viruses classified in Orthomyxoviridae family. These viruses have a genome composed of
eight single-stranded, negative sense RNA molecules. NS1 protein, which is the subject of this work, is encoded on the eighth
segment, the smallest segment of the viral genome. It is known that one of the most important functions of the NS1 protein
is to block the host interferon defense mechanisms. In this work, it was aimed to detect of the host cellular proteins related
with influenza virus NS1 protein by using yeast two-hybrid method. Human and avian influenza A virus NS1 protein was used
as a bait and assayed for interaction with the proteins encoded by cDNAs of HEK293 cells. Fourteen candidate genes that may
be related with the NS1 protein were determined. Among these genes, the full length sequence of PSMB4 and EEF1G gene
were cloned in pCHA, a mammalian expression vector, to use in research that carried out with mammalian cells in future. The
other candidate genes were named as NKG1 - NKGn. How the specified candidate proteins interact with NS1 protein and how
effect influenza virus replication were not been evaluated within the scope of this work. Elucidation of the action mechanisms
of these proteins require detailed studies on each candidate protein, one by one. Data obtained in this works will be base for
fighting against viral pathogens.
*This work was supported by a grant from scientific research foundation of Marmara UNIVERSITY (grant number: SAG-CYLP-130313-02065, 2013) and The Scientific and Technological Research Council of Turkey (grant number: 112S518).
PP 6 COMPONENTS, ANTIOXIDANT AND IMMUNOSTIMULATORY ACTIVITIES OF HYPERICUM TOMENTOSUM
AHMED KABOUCHE 1, AICHA BOURATOUA 2, OUASSILA TOUAFEK 2, MESBAH LAHOUEL 3, SAKINA ZERIZER 4, ZAHIA KABOUCHE 2
UNIVERSITY OF CONSTANTINE 1, INATAACONSTANTINE, ALGERIA.
UNIVERSITY OF CONSTANTINE 1, DEPARTMENT OF CHEMISTRY, LABORATORY OF THERAPEUTIC SUBSTANCES (LOST),
CONSTANTINE, ALGERIA.
3
UNIVERSITY OF JIJEL, FACULTY OF SCIENCES, LABORATORY OF MOLECULAR TOXICOLOGY JIJEL, ALGERIA
4
UNIVERSITY OF CONSTANTINE 1, FACULTY OF SCIENCES, DEPARTMENT OF BIOLOGY, CONSTANTINE, ALGERIA.
1
2
The genus Hypericum L. (Clusiaceae) includes numerous species which have been used as medicinal plants for centuries
in the treatment of trauma, burns, rheumatism, neuralgia, gastroenteritis, ulcers, hysteria, bedwetting and depression.
Pholoroglucinols, isolated from Hypericum species, have reported to possess antidepressant properties. We report here,
the isolation of nineteen compounds (a phloroglucinol, flavonoids, phenolic acids, sterols and fatty acids) from the aerial
parts of Hypericum tomentosum L. The structures of the identified compounds were established on the basis of physical and
spectroscopic analysis, and by comparison with literature data. In vivo and in vitro protective effect of the butanolic extract of
H. tomentosum (BEHT) against acute oxidative stress induced by a single dose of 20 mg/kg epirubicin (an anticancer drug) was
evaluated in female Wistar rat using kidney and heart cytosolic fraction. Scavenging effect of BEHT, lipid peroxidation (MDA),
glutathione (GSH) concentration and Catalase activity were measured. BEHT extract restored the renal and heart functions
and clearly shows a protective effect against epirubicininduced oxidative stress. In addition, the immunostimulant potential
of the BEHT on the phagocytic activity was measured by the carbon clearance rate test. The BEH exhibited a dose-dependent
immunostimulant effect on the reticuloendothelial system.
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PP 7 DESIGN, SYNTHESIS AND ANTICOAGULANT ACTIVITY OF NEW FLEXIBLE CALIX[8]ARENE SULFONIC ACIDS
ZAHIA KABOUCHE 1, SEIFEDDINE REKKAB 1, MESBAH LAHOUEL 2, TAIBI BEN HADDA 3, CAROLINE FELIX4
UNIVERSITY OF CONSTANTINE 1, DEPARTMENT OF CHEMISTRY, LABORATORY OF THERAPEUTIC SUBSTANCES (LOST), ALGERIA.
UNIVERSITY OF JIJEL, FACULTY OF SCIENCES, LABORATORY OF MOLECULAR TOXICOLOGY ,ALGERIA
3
LABORATOIRE DE CHIMIE DES MATéRIAUX, UNIVERSITé MOHAMMED-IER, MOROCCO
4
LABORATOIRE D’APPLICATION DE LA CHIMIE à L’ENVIRONNEMENT, UMR 5634, UNIVERSITY, FRANCE
1
2
Calix[n]arenes are macrocyclic molecules, consisting of several phenol units (four to eight) connected via methylene bridges
into ortho position with respect to the hydroxy group. They are generally known to possess the properties-ability to complex
both metal ions and organic molecules. Functionnalized calixarenes are of particular interest because of their potential uses
in complexation electrochemistry, catalysis and in selective enrichment of rare earth metal ions. We report here the synthesis
of flexible calix[8]arenes, bearing a propanosulfonic or a butanosulfonic group at the lower ring and the effect of these watersoluble calix[8]arene sulfonic acids by sub-chronic administration on some hematological parameters using blood samples
obtained from rat. We investigated whether a change in blood coagulation parameters after natural calixarenes administration
in Wistar rats at single dose inhibits platelet aggregation induced by vitamin K or after in vitro incubation of these compounds
with rat fresh blood. The investigation of the anticoagulant activity of the synthesized water-soluble calix[8]arene sulfonic acids
is justified by the structure–activity relationship, which is presented here by the use of POM calculations.
PP 8 SYNTHESIS OF NOVEL 1,3,4-THIADIAZOLE DERIVATIVES FROM L-METHIONINE AND EVALUATION OF THEIR ANTIINFLUENZA VIRUS ACTIVITY
ESRA TATAR 1, SEDA YALDIZ 1, İLKAY KÜÇÜKGÜZEL 1, LIEVE NAESENS 2
1
2
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ISTANBUL, TURKEY
REGA INSTITUTE FOR MEDICAL RESEARCH, KU LEUVEN,BELGIUM
Influenza viruses are single-stranded, negative-sense RNA viruses that belong to the Orthomyxoviridae family and affect birds
and several mammals [1]. They are categorized as type A, B, and C according to antigenic differences of their nucleoprotein
and matrix protein components. Seasonal influenza, also known as the flu, is a highly contagious and acute infection of the
upper and lower respiratory tract [2]. This disease causes substantial morbidity and mortality as well as considerable economic
losses during the epidemic periods. Besides, influenza A viruses are notorious for their pandemic potential which is related
to reassortment between avian, human and/or swine influenza viruses [1]. Medications currently used for the prophylaxis
and treatment of influenza include the M2 ion channel blockers (amantadine and rimantadine) and the neuraminidase
(NA) inhibitors (oseltamivir and zanamivir) [3]. An important drawback of these antivirals is that, in order to be effective,
these drugs must be given within 48 h after onset of symptoms. Besides, oseltamivir and zanamivir are expensive and their
synthesis is time-consuming [2]. During recent years, the emergence of mutant viruses showing resistance to neuraminidase
inhibitors (particularly oseltamivir) has been considered as an increasing clinical problem . Whereas antiviral agents play a
key role in treatment, influenza prevention mainly depends on vaccination. However, these vaccines require annual updating
due to antigenic drift and reassortment of the hemagglutinin (HA) and neuraminidase (NA) genes [4]. Given the drawbacks of
current antiviral therapeutics, there is an urgent need for novel influenza virus inhibitors with a unique mode of action. , We
here present the design and synthesis of a series of novel N-[(1S)-1-[5-(methylamino)-1,3,4-thiadiazol-2-yl]-3-(methylsulfanyl)
propyl]benzamide derivatives. Our synthetic protocol yielded the target compounds in five steps starting from L-methionine.
All synthesized compounds were checked for purity using chromatographic techniques and elemental analysis; and were
characterized by their IR, 1H NMR and 13C NMR spectral data besides pozitive/negative ion MS/MS (ESI) analyses. Novel
1,3,4-thiadiazoles were evaluated for antiviral activity against influenza A (H1N1 and H3N2) and influenza B virus in MadinDarby canine kindey (MDCK) cell cultures. The results will be presented in detail.
References
1] Tintori et.al., Bioorg Med Chem Lett 24 (2014) 280-282.
[2] Severson et.al., J Biomol Screen 13 (2008) 879-887.
[3] Vanderlinden et.al., J Virol 84 (2010) 4277-4288. [4] De Clercq, Nat Rev Drug Discov 5 (2006) 1015-1025.
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PP 9 DEVELOPMENT OF SOME NOVEL THIOUREAS DERIVED FROM 1,3,4-THIADIAZOLES AND 1,2,4-TRIAZOLES AS
ANTITUBERCULAR AGENTS
ESRA TATAR 1, İLKAY KÜÇÜKGÜZEL 1, Ş.GÜNIZ KÜÇÜKGÜZEL 1, SEVGI KARAKUŞ 1, SINEM ÖKTEM-OKULLU 2, NIHAN ÜNÜBOL 2,
TANIL KOCAGÖZ 2
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, HAYDARPAŞA 34668
İSTANBUL, TURKEY
2
ACIBADEM UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL MICROBIOLOGY, MALTEPE 34848 ISTANBUL,
TURKEY
1
The data based on WHO’s Global Tuberculosis Report 2013 [1] comprises of 1.3 million TB deaths, 8.6 million new TB case of
which 1.1 million are HIV (+) patients. Long-term and relatively low-effective multidrug treatment regimen for TB is not welltolerated moreover severe resistance to first line anti-TB drugs has already been developed. According to the literatüre apprising
clinically employed second line antituberculosis drugs; ethionamide, prothionamide, thioacetazone and isoxyl with thioamide
and/or thiourea moieties [2] and our ongoing efforts [3] to obtain novel thiourea derivatives with antituberculosis activity
1-[5-(4-aryl)-1,3,4-thiadiazole-2-yl]-3-substituted thioureas, 1-{3-(methylsulfanyl)-1-[5-(phenylamino)-1,3,4-thiadiazole-2-yl]
propyl}-3-arylthioureas and 1-[4-aryl]-3-[3-(methylsulfanyl)-1-(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)propyl]
thioureas were synthesized and evaluated against Mycobacterium tuberculosis H37Rv strain. Except for 1-[5-(4-chlorophenyl)1,3,4-thiadiazole-2-yl]-3-(4-fluorophenyl)thiourea (KUC060107) and 1-[5-(4-fluorophenyl)-1,3,4-thiadiazole-2-yl]-3-(4fluorophenyl)thiourea (KUC060116) with the MIC value of 4 µg/ml each, our compounds showed moderate antituberculosis
activity with the MIC values of 8-64 µg/ml.
[1] WHO’s Global Tuberculosis Report 2013 [2] Nishida et.al, Chem-Biol Interact. 192 (2011) 21. [3] Küçükgüzel et.al., Bioorg
Med Chem Lett. 11 (2001) 1703. [4] Küçükgüzel et.al.,Eur J Med Chem., 43 (2008) 381.
PP 10 PREVALENCE OF MYCOPLASMA HOMINIS AND UREOPLASMA UREALYTICUM IN PREGNANT AND NON-PREGNANT
WOMEN AND THEIR SUSCEPTIBILITIES TO VARIOUS ANTIBIOTICS
YASEMIN ÖZTÜRK 1, ÖZGE KIZILKALE YILDIRIM 2, ZEHRA KIPRITÇI 1, YEŞIM GÜROL 1, GÜLDEN ÇELIK 1, MERAL BIRBIR 3, CEM
FIÇICIOĞLU 2
DEPARTMENT OF CLINICAL MICROBIOLOGY, YEDITEPE UNIVERSITY HOSPITAL, KOZYATAGI, ISTANBUL, TURKEY
DEPARTMENT OF OBSTETRICS AND GYNECOLOGY, YEDITEPE UNIVERSITY HOSPITAL, KOZYATAGI, ISTANBUL, TURKEY
3
DIVISION PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA
UNIVERSITY, GOZTEPE, ISTANBUL, TURKEY
1
2
Mycoplasma hominis and Ureoplasma urealyticum may cause infections of the genitourinary tract in humans. These
microorganisms may also cause Bartholin’s gland abscess, vaginitis, cervicitis, pelvic inflammation. Furthermore, Mycoplasma
hominis may cause meningitis and brain abscess in infants (1). Hence, prevalences of both Mycoplasma hominis and Ureoplasma
urealyticum were investigated in the 60 pregnant and 56 non-pregnant patients between 18–44 years of age in this study.
Identification and antibiotic susceptibilities of Mycoplasma hominis and Ureoplasma urealyticum were performed using AF
Genital System (Liofilchem, Italy). The antibiotic susceptibilities of these microorganisms to tetracycline (8 µg/mL), pefloxacine
(16 µg/mL), ofloxacin (4 µg/mL), doxycycline (8 µg/mL), erythromycin (16 µg/mL), clarithromycin (16 µg/mL), minocycline (8
µg/mL), josamycin (8 µg/mL) and clindamycin (8 µg/mL) were also investigated using Liofilchem AF genital System. Ureoplasma
urealyticum and Mycoplasma hominis were isolated from 11 (18.3%) and 3 (5%) pregnant patients, respectively. Ureoplasma
urealyticum was isolated from 9 (16%) non-pregnant patients, but Mycoplasma hominis was not isolated. Mycoplasma hominis
resistance in pregnant patients was detected as following; josamycin resistance of 66.6%, tetracycline, erythromycin and ofloxacin
resistance of 33.3%. Although in pregnant patients josamycin resistant rate was 81.8% in Ureoplasma urealyticum, ofloxacin and
clindamycin resistant rates were 27.3% and 9.09%, respectively. In non-pregnant patients, Ureoplasma urealyticum resistance
rates were as follows; josamycin (22.2%), ofloxacin (11.1%) and erythromycin (11.1%). As a conclusion, the prevalence of both
Mycoplasma hominis and Ureoplasma urealyticum in pregnant patients was higher than in non-pregnant women.
1.Taylor-Robinson D, Lamont R. Mycoplasmas in pregnancy. BJOG 2011; 118:164–174.
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PP 11 ERADICATION OF ANTIBIOTIC-RESISTANT HIDE MICROORGANISMS USING COMBINED ALTERNATING AND DIRECT
ELECTRIC CURRENTS AND ANTIBACTERIAL AGENT
MERAL BIRBIR 1, ESIN YILMAZ 2, YASAR BIRBIR 3, PINAR CAGLAYAN 1
DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA
UNIVERSITY, ISTANBUL, TURKEY
2
INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY
3
DEPARTMENT OF ELECTRIC AND ELECTRONIC ENGINEERING, FACULTY OF TECHNOLOGY, MARMARA UNIVERSITY, ISTANBUL,
TURKEY
1
Common use and misuse of antibiotics in human and animals have resulted in the development and spread of antibiotic
resistant-Gram negative and Gram positive bacteria in different sectors (1). Prevalence of antibiotic-resistant bacteria in leather
industry may cause health problems for workers. Hence, the aim of the study was to examine resistance of Gram-positive
and Gram-negative hide bacteria against amikacin (30 µg), trimethoprim- sulfamethoxazole (25 µg), cefuroxime sodium (30
µg), cefoxitin (30 µg), streptomycin (10 µg), nalidixic acid (30 µg), novobiocin (5 µg), oxolinic acid (2 µg), mupirocin (20 µg)
and spectinomycin (25 µg) and to determine effective inactivation method which may be used in soak liquor. Mixed culture
containing Enterococcus avium, Staphylococcus intermedius, Bacillus lentus, Aerococcus viridans, Enterobacter cloaceae and
Pseudomonas putida was used and antibiotic resistance of the mixed culture against the test antibiotics was determined
using disc diffusion method. The inactivation effect of a combined electric current treatment using both 1 A direct and 1.5
A alternating electric currents, followed by 1.5 g/L of (41% sodium dimethyl dithiocarbamate) treatment on the antibioticresistant mixed culture was examined in a liquid medium containing 3% NaCl and organic substances such as hide-soak liquor.
Antibiotic-resistant mixed culture treated with the electric current was completely destroyed after three hours exposure time
with 1.5 g/L of test agent and 7.70 Log10 reduction factor of the mixed culture was detected. In conclusion, electric currents
treatment in combination with antimicrobial agent will eradicate antibiotic-resistant microorganisms, hence we suggest using
this system in leather industry.
1. WHO Regional Office for Europe, Tackling antibiotic resistance from a food safety perspective in Europe, 2011. Copenhagen:
(www.euro.who.int).
PP 12 ANTIBIOTIC RESISTANCE OF GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA ISOLATED FROM SALTED HIDES AND
THEIR CONTROL USING ANTIBACTERIAL AGENT
MERAL BIRBIR 1, PINAR CAGLAYAN 1, ESIN YILMAZ 2
DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA
UNIVERSITY, ISTANBUL, TURKEY
2
INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY
1
Bacterial resistance against various antibiotics may cause important health problems in people working in different industries.
Therefore, the goal of the study was to determine resistance of Gram-positive (Enterococcus avium, Staphylococcus intermedius,
Bacillus lentus and Aerococcus viridans) and Gram-negative (Enterobacter cloaceae and Pseudomonas putida) bacteria against
various antibiotics and to examine their inactivation using commonly applied antibacterial agent in the leather industry. The
test microorganisms used in this study were isolated from salted hides and identified with API test kits in previous studies.
Antibiotic resistance of the test microorganisms against ceftazidime (30 µg), aztreonam (30 µg), polymyxin B (300 iu) and
bacitracin (0.04 iu) were tested using disc diffusion technique. All isolates exhibited resistance against all antibiotics. Then a
mixed culture of these antibiotic-resistant microorganisms (107 CFU/mL) was prepared. The test agent containing 41% sodium
dimethyl dithiocarbamate was used to inactivate these antibiotic-resistant microorganisms. Fifteen different concentrations of
test agent ranging from 0.50 to 7.5 g/L were prepared. The antibacterial effect of different concentrations of the agent against
mixed culture was examined using the agar disk diffusion method on nutrient agar containing 3% NaCl. Although inhibition
zone diameter of 10 mm belonging to mix culture was observed around the discs containing between 0.50-1.5 g/L of the agent,
inhibition zone diameter of 20 mm belonging to mixed culture was observed around the discs containing between 6.5-7.5 g/L of
the agent. In conclusion, inhibition zones of antibiotic-resistant test bacteria increased proportionally with the concentrations
of antimicrobial agent.
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PP 13 INACTIVATION OF ANTIBIOTIC-RESISTANT SPECIES BELONGING TO STAPHYLOCOCCUS, BACILLUS, GRACILIBACILLUS
AND IDIOMARINA VIA ELECTRIC CURRENT
PINAR CAGLAYAN 1, YASAR BIRBIR 2, MERAL BIRBIR 1, CRISTINA SáNCHEZ-PORRO 3, ANTONIO VENTOSA 3
DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, UNIVERSITY
OF MARMARA, ISTANBUL, TURKEY
2
DEPARTMENT OF ELECTRIC AND ELECTRONIC ENGINEERING, FACULTY OF TECHNOLOGY, MARMARA UNIVERSITY, ISTANBUL,
TURKEY
3
DEPARTMENT OF MICROBIOLOGY AND PARASITOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF SEVILLA, SEVILLA, SPAIN
1
Salted skins contain proteolytic and lipolytic moderately halophilic bacteria originated from salt, and these microorganisms may
cause deterioration of the skins. In this study, we examined antibiotic resistance of protease and lipase positive Staphylococcus
saprophyticus, Bacillus pumilus, Bacillus licheniformis, Gracilibacillus dipsosauri and Idiomarina loihiensis against various
antibiotics. Resistance of the test isolates against seven different antibiotics was examined using disc diffusion technique.
Although all isolates were found to be resistant against amikacin (30 µg), streptomycin (10 µg), spectinomycin (25 µg), polymyxin
B (300 iu) and oxolinic acid (2 µg), conversely all isolates were susceptible to meropenem (10 µg) and imipenem (10 µg).
To prevent growth of antibiotic-resistant bacteria in leather industry and accomplish effective skin preservation, inactivation
effect of direct electric current (DC) and alternating electric current (AC) treatments on these test isolates was examined. Four
different electric current treatments (0.5A and 1A of DC and 0.5A and 1A of AC) were separately applied into brine solutions
containing 25% NaCl and mixed culture of test bacteria. Mix culture of test bacteria was killed in 1 min by 0.5A DC and 1A DC
treatment; however, 0.5A AC and 1A AC treatments eliminated all bacteria respectively in 15 min and 10 min. As a conclusion,
AC and DC treatments were found fairly effective to eradicate antibiotic-resistant proteolytic and lipolytic moderately halophilic
bacteria in brine curing liquors. Therefore, we highly suggest using this electrochemical disinfection sytem in leather industry.
PP 14 ISOLATION AND IDENTIFICATION OF SERRATIA SPECIES ON SALTED HIDES AND SKINS, THEIR SUSCEPTIBILITIES TO
VARIOUS ANTIBIOTICS
KUBRA ULUSOY 1, MERAL BIRBIR 2, PINAR CAGLAYAN 2
INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA
UNIVERSITY, ISTANBUL, TURKEY
1
2
Hides and skins may contain pathogenic members of the family Enterobacteriaceae that inhabit animal intestines. The aim of
this study was to isolate Serratia species on the salted hides and skins and identify these microorganisms using API 20E test
kit (Biomèrieux, France). Proteolytic and lipolytic activities of these microorganisms were investigated and Serratia species
susceptibility to different antibiotics were examined. Although four different Serratia species were isolated from the hide
samples, six different Serratia species isolated from the skin samples. Serratia species were isolated from three hide and five
skin samples. Serratia odorifera, Serratia liquefacicens, Serratia plymuthica and Serratia rubidaea were isolated from both hide
and skin samples, but Serratia ficaria and Serratia marcescens were found only on sheep skins. Among the Serratia isolates,
Serratia liquefacicens, Serratia rubidaea and Serratia marcescens showed both proteolytic and lipolytic activities. The other
Serratia species showed proteolytic or lipolytic activities. Sixty-seven, fifty, eighty-three, thirty-three and thirty-three percent
of Serratia species were found to be resistant against ampicilline (10 µg), amoxicillin-clavulanate (30 µg), aztreonam (30 µg),
cefoxitin (30 µg) and ceftriaxone (30 µg), respectively. Almost all Serratia species were susceptible to imipenem (10 µg) and
meropenem (10 µg), but Serratia ficaria alone was resistant against meropenem. We gather that high frequency of proteolytic,
lipolytic and antibiotic-resistant Serratia species on the salted hides and skins may pose health risks to tannery workers and
cause hide deterioration. Therefore, effective inactivation treatments should be applied in leather industry to kill pathogenic
enteric bacteria.
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PP 15 CHARACTERIZATION AND ELECTROCHEMICAL INACTIVATION OF ANTIBIOTIC RESISTANT-ACINETOBACTER JOHNSONII
ISOLATED FROM SALTED SHEEP SKINS
CAN AKPOLAT 1, YASAR BIRBIR 2, MERAL BIRBIR 3, ANTONIO VENTOSA 4, PINAR CAGLAYAN 2, CRISTINA SáNCHEZ-PORRO 4
INSTITUTE OF PURE AND APPLIED SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF ELECTRIC AND ELECTRONIC ENGINEERING, FACULTY OF TECHNOLOGY, MARMARA UNIVERSITY ISTANBUL,
TURKEY
3
DIVISION OF PLANT DISEASES AND MICROBIOLOGY, DEPARTMENT OF BIOLOGY, FACULTY OF ARTS AND SCIENCES, MARMARA
UNIVERSITY, ISTANBUL, TURKEY
4
DEPARTMENT OF MICROBIOLOGY AND PARASITOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF SEVILLA, SEVILLA, SPAIN
1
2
Lipolytic halophilic bacteria on salted skins may cause production of unevenly finished leathers. Hence, the prevalence of
lipolytic moderately halophilic Acinetobacter johnsonii on the salted sheep skins, its phenotypic characteristics and resistance
against various antibiotics were examined. Eleven isolates of Acinetobacter johnsonii were isolated from the two skin samples
and characterized with comparative partial 16S rRNA gene sequence analysis. Acinetobacter johnsonii grew in the media
containing 3-25% (w/v) NaCl and between pH 7 and 9. This microorganism was non-motile, Gram-negative and aerobic rod.
It showed positive catalase, negative oxidase reactions, produced NH3 from peptone and hydrolysed Tween 80. H2S and
indole were not produced and gelatin was not hydrolysed. This isolate was resistant against amikacin (30 µg), tobramycin (10
µg), kanamycin (30 µg), streptomycin (10 µg), aztreonam (30 µg), gentamicin (10 µg), but susceptible to imipenem (10 µg),
trimethoprim/sulfamethoxazole (25 µg) and piperacillin/tazobactam (110 µg). Five, three and one minute of 1A direct electric
current treatment were enough to exterminate Acinetobacter johnsonii in the treatment media containing nutrient broth with
3% NaCl, nutrient broth with 25% NaCl and only 25% NaCl, respectively. Ten, five and one minute of 1A alternating electric
current treatment were enough to annihilate Acinetobacter johnsonii in the treatment media containing nutrient broth with 3%
NaCl, nutrient broth with 25% NaCl and only 25% NaCl, respectively. In conclusion, direct and alternating electric currents were
effective treatment methods to exterminate antibiotic-resistant Acinetobacter johnsonii in leather industry.
PP 16 STRUCTURE-ACTIVITY-RELATIONSHIP ON MONOAMINE OXIDASE CATALYZED OXIDATION OF SUBSTITUTED
BENZYLAMINES: COMPETING PROTON/HYDRIDE TRANSFER MECHANISMS
MEHMET ALİ AKYÜZ 1, VİLDAN ENİSOĞLU ATALAY 2, SAFİYE SAĞ ERDEM 1
1
2
MARMARA UNIVERSITY CHEMİSTRY DEPARTMENT GÖZTEPE ISTANBUL
USKUDAR UNIVERSITY DEPARTMENT OF BİOENGİNEERİNG ÜSKÜDAR ISTANBUL
Monoamine oxidase A and B enzymes catalyze the oxidation of neurotransmitter amines and regulate their level. MAO inhibitors
are used in the treatment of depression, Parkinson and Alzeimer. This study aims to enlighten the chemical steps of MAO catalyzed
amine oxidation because it is crucial for rational design of new selective drugs for the treatment of neurological disorders. As a
continuation of our previous computational studies (1-3) here we focus on whether MAO-A and MAO-B may have the same or
different mechanisms by including their active site aminoacids in the calculations. Oxidation of p-X benzylamines by MAO-A and
MAO-B was modelled with quantum chemical DFT method at the ONIOM(B3LYP/6-31+G(d,p):PM6) level and semiempirical PM6
methods. Interestingly, for MAO-A, substituents showed two opposing trends: Log of calculated rate constants of p-X=OCH3,
H, F, CH3, NO2, CF3 exhibits a (+) linear relationship with the log of experimental rate constants (R2=0.893), which is in line
with the proton transfer mechanism. On the contrary, p-X=Br, Cl, OH, F, CH3, N(CH3)2) exhibit a relationship with a (-) slope,
supporting the hydride transfer mechanism. These results suggest that two competing mechanisms are possible for MAO-A
monitored by the electronic nature of the substituent.
We acknowledge TÜBİTAK for financial support of project: KBAG-113Z616
References
1. Erdem S. S., Karahan Ö., Yıldız İ., Yelekçi K., Org. Biomol. Chem. 4, 646 (2006).
2. Atalay V. E., Erdem S. S., Computational Biology and Chemistry 47, 181 (2013).
3. Akyüz M. A., Erdem S. S., J. Neural Transm. 120, 937 (2013).
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PP 17 IMPROVING ANTIPROLIFERATIVE EFFECT OF SIROLIMUS ON HUMAN T-CELLS USING FUSOGENIC LIPOSOMES
HADI VALIZADEH , PARVIN ZAKERI-MILANI , SAEED GHANBARZADEH
FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
Fusogenic liposomes are unique delivery vehicles capable of introducing their contents directly and efficiently into the
cytoplasm. The objective of this study was to evaluate the potential of fusogenic liposomes containing Sirolimus to
improve its antiproliferative effect on T- lymphocyte cells. Conventional liposomes containing Sirolimus were prepared from
Dipalmitoylphosphatidylcholine (DPPC) and cholesterol using the modified ethanol injection method. To prepare fusogenic
liposomes, dioleoylphosphatidylethanolamine (DOPE) was added to the conventional liposome formulation. The liposomes were
characterized by their size, zeta potential, encapsulation efficiency percent (EE%) and chemical stability during 6 months. The in
vitro release of liposomes, antiproliferative effect and liposome uptake of both types of liposomes with optimized formulations
were studied on human T-lymphocyte cells employing the MTT assay and fluorescein isothiocyanate-loaded liposomes. The
particle size of the liposomes was evaluated between 138 and 650 nm and mean zeta potential was in the range of -32.95
to -45.60 mV. The average EE% of the prepared conventional and fusogenic liposomes were 76.9 % and 80.5, respectively.
Liposomal formulations released only 10-20 % of encapsulated drug without any burst effect. In vitro immunosuppressive
evaluation on T-cells showed that fusogenic liposomes have the best antiproliferative effects and uptake on T-lymphocyte cell
compared to the conventional liposomes. Our results indicated that fusogenic liposomes can be useful carriers for improving
the inhibition of T-cell proliferation.
PP 18 EFFECT OF OCCUPATIONAL EXPOSURE TO AflATOXINS IN BAKERY WORKERS
NIMET EMEL LÜLECI 1, SEHER KARSLI ÇEPPIOĞLU 2, TUĞÇE KOÇ 2, YAŞAR KESKIN 1, TÜRKAN YURDUN 2
DEPARTMENT OF PUBLIC HEALTH, SCHOOL OF MEDICINE, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, HAYDARPASA-ISTANBUL/
TURKEY
1
2
Aflatoxins (AFs) are secondary metabolites produced by certain Aspergillus spp. in particular A. flavus and A. parasiticus. AFs
(B1, B2, G1 and G2) are all toxic, mutagenic and carcinogenic compounds and they are major risk factor for hepatocellular
carcinoma. Aspergillus spp. grows on grains and other agricultural crops; therefore, ingestion of contaminated foods represents
the main route of entry of AFs to the body. Occupational exposure to AFs occurs by inhalation of flour dust generated during
the handling and processing of contaminated crops. In this study, AFs exposure in bakery workers was investigated with urinary
AF metabolite levels. AFs were isolated from urine using immunoaffinity clean-up followed by derivatization with trifluoroacetic
acid and reversed-phase liquid chromatography with fluorescence detection. The isocratic mobile phase consisted of water (5%
acetic acid):methanol:acetonitrile (64:18:18). The overall time of analysis was lower than 15 min. for AFs. AFB2a (corresponding
to AFB1) was detected in four (6.45%) of 62 human urine samples examined. However, this study needs to extend in order to
understand the relation between the AFs exposure and AF levels in human urine.
This work was supported by Research Foundation of Marmara UNIVERSITY (SAĞ-A-101012-0310).
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PP 19 DETERMINATION OF LEAD, NICKEL, COBALT AND CHROMIUM LEVELS IN COSMETIC PRODUCTS
ZERRIN GÜNGÖR 1, HANDE SIPAHI 1, MOHAMMED CHAREHSAZ 1, BUĞRA SOYKUT 2, ONUR ERDEM 2, AHMET AYDIN 1
1
2
YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF TOXICOLOGY
GULHANE MILITARY MEDICAL ACADEMY, DEPARTMENT OF TOXICOLOGY
Evidence of the use of cosmetics has been found in civilization as early as ancient Mesopotamia. Cosmetics are still much
preferred by both men and women and have quite a large market share. However, modern cosmetics may contaminated by
potentially toxic elements and heavy metals (1). The aim of this study was to investigate the concentration of Pb and allergen
metals such as Ni, Co and Cr in the most commonly used brands of makeup products, body lotions and nail polish in Turkey.
Heavy metal levels were determined by atomic absorption spectrophotometer in total 48 cosmetic products purchased from
local markets and large cosmetic stores in Istanbul. According to our results, the levels of Ni generally lower than 20 μg/g, the
FDA limit for impurities in color additives (2). The highest concentration of Pb was found in pink color of eye shadow compared
to three other colors of same brand. Although Cr, Co, Ni and Pb are prohibited by Turkey regulation (3), it was determined that
all samples generally include these metals. Despite skin penetration with cosmetic substances is negligible, local effects such as
irritation, sensitization, allergy or photoreaction may occur. As a result, althouhg removal of these metals from cosmetics after
manufacture is not possible, careful selection of the raw material can improve the quality of the products.
1. Volpe, M., Nazzaro, M., Coppola, R., Rapuano, F. and Aquino, R. 2012. Determination and assessments of selected heavy
metals in eye shadow cosmetics from China, Italy, and USA. Microchemical Journal, 101 pp. 65-69. 2. Cosmetic Legislation,
TC Sağlık Bakanlığı, Kozmetik Yönetmeliği, 2006, Accessed January 2013, http://www.saglik.gov.tr/TR/belge/1-472/kozmetikyonetmeligi.html 3. FDA, Summary of Color Additives Listed for Use in the United States in Food, Drugs, Cosmetics, and Medical
Devices, Color Additives Approved for Use in Cosmetics, Part 73, Subpart C: Color Additives Exempt from Batch Certifi cation,
2007, Accessed September 2013, http://www.cfsan.fda.gov/dms/opa-col2.html
PP 20 PREPARATION AND CHARACTERIZATION OF THE SKIN CARE PRODUCTS BEARING NIOSOME ENCAPSULATED AESCINE
LEMAN CELİK SUREN , NEFISE ÖZLEN ŞAHIN
MERSIN UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
Aescine, a triterpen saponine mixture, has been used in pharmacy and MEDICINE due to its various therapeutic effects.
Recently, aescine has been used in some cosmetic products such as shampoos, body wash foams or skin care products (13). Niosomes are non-ionic vesicules prepared employing nanotechnology. Based on the nature of their structure, they can
be used to formulate both lipophilic and hydrophilic active substances and allow to obtain the desired effect upon topical
administration. Also, they provide targeting and controlled release of active substance. In this project, skin care products of
aescine were prepared following its encapsulation in niosomes by nanotechnology and then, in vitro characterization studies
including the cell culture test for biological activity were carried out. In conclusion, it was determined that it’s possible to obtain
optimum cosmetic potency without any significant irritation reaction with aescine encapsulated niosomal skin care products.
1. Ulbricht C, Tiffany N, Boon H, Basch E. Horse Chestnut. Journal of Herbal Pharmacotherapy. 2002; 2(1):71-85.
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PP 21 HIGH GLUCOSE POTENTIATES COLLAGEN-STIMULATED PLATELET AGGREGATION AND APOPTOSIS
AZIZE SENER 1, NAZLI GUL ALTINDIS 1, OZGE DOGAN 1, OZGE CEVIK 2
1
2
FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, MARMARA UNIVERSITY, ISTANBUL, TURKEY
FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, CUMHURIYET UNIVERSITY, SIVAS, TURKEY
Diabetes mellitus (DM) is associated with various cardiovascular diseases, including platelet hyperactivity, which are major
causes of morbidity and mortality in DM. Hyperglycemia stimulates platelet function. However, the effect of acute high glucose
on platelet apoptosis is not yet clearly defined. The aim of the present study was to examine effects of acute short-term high
glucose on platelet aggregation and apoptosis (Ca(2+) mobilization, caspase 3 activation, and Bcl-2 protein levels) in resting or
collagen-stimulated platelets. Washed platelets were incubated for 1 h with 5 mmol/l or 25 mmol/l D-glucose in the presence or
absence of collagen. After incubation, mitochondrial reactive oxygen species production (mROS), cytosolic Ca(2+) concentration,
caspase 3 activity and Bcl-2 protein level were analyzed by fluorometer or ımmunoblotting. Incubation of collagen- stimulated
platelets with high glucose caused increases in platelet aggregation, cytosolic calcium concentration, mROS level, caspase 3
activity (p<0.05). In addition to that, high glucose significantly reduced Bcl-2 levels compared to the control group (p<0.05).
In resting platelets, it had no significant effects on cytosolic Ca(2+) concentration and apoptosis signals. As a result, platelet
aggregation, mitochondrial oxidative changes and apoptosis signaling pathway are induced by high glucose in the presence of
collagen. High glucose alone does not affect platelet survival in resting platelets. These findings can provide novel therapeutic
targets for DM thrombotic complications.
PP 22 EFFECT OF INTERLEUKIN 1 β ON PLATELET APOPTOSIS
AZIZE SENER 1, GÖZDE EGEMEN 1, DERYA OZSAVCI 1, OZGE CEVIK 2
1
2
FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, MARMARA UNIVERSITY, ISTANBUL, TURKEY
FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, CUMHURIYET UNIVERSITY, SIVAS, TURKEY
Platelets are essential for hemostatic process, but they also play an important pro-inflammatory role. They are rich sources of
chemokines, cytokines, and growth factors that are packaged in storage granules. After platelet activation, these mediators
influence wound repair, and vascular remodeling by signaling target cells and inducing leukocyte accumulation. One of these
cytokines is interleukin-1 beta (IL-1β) (1). It induces apoptosis in several cell types. However, its effect on platelet apoptosis
is unknown. This study investigated the effect of IL-1β on induction or inhibition of apoptosis in blood platelets. As indicators
of apoptosis, phosphatidylserine translocation, mitochondrial membrane potential and caspase-3 activity were detected in
ADP activated platelets. Platelets incubated with ADP (20µM) and ADP plus recombinant IL-1 β (20 ng/ml ) at 37 °C for 30 min.
Apoptotic cells were stained with Annexin-V-FITC for phosphatidylserine translocation and JC-1 dye for mitochondrial membrane
potential. They were analyzed by flow cytometry. Interleukin-1 β induced increases in phosphatidylserine translocation and
caspase-3 activity mediated ADP. Mitochondrial membrane potential did not change after IL-1 β treatment in our in vitro
conditions. These results suggest that IL-1 β can induce apoptosis via death receptor pathway in ADP activated platelets and
may contribute to thrombocytopenia associated with inflammation.
1.Lindemann S, Tolley ND, Dixon DA Mc Intyre TM, Prescott SM,. Zimmerman GA, Weyrich AS. Activated platelets mediate
inflammatory signaling by regulated interleukin 1, The Journal of Cell Biology, 154:485-490, 2001.
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PP 23 EXPRESSION OF ADIPONECTIN RECEPTORS IN PANCREAS OF HIGH-FAT FED RATS
AZİZE SENER 1, OZGE DOGAN 1, NAZLI GUL ALTİNDİS 1, OZGE CEVİK 1
1
2
FACULTY OF PHARMACY, BIOCHEMISTRY DEPARTMENT, MARMARA UNIVERSITY, ISTANBUL, TURKEY
FACULTY OF PHARMACY, BİOCHEMİSTRY DEPARTMENT, CUMHURİYET UNIVERSITY, SİVAS, TURKEY
Obesity is strongly associated with insulin resistance. Adipose tissue produces small molecules called adipokines, which are
important in modulating glucose, lipid metabolism. Adiponectin is a adipokine and promotes insulin sensitivity, decreases
inflammation and promotes pancreatic beta cell survival (1). Adiponectin acts through two receptors, AdipoR1 and AdipoR2.
This study investigated the effects of high fat (HF) diet-induced changes on the serum adiponectin levels and expression of
adiponectin receptors (AdipoR1 and AdipoR2) in pancreas. Female rats were fed standart diet or HF (46% energy from fat) for
12 weeks. We used sunflower oil, the rich from n-6 polyunsaturated fatty acids (PUFA), as fat source. HF diet increased body
weight and visceral adipose tissue, slightly increased glucose levels and decreased serum adiponectin levels. We observed the
marked protein expression of adiponectin receptors AdipoR1 and AdipoR2 in rat pancreas. In HF fed rats, protein expression
of pancreatic Adipo R1 and Adipo R2 significantly increased. In conclusion, pancreas cells is sensitive to circulating adiponectin
levels. Protein expression of adiponectin receptors in pancreas was up-regulated by HF induced low adiponectin levels.
1.Wijesekara N, Krishnamurthy M, Bhattacharjee A, Suhail A, Sweeney G, Wheeler MB. Adiponectin-induced ERK and Akt
phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion. J Biol
Chem. 2010 29;285(44):33623-31.
PP 24 ANTIDERMATOPHYTIC AND ANTIMYCOBACTERIAL ACTIVITY OF MANNICH BASES OF KOJIC ACID WITH CYTOTOXICITY
EVALUATION
MUTLU AYTEMİR 1, GÜLŞAH KARAKAYA 1, BERRİN ÖZÇELİK 2
1
2
HACETTEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
GAZİ UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMECEUTİCAL MİCROBİOLOGY
The introduction of new oral therapies have improved cure rates of cutaneous mycoses however approximately 20% of the
patients with oncomycos are still failing on antifungal therapy (1). Tuberculosis caused by Mycobacterium tuberculosis is the
leading bacterial cause of death (2). The increasing numbers of drug resistance and the lack of sufficient chemical diversity to
existing azole antifungal represent a serious challenge for tuberculosis control. Previously, Mannich bases of hydroxypyrone
derivatives were synthesized in our laboratory and examined for their anticonvulsant, antibacterial, antifungal and antiviral
activities with cytotoxicity (3). Hence we will present the results of a preliminary evaluation of cytotoxicity, antidermatophytic
and antimycobacterial activities of thirteen Mannich bases of kojic acid. In vitro antidermatophytic activity of the derivatives
against Microsporum gypseum, Trichophyton mentagrophytes var. erinacei and Epidermophyton floccosum will be screened
as broth microdilution method. Cytotoxicity will be evaluated by the maximum non-toxic concentrations (MNTCs), which was
determined by the method described previously based on cellular morphologic alteration. As for antimycobacterial activity
the breakpoint concentrations of the compounds will be determined against standard strains of M. tuberculosis H37Rv and M.
avium (ATCC 15769) clinical isolated strains by using the colorimetric resazurin microtiter assay (REMA). This study is supported
by TÜBİTAK. Project no: SBAG-113S527.
References
1. Peres, N.T.A., Maranhao, F.C.A, Martinez-Rossi, N.M. Dermatophytes: host-pathogen interaction and antifungal resistance,
An Bras Dermatol 2010; 85(5): 657-67.
2. Pavan F.R. et al., Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae), Quim.
Nova 2009; 32(5): 1222-1227.
3. Karakaya, G., Aytemir, M.D., Özçelik B., Çalış, Ü., Design, synthesis and in vivo/in vitro screening of novel chlorokojic acid
derivatives, J. Enz. Inh. Med. Chem. 2013; 28(3): 627–638.
PP 25 IMPLEMENTATION OF MEDICATION RECONCILIATION AND MEDICATION REVIEW SERVICES CONDUCTED BY
PHARMACIST IN HOSPITALIZED ELDERLY PATIENTS
AYSU SELCUK 1, MESUT SANCAR 1, BETUL OKUYAN 1, REFİK DEMİRTUNÇ 2, FİKRET VEHBİ IZZETTİN 1
1
2
DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY-FACULTY OF PHARMACY, ISTANBUL, TURKEY
DEPARTMENT OF INTERNAL MEDICINE, HAYDARPASA NUMUNE TRAİNİNG AND RESEARCH HOSPİTAL,ISTANBUL, TURKEY
The aim of the present study is to implement medication reconciliation service conducted by pharmacist at admission to hospital
and retrospectively drive medication review to detect possible medication related problems in hospitalized elderly patients.
This study was conducted in internal MEDICINE ward of a research and training hospital between April 24 and June 30, 2014.
Patients hospitalized with any reason during the present study were eligible if they were 65 years or older, utilized chronically at
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least one medication before hospitalization, and accepted to participate to the present study. Pharmacist conducted medication
reconciliation services to determine any discrepancies between a patient’s home medication and medications prescribed on
admission to the hospital within 48 hours of admission. Estimated glomerular filtration rate was calculated by The CockcroftGault Equation. Retrospectively inappropriate medication utilization and medication related problems during hospitalization
were also investigated by using Beer’s Criteria Update 2012 and PCNE DRP (Pharmaceutical Care Network Europe Drug Related
Problem) Classification V6.2; respectively. The frequency of potentially high-risk medication utilization was also determined.
The physician’s acceptance rate of pharmacist’s recommendation during medication reconciliation and medication review was
also assessed. A total of a hundred hospitalized elderly patients (mean age, 76,58 ± 8,36 years; 53 female / 47 male) included
in the study. The most frequently seen comorbidity was hypertension. When evaluated patients’ body mass index, it was
found that 53% of them were more than normal levels. Estimated glomerular filtration rate was found less than 30 mL/min in
30% of them. 66% of the patients did not take any support for medication utilization. The number of medication usage was
increased in 44% of them after hospitalized. Of them, 89% were exposed to polypharmacy and 39% of patients were exposed
to hyperpolypharmacy. Inappropriate medication utilization was found in 22% of them according to Beer’s criteria. High-risk
medication utilization was found in 74% of them and low-molecular-weight heparin was found the most common utilized highrisk medication in study population. A total of 289 medication related problems were determined and the most frequently
determined medication related problems were drug not taken/administered at all and drug-drug interactions; respectively.
It was determined clinically significant drug- drug interactions in 36% of them. In medication reconciliation process, 86% of
309 medication discrepancies were found as unintended discrepancies among 74 patients. The physician’s acceptance rate
of pharmacist’s recommendation during medication reconciliation and medication review was found as 84%. As a conclusion,
it was found that medication related problems and inappropriate medication utilization at admission would be prevented by
medication reconciliation and review services driven by pharmacists.
PP 26 DETERMINATION OF CYP2C19 POLYMORPHISMS, ADVERSE DRUG REACTION, AND MEDICATION ADHERENCE IN
PATIENTS UTILIZED SELECTIVE SEROTONIN REUPTAKE INHIBITORS
SEMANUR DENIZ 1, MESUT SANCAR 1, BETUL OKUYAN 1, PINAR ATA 2, OZLEM BINGOL OZAKPINAR 3, ANIL TALAS 4, TUFAN
GUNES 4, MECIT CALISKAN 4, FIKRET VEHBI IZZETTIN 1
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
DEPARTMENT OF MEDICAL GENETICS, MARMARA UNIVERSITY- FACULTY OF MEDICINE, ISTANBUL, TURKEY
3
DEPARTMENT OF BIOCHEMISTRY, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
4
DEPARTMENT OF PSYCHIATRY, HAYDARPASA NUMUNE TRAINING & RESEARCH HOSPITAL, ISTANBUL, TURKEY
1
2
The aim of the study is to determine cytochrome P-450 2C19 (CYP2C19) enzymes polymorphisms, adverse drug reactions, and
medication adherence in patients who were diagnosed with major depression utilized selective serotonin reuptake inhibitors.
This study was conducted in outpatient psychiatry clinic between December 2012 and May 2013. The patients were eligible
if they used selective serotonin reuptake inhibitors (sertraline, citalopram or escitalopram) at least four week and were 18
years and older. Demographic and clinical data were collected from the patients who accepted to participate to the present
study. Polymorphisms were determined from genomic DNA by using ‘Real-Time Polymerase Chain Reaction’ method. ‘Toronto
Side Effects Scale’ was used to determine the adverse drug reaction (1) and also in the four items (Morisky, Green and Levine)
adherence scale was used to assess patients’ medication adherence (2, 3). Fifty-three major depression patients (mean of age:
33.25 ± 11.29 years old; male/female: 7/46) were included in this study. The patients were treated with sertraline (58.5%),
escitalopram (37.7%), citalopram (3.8%). The most common adverse drug reactions that patients reported were drowsiness/
daytime somnolence (54.7%), malaise or fatigue (43.4%), sweating (43.4%), nausea (41.5%) and dry mouth (41.5%). Only nine
(17%) patients were found high adherent to their medication. When evaluating the CYP2C19 polymorphisms of patients, 37.7%,
24.5% and 20.8% of the patients were classified as intermediate, extensive and ultra-rapid metabolizers; respectively. Allele
frequencies of CYP2C19*17 and CYP2C19*2 was calculated as 24.5% and 27.4%; respectively. When compared with individuals
with extensive metabolizers, it was found higher adverse drug reaction scores in individuals with intermediate phenotype
and lower adverse drug reaction scores in individuals with ultra-rapid phenotype, but these differences were not statistically
significant (p>0.05). Although patients with lower adverse drug reaction scores were more adherent to their medications;
no statistically significant difference were found between the groups (p>0.05). The fact that the differences between the
groups are not statistically significant is considered to arise from the number of the patients conducted in the study. Largescale studies are needed to put forth more clearly the differences of adverse effects and treatment results depending on the
pharmacogenetic characteristics. According to our study population which have a greater rate of intermediate metabolizer
and low adherence rate, we believe that the patient counselling and monitoring is critical for these patients on antidepressant
therapy. 1- Vanderkooy JD, Kennedy SH, Bagby RM. (2002). Antidepressant side effects in depression patients treated in a
naturalistic setting: a study of bupropion, moclobemide, paroxetine, sertraline, and venlafaxine.
W Can J Psychiatry, 47 (174-80), 2- Morisky DE, Green LW, Levine DM. (1986). Concurrent and Predictive Validity of a SelfReported Measure of Medication Adherence and Long-Term Predictive Validity of Blood Pressure ControlMed Care, 24(1):
67–74. 3- Yılmaz S. (2004). ‘Medication side effects and medication adherence in psychiatric patients’ Master of Science Thesis
in Turkish. Univeristy of Istanbul, Health Science Institute İstanbul, (Consultant: Assoc.Prof.Dr. Sevim Buzlu).
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PP 27 ASSESSMENT OF KNOWLEDGE AND ATTITUDE TOWARDS OSTEOPOROSIS AMONG WOMEN ATTENDING COMMUNITY
PHARMACY SETTINGS
BETUL OKUYAN , MEHMET ALI ACAR , BERRA KILIC , HALE KÖME , ERLIASA BAMI , MESUT SANCAR
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
The aim of the study was to assess the knowledge and attitude about osteoporosis, in women 40 years and older who attend
community pharmacy for any reason. This study was carried out within community pharmacies from March to May 2014 among
subjects who came to community pharmacy for any reason and accepted to participate after being informed about the present
study. Participants included were women of 40 years and older that had never been diagnosed with osteoporosis before, and
that had not been using any antiresorptive agent. Subjects demographic and clinical data has been collected. The knowledge
about osteoporosis was assessed by the OKAT - Osteoporosis Knowledge Assessment Tool (1). OKAT was scored from 0 to 20. The
study was performed on a total of 192 subjects of a mean average age of 54.61 ± 9.05 years. Of the subjects, 66.1% possessed
drinking milk and consuming dairy products habits. Meanwhile about 85.0% used to drink more than 2 cups of tea/coffee daily.
In addition 83.8% of the participants had smoking habit, while 89.6% were aware that smoking can contribute to osteoporosis.
About 95.8% used to drink alcohol once in a while when about 65.0% accepted they knew that alcohol effects bone integrity.
It was noticed that BMI (Body Mass Index) of the subjects showed that approximately 72.0% of them were overweight, with
65 participants being obese. Of them, 77.5% tended to think that physical activity is beneficial against osteoporosis, while
only 53.1% of the subjects accepted to be active in exercising. It was revealed that 74.5% knew some symptoms caused by
osteoporosis and 87.0% were conscious that osteoporosis increases the risk for fractures. The total mean score of OKAT was
calculated as 11.92±3.27. At the end of the study it was concluded that the biggest part of women included were aware of
osteoporosis as a problem and its high incidence in women. Still more information and advice concerning lifestyle changes,
prevention measures and treatment of osteoporosis must be provided, as well as encouragement to modify attitude towards
osteoporosis with these changes as soon as possible in order to get less affected by this disorder.
1. Winzenberg TM, Oldenburg B, Frendin S, Jones G. The design of a valid and reliable questionnaire to measure osteoporosis
knowledge in women: the Osteoporosis Knowledge Assessment Tool (OKAT). BMC Musculoskelet Disord. 2003 Jul 24;4:17.
PP 28 THE ROLE OF PHARMACIST IN DETECTING ANGIOTENSIN CONVERTING ENZYME INHIBITORS INDUCED DRY COUGH AT
COMMUNITY PHARMACY SETTING
GONCA CÖMERT ATALAY 1, MESUT SANCAR 1, BETUL OKUYAN 1, SULEYMAN ATALAY 2, FIKRET VEHBI IZZETTIN 1
1
2
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
DEPARTMENT OF SURGERY, HAYDARPASA NUMUNE EDUCATION AND RESEARCH HOSPITAL, ISTANBUL, TURKEY
The aim of this study is to determine role of pharmacist in detecting angiotensin converting enzyme (ACE) inhibitors induced
dry cough at community pharmacy setting. The study was conducted between January 01 and June 30, 2013 at a community
pharmacy located in Istanbul. The patients were eligible for the present study if they were 18 years and older, came to community
pharmacy for any reason, used ACE inhibitors at least four weeks, accepted to participate after information regarding aim and
method of the study. The demographic and clinical data of the patients were collected. The knowledge and attitude about
ACE inhibitors were assessed at baseline. If the patients had a dry cough complaint, the pharmacists referred these patients to
physicians for further diagnosis and treatment. The changes after all patients who had a dry cough, referring to the physicians
by the pharmacist, were questioned after a month by telephone call. ‘Leicester Cough Questionnaire (LCQ)’ was applied to
patients who had dry cough to assess the effect of ACE inhibitors induced dry cough on patients’ quality of life (1). The LCQ was
scored from 3 to 21. Among 70 patients used ACE inhibitors, 56% of patients were female and the mean age of the patients was
58.5±10.72. Among 70 patients, 84% of them did not know the possible adverse drug reaction related to use of ACE inhibitors.
In 26 patients out of a total of 70 patients had dry cough complaint while using ACE inhibitors. It is found that 81% of patients
who had dry cough did not know that dry cough could be related to ACE inhibitors utilization. The mean total score of LCQ was
calculated as 14.40 (12.00-15.85) in these patients. When evaluating attitude of patients towards dry cough, %85 of them had
previously used different medications to eliminate their dry cough complaint. In 42% of them who had dry cough complaint
during the therapy with ACE inhibitors and visited the physician after pharmacist consultation, their physician substituted the
ACE inhibitors with other agents. However, only 54% of them reported that their dry cough complaint has been relieved after
medication modification by their physician. Pharmacists may take more professional responsibility in patients under treatment
of ACE inhibitors to eliminate medication related problems, which could be resulted in improvement in patients’ quality of life.
1. Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for
patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax. 2003 Apr;58(4):339-43.
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PP 29 ASSESSMENT OF PATIENTS’ KNOWLEDGE AND ATTITUDE TOWARDS METHOTREXATE UTILIZATION
HATICE IKRA DUMLU , BETUL OKUYAN , MESUT SANCAR , FIKRET VEHBI IZZETTIN
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
The aim of this study is to retrospectively determine the knowledge and attitudes of patients towards methotrexate utilization.
A retrospective descriptive study was conducted in rheumatology clinic of a training and research hospital. The patients were
eligible for the present study if they were 18 years and older, and accepted to participate after being informed about the
present study, using methotrexate for at least four weeks. The questionnaire designed by investigators was applied to patients
to assess knowledge and attitudes of patients towards methotrexate utilization. Among 50 participants, 72% of them were
female and the mean age of the patients was 51.76 ± 12.90. The most of the patients were married and had a low education
level. When evaluating usage of methotrexate, thirty-eight participants utilized orally, while twelve of them used parenteral
dosage form. Most of them utilized methotrexate once a week and more than six months along. In the study 52% of them were
not declared correctly a reason for administration of methotrexate and 36% of them did not know what to do if they missed a
dose of methotrexate. Most of them (96%) did not know anything about adverse effect of methotrexate. Among nine of fifty
patients, who had an indication for contraception, it was determined that 89% of them did not use any contraception method
during treatment with methotrexate. Of all participants, 82% used folic acid concurrently with methotrexate treatment. As
a conclusion, it was found that participants of the present study have poor knowledge and attitudes towards methotrexate
utilization. Pharmacists could be involved in management of patients treated with methotrexate by providing patient education
and monitoring.
PP 30 EVALUATION OF DRUG BURDEN INDEX AND MEDICATION UTILIZATION IN GERIATRIC PATIENTS AT COMMUNITY
PHARMACY
MESUT SANCAR , IREM GIRGIN , AYSU SELCUK , SEONKYEONG YANG , FIKRET VEHBI IZZETTIN , BETUL OKUYAN
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
The aim of the present study was to evaluate medication utilization including determination of polypharmacy and patients’
knowledge about medication, assessment of physical risk in medication utilization and evaluation of drug burden index among
geriatric patients. This study was conducted in community pharmacy located in Canakkale, Turkey between July and August
2012. Patients were eligible for the present study if they were 65 years old or older, used at least one medication at least four
weeks, they did not take any support for medication utilization, and accepted to participate the present after get required
information regarding the aim and method of the study. Patients’ demographic data and clinical data were collected. Medication
utilization physical risk assessment has been evaluated by using sub-scale developed by Lubinga et al. (1). Patients’ medication
knowledge and drug burden index have been also evaluated. Of the 100 geriatric patients, 52.5% were 65-74 years old and 52%
of them were females. Of them, 84% were exposed to polypharmacy and 4% of patients were exposed to hyperpolypharmacy.
DBI score has been calculated in a total of seventy-five patients. The DBI scores were between 0-1 in sixty-six patients and
were more than one in 9 patients. Of them, 52% had low medication knowledge. When evaluated patients’ dexterity on usage
of dosage form, most of the patients experienced no difficulties during medication utilization. However; only 43% of patients
showed fine manipulation skills. It is important to detect and prevent medication related problems in geriatric patients at
community pharmacy setting. This will be beneficial to enhance the medication adherence in elderly patients.
1.Lubinga SJ, Millar I, Babigumira JB. Pilot evaluation of the psychometric properties of a self-medication Risk Assessment Tool
among elderly patients in a community setting. BMC Res Notes. 2011; 4:398.
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PP 31 DETERMINATION OF DRUG RELATED PROBLEM AND DRUG BURDEN INDEX IN ELDERLY PATIENTS
BETUL OKUYAN , ZEHRA AYDINLI , IPEK CELIK , EFE DOGUKAN DINCEL , TUGCE SAY , DILAY YAVUZ , AYSU SELCUK , SEONKYEONG
YANG , MESUT SANCAR
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
The aim of the present study was to determine medication related problems and drug burden index in elderly patients at
community pharmacy. This cross-sectional descriptive study was conducted between February and May 2014. Patients were
eligible for the present study if they were 65 years old or older, they did not take any support for medication utilization, and
accepted to participate study. Potentially inappropriate medications were defined as updated 2012 Beer’s Criteria. Cognitive
function has been evaluated by using revised Turkish version of Mini Mental State Examination (rMMSE-T) was scored between
0-30 (1). Drug burden index have been also calculated. Among 123 elderly patients, 43.1% of them were female and the
mean age of the patients was 71.50 ± 6.71. The most of the patients were married (74.0%) and had a low education level. The
mean of total medication utilized in patients was 5.20± 1.53 and eighty patients used five and more medication. The mean of
rMMSE-T score was 23.56± 4.44. 56.91% (n=123) of the patients were prescribed with potentially inappropriate medications.
The frequency of DBI exposure was high (76.5%) in elderly patients. The DBI scores were between 0-1 in eighty-one patient
and more than one in 13 patients. As a conclusion, it was found higher rate of drug burden index and polypharmacy in elderly
patients in the present study. Pharmaceutical care conducted in community pharmacy would be beneficial in preventing and
determining of medication related problems.
1.Keskinoglu P1, Ucku R, Yener G, Yaka E, Kurt P, Tunca Z. Reliability and validity of revised Turkish version of Mini Mental State
Examination (rMMSE-T) in community-dwelling educated and uneducated elderly. Int J Geriatr Psychiatry. 2009;24(11):124250.
PP 32 EVALUATION OF DRUG BURDEN INDEX IN ELDERLY PATIENTS UTILIZED DISPOSABLE INSULIN PEN
BETUL OKUYAN , ZEHRA AYDINLI , IPEK CELIK , EFE DOGUKAN DINCEL , TUGCE SAY , DILAY YAVUZ , AYSU SELCUK , SEONKYEONG
YANG , MESUT SANCAR
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
The aim of the present study was to evaluate patients’ attitude and knowledge about disposable insulin pen utilization and
calculate drug burden index among elderly patients at community pharmacy. This cross sectional descriptive study was
conducted between February and May 2014. Patients were eligible for the present study if they were 65 years old or older,
prescribed at least a disposable insulin pen for at least 4 weeks, did not take any support for medication utilization and accepted
to participate to the present study. Cognitive function has been evaluated by using revised Turkish version of Mini Mental
State Examination (rMMSE-T) was scored between 0-30; the score under 22 or less and 18 or less were labelled as cognitive
impairment in educated and uneducated elderly; respectively (1). The steps for proper administration and storage were
evaluated in utilization of disposable insulin pens. Drug burden index have been also calculated. A total of forty-five elderly
patients (mean of age: 72.18±5.77 years old; male/female: 27/18) utilized disposable insulin pen were included in this study. Of
them, 40% had cognitive impairment according to rMMSE-T scores. The DBI scores were between 0-1 in twenty-eight patients
and were more than one in three patients. Most of them were failure to hold needle adequate period before withdrawal of pen
needle from skin (80.0%), failure to prime needle (60.0%), failure to store in-use pen at room temperature (53.3%), and failure
discard the insulin pen before expire date reported by manufacturer (44.4%). When evaluated discard pen needle after each
injection, 84.4% of them stored their disposable insulin pen with needle.Although the small sample size is a limitation of the
present study, it was concluded that patients’ cognitive function and drug burden index should be considered when selected
disposable insulin pen for elderly and pharmacist would take a role in education and monitoring of disposable insulin pen
among elderly patients.
1.Keskinoglu P, Ucku R, Yener G, Yaka E, Kurt P, Tunca Z. Reliability and validity of revised Turkish version of Mini Mental State
Examination (rMMSE-T) in community-dwelling educated and uneducated elderly. Int J Geriatr Psychiatry. 2009;24(11):124250.
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PP 33 EVALUATION OF DRUG BURDEN INDEX IN ELDERLY PATIENTS UTILIZED INHALER
BETUL OKUYAN , ZEHRA AYDINLI , IPEK CELIK , EFE DOGUKAN DINCEL , TUGCE SAY , DILAY YAVUZ , AYSU SELCUK , SEONKYEONG
YANG , MESUT SANCAR
CLINICAL PHARMACY DEPARTMENT, MARMARA UNIVERSITY- FACULTY OF PHARMACY, ISTANBUL, TURKEY
The aim of the present study was to evaluate patients’ inhalation skills and calculate drug burden index (DBI) among elderly
patients utilized metered-dose inhalers, diskuses, turbuhalers and aerolizers at community pharmacy.This cross sectional
descriptive study was conducted between February and May 2014. Patients were eligible for the present study if they were
65 years old or older, used at least one inhaler device, did not take any support for medication utilization and provided their
consent. Patient demographic, clinical and medication data were recorded with face-to-face interview. Cognitive function has
been evaluated by using revised Turkish version of Mini Mental State Examination (rMMSE-T) was scored between 0-30 (1).
Patients’ inhaler use attitudes were evaluated essential steps during inhaler use for each inhaler device. Drug burden index has
been also calculated.A total of thirty-seven elderly patients (mean of age: 71.65±5.47 years old; male/female: 20/17) utilized
aerolizer (70.27%), metered dose inhaler (54.05%), diskus (21.62%), and turbuhaler (10.81%) were included in this study. The
number of inhaler utilized by elderly patients was one (48.60%), two (45.90%) and three (5.40%). The mean of rMMSE-T score
was calculated as 23.62±4.08. Twenty seven elderly patients utilized five or more medications. Among twenty five elderly
patients who utilized anticholinergic and sedative medications; DBI index was calculated equal and less than one in twenty two
and more than one in three patients. When evaluating patients’ steps while using their inhaler; only five patients could correctly
follow all steps during inhaler utilization. Most of patients were failure to hold their breath for ten second after inspiration and
wait a few seconds before next dose. Although present study had a little sample size; our results presented the importance of
evaluation drug burden index and cognitive function in elderly patients, who used inhalers which required special skills and had
polypharmacy.
1.Keskinoglu P, Ucku R, Yener G, Yaka E, Kurt P, Tunca Z. Reliability and validity of revised Turkish version of Mini Mental State
Examination (rMMSE-T) in community-dwelling educated and uneducated elderly. Int J Geriatr Psychiatry. 2009;24(11):124250.
PP 34 PROTECTIVE EFFECTS OF FERULIC ACID AND CURCUMIN AGAINST CISPLATIN-INDUCED NEPHROTOXICITY IN RATS
ERLIASA BAMI 1, BETUL OKUYAN 1, OZLEM BINGOL OZAKPINAR 2, ZARIFE N. OZDEMIR KUMRAL 3, KUTAY KOROGLU 4, FERIHA
ERCAN 4, ZEYNEP CIRAKLI 5, TURGUT SEKERLER 2, FIKRET VEHBI IZZETTIN 1, MESUT SANCAR 1
DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY
DEPARTMENT OF BIOCHEMISTRY, MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY
3
DEPARTMENT OF PHYSIOLOGY, MARMARA UNIVERSITY FACULTY OF MEDICINE, ISTANBUL, TURKEY
4
DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, MARMARA UNIVERSITY FACULTY OF MEDICINE, ISTANBUL, TURKEY
5
DEPARTMENT OF BIOCHEMISTRY, BAKIRKOY DR. SADI KONUK TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY
1
2
This study aims to evaluate protective effects of phenolic compound ferulic acid and curcumin against cisplatin induced
nephrotoxicity in rats. Rats were divided into six groups consisting of six animals: three control groups, one toxicity group, and
two treatment groups. Serum saline (1mL/kg), ferulic acid (50 mg/kg), and curcumin (100 mg/kg) were administered by oral
gavage throughout five days. Single dose (10mg/kg) i.p. cisplatin was administered on the second day of experiment. Kidneys
were removed after 72 hours of cisplatin administration within each group. Malondialdehyde (MDA) levels, myeloperoxidase
(MPO) levels, and total antioxidant status (TAS) were measured in rat kidney tissues. Ferulic acid and curcumin significantly
decreased kidney MPO levels, which had increased as a result of cisplatin administration (p<0.05). Cisplatin caused an obvious
decrease in kidney TAS levels, while ferulic acid (50 mg/kg) and curcumin (100 mg/kg) administration significantly increased TAS
levels in treatment groups (p<0.05). Although a slight decrease was noticed in kidney MDA levels after treatment with ferulic
acid and curcumin when compared to toxicity group, no statistically significant differences were observed (p>0.05). Based on
this study we suggest that ferulic acid and curcumin supplementation expelled beneficial effects against cisplatin toxicity on rat
kidneys, therefore it appears that both ferulic acid and curcumin may be effective in preventing cisplatin induced nephrotoxicity.
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PP 35 PROTECTIVE EFFECTS OF FERULIC ACID AND CURCUMIN AGAINST TESTICULAR OXIDATIVE DAMAGE INDUCED BY
CISPLATIN IN RATS
ERLIASA BAMI 1, BETUL OKUYAN 1, OZLEM BINGOL OZAKPINAR 2, ZARIFE N. OZDEMIR KUMRAL 3, KUTAY KOROGLU 4, FERIHA
ERCAN 4, ZEYNEP CIRAKLI 5, TURGUT SEKERLER 2, FIKRET VEHBI IZZETTIN 1, MESUT SANCAR 1
DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY
DEPARTMENT OF BIOCHEMISTRY, MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY
3
DEPARTMENT OF PHYSIOLOGY, MARMARA UNIVERSITY FACULTY OF MEDICINE, ISTANBUL, TURKEY
4
DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, MARMARA UNIVERSITY FACULTY OF MEDICINE, ISTANBUL, TURKEY
5
DEPARTMENT OF BIOCHEMISTRY, BAKIRKOY DR. SADI KONUK TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY
1
2
The purpose of the present study was to provide information about the protective effects of phenolic compound ferulic acid
and curcumin against cisplatin induced toxicity in rat testis. A total of 36 male rats were divided into six groups each consisting
of six animals: three control groups, a toxicity group, and two treatment groups. Serum saline (1mL/kg), ferulic acid (50 mg/kg),
and curcumin (100 mg/kg) were administered by oral gavage for five days. Single dose 10mg/kg i.p. cisplatin was administered
on the second day of the experiment. Animals were sacrificed 72 hours due to cisplatin administration and rat testis was
removed within each group. Malondialdehyde (MDA) levels, myeloperoxidase (MPO) levels, and total antioxidant status (TAS)
were measured in rat testicular tissues. Ferulic acid and curcumin significantly decreased testis MPO levels, which had increased
as a result of cisplatin administration (p<0.05). TAS levels depletion was obvious in cisplatin administered testicular tissues,
while this situation was significantly reversed in treatment groups by an increase in TAS levels after treatment with ferulic acid
and curcumin (p<0.05). A slight improvement in the MDA levels was noticed after treatment with ferulic acid (50 mg/kg), and
curcumin (100 mg/kg) when compared to toxicity group, however MDA levels did not differ significantly (p>0.05). The current
study showed that ferulic acid and curcumin administrations were able to attenuate testicular oxidative damage induced by
cisplatin, leading thus in protective effect on the reproductive system of male rats.
PP 36 AN EVALUATION ON BEAUVERIA BASSIANA, ITS MICOTOXINS AND BIOACTIVITY
ENGIN KILIC
DEPARTMENT OF PHARMASOTIC MICROBIOLOGY, BASIC SCIENCE OF PHARMACY, FACULTY OF PHARMACY, ERZINCAN
UNIVERSITY, ERZINCAN, TURKEY
Beauveria bassiana occurs naturally in soils throughout the world and it is flamentous fungi. It produces beauvercin, a toxin
that weakens the immune system of the hosts. Beauvercin is a cyclıc hexadepsipeptide mycotoxin, which has insecticidal,
antimicrobial, antiviral and cytotoxic. İt is a potantial bioagents for pesticides and MEDICINEs. We reviews the important of
B. bassiana, the structure of chemical and bioactivity (insecticidal activite, anticancer activity, antibacterial activity, antifungal
activity, antiviral activity) of a fungal product beauvercin. Key Word: Fungi, Beauveria bassiana, beauvercin, anticancer activity,
antibacterial activity, antifungal activity, antiviral activity, insecticidal activite
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PP 37 ANTIOXIDANT AND ANTIMICROBIAL ACTIVITIES OF MARRUBIUM VULGARE AND ANACYCLUS PYRETHRUM
DIFFERENT EXTRACTS
BOUAMRA DALILA 1, BAKI CHEKIB ARSLANE 1, BOUCHEBOUR ABDELHAMID 1, HARZALLAH DAOUD 2, CRISTANI MARIATERESA 3,
FRATANTONIO DEBORAH 3, GINESTRA GIOVANNA 3, NOSTRO ANTONIA 3
LABORATORY OF CHRONIC DISEASES APPLIED PHYTOTHERAPY, FACULTY OF NATURAL AND LIFE SCIENCES, UNIVERSITY
FERHAT ABBAS, SETIF 1, 19000, ALGERIA
2
LABORATORY OF APPLIED MICROBIOLOGY, FACULTY OF NATURAL AND LIFE SCIENCES, UNIVERSITY FERHAT ABBAS, SETIF 1,
19000, ALGERIA
3
DEPT. DRUG SCIENCES AND HEALTH PRODUCTS, UNIVERSITY OF MESSINA, MESSINA, ITALY
1
In this study, the methanol, hexane and ethyl acetate extracts of both Marrubium vulgare and Anacyclus pyrethrum were
investigated for antioxidant and antimicrobial activities. The extracts were evaluated for phenolic content with Folin-Ciocalteau
colorimetric method, and the results demonstrated the richness of all extracts in polyphenols with mild concentration
differences. The ABTS (2,2-azobis-3-ethylbenzthiazoline-6-sulfonic acid) , DPPH (Diphenyl-1-picrylhydrazyl), FRAP (Ferric
Reducing Antioxidant Power), and ORAC (Oxygen Radical Absorbance Capacity) assays were carried out to evaluate the
antioxidant activity of the extracts, and the outcomes of the ABTS, DPPH and FRAP tests showed that Marrubium vulgare
hexane extract had the highest antioxidant activity (0.022±0.006 mmol TE/g.; 0.003±0.001 mmol TE/g and 0.140±0.024 mmol
Fe2+/g. respectively) while the ORAC assay referred the latter to the hexane extract of Anacyclus pyrethrum (0.666±0.011
µmol TE /g). Additionally, the AGE formation assay was performed to assess the glycation inhibitory activity of the extracts,
and the results showed that the hexane extract of Marrubium vulgare got the highest activity (IC50 = 1.24%). The disc-diffusion
method, that was performed to investigate the antimicrobial activity, revealed that all the extracts have inhibitory effects on
Staphylococcus aureus ATCC 6538 and the ethyl acetate extract of Anacyclus pyrethrum got the best results.
PP 38 COMPARATIVE ANALYSIS OF FIVE DIFFERENT GENERIC BRANDS OF PREDNISOLONE TABLET MARKETED IN LIBYA
ASMA BEN AHMED 1, HAJER ALBORAWY 1, ALAA MASHINA 1, PRADEEP VELAUTHAM 2, ABDULMONEM GOBASSA 2,
EMHEMMED ELGALLAL 2, MOHAMED EL ATTUG* 1
1
2
1DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, UNIVERSITY OF TRIPOLI, TRIPOLI- LIBYA
2 CENTRE FOR FOOD AND DRUG CONTROL, GURGI, TRIPOLI-LIBYA
Generic MEDICINEs have been increasingly used in recent years, primarily as a cost saving measure in healthcare provision.
Generic MEDICINEs are typically 20 – 90 % cheaper than originator equivalents. Physicians often continue to prescribe brandname drugs to their patients even when less expensive pharmacologically equivalent generic drugs are available. Unfortunately
Physicians in general and Libyan Physicians in particular tend to prescribe brand-name drugs, even without evidence of their
therapeutic superiority. There are several generic brands of Prednisolone are available in the Local market. However, their
pharmaceutical quality which affect safety and efficacy is unknown. Hence, prescribing of some generic products may lead
to serious health consequences. It is important, from a quality control point of view, to perform a comparative analytical
evaluation between trademarked and generic formulations to assure the quality of generics. Therefore the aim of this study
was to assess the quality of 5 mg Prednisolone tablets produced by five Pharmaceutical manufacturers from Turkey, United
Kingdom, India, UAE and Egypt under different trade names. The quality of five commercial brands of Prednisolone of the same
strength from different manufacturer were selected. The physicochemical parameters through the evaluation of uniformity
of tablet weight, friability, hardness, thickness, disintegration, microbiological, identification, dissolution and assay of the five
brands of prednisolone tablets were assessed using official (Pharmacopeial), non-official methods and in house validated
methods. All generic products complied with the official specification the limits for the friability, hardness tests, uniformity
of weight and thickness uniformity, except one product from Middle East do not comply with the limits for the friability test
which is more than 1 %, hardness was less than 40 N, highest RSD % (3.5 % for thickness) and (3.0 % for uniformity of weight).
All generic products complied with microbial tests, absent of microorganisms count and total yeast & mold count. So It can be
assumed that it is not as therapeutically effective and is not approved.
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PP 39 SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW TETRAZOLE DERIVATIVES
LEYLA YURTTAŞ 1, ZAFER ASIM KAPLANCIKLI 1, GÜLŞEN AKALIN ÇİFTÇİ 2, HALİDE EDİP TEMEL 2
1
2
DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, FACULTY OF PHARMACY, ANADOLU UNIVERSITY, ESKİŞEHİR, TURKEY
DEPARTMENT OF BİOCHEMİSTRY, FACULTY OF PHARMACY, ANADOLU UNIVERSITY, ESKİŞEHİR, TURKEY
Tetrazole derivatives possess very interesting pharmacological and biological properties and are reported to exhibit variety of
biological activities such as antibacterial, antifungal, antiviral, anticonvulsant, analgesic, anti-inflammatory, antinociceptive,
anesthetic, hypoglycemic, antiallergic, antitubercular and anticancer activities. In particular, 1-substituted tetrazole and
5-thio-substituted tetrazoles have been used in the synthesis of pharmacologically active drugs [1]. The aim of the present
work is to synthese a novel series of tetrazole derivatives and to investigate their potential cytotoxic properties and also
anticholinesterase activity on acetylcholinesterase and butyrylcholinesterase enzymes. N-(arylidene)-4-[(1-phenyl-1Htetrazole-5-yl)thio]butanohydrazide derivatives (3-28) derivatives were synthesized using 1-methyl-1H-tetrazole-5-thiol and
ethyl 4-chlorobutanoate as starting materials. The obtained ester compound (1) was reacted with hydrazine hydrate, then with
appropriate aromatic aldehydes to gain final compounds. The structures of the compounds were confirmed by IR, 1H-NMR,
13C-NMR, mass spectra and elemental analysis. The biological activity studies are in progress.
1. Kaplancıklı ZA, Yurttaş L, Özdemir A, Turan-Zitouni G, Akalın Çiftçi G, Ulusoylar Yıldırım Ş, Abu Mohsen U. Synthesis and
antiproliferative activity of new 1,5-disubstituted tetrazoles bearing hydrazone moiety. Med Chem Res. 2014; 23:1067-1075.
PP 40 IN VITRO ANTITUMOR ACTIVITY EVALUATION OF NEW 1,2-DISUBSTITUTED BENZIMIDAZOLE DERIVATIVES
LEYLA YURTTAŞ 1, ŞEREF DEMIRAYAK 2, GÜLŞEN AKALIN ÇİFTÇI 3
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, ANADOLU UNIVERSITY, ESKIŞEHIR, TURKEY
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, SCHOOL OF PHARMACY, MEDIPOL UNIVERSITY, ISTANBUL, TURKEY
3
DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, ANADOLU UNIVERSITY, ESKIŞEHIR, TURKEY
1
2
Since we have worked on 1,2-disubstituted benzimidazole derivatives and their anticancer activities, we have reported some
anticancer active 1,2-disubstituted benzimidazole derivatives in a few studies (1,2). In this study, we have identified the
synthesis of new benzimidazole derivatives named 1-(2-aryl-2-oxoethyl)-2-(thioamido)benzimidazoles and also their antitumor
activity evaluation. The compounds (3a-n) were synthesized according to the procedure described in our previous study (3).
The anticancer activity evaluation studies are going on according to the MTT assay, BrdU method, and flow cytometric analysis
on C6 and A549 tumor cells.
1. Demirayak S, Kayagil I, Yurttas L. Microwave supported synthesis of some novel 1,3-Diarylpyrazino[1,2-a]benzimidazole
derivatives and investigation of their anticancer activities Eur J Med Chem. 2011;46:411-416. 2. Demirayak S, Abu Mohsen
U, Karaburun AC. Synthesis and anticancer and anti-HIV testing of some pyrazino[1,2-a]benzimidazole derivatives. Eur J Med
Chem. 2002;37:255-260. 3. Yurttaş L, Demirayak S, Çiftci GA, Yıldırım ŞU, Kaplancıklı ZA. Synthesis and biological evaluation of
some 1,2-disubstituted benzimidazole derivatives as new potential anticancer agents. Arch Pharm Chem Life Sci. 2013;346:403414.
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PP 41 SPECIFIC KILLING OF HIGHLY METASTATIC BREAST CANCER CELLS BY TYPE 1 PILIATED ESCHERICHIA COLI
MERVE SUZAN ZEDEN , ENDER VOLKAN
CYPRUS INTERNATIONAL UNIVERSITY
Pili are filamentous, polymeric protein appendages assembled by bacteria. Type 1 pili, assembled by uropathogenic Escherichia
coli (UPEC) via the chaperone-usher pathway, are virulence factors in urinary tract infections (UTIs). Type 1 pili mediate binding
with the mannose residues on the bladder surface, to invade the host cells. In vitro studies demonstrated that β1 and α3 integrins
are also key receptors for type 1 piliated UPEC. The function of such integrins seems to be versatile ranging from cell adhesion
to migration on extracellular matrix. Interestingly, β1 and α3 integrins are highly expressed on highly metastatic breast cancer
cell lines MDA-MB-231. To test the hypothesis that type 1 piliated UPEC may exert toxicity on MDA-MB-231 cancer cells, we
have co-cultured statically grown, normalized, piliated cultures of UTI89 strain of UPEC with a confluent layer of MDA-MB-231
cells for 1 hour. Statically grown, piliated cultures of UTI89 were observed to cause significantly higher death rates (p < 0.02) on
MDA-MB-231, when compared with the media control, shaking cultures or the control strain of C600. Tryphan blue assay and
microscopic investigations were utilized to observe cancer cell death. Interestingly, this significant type 1 pili-mediated toxicity
was specific to highly metastatic MDA-MD-231 cells as lowly metastatic MCF7 cells did not experience significantly increased
killing, suggesting that pili may have a role in targeting metastatic tumor cells. These findings indicate that studies on bacterial
factors like chaperone-usher pili can help improve our approaches of designing therapeutics for treatment of not only infections
but also other diseases like cancer.
PP 42 ANTIMICROBIAL ACTIVITY OF VARIOUS MOUTHRINSES AGAINST STREPTOCOCCUS MUTANS, LACTABACILLUS CASEI, L.
ACIDOPHILUS AND CANDIDA ALBICANS
GÜLBIKE DEMIREL 1, MÜJDE ERYILMAZ 2, NURTEN ALTANLAR 2, GÜRKAN GÜR 1
1
2
DEPARTMENT OF RESTORATIVE DENTISTRY, FACULTY OF DENTISTRY, ANKARA UNIVERSITY, ANKARA, TURKEY
DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, FACULTY OF PHARMACY, ANKARA UNIVERSITY, ANKARA, TURKEY
Mouthrinses are used for several reasons such as to freshen breath, to control dental caries, to prevent gingivitis and to reduce
plaque formation on teeth. The main advantage of mouthrinses is their ability to deliver antimicrobial properties to all accessible
surfaces in the mouth (1, 2). The aim of this in vitro study was to determine the antimicrobial activities of commonly used
mouthrinses against different oral microorganisms. Six commercially available mouthrinses (Colgate Total, Colgate Pro-argin,
Colgate Plax, Listerine, Oral B Pro-expert and Oderol) were used in the study. The antimicrobial activities of mouthrinses against
Streptococcus mutans ATCC 25175, Lactobacillus casei (RSM:900), Lactobacillus acidophilus ATCC 11975 and Candida albicans
ATCC 10231 were evaluated by disc diffusion and tube dilution methods. Chlorhexidine gluconate was used as positive control.
The diameters of the inhibition zones were measured in millimeters and the experiment was repeated twice. According to the
results, Colgate Total, Colgate Plax, Oral B Pro-expert and Oderol showed good antimicrobial activity against test microorganisms
compare with Colgate Pro-argin and Listerine. We found the chlorhexidine and cetylpyridinium chloride included mouthrinses
more active than other products tested. In conclusion, the daily usage of mouthrinses will help to provide oral hygiene.
1. Silverman S, Wilder R. Antimicrobial mouthrinse as part of a comprehensive oral care regimen. JADA. 2006; 137:22S-26S. 2.
Chen Y, Wong RWK, Seneviratne CJ, Hagg U, McGrath C, Samaranayake LP. Comparison of the antimicrobial activity of Listerine
and Corsodyl on orthodontic brackets in vitro. Am J Orthod Dentofacial Orthop. 2011; 140:537-542.
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PP 43 SYNTHESIS, MOLECULAR DOCKING, AND ANTITUMORAL ACTIVITY OF ALNUSTONE-LIKE COMPOUNDS AGAINST
ESTROGEN RECEPTOR α-POSITIVE BREAST CANCER
KAAN KÜÇÜKOĞLU 1, HATİCE SEÇİNTİ 1, AYKUT ÖZGÜR 2, HASAN SEÇEN 1, YUSUF TUTAR 3
FACULTY OF PHARMACY ATATÜRK UNIVERSITY, ERZURUM
FACULTY OF PHARMACY GAZİOSMANPAŞA UNIVERSITY, TOKAT
3
FACULTY OF PHARMACY CUMHURİYET UNIVERSITY, SIVAS
1
2
Breast cancer is the most common cancer type worldwide among women. In the United States, breast cancer is 14.1% of all
expected cancer cases and approximately 232,340 new cases and 39,620 deaths will be estimated in 2013 (1). Alnustone, a nonphenolic diarylheptanoid, was first isolated from Alnus pendula (Betulaceae) and characterized four decades ago (2). Recently,
it was reported that alnustone exhibited significant antitumor activity against Bel-7402 (human hepatocellular carcinoma cells)
cell lines (3). New alnustone-like compounds were synthesized by condensating 4-phenyl-2-butanones and cinnamaldehydes.
Condensations of 4-phenyl-2-butanones and cinnamaldehydes were performed in situ enamination using pyrrolidine and acetic
acid in diethyl ether. Ten different alnustone-like compounds differing with aryl substituents were prepared with a variety of
yields. The cytotoxic activity of alnustone-like compounds were evaluated against MCF-7 cells and tamoxifen and paclitaxel were
used as positive control to compare with the alnustone-like compounds. Cell proliferation assay showed that compounds 1, 10,
12, 14, and 17 (Group A) displayed paclitaxel like activity and on the other hand, compounds 15, 16, and 19 (Group B) displayed
tamoxifen like activity. And, compounds 15 and 18 (Group C) displayed a transition activity between these drugs. Structure and
function of the designed compounds correlates with the biochemical behavior of the breast cancer cell survival. The designed
compounds may be developed for drug resistance and may potentially decrease the side effects of the commercially available
drugs in the future.
1. Surveillance, Epidemiology, and End Results Program. National Cancer Institute. http://seer.cancer.gov/statfacts/html/breast.
html (accessed 03.03.2014) 2. Suga T, Asakawa Y, Iwata N. 1,7-Diphenyl-1,3-heptadien-5-one: a new ketone from Alnus pendula
(Betulaceae). Chem Ind (London). 1971;27:766. 3. Li Y, Yang L, Wang C, Chou G, Wang Z. Chemical constituents from seeds of
Alpinia katsumadai Hayata and their anti-tumor activity. Shang Hai Zhong Yi Yao Da Xue Xue Bao. 2010;24:72-75.
PP 44 EVALUATION OF THE CYTOTOXICITY OF SOME HYDRAZONE COMPOUNDS AGAINST FOUR HUMAN CANCER CELL LINES
KAAN KÜÇÜKOĞLU 1, HALISE INCI GÜL 1, HIROSHI SAKAGAMI 2
1
2
FACULTY OF PHARMACY ATATÜRK UNIVERSITY, ERZURUM
FACULTY OF PHARMACY MEIKAI UNIVERSITY, JAPAN
Hydrazones and Mannich bases are group of compounds which are known to have anticancer and cytotoxic activities (1,2).
Some new hydrazone compounds, N,N-bis[1-aryl-3-(pyrrolidine-1-yl)propylidene]hydrazine dihydrochlorides, were synthesized
by condensating corresponding mono Mannich base and hydrazine hydrate in ethanolic acetic acid. Precursor mono Mannich
bases were prepared by using acetophenone derivatives, paraformaldehyde, pyrrolidine and hydrochloric acid in ethanol. Seven
different hydrazone compounds with different aryl substituent were synthesized in moderate yields. The aryl part was changed
as phenyl in R1, 4-methylphenyl in R2, 4-methoxyphenyl in R3, 4-hydroxyphenyl in R4, 4-chlorophenyl in R5, 3-methoxyphenyl
in R6, 4-fluorophenyl in R7. The cytotoxic activity of hydrazone compounds were evaluated against three human oral squamous
cell carcinoma cell lines (HSC-2, HSC-3, and HSC-4) and human promyelocytic leukemia cells (HL-60) and three normal human
oral cell types [gingival fibroblast (HGF), pulp cell (HPC), periodontal ligament fibroblast (HPLF)]. The most powerful compound
in this series was 4-methylphenyl derivative compound R2 which showed cytotoxic activity with mean CC50 = 21 μM against
four tumor cell lines and this compound had stronger cytotoxic activity than the reference compound peplomycin. Compound
R6, a 3-methoxyphenyl derivative, and compound R5, a 4-chlorophenyl derivative, had significant cytotoxic activities with 40
μM and 64 μM mean CC50 values, respectively. Compound R3 which was 4-methoxyphenyl derivative had the highest tumorspecifity with 1.4 value. In conclusion, hydrazones synthesized having a pyrrolidine moiety as potential anti-cancer candidate
deserved further structural modification and pharmacological evaluation.
1. Gul HI, Das U, Pandit B, Li PK. Evaluation of the cytotoxicity of some mono-Mannich bases and their corresponding azine
derivatives against androgen-independent prostate cancer cells. Arzneimittelforschung 2006;56:850-854. 2. Cocco MT, Congiu
C, Lilliu V, Onnis V. Synthesis and in vitro antitumoral activity of new hydrazinopyrimidine-5-carbonitrile derivatives. Bioorg Med
Chem. 2006;14:366-372.
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PP 45 ACTION OF N,N’-BIS[1-(4-FLUOROPHENYL)-3-(PIPERIDINE-1-YL)PROPYLIDENE]HYDRAZINE DIHYDROCHLORIDE ON
MITOCHONDRIAL RESPIRATION
KAAN KÜÇÜKOĞLU 1, HALISE INCI GÜL 1, RENGUL CETIN-ATALAY 2, YOSRA BARATLI 3, ANNE-LAURE CHARLES 3, MURAT
SÜKÜROĞLU 4, MUSTAFA GÜL 1, BERNARD GENY 3
FACULTY OF PHARMACY ATATÜRK UNIVERSITY, ERZURUM
FACULTY OF PHARMACY BILKENT UNIVERSITY, ANKARA
3
FACULTY OF PHARMACY UNIVERSITY DE STRASBOURG, FRANCE
4
FACULTY OF PHARMACY GAZI UNIVERSITY, ANKARA
1
2
Hepatocellular carcinoma (HCC) is such a cancer type that the treatment options are very limited, the only curative treatment
procedure is surgery and HCC cells have high resistance to chemotherapeutic agents (1). N,N’-Bis[1-(4-fluorophenyl)-3(piperidine-1-yl)propylidene]hydrazine dihydrochloride which was called P7 in the literature (2) was synthesized by the reaction
of 1-aryl-3-(piperidine-1-yl)-1-propanone hydrochloride with hydrazine hydrate in ethanolic acetic acid. The chemical structure
of this compound was confirmed by UV, 1H NMR, 13C NMR and HRMS spectra. The cytotoxic activity of P7 was tested against
human hepatoma (Huh7) and breast cancer (T47D) cells. This compound was found to have more potent cytotoxic activity
against Huh7 cells with 8.01 μM IC50 value than the reference compound 5-FU. In addition, the action of P7 on the mitochondrial
respiratory chain complexes was measured. Compound P7 inhibited the mitochondrial respiration significantly at 144, 264 and
424 μM concentrations dose-dependantly in liver homogenates. Therefore, inhibition of mitochondrial respiratory chain by the
compound P7 suggests that inhibition of mitochondrial respiration may be one of the contributing mechanisms to the cytotoxic
activity of P7. The results suggest that P7 deserved further structural modification and pharmacological evaluation as potential
anti-cancer candidate.
1. Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol.
2007;4:424-432. 2. Kucukoglu K, Gul HI, Cetin-Atalay R, Baratli Y, Charles A-L, Sukuroglu M, Gul M, Geny B. Synthesis of new
N,N’-bis[1-aryl-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides and evaluation of their cytotoxicity against human
hepatoma and breast cancer cells. J Enzyme Inhib Med Chem. 2013;Early Online: 1-7, doi: 10.3109/14756366.2013.795562.
PP 46 EXTEMPORANEOUS PEDIATRIC SUSPENSION OF SPIRONOLACTONE: FORMULATION AND STABILITY STUDY
AMEL CHENAFA 1, LINDA AOUAD 2, IMANE SEDIRI 1, ISMAHAN DJEBBAR 1
1
2
DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE, DJILLALI LIABES UNIVERSITY, SIDIBELABBES, ALGERIA
FACULTY OF MEDICINE, DJILLALI LIABES UNIVERSITY, SIDIBELABBES, ALGERIA
The specialties intended for adults are often inadequate marketed for pediatric use, such as for a galenic form or in the dosage.
In industry, the development of a pediatric drug is confronted to various problems. So, the hospital pharmacies have to
respond to adaptation needs of pharmaceutical forms for pediatric use. The objective of our work is to develop an oral form of
spironolactone for pediatric use since no adapted form to child is commercialized. Therefore an extemporaneous suspension
of spironolactone was prepared at the concentration of 1mg/ml from 25mg tablets and stored in amber glass bottles. Physical
and chemical stability was studied in three temperatures: 5°C, 25°C and 40°C and evaluated at 0, 7, 14, 28, 42, 56, 70 and 90
days. The microbiological stability was also conducted at D0, D15 and D30. No organoleptic changes have been detected on
the suspension conserved at 25 and 5°C and pH values are around the optimum pH of the spironolactone stability (≈ 4,5)(1).
Sheltered from light, the developed suspension of spironolactone remained stable at the temperature of 5°C.
1. Ana, C. Salgado, M. Luísa Rosa, M.Aida Duarte and António J.Almeida, Stability of spironolactone in an extemporaneously
prepared aqueous suspension: the importance of microbiological quality of compounded paediatric formulations, The European
Journal of Hospital Pharmacy Science, Volume 11, 2005, P. 68 - 73
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PP 47 DEVELOPMENT OF TWO TRADITIONAL IMPROVED PREPARATIONS BASED ON SPONTANEOUS PLANT IN ALGERIA
AMEL CHENAFA , MUSTAPHA CHELGHOUM , DJAHIDA ELGOUTNI , SIHEM HAFDI
DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE, DJILLALI LIABES UNIVERSITY, SIDIBELABBES, ALGERIA
Anthemis nobilis and Thymus vulgaris are two plants widely used in traditional MEDICINE, and very popular in Algeria for
the treatment of inflammatory conditions (Roman chamomile) and bronchitis (thyme) (1). Numerous scientific studies have
confirmed the pharmacological properties of different extracts of the aerial parts of the two plants. The objective of our study
is the valorization of these two spontaneous plants by an adequate galenic formatting of the methanolic extract of chamomile
and essential oil of thyme. The quality control of plant material was performed according to the recommendations of the
European Pharmacopoeia. The extraction was performed by steam distillation of the leaves of thyme to obtain the essential
oil and by Soxhlet for flower heads of Chamomile. Taking into account the physical and chemical properties of raw materials,
the choice of the dosage form is focused on a 2 % ointment methanolic extract of chamomile and suppositories 150 mg of
thyme essential oil. The results of quality control of plant material are conform to standards. Suppositories obtained have a
white and homogeneous color. The resulting ointment is brown, with a smooth appearance without any lumps. The pH is 6.8.
The development of these two dosage forms can be part of a broader outreach to drug herbal perspective, and the use of
chamomile and thyme, which are two plants available in nature.
1. Basch E, Catherine U et al. Thyme (Thymus vulgaris L.), Thymol, Monograph from natural stansard. Journal of Herbal
Pharmacotherapy 2004, Vol. 4(1): 49-67.
PP 48 THE FOLK MEDICINAL PLANTS OF ÇATAK (VAN-TURKEY)
GIZEM BULUT , ERTAN TUZLACI , RABIA SENA TÜRKER
MARMARA UNIVERSITY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY
This study was made to reveal the plants used as traditional folk medicine in Çatak (Van) situated in east of Turkey. The
specimens of the plants used as folk remedies have been collected and the information about the local names, the part(s) used,
the ailments treated, the therapeutic effect, the preparation, the methods of administration, and the duration of treatment
has been recorded. The ethnopharmacological information was obtained from the local people by personal interviews carried
out face to face. The plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara University. As a result of
identification of the plant specimens, 33 species, used as a traditional folk medicine in Çatak, have been determined. According
to the majority of the informants, the plants are mostly used for cold, wound, anthelmintic and kidney stones.
PP 49 THE FOLK MEDICINAL PLANTS OF HATAY (TURKEY)
GIZEM BULUT , ERTAN TUZLACI , SEÇKIN YATKIN
MARMARA UNIVERSITY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY
This study was made to reveal the plants used as traditional folk medicine in Hatay situated in south of Turkey. The specimens
of the plants used as folk remedies have been collected and the information about the local names, the part(s) used, the
ailments treated, the therapeutic effect, the preparation, the methods of administration, and the duration of treatment has
been recorded. The ethnopharmacological information was obtained from the local people by personal interviews carried out
face to face. The plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara University. As a result of
identification of the plant specimens, 30 species, used as a traditional folk medicine in Hatay, have been determined. According
to the majority of the plants which have similar usage the plants are mostly used for wound, stomach ailments, cold and
diabetes.
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PP 50 THE FOLK MEDICINAL PLANTS OF SARIYER (İSTANBUL-TURKEY)
ERTAN TUZLACI , GIZEM BULUT , CIHAN ÖNDER
MARMARA UNIVERSITY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY
This study was made to reveal the plants used as traditional folk MEDICINE in Sarıyer (İstabul) situated in northwest of Turkey.
The specimens of the plants used as folk remedies have been collected and the information about the local names, the part(s)
used, the ailments treated, the therapeutic effect, the preparation, the methods of administration, and the duration of treatment
has been recorded. The ethnopharmacological information was obtained from the local people by personal interviews carried
out face to face. The plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara UNIVERSITY. As a result
of identification of the plant specimens, 33 species, used as a traditional folk MEDICINE in Sarıyer, have been determined.
According to the majority of the plants which have similar usage, the plants are mostly used for gastrointestinal system diseases,
wound, cold and diabetes.
PP 51 THE FOLK MEDICINAL PLANTS OF KIZILTEPE (MARDİN-TURKEY)
ERTAN TUZLACI , GIZEM BULUT , SÜLEYMAN OK
MARMARA UNIVERSITY OF PHARMACY DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY
This study was made to reveal the plants used as traditional folk MEDICINE in Kızıltepe (Mardin) situated in southeast of Turkey.
The specimens of the plants used as folk remedies have been collected and the information about the local names, the part(s)
used, the ailments treated, the therapeutic effect, the preparation, the methods of administration, and the duration of treatment
has been recorded. The ethnopharmacological information was obtained from the local people by personal interviews carried
out face to face. The plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara UNIVERSITY. As a result
of identification of the plant specimens, 16 species, used as a traditional folk MEDICINE in Kızıltepe, have been determined.
According to the majority of the informants, the plants are mostly used for urinary system diseases, heart diseases, shorthness
of breath diabetes stomach diseases.
PP 52 PREPARATION AND CHARACTERIZATION OF LOVASTATIN POLYMERIC MICROPARTICLES BY COACERVATION METHOD
FOR DISSOLUTION ENHANCEMENT
SUHAIR AL-NIMRY , MAI KHANFAR
FACULTY OF PHARMACY JORDAN UNIVERSITY SCIENCE AND TECHNOLOGY, JORDAN
Lovastatin is a highly lipophilic and poorly water soluble drug (BCS class II drugs). Oral absorption of lovastatin is about 30% of
the dose. It undergoes extensive first-pass extraction resulting in low and variable bioavailability. The objective was to enhance
the dissolution and release of the drug from the dosage form. Polymeric microparticles were prepared by coacervationphase separation method. The method was optimized through studying effects of type of polymer; drug:polymer ratio; type
of organic solvent; and concentration of SDS surfactant on particle size, particle size distribution, and in-vitro drug release.
Polymeric microparticles were characterized using different techniques. In-vitro drug release into 0.1N HCl was evaluated and
compared to that from physical mixtures and of unprocessed drug. Microparticles prepared using Eudragit® L 100 at a ratio
of 1:2 (drug:polymer), ethanol as a solvent, SDS at a concentration of 0.25%, were optimum. SEM images and PXRD patterns
indicated that the drug was transformed into an amorphous solid. The results of FTIR, DSC and PXRD indicated the absence
of any interaction between drug and polymer. Compressibility index and Hausner ratio, indicated that flow properties were
enhanced and that addition of glidants can be useful. Release of drug from both polymeric microparticles and physical mixture
was enhanced as compared to the unprocessed drug. It was faster and almost complete within 15 min from the polymeric
microparticles as compared to that from physical mixture. In conclusion, the optimized microparticles proved to be useful in
enhancing the release of the drug 5 folds.
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PP 53 SIMULTANEOUS DETERMINATION OF B1, B2, B3, B9, AND B12 VITAMINS IN APPLE BY HPLC-DAD
HALİL İBRAHİM ULUSOY
FACULTY OF PHARMACY CUMHURIYET UNIVERSITY, SIVAS, TURKEY
Vitamins are organic compounds that promote and regulate essential biochemical reactions within the human body, which is
generally unable to synthesize these compounds — they have to be obtained from food in trace amounts for growth, health,
and reproduction, and the lack of these compounds in the diet results in overt symptoms of deficiency (1). The qualitative and
quantitative analysis of vitamins in foods, whether inherently present or added during food manufacture, also in plasma, serum,
and pharmaceuticals, has become extremely important to the food industry, to assess the nutritional quality of foodstuff, and to
the medical and pharmaceutical industries, for protection or control of human health (2). A new HPLC method was developed
for the simultaneous determination of five water-soluble vitamins, viz. thiamine, riboflavin, nicotinamide, cyanocobalamin, and
folic acid in apple samples. Separation was achieved at 40 °C on a Inertsil C18 (250 mm×4,6×5 µm) analytical column. Gradient
elution was performed by using H2O/CH3OH (50/50), pH:3.00 and pH 5.20 phosphate buffers at a flow rate of 0.6 mL/min.
Detection was performed with a photodiode array detector at 267 (B2, B3) , 282 (B9), 244 (B1), 361 (B12) nm. Each vitamin was
quantitatively determined at its maximum wavelength. Spectral comparison was used for peak identification in real samples.
Detection limits were in the range of 0.35-1.45 µg mL-1. The preparation of apple samples was performed by using microwave
extraction system. Extraction recoveries from sample matrices ranged from 94.6% to 104.0%.
PP 54 INVESTIGATION ON THE TOXIC POTENTIAL OF TRIBULUS TERRESTRIS IN VITRO
GUL OZHAN , MAHMOUD ABUDAYYAK , TARBIN JANNUZZI , BUKET ALPERTUNGA
FACULTY OF PHARMACY ISTANBUL UNIVERSITY, TURKEY
Tribulus terrestris L. (Zygophyllaceae) has been commonly used to energize, vitalize, and improve sexual function and physical
performance in men. This study investigates the potential cytotoxic and genotoxic, and endocrine disrupting activities of T.
terrestris in vitro. The whole plant was extracted with water, methanol, and chloroform. The genotoxic potential of T. terrestris
extracts at 3-2400 mg/mL was assessed by Comet assay in a rat kidney cell line (NRK-52E) and by Ames assay in Salmonella
typhimurium TA98 and TA100 strains. Endocrine disrupting effects of the extracts at concentrations of 0.22-25 000 mg/mL were
assessed by YES/YAS assay in Saccharomyces cerevisiae. Cytotoxic activity of the extracts was determined by the MTT test in
NRK-52E cells. The different exposure times were used for four tests (3-48 h). The methanol extract of T. terrestris IC50 value
was 160 mg/mL. The other extracts did not show cytotoxic effects. In the Comet and Ames genotoxicity assays, none of the
extracts possessed genotoxic activities at concentrations of 0-2400 mg/mL. Only the water extract of T. terrestris induced frame
shift mutations after metabolic activation. The water extract also showed estrogenic activity by YES/YAS assay in S. cerevisiae
at the higher concentrations than 27 mg/mL (higher than 2.6-fold), while the other T. terrestris extracts had anti-estrogenic
properties. T. terrestris had estrogenic and genotoxic activities. The study was useful in determining its toxicological effects and
the precautions regarding consumption.
PP 55 THE EFFECTS OF AGING ON THE FUNCTIONAL AND STRUCTURAL PROPERTIES OF THE RAT BASILAR ARTERY
NIHAL TUMER , HALE ZERRIN TOKLU , JUDY DELP , SEHKAR OKTAY , PAYAL GHOSH , KEVIN STRANG , MICHAEL DELP , PHILIP
SCARPACE
PHARMACOLOGY AND THERAPEUTICS APPLIED PHYSIOLOGY AND KİNESİOLOGY UNIVERSITY OF FLORIDA, ABD
Aging leads to progressive pathophysiological changes in blood vessels of the brain and periphery. The aim of this study was
to evaluate the effects of aging on cerebral vascular function and structure. Basilar arteries were isolated from male Fischer
344 cross Brown Norway (F344xBN) rats at 3, 8 and 24 months of age. The basilar arteries were cannulated in the pressurized
system (90 cm H2O). Contractile responses to KCl (30-120mM) and endothelin-1 (10-11-10-7 M) were evaluated. Responses
to acetylcholine (ACh) (10-10-10-4 M), diethylamine (DEA)-NONO-ate (10-10-10-4 M), and papaverin (10-10-10-4 M) were
assessed to determine both endothelium-dependent and endothelium-independent responsiveness. Advanced aging (24
months) decreased responses of the basilar artery to both the contractile and relaxing agents; whereas, DEA-induced dilation
was significantly higher in the 8 month old group compared with the younger and older groups. The arterial wall-to-lumen
ratio was significantly increased in 24 month old rats. Smooth muscle cell count was also decreased in old rats. These findings
indicate that aging produces dysfunction of both the endothelium and the vascular smooth muscle in the basilar artery. Aging
also alters wall structure of the basilar artery, possibly through decreases in smooth muscle cell number and concomitant
hypertrophy.
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PP 56 INVESTIGATION OF THE PROTECTIVE EFFECT OF CINNAMOMUM CASSIA BARK EXTRACT AGAINST H2O2-INDUCED
OXIDATIVE DNA DAMAGE IN HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND ANTIOXIDANT ACTIVITY
SUMRU SOZER KARADAGLI , BORTE AGRAP , FERZAN LERMIOGLU ERCIYAS
FACULTY OF PHARMACY EGE UNIVERSITY , IZMIR, TURKEY
Cinnamon, one of the most widely used spices in the world, has been shown to have various biological functions including
antidiabetic and antitumor activities. Its antidiabetic and antitumor effects were linked with its strong antioxidant activity. In
the present study we aimed to investigate the antioxidant activity and possible protective effect of Cinnamomum cassia bark
water extract against H2O2-induced oxidative DNA damage. Viability of lymphocytes was determined by Trypan Blue test.
For the evaluation of the antioxidant activity, total phenol and flavonoid contents and 2,2-diphenyl-1-picrylhydrazyl (DPPH)
inhibitory activity of the extract were determined. DNA damage was determined by alkaline comet assay in human peripheral
blood lymphocytes. Lymphocytes exhibited >86 % survival up till the concentration of 800 μg/ml of the extract. Total phenol
and flavonoid contents were calculated as 10.6 g ± 0.001 gallic acid equivalents/ 100 g dry weight and 2.25±0.004 g quercetin
equivalents/100 g dry weight of the extract, respectively. The extract concentration providing 50 % inhibition of DPPH was
found as 76.68 μg/ml. Cinnamomum cassia bark water extract at ≥100 μg/ml concentrations caused significant protection
against H2O2-induced oxidative DNA damage in lymphocytes. Our results support the suggestions that Cinnamomum cassia
bark water extract could be beneficial as a prophylactic agent in prevention of oxidative stress-related diseases.
1.Singh R, Koppikar SJ, Paul P, Gilda S, Paradkar AR, Kaul-Ghanekar R. Comparative analysis of cytotoxic effect of aqueous
cinnamon extract from Cinnamomum zeylanicum bark with commercial cinnamaldehyde on various cell lines. Phar Bio 2009;
47:1174-9. 2.Wondrak GT, Villeneuve NF, Lamore SD, Bause AS, Jiang Tao Z, Donna D. The Cinnamon-Derived Dietary Factor
Cinnamic Aldehyde Activates the Nrf2-Dependent Antioxidant Response in Human Epithelial Colon Cells. Molecules 2010;
15:3338–55. *This abstract has been presented in Marmara Pharmaceutical Journal 18: 43-48, 2014.
PP 57 PHYTOCHEMICAL ANALYSIS OF HELIOTROPIUM LASIOCARPUM SUBSP. LASIOCARPUM FISCH. ET MEY.
(BORAGINACEAE)
MELDA DÖLARSLAN 1, AYŞE ŞAHİN YAĞLIOĞLU 2, MURAT TEMIRTÜRK 2, EBRU GÜL 3, İBRAHIM DEMIRTAŞ 2
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
3
DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 18100, CANKIRI, TURKEY
1
2
Heliotropium lasiocarpum subsp. lasiocarpum Fisch. Et Mey. belongs to the family Boraginaceae, the plants of family use
decorative plants, spices, and useful for the preparation of dyestuffs. Active agents of the family are mucilage derivatives
(arabinose, glucose and galactose), Pyrolizidinalkaloits (Amabilin, Supinidin, Lycopsamin, Intermedin, 7-Asetil-Lycopsamin
ve 7-Asetilintermedin). Also, The family contains tannins, saponins, resins, starches, silicic acids, vitamin C and minerals. H.
lasiocarpum Fisch. Et Mey. are semi boy grows, perennial and annual herbaceous plants (1). This plant acts as an antidote
against all deadly poison and uses antipyretic, the gall enhancer and wound healing (2). In this study, H. lasiocarpum were
collected from Çankırı. This plant were separated as airel parts and root and dried at room temperature (25°C) in the shade. The
extracts of these materials which were acetone, chloroform, ethyl acetate and ethanol, extracts, respectively were prepared.
The fatty acides of acetone and chloroform extracts by GC-MS and phenolic compounds in ethyl acetate and ethanol extracts by
the HPLC-TOF-MS were performed. As a result of GC-MS analyzes were detected 12 compounds. The choloroform extract of H.
lasiocarpum root and airel parts and the acetone extract of this plant roots were determined linoleic acid the main component.
However, the acetone extract of the airel parts were detected linolenic acid. The main component were rosmarinic acid from
the ethanol and ethyl acetate extracts of the root; vanillic acid from the ethyl acetate extracts of the airel parts and rutin from
the ethanol extracts of the same parts by HPLC-TOF-MS.
1. Davis, P. H., 1965-1988, Flora of Turkey and the East Aegean Islands, vol. 1-9, Edinburgh: Edinburgh UNIVERSITY Pres. 2.
Baytop, T. 1999. Türkiye’de Bitkiler İle Tedavi, Nobel Tıp Kitabevleri, İstanbul.
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PP 58 PHYTOCHEMICAL ANALYSIS, DYESTUFF POTENTIAL AND CYTOTOXIC ACTIVITY OF ANTHEMIS TINCTORIA VAR.
TINCTORIA (ASTERACEAE)
AYŞE ŞAHİN YAĞLIOĞLU 1, FERDA ESER 2, MELDA DÖLARSLAN 3, İBRAHIM DEMIRTAŞ 1
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE AND EDUCATION, GAZIOSMANPASA UNIVERSITY, 60240 TOKAT, TURKEY
3
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
1
2
Anthemis species are used in pharmaceutics, cosmetics and food chemistry. Extracts of the plant are used as antiseptic,
anti-inflammatory, antibacterial, antispasmodic, sedative agents, soothing the pain and irritation, ulcers and wound healing,
treatment of cystitis and dental afflictions in folk medicine(1). The plant is also used to dye fabrics for obtain yellow color (2).
In this study, Anthemis tinctoria var. tinctoria (Asteraceae) was collected from Çankırı. Species identification of the collected
materials was performed. The parts of the plant were separated as flowers, stem and roots and dried at room temperature
(25°C) in the shade. Ethanol and water extracts of each part were succesfully prepared by maseration method. The analysis
of ethanol and water extracts were performed by HPLC-TOF/MS . HPLC-TOF-MS analyzes of the plant were resulted twelve
compounds and, chlorogenic acid and apigenin-7-glikozit from water and ethanol extract of the stem; gentisic acid from the
water extract of the stem; chlorogenic acid and 4-hydroxybenzoic acid from ethanol extract of the root; gentisic acid and
4-hydroxybenzoic acid from the water extract of the root as the main components. The obtained cytotoxic activities of all
extracts were determined by LDH assays against C6 cells. The extracts were detected cytotoxic activities and was found to
be less toxic than 5-fluorouracil used as a standard. Dyeing performance of the plant was also studied and the results were
evaluated in terms of color strength (K/S). Best color strength values were obtained in the dyeing of cotton fabric (K/S=9.19; K/
S=8.50) fors tem and flowers, respectively.
1. Mann C., Staba, E. J., (1986). The chemistry, pharmacology, and commercial formulations of chamomile. In: Herbs, Spices,
and Medicinal Plants: Recent Advances in Botany, Horticulture, and Pharmacology, Vol. 1(Craker L. E. and Simon J. E., eds.).
Oryx Press, Phoenix, AZ, pp. 235-280. 2. Çakılcıoğlu U, Türkoğlu İ, Kürşat M. Harput (Elazığ) ve Çevresinin Etnobotanik Özellikleri,
Doğu Anadolu Bölgesi Araştırmaları, 2007; 22-28.
PP 59 GC-MS ANALYSIS OF CENTAUREA VIRGATA LAM. (ASTERACEAE) HEXANE AND CHLOROFORM EXTRACTS
AYŞE ŞAHİN YAĞLIOĞLU 1, MELDA DÖLARSLAN 2, FATIH AVCI 1, EBRU GÜL 3, İBRAHIM DEMIRTAŞ 1
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
3
DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 18100, CANKIRI, TURKEY
1
2
The genus Centaurea L. (Asteraceae) is represented by a diversity of species, distributed in particular in southwest, central and
east of the Turkey (1). There are traditional uses of the some Centaurea species including antidiarrhoeic, antipyretic, diuretic,
choleretic, antiinflammatory and antibacterial effects (2). In this study, Centaurea virgata Lam. (Asteraceae) was collected
from Çankırı. Species identification of the collected materials were performed. This plant were separated as flowers, steam
and root and dried at room temperature (25 °C) in the shade. The extracts of these materials were prepared hexane and
chloroform, respectively, by maseration methods. The components of hexane and chloroform extracts were determined by
GC-MS. As a result of GC-MS analyzes were detected 21 components. The components were obtained as five mono saturated
fatty acids, two mono unsaturated fatty acids, two polyunsaturated fatty acids and twelve other compounds. Taraxasterol from
the flowers chloroform and the steam hexane extracts (62.44 and 66.50 % respectively); palmitic acid from the steam and the
root dichloromethane extracts (58.57 and 36.49 % respectively); palmitoleic acid from the root hexane extract (38.72 %) were
detected as the main components.
1. Wagenitz G (1986). Centaurea in South-West Asia: Patterns of distribution and diversity, Proc. Royal Soc. Edinburgh 89: 1121. 2. Kargioglu M, Cenkci S, Serteser A, Konuk M, Vural G (2010). Traditional uses of wild plants in the middle Aegean region of
Turkey. Hum. Ecol. 38:429-450.
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PP 60 PHYTOCHEMICAL ANALYSIS OF CRAMBE ORIENTALIS L. (BRASSICACEAE)
AYŞE ŞAHİN YAĞLIOĞLU 1, MELDA DÖLARSLAN 2, TUĞÇE ÇOŞAR 1, EBRU GÜL 3, İBRAHIM DEMIRTAŞ 1
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
3
DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 18100, CANKIRI, TURKEY
1
2
In the industrial area, Crambe L., which is promising one of the new plant contain percent 35-60% oil in oil the seeds and
it also constitutes 57% erucic acid. Crambe L. due to this feature are used in many areas of industry, such as biodiesel, oil
industry, machinery industry. Also after oil remaining portion is an important food source for animals (1). In this study, Crambe
orientalis L. (Brassicaceae) were collected from Çankırı. Species identification of the collected materials were performed. This
plant were separated as flowers, leaves and stems and dried at room temperature (25 °C) in the shade. The extracts of these
materials which were acetone, chloroform, ethyl acetate and ethanol, extracts, respectively were prepared. The fatty acides of
acetone and chloroform extracts by GC-MS and phenolic compounds in ethyl acetate and ethanol extracts by the HPLC-TOF/
MS were performed. As a result of GC-MS analyzes were detected 11 compounds, palmitic acid and linolenic acid as the main
component. The 16 different phenolic compounds were determined from HPLC-TOF-MS and were obtained 4-hydroxybenzoic
acid and rutin as the main components.
1. Baytop, T. 1999. Türkiye’de Bitkiler İle Tedavi, Nobel Tıp Kitabevleri, İstanbul.
PP 61 GC-MS ANALYSIS OF THYPHA SHUTTLEWORTHII W. D. J. KOCH & SOND. (TYPACEAE) HEXANE AND
DICHLOROMETHANE EXTRACTS
AYŞE ŞAHİN YAĞLIOĞLU 1, MELDA DÖLARSLAN 2, EDA KIYMAZ 1, SELIN KÖKEN 1, EBRU GÜL 3, İBRAHIM DEMIRTAŞ 1
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
3
DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 18100, CANKIRI, TURKEY
1
2
The root portion of Typha shuttlewortthi W. D. J.Koch & Sond. (Typaceae) is used urine enhancer and as urinary tract antiseptics
in infusion. If the flower parts is used hernia and at treatment of burns as ointment which prepared with rancid oil (1). In this
study, Thypha shuttleworthii W. D. J.Koch & Sond.(Typaceae) was collected from Çankırı. Species identification of the collected
materials were performed. This plant were separated as flowers, steam and root and dried at room temperature (25 °C) in the
shade. The extracts of these materials were prepared hexane and dichloromethane, respectively, by maseration methods. The
components of hexane and dichloromethane extracts were determined by GC-MS. As a result of GC-MS analyzes were detected
42 components. The components were obtained as eight saturated fatty acids, two polyunsaturated fatty acids and thirty two
other compounds. Palmitic acid (27.79 %) from the root dichloromethane, Sitosterol (20.17 %) from the root hexane extracts;
lupeol and beta-amyrin from the flower dichloromethane extracts (48.17 and 28.68 % respectively) were detected as the main
components.
1. Baytop, T. 1999. Türkiye’de Bitkiler İle Tedavi, Nobel Tıp Kitabevleri, İstanbul.
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PP 62 PHYTOCHEMICAL ANALYSIS AND SOIL PROPERTIES OF CARDARIA DRABA (L.) DESV. SUBSP. DRABA (L.) DESV.
(BRASSICACEAE)
AYŞE ŞAHİN YAĞLIOĞLU 1, MELDA DÖLARSLAN 2, DUYGU GÜNEŞ 1, EBRU GÜL 3, İBRAHİM DEMİRTAŞ 1
DEPARTMENT OF CHEMİSTRY, FACULTY OF SCİENCE, CANKİRİ KARATEKİN UNIVERSITY, 18100 CANKİRİ, TURKEY
DEPARTMENT OF BİOLOGY, FACULTY OF SCİENCE, CANKİRİ KARATEKİN UNIVERSITY, 18100 CANKİRİ, TURKEY
3
DEPARTMENT OF FOREST ENGİNEERİNG, FACULTY OF FOREST, CANKİRİ KARATEKİN UNIVERSITY, 18100, CANKİRİ, TURKEY
1
2
Cardaria draba (L.) Desv. subsp. draba (L.) Desv. (Brassicaceae) is used as suppressors of gas and gain energy. Also, the plants
young leaves are eaten salad (1, 2). This plant is perennial and known as “Kediotu” , “Kır teresi” and “Yabanı Tere” between
people (2). In this study, C. draba (L.) Desv. were collected from semi-aired soils which shows medium coarse (clay loam, sandy
clay loam, loam), high acidic (5.5-6.9 pH) and rich soil organic matter properties in Çankırı. Species identification of the collected
materials were performed. This plant were separated as flowers, root and airel parts and dried at room temperature (25 °C)
in the shade. The extracts of these materials which were acetone, chloroform, ethyl acetate and ethanol extracts, respectively
were prepared by maseration methods. The fatty acides of acetone and chloroform extracts by GC-MS and phenolic compounds
in ethyl acetate and ethanol extracts by the HPLC-TOF/MS were performed. As a result of GC-MS analyzes were detected 32
compounds and palmitic acid as the main component. The 19 different phenolic compounds were determined from HPLC-TOFMS and were obtained kaempferol, rutin, 4-hydroxybenzaldehyde ve 4– hydroxy benzoic acid as the main components.
1.Deniz L, Serteser A, Karlıoğlu M. Uşak Üniversitesi ve Yakın Çevresindeki Bazı Bitkilerin Mahalli Adları ve Etnobotanik Özellikleri,
AKÜ Fen Bilimleri Dergisi, 2010; 01: 57-72. 2. Çakılcıoğlu U, Türkoğlu İ, Kürşat M. Harput (Elazığ) ve Çevresinin Etnobotanik
Özellikleri, Doğu Anadolu Bölgesi Araştırmaları, 2007; 22-28.
PP 63 MOMORDICA CHARANTIA CAN BE UPREGULATE ESTROGEN RESEPTORS ESRα/ESRβ GENE LEVELS IN OVARIECTOMY
RATS
OZGE CEVIK 2, HIKMET AKPINAR 1, RABIA OBA 1
1
2
FACULTY OF PHARMACY MARMARA UNIVERSITY, ISTANBUL, TURKEY
FACULTY OF PHARMACY CUMHURIYET UNIVERSITY, SIVAS, TURKEY
Changes resulted by the decrease in 17-β Estradiol (E2) and its replacement with Estrone hormone in menopause, both cause
quality of life to reduce and various diseases to appear. Studies carried out recent years prove that, hormone replacement therapy
has resulted in pathological consequences, and these studies recommend the use of alternative herbal approaches. In this study,
we aimed at investigating the antioxidant effect of Momordica charantia (Bitter melon) on experimental ovariectomized rats
and the changes in estrogen receptor gene levels (ESR-α, ESR-β). In the study, overectomy model was composed by ligaturation
and applied fruit extract of Momordica charantia (MCE, 2g/kg orally) for 30 days. Serum E2 levels were observed by ELISA,
tissue cytokine levels (TNF-alpha, IL-6, IL-10) and NF-kB protein expressions were measured by western blotting. Estrogen genes
ESR-α, ESR-β were observed by RT-PCR. In our findings, serum E2 decreased in overectomy group (p<0.05) and reduced by the
application of MCE (p<0.05). MCE suppressed pro-inflammatory cytokines as TNF-α and IL-6 in uterus tissue (p<0.05 -0.001).
On the other hand, the IL-10 levels were up regulated with MCE treatment (p<0.01). While ESR-α, ESR-β gene were reduced
in overectomy, increase was observed by means of MCE application (p<0.05-0.001). In consequence; Momordica charantia
plant has displayed an effect on ovariectomized rats in both gene and protein level, by the effect of phytoestrogen and antiinflammatory; and it may contribute to the development of new medicine that can be used in the period of menopause.
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PP 64 ANTIOXIDANT AND ANTI-APOPTOTIC EFFECT OF MOMORDICA CHARANTIA ON UTERUS TISSUE IN OVARIECTOMY
RATS
OZGE CEVIK 1, HIKMET AKPINAR 2, RABIA OBA 2
1
2
CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY
Aging and hormonal regulation differences can trigger oxidative stress which is mainly due to an increased production of
oxygen free radicals and a suppression of antioxidant defensive. Momordica charantia (MC) is composed of special biologically
active chemicals. The present study was designed to investigate the effect of MC on anti-apoptotic proteins and oxidative
stress status on a postmenopausal rat model. In the study, overectomy model was composed by ligaturation method and
gavage with 2g/kg fruit extract of Momordica charantia (MCE) applied on the rats during 30 days. Oxidative stress markers
(8-OHdG,MDA,GSH,SOD,MPO) were measured. For apoptotic status in tissue were analyzed pro-caspase-3, cleaved caspase-3,
caspase-9, cleaved caspase-9, Bcl-2 by western blotting. In our findings, increasing serum 8-OHdG levels on ovariectomized
rats were reduced by MCE application. It was observed that the MCE increased SOD,GSH considerably that had been reduced
in overectomy; and reduced increasing MDA,MPO (p<0.05-0.001). Concerning extrinsic and intrinsic apoptosis, the caspase-3
protein expression levels increased in OV group rat uterine tissue (p<0.05) and decreased with MCE treatment (p<0.01). At the
same time, our data showed that pro-caspase-9 protein expression in the OV group elevated (p<0.05) while this increase was
reversed with MCE treatment (p<0.01). MCE treatment Bcl-2 protein expression was higher than that in OV group (p<0.01). This
study showed that MC fruit extract has a potential antioxidant effect as radical scavenging activity of the extract against radicals
which include bioactive molecules. In addition to MCE treatment decreased uterine apoptotic stimulation in ovariectomy rats.
PP 65 ESTROGENIC EFFECTS OF MOMORDICA CHARANTIA IN HISTOLOGICAL CHANGES ON UTERUS TISSUE
RABIA OBA 1, HIKMET AKPINAR 1, OZLEM TUGCE CILINGIR 2, ZARIFE NIGAR OZDEMIR 3, SULE CETINEL 2, OZGE CEVIK 4
MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY
MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY
3
MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PHYSIOLOGY
4
CUMHURIYET UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY
1
2
Estrogens are 18-carbon steroid hormone which are very high hormone levels in reproductive aged-women. The amount of
estrogen produced by the ovary is a significant downward after menopause. In recent years there has been increased the use
of phytoestrogens in the treatment of menopause. In this study, we aimed at investigating the effect of Momordica charantia
(MC) and structural changes of uterus tissue on experimental ovariectomized rats. In the study, overectomy model (OV) was
used and MCE applied with gavage (2g/kg) for rats. The weight of the rats was recorded every the third day and uterine weight
was measured after the decapitation. Uterus tissue samples were fixed in 10% formaldehyde and hematoxylin-eosin staining
were performed for light microscopic evaluations. It is known that body weight is inversely to relation with uterine weight in
ovariectomy. Uterine/BW ratio decreased in the OV group (p<0.001) and reversed with MCE (p<0.05). In overectomized rats
we detected cell infiltration related with the loss of cytoplasm in epithelial cells. Irregular endometrial stroma was detected
in estradiol applied group. Compare with overectomized group epithelial cells have more regular morphology and less cell
infiltration were observed. In comparison with the overectomized group, MCE applied group has more regular surface epithel
and uterus glands which are more like control group. In contrast with overectomized group very less amount of neutrophil
infiltration has observed. MC suppressed cell damage in uterus tissue in ovariectomized rat which has therapeutic potential to
prevent the development of cell degenerative complications.
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PP 66 MOMORDICA CHARANTIA AND ESTRADIOL IMPACT OXIDATIVE STRESS RESPONSES ON LIVER IN OVARIECTOMIZED
RAT
RABIA OBA 1, HIKMET AKPINAR 1, ZARIFE NIGAR ODEMIR 2, OZLEM TUGCE CILINGIR 3, SULE CETINEL 3, OZGE CEVIK 4
MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY
MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PHYSIOLOGY
3
MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY
4
CUMHURIYET UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY
1
2
The lack of protective action of estrogens (E2) is known to cause serious metabolic disturbances, and oxidative stress is thought
to be one of the suspected mechanisms. To estimate the impact of MCE Estrogen deficiency on the oxidative and antioxidative
status in the liver of the ovariectomized rats. Female rats were separated into four groups: (i) sham ; (ii) ovariectomy (OV)
rats; (iii) OV+E2 (250 µg/kg, im) and (iv)OV+MCE (2g/kg, orally). The histopathological assessment of the liver was performed
using hematoxylin and eosin staining. Histological preparations were evaluated in the light microscope. The tissue levels of
oxidative status markers such as MDA,GSH,SOD, CAT, GST and MPO levels were measured in liver. Liver GSH and CAT levels
were significantly increased in MCE or EST treated rat when compared to OV. SOD and GST increasing were not significantly.
The levels of MDA were significantly increased in OV group. EST or MCE treated rats had significant reductions in MDA
levels in liver compared to sham. There was no big changing in MPO levels for each group. OV group, hepatic tissue showed
extensive cytoplasmic lacking and activated Kupffer cells. Necrosis, hepatocyte apoptosis, nonparenchymal cell apoptosis, and
macroscopic and microscopic peliosis were markedly reduced or minimized in MCE treated rats. In summary, MCE treatment
also induced antioxidant molecules/enzymes and inhibited lacking of estradiol-mediated increase in oxidative damage in liver
tissues. Decreased oxidative stress, and increased cell regeneration and formation in MCE rats suggested a protective role of
phytoestrogen against oxidative stress induced ovariectomized degeneration.
PP 67 EVALUATION OF ESTROGENIC EFFECTS OF MOMORDICA CHARANTIA ON THE KIDNEY OF OVARIECTOMIZED RATS
RABIA OBA 1, HIKMET AKPINAR 1, ZARIFE NIGAR OZDEMIR 2, OZLEM TUGCE CILINGIR 3, SULE CETINEL 3, OZGE CEVIK 4
MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY
MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PHYSIOLOGY
3
MARMARA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY
4
CUMHURIYET UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY
1
2
Momordica charantia (MC) is a medicinal plants that have served through the ages as the mainstay in the treatment of variety
of diseases and preservation of human health. Estrogen (E2) has been demonstrated to exert beneficial effects on kidney.
Consequently, the aim of the present study is to investigate the estrogenic effects of MC fruit extract (MCE) on the kidney
of rats. Female rats were separated into four groups: (i) sham ; (ii) ovariectomy (OV) rats; (iii) OV+E2 (250 µg/kg, im) and (iv)
OV+MCE (2g/kg, orally). A structural change in kidney was examined on the light microscope by means of H&E staining. The
tissue levels of oxidative status markers such as MDA,GSH,SOD, CAT, GST and MPO levels were measured in kidney. Kidney MDA
levels increased in OV and decreased with MCE or EST treatment. SOD, GST and MPO levels were not significantly different
among treatment with OV. GSH and CAT levels increased with MCE or EST treatment in OV rats. Control animals showed
normal kidney histology. The glomeruli were well demonstrated with normal bowman space. OV kidney showed atrophy of the
glomeruli and the tubules were fairly preserved. Administration of the extracts and EST improves cellular regeneration which
is quite prominent in OV. The histopathological findings indicated that there were no histopathological lesions observed in the
OV experimental groups treated with MCE fruit extract. From this study, we inferred that Momordica charantia administered in
OV rats have antioxidant and protective properties that could prevent damage to the kidneys.
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PP 68 PROTECTIVE EFFECTS OF POLYGONUM COGNATUM MEISSN AGAINST STZ INDUCED DIABETES ON PANCREATIC TISSUE
OZGE CEVIK 1, RABIA OBA 3, OZLEM TUGCE CILINGIR 2, SULE CETINEL 2, OZLEM OZAKPINAR 3, HALIL AKSOY 3, DERYA OZSAVCI 3,
AZIZE SENER 3
CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY
MARMARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, ISTANBUL, TURKEY
3
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
1
2
Diabetes mellitus is major endocrinological problem for worldwide. It is known that pancreatic beta-cell dysfunction involve
in diabetes and this condition produce oxidative stress. Medicinal plants play an important role in the treatment of diabetes
mellitus and there are many and different therapeutic strategies in the management of diabetes. To investigate the role of
Polygonum cognatum meissn (PCM) plants in the progression of pancreas in type 2 diabetes, we evaluated STZ induced diabetic
rat model. Cytotoxicity of PCM different concentration (1, 2, 4, 8 and 16 mg/mL) were measured with MTT assay in NIH3T3 mouse fibroblast. Diabetes was induced in rats using single dose of 45 mg/kg STZ and PCM was studied orally 2g/kg
for 20 days. Pancreatic tissue MDA, MPO, GSH and SOD levels was elevated in diabetic rats. Tissue damages were observed
from H&E staining examination. MTT assay showed that the lower dosed PCM was found more effective for cell viability. Oral
administration of PCM to diabetic rats resulted in a decrease in the levels MDA (p˂0.001) and MPO levels (p˂0.001) compare
to diabetes group. PCM also resulted in the incerases of SOD and GSH coming to near control (p˂0.01-0.001). These results
indicate that PCM ameliorated the diabetes-induced changes in oxidative stress. PCM can contribute to development a new
therapeutic target for diabetes mellitus.
PP 69 ANTIOXIDANT EFFECTS OF POLYGONUM COGNATUM MEISSN ON RAT LIVER TISSUE IN STZ INDUCED DIABETIC
MODEL
RABIA OBA 1, OZLEM TUGCE CILINGIR 2, SULE CETINEL 2, OZGE CEVIK 3
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
MARMARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, ISTANBUL, TURKEY
3
CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY
1
2
Diabetes mellitus is known that a metabolic disorder and characterize by hyperglycemia, abnormal lipid, and protein
metabolism. Whatever the complication can be insulin targeting tissue mainly in liver, skeletal muscle, and adipocytes in early
stage of diabetes. In this study we investigated effects of Polygonum cognatum meissn plants on liver tissue in diabetic rats.
PCM aqueous extract was prepared by fresh leaves. Diabetes was induced in rats using single dose of 45 mg/kg streptozotocin
(STZ) and rats selected randomly as control, diabetes, PCM groups. PCM was given orally 2g/kg dose for 20 days to STZ-induced
diabetic rats. End of 20 days rats liver tissues collected for analysis MDA, MPO, GSH and SOD levels. Liver tissue histopathological
changes were observed with haematoxylin-eosin staining. Liver MDA (p˂0.01) and MPO (p˂0.001) levels were decreased versus
to diabetes groups. The elevated liver levels of GSH, which is a small peptide that is an indicator of anti-oxidative status, were
significantly increased in diabetic rats applied PCM group. Similarly, the Liver SOD activity was also improved in PCM group
versus to diabetic groups (p˂0.05), there was no significantly changing versus to control groups. Histological data showed that
PCM has a effective on hepatic proliferative and regenerative response. These results from the scientific basis supporting the
oral administration of PCM extracts to the diabetic rats slightly improved antioxidant molecules and also alleviated various
oxidative stress indices of the liver of the diabetic rats.
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PP 70 EFFECT OF POLYGONUM COGNATUM ON HISTOLOGICAL STRUCTURE OF KIDNEY IN STZ-INDUCED DIABETIC RATS
RABIA OBA 1, OZLEM TUGCE CILINGIR 2, SULE CETINEL 2, OZGE CEVIK 3
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
MARMARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY, ISTANBUL, TURKEY
3
CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY
1
2
Complementary and alternative therapy is treatments that are more popular studies for diabetes metabolism in animal models.
Diabetes has long-term complication affecting the retina, kidney, and nervous system; thirty percent of diabetic patients develop
nephropathy. The aim of our study was the screening for oxidative status on kidney tissue model used Polygonum cognatum
meissn treatment in diabetic rats. PCM was collected and aqueous extract prepared with homogenization from fresh leaves. Rats
were orogastrically treated with PCM (2g/kg) throughout a 20-day interval after diabetes, which was induced by intraperitonal
administration of STZ (45 mg/kg). Control and diabetic group was orally administered only isotonic saline. End of 20 days of
PCM administration, rats kidney tissues collected and was stored at -800C until for the detection of MDA, MPO, GSH and SOD
levels. Assessment of kidney damages was stained with hematoxylin and eosin for general morphology analysis. The levels of
MDA, which is a major degradation product of lipid peroxidation, were significantly decreased in PCM group with respect to
diabetic group (p˂0.01). However, in the diabetic group, treated with PCM, diabetes-induced increases in MPO activity were
significantly inhibited (p˂0.001). The GSH and SOD levels were significantly increased in diabetic rats with PCM treatment
(p<0.001). By HE staining the diabetic groups showed serious histological modifications. PCM rats kidney had alterations in
organized tubular structure, decreasing tubular vacuolization and increasing regeneration. These findings emphasize that PCM
is not only antioxidant effects but may also provide therapeutic targets to the prevention of diabetic complications.
PP 71 REGULATION OF INSULIN RECEPTOR SUBSTRATE (IRS) GENES IN THE PANCREAS OF DIABETIC RATS SUBMITTED TO
POLYGONUM COGNATUM MEISSN
OZGE CEVIK 1, RABIA OBA 2
1
2
CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling and mediate different biological signals such
as growth, survival, and metabolism. The objective of the present study was to evaluate anti-diabetic effects of Polygonum
cognatum meissn (PCM) in type 2 diabetic rats. Rats were made diabetic using single dose streptozotocin (45 mg/kg)and PCM
applied for 20 days. Rats were monitored for 20 day for adverse side effects, blood glucose, and insulin requirements and
were sacrificed under anesthesia, and the pancreas was immediately removed and placed into cold lysis buffer for protein
and gene analyses. Western blotting, RT-PCR and ELISA assay analyses were completed to evaluate protein and gene levels.
Circulating serum glucose concentrations decreased (p˂0.05)and insulin concentrations increased (p˂0.01) in diabetic rats
treated with PCM. Expression of Bcl-2 protein in the pancreas was greater in diabetic rats treated PCM, as compared with
diabetic rats (p˂0.01). PI3-kinase expression reduced in pancreases tissue of diabetic rats (p˂0.05) compare to control while
in PCM treatment groups was not significantly changes. Phopsho-AKT activation was increased with PCM administration. A
significant decrease in IRS-1 (p˂0.01) and IRS-2 (p˂0.05) gene levels were observed in the diabetic pancreas. On the other hand
IRS-1 gene level was increased with PCM administration (p˂0.001) but IRS-2 was not change. Taken together, these data indicate
that PCM trigger to IRS-1 mediating metabolic effects of insulin in pancreas tissue, and upregulation of IRS in β cells could be
prevent or treat for β cell failure and many forms of diabetes.
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PP 72 INHIBITION OF PANCREATIC LIPASE BY CULINARY PLANT EXTRACTS
DAMLA ANBAR 1, AYŞE OGAN 1, CİHAN GÜNDÜZ 1, ÖZKAN DANIŞ 1, MUSTAFA MUHLİS ALPARSLAN 2, MUSTAFA BULUT 1, SEDA
YILMAZ 1, ÜMİT SALAN 1
1
2
FACULTY OF PHARMACY MARMARA UNIVERSITY, ISTANBUL, TURKEY
FACULTY OF PHARMACY CUKUROVA UNIVERSITY, ADANA, TURKEY
Obesity is a strong risk factor for various diseases, such as hypertension, arteriosclerosis and diabetes (1).Therefore, an effective
way to prevent obesity is to inhibit fat absorption from intestines. Pancreatic lipase (PPL) is a key enzyme for lipid absorption.
Only a few substances such as orlistat (tetrahydrolipstatin) interact directly with lipases but, causes unpleasant side effects on
gastrointestinal system and kidneys (2). One of the approaches to reduce obesity is treatment with natural products. Many plants
have been reported to inhibit lipase activity which is attributable to the presence of secondary metabolites such polyphenols,
benzopyrones whose members include flavonoids, saponins, coumarins etc. are active inhibitors of PPL (3). In our study using
porcine pancreatic lipase, a series of plants were screened for their pancreatic lipase) inhibitory activities and compared to
lipase inhibitory activities of coumarin derivatives synthesized in our laboratory According to the results; green tea, green apple
and avocado extracts had the highest antilipase activities however coumarin derivaties displayed no considerable antilipase
activities. 1. Kopelman PG. Obesity as a Medical Problem. Nature. 2000;404:635-643. 2. Ballinger A, Peikin SR. Orlistat: Its
Current Status As an Anti-Obesity Drug. Eur J of Pharmacol. 440;2002:109 –117. 3. de la Garza AL, Milagro FI, Boque N, Campion
J, Martinez JA. Natural Inhibitors of Pancreatic Lipase as New Players in Obesity Treatment. Planta Med.2011;77:773–785.
PP 73 EVALUATION OF DNA DAMAGE IN PETROL STATION PUMPERS OCCUPATIONALLY EXPOSED TO PETROL VOLATILE
PINAR SINEM OMURTAG 1, NEBAHAT AKDEMIR 2, AYFER TOZAN-BECEREN 2, GÜLDEN ZEHRA OMURTAG 3, SEMRA ŞARDAŞ 2
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE AND LETTERS, ISTANBUL TECHINICAL UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
3
DEAN OF MARMARA UNIVERSITY, ISTANBUL ,TURKEY
1
2
According to the International Agency for Research on Cancer (IARC), exposure of petrol volatile is classified as human
carcinogen. Petrol station workers are potentially exposed to a wide range of petroleum-derived such as hydrocarbons and
chemical substances. Benzene, toluene and xylene are produced by distillation in the aromatic units and used as raw materials
for petrol and petrochemical products. This study deals with evaluation of the genotoxic effects of occupational exposure to
benzene, toluene and xylene in the petroleum station workers in Istanbul, Turkey. The workers in petrol station who were
volunteers for this study (n=25) were selected randomly and controls (n=14) from the general population with no history
of occupational exposure. The comet assay was used to evaluate effects of occupational exposure to petrol volatile on DNA
damage (1). In the light of the results, it can be said that exposure to petrol and petroleum products have a potential to give
genotoxic damage. To support these results other methods can be used with Comet assay technique to evaluate the DNA
damage coming from petroleum derivatives.
1. Karabıyık L, Şardaş S, Polat U, Kocabaş NA, Karakaya AE. (2001). Comparison of genotoxicity of sevoflurane and isoflurane in
human lymphocytes studied in vivo using the comet assay. Mutat Res, 492:99-107.
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PP 74 INVESTIGATION OF ANTIOXIDANT’S ANTIMUTAGENIC EFFECTS BY THE AMES TEST
AYFER TOZAN-BECEREN , BETÜL SARIKAYA , GÜLDEN ZEHRA OMURTAG , SEMRA SARDAS
DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Nowadays, several test systems have been developed in order to observe the mutagenic effects of chemical agents which
play crucial roles in human health. The Ames Test is one of these test systems. With the Ames Test, some bacterial mutants
have been discovered to investigate the mutagenic effects of the chemicals. Various strains of Salmonella typhimurium are
one of the groups of the bacterial mutants in question. The aim of this study is to investigate possible antimutagenic effect
of Pelargonium sidoides which have an antioxidant effect towards carcinogenic substance called 2-Aminofluorene by Ames/
Salmonella/Microsome test kit in the absence and presence of metabolic activation. TA 98 and TA 100 strains were used in these
experiments. TA 98 is designed for frame-shift mutagens and TA 100 is designed for base-pair mutagens. The antimutagenic
activity was screened in two groups with or without S9 metabolic activation. The results were evaluated the mean average values
and compared with positive and negative controls. In conclusion, it was shown that Pelargonium sidoides have antimutagenic
effect towards TA 98 and TA 100 without S9 metabolic activation (p>0.05) but have no antimutagenic effect towards TA 98 and
TA 100 with S9 metabolic activation (p<0.05).
PP 75 SYNTHESIS OF NOVEL HYDRAZIDE-HYDRAZONES DERIVED FROM TOLMETIN AS ANTICANCER AGENTS
DERYA KOÇ 1, PELİN ÇIKLA-SÜZGÜN 1, ÖZLEM BİNGÖL-ÖZAKPINAR 2, DERYA ÖZSAVCI 2, Ş.GÜNİZ KÜÇÜKGÜZEL 1
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, HAYDARPAŞA 34668
İSTANBUL, TURKEY.
2
MARMARA UNIVERSITY, FACULTY OF PHARMACY,DEPARTMENT OF BIOCHEMISTRY, HAYDARPAŞA 34668 İSTANBUL, TURKEY
1
Tolmetin ([1-methyl-5-(4-methylbenzoyl)-1H-pyrol-2-il]acetic acid), is a non-steroidal anti-inflammatory drug which acts
by inhibiting prostaglandin synthesis [1,2]. Tolmetin, reported antitumor effect on colon cancer [3] and investigated for
biochemical modulator of anticancer drugs [4]. Tolmetin is used as a starting compound for the synthesis of [1-methyl-5(4-methylbenzoyl)-1H-pyrol-2-yl]acetic acid hydrazide and related hydrazide-hydrazones. A novel series of new tolmetin
hydrazide derivatives, 2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrol-2-yl]-N-[(substitutedphenyl/5-nitro-2-furyl)methylidene]
acetohydrazide hydrazones have been synthesized in this study. The characterization of these compounds were identified by
the help of elemental analysis, UV, IR and 1H-NMR spectral data while the purities of them were proved with elemental analysis
and TLC. Tolmetin and 2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrol-2-yl]-N-[(2,6-dichlorophenyl)methylidene]acetohydrazide
[4g] (SGK 417) were evaluated for cell viability and growth inhibition by HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) of
MTT assay and cytotoxicity at different doses (10-6-10-2M). Compound 4g exhibited anticancer activity with IC50 value 76 µM
against colon cell line HT-29 and did not displayed cytotoxicity towards NIH3T3 rat fibroblast cell compared tolmetin. Apoptosis
levels of compound 4g were determined.
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PP 76 RHEOLOGICAL EVALUATION OF DICLOFENAC DIETHYLAMINE CONVENTIONAL GEL, EMULGEL, AND A
NANOEMULSION-BASED GEL FORMULATION
RANIA HAMED
AL-ZAYTOONAH UNIVERSITY OF JORDAN
The objective of this study was to prepare a nanoemulsion-based gel formulation (nanogel) of diclofenac diethylamine amine
(DDEA) in 1.25%w/w Carpobol® 934 as a potential vehicle for transdermal drug delivery and to compare the rheological
properties of DDEA nanogel with those of a conventional DDEA gel and emulgel. Twenty-seven o/w nanoemulsion formulations
containing 1.16%w/w DDEA were prepared. Nanoemulsions were evaluated for thermodynamic stability and characterized for
mean droplet size (MDS) and polydispersity index (PDI). The optimized DDEA nanoemulsion, and DDEA conventional gel and
emulgel were dispersed in 1.25%w/w Carpobol® 934. Oscillatory rheological analysis of the gels was performed where the
storage modulus G’ and loss modulus G” were determined over a frequency range of 1-100 rad/sec. Based on the pseudo-ternary
phase diagram and solubility studies, the optimized DDEA nanoemulsion was composed of 1.16%w/w DDEA, 10%w/w oleic
acid, 55%w/w Smix (Tween 20:ethanol, 2:1), and 34%w/w distilled water. MDS of nanoemulsions was ~10 nm with an average
PDI of 0.5. DDEA gel, emulgel and nanogel exhibited elastic behavior where G’ dominated G” at all frequencies. Conventional gel
exhibited higher G’ and G” values than emulgel, which indicated the formation of a strong gel network. Nanogel exhibited the
lowest rheological properties. DDEA conventional gel, emulgel, and nanogel dispersed in 1.25%w/w Carpobol® 934 exhibited
different rheological properties with nanogel exhibited the least elastic and viscous properties. Understanding these properties
is crucial to predict the in vitro permeation of drugs from these systems and their potential to enhance skin penetration.
PP 77 THE EFFECT OF POLYMER PROPERTIES ON THE IN VITRO RELEASE OF QUETIAPINE FUMARATE, A BCS CLASS II DRUG,
FROM A CONTROLLED RELEASE MATRIX TABLETS
RANIA HAMED 1, LINA HAMMAD 2, AIMAN ABBAS 2
1
2
AL-ZAYTOONAH UNIVERSITY OF JORDAN
HIKMA PHARMACEUTICALS
The aim of this study was to prepare oral controlled release matrix tablets (MT) of BCS class II drug, Quetiapine Fumarate (QF),
using a range of release controlling polymers with different properties, and to correlate these changes with the rheological
properties of the polymer gels and the in vitro release of the drug. Two sets of MT were prepared: (1) MT composed of different
blends of the hydrophilic hydroxypropylmethylcellulose (HPMC) polymer of different viscosity grades (HPMC K100LV and HPMC
K4M), and (2) MT composed of various blends of HPMC K100LV polymer with the hydrophobic polymer, polyethyleneglycol
behenate (GB HD5 ATO). The in vitro release of QF from the MT and rheological characterization of gels following tablet hydration
were assessed. For hydrophilic MT, as the proportion of the more viscous HPMC K4M increased, time for 50% and 90% QF
release decreased significantly. QF release from MT containing a combination of HPMC K100LV and GB HD5 ATO, was higher
than that of the hydrophilic MT. QF release from the hydrophilic HPMC MT tablets was found to correlate with the storage
modulus G’ and loss modulus G” of the gel formed from their hydration. The hydrophilic gel G’ and G’’ values were found to be
100-fold higher than the gel formed from the hydration of HPMC:GB HD5 ATO blends, which explains the lower release rates
from hydrophilic MT. QF release rate from MT is affected by polymer properties and correlated with the rheological properties
of the gels formed from polymer hydration.
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PP 78 THE USE OF PERFORMANCE ENHANCING DRUGS IN 16-22 AGE GROUP ALPINE DISCIPLINE SKIERS AND SOCCER
PLAYERS
İ.BANU AYÇA , ŞINASI ÜNAL , ATILA ABDULLAHI
MARMARA ÜNİVERSİTESİ BEDEN EĞİTİMİ VE SPOR YÜKSEKOKULU, ISTANBUL, TURKEY
55 soccer players and 25 Alpine discipline skiers living in the Macedonia were randomly surveyed regarding their knowledge
and usage certain medications for the purpose of enhancing their sports performance.Results were evalated in the sense of
frequency(f) and percentage distiribution (%) by using SPSS 15.0 package program. 72.7%(f:40) of soccer players and 80.0%(f:20)
of skiers though that drugs have a positive effects on sports performance. The soccer players and skiers were asked to name
the drugs that could be used performance enhancement ; the soccer players 63.6%(f:35) replied as vitamins,14.5%(f:8) replied
as anabolic steroids; the skiers 60%(f:15) replied as anabolic steroids,36%(f:9) replied as vitamins and central nervous system
stimulants.The soccer players and skiers reported that to use vitamins (B1,B2,B6,B12 and C vitamin) as orally and injectable
form. 27.3% (f:15) soccer players and 16.0%(f:4) skiers reported to use drugs for enhancing their performance. Among the
drug used players ; 86.7%(f:13) soccer players and 50%(f:2) skiers reported to use drugs one a day for the whole year.80%(f:44)
soccer players and all of the skiers (f:25) thought that drugs have side-effects.56.4%(f:31) soccer players and 56% (f:14) skiers
thought that the main potential side-effects of the drug used were reported as dependency. 76.4%(f:42) soccer players and
84%(f:21)skiers thought that drug used in sports have the main effects of increasing endurance.The results of the questionnaire
suggests that drug-use with the aim of performance-enhancement was not common among 16 to 22 age group the soccer
players and skiers,and they were not adequately informed on the effects and side-effects of the drugs.
PP 79 ASSESMENT OF ENERGY-DRINK AND VITAMIN SUPPLEMENT UTILIZATION PROFILE OF 10-14 AGE GROUP CHILDREN
FROM DIFFERENT SPORTIVE BRANCHES
İ.BANU AYÇA 1, VOLKAN ŞIRINOĞLU 2
1
2
MARMARA ÜNİVERSİTESİ BEDEN EĞİTİMİ VE SPOR YÜKSEKOKULU,ISTANBUL,TURKEY
TEŞVIKIYE SPOR KLUBÜ,ISTANBUL,TURKEY
The aim of this study was to assess the ergojenic aid, energy-drink and vitamin-mineral combination supplement
utilization profile of 10-14 age group children. It was conducted on 260(115 girl and 145 boy)children from 6 different
(tennis,swimming,waterpolo,track and field,basketball,volleyball) sportive branches.The players were asked to fill in a standart
questionnaire , where information about their utilization profiles of energy-drinks, ergojenic aid and multivitamin-mineral
combination supplements were sought trough various questions. Results were evaluated in the sense of frequency(f) and
percentage distribition(%) by using SPSS 15.0 package program. Among the 115 girl players ; 31% (f:36)reported to use
multivitamin-mineral combination supplements, 16.5% (f:19) reported to use ergojenic aid and 1.7% (f:2) reported to use
protein powder . 83.35% (f:97) of the girl players reported to consume energy-drinks.49.5%(f:48) of them reported to make
their choices according to the taste; while,17.5% (f:17) made their choices according to the ingredients. Among the 145 boys
; 37.93%(f:55) to use multivitamin-mineral combination supplements, 31%(f:45) reported to use ergojenic aid, 2.1%(f:3)
reported to use protein powder. 92.41% (f:134) of the boy players reported to consume energy-drinks. 56% (f:75) of them
reported to make their choices according to the taste; while, 11.9% (f:16) made their choices according to the ingredients. All
users of vitamins; they reported to use multivitamin-mineral combination supplements once a day for every month or reported
to use them one a day throught the training days.The results of the questionnaire suggest that energy-drinks and multivitaminmineral combination use were common among children players.They must be informed on the effects, adverse effects of these
supplements.
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PP 80 EVALUATION OF DRUG, NUTRITIONAL SUPPLEMENT AND VITAMIN USAGE HABITS OF AMATEUR GOLF PLAYERS WHO
ARE MEMBER OF GOLF CLUB
İ.BANU AYÇA 1, ŞEHMUS IŞIK 2
1
2
MARMARA ÜNİVERSİTESİ BEDEN EĞİTİMİ VE SPOR YÜKSEKOKULU,ISTANBUL, TURKEY
KEMER GOLF&COUNTRY CLUBS, ISTANBUL, TURKEY
A survey was applied on 50 (25 female, 25 male) amateur golf players who are member of a golf club in İstanbul and it was
aimed to evaluate their drug, nutritional supplement and vitamin usage habits. Results were evaluated in the sense of frequency
(f) and percentage distribution (%) by using SPSS 15.0 package program. 40% (f:20) of amateur golf players think vitamins
positively effect performance at golf. 52% (f:26)of participants stated they use nutritional supplement. 53.85% (f:14) of them
reported to use amino acid/protein powders. 76.9% (f:20) of nutritional supplement users stated the reason for using is muscle
hypertrophy and to prevent injuries. All of the players reported to use vitamin, 20% (f: 10) of them stated vitamins regulate
metabolic cases, 16% (f: 8) stated vitamins enhance immune system. They stated that the reason for using vitamins is to gain
resistance against diseases 36% (f:18). Factors which have effect on choice of trademark are 40% (f: 20) product ingredient .60%
(f: 30) of participants stated they obtain vitamin from pharmacy. 40% (f: 20) of participants stated they use vitamin a few days
in a week, 28% (f: 14) stated they use regularly. In case of any health problem, 38% (f: 19) of participants stated that they use
drugs which they have used in similar occasions before. 74% (f: 37) of participants stated they bought product from herbalists.
As a result ; amateur golf players do not have sufficient knowledge about performance enhancing drugs at golf sport, however
they use vitamins commonly which they believe to have positive effect on performance.
PP 81 PLANTS USED FOR LITHOTRIPSY IN TRADITIONAL MEDICINE
SHAMIM SAHRANAVARD 2, SOMAYEH ESMAEILI 1
TRADITIONAL MEDICINE AND MATERIA MEDICA RESEARCH CENTER, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES,
TEHRAN, IRAN
2
DEPARTMENT OF TRADITIONAL PHARMACY, SCHOOL OF TRADITIONAL MEDICINE, SHAHID BEHESHTI UNIVERSITY OF
MEDICAL SCIENCES, TEHRAN, IRAN
1
The prevalence and incidence of kidney stones is increasing globally. Kidney stone formation is usually due to genetic and
environmental factors (1). The introduction of new techniques for removing stones has improved the management of urolithiasis,
but recent studies show that they associated with several adverse effects (2). Some herbal remedies have long been used to
treat urinary stone disease, therefore might be an alternative treatment with an effective, safe and culturally acceptable nature
of urinary stones (3). In this study, we investigated plants used in breaking the calculi in the most famous Iranian traditional
medicine books including Canon, al-Hawi, al-Abniah ‘an Haqaeq al Adwia and Tuhfat al-Mu’minin and selected those which
were effective in managing this condition. Seventeen plants were identified as herbal remedies to treat urolithiasis by breaking
stones.The plants were identified by matching their names with scientific names using different comprehensive glossaries. We
also searched scientific literature for pharmacological evidence of their effectiveness. Data showed that eight different genera
of these plants have been pharmacologically investigated and exhibited significant anti-urolithiasis activity.
1- RomeroV, Akpinar V, Assimos D.G .Kidney Stones: A Global Picture of Prevalence, Incidence, and Associated Risk Factors. Rev
Urol. 2010; 12(2-3): 86-96. 2- Ghalayini IF, Al-Ghazo , Harfeil M.N.A. Prophylaxis and therapeutic effects of raspberry (Rubus
idaM.Aeus) on renal stone formation in Balb/c mice. International Braz J Urol. 2011; 37 (2): 259-267. 3- Guerocak S, Kuepeli B.
Consumption of Historical and Current Phytotherapeutic Agents for Urolithiasis: A Critical Review. J Urol. 2006; 176: 450-455.
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PP 82 PLANTS USED FOR LITHOTRIPSY IN TRADITIONAL MEDICINE
SAEEDEH GHAFARI 1, SHAMIM SAHRANAVARD 2, SOMAYEH ESMAEILI 2
TRADITIONAL MEDICINE AND MATERIA MEDICA RESEARCH CENTER, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES,
TEHRAN, IRAN
2
DEPARTMENT OF TRADITIONAL PHARMACY, SCHOOL OF TRADITIONAL MEDICINE, SHAHID BEHESHTI UNIVERSITY OF
MEDICAL SCIENCES, TEHRAN, IRAN
1
The prevalence and incidence of kidney stones is increasing globally. Kidney stone formation is usually due to genetic and
environmental factors (1). The introduction of new techniques for removing stones has improved the management of
urolithiasis, but recent studies show that they associated with several adverse effects (2). Some herbal remedies have long been
used to treat urinary stone disease, therefore might be an alternative treatment with an effective, safe and culturally acceptable
nature of urinary stones (3). In this study, we investigated plants used in in the most famous Iranian traditional medicinebooks
including Canon, al-Hawi, al-Abniah ‘an Haqaeq al Adwia and Tuhfat al-Mu’minin and selected those which were effective in
managing this condition. Seventeen plants were identified as herbal remedies to treat urolithiasis by breaking stones.The plants
were identified by matching their names with scientific names using different comprehensive glossaries. We also searched
scientific literature for pharmacological evidence of their effectiveness. Data showed that eight different genera of these plants
have been pharmacologically investigated and exhibited significant anti-urolithiasis activity.
1- RomeroV, Akpinar V, Assimos D.G .Kidney Stones: A Global Picture of Prevalence, Incidence, and Associated Risk Factors. Rev
Urol. 2010; 12(2-3): 86-96. 2- Ghalayini IF, Al-Ghazo , Harfeil M.N.A. Prophylaxis and therapeutic effects of raspberry (Rubus
idaM.Aeus) on renal stone formation in Balb/c mice. International Braz J Urol. 2011; 37 (2): 259-267. 3- Guerocak S, Kuepeli B.
Consumption of Historical and Current Phytotherapeutic Agents for Urolithiasis: A Critical Review. J Urol. 2006; 176: 450-455.
PP 83 5-HTTLPR&BDNF VAL66MET POLYMORPHISMS AND MAJOR DEPRESSION PATIENTS TREATED WITH CITALOPRAM
ZUHAL UÇKUN 1, HATICE ÖZDEMİR 2, BORA BAŞKAK 3, ERGUVAN TUBA ÖZEL KIZIL 3, HALISE DEVRIMCI ÖZGÜVEN 3, SINAN
SÜZEN 3
DEPARTMANT OF TOXICOLOGY, FACULTY OF PHARMACY, UNIVERSITY OF MERSIN, MERSIN, TURKEY
DEPARTMANT OF PSYCHIATRY, FACULTY OF MEDICINE, UNIVERSITY OF KIRIKKALE, KIRIKKALE,TURKEY
3
DEPARTMANT OF PSYCHIATRY, FACULTY OF MEDICINE, UNIVERSITY OF ANKARA, ANKARA, TURKEY
1
2
The aim of this study was to determine the relationship between 5-HTTLPR&BDNFVal66Met polymorphismsand the response
to citalopram (CIT, 10-40 mg/day) in major depression patients. Fourty-six patients with major depression were determined
according to Diagnostic and statistical manual of mental disorder-IV criteria (DSM-IV) and were genotyped for 5-HTTLPR&BDNF
Val66Met polymorphism using PCR and PCR-RFLP techniques, respectively. Clinical response to CIT was determined by 17 items
Hamilton rating scale (HAM-D). For 5-HTTLPR&BDNF Val66Met, the results were obtained 36 (78%) subjects for treatment
response (R+) and 10 (22%) subjects for treatment nonresponse (R-). There were statistically not difference in between R+
subjects and R- subjects. In terms of odds ratio,odds ratio for LL + LS genotypes versus SS genotypes and L allele versus S allele
were 1,333 (95% CI 0.251-6.929, p>0.05), and 1.571 (95% CI 0.506-4.987, p>0.05), respectively. Also, odds ratio for Val/Met
+ Met/Met genotypes versus Val/Val genotype and Met allele versus Val allele were 2.857 (95% CI 0.450-22.817, p>0.05),
and 1.888 (95% CI 0.444-9.190, p>0.05), respectively. In spite of statistically insignificant data, it could be reached predictive
information that subjects having L allele might have better in response to CIT treatment than those having S allele, and that
subjects having Met allele might have better in response to CIT treatment than subjects having Val allele. (This study was
supported by The Scientific and Technological Research Council of Turkey, Project No: 109S147).
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PP 84 THE RELATIONSHIP BETWEEN CYP2C9 PHARMACOGENETICS AND DOSE-RELATED ADRS
ZUHAL UÇKUN
DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MERSIN UNIVERSITY, MERSIN, TURKEY
The aim of this study is to investigate the relationship between variations in CYP2C9 gene and dose-related adverse drug
reactions. Adverse drug reactions (ADRs) are a major clinical problem among patients used drugs all over the world. ADRs are
widespread causes of hospitalization, morbidity and mortality. Most of ADRs are preventable, especially dose-related. Impaired
drug metabolism is a primary cause of ADRs. Recently, there has been a great deal of interest in the role of CYP450 genes
polymorphisms in the pathogenesis of ADRs. CYP2C9 enzyme metabolizes approximately 15% of clinical drugs. The CYP2C9
gene encoding CYP2C9 enzyme consists of nine exons encoding a protein of 490 amino acids. To date, at least 56 allelic variants
(*1B through *58) of the CYP2C9 gene have been described. Functionally important variant alleles of CYP2C9 gene are*1B,*2,
*3, *4, *5,*6, *11 and *13. The two most common allelic variants in the CYP2C9 gene are CYP2C9*2 and CYP2C9*3, which lead
to poor metabolism phenotypes. CYP2C9*2 and CYP2C9*3 encode enzymes which are about 12 and 5% as efficient as the wildtype, respectively. Changes in metabolic activity caused by genetic variants in CYP2C9 play a major role in pathogenesis because
of ADRs. Patients with low enzyme activity are at risk of ADRs, particularly for CYP2C9 substrates with a narrow therapeutic
index. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, particularly during the initial
phase of treatment. Therefore, in order to avoid ADRs, it can be important to know genotype and phenotype.
PP 85 PREPARATION AND CHARACTERIZATION OF OXACEPROL LOADED PLGA (POLY-LACTIDE-CO-GLYCOLIDE)
NANOPARTICLES
EMİNE ALARÇİN 1, ÇAĞLAR DEMİRBAĞ 2, SEHER KARSLI ÇEPPİOĞLU 3, OYA KERİMOĞLU 1
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTİCAL TECHNOLOGY, İSTANBUL, TURKEY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTİCAL CHEMİSTRY, İSTANBUL, TURKEY
3
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTİCAL TOXİCOLOGY, İSTANBUL, TURKEY
1
2
Oxaceprol is an amino acid derivative, which has been used for several years for the symptomatic treatment of degenerative
and inflammatory joint disease in Europe without serious side-effects (1). Nanoparticles have been extensively used as drug
delivery systems for a variety of drugs, to regulate the drug release speed, increase the permeability of the biological membrane,
change the distribution of drugs in the body and improve bioavailability (2). PLGA is also one of the most successfully used
biodegradable nanosystem for the development of nanomedicines because of its excellent biocompatibility and biodegradability
(3). The aim of this study was to encapsulate oxaceprol in PLGA nanoparticles for intra-articular injection using a water-in-oilin-water emulsification method and characterize the oxaceprol loaded and free nanoparticles by particle size distribution, zeta
potential and surface morphology. Particles were sized by laser diffractometry using a ZetaSizer Nano ZS 3600 Malvern. The
surface morphology of the nanoparticles was determined by a scanning electron microscobe. The influence of the formulation
parameters (amount of stabilizer, polymer:drug ratio, stirring speed) on particle size, zeta potential and surface morphology
were investigated. Oxaceprol loaded PLGA nanoparticles were successfully prepared. The nanoparticles exhibited spherical
shape and particle size changed by different polymer ratio, drug ratio, amount of stabilizer and stirring speed of the emulsion.
Krüger K, Klasser M, Mössinger J, Becker U. Oxaceprol – a randomised, placebo-controlled clinical study in osteoarthritis with
a non-conventional non-steroidal anti-inflammatory drug. Clinical and Experimental Rheumatology 2007; 25: 29-34. Mo L,
Hou L, Guo D, Xiao X, Mao P, Yang X. Preparation and characterization of teniposide PLGA nanoparticles and their uptake in
human glioblastoma U87MG cells. International Journal of Pharmaceutics 2012; 436: 815-24. Merlin JPJ, Venkadesh B, Hussain
R, Rajendra Prasad N, Shibli, Anupama VR, Rajan SS. Paclitaxel loaded poly-d,l-lactide-co-glycolide nanoparticles: Enhanced
anticancer effect in non-small cell lung carcinoma cell line. Biomedicine&Preventive Nutrition 2013;3: 1-9.
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PP 86 A NEW VALIDATED HPLC-DAD METHOD FOR THE SIMULTANEOUS DETERMINATION OF SIX FLAVONOIDS IN FOUR
SCUTELLARIA SPECIES
HILAL BARDAKCI , EBRU TÜRKÖZ ACAR , HASAN KIRMIZIBEKMEZ
FACULTY OF PHARMACY YEDITEPE UNIVERSITY
The genus Scutellaria L. which belongs to the family Lamiaceae, encompasses about 350 species [1]. 16 species of Scutellaria grow
wild in the flora of Turkey [2]. Antitumor, antiangiogenic, hepatoprotective, antioxidant, anticonvulsant and neuroprotective
effects of several Scutellaria species have been reported. The chemical composition of Scutellaria species have also been studied
since 1889 and over 295 phytoconstituents have been isolated [1]. In this study we have developed a simple, sensitive, precise,
accurate and a validated reversed phase high performance liquid chromatographic method for the simultaneous determination
of common flavonoids of Scutellaria genus (scutellarein 7-O-β-D-glucopyranoside, hispidulin 7-O-β-D-glucuronopyranoside,
apigenin 7-O-β-D-glucopyranoside, hispidulin 7-O-β-D-glucopyranoside, luteolin, apigenin) in MeOH extract of the aerial parts
of S. hastifolia, S. velenovskyi, S. orientalis ssp. pinnatifida and S. albida ssp. albida. The method involved the use of Zorbax®
XDB C18 column (4.6 x 150 mm, 3.5 µm) at 25 °C with the mixture of ACN and water gradient (15-50% ACN in 30 min.),
constant flow rate 0.8 mL/min) as a mobile phase and detection at 340 nm. Calibration plots were linear in the range of 5- 120
µg/mL for scutellarein 7-O-β-D-glucopyranoside and for apigenin 7-O-β-D-glucopyranoside, 5- 75 µg/mL for hispidulin 7-O-βD-glucuronopyranoside 1- 75 µg/mL for hispidulin 7-O-β-D-glucopyranoside, aglycones apigenin and luteolin. The amounts
of above phytoconstituents varied among the species. This method can be used for the determination of flavonoids which
constitute one of the major chemical classess of the genus Scutellaria.
1. Shang X., He X., He X., Li M., Zhang R., Fan P., Zhang Q., Jia Z., The genus Scutellaria an ethnopharmacological and phytochemical
review, J Ethnopharmacol 2010; 128, 279-313. 2. Edmonson J.R. Scutellaria L. In “Flora of Turkey and East Aegan Islands” Davis
P.H. (ed.) Edinburgh UNIVERSITY Press. Edinburgh. pp. 78-100 (1982).
PP 87 IN VIVO MODELING STUDY TO DETERMINE THE EFFECT OF CONVOLVULUS SPECIES AS A POTENTIAL DRUG
SEVILAY CENGIZ 1, GÜLTEN TAŞDELEN 2, RAMAZAN MAMMADOV 2
PAMUKKALE UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, DENIZLI,
TURKEY
2
PAMUKKALE UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF BIOLOGY, DENIZLI, TURKEY
1
Convolvulus galaticus was used in the present study, since there have been some literatures about Convolvulaceae family
which point out their pharmaceutically important characteristics such as prevention of memory and nervous system problems,
activation of intestines, and inhibition of tumor growth (1-3). The effects of C.galaticus ethanol extract as a potential drug
source on the blood parameters and liver/kidney antioxidant enzyme activities of Wistar type female rats were determined
in in vivo conditions. All the rats studied (A: control group; B, C: groups which include %0.5 and %1 C.galaticus extract in
their diet, respectively) were fed for one month and sacrificed under anesthesia at the end of this period. Results show that
liver SOD, CAT and GPx activities of group B decreased significantly (from 18.63 to 11.70, 10.69 to 4.88 and 2.21 to 0.73 U/
mg protein, respectively), however they increased again in group C (from 11.70 to 17.46, 4.88 to 6.21 and 0.73 to 0.81 U/mg
protein, respectively). The statistically significant difference was observed between the LPO levels of group A and B (p<0.05).
The increase in SOD activity may reduce the liver damage, and therefore no significant difference between the LPO levels was
observed between the groups A and C. Besides, AST results are compatible with both these observations. The ethanol extract of
C.galaticus causes no significant damage on kidney, LPO and urea results were also consistent with this observation. Eventually,
it can be concluded that the specified doses of C.galaticus can be used for further experiments.
References
1) Liu L-F, Durairajan SSK, Lu J-H, Koo I, Li M. In vitro screening on amyloid precursor protein modulation of plants used in
Ayurvedic and Traditional Chinese MEDICINE for memory improvement. J. Ethnopharmacol. 2012; 141:754-760.
2) Bihaqi SW, Sharma M, Singh AP, Tiwari M. Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity
in rat brain. J. Ethnopharmacol. 2009; 124:409-415.
3) Sadeghi-Aliabadi H, Ghasemi N, Kohi M. Cytotoxic effect of Convolvulus arvensis extracts on human cancerous cell line. Res.
Pharm. Sci. 2008; 3(1):31-34.
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PP 88 MARINE BIOTECHNOLOGY FOR DRUG DISCOVERY: “WHY ALGAE ARE BECOMING MORE IMPORTANT DAY BY DAY?”
SEVILAY CENGIZ
PAMUKKALE UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, DENIZLI,
TURKEY
There has been a rapid increase in the number of cancer cases in recent years and natural products are gaining importance in
treatments as a result of many side effects of currently used drugs. According to the report of WHO, even more than 50% of
drugs used in clinical applications and 60% of drugs in cancer treatment are of natural origin (1). Although a lot of investigations
are found in the literature which evaluates the potential of terrestrial organisms as pharmaceutical raw materials, there are
only a few studies for aquatic organisms. It was shown that there are significant structural and chemical differences between
the secretions of terrestrial organisms and marine organisms that evolved to secrete active metabolite to cope with extreme
pressure, temperature, salinity, etc (2,3). Despite intensive research on marine organisms, there are only 13 components
currently used in clinical applications. The main problem that limits the conversion of potential components to end products
is ensuring sustainable sources. Microalgae species are very important sources with its rich content of active metabolites and
easy cultivation conditions (3). More than 50% of microalgal species are capable of killing the cancer cells through the bioactive
metabolites by influencing the cell signaling system (1). These features of the microalgae may be a proof that it can be a
promising source in developing cancer treating drugs. These investigations may be supported by collecting the obtained results
in related databases in order to reevaluate by all researchers interested in the subject.
References
1) Sithranga Boopathy N, Kathiresan K. Anticancer Drugs from Marine Flora: An Overview. Journal of Oncology, 2010;
doi:10.1155/2010/214186.
2) Hussain Md. S, Fareed S, Ansari S, Sajid Khan M. Marine natural products: A lead for Anti-cancer. Indian Journal of GeoMarine Sciences, 2012; 41(1):27-39.
3) Jimeno J, Faircloth G, Fernández Sousa-Faro JM, Scheuer P, Rinehart K. New Marine Derived Anticancer Therapeutics ─ A
Journey from the Sea to Clinical Trials. Mar. Drugs 2004; 2:14-29
PP 89 OPIOID MEDIATED ANTINOCICEPTIVE ACTIVITY OF AGOMELATINE
MERVE KASAP , ÖZGÜR DEVRIM CAN
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY
Agomelatine is a new antidepressant drug with anxiolytic properties, acts through a unique mechanism of action, as a
melatonin MT1 and MT2 receptor agonist and a 5-hydroxytryptamine (5-HT)2C receptor antagonist. This study was planned to
investigate possible antinociceptive effect of agomelatine on acute nociceptive stimulus. Hot plate, tail-clip and writhing tests
were performed with this purpose. Agomelatine administrated at 40 mg/kg, increased the reaction time of animals both in hotplate and tail-clip tests, suggesting the anti-nociceptive activity which is related to both supraspinal and spinal mechanisms.
This drug also reduced the number of acetic acid induced writhing behaviors indicating the presence of peripherally mediated
anti-nociceptive activity, as well as centrally mediated ones. Anti-nociceptive activity of agomelatine seems to be unrelated
with probable motor impairment, which may interfere with the test results and give false positives because the Rota-rod tests
showed no significant effect on the motor coordination of animals. Anti-nociceptive effect of agomelatine disappeared by
naloxone (5.48 mg/kg, i.p) pre-treatment in all of the tests indicating that some opioidergic mechanisms were involved in the
observed pharmacological activity of agomelatine. Further studies are needed to clarify responsible opioid receptor subtypes.
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PP 90 SYNTHESIS AND ANTICHOLINESTERASE INHIBITORY ACTIVITY OF SOME NOVEL BENZIMIDAZOLE DERIVATIVES
ÜMIDE DEMIR ÖZKAY 1, NAFIZ ÖNCÜ CAN 2, YUSUF ÖZKAY 3
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKIŞEHIR, TURKEY
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTICAL CHEMISTRY, ESKIŞEHIR, TURKEY
3
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKIŞEHIR, TURKEY
1
2
Alzheimer’s disease (AD) is the most common cause of dementia for older people. Its treatment is based on the use of cholinesterase
inhibitors. The pathogenesis of AD is caused by decreasing the acetylcholine (ACh). In the brain, acetylcholinesterase (AChE)
terminates the activity of ACh by hydrolysing it to acetic acid and choline (1). In the present study some new benzimidazole
derivatives were synthesized in order to investigate their inhibitory potency against AChE and butrylcholineesterase (BChE).
Structures of the target compounds were confirmed by spectral data and elementary analysis. Elman’s colorimetric method [2]
was used in enzymatic studies. Synthesized compounds showed low inhibitory potency against BChE. On the other hand AChE
inhibitory potencies of some compounds in the series were comparable with that of reference drug donepezil. 1. Masoud MS,
Ali AE, Ghareeb DE, Nasr NM. Synthesis and characterization of cephradine metal complexes as Alzheimer disease therapeutic
agent: An in vitro kinetic study on acetylcholinesterase and monoamine oxidase. J. Chem. Pharm. Res. 2013;18:1325-1334.
2. Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase
activity. Biochem. Pharmacol. 1961;7:88-95.
PP 91 THE PLACE OF HERBAL PRODUCTS IN MALATYA PHARMACIES
NARİN SADIKOĞLU
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, İNÖNÜ UNIVERSITY, MALATYA, TURKEY
Nowadays, herbal products are sold often in spice shops, markets and on the internet. Their place in the pharmacy and in
particular to investigate about the situation in Malatya in 2013, pharmacists who located in the city of Malatya pharmacies were
interviewed. Questionnaire survey of pharmacists who accept the offer of 25 based on the information we have, that there is
not given enough attention to herbal medicine and 2-3 kinds of products as per the pharmacy is found to exist. Because it is
not approved by the Ministry of Health, pharmacists does not want to keep herbal products in pharmacies. Pharmacists have
expressed, especially the use of herbal tea is not controlled and is causing many side effects and they do not want to take this
responsibility, provided the use is controlled and approved by the Ministry of Health, they would have at the pharmacy.
PP 92 GAS6 HAS A MITOGENIC EFFECT ON MEGAKARYOPOIESIS
OZLEM BINGOL OZAKPINAR 1, ANNE-MARIE MAURER 2, CAFER ADIGUZEL 3, FIKRIYE URAS 1
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, İSTANBUL, TURKEY
MARMARA UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF HAEMATOLOGY, İSTANBUL, TURKEY
3
MEDICAL PARK HOSPITAL, İSTANBUL TURKEY
1
2
Megakaryopoesis is characterized by a set of cellular events in the formation of mature megakaryocytes from hematopoietic
stem cells (HSC). Giving the patient ex vivo megakaryocyte-differentiated progenitor cells rather than short-lived platelets might
be a good strategy. This study was intended to assess possible effects of GAS6 on megakaryopoeisis. Material and Methods:
CD34+ HSCs were isolated from peripheral blood of healthy donors. These cells were differentiated into megakaryocytes with
a two-stage liquid culture method for 21 days. During differentiation of these cells 100, 250 and 500 ng/ml GAS6 protein
were added to medium (n=5). Also, cells were treated with GAS6 antibody of 4 ng/ml and 8 ng/ml concentration in parallel
experiments (n=2). Cells taken at days 7 and 14 of culture were analyzed by flow cytometry. It was detected that CD34 + cell
ratio decreased significantly at 250 ng/ml and 500 ng/ml GAS6 concentrations (p <0.05) on day 7. In addition, CD 34+/CD 41+
cells ratio was increased significantly at 250 ng/ml GAS6 concentration. In parallel to these findings, GAS6 antibody was noted
to inhibit the proliferative effect when added to the medium in the early stages. In the light of these findings, it could be argued
that GAS6 is a growth factor for maintaining ex vivo expansion of MPH by increasing the number of CD34+ cells. Furthermore,
a good approach might be to substitute megakaryocyte-differentiated progenitor cells instead of platelets. In clinical practice
of MPH, these results are promising.
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PP 93 CURCUMIN PREVENTS UTERI ISCHEMIA-REPERFUSION INJURY VIA ITS ANTIOXIDATIVE AND ANTIAPOPTOTIC EFFECTS
OZLEM BINGOL OZAKPINAR 1, BETUL FEYZA ULUSOY 1, TURGUT SEKERLER 1, SADIK SAHIN 2, NAZIYE OZKAN 3, ANNE-MARIE
MAURER 4, FIKRIYE URAS 1
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, İSTANBUL, TURKEY
ZEYNEP KAMIL GYNECOLOGIC AND PEDIATRIC TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY
3
MARMARA UNIVERSITY, VOCATIONAL SCHOOL OF HEALTH SERVICES, İSTANBUL, TURKEY
4
MARMARA UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF HAEMATOLOGY, İSTANBUL, TURKEY
1
2
Curcumin is a major chemical component produced from the rhizome of the plant Curcuma longa. It has been demonstrated
that curcumin functions as an antioxidant, anti-inflammatory, antiproliferative, antiangiogenic and anti-atherosclerotic, and
protects ischemia-reperfusion injury in various tissues. Ischemia-reperfusion (I/R) injury has detrimental effects on transplanted
organs including uteri. The major consequence of I/R injury is oxidative stress leading to the generation of reactive oxygen
species (ROS). Uterine transplantation (UT) has been gaining popularity around the world in the past few years. The aim of the
present study was to examine the antioxidative and antiapoptotic effects of curcumin on uterine I/R injury induced by distal
abdominal aortic occlusion in rats. For this purpose, the rats were randomized into three groups of seven rats each. Group I
(the control group) consisted of rats that did not receive any treatment, group II (the uterine I/R injury group) of rats exposed
to 0.5 hour of ischemia and 1hour of reperfusion, group III (curcumin group) of rats that received intraperitonealy curcumin
(200 mg/kg) 0.5 hour before the induction of I/R. Then, the rat uterine tissue levels of MDA, TAC, caspase-3, 8 and 9 were
measured. Furthermore, the rat uterine specimens were histologically evaluated. Biochemical analysis results showed that
curcuimin decreased the MDA and caspase-3 and 9 levels, and increased the uterine tissue levels of TAC. The results of the
present study demonstrate that curcumin has protective effects against uterine I/R injury, and these protective effects may be
due to its antioxidant, antiapoptotic and antiinflammatory properties.
PP 94 ANALYSIS OF PHARMACISTS’ PERCEPTION AND ATTITUDES TOWARDS GENERIC DRUGS AND GENERIC SUBSTITUTION
IN ALGERIA
ACHOURI MOHAMED YACINE , ALLEG ABDELATIF OUSSAMA , MOULAI MOHAMED CHERIF LOUAZZANI , MOHAMED ADIL
SELKA
DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE SID BEL ABBES, ALGERIA
This study aims to assess the perception and attitudes of community pharmacists in Sidi-Bel-Abbes (North of Algeria) towards
generic drugs. This is a descriptive and cross-sectional survey, conducted between 1st April 2014 and 30st May 2014. The target
population consisted of 118 pharmacists practicing in pharmacies in Sidi-Bel-Abbes. Data collection was conducted through a
questionnaire consisting of thirteen (13) items. Fifty six (67%) of community pharmacists in the town of Sidi-Bel-Abbes believe
that generics have a lower quality compared to the originator. 52 respondents (62%) were in no apprehension towards generics
and 63% believe that the generics substitution has led to change the relationship between a pharmacist and patient. In order to
promote the practice of generic medicines in Qatar, an educational program should be implemented in Algeria.
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PP 95 DETERMINATION OF MAJOR PHENOLIC COMPOUNDS OF POMEGRANATE WINES WITH REVERSE PHASE HPLC-DAD
METHOD
CAGLAR DEMIRBAG , SERAP AYAZ SEYHAN , GULER YALCIN , NESE ERDINC
MARMARA UNIVERSITY FACULTY OF PHARMACY, ISTANBUL, TURKEY
Pomegranate (Punica granatum L.) is an edible fruit and it has been used as a medicine in many different cultures. Many
phytochemicals have been identified in pomegranate leafs, flowers and fruits. These phytochemicals are classified as
ellagitannins, gallotannins, ellagic acid derivatives, catechin, procyanidin, anthocyanins, anthocyanidins, flavanols, organic
acids, fatty acids, triglycerides, steroids, terpenoids and alkaloids (1). Pomegranate was used for the treatment of diseases
such as oral aphthae, ulcers and diarrhea in India, China and Middle East in ancient times. Nowadays there are many studies on
therapeutic activity of pomegranate due to the variety of antioxidant compounds content and the studies have been reported
that extracts from different parts of plant has therapeutic activity (2). We have developed a reverse phase HPLC-DAD method for
the determination of major phenolic compounds in pomegranate which are produced in Turkey. The HPLC analysis were carried
on C18 column and gradient elusion of Acetonitrile: Phosphate Buffer mobile phase system were used. We have experienced
some stability problems with one of the analysed ellagitannins. The future goal of this study is to solve stability problem and
apply the method to some pomegranate wine brands which are produced in Turkey.
1. Özkal N, Dinç S. (1993). Punica granatum L. (Nar) Bitkisinin Kimyasal Bileşimi ve Biyolojik Aktiviteleri. Ankara Ecz Fak Der,
22(1-2):38-50. 2. Noda Y, Kaneyuki T, Mori A, Packer L. (2002). Antioxidant activities of pomegranate fruit extract and its
anthocyanidins: delphinidin, cyaniding, and pelargonidin. J Agric Food Chem, 50 (1):166–171.
PP 96 ANTIBACTERIAL ACTIVITY OF THE ESSENTIAL OIL OF ORIGANUM GLANDULOSUM ON BACTERIAL STRAINS OF
HOSPITAL ORIGIN MOST IMPLICATED IN NOSOCOMIAL INFECTIONS
LARDJAM ABDERRAHMENE , MAZID RYM , BOUDGHENE STAMBOULI YASMINE , IZAROUKEN ASSIA , DALI YAHIA , DJEBLI
NOUREDDINE , TOUMI HOUARI
DEPARTMENT OF PHARMACY ORAN ALGERIA
Origanum glandulosum is an aromatic plant, common in Algeria and widely used by local people for its medicinal properties. The
essential oil from this plant, which grows in the west of Algeria, was studied to evaluate and determine its antibacterial activity.
The extraction of the essential oil was performed by water steam distillation; the yield obtained from the aerial parts (1.78%)
is interesting, its chromatographic profile revealed by TLC showed the presence of phenolic compounds thymol and carvacrol.
The evaluation of the activity of the essential oil of Origanum glandulosum on bacterial strains of hospital origin, ATCC, MRB,
and HRB, most implicated in nosocomial infections (Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 43300,
Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus
resistant to meticillin, Enterococcus faecium, VA R and R TEC, Acinetobacter baumanii, IMP R and R CAZ, Klebsiella pneumonia
carbapenemase-producing) by the method of aromatogramme and microatmosphere, shows that the antibacterial potency of
this oil is very high, expressed by significant inhibition diameters on all strains except Pseudomonas aeruginosa, and low MICs
and is characterized by a bactericidal action.
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PP 97 DETERMINATION OF CADMIUM, LEAD AND SELENIUM CONCENTRATIONS IN TURKISH HERBAL TEAS
DILEK BILGIC ALKAYA , SERAP KARADERI , GULBIN ERDOGAN , AYSEN KURT CUCU
MARMARA UNIVERSITY
The use of herbal teas is now widespread in our community. The presence of heavy metals and trace elements in the herbal
teas has received special attention because they are directly related to health. The main sources of heavy metals in plants are
their growth media, nutrients, agro inputs and soil. Other sources may include pesticides and fertilizers. Elevated heavy metal
levels cause damage to plants such as delayed flowering, lower chlorophyll content and reduction in the number and quality
of shoots. Owing to the importance of heavy metals present in herbal teas, this study was carried out to determine their
concentrations and reliability of usage of these plants. Ten different brand teas purchased from herbalist. Concentration of
three elements Pb, Cd and Se were measured in ten samples of different species of teas using flame and electrothermal atomic
absorbtion spectrophotometry after microwave digestion method. The samples were digested with concentrated HNO3 in
closed Teflon PFA vessels in a microwave oven. Metal concentrations in several samples were in excess of FAO/WHO and Turkish
Regulations, indicating that consumption of these irrigated foods may represent an important exposure pathway to humans .
Also passing time to blood of metals in teas are compared at 2, 5 and 10 minutes and it has been seen that amount of metal has
been increased when the passing time to blood has been increased.
References
1.Antun Kucak and Maja Blanusa.Validation of microwave digestion method for determination of trace metals in mushrooms.
Arh hig rada toksicol, Vol. 49 (4), 335-342, (1998).
2. I. Baranowska, K. Srogi, A. Włochowicz, K. Szczepanik. Determination of Heavy Metal Contents in Samples of Medicinal Herbs.
Polish Journal of Environmental Studies Vol. 11(5), 467-471, (2002).
PP 98 GLYCATED TRANSFERRIN INDUCED OXIDATIVE STRESS IN HUMAN PLATELETS
BAHAR GOKER 1, OZGE CEVIK 2, OZLEM OZAKPINAR 1, HALIL AKSOY 1, DERYA OZSAVCI 1, AZIZE SENER 1
1
2
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY , SIVAS, TURKEY
Iron is essential for life in cells and soluble iron can generate reactive oxygen species (ROS). Non-enzymatic glycosylation of
a variety of transferrin (TrF) proteins has been shown that release to iron and produce occur in different diseases advanced
glycation end products (AGEs). The aim of this study is to determine the effects of in vitro glycation of TrF in human platelets.
Human commercial apo-TrF was dissolved in PBS and incubated with different concentration glucose (0, 5.6, 11.1, 22,2 ve 33,3
mmol/L) under sterile conditions at 370C for 10 days. After incubation, protein glycation were determined by NBT reduction
assay. Human platelet was isolated from healthy volunteers and suspended with HEPES buffer. Platelets were incubated with
different concentration glycated transferrin (g-TrF) with/without ADP. Then some oxidative stress marker (MDA, GSH, SOD,
NO) were measured with ELISA. Platelet MDA levels were increased high concentration g-TrF compare to control and TrF group
(p˂0.05-0.001). GPx levels decreased with incubated high concentration g-TrF compare to control and TrF group (p˂0.05-0.01).
However, there was no significant change in platelets GSH and SOD levels compare to TrF group. NO level was decreased in
dose dependent g-TrF incubated platelets (p˂0.05-0.001). The results reported here clearly demonstrate that in vitro glycated
transferrin causes platelet oxidative stress and apoptosis induction resulting in the formation of AGEs and free iron releasing.
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PP 99 ROLE OF THE GLYCATED TRANSFERRIN ON ACTIVATION AND APOPTOSIS OF HUMAN PLATELETS
OZGE CEVIK 1, BAHAR GOKER 2
1
2
CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, SIVAS, TURKEY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL,TURKEY
Transferrin receptor (TFR) is an essential protein that cell surface receptor for transferrin (TrF) circulation and involved in iron
uptake and the regulation of cell growth. Protein glycosylation’s can modify structure properties and plays an important role
in receptor–ligand and cell–cell interactions. In this study the interaction between the platelet transferrin receptor and the
platelet activation with glycated transferrin (g-TrF) protein was investigated. G-TrF was produce with different concentration
glucose (0, 5.6, 11.1, 22,2 ve 33,3 mmol/L) in commercial apo-TrF. TrF modifications were determined using HPLC and protein
glycations were determined by NBT reduction assay using control as BSA. Human platelet was isolated from healthy volunteers
and suspended with HEPES buffer. Platelets were incubated with different concentration glycated transferrin (g-TrF) with/
without ADP. Then detection for TFR2 binding and p-selectin (CD62p) binding for activation of platelets were measured using
flow cytometer (FACS). At the same time platelet caspase-3 activity was determined by ELISA. Incubation of platelets with the
g-TrF elicited protein modification in a dose- and time-dependent manner. In FACS data showed that ADP activated platelets
were high binding with TFR2 receptor compare to non-activated platelets (p˂0.001). Importantly, FACS analysis revealed
significant up-regulation of CD62p binding in platelets following dose dependent g-TrF incubation (p˂0.01). Platelet Caspase-3
activity were increased with dose dependent g-TrF groups (p˂0.05-0.001). We show that platelets have TFR2 receptor for iron
regulation and cellular function and g-TrF production may promote proapoptotic events in blood circulation.
PP 100 PROTEOMIC PERSPECTIVE FOR HUMAN PLATELETS INTERACTION WITH GLYCATED TRANSFERRIN
OZGE CEVIK 1, AHMET TARIK BAYKAL 2, BAHAR GOKER 3
CUMHURIYET UNIVERSITY, FACULTY OF PHARMACY DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
MEDIPOL UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL BIOCHEMISTRY, ISTANBUL, TURKEY
3
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
1
2
Platelets are enucleate cells that are considered as a crucial role in hemostasis. Glycosylation of proteins is known that posttranslational modification, strongly influencing many of their functional aspects, including cellular localization, turnover and
protein quality control. To investigate platelet protein expression induced by glycated transferrin (g-TrF), washed human platelets
were incubated in HEPES buffer with g-TrF and/or ADP. 2D-PAGE and LC/MS/MS applied to examine the platelet proteins
expression analysis. Platelets washed with ammonium bicarbonate buffer and total protein was quantified. The first dimension
separation was performed on an isoelectric focusing using pH 3-10 and pH 5-8 strips. Second dimension, strips were applied
directly to 10% SDS-polyacrylamide gels and used silver staining. After the spot selection, specific trypsin digested peptides were
analyzed in mass spectrometry. Spot analysis showed that, especially membrane structural proteins and cytoskeletal proteins
were changed with g-TrF incubation in platelets. Activated platelets by g-TfR causes dramatic changes in their morphology.
Modification of specific platelet proteins after activation appears can be related to both changes in cytoskeleton structure and
granule contents. Our data support the hypothesis that g-TrF interacts with platelet transferrin receptors and triggered platelet
functions as structural proteins. This result is preliminary and all proteins need to be confirmed starting point for studying the
protein signaling pathways.
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PP 101 SYNTHESIS AND BIOCHEMICAL MECHANISM EVALUATION OF NEW BENZIMIDAZOLE DERIVATIVES BEARING
PYRIDYL/PYRIMIDINYL PIPERAZINE MOIETY
GULSEN AKALIN CIFTCI 1, HALIDE EDIP TEMEL 1, LEYLA YURTTAS 2
1
2
ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF BIOCHEMISTRY, ESKISEHIR, TURKEY
ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKISEHIR, TURKEY
Benzimidazoles are bioactive compounds which they have broad range of pharmacological activities such as antifungal,
anti-helmintic, anti-HIV, antihistaminic, antiulcer, cardiotonic, and antihypertensive (1). In recent years, they have attracted
particular interest due to their anticancer activity or as potential in vitro anticancer agents (2,3). In this study 1-[2-oxo-2(4-substituted phenyl)ethyl]benzimidazol-2-yl)methyl 4-(pyridyl/pyrimidin-2-yl)piperazine-1-carbodithioate derivatives (2a-n)
were synthesized and were identified using IR, 1H-NMR, 13C-NMR, and MS data. Intermediate products were prepared with
the reaction of 2-(chloromethyl)benzimidazole and sodium salts of 4-(2-pyridyl/pyrimidinyl)piperazine-1- dithiocarbamic acids
in acetone at room temprature with stirring (1a, 1b). Final compounds (2a-l) were gained with the reaction of the obtained
compounds 1a and 1b and α-bromoacetophenone derivatives in acetone. Anticholinesterase activities of the final compounds
will be evaluted with Ellman method. Furthermore, cytotoxic activity of these compounds will be measured bty MTT method.
1. Chawla A, Ramandeep K, Goyal A. Importance of microwave reactions in the synthesis of novel benzimidazole derivatives:
A review. J Chem Pharm Res. 2011;3:925-944. 2. Husain A, Rashid M, Mishra R, Parveen S, Shin DS, Kum D. Benzimidazole
bearing oxadiazole and triazolo-thiadiazoles nucleus: Design and synthesis as anticancer agents. Bioorg Med Chem Lett.
2012;22:5438-5444. 3. Yurttaş L, Demirayak S, Akalın Çiftci G, Yıldırım ŞU, Kaplancıklı ZA. Synthesis and biological evaluation of
some 1,2-disubstituted benzimidazole derivatives as new potential anticancer agents. Arch Pharm Chem Life Sci. 2013;346:403414.
PP 102 EVALUATION OF ANTICHOLINESTERASE AND CYTOTOXIC PROPERTIES OF NEW MORPHOLINE DITHIOCARBAMATE
DERIVATIVES BEARING BENZIMIDAZOLE MOIETY
HALİDE EDİP TEMEL 1, GÜLŞEN AKALIN ÇİFTÇİ 1, LEYLA YURTTAŞ 2
1
2
ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF BİOCHEMİSTRY, ESKİŞEHİR, TURKEY
ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, ESKİŞEHİR, TURKEY
In this present study, new morpholine dithiocarbamate derivatives bearing 1-(2-aryl-2-oxoethyl)-2-substituted benzimidazole
moiety were synthesized and their potential anticholinesterase and cytotoxic properties were investigated. Benzimidazole
scaffold is an important pharmacophore that has been extensively utilized as a drug in medicinal chemistry for years (1). Among
them 1-(2-aryl-2-oxoethyl)-2-substituted benzimidazole derivatives have a particular interest as a result of studies which we
have been reported before with satisfactory anticancer activity results (2,3). Additionally, gefitinib, a recent morpholine carrying
anticancer drug, is expected to play a significant role in designing and synthesizing new drugs (4). In this manner, we have
synthesized benzimidazole and morpholine including compounds (2a-l). The structures of the final compounds were elucidated
by IR, 1H-NMR, 13C-NMR, and MS spectroscopy. Final compounds were achieved with the reaction of (benzimidazol-2-yl)
methyl morpholine-4-carbodithioate and α-bromoacetophenone derivatives in acetone at room temprature with stirring. The
anticholiesterase and cytotoxic activity studies are in progress.
1. El-Nassan HB. Synthesis, antitumor activity and SAR study of novel [1,2,4]triazino[4,5-a]benzimidazole derivatives. Eur J Med
Chem. 2012;53:22-27. 2. Demirayak S, Kayagil I, Yurttas L. Microwave supported synthesis of some novel 1,3-Diarylpyrazino[1,2-a]
benzimidazole derivatives and investigation of their anticancer activities Eur J Med Chem. 2011;46:411-416. 3. Yurttaş
L, Demirayak S, Akalın Çiftci G, Yıldırım ŞU, Kaplancıklı ZA. Synthesis and biological evaluation of some 1,2-disubstituted
benzimidazole derivatives as new potential anticancer agents. Arch Pharm Chem Life Sci. 2013;346:403-414. 4. Surve P,
Ravindran S, Acharjee A, Rastogi H, Basu S, Honrao P. Metabolite characterization of anti-cancer agent Gefitinib in human
hepatocytes. Drug Metab Lett. 2013;7:126-136.
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PP 103 SYNTHESIS AND BIOCHEMICAL MECHANISMS OF BISTHIAZOLE DERIVATIVES ACTION
GÜLHAN TURAN-ZİTOUNİ 1, MEHLİKA DİLEK ALTINTOP 1, AHMET OZDEMİR 1, HALİDE EDİP TEMEL 2, GÜLŞEN AKALIN ÇİFTÇİ 2,
ZAFER ASIM KAPLANCİKLİ 1
1
2
ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, ESKİŞEHİR, TURKEY
ANADOLU UNIVERSITY, PHARMACY FACULTY, DEPARTMENT OF BİOCHEMİSTRY, ESKİŞEHİR, TURKEY
Thiazoles are thus important molecules. They exhibit a variety of activities such as antimicrobial, antiretroviral, antineoplastic
antithrombotic including anticholinesterase. Recently the applications of thiazoles were found in drug development for the
treatment of allergies, hypertension, inflammation, schizophrenia, bacterial, HIV infections and more recently for the treatment
of pain (1,2). Thus bisthiazole has been a hot topic of investigations. We aimed to investigate the therapeutic values of bisthiazole
derivatives. 3,3-Dimethoxy-N4,N4-bis(4-phenylthiazol-2-yl)biphenyl-4,4-diamine derivatives (1-10) were synthesized via
the ring closure of 1,1-(3,3-dimethoxybiphenyl-4,4-diyl)bis(thiourea) (A) with phenacyl bromides. Each derivative was also
evaluated for their cytotoxic activity by MTT method and ability to inhibit AChE and BuChE using a modification of Ellmans
spectrophotometric method. Compound 8 can be identified as the most potential anticholinesterase agent due to its inhibitory
effects on AChE and BuChE with IC50 values of 5.86 ± 0.92 µg/mL and 33.33 ± 1.29 µg/mL, respectively.
1. Turan-Zitouni G, Ozdemir A, Kaplancikli ZA, Altintop MD, Temel HE, Çiftçi GA. Synthesis and biological evaluation of some
thiazole derivatives as new cholinesterase inhibitors. J Enzyme Inhib Med Chem. 2013;28(3):509-14. 2. Siddiqui N, Arshad MF,
Ahsan W, Alam MS. Thiazoles: a valuable insight into the recent advances and biological activities. Int J Pharm Sci Drug Res
2009;1:136–143.
PP 104 SYNTHESIS, CHARACTERIZATION AND IN VITRO ANTIBACTERIAL ASSESSMENTS OF A POLY[MALEIC ANHYDRIDE-ALTACRYLIC ACID]/ACRIFLAVINE CONJUGATE
GULDEREN KARAKUS 1, HATICE KAPLAN CAN 2, NEVIN TUZCU 1
1
2
CUMHURIYETUNIVERSITY, SIVAS, TURKEY
HACETTEPE UNIVERSITY, ANKARA, TURKEY
Researchers are trying to find ways of improving therapeutic efficacy such as lower cost, biocompatible, multifunctional, fewer
side effects, less toxic of traditional lower molecular weight drugs to the polymeric systems by modifying techniques (1).
Synthetic polymers are known as the most versatile class of biomaterials useful for controlled drug delivery systems, applied
in the medical and biotechnologies, as well as in the food and cosmetics industries (2). In this study water-soluble poly[maleic
anhydride-alt-acrylic acid] (MAAA) copolymer was synthesized by free-radical chain polymerization reaction, in 1,4-dioxane
in the presence of benzoyl peroxide (BPO), 0.1 %, as the radical initiator at 70 °C under a nitrogen atmosphere. The purified
copolymer was then modified with an anti-external fungal and anti-cancer active agent, acriflavine (AF). The modification
reaction was performed 48 h at 70 °C in dimethylformamide (DMF), using triethylamine (TEA) as the catalyst (3). Structural
characterization of the copolymer (MAAA), and modified product (MAAA/AF) was carried out by Fourier Transform Infrared
(FTIR) and Nuclear Magnetic Resonance (1H-NMR and 13C-NMR). FTIR, 1H-NMR, and 13C-NMR spectra confirmed that AF
was successfully bound to the MAAA copolymer backbone by ring-opening reaction. A reaction mechanism was then also
suggested for the conjugation reaction. Antimicrobial susceptibility of the MAAA, AF, and MAAA/AF was evaluated by Kirby
Bauer Disc Diffusion method on Mueller–Hinton Agar by using Enterecoccus faecium, Enterohaemorrhagic Escherichia coli
(EHEC), Staphylococcus aureus and Listeria monocytogenes. Results obtained indicated that MAAA/AF had antibacterial activity
on Enterohaemorrhagic Escherichia coli (EHEC) and Staphylococcus aureus at 50, 40, and 30 µg.
1. Kadaji VG, V. Betageri G. Water soluble polymers for pharmaceutical applications. Polymers 3. 2011;1972-2009. 2. Kenawy
ER, Abdel-Hay F, El-Newehy M, Ottenbrite RM. Effect of pH on the drug release rate from a new polymer-drug conjugate system.
Polym Int. 2008;57: 85-91. 2. Karakus G, Akin Polat Z, Yenidunya AF, Zengin HB, Karakus CB Synthesis, characterization and
cytotoxicity of novel modified poly[(maleic anhydride)-co-(vinyl acetate)]/noradrenaline conjugate. Polym Int. 2013;62:492500.
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PP 105 AN INVESTIGATION OF THE PH EFFECT ON THE STABILITY BEHAVIOR OF POLYMER-DRUG SYSTEM INCLUDING
HYDROXYUREA
GULDEREN KARAKUS 1, NUR MELEK CETIN 2, DOLUNAY SAKAR 2
1
2
CUMHURIYET UNIVERSITY, SIAVS, TURKEY
YILDIZ TECHNICAL UNIVERSITY, ISTANBUL, TURKEY
Polymers have been used as a main tool to control the drug release rate from the formulations (1). If a polymeric carrier is to be
used, the next step is to design a type of polymeric structure that will permit obtaining the desired release conditions. Therefore,
the polymeric structure should be biodegradable, dissemblable, and undissemblable (2). Improving delivery techniques that
minimize toxicity and improve efficacy offers great potential benefits to patients, and opens up new markets for pharmaceutical
and drug delivery companies (3). In this work, poly (maleic anhydrite-co-vinyl acetate) (abbreviated as MAVA) copolymer
and Hydroxyurea (HX) is used to treatment types of cancer were used for synthesizing of MAVA-HX bioactive polymeric drug
delivery system. At specific intervals, the stability behaviors of MAVA-HX system have been examined by Zeta Potential Analyzer
and UV Spectrophotometer at different pHs. Zeta potential, mobility, and particle size of prepared polymer-drug system were
determined by using the Zeta Potential Analyzer in water with different pHs. Absorption and permeability of MAVA/HX, MAVA
and HX were also determined by UV Spectrophotometer.
1. Raizada A, Bandari A, Kumar B. Polymers in Drug Delivery. A Review. 2002;79:7-27. 2. Vilar G, Tulla-Puche J, Albericio F. Curr
Drug Deliv. 2012;9(4):367-94. 3. Kaparissides C, Alexandridou S, Kotti K, Chaitidou S. Recent Advances in Novel Drug Delivery
Systems. 2006.
PP 106 STRUCTURAL SIMILARITY AMONG RIBOSWITCHES AND RRNAS: RIBOSWITCHES AS HIGH AFFINITY TARGETS FOR
PAROMOMYCIN
ELNAZ MEHDIZADEH AGHDAM 1, ABOLFAZL BARZEGAR 2, MOHAMMAD SAEID HEJAZI 3
STUDENT’S RESEARCH COMMITTEE AND FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
RESEARCH INSTITUTE FOR FUNDAMENTAL SCIENCES (RIFS), UNIVERSITY OF TABRIZ, TABRIZ, IRAN
3
DEPARTMENT OF PHARMACEUTICAL BIOTECHNOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
1
2
Riboswitches, as cis acting non-coding RNA elements, regulate gene expression via specific binding of various small molecules
without proteins interpretation. Some previous studies report possible structural relation between riboswitches and rRNAs.
In this study we aimed to find out the structural and functional level of similarity among riboswitches and rRNA structures
including binding of aminoglycosides to aptamer domain of riboswitches through computational tools. For this, paromomycin
was chosen as a model. First, the PDB structures of ten classes of riboswitches were selected. Following structure based
alignment on selected riboswitches domains, top similar rRNAs with high secondary structure identity were selected. Then,
multiple, global and local pairwise alignments were conducted on selected rRNA sequences. Highly similar rRNA motifs with
riboswitches (including “A site”) were sorted out. At last, the probable functional similarity of riboswitches with “A site motif” of
16S rRNA were studied based on the affinity of paromomycin antibiotic to riboswitches using docking by AutoDock 4.2. Statistical
analyses on binding energies were performed using one-way analysis of variance (ANOVA). Conserved structural rRNA building
blocks such as “hairpin loop containing UUU”, “peptidyl transferase center conserved hairpin A loop” were detected in different
riboswitches. However, no particular sequence based similarity was identified. Interestingly, docking analysis showed significant
high binding energies of paromomycin with different riboswitches in comparison to the binding energy of paromomycin with
“16S rRNA A site” (p <0.001). These findings clearly support the evolutionary origin of riboswitches/rRNAs and consideration of
riboswitches as potential targets for aminoglycosides.
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PP 107 PREPARATION AND CHARACTERIZATION OF INJECTABLE HYALURONIC ACID DERIVATIVE GELS CONTAINING DICLOFENAC
SODIUM
SHEIDA SHARBATI
SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN
Hyaluronic Acid (HA) polymers are widely used in osteoarthritis and also in drug delivery. In this study Diclofenac Sodium was
used as the model drug. Hyaluronate Sodium, Hyaluronic Acid and Cross-linked Hyaluronate Sodium loaded in each formulation.
To measure syringability, viscosity of gels was determined. Drug Release study was carried out using dialysis membrane at pH
7.4. Kinetic studies were subsequently carried out to determine the optimum model as well as mechanism of drug release. The
results showed that gels containing HA 4% and NaHA 2% had the highest and lowest viscosity respectively. Drug release results
indicated the the slowest drug release profile is related to the gel containing cross-linked NaHA 4%. Results of kinetic study
showed that Higuchi model could predict the process of drug release better than other models employed. Moreover, based
on the Peppas index (n), the release seems to follow the non-fickian diffusion process. There was a highly significant (p≤0.001)
correlation between types of polymers and drug release profile. In conclusion, our results indicate hyaluronate polymers are
suitable candidates for sustaining drug release. And may be used as an appropriate drug delivery system. An anti-inflammatory
drug loaded in HA polymers could produce a formulation with promising outcomes and could be more effective in osteoarthritis.
PP 108 THE EFFECT OF POLOXAMER 188 ON THE PHYSICAL PROPERTIES OF CARVEDILOL BINARY AND TERNARY SOLID
DISPERSIONS
NAZLI POURMOHAMMAD
SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN,IRAN
The solid dispersion (SD) technique provides an efficient method to improve the dissolution rate and solubility of poorly
water soluble drugs. Hydrophilic compounds such as poloxamer188 (P188) have been used successfully as a carrier for the
preparation of SDs. Carvedilol (CA) used in the treatment of hypertension and congestive heart failure is a poorly soluble drug
with lower dissolution rate and bioavailability. The objective of this study was to prepare and evaluate dissolution rate and
physicochemical properties of CA from binary and ternary P188-based solid dispersions. Binary and ternary SDs were prepared
using CA: P188 and CA: polyethylene glycol 6000 (PEG) with different ratios by solvent evaporation method. The solubility,
dissolution rate and efficiency (DE60) dispersions were evaluated. Samples were also characterized using DSC (Differential
scanning calorimetry), IR spectroscopy. According to the results, all binary and ternary SDs improved the dissolution rate of
CA significantly (p< 0.05). The best results were obtained from CA: P188 and CA: PEG: P188 with the ratios of 1:7 and 1: 4: 3,
respectively, (DE60= 62% and 84%) compared to the intact drug and (DE60= 13%) related physical mixtures (DE60 =44% and
47%). The solubility of above mentioned samples were also enhanced significantly (p< 0.01). DSC, IR and analysis showed no
chemical reaction between ingredients during the preparation method. In conclusion, formulation of P188-based SDs markedly
improves carvedilol dissolution characteristics in binary and ternary dispersions.
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PP 109 FORMULATION OF METFORMIN HYDROCHLORIDE FLOATING SUSTAINED RELEASE TABLET
SAEED SALARI
SHAHID BEHESHTI MEDICAL UNIVERCITY, TEHRAN, IRAN
The purpose of this study was to develop a gastroretentive formulation of metformin hydrochloride in the form of a floating
tablet capable of remaining in the stomach for a reasonable length of time as well as producing sustained drug release over
a period of 12 hours.Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the
treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Metformin
has an oral bioavailability of 50–60% under fasting conditions, and excretion 20-30% intact in stool. metformin could be used
daily up to three times daily, its compliance could be low in the user. An extended release dosage form could help to reduce
the frequency of use and improving the pharmacokinetic indices of the drug(such as bioavailability)and the provision of
improved drug efficiency. Various amounts of different polymers including HPMC K4M, HPMC K15M, ethyl cellulose, carbomer
934P, Polyethylene Oxide and sodium carboxy methyl cellulose were employed for this study.In order to study the effect of
different weight ratio of sodium bicarbonate as the gas generating agent, on the floating properties of the resulting tablets,
was investigated.The above excipients were mixed with metformin HCl and were blended with 0.5% magnesium stearate and
compressed using a single-punch tablet machine equipped with convex faced 12 mm diameter punches. Overall, 31 formulations
were prepared and tested in terms of hardness, thickness, friability, as well as floating lag time and duration of floating. The
studies showed that the type and the amount of polymers and the amount of filler and sodium bicarbonate used could influence
the floating properties of tablets.Next, the formulations that were found acceptable based on physicochemical tests and also
had appropriate floating properties were selected for the dissolution studies. Dissolution profile of each formulation was
determined for 12 hours using the USP apparatus II (paddle) dissolution tester in pH=3.5 HCl medium at 370C and at a stirring
speed of 50 rpm..Ultimately, formulations F20 containing 19% HPMC K4M,15% carbomer 934p, 10% sodium bicarbonate; F22
containing 19% HPMC K4M, 7.5% ethyl cellulose, 7.5% carbomer 934p, 10% sodium bicarbonate bicarbonate were chosen since
they had desirable floating properties, appropriate drug release profile, and also complied with the other physicochemical test
conducted. Next, complementary studies including the determination of swelling index, kinetics of drug release, the swelling
index for selected formulation measurement, assay of active ingredient and weight variation were carried out on the selected
formulations.Drug release kinetic studies performed on selected formulations showed the higuchi model could forecast the
process of drug release from the chosen floating tablet formulations better than the other kinetic models employed. Moreover
based on the Peppas index obtained for the release seems to follow the Fickian diffusion process.
PP 110 EFFECTS OF ANTIBIOTICS ON POLYMORPHONUCLEAR LEUKOCYTE FUNCTIONS, OXIDATIVE STRESS, OXIDANT AND
ANTI-OXIDANT ENZYMES IN BRONCHIECTASIS
BURÇAK GÜRBÜZ 1, ÜMRAN SOYOĞUL GÜRER 1, ÖZGE ÇEVIK 2, İRFAN YALÇINKAYA 3, GÜLNAZ NURAL BEKIROĞLU 4, ADILE
ÇEVIKBAŞ 1
DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, İSTANBUL, TURKEY
DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, CUMHURIYET UNIVERSITY, SIVAS, TURKEY
3
MINISTRY OF HEALTH, SÜREYYAPAŞA CHEST DISEASES AND THORACIC SURGERY TRAINING AND RESEARCH HOSPITAL,
ISTANBUL,TURKEY
4
DEPARTMENT OF BIOSTATISTICS AND MEDICAL INFORMATICS, FACULTY OF MEDICAL, MARMARA UNIVERSITY, İSTANBUL,
TURKEY
1
2
The in vitro effects of colistin (4 µg/ml), tigecycline (0.87 µg/ml), rifampicin (7 µg/ml) and imipenem (30 µg/ml) alone and
in combinations at therapeutic concentrations and malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione
peroxidase (GSH-Px) and myeloperoxidase (MPO) activities were investigated on polymorphonuclear leukocyte (PMN)
functions (phagocytic and intracellular killing activity) of patients with bronchiectasis. PMNs were isolated from venous
blood by Ficoll-hypaque gradient centrifugation method. Phagocytic activity and intracellular killing activities were assayed
by modified Alexander’s method. MDA level was detected by Beuge’s method which is as an indicator of lipid peroxidation.
SOD, GSH-Px and MPO activities were assayed by Sun’s, Paglia and Valentine’s and Hillegas’s methods respectively. All results
were statistically evaluated. The PMN’s phagocytic (p<0.0001) and intracellular killing activity (p=0.0113, p=0.0020, p=0.0056,
p=0.0013, p=0.0008, p=0.0014, p=0.0061, p=0.0036, p=0.0012) of patients with bronchiectasis significantly increased when
compared to control values. Enzyme activities (SOD, GSH-Px and MPO) and MDA levels significantly decreased (p<0.001) in
patients with bronchiectasis when compared to control values.
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PP 111 FORMULATION AND IN VITRO EVALUATION OF ZOLPIDEM TARTRATE BILAYER TABLETS.
AZIN YAGHMAEIAN
SCHOOL OF PHARMACY, SHAHEEDBEHESHTI UNIVERSITY OF MEDICAL SCIENCES AND HEALTH SERVICES, TEHRAN, IRAN
Zolpidem Tartrate, a non-benzodiazepine agent, is one of the most frequently prescribed hypnotic drugs. Zolpidem was proven
as effective as benzodiazepine in the management of short-term insomnia. The purpose of this study was to design bilayer
tablet of Zolpidem Tartrate. Bilayer tablets comprised two layers, in which the one layer is formulated to obtain immediate
release of the drug, with the aim of reaching a high serum concentration in a short period of time; and The second layer
is a controlled release matrix, which is designed to maintain an effective plasma level for a prolonged period of time. The
immediate release layer comprised croscarmellose sodium as a super disintegrant and the controlled release layer comprised
Hydroxypropyl methylcellulose (HPMC K4M, K15M), ethyl cellulose, Eudragit RLPO as the release retarding polymers. Direct
compression method was used for preparation of the bilayer tablets. Tablets were investigated for physicochemical properties
and in-vitro performance. In vitro dissolution studies were carried out in a USP apparatus I, using 500mL of 0.01N HCl as
dissolution medium. The release profiles of drug from the tablets were analysed by using UV-Visible spectrophotometer at 295
nm. Optimized formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release
for 6 h. Formulation containing 3 mg croscarmellose sodium and 40 mg HPMC K15M was selected as promising formulation
among all the developed formulations.The release of Zolpidem Tartrate was found to follow a pattern of Korsmeyer-Peppas,
with Quasi-Fickian diffusion.
PP 112 METHYLPREDNISOLONE ACETATE–EUDRAGIT® RS100 ELECTROSPUNS: PREPARATION AND PHYSICOCHEMICAL
CHARACTERIZATION
AZIN JAHANGIRI , NAZILA JAFARI AGHDAM , SHAHRIAR PAYAB , MOHAMMAD BARZEGAR JALALI , KHOSRO ADIBKIA
DRUG APPLIED RESEARCH CENTER AND FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
The purpose of the present study was to formulate and evaluate the physicochemical characteristics of methylprednisolone
acetate -Eudragit® RS100 nanofibers (NFs) and nanobeads (NBs). The NFs and NBs of methylprednisolone with eudragit®
RS100 were prepared using electrospinning technique (1). The effect of several process parameters, i.e., drug/polymer ratio
and polymer concentration were considered on the size of the nanoformulations. The physicochemical and morphological
characteristics of them were evaluated as well. X-Ray crystallography and Differential Scanning Calorimetry studies indicated
that the drug crystallinity was notably reduced during the process of electrospinning. FT-IR analysis did not indicate significant
interaction between drug and polymer. In vitro drug release studies of prepared electrospuns showed faster drug release
pattern compared to the pure drug. The release data were best fitted to the Weibull model and the corresponding shape factor
value of the model were less than 0.75, indicating diffusion-controlled drug release. According to this findings, formulation of
the methylprednisolone–eudragit® RS100 NFs and NBs was able to modify the physicochemical characteristics of the drug and
may well increase the efficacy of drug. In conclusion, electrospinning could be considered as a simple, surfactant free and cost
effective method for fabricating the drug-polymer nanofibers and nanobeads.
1. Matthews JA, Wnek GE, Simpson DG, Bowlin GL. Electrospinning of collagen nanofibers. Biomacromolecules. 2002;3(2):2328.
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PP 113 PHYSICOCHEMICAL CHARACTERIZATION OF METHYLPREDNISOLONE ACETATE-PLGA NANOPARTICLES PREPARED VIA
ELECTROSPRAYING METHOD
AZIN JAHANGIRI 1, YOUSEF JAVADZADEH 2, SHAHRIAR PAYAB 2, POOYA NOORIZADEH 2, KHOSRO ADIBKIA 2
1
2
STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
BIOTECHNOLOGY RESEARCH CENTER AND FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
The objective of this study was to formulate methylprednisolone acetate - PLGA nanoparticles via electrospraying method (1).
The electrospuns prepared with different drug: polymer ratios and the various polymer solution concentrations. Physicochemical
properties, morphological features and particle size of prepared nanoparticles were evaluated as well. Laser particle size
analyzer and scanning electron microscopy was benefited to study particle size and morphology. The drug crystallinity was
investigated using X-Ray crystallography and differential scanning calorimetry. Fourier transform infrared spectroscopy was
employed to detect any possible interaction between the drug and polymer during the preparation process. The optimum
nanobeads with smooth surfaces and particle size of (164 ± 48nm) were prepared using drug: polymer ratio of 1:5 and the
polymer solution concentration of 10%. The drug crystallinity was decreased notabely in the PLGA contained electrospuns and
no chemical interaction between the drug and polymer molecules was detected. All the fabricated formulations illustrated
sustained drug release profiles compared to the pure drug and physical mixtures. Considering these findings, it was concluded
that electrospraying is a simple and cost effective method for preparing the controlled release drug-polymer nano/micro
particles.
1. Bock N, Dargaville TR, Woodruff MA. Electrospraying of polymers with therapeutic molecules: State of the art. Progress in
Polymer Science. 2012;37(11):1510-51.
PP 114 EFFECTIVE FACTORS ON SALT SELECTION IN PHARMACEUTICAL INDUSTRIES
AZIN JAHANGIRI 1, FARNAZ MONAJJEMZADEH 2
1
2
STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
DEPARTMENT OF PHARMACEUTICAL AND FOOD CONTROL, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
Selection of an appropriate salt is a crucial part of the drug development procedure and can extensively decrease the time need
for a drug substance to enter the market. Salt selection studies are typically carried out in early stages of drug development
processes. Salts are used to alter the physicochemical, biological and economical properties of a drug substance for different
purposes mainly enhancement of solubility. Moreover, they could be used for improving taste, stability, manufacturability
and bioavailability of drugs. Salt formation is the most common and effective method of increasing solubility and dissolution
rates of acidic and basic drugs. The primary step involves the determination of the ionizable groups in drug structure that
can be manipulated under the situation necessary to make salt forms. Salt screening process usually performed based on
physicochemical characteristic such as crystallinity, low hygroscopicity, suitable melting point, dissolution rate, solubility,
stability and bioavailability. If the proper salt is selected, following development will be facilitated. Here, we are going to discuss
importance of salt selection and how it is performed with case studies, also factors that affecting the rational salt selection
process for drug candidates.
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PP 115 FREE RADICAL SCAVENGING, METAL CHELATING ACTIVITIES AND REDUCING POWER OF PLANTAGO LANCEOLATA
EXTRACTS
SENATOR ABDERRAHMANE , LAOUICHA SALIHA , MESSAOUDI DALILA , KADA SEOUSSEN , BOURICHE HAMAMA
LABORATORY OF APPLIED BIOCHEMISTRY, UNIVERSITY SETIF 1, ALGERIA
This study aims to detect the in-vitro antioxidant capacity of the methanolic and aqueous extracts of the aerial part of plantago
lanceolata, a plant from the Algerian pharmacopeia, and to estimate its phenolic and flavonoid content. Total phenolic and
flavonoid content was estimated by Folin-Ciocalteau’s reagent and Aluminium chloride colorimetric method, respectively. The
antioxidant activity was determined by using DPPH, metal chelating and reducing power assays. Results showed that methanolic
extract contains total polyphenols and flavonoids more than the aqueous extract. Compared to the synthetic antioxidant BHT,
used as standard antioxidant, aqueous and methanolic extracts exhibited high antiradical activity against the free radical DPPH,
with IC50 of 38.94 ± 0.83 and 66.44 ± 1.04 µg/ml, respectively. This activity was increased with the increasing concentration
and became stable when it reached 86% and 80%, respectively. Moreover, the aqueous and methanolic extracts showed a
good concentration-dependent chelating activity with IC50 of 53.61 ± 1.51 mg/ml and 105.78 ± 14.56 mg/ml, respectively. At
the same concentration (200µg/ml), the aqueous extract exerted an important chelating effect (95%), whereas methanolic
extract showed only 71%. These values are lower than that of EDTA, used as standard chelator. Both extracts showed a good
concentration-dependent reducing power, with IC50 of 52.27 ± 5.64 µg/ml and 54.54 ± 0.82 µg/ml, respectively. These findings
suggest that Plantago lanceolata extracts possess phenolic and flavonoid constituents that are responsible for antioxidant
activity and may be exploited as biopreservatives in food applications and in traditional medicinal use.
PP 116 ANTIBACTERIAL ACTIVITY OF ALGERIAN PLANTAGO LANCEOLATAL
ZERROUG MOHAMED MİHOUB 1, LAOUİCHA SALİHA 2, BOURİCHE HAMAMA 2, SENATOR ABDERRAHAMANE 2
1
2
LABORATORY OF APPLİED MİCROBİOLOGY, FACULTY SNV, UNIVERSITY FERHAT ABBAS SETİF 1, ALGERİA
LABORATORY OF APPLİED BİOCHEMİSTRY, FACULTY SNV, UNIVERSITY FERHAT ABBAS SETİF 1, ALGERİA
The aim of this work is to evaluate the anti-bacterial activity of the extracts of the aerial part of Plantago lanceolata L, known
in Algeria under the name of El-Lisan -Haml. This herb is known in traditional medicine for the astringent, healing, antiinflammatory and antitussive. The antibacterial activity of methanol and aqueous extracts of P. lanceolata was evaluated by
the agar diffusion disc technique against 6 Gram negative bacterial strains (Pseudomonas aeruginosa ATCC 27853, Escherichia
coli ATCC 25922, Salmonella typhimurium ATCC 13311, Acinetobacter baumannii ATCC 19606, Proteus mirabilis ATCC 35659
and Klebsiella pneumoniae ATCC 700603) and 4 strains Gram positive (Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC
10876, Enterococcus faecalis ATCC 49452 and Listeria monocytogenes ATCC 15313). Both extracts were used at a concentration
of 100 mg/ml. The results of antibacterial activity revealed that the aqueous extract inhibited the growth of four bacterial strains.
at has Considerable antibacterial effect was obtained against Proteus vulgaris and Salmonella typhimurium with inhibition
zones of 13.11±0.38 and 19.78±0.19 mm respectively. Pseudomonas aeruginosa and Bacillus cereus were less sensitive; zones
of inhibition were 8.0±0.0, and 7.32±0.58 mm (p<0.05). respectively. The effect of aqueous extract was more important than
the amocixilline (Amox), used as reference. The methanol extract inhibited the growth of Salmonella typhimurium with zone of
inhibition 16.72±1.68, but was less effective against Proteus vulgaris and Listeria monocytogenes which their zones of inhibition
were 11.44±0.20 and 8.0±0.0 (p<0.05) respectively.
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PP 117 FORMULATION AND OPTIMIZATION OF PLGA NANOPARTICLES CONTAINING AZITHROMYCIN USING BOX–BEHNKEN
DESIGN
TAYEBEH GHARİ 1, SEYED ALİREZA MORTAZAVİ 1, MOHAMMAD REZA KHOSHAYAND 1, KAMBİZ GİLANİ 1, FARZAD KOBARFARD 1
SHAHİD BEHESHTİ UNIVERSITY OF MEDİCAL SCİENCES, TEHRAN, IRAN
SHAHİD BEHESHTİ UNIVERSITY OF MEDİCAL SCİENCES, TEHRAN, IRAN
3
TEHRAN UNIVERSITY OF MEDİCAL SCİENCES, TEHRAN, IRAN
4
TEHRAN UNIVERSITY OF MEDİCAL SCİENCES, TEHRAN, IRAN
5
SHAHİD BEHESHTİ UNIVERSITY OF MEDİCAL SCİENCES,TEHRAN, IRAN
1
2
The aim of this study was the preparation, optimization, and in vitro evaluation of Azithromycin (AZI) encapsulated nanoparticles
to overcome the problems associated with the treatment of pneumonia, chronic obstructive pulmonary disease, and cystic
fibrosis and to improve the AZI dissolution rate (1-2). To achieve these goals, AZI-loaded poly(DL-lactide-co-glycolide) (PLGA)
nanoparticles were prepared using the nanoprecipitation method and characterized. The Box–Behnken design (BBD) was
employed to optimize the effects of different variables on particle size and drug encapsulation efficiency of nanoparticles.
The results of optimized formulations showed a polydispersity index of 0.06%, an average diameter of 183 ± 1.8 nm, and
encapsulation efficiency of 57.83 ± 4.8 %. The prepared particles had spherical shape, and the in vitro drug release profile
showed a biphasic pattern, showing an initial burst release of 23% in the first 2 h followed by a sustained release for up to 24 h.
1. Yousef AA, Jaffe A. The Role of Azithromycin in Patients with Cystic Fibrosis. Paediatr Respir Rev. 2010;11:108-14. 2. Sakito O,
Kadota J, Kohno S, Abe K, Shirai R, Hara K. Interleukin 1 beta, tumor necrosis factor alpha, and interleukin 8 in bronchoalveolar
lavage fluid of patients with diffuse panbronchiolitis: a potential mechanism of macrolide therapy. Respiration. 1996;63:42-8.
PP 118 AN ETHNOBOTANICAL STUDY OF ANTI-RHEUMATIC PLANTS IN THE REGIONS OF SIDI BEL ABBES, IN THE NORTH OF
ALGERIA
SELKA MOHAMMED ADIL 1, ACHOURI MOHAMMED YACINE 2
LABORATORY OF PHARMACOGNOSY, DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE SID BEL ABBES, ALGERIA.
LABORATORY OF PHARMACEUTICAL BIOPHYSICS ,DEPARTMENT OF PHARMACY, FACULTY OF MEDICINE SID BEL ABBES,
ALGERIA
1
2
Rheumatism is a group of very various diseases that affect the joints and sometimes causes unbearable and disabling pains Non
steroidal anti-inflammatory drugs (NSAIDs) and analgesics are their main treatment but they can cause very dangerous side
effects like ulcers and gastrointestinal bleeding, however traditional herbal remedies without side effects exist and can treat
advantageously these diseases(1). This work ames to make an to make an inventory of anti rheumatic plants in the region of Sidi
Bel Abbes, in the north of Algeria. Two ethnobotanical studies were conducted, one with Sidi Bel Abbes population ( n = 200)
and the other with the herbalists of the same region (n = 16). The results showed that Inula viscosa was the most used plant
(35.71%). Followed by Origanum vulgare (19.04%), Anacyclus pyrethrum (14.28%), Eugenia caryophyllata (14.2%) and Ortica
dioica (14, 10%). Leaves are the most used parts (57.72%) , infusion and poultice are the most used modes. As an exemple,
Some Magistral Preparations were made from plants found in the studie: nettle tincture of oregano oil, poultice made of clove
and Tincture of nettle. This study helped to identify 42 different species of medicinal plants used by the population and the
herbalists of Sidi Bel Abbes. The main action of these species being the treatment of rheumatism, for their anti-inflammatory
and analgesic effects. The majority of identified plants could be a potential treatment against this disease.
1. Anton R. Plantes médicinales traditionnelles: suppléments alimentaires et (ou)médicaments. Des sources du savoir aux
médicaments du futur. IRD Editions.
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PP 119 EFFECT OF IONIC SURFACTANTS ON THE ACTIVATED CARBON ADSORPTION OF DRUGS
ELIF CALISKAN SALIHI 1, MEHMET MAHRAMANLIOGLU 2
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, HAYDARPASA,
ISTANBUL, TURKEY
2
ISTANBUL UNIVERSITY, ENGINEERING FACULTY, CHEMISTRY DEPARTMENT, AVCILAR, ISTANBUL, TURKEY
1
The adsorption techniques employing solid sorbents are widely used to remove certain classes of chemical pollutants from waters,
especially those that are hardly destroyed in conventional wastewater treatment plants (1). Surfactants and other amphiphiles
are known to influence the adsorption of many compounds and may be present in the environment from wastewaters or
other sources (2). The work described here examines the adsorption of three drugs; trimethoprim [TM], carbamazepine [CM],
ibuprofen [IBU]; onto activated carbon in aqueous solutions and in the presence of different type of surfactants such as anionic;
sodiumdodecyl sulfate and cationic; dodecyltrimethylammonium bromide. The adsorption experiments were carried out as a
function of time and initial concentration; and also performed in the presence of surfactants at the concentrations below and
above the critical micelle concentrations. The adsorption capacity values found for the adsorption of drugs in aqueous solutions
followed the order: TM < CM < IBU. It was observed that the presence of surfactants caused a decrease in adsorption capacities,
without affecting the equilibrium time of the adsorption processes for all drugs used.
1. Janoš P, Šmídová V. Effects of surfactants on the adsorptive removal of basic dyes from water using an organomineral
sorbent-iron humate. J Colloid Interf Sci. 2005;291:19-27. 2. Hari A C, Paruchuri R A, Sabatini D A, Kibbey T C G. Effects of pH
and cationic and nonionic surfactants on the adsorption of pharmaceuticals to a natural aquifer material. Environ Sci Technol.
2005;39(8):2592-2598.
PP 120 CHEMICAL REGENERATION OF ACTIVATED CARBON LOADED WITH PHARMACEUTICALS
ELIF CALISKAN SALIHI 1, MEHMET MAHRAMANLIOGLU 2
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, HAYDARPASA,
ISTANBUL, TURKEY
2
ISTANBUL UNIVERSITY, ENGINEERING FACULTY, CHEMISTRY DEPARTMENT, AVCILAR, ISTANBUL, TURKEY
1
The major drawback for wastewater treatment utilization comes from economic consideration. The commercial activated
carbons are expensive, rendering its infeasibility for large scale operation (1). Regeneration is normally cheaper than replacement
and chemical regeneration is attractive because it can be done relatively rapid in situ and no carbon attrition or pore structure
degradation occurs compared with other methods (2). The aim of this study is to investigate the regeneration of activated
carbon (AC) exhausted with promethazine hydrochloride (PM) using alcohols. AC was loaded with the pharmaceutical using an
excess of a highly concentrated PM solution, as described in elsewhere (3). Desorption of PM as a function of time was studied
with diffrent alcohols and alcohol/water mixtures of several ratios. Maximum desorption was obtained in 24 hours by using the
mixture of isopropanol/water. The changes in regeneration efficiencies after successive adsorption-regeneration cycles were
also compared.
1. Putra E K, Pranowo R, Sunarso J, Indraswati N, Ismadji S. Performance of activated carbon and bentonite for adsorption
of amoxicillin from wastewater: Mechanisms, isotherms and kinetics. Water Research. 2009;43:2419-2430. 2. Lu P J, Lin HC,
Yu W T, Chern J M. Chemical regeneration of activated carbon used for dye adsorption. Journal of the Taiwan Institute of
Chemical Engineers. 2011;42,305-311. 3. Caliskan E, Bermudez J M, Parra J B, Menendez J A, Mahramanlioglu M, Ania C O. Low
temperature regeneration of activated carbons using microwaves: Revising conventional wisdom. Journal of Environmental
Management. 2012;102:134-140.
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PP 121DESIGN AND OPTIMISATION OF TRANSDERMAL FORMULATIONS CONTAINING BETAHISTINE
SEVINÇ ŞAHBAZ , BETÜL DORTUNÇ
FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, MARMARA UNIVERSITY, 34668 HAYDARPAŞA,
ISTANBUL, TURKEY
Betahistine (BH), used in the treatment of Méniѐre’s syndrome, is a good candidate for transdermal delivery because of its low
molecular weight (209,1), short elimination half life (3-5 hours), low daily dosage range (24-48 mg), frequent dosing regimen (3
times a day) and liquid state. Furthermore the drug is contraindicated in the presence of peptic ulcer (1). The aim of this study
is to prepare and optimise transdermal formulations of BH. To prepare the formulations, FDA approved polymers, Eudragit RL
100 and Eudragit RS 100, were chosen as matrix forming polymers which are widely used in controlled release dosage forms
(2). Formulations were prepared using different ratios of these two polymers and as the polymers do not have the elasticity
needed, triethyl citrate (TEC), polyethylene glycol (PEG) 400, glycerine, propylene glycol were tested as plasticisers. Acetone and
ethanol were preferred as solvents and the drug BH was used in different amounts. All the ingredients were evaluated for their
excipient- drug compatibility using Differantial Scanning Calorimetry (DSC) tests (3). Solvent evaporation technique was used for
preparing the formulations and they were evaluated for their macroscopic properties (general appearance, transparency, color,
softness, homogeneity and flexibility). Results of all these parameters were examined and optimal ratios were determined.
1. Martindale The Extra Pharmacopoeia. 34th ed. London: The Pharmaceutical Press; 2005. 2. Gao Y, Liang J, Liu J, Xiao Y.
Double-layer weekly sustained release transdermal patch containing gestodene and ethinylestradiol. Int. J. Pharm. 2009; 377
(1-2): 128-134. 3. Verma PRP, Chandak AR. Development of matrix controlled transdermal delivery systems of pentazocine: In
vitro/in vivo performance. Acta Pharm. 2009; 59: 171–186.
PP 122 BIOPHYSICAL STUDIES OF RESPONSIVE DNA BLOCK CO-POLYMER CONJUGATES
GÖKÇEN YAŞAYAN 1, JOHANNES P. MAGNUSSON 2, STEPHANİE ALLEN 2, MARTYN C. DAVİES 2, CAMERON ALEXANDER 2
1
2
DEPARTMENT OF PHARMACEUTİCAL TECHNOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
SCHOOL OF PHARMACY, UNIVERSITY OF NOTTİNGHAM, NOTTİNGHAM, UK
Nucleic acid nanotechnology offers a range of possibilities for new materials with sophisticated functions. Information encoded
into DNA-and RNA-based materials can encompass not only biological signals, but also structural and architectural function.
Pioneering work by Seeman and others has shown that synthetic structures of great complexity can be assembled by reprogramming DNA assembly modes. (1) This study aims to investigate the solution properties of two novel multi-responsive
DNA-polymer conjugates. These materials combine “smart” thermoresponsive tri(ethylene glycol) ethyl ether methacrylate
chains and oligomeric nucleic acids with ‘toehold’ sequences. DNA strand displacement could be modulated by toehold
sequences via hybridisation. Toehold sequences, or sticky ends, are short single stranded DNA segments that placed to a DNA
strand. (2, 3) Characterisation studies of DNA-polymer conjugates were carried mainly by a biophysical technique, AFM, to have
information of conjugate properties in solution at the nanoscale. Solution behaviours of the conjugates were probed, including
DLS and zeta potential measurements. All these techniques have been used to characterise the changes in conformation of the
conjugates as they can be ‘switched’ by a) temperature changes, b) addition of DNA strands designed to disrupt self-assembly.
1. Chakraborty B, Sha RJ, Seeman NC. A DNA-based nanomechanical device with three robust states. Proceedings Of The National
Academy Of Sciences Of The United States Of America. 2008;105(45):17245-9. 2. Kuzuya A, Komiyama M. DNA origami: Fold,
stick, and beyond. Nanoscale. 2010;2(3):310-22. 3. Chakraborty B, Sha R, Seeman NC. A DNA-based nanomechanical device with
three robust states. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(45):17245-9.
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PP 123 ACTIVATION OF AMPK BY A769662 ATTENUATES LPS INDUCED ACTIVATION OF NEUTROPHILS IN LUNG IN RAT
MARYAM RAMESHRAD 1, ALIREZA GARJANI 2, NASRIN MALEKI-DIZAJI 2, HAMID SORAYA 3, HALEH VAEZ 2
STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
3
DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, URMIA UNIVERSITY OF MEDICAL SCIENCES, URMIA, IRAN
1
2
Activation of AMP-activated protein kinase (AMPK) has been shown to have anti-inflammatory effects. In this study, we
determined the effects a direct activator of AMPK, A769662, on LPS induced lung injury. Wistar rats were randomly assigned to
one of 3 groups (n=3): normal control was given vehicle, ip; lipolysaccharide (LPS; 0.5 mg/kg), and LPS (0.5 mg/kg) plus A769662
(10 mg/kg). After 9 hours, the heart and lung were removed. Ordinary ANOVA with LSD post-hoc test was used to compare the
groups. Compared with control, MPO activity in lung and percentage of neutrophil in peripheral blood markedly were high in
LPS group (p<0.001). A769662 significantly decreased both the elevated MPO activity in lung and neutrophil count in peripheral
blood (p<0.05 and p<0.01; respectively). Intraperitoneal LPS injection increased the level of MyD88 (p<0.05) in heart but not
lung tissue. In comparison to LPS group, administration of A769662 resulted in activation of AMPK (p<0.001) with reduction in
MyD88 (p<0.01) level in the heart without any effects on the level of these markers in lung. Totally, LPS in i.p, triggers a signal
at systemic or lung level, leading to the accumulation of neutrophils in peripheral and pulmonary vasculature, but failing to
induce a full signal at the epithelial level (2) to increase the MyD88 as LPS receptor, what we see in heart. Activation of AMPK
in cardiovascular by A769662 attenuates neutrophil activity and could decrease the severity of LPS lung injury. In this regard,
AMPK activation could become a valid therapeutic target in endotoxemia.
PP 124 ENDOTOXIN TREATMENT IN ISOLATED RAT HEART: TNF-α RISE DUE TO ACTIVATION OF MYD88
MARYAM RAMESHRAD 1, ALIREZA GARJANI 2, NASRIN MALEKI-DIZAJI 2, HALEH VAEZ 2, HAMID SORAYA 3, AILAR NAKHLBAND 4
GIFTED AND TALENTED STUDENT SUPPORTING UNIT, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
2
DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
3
DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, URMIA UNIVERSITY OF MEDICAL SCIENCES, URMIA, IRAN
4
RESEARCH CENTER FOR PHARMACEUTICAL NANOTECHNOLOGY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
1
Lipopolysaccharide (LPS) Binding Protein (LBP) bound endotoxins are recognized by CD14/ toll-like receptor-4 (TLR4)-MD-2
complex in innate immune cells which delivers a signal through the plasma membrane and stimulate TNF-α release when the
immune system is intact (1). This study is designed to answer whether isolated rat heart, which is detached from the immune
system, is capable of producing TNF-α through TLR4 activation. Using langendorff method, LPS in 120 ml of the modified Krebs–
Henseleit-buffer (KHBS) at final concentration of 1µg/ml was perfused at recycling mood for 120, 180, 240, 300, and 360min
in separate groups. In the other protocol to evaluate the effect of LBP and CD14 in presenting LPS to its receptor, KHBS was
supplemented with fetal-bovine-serum (FBS) 2% and method was repeated for 180 min. To assess the TOLR4 activity and TNFα
release, ELISA, western blotting, real time-PCR were used. Compared with control, LPS time dependently increased the level of
myocardial TLRs adapter-protein, MyD88 (p<0.05) and TNF-α (p<0.05) content of heart tissue during 6 hours. Supplementing
with FBS-KHBS had no significant effect on the LPS induced elevation of MyD88 and TNF-α level. The results of this study shows
for the first time that myocardial tissue is independently capable of producing TNFα probably through MYD88 activation.
1. Miyake K. Innate recognition of lipopolysaccharide by CD14 and toll-like receptor 4-MD-2: unique roles for MD-2. Int
Immunopharmacol. 2003;3(1):119-28.
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PP 125 PHYTOCHEMICAL SCREENING AND STUDY OF THE EFFECTS OF ETHANOL EXTRACT OF OCIMUM BASILICUM (BASIL)
ON CARRAGEENAN INDUCED PAW EDEMA IN RATS
MARYAM RAMESHRAD 1, RONAK SALEHIAN 1, NASRIN MALEKI-DIZAJI 2, FATEMEH FATHIAZAD 3, ALIREZA GARJANI 2, SANAZ
HAMEDEYAZDAN 1
STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
3
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
1
2
The objectives of the present study were phytochemical screening and study of the effects of ethanol extract of Ocimum
basilicum (basil) on carrageenan induced paw edema in rats. The leaves of the plant were extracted with ethanol by maceration
and subjected to colorimetry to determine flavonoids and phenolic compounds. The animals received an intraperitoneal (i.p)
injection of Ocimum basilicum extracts (2.5, 5, 10 mg/kg) 1 hr before subcutaneous (s.c) injection of carrageenan 1% (w/v) in
the left paw were compared with control group. Data were expressed as a percentage of increase in the paw thickness and
were compared with those of pre-injection values. Myeloperoxidase (MPO) activity was determined, and a histopathological
study was carried out in paw tissue 4 hr after induction of inflammation. Phytochemical screening indicated the presence of
phenolic compounds (7.34 %) and flavonoids (1.9%). All doses of extract significantly reduced maximum paw thickness after the
induction of inflammation (p < 0.001) and inducted a marked reduction in MPO activity (p<0.01, p<0.001, p<0.001: respectively)
compare to the control group. Histological examination showed a marked reduction in tissue edema and inhibition leucocyte
infiltration in treated rats. The results of the study demonstrate that Ocimum basilicum strongly reduced the inflammation of
carrageenan-injection and suggest that the anti-inflammatory effects could be related to inhibition leucocyte infiltration.
PP 126 SYNTHESIS, BIOLOGICAL ACTIVITY AND MOLECULAR DOCKING STUDIES OF NOVEL 3-(SUBSTITUTED-BENZYLIDENE)5-(4-FLUOROPHENYL)INDOLIN-2-ONE DERIVATIVES AS INHIBITORS OF C-SRC TYROSINE KINASE
ZÜHAL KİLİC-KURT 1, FİLİZ BAKAR 2, SÜREYYA ÖLGEN 1
1
2
DEPARTMENT OF PHARMACEUTİCAL CHEMİSTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY
DEPARTMENT OF BİOCHEMİSTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY
The c-Src is a member of the largest family of nonreceptor protein tyrosine kinase (1). c-Src plays an important role in the signal
transduction pathways that regulates cancer cell proliferation, apoptosis and angiogenesis. Therefore c-Src has became potential
target for many cancers including colon, breast, lung, ovary, and prostate (2). In the present work, we describe the preparation of
novel 3-(substituted-benzylidene)-5-(4-fluorophenyl)indolin-2-one derivatives and their c-Src tyrosine kinase inhibitory activity.
In addition, the molecular docking study for these compounds carried out by Autodock vina to evaluate the relationships between
their structures and binding properties with active site of c-Src kinase. For the synthesis of target compounds, 5-iodo indolin2-one were obtained by a Wolff–Kishner reduction of 5-iodoisatin. Synthesis of 5-(4-fluorophenyl)indolin-2-one was achieved
by palladium-catalyzed Suzuki cross-coupling reaction of 5-iodo indolin-2-one with p-fluorophenylboronic acid. Finally, target
compounds was obtained by condensation of 5-(4-fluorophenyl)indolin-2-one with substituted benzaldehydes in ethanol at
reflux. The activity results showed that among the synthesized compounds, 3-(4-chloro benzylidene)-5-(4-fluorophenyl) indolin2-one, 5-(4-fluorophenyl)-3-(4-methoxy benzylidene) indolin-2-one and 3-(4-(dimethylamino) benzylidene)-5-(4-fluorophenyl)
indolin-2-one showed good inhibitory activities with IC50 values of 10.08 µM, 1.98 µM and 1.02 µM. According to the docking
results, all of compounds located in the active site of c-Src kinase. Among the active compounds only the best active compound
(3-(4-(dimethylamino) benzylidene)-5-(4-fluorophenyl) indolin-2-one) created a hydrogen bond between indole nitrogen and
carbonyl oxygen of the Met 341. Therefore, this study provides new promising compounds with good enzymatic inhibitory
activities for further development of new anticancer drugs targeting c-Src tyrosine kinase.
1. Zhang S, Yu D. Targeting Src family kinases in anti-cancer therapies: turning promise into triumph. Trends in Pharmacological
Sciences. 2012; 33(3): 122-128. 2. Edwards J. Src kinase ınhibitors: an emerging therapeutic treatment option for prostate
cancer. Expert Opin. Investig. Drug. 2010; 19(5): 605-614.
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PP 127 NOVEL INDOLIN-2-ONE DERIVATIVES AS C-SRC TYROSINE KINASE INHIBITORS: SYNTHESIS, BIOLOGICAL EVALUATION
AND MOLECULAR DOCKING STUDY
ZÜHAL KILIC-KURT 1, FILIZ BAKAR 2, SÜREYYA ÖLGEN 1
1
2
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY
DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, ANKARA UNIVERSITY
Protein kinases are important targets in cancer. c-Src kinase is a member of nonreceptor tyrosine kinase, known as the ‘Src
family of kinases’ (SFKs) (1). Aberrantly activated c-Src lead to development of cancer, including lung, prostate, and breast
(2). Inhibition of Src and SFKs therefore represents a logical strategy for investigation in the treatment of cancer (3). In this
study, synthesis, biological activities and molecular docking studies of novel indolin-2-one derivatives as inhibitors of c-Src
are described. Synthesis of the title compounds, firstly, indolin-2-one was prepared by a Wolff-Kishner reduction of isatine.
5-Nitro indolin-2-one was synthesized by nitration of indolin-2-one. Subsequent catalytic hydrogenation led to 5-amino indolin2-one. Reaction of 5-amino indolin-2-one with ethylisocyanate and benzylisothiocyanate afforded the 1-ethyl-3-(2-oxoindolin5-yl)urea and 1-benzyl-3-(2-oxoindolin-5-yl)thiourea. Condensation of these ureidoindolin-2-ones with various benzaldehyde
afforded the target compounds. An array of 16 diversely 3,5-disubstituted indolin-2-ones was evaluated against c-Src. Among
the screened compounds, 1-ethyl-3-(3-(4-fluoro benzylidene)-2-oxoindolin-5-yl) urea, 1-benzyl-3-(3-(4-carboxy benzylidene)2-oxoindolin-5-yl) thiourea, 1-benzyl-3-(3-(4-fluoro benzylidene)-2-oxoindolin-5-yl) thiourea and 1-benzyl-3-(3-(2,4-difluoro
benzylidene)-2-oxoindolin-5-yl) thiourea showed good inhibition with IC50 values of 2.06, 2.01, 1.38 and 1.24 µM. Docking
simulation was performed to synthesized compounds into the c-Src active site to determine the probable binding conformation.
By the dock results, it was determined that all compounds located into active site of c-Src and exhibited the good binding
affinities into c-Src with hydrogen bonds. For the best active compound (1-benzyl-3-(3-(2,4-difluoro benzylidene)-2-oxoindolin5-yl) thiourea), one hydrogen-bond interaction with OH of Thr 338 was found by carbonyl group of indole ring. This study
provides insights for further optimizing of indolin-2-ones for the discovery of the c-Src kinase inhibitors.
1. Lieu C, Kopetz S. The Src Family of protein tyrosine kinases: a new and promising target for colorectal cancer therapy. Clinical
Colorectal Cancer. 2010; 9: 89-94. 2. Lee K, Kim J, Jeong K-W, Lee KW, Lee Y, Song JY, Kim MS, Lee GS, Kim Y. Structure-based
virtual screening of Src kinase inhibitors. Bioorg. Med. Chem. 2009; 17: 3152-3161. 3. Saad F, Lipton A. SRC kinase inhibition:
Targeting bone metastases and tumor growth in prostate and breast cancer. Cancer Treatment Reviews. 2010; 36: 177-184.
PP 128 SYNTHESİS OF PLATINUM(II) COMPLEXES OF 2-CYCLO-SUBSTITUEBENZİMİDAZOLE AND THEİR CYTOTOXİC EFFECTS
AZIME BERNA OZCELIK 1, FATMA GUMUS 1, RAHSAN ILIKCI SAGKAN 2, UGUR MUSABAK 2
1
2
GAZI UNIVERSITY, ANKARA, TURKEY
UNIVERSITY OF GULHANE MILITARY MEDICINAL ACADEMIA, ISTANBUL, TURKEY
In clinical practice, platinum-based complexes are most widely used for the treatment of cancer.1 Cisplatin, Carboplatin and
Oxaliplatin are used for treating various types of cancer, including genitourinary, colorectal and non-small cell lung cancer.2
However, the clinical success of cisplatin is limited by severe side effect and intrinsic and acquired drug resistance.3 One
strategy to overcome cisplatin resistance is to design new platinum complexes that specifically deal with some or even all of
the resistance mechanism.1 In the present study, to investigate the role of the hydrophobic substituents on position 2 of the
benzimidazole carrier ligands, cis or trans Pt(II) complexes having 2-cycloalkylsubstitutedbenzimidazole carrier ligands were
synthesized and evaluted for their preliminary in vitro cytotoxic activities against OVCAR-3 and HeLa cell lines. We also report
the effect of the most activite compound among the tested compounds on the cell cycle modification and apoptosis.
1. Rosenberg B, Van Camp L, Trosko JE, Mansour V H. Platinum compounds: a new class of potent antitumour agents. Nature
1969;222:385-386. 2. Jung Y, Lipard SJ. Direct cellular responses to platinum-induced DNA damage. Chem Rev 2007; 107:13871407 3. Farrell N, Qu, Y, Hacker, M. P. Cytotoxicity and antitumor activity of bis(platinum) complexes. A novel class of platinum
complexes active in cell lines resistant to both cisplatin and 1,2-diaminocyclohexane complexes. J. Med. Chem. 1990,33: 2179–
2184.
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PP 129 ERLOTINIB LOADED POLYMERIC NANOPARTICLES: SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY EVALUATION
LEILA BARGHI 1, HADI VALIZADEH 2, DAVOUD ASGARI 2, JALEH BARAR 3
FACULTY OF PHARMACY AND STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
3
RESEARCH CENTER FOR PHARMACEUTICAL NANOTECHNOLOGY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
1
2
Development of polymeric nanoparticles of erlotinib hydrochloride was the main objective of this study. For this purpose
poly caprolactone - poly ethylene glycol - poly caprolactone (PCEC) copolymers with different composition were synthesized
via ring opening polymerization. Formation of these triblock copolymers was confirmed by HNMR as well as FT-IR. Erlotinib
loaded nanoparticles were prepared by means of synthesized copolymers via solvent displacement method. Physicochemical
properties of obtained polymeric nanoparticles depend on composition of used copolymers. Size of particles decreased with
decreasing the PCL/PEG molar ratio in used copolymers. Loading efficiency of prepared formulations is declined by decreasing
their particle size. The release behavior of erlotinib from the polymeric nanoparticles exhibited a sustained pattern without any
burst release. From the release profiles, it can be found that erlotinib release rate from polymeric nanoparticles decrease with
an increase of CL/PEG molar ratio of used block copolymers. Based on MTT assay results, cell growth inhibition of erlotinib has a
dose and time dependent pattern. After 72 hours of exposure, the 50% inhibitory concentration (IC50) of erlotinib hydrochloride
was appeared to be 14.8 μM. From the results obtained, it can be concluded that the prepared PCEC nanoparticles in this study
might have the potential to be considered as novel delivery system for erlotinib.
PP 130 ANTIBACTERIAL ACTIVITY OF ALGERIAN PLANTAGO LANCEOLATA L
MOHAMED MIHOUB ZERROUG 1, SALIHA LAOUICHA 2, ABDERRHAMANE SENATOR 2, HAMAMA BOURICHE 2
1
2
LABORATORY OF APPLIED MICROBIOLOGY, FACULTY SNV, UNIVERSITY FERHAT ABBAS SETIF 1, ALGERIA
LABORATORY OF APPLIED BIOCHEMISTRY, FACULTY SNV, UNIVERSITY FERHAT ABBAS SETIF 1, ALGERIA
The aim of this work is to evaluate the anti-bacterial activity of the extracts of the aerial part of Plantago lanceolata L, known
in Algeria under the name of El-Lisan -Haml. This herb is known in traditional MEDICINE for the astringent, healing, antiinflammatory and antitussive. The antibacterial activity of methanol and aqueous extracts of P. lanceolata was evaluated by
the agar diffusion disc technique against 6 Gram negative bacterial strains (Pseudomonas aeruginosa ATCC 27853, Escherichia
coli ATCC 25922, Salmonella typhimurium ATCC 13311, Acinetobacter baumannii ATCC 19606, Proteus mirabilis ATCC 35659
and Klebsiella pneumoniae ATCC 700603) and 4 strains Gram positive (Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC
10876, Enterococcus faecalis ATCC 49452 and Listeria monocytogenes ATCC 15313). Both extracts were used at a concentration
of 100 mg/ml. The results of antibacterial activity revealed that the aqueous extract inhibited the growth of four bacterial strains.
at has Considerable antibacterial effect was obtained against Proteus vulgaris and Salmonella typhimurium with inhibition
zones of 13.11±0.38 and 19.78±0.19 mm respectively. Pseudomonas aeruginosa and Bacillus cereus were less sensitive; zones
of inhibition were 8.0±0.0, and 7.32±0.58 mm (p<0.05). respectively. The effect of aqueous extract was more important than
the amocixilline (Amox), used as reference. The methanol extract inhibited the growth of Salmonella typhimurium with zone of
inhibition 16.72±1.68, but was less effective against Proteus vulgaris and Listeria monocytogenes which their zones of inhibition
were 11.44±0.20 and 8.0±0.0 (p<0.05) respectively.
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PP 131 INFLUENCE OF THE PH AND BUFFER CONCENTRATION ON THE AGGREGATION OF HUMAN ALPHA INTERFERON IN
AQUEOUS SOLUTION
FARANAK SALMANNEJAD 1, NASTARAN NAFISSI-VARCHEH 2, ALIREZA SHAFAATI 3, REZA ABOOFAZELI 1
DEPARTMENT OF PHARMACEUTICS, SCHOOL OF PHARMACY, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN,
IRAN
2
DEPARTMENT OF PHARMACEUTICAL BIOTECHNOLOGY, SCHOOL OF PHARMACY,SHAHID BEHESHTI UNIVERSITY OF MEDICAL
SCIENCES, TEHRAN, IRAN
3
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, SCHOOL OF PHARMACY, SHAHID BEHESHTI UNIVERSITY OF MEDICAL
SCIENCES, TEHRAN, IRAN
1
Stabilization protein molecules in order to achieve an acceptable shelf life is the most challenging obligation in the development
of protein formulations (1). Protein aggregation is one of the most common and critical manifestations of protein instabilities,
encountered in almost all stages of protein drug development (2). The aim of this study was to evaluate the effect of buffer
conditions on the aggregation propensity of recombinant human interferon alpha2b (rhIFNα2b) during thermal stress. The
protein was incubated for 1 h at 40–70 °C and for up to 240 h at 50 °C and its aggregation tendency was then studied using
different analytical methods. The effects of various pH (5, 6 and 7) and buffer concentrations (10, 55 and 100 mM) on the
aggregation of the protein following incubation at 50 °C for 72 h were also evaluated. The results obtained for samples
incubated at 50 °C for up to 240 h showed that optical density at 350 nm and the amount of higher molecular weight aggregates
increased whereas the monomer content decreased significantly (p<0.05), directly proportional to the incubation time. Data
obtained from the incubation of samples at 50 °C for 72 h showed that regardless of the buffer concentration, the percentage
of monomer at pH 6 was significantly higher than that at pH 7 and pH 5 (p<0.05). At constant pH, although not significant, the
same trend was observed when the buffer concentration increased to 100 mM. In conclusion, understanding the effects of such
factors would play a key role in rhIFNα2b stabilization and in turn the development of stable therapeutic formulations.
1. Wang W, Singh S, Zeng DL, King K, Nema S. Antibody structure, instability, and formulation. Journal of pharmaceutical sciences.
2007;96(1):1-26. 2. Wang W, Nema S, Teagarden D. Protein aggregation: pathways and influencing factors. International journal
of pharmaceutics. 2010;390(2):89-99.
PP 132 EFFECT OF METFORMIN ON LPS-INDUCED MYD88 ACTIVATION IN RAT HEARTS
HALEH VAEZ 1, MARYAM RAMESHRAD 1, ALIREZA GARJANI 2
1
2
STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
DEPARTMENT OF PHARMACOLOGY & TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL
Metformin has a protective effect in inflammatory processes through activation of AMP-activated protein kinase (AMPK). In the
present study, the effect of metformin, on Myeloid differentiation primary response 88 protein (MYD88), a signal transducer
in toll-like receptor (TLR4) pathway, and its relation with AMPK phosphorylation level, in Lipopolysaccharide (LPS) induced
inflammation is assessed in rat heart. Male Wistar rats were randomly divided in 3 groups (n= 5) and treated intraperitoneally
according to this protocol: control group received normal saline (N/S, 0.5 ml), LPS group received LPS (0.5 mg/kg in 0.5 ml N/S)
and metformin treated group received metformin (100 mg/kg) + LPS (0.5 mg/kg) in 0.5 ml N/S. Nine hours after injections hearts
were removed and the protein content of MYD88 and the ratio of AMPK phosphorylation were evaluated by western blotting.
Compared with control, LPS significantly increased MYD88 protein content in the heart (p< 0.05) and a single dose of metformin
at 100 mg/kg significantly inhibited the LPS induced MYd88 expression p (p< 0.05). Furthermore, these results were accordance
with an increase in the AMPK activation and metformin treatment significantly increased the ratio of phosphorylated AMPK
compared to LPS group (p< 0.05). Metformin with inhibitory effect on MYD88 expression can be effective in TLRs pathway
induced inflammation. The AMPK activation can be the responsible mechanism for this protective effect of metformin.
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PP 133 WHAT ARE THE EFFECTS OF HISTONE METHYLATION INHIBITOR AND/OR HISTONE DEACETYLASE INHIBITOR ON
HISTONE LYSINE TRIMETHYLATION OR ACETYLATION IN BREAST CANCER CELL LINES?
ASLIHAN DAGDEMIR 1, SEHER KARSLI-CEPPIOGLU 2, GAëLLE JUDES 1, MAUREEN ECHEGUT 1, FRéDéRIQUE PENAULT-LLORCA 1,
ANDRé LEBERT 3, YVES-JEAN BIGNON 1, DOMİNİQUE BERNARD-GALLON 1
DEPARTMENT OF ONCOGENETICS, CENTRE JEAN PERRIN, CBRV, 28 PLACE HENRI DUNANT, BP 38, 63001 CLERMONTFERRAND, FRANCE.
2
DEPARTMENT OF TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, TIBBIYE CAD. NO:49 34668 ISTANBUL,
TURKEY
3
UNIVERSITY BLAISE PASCAL, INSTITUT PASCAL UMR 6602 CNRS/UBP, AUBIèRE, FRANCE
1
The Histone Deacetylase Inhibitors (HDACi) and Histone Methylation Inhibitors (HMTi) were known to interact with epigenetic
modifications. We aimed to demonstrate the mechanisms of HDACi and HMTi on modified histones H3K27me3, H3K9ac and
H3K4ac in MCF-7 and MDA-MB-231 breast cancer cell lines. Breast cancer cell lines were treated with HMTi 3-Deazaneplanocin
A hydrochloride (DZNep) [5µM], HDACi Sodium Butyrate (NaBu) [2mM] and Suberoylanilide Hydroxamic acid (SAHA) [1μM] for
48 hours. We applied chromatin immunoprecipitation (ChIP) followed by QPCR of 6 selected genes (EZH2, BRCA1, ERa, ERb,
SRC3, P300). Western Blot was performed and mRNA levels were analyzed for each cell line. According to our results; SAHA
and NaBu increased acetylation at lysine 4 of histone H3 in MCF7 cell line and DZNep decreased methylation on H3K27me3
marks with a slight difference in MDA-MB-231 cell line. We demonstrated that DZNep acted globally and it could inhibit both
activating and repressive histone marks, while mRNA expression levels, conversely, were increased with the treatments of
NaBu and SAHA especially in MCF 7 cell line. These results suggested that HDACi and HMTi have beneficial effects on the genes,
which are upregulated in cancer; however they have adverse effects for downregulated genes, so the action did not seem to
be specific for genes. Our results add a new outlook of complication to epigenetic dysregulation in cancer and also established
histone modifications-mediated silencing or enhancing for up-and-coming therapeutic target. Our data demonstrate that
HDACi disposed to modify the transcription into the demethylation and acetylation of the histones in breast cancer cell lines.
PP 134 MOLECULAR FARMING OF TRAIL
HAMID REZA HEIDARI 1, BAHRAM KAZEMI 2, HOSSEIN NADERI-MANESH 3
STUDENT’S RESEARCH COMMITTEE AND FACULTY OF PHARMACY, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES,
TEHRAN, IRAN
2
CELLULAR AND MOLECULAR BIOLOGY RESEARCH CENTER, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN,
IRAN
3
DEPARTMENT OF BIOPHYSICS, FACULTY OF BIOLOGICAL SCIENCES, TARBIAT MODARES UNIVERSITY, TEHRAN, IRAN
1
Molecular Farming has been considered as a promising field for production of biopharmaceuticals. In this study, production
of TNF related apoptosis inducing ligand (TRAIL) has been tackled in Nicotiana tabacum using Agrobacterium Tumefaciens
LBA 4404. Initially, the desired coding sequence was obtained using PCR technique on the constructed human cDNA library;
afterward the other necessary requirements for expression of the product in plant cell system were provided through subcloning into helper and final 0179-pGreen expression vectors. The final construct was cloned into A. tumefaciens LBA 4404;
subsequently the N. tabacum cells were transformed through co-culture method. The expression of the ligand was confirmed
by western blot analysis on the total protein extract from selected N. tabacum cells. The protein of interest was extracted
through chromatographic technique and biological activity was evaluated through MTT assay. The results indicated that one
gram of N. tabacum cells can successfully produce 15µg recombinant TRAIL.
-134-
PP 135 PHENOLIC CONTENT OF NEPETA FISSA CA MEYER AND ITS ANTIPROLIFERATIVE ACTIVITY AGAINST HELA CELL LINES
FERDA ESER 1, IBRAHİM DEMIRTAS 2, SERKAN KOLDAS 2, LUTFİ BEHCET 3
FACULTY OF PHARMACY GAZIOSMANPASA UNIVERSITY, TOKAT, TURKEY
FACULTY OF CANKIRI KARATEKİN UNIVERSITY, CANKIRI, TURKEY
3
FACULTYBINGOL UNIVERSITY, BINGOL, TURKEY
1
2
The genus Nepeta (Lamiaceae) comprise about 400 species and have been used in folk MEDICINE for centuries due to its
antiseptic, astringent, anti-tussive anti-spasmodic, anti-asthmatic, anti-bacterial, antifungal, anti-viral and diuretic properties
(1). In this study, we aimed to determine the phenolic content of various extracts of N. fissa and the antiproliferative activity
of N. fissa against HeLa cell lines. For this purpose, ground and dried parts of N. fissa were boiled with distilled water for 2 h.
After filtration, the aqueous extract was extracted with ethyl acetate and the organic layer was dried via CaCl2, filtered and
evaporated to yield 2.29 g extract (Fr A). Other parts of the plant material were extracted by maceration with CHCl3/MeOH (1:1)
at room temperature. After filtration, the extract was concentrated to dryness under reduced pressure by rotary evaporation
at 60˚C to give a mass of 144.97 g. It was dissolved in methanol and extracted with hexane. This procedure produced hexane
fraction (Fr B; 11.32 g). Methanol phase was evaporated and dissolved with distilled water and then extracted with CH2Cl2 to
give Fr C (19.71 g). Water phase was extracted with Ethly acetate to yield 1.7 g crude extract (Fr D). Finally, the water layer was
lyophilized at -80˚C (Fr E). The content of the each extract was screened by HPLC-TOF and analyzed for antiproliferative activity
against HeLa cell lines. The CH2Cl2 (Fr C) and Ethly acetate (Fr D) extracts were found more active than the others.
PP 136 PHYTOCHEMICAL ANALYSIS AND CYTOTOXIC ACTIVITY OF COLUTEA CILICICA
FERDA ESER 1, AYSE SAHİN YAGLIOGLU 2, IBRAHIM DEMIRTAS 2, ADEM ONAL 1
1
2
FACULTY OF PHARMACY GAZIOSMANPASA UNIVERSITY, TOKAT, TURKEY
FACULTY OF PHARMCY CANKIRI KARATEKIN UNIVERSITY, CANKIRI,TURKEY
The genus Colutea comprises about 28 species (Fabaceae), deciduous flowering shrubs peculiar to Southern Europe, North
Africa and Southwest Asia. Colutea cilicica Boiss. & Bal., generally known as “bladder senna”, is native to the Mediterranean,
and it is mostly grown for its attractive yellow flowers and fruit. The fruits of the plant play an important role in Turkish folk
mediciner because of its antiinflammatory effect and wound healing activity (1, 2). The decoctions of fruiting branches are
generally used for the treatment of abscesses and wounds of kids. In addition, the ash of the plant is used to make ointment
in vegetable oil. The wound healing property of the plant is promoted through several of its constituents, such as flavonoids,
triterpenes and alkaloids (3). In this study, Colutea cilicica (Fabaceae) was collected from Tokat region. Aerial parts of the
plant including flowers, leaves and stem were dried at room temperature (25°C) in the shade and subjected to extraction with
methanol:chloroform (1:1) by maseration method. After filtration and evaporation processes, analysis of the crude extract was
performed using HPLC-TOF-MS. According to the results, 4-hydroxybenzoic acid was determined as the main components of
the flowers and the stem, as well. The main component of the leaves was identified as rutin. The antiproliferative activities of all
extracts were also studied against C6 cells using the BrdU ELISA method. The extracts were shown to have low antiproliferative
activity than 5-fluorouracil used as a standard.
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PP 137 PHYTOCHEMICAL ANALYSIS, DYEING POTENTIAL AND CYTOTOXIC ACTIVITY OF ALKANNA ORIENTALIS (L.) BOISS
(BORAGINACEAE)
FERDA ESER 1, AYSE SAHİN YAGLIOGLU 2, MELDA DOLARSLAN 2, IBRAHİM DEMIRTAS 2, EBRU AKTAS 1, ADEM ONAL 1
1
2
FACULTY OF PHARMACY GAZIOSMANPASA UNIVERSITY, TOKAT, TURKEY
FACULTY OF PHARMACY CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY
Alkanna orientalis L. which belongs to the Boraginaceae family, generally use as spices, is useful for the preparation of dyestuffs.
Active agents of the family are mucilage derivatives (arabinose, glucose and galactose), Pyrolizidinalkaloits (Amabilin, Supinidin,
Lycopsamin, Intermedin, 7-Asetil-Lycopsamin ve 7-Asetilintermedin). Furthermore, the family contains tannins, saponins,
resins, starches, silicic acids, vitamin C and minerals (1). The root of the plant contains naphthoquinone derivatives (rate of
5-6%) which is a red dye, mainly Alkannin (1). In this study, Alkanna orientalis (Boraginaceae) was collected from Çankırı region.
The roots of the plant were dried at room temperature (25 °C) in the shade. The extracts of the root were prepared with ethanol
and water, respectively, by maseration method. The analysis of ethanol and water extracts was performed by HPLC-TOF/MS.
As a result of HPLC-TOF-MS analyzes, ten compounds were determined and, rosmarinic acid and 4-hydroxybenzoic acid were
found the main components of the ethanol and water extracts, respectively. The obtained cytotoxic activities of all extracts
were determined by LDH assays against C6 cells. The extracts were detected in terms of cytotoxic activities and were found to
be less toxic than 5-fluorouracil used as a standard. Dyeing potential of the plant was also studied using different mordanting
techniques and fiber types. Best color strength (K/S=8.25) was obtained in the presence of AlK(SO4)2 mordant, using metamordanting method for cotton fabric.
PP 138 FABRICATION OF FULVESTRANT LOADED MODIFIED RELEASED NANOPARTICLES: EFFECT OF COPOLYMER
MOLECULAR WEIGHT ON PARTICLE CHARACTERISTICS
CANAN HASCICEK 1, CEYDA TUBA SENGEL-TURK 1, FILIZ BAKAR 2, NET DAS-EVCIMEN 2, MEHMET GUMUSTAS 3, A. SIBEL OZKAN
, AYHAN SAVASER 4, YALÇIN OZKAN 4
3
ANKARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, ANKARA, TURKEY
ANKARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ANKARA, TURKEY
3
ANKARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTICAL CHEMISTRY, ANKARA, TURKEY
4
GULHANE MILITARY MEDICAL ACADEMY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, ANKARA, TURKEY
1
2
Breast cancer treatment has evolved dramatically in the last few years and perhaps the most rapidly developing research area
today. Fulvestrant (FLV) is a novel estrogen receptor (ER) antagonist that competitively binds to the ER with a much greater
affinity than that of tamoxifen. In our previous study, FLV-loaded PEG-block-PLGA polymeric nanoparticles were successfully
prepared by using salting out-emulsion-evaporation technique and various physical characteristics were investigated in terms
of the encapsulation efficiency, particle size, surface charge, in-vitro drug release profiles, kinetics and mechanisms (1). In this
part of our research, the shape of nanoparticles was examined by AFM. The existence of a possible drug-excipient interaction
was investigated by using DSC and XRD analyses. The antiproliferative activity of free and nanoparticle conjugated forms of FLV
was determined against MCF-7 breast cancer cell line. The colloidal size and the spherical shape of the particles were proved
based on the AFM images. The DSC thermograms and the XRD patterns indicated that there was no interaction between FLV
and the excipients. The potency of the nanoparticles on the proliferation proficiency of MCF-7 cells was observed for the period
of 24 and 48 h. The cell culture studies showed that both of the pure drug and the FLV loaded nanoparticles presented high
cytotoxicity in breast cancer cell line.
1. Hascicek C, Sengel-Turk CT, Bakar F, Das-Evcimen N, Gumustas M, Ozkan AS, Savaser A, Ozkan Y. Fabrication of Fulvestrant
Loaded Modified Released Nanoparticles: Comparision of Copolymer Molecular Weight. 13th European Symposium on
Controlled Drug Delivery, The Netherlands, April 16-18, 2014 : 121-122.
-136-
PP 139 COMPLEXATIONS OF L-TYROSINE AND ITS METHYL ESTER WITH CU(II): TEMPERATURE DEPENDENCE OF THE
FORMATION CONSTANTS
A. SEZA BAŞTUĞ 1, DENIZ ÇIKLA YILMAZ 2, MÜRŞID PEKIN 2
DIVISION OF GENERAL CHEMISTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, HAYDARPAŞA 34668, İSTANBUL,
TÜRKIYE
2
DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, HAYDARPAŞA 34668, İSTANBUL,
TÜRKIYE
1
Studies on metal complexes of biologically important substances are very important to provide valuable information on
their metabolism. Considerable studies have been carried out on the complexations between metal ions and bioligands
[1,2]. Here, formation constants of Cu(II) with L-tyrosine and its methyl ester and acidity constants of them were determined
potentiometrically [3] at 5.0, 20.0 and 35.0 C and I = 0.10 mol/L. ΔG, ΔH and ΔS were determined for protonation of ligands
and for complexations of them with Cu(II). The results are tried to explain according to hard and soft acids and bases rule
[1,2,4,5]. Protonation of –NH2 group are found to be endothermic for Cu-Tyr and exothermic for Cu-TyrE systems. Driven force
of the latter is both ΔH and ΔS [1,2]. pK of Tyr and TyrE increase with increasing temperature; driven force is ΔS alone in this
protonation. ΔH of Tyr-Cu(II) complexation are found to be positive. Contribution of ΔS to ΔG is 100% [4,5]. Occurring both
enthalpic and entropic stabilization together for Cu-TyrE complexations implies that O atom of –COO– group is participated
more effectively in Tyr-Cu(II) complex formation [2,4,5]. Cu-TyrE complexation may be included predominantly Cu-N bonds and
therefore its formation constant was found smaller than that of Cu-Tyr.
1. Bastug, etal, J. Coord. Chem., 64(2), 281(2011) 2. Şişmanoğlu etal, Dyes and Pigments 70(2), 142(2006) 3. Pekin, etal,
Toxicolog. Environ. Chem., 80(3-4), 165(2001) 4. Bastug etal, Chim. Acta Turcica, 26, 117(1998) 5. Bastug etal, Rev. Inorg. Chem.,
27, 53(2007)
PP 140 CARMINIC ACID: TEXTILE, COSMETIC AND FOOD COLORANT
SEVIM KARABULUT 1, TÜRKAN YURDUN 2, GÜLBIN ERDOĞAN 3, EMRE DÖLEN 3
DEPARTMENT OF ANALYTICAL CHEMISTRY, INSTITUE OF HEALTH SCIENCE, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
3
DEPARTMANT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
1
2
Natural pigments and colorants are widely used in the world in many industries such as textile dyeing, food processing or
cosmetic manufacturing. Carminic acid (7-α-D glycopyranosyl-9, 10 dihydro-3,5,6,8-tetrahydroxy-1-methyl-9,10-dioxo-2
anthracenecarboxy-lic acid; E-120, color index no. 75470) is a natural dyestuff extracted from dried females of the cochineal
insect (Dactylopius coccus Costa). Carmine dyestuff is frequently used in the cosmetic, pharmaceutical, food and textile
industries. It is used in cases of severe coughing, the treatment of spasmotic problems and urinary problems as a homeopathic
medicine. It was permitted to be used as a food coloring by the European Union in 1994 and by the United States in 2002. It is
a unique natural red dye which is permitted by Food and Drug Administration (FDA) as an eye shadow at cosmetic. Synthetic
dyes which are used for coloring have toxic, carcinogenic, allergic effect and their waste cause environmental pollution. Despite
the lots of negative qualities of synthetic dyes, natural dyes have the advantages such as minimum environmental pollution
and low risk factor to human health. Istanbul Naval Museum is one of the important museums in Istanbul/Turkey, the textiles
in this museum have not yet been evaluated through chemical analysis. In this study, the dyestuff components of 90 historical
textile samples were identified by high performance liquid chromatography with diode array detector. As a result, carminic acid
dyestuff was identified in 23 red-coloured samples.
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PP 141 APPLICABILITY OF TWO SURFACTANTS IN ENHANCING THE PHYSICOCHEMICAL PROPERTIES AND INTESTINAL
ABSORPTION OF SIROLIMUS FROM SELF-NANOEMULSIFYING FORMULATIONS: A COMPARISON
ZIBA ESLAMBOULCHILAR 1, HADI VALIZADEH 2, PARVIN ZAKERI-MILANI 2
DEPARTMENT OF PHARMACEUTICS, SCHOOL OF PHARMACY, ZANJAN UNIVERSITY OF MEDICAL SCIENCES, ZANJAN, IRAN STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
2
DEPARTMENT OF PHARMACEUTICS, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
1
Components of self-nanoemulsifying drug delivery systems (SNEDDS), including surfactants, exhibit solubilizing, emulsifying and
bioavailability enhancing properties and control many characteristics of these formulations. This study aimed on investigating
and comparing the applicability of two different surfactants (Cremophor RH 40 and Labrasol) in enhancing physicochemical
properties, in vitro release and intestinal absorption of sirolimus from SNEDDS formulations. Box–Behnken design and
desirability function were used to design and optimize SNEDDS formulations. Surface properties of vehicles, formulations
and diluted nanoemulsions were investigated. Formulations prepared containing either Cremophor RH 40 or Labrasol and
their emulsification efficiency, droplet size, polydispersity index, zeta potential, drug release and intestinal permeability were
determined and compared. Formulation containing more Cremophor RH 40, exhibit lowest surface tension. Droplet size of
optimized Cremophor-based SNEDDS formulation was 45.38 nm vs. 256.4 for Labrasol-based one. Formulations revealed
significant increase in drug release (more than 85% in 5 min). Intestinal permeability of sirolimus in formulations containing
Cremophor RH 40 and different cosurfactants and oils were significantly higher than that of control sirolimus solution. Effective
permeability (Peff) value of Cremophor-based formulation was 3.46 times higher than that of sirolimus solution in comparison
to 2.23 times for Labrasol-based formulation. The best physicochemical properties and intestinal permeability enhancement
was observed applying Cremophor RH 40 as surfactant with Capryol PGMC and Transcutol as oil and cosurfactant. As a result,
incorporating sirolimus in SNEDDS formulations could promisingly enhance its intestinal permeability. Compared to Labrasol,
application of Cremophor cause more improvement in physicochemical properties, dissolution and intestinal permeability of
sirolimus.
PP 142 BINDING PROPERTIES AND INTERACTIONS OF AMPHIPHILIC PHENOTHIAZINE DRUG THIORIDAZINE HYDROCHLORIDE
WITH β-CYCLODEXTRIN
NEŞE ERDINÇ 1, SINEM GÖKTÜRK 2
1
2
MARMARAUNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANAYLITICAL CHEMISTRY
MARMARAUNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL BASIC SCIENCES, GENERAL CHEMISTRY
Cyclodextrins can increase the apparent solubility and dissolution rate of poorly water soluble drug candidates improving
their biopharmaceutical performance. Placing inside the cyclodextrin molecular cavity the substrate can considerably improve
physico-chemical and pharmacological properties (solubility, stability, bioactivity, etc.). β-Cyclodextrin (β-CD) has an amphiphilic
character due to an apolar cavity that shows a certain degree of selectivity in binding organic and inorganic compounds
and a hydrophilic annulus consisting of a number of hydroxyl groups [1,2]. Generally, hydrophobic molecules or those with
hydrophobic residues have the highest affinity with the CD cavity in aqueous solution, and it is well established that the ability
of β-cyclodextrin to enhance drug stability and solubility depends on formation of inclusion complexes. In the present study
Thioridazine hydrochloride (THCl), known as an amphiphilic phenothiazine drug [3], has been chosen a model drug to study the
interaction with β-CD in aqueous media. The interaction of THCl with β-CD has been studied by means of UV-vis spectroscopy.
Aqueous solutions of THCl containing wide concentration range of β-CD have been prepared and the absorbance spectra
recorded. The changes of absorbance were observed as a function of the concentration of β-CD added. A comparison of the
binding constants (Kb) and fraction of bound THCl to β-CD were calculated from the Benesi–Hildebrand Equation for different
concentrations of THCl. Additionally, the effect of β-CD on the CMC of THCl was also studied. The results are discussed in terms
of surface activity and binding tendency of THCl to different concentrations of β-CD.
References:
[1] Raoa VM, Nerurkar M, Pinnamaneni S, Rinaldi F, Raghavan K. Int. J. Pharma. 2006; 319 98–106.
[2] Göktürk S, Çalışkan E, Talman RY, Var Ü. TheScientificWorldJournal, 2012; 718791 1-12.
[3] Erdinc N, Göktürk S, Tunçay M. Colloids and Surfaces B: Biointerfaces 2010; 75: 194–203.
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PP 143EVALUATION THE ANTICHOLINESTERASE INHIBITORY EFFECTS OF THE ROOT OF VALERIANA ALLIARIFOLIA EXTRACT
LAAYA SAADAT 1, HOSSEIN NAZEMIEH 2, YADOLLAH AZARMI 3, HALEH VAEZ 4
STUDENT RESEARCH COMMITTEE ,TABRIZ UNIVERSITY OF MEDICAL SCIENCE,TABRIZ,IRAN
DEPARTMENT OF PHARMACOGNOSY , FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES ,TABRIZ, IRAN
3
3DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ , IRAN
4
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY , TABRIZ UNIVERSITY OF MEDICAL SCIENCES ,
TABRIZ , IRAN
1
2
Valeriana alliarifolia has a wide distribution in Iran ,and few studies have been done on this plant .The objectives of the present
study were evaluation the anticholinesterase inhibitory effects of methanolic and hexane extract of valeriana alliarifolia. The
air-dried underground parts of the plant were extracted,and using TLC and UV spectrophotometry methods to determine
valepotriates compound. Biventer cervicis muscle preparation from chickens aged 3-10 days were isolated, and the actions
of carbachol and acethylcholine were studied in the presence of the extract on the isolated chicken biventer cervicis muscle
.The log dose-response curves for both carbachol and acethylcholine in the presense of methanolic extract(100 / μ ml)did not
differ with control dose-response,so methanolic extract was fractionated with ethylacetat , n-butanol and water. The log doseresponse curves for both carbachol and acethylcholine in the presense of water and ethylacetat extract did not differ with
control dose-response, but, The log dose-response curves for acethylcholine was moved to up in the presense of n-butanolic
extrat (100 μ/ml,P<0.05).The log dose-response curves for both carbachol and acethylcholine were moved to down in the
presense of hexane extract .The result of the study suggests that the n-butanolic extract may have anticholinesterase effect.
PP 144 STUDY THE EFFECTS OF HESPERIDIN AS A FLAVONOID ON CARDIAC HEMODYNAMIC AND INFARCTED SIZE AND
LACTATE CONCENTRATION IN ISCHEMIC-REPERFUSION ISOLATED RAT HEART
MAHDIYEH PASHAII 1, MARYAM RAMESHRAD 2, HALEH VAEZ 3, NEGISA SEYEDTOUTOUNCHI 4, ALIREZA GARJANI 5, FATEMEH
FATHIAZAD 6
STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
3
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
4
STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN 2GIFTED AND TALENTED
STUDENT SUPPORTING UNIT, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ
5
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES,
TABRIZ, IRAN
6
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
1
2
Hesperidin as a flavonoid has been shown to have strong anti-oxidant and anti-inflammatory activities. The aim of the present
study is to investigate the effects of Hesperidin on cardiac hemodynamic,size infarct ,arrhythmia and lactate concentration.
Male Wistar rats were heparinized and anesthetized then harvested heart was cannulated immediately to the langendorff
apparatus and prepared for left coronary artery ligation. The control and solvent (DMSO) group received Krebs-Henseleit Buffer
Solution (KHBS) during stabilization , ischemia and reperfusion period ,while for other groups KHBS with Hesperidin (1,2.5,5
mcg/ml in separate groups) should be infused 5 minutes before occlusion and during the ischemia and reperfusion period. After
reperfusion double staining strategy (Evans blue and TTC) were used. The percentage of infarct size was determined by Image-j
software.Hemodynamic parameters and arrhythmia in control ver. Hesperidin 1,2.5, 5 mcg/ml were compared too and lactate
concentration were measured in three time of this process (end of stab & ischemia and in 60th minute of reperfusion). The
results demonstrated that Hesperidin caused a significant reduction in salvose & triplet and total number of arrhythmia(p<.05).
The infarct size has been reduced signifacantly by hesperidin(1,2.5,5mcg/ml,p<.001).Lactate concentration has been reduced
significantly(1,5 mcg/ml,p<.05) . The results of the study suggests that Hesperidin has protective effects against I/R injuries in
isolated rat heart and it has reduced infarct size dose dependently.
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PP 145 OPTIMIZATION OF THE EXTRACTION OF PHENOLIC COMPOUNDS FROM BLUEBERRY
SERAP AYAZ SEYHAN , CAGLAR DEMIRBAG , GÜLER YALCIN
MARMARA UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF ANALYTICAL CHEMISTRY, ISTANBUL, TURKEY
In recent years, berries have gained growing consumers’ attention due to their potential health benefits. Among berries,
blueberries (Vaccinium corymbosum L) have been known for their anticarcinogenic effects due to their ability to reduce
oxidative stres. These properties made blueberries popular and many studies were carried out about them. Blueberries
(Vaccinium corymbosum L.) contain high amounts of sugars and acids as well as phenolic compounds that display potential
health-promoting effects. Furthermore blueberries are grown in large scale in Black Sea Region of Turkey and they are currently
being promoted as a rich source of antioxidants (1,2,3). The extraction condition of the blueberries samples in the peresent
study. Extraction was carried out from lyophilized blueberries samples at different temperature, time and solvent. The amount
of total phenolics compounds found for each condition and the optimal conditions were determined.
1. Çelik H. (2004). Karadeniz için Yeni Bir Meyve Türü Likapa (Yaban Mersini). Doğa, Çevre ve Kültür Dergisi Ekoloji Magazin
Sayı:1, Ocak-Mart 2004: 50-53. 2. Rossi M., Giussani E., Morelli R. (2003). Effect of fruit blanching on phenolics and radical
scavenging activity of highbush blueberry juice. Food Research International 36, 999–1005. 3. Çelik, H., (2005). Yaban mersini
(Likapa) yetiştiriciliği. HASAD Yay. 128 s
PP 146 THE ANALYSIS OF TETRACYCLINES IN FOOD
ONUR DEMIRTAS , SERAP AYAZ SEYHAN
MARMARA UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF ANALYTICAL CHEMISTRY, ISTANBUL, TURKEY
Tetracyclines are wide spectrum antibiotics. Thereby they have a wide range of usage and by inhibition of protein synthesis they
show bacteriostatic effect. They are used in medical science, VETERINARY science, dentistry. The problems which happens when
they are taken unboundedly are getting bigger in accordance with this wide range of usage. The most widespread problem is the
developing resistence. Developing resistence lay the groundwork for health problems worldwide. One of another fundamental
problem is the tatracycline remains in food which appears using it unconsciously in VETERINARY science. Therefore their usage
should be kept under control by public outhority. In this study, according to the literature search of in the last decade are given
information about the use of tetracyclines and in food analysis.
PP 147 APPLICATION OF THE DEVELOPED HPLC-DAD METHOD OF ELLAGIC ACID AND RESVERATROL TO FOUR BLUEBERRY
SAMPLES GROWN IN THE TURKEY
SULEYMAN SEYHAN 1, GULER YALCIN 2
1
2
MARMARA UNIVERSITY INSTITUTE OF HEALTH SCIENCES,ISTANBUL, TURKEY
MARMARA UNIVERSITY FACULTY OF PHARMACY DEPARTMENT OF ANALYTICAL CHEMISTRY, ISTANBUL, TURKEY
Many research studies have indicated that fruits and vegetables are contains several components which are recuperative effects
for human health. (1). As a result of many studies, it has been long known that consumption of fruits and vegetables reduces
the risk of cancer and cardiovascular disease. Blueberries has a strong antioxidant property and consequently potential healthpromoting effects. Ellagic acid (phenolic acids group) and resveratrol (stilbenes group) are naturally occurring compounds
belonging to one of the group of phenolic compound found in grapes, berries and fruit juise. They are the most explored phenolic
compound, which are known to posses a variety of pharmacological and biological activities such as antioxidant, antitumor
effects (1,2,3). In this study, we reported the amount of ellagic acid and resveratrol in four different blueberry varieties, grown
in the Black Sea Region of Turkey, (Bluecrop, Brigitta, Darrow and Bluejay) by high performance liquid choromatography and
diode array detector. The recovery was % 91.85 for ellagic acid and % 84.97 for resveratrol. In the four blueberry varieties the
amount of ellagic acid was 1.65 - 9.16 mg/kg and the amount of resveratrol was 2.95-9.31 mg/kg.
1. Amakura Y., Okada M., Tsuji S., Tonogai Y. (2000) High-performance liquid chromatographic determination with photodiode
array detection of ellagic acid in fresh and processed fruits. J. Chromatogr A, 896: 87–93. 2. Soong Y.Y., Barlow J.P. (2006).
Quantification of gallic acid and ellagic acid from longan (Dimocarpus longan Lour.) seed and mango (Mangifera indica L.) kernel
and their effects on antioxidant activity. Food Chem, 97: 524–530. 3. Garcıa Moral P., Arın M.J., Resines J.A., Dıez M.T. (2007).
Determination of ellagic acid in oak leaves and in sheep ruminal fluid by RP-HPLC. J. Chromatogr B, 855:276–279.
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PP 148 OBESITY RELATED ADIPOKINE EXPRESSION AND ION LEVELS IN 3T3-L1 CELLS UNDER OXIDATIVE STRESS
BELGIN SÜSLEYİCİ DUMAN 1, MELIHA KOLDEMİR GÜNDÜZ 1, PENBE ÇAĞATAY 2, NUR BAKIR 1, ADNAN AYDIN 3
MARMARA UNIVERSITY, FACULTY OF SCIENCE AND ARTS, DEPARTMENT OF MOLECULAR BIOLOGY, İSTANBUL, TURKEY
DEPARTMENT OF BIOSTATISTIC AND MEDICAL INFORMATICS, ISTANBUL MEDICAL FACULTY, ISTANBUL UNIVERSITY, İSTANBUL,
TURKEY
3
ISTANBUL BILIM UNIVERSITY, SCHOOL OF HEALTH, DEPARTMENT OF NUTRITION AND DIETETICS, ISTANBUL, TURKEY
1
2
The effects of oxidative stress agents such as saturated fatty acid (stearic acid), non-saturated fatty acid (linoleic acid) and
hydrogen peroxide (H2O2) exposure on fat mass and obesity related (FTO) and CD68 gene expressions and intracellular ion
levels in differentiated 3T3-L1 adipocytes were studied. 3T3-L1 fibroblasts differentiated into mature adipocytes were real time
monitored by using iCELLigence system. CD68 and FTO gene expression levels were determined with qPCR in nanocycler. Ion
levels were measured by using ion selective electrode method. The exposure times of oxidative stressors were determined
according to the IC50 values obtained by real time analysis for various concentrations. Stearic acid was found to have no
effect on intracellular ion levels whereas decreased gene expression levels of both CD68 and FTO. Linoleic acid application
resulted in positive correlation between FTO gene expression and intracellular calcium levels. As a response to 24h and 800µM
H2O2 exposure, significant positive correlation was found to exist between intracellular potassium (K) levels and CD68 gene
expression. Long time low concentration (24h/600µM) H2O2 administration has been found to correlate negatively for CD68
gene expression and intracellular sodium (Na) levels in 3T3-L1 cells. Among the studied oxidative stress producing agents;
the FTO and CD68 gene expression levels were found to be in positive correlation in response to linoleic acid (24h/480µM)
exposure. In conclusion, oxidative stress agents such as H2O2, stearic and linoleic acid in long term (24h) have reducing effect
of gene expression for obesity related gene such as CD68 and FTO.
PP 149OBESITY RELATED ADIPOKINE EXPRESSION AND ION LEVELS IN 3T3-L1 CELLS UNDER OXIDATIVE STRESS
BELGIN SÜSLEYİCİ DUMAN 1, MELIHA KOLDEMİR GÜNDÜZ 1, PENBE ÇAĞATAY 2, NUR BAKIR 1, ADNAN AYDIN 3
MARMARA UNIVERSITY, FACULTY OF SCIENCE AND ARTS, DEPARTMENT OF MOLECULAR BIOLOGY, İSTANBUL, TURKEY
DEPARTMENT OF BIOSTATISTIC AND MEDICAL INFORMATICS, ISTANBUL MEDICAL FACULTY, ISTANBUL UNIVERSITY, İSTANBUL,
TURKEY
3
ISTANBUL BILIM UNIVERSITY, SCHOOL OF HEALTH, DEPARTMENT OF NUTRITION AND DIETETICS, ISTANBUL, TURKEY
1
2
The effects of oxidative stress agents such as saturated fatty acid (stearic acid), non-saturated fatty acid (linoleic acid) and
hydrogen peroxide (H2O2) exposure on fat mass and obesity related (FTO) and CD68 gene expressions and intracellular ion
levels in differentiated 3T3-L1 adipocytes were studied. 3T3-L1 fibroblasts differentiated into mature adipocytes were real time
monitored by using iCELLigence system. CD68 and FTO gene expression levels were determined with qPCR in nanocycler. Ion
levels were measured by using ion selective electrode method. The exposure times of oxidative stressors were determined
according to the IC50 values obtained by real time analysis for various concentrations. Stearic acid was found to have no
effect on intracellular ion levels whereas decreased gene expression levels of both CD68 and FTO. Linoleic acid application
resulted in positive correlation between FTO gene expression and intracellular calcium levels. As a response to 24h and 800µM
H2O2 exposure, significant positive correlation was found to exist between intracellular potassium (K) levels and CD68 gene
expression. Long time low concentration (24h/600µM) H2O2 administration has been found to correlate negatively for CD68
gene expression and intracellular sodium (Na) levels in 3T3-L1 cells. Among the studied oxidative stress producing agents;
the FTO and CD68 gene expression levels were found to be in positive correlation in response to linoleic acid (24h/480µM)
exposure. In conclusion, oxidative stress agents such as H2O2, stearic and linoleic acid in long term (24h) have reducing effect
on obesity related gene (CD68 and FTO) expressions.
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PP 150 CYTOTOXIC AND APOPTOTIC POTENTIAL OF PRIMULA AURICULATA METHANOLIC EXTRACT
SAHAR BEHZAD , MAHMOUD MOSADDEGH
DEPARTMENT OF PHARMACOGNOSY, SCHOOL OF PHARMACY, SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES, TEHRAN,
IRAN
Colorectal carcinoma (CRC), one of the most commonly seen cancers globally is the third in men and forth in women highest
cancer mortality in Iran(1, 2). Chemotherapy remains one of the major non-surgical therapeutic approaches for patients with
advanced CRC. However, the toxicity of these chemotherapy MEDICINEs to normal tissues and cells has been a major obstacle
in successful cancer treatment. Faced with these major problems, the development of novel anticancer agents is urgently
required. Primula auriculata is one of the most important local medicinal plants for eye infectious diseases in Hamedan district
(locally named Tootia). The aim of this study was to investigate the cytotoxic effect and apoptotic induction of methanolic
extract (ME) of Primula auriculata on HT-29 human colon Adenocarcinoma. Cell proliferation was measured by MTT assay and
apoptosis induction was analyzed by fluorescence microscopy (annexin V/propidium iodide double staining and TUNEL assay)
and Apoptotic index was assessed. The results indicated that ME induced suppression of cell viability in dose dependent manner
(IC50= 43.34 μg/mL). With double staining and TUNEL assay, treated cells exhibited typical characteristics of apoptotic cells,
suggesting that ME may be a potent source for the development of novel anticancer agent to treatment of colorectal cancer.
1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10-29. 2. Davoudi Monfared E, Heidarnia
MA, Akbari ME, Yavari P, Abadi A. Associations of Demographic and Socioeconomic Factors With Complete Treatment and
Follow up of Colon Cancer. Iran J Cancer Prev. 2012;5(4):203-9.
PP 151 QNAR MODEL FOR THE PREDICTION OF METALOXIDE NANOPARTICLES BIOLOGICAL ACTIVITIES
SA. SOLTANI1,3,S. SOLTANI2
DRUG APPLIED RESEARCH CENTER, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
PHARMACY FACULTY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
3
STUDENT RESEARCH COMMITTEE, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
1
2
The role of nanomaterials is rapidly increasing in many aspects of human life. Following the development of new nanomaterials
the questions about their possible interaction with biological systems should be answered. In order to save time and resources
both design of specific nanomaterials and determination of their biological properties could be done using predictive models
prior to lab based experiments. Application of computer based material design methods to nanomaterials have attracted during
last decades and among them developing quantitative nanomaterial activity/property relationships (QNA(P)R) was investigated.
In this study a number of quantum mechanical descriptors was used to develop a QNAR model for the prediction of toxicity of
metal oxide nano particles. LD50 values of MOx nanomaterials on E.Coli were obtained from a
Reference
[1]. The 9 different calculated and experimental physicochemical properties were checked using stepwise MLR method to find
the significant descriptors. The selected descriptor was used to develop linear and quadratic QNAR models. According to the
developed models toxicity of untested nanomaterials could be evaluated theoretically. The best predictors for the studied toxicity
was ionic index of metal cation and metal oxide atomization energy.
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PP 152 SPECTROPHOTOMETRIC DETERMINATION OF FORMOTEROL FUMARATE IN PURE FORM AND PHARMACEUTICAL
PREPARATIONS
GIZEM CAKIR 1, DUYGU TASKIN 2, SIDIKA SUNGUR 2
1
2
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, YENI YUZYIL UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, YENI YUZYIL UNIVERSITY, ISTANBUL, TURKEY
A simple, accurate, rapid and sensitive method has been developed for the determination of formoterol fumarate in its pure
and pharmaceutical dosage forms. The method is based on the formation of a yellow coloured ion-pair, due to reaction of
formoterol fumarate and methyl orange which shows maximum absorption at 428 nm after extraction with chloroform. The
optimum conditions for ion-pair formation were investigated with the respect to pH of the aqueous solution, extraction solvent
and the amount of the reagent. The effect of pH was investigated in the range of 2.0 to 8.0. Chloroform, toluene, dichlorometane,
benzene and carbon tetrachloride were tested as solvents for extraction.Maximum absorbance was obtained at pH 4.0 and
with chloroform as extraction solvent. The calibration was linear over the concentration range of 4-20 µg/ml. Commercially
available pharmaceutical preparations containing formoterol fumarate were assayed using the developed method.The results
were statistically compared with those obtained by the reference method in terms of accuracy and precision.
PP 153 SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME 4-SUBTITUTED-N’-(1-(4-MORPHOLINOPHENYL)ETHYLIDENE)
BENZOHYDRAZINE DERIVATIVES
BEDRIYE SEDA KURŞUN AKTAR 1, YUSUF SICAK 2, EMINE ELÇIN ORUÇ EMRE 3, MEHMET ÖZTÜRK 2, İBRAHIM DEMİRTAŞ 4,
AYŞEGÜL KARAKÜÇÜK İYIDOĞAN 3
DEPARTMENT OF PROPERTY PROCTECTİON AND SECURİTY, YAPRAKLI VOCATİONAL SCHOOL, ÇANKIRI KARATEKİN UNIVERSITY,
ÇANKIRI, TURKEY
2
DEPARTMENT OF CHEMİSTRY, FACULTY OF SCİENCES, MUĞLA SITKI KOÇMAN UNIVERSITY, MUGLA, TURKEY
3
DEPARTMENT OF CHEMİSTRY, FACULTY OF ARTS AND SCİENCES, GAZİANTEP UNIVERSITY, GAZİANTEP, TURKEY
4
DEPARTMENT OF CHEMİSTRY, FACULTY OF SCİENCES, ÇANKIRI KARATEKİN UNIVERSITY, ÇANKIRI, TURKEY
1
In present research, with the aim of obtaining new antioxidant, anti-Alzheimer agents, novel series 4-subtituted-N-(1-(4morpholinophenyl)ethylidene)benzohydrazine derivatives were synthesized. These derivatives have been synthesized by
reaction 1-(4-morpholinophenyl)ethanone with 4-substitutedbenzohydrazide. The antioxidant capacity of hydrazone derivatives
was determined as β-carotene-linoleic acid, DPPH radical scavenging, superoxide anion radical scavenging, ABTS cation radical
scavenging, and CUPRAC methods (1). In vitro inhibitory activity of acetylcholinesterase and butyrylcholinesterase enzymes
related with Alzheimers disease was determined using Ellmans method (2). Also, to determine the inhibitory activity of urease
will be used Mobley method (3).
1. Öztürk M, Aydoğmuş-Öztürk F, Duru ME, Topçu G. Antioxidant activity of stem and root extracts of Rhubarb (Rheum ribes):
An edible medicinal plant. Food Chemistry. 2007; 103: 623-630. 2. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new
and rapid colorimetric determination of acetylcholinesterase activity. Biochemistry and Pharmacology and Behaivor. 1961; 7:
88–95. 3. Mobley HLT, Island MD, Hausinger RP. Microbial Ureases-Significance, Regulation, and Molecular Characterization.
Microbiological Reviews. 1989; 53: 85–108.
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PP 154 PLANTS USED AS NATURAL DYE SOURCES IN WESTERN PART OF ALADAGLAR / NIGDE
EBRU OZDEMIR NATH 1, KERIM ALPINAR 2
1
2
FACULTY OF PHARMACY YENI YUZYIL UNIVERSITY, ISTANBUL, TURKEY
FACULTY OF PHARMACY KEMERBURGAZ UNIVERSITY, ISTANBUL, TURKEY
Some of the chemical dyes were found to be associated with hazards effecting human’s health by leading skin diseases and lung
problems. Therefore, the scientists started searching the substitutes of synthetic substances and this has led the use natural
dyes more. The Aladağ Mountains are the extension of the Taurus Mountains in the west of the Eastern Taurus Mountain Range
and harbors the highest peak thereof. The area is usually reached from Niğde side. Its plant diversity is very rich because of
its localization where 2 phyto-geographical regions meet (Mediterranean, Irano-Turanian). Yoruks are very familiar in natural
dye plants. An ethnobotanical study was conducted between 2004 and 2005 in order to determine wild plants used in West
of Niğde-Aladağlar. During the six field trips held, 14 settlements that are placed in the Western part of Niğde-Aladağlar were
visited. During these trips 200 specimens were collected from their natural habitat and information regarding how to use these
plants were gathered from the villagers (such as; local names of the plants, local uses, used parts, preparation of natural dye).
Collected plant specimens and some parts of the plant samples are kept in ISTE (The Herbarium of the Faculty of Pharmacy in
Istanbul UNIVERSITY). Among all collected plants, 9 species have been determined to be natural dye sources. Plants used as
natural dye sources in Aladağlar / Niğde are presented as a table. This table comprises various features of these plants (local
names, plants parts used in dye, the hazes obtained from dye plants, main coloring component).
1. Deveoğlu, O., Karadağ, R., Genel Bir Bakış: Doğal Boyarmaddeler, Fen Bilimleri Dergisi, Marmara Üniversitesi, İstanbul, 2011;
23: 21‐32. 2. Karadağ, R. Doğal Boyamacılık, Geleneksel El Sanatları ve Mağazalar İşletme Müdürlüğü Yayınları, Ankara, 2007.
PP 155 NATURAL DYE PLANTS IN SAVAşTEPE (BALıKESIR)
EBRU OZDEMIR NATH 1, SUKRAN KULTUR 2
FACULTY OF PHARMACY YENI YUZYIL UNIVERSITY, ISTANBUL, TURKEY
2
FACULTY OF PHARMACY ISTANBUL UNIVERSITY
1
Natural dyes are recently becoming object of consumer interests because of the harmful effects of the synthetic dyes. The dyeing
with natural colourants was one of the oldest techniques practiced by the ancient civilization people. Turkey has a rich potential
from the natural dye plants. An ethnobotanical study was conducted between 2013 and 2014 in order to determine wild plants
used in Savaştepe. Savaştepe is a town and district of Balıkesir Province in the Marmara region of Turkey. It has an area of 430
km. Its plant diversity is very rich because of its localization meeting point of 2 phytogeographic regions (Mediterranean, EuroSiberian). The population is 19.818 (as of 2011). Savaştepe has 44 villages. Karakeçili Yoruk communities are living in 15 villages.
Specially Yoruks are quite interested in natural dye plants. During the 4 field trip, The villages that are placed in Savaştepe were
visited. Local people are interviewed in the area and the plant specimens used as a dye source were collected. The collected
specimens were identified and kept in the Herbarium of the Faculty of Pharmacy, Istanbul UNIVERSITY (ISTE). It has been
recorded that villagers are using 26 plant species as a natural dye source. Plants used as natural dye sources in Savaştepe are
structured as table. This table is based on the various features of these plants (local names, plants parts used for dyeing, the
colors obtained from dye plants, main colouring component).
1.Deveoğlu, O., Karadağ, R., Genel Bir Bakış: Doğal Boyarmaddeler, Fen Bilimleri Dergisi, Marmara Üniversitesi, İstanbul, 2011;
23 : 21‐32. 2. Karadağ, R. Doğal Boyamacılık, Geleneksel El Sanatları ve Mağazalar İşletme Müdürlüğü Yayınları, Ankara, 2007.
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PP 156 PROTECTIVE EFFECT OF MORALBOSTEROID ISOLATED FROM MORUS ALBA AGAINST CARBON- TETRACHLORIDE
INDUCED HEPATOTOXICITY IN WISTAR RATS
GAURAV GUPTA 1, AFZAL MUHAMMAD 2, IMRAN KAZMI 2, FIROZ ANWAR 2
1
2
INTERNATIONAL MEDICAL UNIVERSITY, KUALA LUMPUR
SIDDHARTHA INSTITUTE OF PHARMACY, DEHRADUN, INDIA
The present work presented here evaluates the hepatoprotective potential of moralbosteroid, isolated from Morus alba,
against carbon tetrachloride induced hepatotoxicity in Wistar albino rats. Hepatoprotective action was estimated by measuring
aspartate amino-transferase (AST), alkaline phosphatase (ALP), serum alanine amino-transferase (ALT), total bilirubin (TB),
and total protein (TP), including glutathione transferase (GST), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation
(LPO) and superoxide dismutase (SOD). The oral administration of carbon tetrachloride significantly increased the LPO level
(13.22±1.59 μM/mg protein) when compared to control. The levels of antioxidant enzymes including CAT, SOD, GPx and GST
were decreased significantly (0.38±0.6 nmol/min/ml, 0.89±0.83 U/ml, 3.90±0.91 μmol and 0.05 ±0.16 U/min/mg proteins
in testicular tissue) as compared to control animals. Moralbosteroid significantly prevented the marked escalation of serum
markers and inhibited the free radical processes by scavenging hydroxyl radicals. It also modulates the levels of LPO and
prominently increases the endogenous antioxidant enzyme levels in hepatocellular toxicity induced by carbon tetrachloride.
The results obtained in this study suggest the preventive influence of moralbosteroid on liver toxicity in rats induced by carbon
tetrachloride comparable with those of Silymarin.
1. Ahmad A, Gupta G, Afzal M, Kazmi I, Anwar F. Antiulcer and antioxidant activities of a new steroid from Morus alba. Life Sci.
2013; 92(3): 202–210.
PP 157 VEGF GENE POLYMORPHISMS AND SUSCEPTIBILITY TO COLORECTAL CANCER IN TURKISH POPULATION
AYŞE TARBIN JANNUZZI , BUKET ALPERTUNGA , GUL OZHAN
DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, ISTANBUL UNIVERSITY
According to the International Agency for Research on Cancer (IARC), colorectal cancer is the third most common cancer in the
world and its etiology involves the interaction of genetic and environmental factors. New blood vessels form through process
called angiogenesis and have essential role in tumour growth, progression and metastasis of malign tumours such as colon
cancer. The Vascular Endothelial Growth Factor (VEGF), one of the most important angiogenic factors, is a specific mitogen
for vascular endothelial cells. Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation, and
they may have a role in an individual’s susceptibility to cancer. In the present case-control study, we carried out to evaluate
whether VEGF SNPs play a role in modulating susceptibility to colorectal cancer or not. We evaluated VEGF 2578 A/C, 460
T/C, and 936 C/T genotypes obtained from 129 patients with colorectal cancer and 103 healthy controls using Polymerase
Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. Odds ratios (ORs) and 95% confidence intervals
(CI) were estimated. In conclusion; 2578 A/C was significantly associated with colorectal cancer risk (OR=1.69; 95% CI=0.972.97; P=0.044) while distribution of 460 T/C and 936 C/T genotypes in cases and controls did not significantly differ. These
results suggest that the VEGF gene polymorphisms might play a role in the development of colorectal cancer. Therefore, VEGF
polymorphisms might be further investigated to use in the determination of risk factors for colorectal cancer and to have
predictive value to anti-VEGF targeted cancer therapies.
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PP 158 THE PROTECTIVE EFFECTS OF BUTHANOLIC EXTRACT OF PARONYCHIA ARGENTEA AGAINST PHOSALONE TOXICITY IN
PREGNANT WISTAR ALBINO RATS.
DJAMILA ZAMA , LEILA BELFARHI , OUAHIBA BENAISSA , FADILA BENAYACHE , SAMIR BENAYACHE
UNITé DE RECHERCHE VALORISATION DES RESSOURCES NATURELLES, MOLéCULES BIOACTIVES ET ANALYSES
PHYSICOCHIMIQUES ET BIOLOGIQUES (VARENBIOMOL), DéPARTEMENT DE CHIMIE, FACULTé DES SCIENCES EXACTES,
UNIVERSITé CONSTANTINE 1, 25000 CONSTANTINE, ALGéRIE.
Polyphenols from plant extracts might play a role in protection against pesticides toxicity. It has been suggested that Reactive
Oxygen Species (ROS) are involved in the toxicity of pesticides. The purpose of the current investigation was to study the
protective effect of buthanolic extract of Paronychia argentea L against the toxicity induced by an organophosphorus pesticide
Chloropyriphos-Ethyl (CE). Pregnant Wistar Albino rats were used in this study, pesticide and plant extract were administered
daily by gavages from the 6th to the 15th day of gestation. On day 19 , animals were dissected and blood samples were
collected and used for the estimation of plasma Malonaldehyde (MDA) as indicator of lipid peroxydation levels (LPO) blood
reduced glutathione(GSH) and erythrocyte superoxide dismutase (SOD) activities. In addition, fetuses were counted, weighed
and examined for the external congenital malformation; and their LPO levels estimated as was that of their livers. The removed
placentas were similarly treated. The data showed a significant increases in the plasma and tissues LPO levels of animals
treated with pesticide while it was decreased in the treated with plant extract. Also, CE caused a significant decrease in
antioxidant enzymes activities and this decrease was reduced in groups treated with plant extract. Moreover, pesticide induced
embryotoxicity as resumption, dead fetus and a reduced of implant number. The present findings establish that (Ph) can cause
a strong induction in LPO production in dam and fetus tissues. While treatment by plant extract reduced /or protect Ph toxicity.
The decrease in LPO levels and the increase in GSH and SOD enzymes’ activities revealed the antioxidant property of this extract.
PP 159 IN VITRO ANTIOXYDANT ACTIVITY, TOTAL POLYPHENOL AND FLAVONOIDS CONTENT OF ETHANOLIC EXTRACT OF
GREEN TEA (CAMELLIA SINENSIS).
SOUMIA LASSED , AMEL AMRANI , LEILA BELFARHI , DJAMILA ZAMA , FADILA BENAYACHE , SAMIR BENAYACHE
UNITé DE RECHERCHE VALORISATION DES RESSOURCES NATURELLES, MOLéCULES BIOACTIVES ET ANALYSES
PHYSICOCHIMIQUES ET BIOLOGIQUES (VARENBIOMOL), DéPARTEMENT DE CHIMIE, FACULTé DES SCIENCES EXACTES,
UNIVERSITé CONSTANTINE1, 25000 CONSTANTINE, ALGéRIE.
Tea is the second most commonly drank liquid on earth after water. Ongoing scientific exploration points that the certain
potential health benefits derived from tea have important implications on human health. The American Medical Association
shows that green tea can lower cholesterol levels and high blood pressure. The National Cancer Institute reports that because
of the highly effective antioxidants in green tea, it can ward off various types of cancer [1]. The present work aims to assess the
total polypfenols and flavonoides content and in vitro antioxidant activity of its ethanolic extract. The antioxidant capacity was
evaluated by applying three methods; DPPH (2, 2-diphenyl, 2-picryl hydrazyl) radical scavenging, inhibition of lipid peroxidation
and OH. Scavenging assay. The extract presented high levels of polyphenolic and flavonoides compounds 700 μg of gallic acid
equivalents/mg extract and 33.74μg quercetin equivalent/mg extract respectively. Using DPPH free radical scavenging assay,
the extract showed remarkable activity; IC50 value 10.95 µg/ml and the highest percentage of the inhibition was 96 % similar to
vitamin C in the same concentration (25µg/ml). On the other hand it exhibited the inhibition of lipid peroxidation with an IC50
value 332.68 µg/ml. The OH. Scavenging assay indicate also that the green tea extract had a significant effect again OH. radical
induced in the assay; IC50 value was 13.18µg/ml compared to ascorbic acid (10µg/ml). In the three methods used the effect
of the extract was dose dependant. The content of polyphenols and flavonoids especially catechins with meta-5,7-dihydroxyl
groups on the A ring, di- or trihydroxyl groups on the B ring and D ring (gallate) allow tea to react with ROS (superoxide radical,
singlet oxygen, hydroxyl/peroxyl radical, peroxynitrite) and gave it a maximal of antioxidant activity[2,3].The results of this study
confirm that the green tea not only a safe beverage but also a potent source of beneficial antioxidants.
References
1- A.B. Sharangi., Medicinal and therapeutic potentialities of tea (Camellia sinensis L.). Food Research International 42: 529–
535(2009).
2- D. A. Balentine., S. A.Wiseman., and L. C. M. Bouwens., The chemistry of tea flavonoids.Critical Reviews in Food Science and
Nutrition. 37(8):693–704(1997).
3- S. Valcic., J. A. Burr., B. N. Timmermann., and D. C. Liebler., Antioxidant chemistry of green tea catechins. New oxidation
products of (-)-epigallocatechin gallate and (-) epigallocatechin from their reactions with peroxyl radicals. Chemical Research
in Toxicology. 13(9): 801–810 (2000).
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PP 160 INTERACTION BETWEEN THE MALE INFERTILITY AND THE GENETIC SUSCEPTIBILITY TO ENDOCRINE DISRUPTORS
MERVE ARICI , GUL OZHAN
ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY.
Reproductive functions are impaired by many environmental, physiologic, and genetic factors. The majority of the environmental
factors are xenobiotics and male-factor infertility reportedly accounts for 30–40% of cases of couple infertility. The recent
publications related to male infertility have reported that many xenobiotics (phthalates, alkylphenols, heavy metals, bisphenol
A etc) being industrially manufactured and occurred by human activity could interfere with human’s normal hormone functions
and have potentialhazardous effects on male reproductive axis causing infertility (1-2). These xenobiotics called endocrine
disruptors (EDs) are metabolized by the enzymes involved phase I enzymes such as cytochrome P450 familyand phase II
enzymes such as N-acetyltransferases (NATs). The activity of these enzymes that are polymorphic may modify the process of
activation and/or detoxification of chemicals. Thus, the effects of EDs exposure might vary between individuals. However, to
date, the impact of genetic variability in the capacity to metabolize xenobiotics on male reproductive functions has not been
studied extensively. In our study, it is aimed to evaluate the interaction between EDs exposure and the metabolizing enzyme
polymorphisms in male infertility risk by reviewing data obtained from the previous studies.
1- Schuppe HC et al. (2000). Andrologia32:255-262. 2- Pflieger-Bruss S et al. (2004). Andrologia36:337-345
PP 161 EPIGENETIC MECHANISMS AND ENDOCRINE DISTRUPTING CHEMICALS
MINE SENYILDIZ , SIBEL OZDEN
ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY
Endocrine-disrupting chemicals are synthetic or natural compounds in the environment that can interfere with endocrine
functions and result in developmental and reproductive abnormalities. More recently, epigenetic-induced alterations in gene
expression, especially in nucleer receptors has emerged as an alternative way in which environmental compounds may exert
endocrine effects. Therefore, we aimed to review the role of DNA methylation and histone modification as two major epigenetic
mechanisms in the toxicity of endocrine distrupting chemicals. Early exposure to diethylstilbestrol, a nonsteroidal synthetic
estrogen, has been reported to cause aberrant CpG methylation and silencing of key uterine cancer (Bromer et al., 2009). DNA
hypermethylation of the estrogen receptor alfa gene induced by phthalates was also reported (Kang and Lee, 2005). Effect of
bisphenol A, a high production chemical with estrogenic properties present in many commonly used products such as food
and beverage containers, baby bottles and dental components, on the F2 generation has also been associated with epigenetic
mechanisms (Dolinoy, 2007). This review will contribute to a better understanding of the key molecular events in the toxicity of
endocrine distrupting chemicals for risk assessment process.
Bromer JG, Wu J, Zhou Y, Taylor HS. Hypermethylation of homeobox A10 by in utero diethylstilbestrol exposure: an epigenetic
mechanism for altered developmental programming. Endocrinology. 2009;150:3376-82. Dolinoy DC, Huang D, Jirtle RL.Maternal
nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci
USA. 2007;104(32):13056-61. Kang SC, Lee BM.DNA methylation of estrogen receptor alpha gene by phthalates. J Toxicol
Environ Health A. 2005;68:1995-2003.
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PP 162 QSAR STUDY OF THIADIAZOLOPIPERAZINYL UREASE INHIBITORS FAAH INHIBITORS
PARIZAD GHAREBAGHI
FACULTY OF PHARMACY ISFAHAN PAYAME NOOR UNIVERSITY, ESFAHAN, IRAN
FAAH is an interacellular serine hydrolase thetcatalyzesthe deactivating hydrolysis of several endogenous lipid amides such
as anandamide (AEA).FAAH inhibitors enhance the activation of CB receptors by blocking the degradation of AEA and may
have anti -inflammatory effects by suppressing the release of inflammatory chemical mediators by stimulating CB receptors.
Quantitative structure-activity relationship of a series of Thiadiazolopiperazinyl urease (TU) inhibitors was studied. This class of
inhibitors of FAAH, by increasing the local endocannabinoid, produce potentially useful effects in models of inflammatory and
possibly neuropathic pain. 31 TU derivatives along with their experimental data (IC50 values) were obtained from literature
and three-dimensional structure of them were constructed using Hyperchem 8. The geometry optimization was carried out
using MM+ followed by semi empirical and the resulted molecules were used to calculate the molecular descriptors (QSAR
Properties, HOMO-LUMO and Dipole moment). Descriptors selection and model development was done using SPSS software
after dividing of the data set to test and train subsets. 2 significant parameters (following equation) was selected by stepwise
regression method using training subset. The results showed that the intercept of the model is not significant and we omit it to
develop the following model. pIC50=0.038 (SAA) -0.027 (SAG) R²=0.906 R² adjust=0.897 F=101.03 S.E.E=0.792 The prediction
error of the model was acceptable according to the experimental RSD values which was reported for the same molecules.
PP 163 THE TOXIC POTENTIAL OF MANCOZEB ON ACHE ACTIVITY OF ZEBRAFISH (DANIO RERIO) TISSUES
GULLU KAYMAK 1, HARIKA EYLUL ESMER 2, FIGEN ESIN KAYHAN 2, NAZAN DENIZ YON ERTUG 1, CANSU AKBULUT 1
1
2
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE AND ARTS, UNIVERSITY, SAKARYA, TURKEY
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCES AND ARTS, UNIVERSITY OF MARMARA, ISTANBUL, TURKEY
The wide use of pesticides, particularly dithiocarbamates, in agriculture often leads to contamination of fresh water ecosystems.
Mancozeb [ethylenebis (dithiocarbamate)] was registered several times by US EPA (1987, 2005) and extensively used as an
active ingredient of fungicides applied worldwide (1,2). The present study aimed to evaluate the effects of Mancozeb on
zebrafish gills and liver tissues that would have close early contact with the aquatic pollutant. Exposure of zebrafish (Danio
rerio) to 5 mgL-1 and 7,5 mgL-1 of Mancozeb for 120 hours except the control group. Protein and acetylcholine esterase enzyme
activity (AChE) were determined using spectrophotometric methods. The results show that protein level was reduced in all
experiments groups when compared to control group. In all groups decreased AChE activity was observed. The intensive use of
mancozeb in agriculture is due to its reported low acute toxicity and scarce persistence in the environment. But despite all this,
mancozeb is a potentially hazardous compound for aquatic biota, particularly fish.
1.US EPA, 1987. Pesticide Fact Sheet Number 125: Mancozeb. Office of Pesticides and Toxic Substances. Washington, DC. 2.US
EPA, 2005. Reregistration Eligibility Decision for Mancozeb. Office of Pesticides and Toxic Substances. Washington, DC.
-148-
PP 164 THE TOXIC POTENTIAL OF MANCOZEB ON ACHE ACTIVITY OF ZEBRAFISH (DANIO RERIO) TISSUES
GULLU KAYMAK 1, HARIKA EYLUL ESMER 2, FIGEN ESIN KAYHAN 2, NAZAN DENIZ ON ERTUG 1, CANSU AKBULUT 1
1
2
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE AND ARTS, UNIVERSITY OF SAKARYA,TURKEY
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCES AND ARTS, UNIVERSITY OF MARMARA, ISTANBUL TURKEY
The wide use of pesticides, particularly dithiocarbamates, in agriculture often leads to contamination of fresh water ecosystems.
Mancozeb [ethylenebis (dithiocarbamate)] was registered several times by US EPA (1987, 2005) and extensively used as an
active ingredient of fungicides applied worldwide (1,2). The present study aimed to evaluate the effects of Mancozeb on
zebrafish gills and liver tissues that would have close early contact with the aquatic pollutant. Exposure of zebrafish (Danio
rerio) to 5 mgL-1 and 7,5 mgL-1 of Mancozeb for 120 hours except the control group. Protein and acetylcholine esterase enzyme
activity (AChE) were determined using spectrophotometric methods. The results show that protein level was reduced in all
experiments groups when compared to control group. In all groups decreased AChE activity was observed. The intensive use of
mancozeb in agriculture is due to its reported low acute toxicity and scarce persistence in the environment. But despite all this,
mancozeb is a potentially hazardous compound for aquatic biota, particularly fish.
1.US EPA, 1987. Pesticide Fact Sheet Number 125: Mancozeb. Office of Pesticides and Toxic Substances. Washington, DC. 2.US
EPA, 2005. Reregistration Eligibility Decision for Mancozeb. Office of Pesticides and Toxic Substances. Washington, DC.
-149-
PP 165 SYNTHESIS, IN VITRO CYTOTOXIC ACTIVITY AND DNA INTERACTIONS OF NEW DICARBOXYLATOPLATINUM(II)
COMPLEXES WITH 2-HYDROXYMETHYLBENZIMIDAZOLE AS CARRIER LIGANDS
SEMRA UTKU 1, AZIME BERNA OZCELIK 2, FATMA GUMUS 2, SUKRAN YILMAZ 3, TAIBE ARSOY 3, LEYLA ACIK 4, AYTEN CELEBI
KESKIN 5
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, MERSIN UNIVERSITY, MERSIN, TURKEY
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, GAZI UNIVERSITY, ANKARA, TURKEY
3
CELL AND VIRUS BANK DEPARTMENT, FOOT AND MOUTH DISEASE INSTITUTE, ANKARA, TURKEY
4
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, GAZI UNIVERSITY, ANKARA, TURKEY
5
DEPARTMENT OF BIOLOGY, FACULTY OF ART AND SCIENCE, KIRIKKALE UNIVERSITY, KIRIKKALE, TURKEY
1
2
Cisplatin is highly effective against testicular, ovarian, and lung cancers but has limited efficacy as monotherapy in breast cancer
patients. Breast cancer is the most frequently diagnosed cancer in women and is frequently hormon-dependent. Many breast
tumors express high level of estrogen receptor or/and progesterone receptor, and these cancers would be good candidates
for cisplatin/carboplatin treatment in conjunction with hormon therapy (1). Cisplatin and its analogues bind to various cellular
components like DNA, RNA, proteins, and membrane phospholipids. Although targets other than DNA may be also important
for these agents, it is generally accepted that DNA is the primary in vivo cytotoxic target of these compounds (2). In this study,
seven new platinum(II) complexes having 2-substituted benzimidazole rings as “carrier-ligands” and bidentate dicarboxylato
groups as “leaving-ligands” were synthesized and evaluated for their in vitro cytotoxic activities against the human HeLa (ER), MCF-7 (ER+) and MDA-MB 231 (ER-) cell lines using MTT assay. The plasmid DNA interactions and inhibition of BamHI and
HindIII restriction enzyme activities of the platinum compounds were also investigated using Agarose Gel Electrophoresis
method. The growth inhibitory effect results showed that the cytotoxicity of complex 2 which was found to be the most active
complex among the synthesized complexes.
1. He Q, Liang CH, Lippard SJ. Steroid hormons induced HMG1 overexpression and sensitize breast cancer cells to cisplatin and
carboplatin. Proc Natl Acad Sci USA 2000;97:5768-5772. 2. Burger H, Loos WJ, Eechoute K, Vermeij J, Mathijssen RHJ, Wiemer
EAC. Drug transporter of platinum-based anticancer agents and their clinical significance. Drug Resist Update 2011;14:22-34.
PP 166 PLASMID DNA BINDING OF PLATINUM(II) COMPLEXES CONTAINING IMIDAZOLE AND 2-PHENYLIMIDAZOLE LIGANDS
CAGLA BOGATARKAN 1, SEMRA UTKU 1, LEYLA ACIK 2
1
2
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, MERSIN UNIVERSITY, MERSIN, TURKEY
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, GAZI UNIVERSITY, ANKARA, TURKEY
Since the discovery that cisplatin (cis-diamminedichloroplatinum(II)) promotes cancer cell death by binding to DNA, thousands
of platinum complexes have been synthesized and screened in the last 30 years. Among these complexes, only carboplatin
and oxaliplatin have received worldwide approval so far, nedaplatin, loboplatin and heptaplatin have gained regionally limited
approval (1). It is well established that cisplatin binds to DNA through covalent bonding, known as platinum-DNA adducts such
as guanine N7 and forms mostly 1,2-intrastrand cross-link, which deforms the DNA structure, preventing DNA replication and
transcription, activate the apoptotic pathway, resulting in cell death. The replacement of ammine groups can result in different
structural and formational alterations in target DNA, which may affect the character of biological effects of the anologues. It
has been shown that increasing cytotoxicity of cisplatin analogues, in which NH3 groups were replaced by more hydrophobic
amine ligands, correlated with growing hydrophobicity of these analogues. One noteworthy approach in the design of new
platinum anticancer drugs is to use physiologically active compounds as ligands. The imidazole ring is a physiologically active
ligand, as a histidine moiety, function as ligands toward transition metal ions in a variety of biologically important molecules
including iron-heme systems, vitamin B12 and its derivatives and several metalloproteins. It also serves as a good ligand in
various transition metal complexes (2). In the present paper, four platinum(II) complexes with the structures cis-[PtL2Cl2] and
cis-[PtL2I2] (L=imidazole or 2-phenylimidazole as “non-leaving groups) which were synthesized by us (3) determined by their
ability to modify the electrophoretic mobility of the form I and II bands of pBR322 plasmid DNA.
1. Wexselblatt E, Yavin E, Gibson D. Cellular interactions of platinum drugs. Inorg Chim Acta 2012;393:75-83. 2. Zivkovic MD,
Rajkovic S, Djuran MI. Reaction of [Pt(Gly-Gly-N,N`,O)I]- with the N-acetylate dipeptide L-methionyl-L-histidine: selective
platination of the histidine side chain by intramolecular migration of the platinum (II) complex. Bioorg Chem. 2008; 36:
161-164. 3. Utku S, Boğatarkan Ç, Gümüş F. Synthesis and Characterization of Platinum(II) Complexes with Imidazole and
2-Phenylimidazole Ligands. International Symposium on Drug Research & Development “From Chemistry to MEDICINE”, P-085
(140), Antalya, Turkey, 27-29 May 2011.
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PP 167 EVALUATION OF NOVEL EXCIPIENTS FOR ENHANCEMENT THE RELEASE OF EZETIMIBE
MAI KHANFAR , MUTAZ SHEIKH SALEM , SANDRA HABABEH
JORDAN UNIVERSITY OF SCIENCE AND TECHNOLOGY-IRBID- JORDAN
Liquisolid technique is a powdered solution technology used to convert a liquid medicament into an acceptably flowing and
compressible powder by physical blending with selected excipients. In this study the Ezetimibe will be used with new coprocessed excipients (compacted Chitin Magnesium silicate and/or Mannitol & their physical mixtures) & compared to Avicel®
PH101 & Aerosil®200 that were used in the original mathematical method of Spireas et.al (1998) with the aim of having a
novel multifunctional excipient that act as carrier, coating, disintegrant at the same time, thus reducing cost & drug excipient
interactions. Compacted powder blends containing different ratios of Chitin, Magnesium silicate & /or Mannitol were prepared
using roller compacter and tested for their surface area, particle size & flowability to be compared with Avicel and then liquisolid
compacts were prepared according to Spireas . For all prepared liquisolid formulation, interactions between the drug & selected
excipients had been detected by a lot of techniques. Co- processing of excipients using roll compactor has a remarkable improve
in the flowability, and compressibility of the powder. The best dissolution profile was achieved by using the compacted Chitin:
Mannitol (20:80)
PP 168 PHARMACODYNAMICAL EVALUATION OF MATRIX TYPE TRANSDERMAL THERAPEUTIC SYSTEMS CONTAINING
CAPTOPRIL
OYA KERIMOGLU 1, SEVINC SAHBAZ 1, OZER SEHIRLI 2, ZARIFE NIGAR OZDEMIR 3, SULE ÇETINEL 4, BETUL DORTUNC1, GOKSEL
SENER 2
FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY MARMARA UNIVERSITY, HAYDARPAŞA,
ISTANBUL, TURKEY
2
FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY MARMARA UNIVERSITY, HAYDARPAŞA, ISTANBUL, TURKEY
3
FACULTY OF MEDICINE, DEPARTMENT OF PHYSIOLOGY MARMARA UNIVERSITY, ISTANBUL, TURKEY
4
FACULTY OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY MARMARA UNIVERSITY, ISTANBUL, TURKEY
1
The objective of this study was to evaluate the pharmacodynamical properties of transdermal therapeutic systems (TTS)
containing captopril together with synthetic and pH independent polymers, Eudragit RL 100 and RS 100 (1). Control group,
hypertension group (HT) and TTS containing captopril hypertension group (HT-CAP) were assessed for the pharmacodynamic
activity of the study. Pharmacodynamic activity of transdermal patches containing captopril was evaluated in rats by the
measurement of systolic blood pressure for 24 hours with the use of the tail cuff method (2). Blood pressure, heart rate,
body and heart weight, heart and body weight ratio were determined. Lactate dehydrogenase (LDH), creatinin phosphocinase
(CPK), glutation (GSH), malondialdehyde (MDA), myeloperoxidase (MPO) and Na+, K+-ATPase were measured in serum of the
rats. Histopathological evaluation of the heart tissue was conducted in order to determine any tissue damage. Blood pressure
values of the TTS containing captopril hypertension group were decreased significantly and became almost similar with the
blood pressure values of the control group. These results indicated that TTS containing captopril prepared with synthetic and
pH independent polymers, Eudragit RL 100 and RS 100, can be considered as a transdermal therapeutic system for chronical
treatment of hypertension and congestive heart failure. However further in vivo pharmacokinetic studies should be performed
in order to determine the blood level of the drug.
1Kerimoğlu O, Keskin E, Dortunç B, Anah Ş. Matrix type transdermal therapeutic system containing captopril: formulation
optimization, in Vitro and Ex Vivo Characterization. Acta Pol. Pharm. 2013; 70 (2): 291-300. 2) Laffan RJ, Peterson A, Hitch SW,
Jeunelot C. A technique for prolonged, continuous recording on blood pressure of unrestrained rats. Cardiovasc. Res. 1972; 6:
319-324.
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PP 169 ANTIOXIDANT ACTIVITY OF FERULAGO HUMULIS BOISS. GROWING IN TURKEY
SEVDA SUZGEC-SELCUK 1, NURTEN OZSOY 2, EMINE AKALIN URUSAK 3
DEPARMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF BIOCHEMISTRY, FACULTY OF PHARMACY, ISTANBUL UNIVERSITY, ISTANBUL, TURKEY
3
DEPARTMENT OF PHARMACEUTICAL BOTANY, FACULTY OF PHARMACY, ISTANBUL UNIVERSITY,ISTANBUL, TURKEY
1
2
The genus Ferulago W.Koch. (Apiaceae) is represented by 34 species of which 18 are endemic in Turkey. Turkey is a major centre
of diversity for Ferulago genus when the endemism rate is considered (1). Ferulago species are known as “çakşırotu”, “kişniş”,
“asaotu”, “kuzubaşı” ve “kuzukemirdi” in different regions of Turkey. Since Dioscoride’s times, Ferulago species have been used
in folk MEDICINE as sedative, tonic, digestive, carminative, aphrodisiac as well as in the treatment of intestinal worms and
hemorrhoids (2). This study was conducted to evaluate polyphenolic contents and antioxidant activities of methanol extracts
from aerial parts and rhizomes of Ferulago humulis Boiss. measuring their ability of inhibiting lipid peroxidation induced by
Fe3+-ascorbate, DPPH• and ABTS•+ scavenging activities, and ferric reducing antioxidant power (FRAP value) (3,4). It was
concluded that methanol extract from the aerial parts of the plant, containing the highest amount of total phenolics and
flavonoids, has the antioxidative potential for chain-breaking inhibition of lipid peroxidation and shows the strongest hydrogen
and a single electron donor activities, thus could serves as free radical scavenger, acts as reductant and provide protection
against oxidative stress. Although the methanol extract from rhizomes did not show any inhibitory effect on lipid peroxidation,
it may also be expected to protect against oxidative damage by scavenging free radicals and acting as reductant. The results
demonsrated the health promoting potential of rhizomes and aerial parts from F. humulis.
References
1. Akalın Uruşak E, Kızılarslan Ç. Fruit anatomy of some Ferulago (Apiaceae) species in Turkey. Turk J Bot. 2013; 37: 434-445.
2. Baytop T. Türkiye’de Bitkilerle Tedavi (Therapy with Medicinal Plants in Turkey, past and present) 2.baskı. İstanbul: Nobel Tıp
Kitapevi; 1999. p. 348-349.
3. Eroğlu Özkan E, Özsoy N, Özhan G, Özbek Çelik B, Mat A. Chemical composition and biological activities of Hypericum
pamphylicum. Ind Crop Prod. 2013; 50: 182-189.
4. Ozsoy N, Kultur S, Melikoglu G, Can A. Screening of the antioxidant potential of the leaves and flowers from Rosa horrida
Fischer. J Med Plants Res. 2013; 7: 573-578.
PP 170 THE PREPARATION AND IN VITRO CHARACTERIZATION OF METFORMIN HCL-LOADED ALGINATE BEADS
BEHZAD MOKHTARE , RUKIYE SEVINC OZAKAR , MELTEM CETIN
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY
Metformin is hypoglycemic agent widely used for management of Type 2 diabetes (1). It is primarily absorbed from the
small intestine and it has a relatively low (50–60%) bioavailability. The extent of metformin absorption is improved when
the gastrointestinal motility is slowed (2). The objective of our study was to prepare and characterize metformin HCl-loaded
alginate beads. Alginate beads were obtained by ionotropic gelation process based on the interaction between sodium alginate
and calcium chloride as a crosslinking agent. The metformin-loading capacity and encapsulation efficiency were 1.98±0.08%
and 33.58±1.56%, respectively. The drug-loaded beads have a mean diameter of 1.85±0.10 mm, a narrow size distribution.
For in vitro release study, beads were incubated in phosphate buffer (pH 6.8) under sink conditions. Approximately 98% of the
encapsulated metformin HCl was released at 9 days. The in vitro release profile showed a sustained release of metformin from
the beads.
This study was supported by Ataturk UNIVERSITY Research Foundation (project number: 2013/057). 1. Shamsa A., Vivian F.
Overview of metformin: special focus on metformin extended release. Expert Opin. Pharmacother. 2012;13(12):1797-1805. 2.
Corti G, Cirri M, Maestrelli F, Mennini N, Mura P. Sustained-release matrix tablets of metformin hydrochloride in combination
with triacetyl-β-cyclodextrin. Eur J Pharm Biopharm. 2008;68:303–309.
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PP 171 CHITOSAN MICROPARTICLES CONTAINING METFORMIN HCL: PREPARATION AND IN VITRO CHARACTERIZATION
BEHZAD MOKHTARE , RUKIYE SEVINÇ ÖZAKAR , MELTEM CETIN
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY
Metformin in the biguanide class has antihyperglycemic effect (1). It is primarily absorbed from the small intestine and it has
a relatively low (50–60%) bioavailability. The extent of metformin absorption is improved when the gastrointestinal motility is
slowed (2). The aim of this study was to formulate and characterize chitosan microparticles containing metformin HCl. These
microparticles were evaluated for particle size and size distribution, encapsulation efficiency and in vitro drug release in pH
6.8. Chitosan microparticles were prepared by the emulsion-crosslinking method. The average particle size of the prepared
microparticles was 9.208±2.16 μm. The drug loading and encapsulation efficiency were about 1.44±0.47% and 20.05±6.92%,
respectively. Approximately 98% of the drug was released from chitosan microparticles in 14 days. These data demonstrated
the efficacy of these microparticles in sustaining the metformin HCL release profile.
This study was supported by Ataturk University Research Foundation (project number: 2013/057). 1. Cetin M, Atila A, Sahin
S, Vural I. Preparation and characterization of metformin hydrochloride loaded-Eudragit®RSPO and Eudragit®RSPO/PLGA
nanoparticles. Pharm Dev Technol. 2013;18(3):570-576. 2. Corti G, Cirri M, Maestrelli F, Mennini N, Mura P. Sustained-release
matrix tablets of metformin hydrochloride in combination with triacetyl-β-cyclodextrin. Eur J Pharm Biopharm. 2008;68:303–
309.
PP 172 NIFEDIPINE-LOADED PLGA NANOPARTICLES: THE PREPARATION AND IN VITRO CHARACTERIZATION
EMRAH OZAKAR 1, MELTEM CETIN 1, ORHAN ATES 2, AHMET HACIMUFTUOGLU 3
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY
DEPARTMENT OF OPHTHALMOLOGY, FACULTY OF MEDICINE, ATATURK UNIVERSITY, ERZURUM, TURKEY
3
DEPARTMENT OF PHARMACOLOGY, FACULTY OF MEDICINE, ATATURK UNIVERSITY, ERZURUM, TURKEY
1
2
In this study, the preparation and in vitro characterization of nifedipine-loaded PLGA nanoparticles (NPs) were aimed. Nifedipin
is a dihydropyridine calcium-channel blocker and rapidly and almost completely absorbed from the gastrointestinal tract, but
undergoes extensive hepatic first-pass metabolism. Thus, it has exhibited low drug bioavailability (1). PLGA NPs were prepared
using nanoprecipitation method. The average size and the zeta potential of nifedipine-loaded nanoparticles was 425±4.96 nm
and 0.417±0.19 mV, respectively. The nanoparticles showed the encapsulation efficiency and drug loading values of 13.03±1.82%
and 2.198±0.3%. Nanoparticles showed highly reproducible drug release profile. Approximately 98% of the loaded drug was
released at 38 days in a phosphate buffer (pH 7.4). These data demonstrated the efficacy of these nanoparticles in sustaining
the nifedipine release profile.
This study was supported by Ataturk University Research Foundation (project number: 2013/012). 1. Sweetman SC (Ed.).
Martindale: The Complete Drug Reference. London: Pharmaceutical Press, Electronic version. 2007.
PP 173 DETERMINATION OF NIFEDIPINE IN PHARMACEUTICAL PREPARATIONS BY LINEAR SWEEP VOLTAMMETRY METHOD
BILAL YILMAZ 1, EMRAH ÖZAKAR 2, SELÇUK KABAN 1, RUKIYE SEVINÇ ÖZAKAR 2, BILGE KAAN AKÇAY 1, MELTEM CETIN 2
1
2
DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY
Nifedipine is a dihydropyridine calcium channel antagonist widely used in the treatment of angina pectoris, hypertension
and other vascular disorders such as Raynaud’s phenomenon (1). The goal of this work was the development of new linear
sweep voltammetry (LSV) method for the direct determination of nifedipine in pharmaceutical preparations without any
time-consuming. This paper describes fully validated simple, rapid, selective and sensitive procedure for the determination of
nifedipine employing LSV method. To determine the linearity of LSV method, standard solutions of nifedipine were prepared in
acetonitrile solution containing 0.1 M LiCIO4. The linear range was found to be 5-50 µg/mL. The regression equation obtained
by least square regression was y=34.884x+173.67 (y and x are mean peak current and concentration, respectively, r =0.999).
The limits of quantitation (LOQ) and detection (LOD) were 4.8 µg/mL and 1.6 µg/mL, respectively. Intra- and inter-day precision,
expressed as the relative standard deviation (RSD) was less than 4.78 %, and accuracy (relative error) was better than 1.85 %.
The developed method was applied to the analysis of the pharmaceutical preparations. The percent analytical recovery values
were found to be 100.7 % (Adalat Crono tablet; 30 mg/tablet) and 98.8 % (Adalat Crono tablet; 60 mg/tablet), respectively. No
interference was found from two tablet excipients at the selected assay conditions. Developed method in this study is accurate,
precise and can be easily applied to Adalat Crono tablets as pharmaceutical preparation.
1. Henry PD. Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 1980; 46:
1047-1058.
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PP 174 DEVELOPMENT AND VALIDATION OF SQUARE WAVE VOLTAMMETRY METHOD FOR DETERMINATION OF NIFEDIPINE
IN PHARMACEUTICAL PREPARATIONS
BILAL YILMAZ 1, EMRAH OZAKAR 2, SELCUK KABAN 1, RUKIYE SEVINC OZAKAR 2, BILGE KAAN AKCAY 1, MELTEM CETIN 2
1
2
DEPARTMENT OF ANALYTICAL CHEMISTRY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, ATATURK UNIVERSITY, ERZURUM, TURKEY
Nifedipine, a lipid soluble drug, is rapidly and completely absorbed from the gastrointestinal tract after oral administration. The
systematic bioavailability of nifedipine is 50-70% due to extensive first-pass metabolism. The elimination half-life of nifedipine
is approximately 2-5 h (1). The goal of this work was the development of new square wave voltammetry method (SWV) for the
direct determination of nifedipine in pharmaceutical preparations. Besides, the method was successfully applied for the quality
control of two commercial nifedipine tablets form to quantify the drug and to check the formulation content uniformity. The
linear range was found to be 5-50 µg/mL. The regression equation obtained by least square regression was y=23.424x+139.74
(y and x are mean peak current and concentration, respectively, r =0.999). The limits of quantitation (LOQ) and detection (LOD)
were 2.7 µg/mL and 0.9 µg/mL, respectively. Intra- and inter-day precision as the relative standard deviation (RSD) was less
than 3.96 %, and accuracy (relative error) was better than 1.55 %. The percent analytical recovery values were found to be 98.7
% (Adalat Crono tablet; 30 mg/tablet) and 101.8 % (Adalat Crono tablet; 60 mg/tablet), respectively. The method has been
effectively and efficiently used to analyze nifedipine pharmaceutical tablets without any interference from the pharmaceutical
excipients. The voltammetric run time of 1 min allows the analysis of a large number of samples in a short period of time.
Therefore, the method can be used effectively without separation for routine analysis of nifedipine in pure form and its
formulations.
1. Henry PD. Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 1980; 46:
1047-1058.
PP 177 THE EFFECT OF MONTELUKAST ON 3-NITROPROPIONIC ACID INDUCED EXPERIMENTAL HUNTINGTON’S DISEASE
MODEL
MERAL YUKSEL 1, SEZGIN AYDEMIR 2, HULYA SAHIN 1, NAZIYE OZKAN 2, NUSRET ERDOGAN 2
DEPARTMENT OF MEDICAL LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA
UNIVERSITY, HAYDARPASA-ISTANBUL, TURKEY
2
DEPARTMENT OF PATHOLOGY LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES,
MARMARA UNIVERSITY, HAYDARPASA-ISTANBUL, TURKEY
1
Huntington’s disease is an autosomal dominant inherited disease, which is associated with cognitive deficits and striatal
neudegeneration. 3-nitropropionic acid (3-NP), is a fungal toxin, inhibits succinate dehydrogenase in Krebs cycle and electron
transport chain. Systemic administration of 3-NP to rats cause neuronal degeneration in striatum and cognitive deficits, like
Huntington’s disease. Montelukast (ML) is a cysteinyl-leukotriene receptor antagonist, which has a reducing effect of inflammation
in various diseases. The aim of this study was to investigate the putative neuroprotective effect of ML against 3-NP induced rat
model. Female Sprague-Dawley rats were included in the study. Rats were divided into four groups; 3-NP group (20 mg/kg/
day), ML group (10 mg/kg/day), 3-NP-ML group and control group (SF). After 10 days, rats were decapitated and brains were
removed. We measure luminol and lucigenin enhanced chemiluminescence (CL) for free radical release, malondialdehyde (lipid
peroxidation) and glutathione levels (an antioxidant) for oxidative stress determination and histopathological observations.
Luminol enhanced CL measurements were increased in 3-NP group with respect to controls (15.3±2.1 vs. 11.8±1,6 rlu/mg;
p<0.05). ML treatment reduced the release of OH, H2O2 and HOCl- radicals, significantly (11.0±2.2 rlu/mg; p<0.01). Superoxide
radical generation via lucigenin CL was significantly higher in 3-NP group, with respect to control group, which was reduced with
ML treatment (15.6±1.4 vs. 8.1±1.2 vs. 9.9±1.1 rlu/mg; p<0.001). MDA levels were higher and GSH levels were lower in 3-NP
group. ML treatment ameliorates the effects, significantly. Histopathologic observations show that striatal lesions after 3-NP
induction are reduced with ML treatment. In conclusion, ML treatment reduces free radical induced oxidative stress lesions in
3-NP induced experimental Huntington’s disease model.
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PP 176 INVESTIGATING PROTEIN BINDING INTERACTIONS OF SIROLIMUS AND MACROLIDE ANTIBIOTICS
HADI VALIZADEH , SAYEH MOSTAFIDI , PARVIN ZAKERI-MILANI
FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
Binding of drugs to plasma and tissue proteins significantly affects the pharmacokinetic and pharmacodynamic behaviors of
drugs. Protein-binding displacement interactions become an important consideration for the patient when multiple drugs are
prescribed. The aim of this project was investigating plasma protein binding of sirolimus and protein binding interaction of
sirolimus with macrolide antibiotics, erythromycin, clarithromycin, and azithromycin. Aqueous solutions containing 2, 4, 6,
8, 10 µg/ml of sirolimus and 0.04 g/ml of human serum albumin were prepared. Ultrafiltration method was used for protein
binding determination. The same process was performed in the presence of macrolide antibiotics. Free sirolimus concentration
in the resulted ultrafiltrate was measured by RP-HPLC. Binding data were analyzed by means of Klotz and Scatchard graphical
procedures. The obtained data showed that the presence of macrolide antibiotics, decreased the protein binding percentage
of sirolimus from 77-80.7% to 40-62% for erythromycin, 38-70% for clarithromycin and 61.2-73% for azithromycin. Decreasing
the protein binding of sirolimus in the presence of macrolide antibiotics was significant (p<0.05). Furthermore the number
of binding sites was decreased while the binding affinity of sirolimus to albumin was increased. According to the results it is
recommended to monitor the plasma concentration of sirolimus in concurrent use of these drugs, and adjusting the dose of
sirolimus, if it is necessary.
PP 177 PATIENT SATISFACTION AND PHARMACY MANAGEMENT
ASLI CULDUZ 1, ADİLE SERKİ 2, NAZLI SENCAN 1
1
2
DEPARTMENT OF PHARMACY MANAGEMENT AND SOCIAL PHARMACY, FACULTY OF PHARMACY, YEDITEPE UNIVERSITY
YEDİTEPE UNIVERSITY
Patient satisfaction is an individual’s cognitive evaluation of, his or her health-care experience. It has become an important factor
of the quality of healthcare services and could be a predictor of health related behavior. Patient satisfaction has been used for
the purpose of performance assessment, reimbursement and quality management of health service delivery. Pharmacies are
the first step access to health services. Pharmacists, who are in constant contact with the patient can be considered as a single
drug advisor. Pharmaceutical care needs more informal and comprehensive relationship between the pharmacist and patient
than basic pharmaceutical dispensing and patient satisfaction measurements evaluates the needs fulfillment. In this study, it
is aimed to discuss the context of patient satisfaction and to describe contemporary worldwide developments regarding the
promotion of the matter. Researches conducted in USA, Canada, Australia and European countries have been reviewed as
patient satisfaction measurements have been developed increasingly in these countries. Patient satisfaction which is an input
and outcome as a performance indicator of pharmacy management, will be considered more in the future.
PP 178 COMPARATIVE STUDY OF ANTIOXIDANT PROPERTIES OF FOUR UMBELLIFERAE SPECIES WILDLY GROWING IN
TURKEY
LEYLA BITIS 1, TURGUT TASKIN 1, ALI SEN 1, GIZEM BULUT 2, ERTAN TUZLACI 2
1
2
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF PHARMACEUTICAL BOTANY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
The fresh young leaves and shoots of Ammi visnaga, Daucus carota, Foeniculum vulgare , Oenanthe pimpinelloides,belong to
the Umbelliferae family are traditionally used as vegetable and MEDICINE by local people in Turkey .The aim of this study is
to reveal antioxidant properties of methanol extracts from these plants which were prepared using Soxhlet apparatus and by
maceration , and to determine their relationship with the phenolic contents.The antioxidant capacity of these species were
assayed with various methods, DPPH free radical scavenging, metal chelating and ABTS radical cation scavenging capacity,
including total phenolics contents by Folin – Ciocalteu reagent .The obtained results were compared with standard antioxidants
such as Ascorbic acid, BHT and EDTA.The methanol extract of Daucus carota, prepared by maceration exhibited stronger DPPH
free radical-scavenging (IC50: 0.320±0.01 mg/mL) and ABTS radical cation scavenging activity (IC50: 1.307± 0.1mg/mL) than
other extracts. The positive correlation was observed between the total phenolic contents and the DPPH free radical , ABTS
radical cation scavening activity; indicating that phenolic compunds are mainly responsible for the antioxidant power of this
extract.The methanol extract of Oenanthe pimpinelloides, prepared using Soxhlet apparatus exhibited stronger DPPH free
radical (IC50: 3.11±0.04 mg/mL) and ABTS radical cation scavenging activity (IC50: 5.21± 0.03 mg/mL) than the others. The
positive correlation was observed between the total phenolic contents and, the DPPH ,ABTS methods, indicating that phenolic
compunds are mainly responsible for the antioxidant power of this extract.Cold extracts showed higher DPPH radical and ABTS
radical cation scavenging activity than hot ones. It was shown, extraction method has an effect on antioxidant capacity.
Acknowledgment : This work was supported by Scientific Research Projects Committee of the UNIVERSITY of Marmara(BAPKO,
project number SAG-B-110412-0077)
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PP 179 TWO FLAVONES FROM SAMBUCUS EBULUS L. LEAVES
ZEHRA ILKE MERIC 1, LEYLA BITIS 2
1
2
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, YENI YÜZYIL UNIVERSITY, 34010,ISTANBUL, TURKEY
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, 34668, ISTANBUL, TURKEY
The aim of this study was to isolate of flavonoids from fractionated extracts of Sambucus ebulus L. leaves. Leaves, flowers
and fruits of Sambucus species (Caprifoliaceae) have been used to treat various disorders in Turkish folk MEDICINE. There are
two Sambucus species in Turkey, Sambucus ebulus L. and Sambucus nigra L. Pharmacological effects have been reported for
Sambucus species as antiviral, antibacterial, anti Helicobacter pylori, antioxidant and wound healing activity. The ethanol extracts
of Sambucus ebulus (leaf, fruit and flower) which was collected from Çatalca in İstanbul at September 2009, have been evaluated
their total phenolic content, antioxidant and anticarcinogenic activities. Leave extract showed the highest activity as antioxidant,
anticarcinogenic and total phenolic content. Therefore, leave extract was chosen for isolation. Plant material was extracted using
Soxhlet apparatus with petroleum ether and ethanol respectively. In addition, toluene, chloroform, ethyl acetate and aqueous
fractions were obtained from diluted ethanol extract by means of liquid-liquid extraciton methods, respectively. Chloroform extract
was chromatographed on a silica-gel column and one flavonol glucoside was isolated. UV, NMR spectra and TLC comparisons with
authentic samples were used for the structure elucidation of the purified compound. Finally; The compound was determined as
Quercetine-3-O-β-galactoside. Also, Kaempferol-3-O-glucoside and Quercetine-3-O-galactoside from ethyl acetate extract were
detected chromatographycally by TLC in comparison with authentic sample.
PP 180 EFFICACY ENHANCEMENT OF HYDROPHOBIC ANTIBIOTICS EMPLOYING RHAMNOLIPID AS BIOSURFACTANT
ABDURRAHIM ELOUZI
FACULTY OF PHARMACY, TRIPOLI UNIVERSITY,LIBRA
Antibiotic resistance has become a global public-health problem, thus it is imperative that new antibiotics continue to be developed.
Major problems are being experienced in human MEDICINE from antibiotic resistant bacteria . Moreover, no new chemical class of
antibiotics has been introduced into MEDICINE in the past two decades. The aim of the current study presents experimental results
that evaluate the capability of biosurfactant rhamnolipid on enhancing the efficacy of hydrophobic antibiotics. Serial dilutions of
azithromycin and clarithromycin were prepared. A bacterial suspension (approximately 5X105 CFU) from an overnight culture in
MSM was inoculated into 20ml sterile test tube each containing a serial 10-fold dilution of the test antibiotic(s) in broth with or
without 200mg/L rhamnolipid. The tubes were incubated for 24 h with vigorous shaking at 37°C. Antimicrobial activity in multiple
antibiotic-resistant gram-negative bacteria pathogens and gram-positive bacteria were assessed using optical density technique.
The results clearly demonstrated that the presence of rhamnolipid significantly improved the efficiency of both antibiotics. We
hypothesized that the addition of rhamnolipid at low concentration, causes release of LPS which results in an increase in cell
surface hydrophobicity. This allows increased association of cells with hydrophobic antibiotics resulting in increased cytotoxicity
rates.
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PP 181 ASSESSMENT OF AND INTERVENTIONS TO SOLVE DRUG RELATED PROBLEMS IN PATIENTS WıTH ASTHMA AND
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) THAT IS NOT FULLY CONTROLLED
GOZDE YESILYAPRAK 1, SULE APIKOGLU-RABUS 1, FIKRET VEHBI IZZETTIN 2
1
2
ENDOTEK SAGLIK GERECLERI, IZMIR, TURKEY
MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT, ISTANBUL, TURKEY
The aim of this study is to assess drug related problems in patients with asthma and chronic obstructive pulmonary disease
(COPD) that is not fully controlled and to make interventions to solve the problems. The control states were assessed by asthma
control test (ACT) or clinical COPD questionnaire (CCQ). Asthma and COPD patients older than 18 years old who visited the
community pharmacy (Hastaneler Eczanesi, Sivas, Turkey) during a six-month period were randomly selected. The patients
whose disease control states were found to be “not fully controlled” were included in our study for further steps. On the
first interview, present and potential drug related problems were assessed, interventions were made, patient satisfaction
questionnaires were administered. For the assessment of the drug-related problems, Turkish translation of the PCNE-DRP
Classification (V6.2) was used. Follow-up interviews were held one month and two months later than the first interview date.
During the interviews, patients reported data was recorded. For the 44 asthma patients, 59 drug related problems and 134
causes for these problems were determined. Eighty-four interventions were made to solve the problems. As a consequence of
interventions, 54.2% of the problems were solved and 10.2% of the problems were partially solved. For the 37 COPD patients,
60 drug related problems and 128 causes for these problems were determined. Ninety-five interventions were made to solve
the problems. As a consequence of interventions, 63.3% of the problems were solved and 16.7% of the problems were partially
solved. As a conclusion, we can suggest that when pharmacists take part in therapy and management of asthma and COPD,
this could lead patients to be more educated about their disease and medications and enhance their adherence to therapy,
pharmacists could significantly help taking the disease under control and achieving better therapy outcomes.
PP 182 ASSESSMENT OF THE EFFECTS OF QUINCE SEED MUCILAGE AND WHEAT GERM OIL ON WOUND HEALING IN RATS
CANAN ATALAY , SULE APIKOGLU-RABUS , FIKRET VEHBI İZZETTIN
MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT
In our study we aimed to investigate the effects of wheat germ oil and quince seed mucilage on cutaneous wound healing in rats.
The study was conducted on three groups of animals, which received topical wheat germ oil and topical quince seed mucilage
as the therapy groups; and usual wound care as the control group. Wound healing was assessed by planimetric measurements
of the contracting wound and the full epithelialization time. The findings yielded that when compared with the control rats,
rats receiving topical wheat germ oil displayed lower wound closure rates in the first four days, while this rate was significantly
higher in the 8., 10. and 12. days. The median duration of complete epithelialization was 11 days for the wheat germ oil group
and 13 days for the control group. Compared with the control group, the topical application of wheat germ oil accelerated
wound healing by reducing the time required for complete epithelialization. On the other hand, the wound closure rates of the
rats receiving quince seed mucilage were not different from those of the control rats different. In conclusion, the application
of wheat germ oil was observed to accelerate wound healing. This finding could suggest an alternative or complementary
approach to wound treatment. On the other hand, we think that the effect of the quince seed mucilage on wound healing
should be assessed using higher concentrations of the preparation at further studies.
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PP 183 CLASSIFICATION FOR DRUG-RELATED PROBLEMS: TURKISH TRANSLATION AND ADAPTATION OF THE PCNE-DRP
CLASSIFICATION (V6.2)
SULE APIKOGLU-RABUS 1, GOZDE YESILYAPRAK 2
1
2
MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT
ENDOTEK SAGLIK GERECLERI, IZMIR, TURKEY
A drug-related problem is an event or circumstance involving drug therapy that actually or potentially interferes with desired
health outcomes. “Drugs-related problem classification systems” have been developed for the determination and characterization
of drugs-related problems, to propose solutions, conduct follow up and document all these activities. One of these systems
is the “drug-related problems classification scheme [PCNA-DRP (Drug Related Problems) Classification]” developed by the
Pharmaceutical Care Network Europe (PCNE). This classification scheme has been designed to be used in the investigation
of the nature and incidence of the drug-related problems; as a process indicator of the quality of the pharmaceutical care
provided; and as an aid in documentation of the drug-related problems identified during the pharmaceutical care process.
The classification system is validated and adapted regularly. The current version is V6.2. As there is no classification system for
the drug-related problems in Turkish, we aimed to translate and adapt the PCNE-DRP Classification (V6.2). As the adaptation
process, the PCNE-DRP Classification was first forward translated in Turkish, then reviewed by an expert panel and then
backward translated by a native English speaker. Pre-testing was done on 20 pharmacists. Pre-testers were asked to comment
on wording of the classification (they were asked about any word they did not understand or they found unacceptable and
make alternative suggestions for it). Each pre-tester was interviewed in-depth one by one. The final version of the instrument
was structured by the expert panel taking into consideration of these comments.
PP 184 A MODEL PROGRAM FOR OBESITY PREVENTION AND CONTROL IN COMMUNITY PHARMACY
SULE APIKOGLU-RABUS 1, GOKCEHAN GULTEKIN 2, FIKRET VEHBI IZZETTIN 1
1
2
MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT, ISTANBUL, TURKEY
SAGLIK ECZANESI, ISTANBUL, TURKEY
The studies show that the worlds population is increasingly getting fat. This uncontrolled weight increase with its problems
arising suggests that measures from all aspects should be taken in order to prevent weight gain. Today, pharmacists have a role
in raising public awareness about obesity in countries such as USA, UK, Denmark, Australia, Germany, Switzerland and Scotland.
The reason for this expanding role is that patients often primarily visit the pharmacies for weight loss or control; pharmacists
can be easily reached without an appointment; and people trust the pharmacists and are able to speak with them comfortably.
Despite this, the majority of the patients report that they would first admit to a doctor or a dietitian for weight loss or control.
Patients concerns on this issue rise on the basis of their thoughts regarding the lack of pharmacists knowledge on the subject
and concerns about the protection of privacy. Patients also think that the workload of the pharmacists will not let them counsel
on weight loss efficiently and there is a bias that the pharmacists would be trying to market weight loss products. In this study,
a model program for “Obesity Prevention and Control in Community Pharmacy” which aims helping to prevent and treat the
increasing obesity cases; informing the patients about the role of the pharmacist in obesity prevention and control; raise
awareness about obesity in general, its harms and the treatment approaches; and teaching healthy life-style, will be introduced.
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PP 185 DEVELOPMENT AND VALIDATION OF THE TURKISH DIABETES-SPECIFIC QUALITY OF LIFE SCALE
SULE APIKOGLU-RABUS 1, DILEK YAZICI 2, MEHMET HURSITOGLU 3, FATIH METE 4, AKIN DAYAN 5, REFIK DEMIRTUNC 5, FIKRET
VEHBI IZZETTIN 1
MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT
MARMARA UNIVERSITY MEDICAL SCHOOL; DEPARTMENT OF ENDOCRINOLOGY AND METABOLISM
3
KANUNI SULTAN SULEYMAN TRAINING AND RESEARCH HOSPITAL; DEPARTMENT OF INTERNAL MEDICINE
4
KANUNI SULTAN SULEYMAN TRAINING AND RESEARCH HOSPITAL; DEPARTMENT OF PEDIATRICS
5
HAYDARPASA NUMUNE TRAINING AND RESEARCH HOSPITAL; DEPARTMENT OF INTERNAL MEDICINE
1
2
One of the primary goals in the treatment of diabetes is to improve patients quality of life. To our knowledge, the only available
diabetes-specific quality of life scale in our country is the Turkish version of the Diabetes Quality of Life Measure. The scale
consists of 46 questions in which the response options are graded using a 5-point Likerts scale. In our study we aimed to develop
the Turkish Diabetes-Specific Quality of Life Scale to measure diabetes-specific quality of life in patients with diabetes as a shorter
and easy to answer alternative. The newly developed quality of life scale was administered to 180 patients with type 2 diabetes,
together with the Nottingham Health Profile for validation studies. Internal consistency was assessed by Cronbachs alpha,
test-retest reliability was evaluated by intra-class correlations, and validity was assessed by principal component analysis. The
Cronbachs alpha value of the newly developed 14-item scale was 0.84. The test–retest reliability was 0.98. Principal component
analysis demonstrated three components, which explained 35.0 percent, 10.8 percent and 8.6 percent of the variation. The
inter-item correlations were smaller than 0.6 in 98.9 percent of the cases. All domains of the Nottingham Health Profile showed
a significant correlation with the new scale, except for the sleep domain. These findings revealed that the Turkish DiabetesSpecific Quality of Life Scale is a valid and reliable tool for measuring quality of life in patients with diabetes.
PP 186 INFORMATION OF PUBLIC PHARMACISTS IN GIVEN DISTRICTS OF ISTANBUL ABOUT NEW STRUCTURING OF DRUG
SAFETY AND EVALUATION OF THEIR APPROACH TO PHARMACOVIGILANCE
GUNSELI CANSU ASKIN , GULDEN ZEHRA OMURTAG , SEMRA SARDAS
MARMARA UNIVERSITY DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY
This study was carried out as a face to face questionnary with pharmacists in Istanbul city in between 31.03.2011-30.04.2011,
with the support of Istanbul Pharmacists’ Chamber. Aim of the study is by using the questionnaire, to survey information and
awareness level of the pharmacists in given districts about the new structuring of drug safety and to increase the awareness
level, contribute to increment and improving of adverse effect notice of pharmacists The questionnaire was carried out with
two group of pharmacists who are graduated before and after year 2005. The questionnaire was applied to 78 community
pharmacists and the pharmacies were located in the neighborhood of Istanbul. The most frequently reported drug classes are,
anti-depressants, non-steroidal anti inflamation drugs, antibiotics, oral contraceptives, anti-obezite drugs. When pharmacists
are being asked about how to find the adverse drug reporting form, it is observed that 59% of pharmacists do not know, 41%
of parmacists know how to find reporting forms. There is no statistical difference according to the year of graduation. Past and
future professional educations which are followed by pharmacists are improving the steps of drug safety Pharmacists are being
asked about the reasons for not-transmitting the adverse drug reaction. Primary reasons are lack of time and information about
how to report the reaction. Pharmacists mostly rely on pharmacy faculties for the better education of adverse drug reaction and
reporting. Pharmacists are informed about adverse drug reaction, reporting forms and pharmacovigilance. For the pharmacists
who are graduated after 2005, it is observed that information and the awareness of basic terms about drug safety is improved
more than the other group. With implemention of pharmacovigilance education into faculty programme, the information about
drug safety improvement and awareness to basic terms of drug safety has increased. There is a huge need for more education,
information, studies and programmes about pharmacovigilance for well-informed healthcare professionals.
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PP 187 EFFECT OF ANTIBIOTICS ON POLYMORPHONUCLEAR LEUKOCYTE FUNCTIONS AND MYELOPEROXIDASE ACTIVITY,
GLUTATHIONE AND MALONDIALDEHYDE LEVELS IN ALLERGIC ASTHMA
PERVIN RAYAMAN 1, ERKAN RAYAMAN 1, ADILE CEVIKBAS1, REFIK DEMIRTUNC 2, AHMET OZER SEHIRLI 3, SEYDA GUL ALAGOZ 4,
UMRAN SOYOGUL GURER 1
DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, İSTANBUL, TURKEY
DEPARTMENT OF INTERNAL MEDICINE, HAYDARPAŞA NUMUNE TRAINING AND RESEARCH HOSPITAL, İSTANBUL, TURKEY
3
DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, İSTANBUL, TURKEY
4
DEPARTMENT OF PNEUMONOLOGY, HAYDARPAŞA NUMUNE TRAINING AND RESEARCH HOSPITAL İSTANBUL, TURKEY
1
2
Oxidative stress may play a critical role in the pathogenesis of inflammatory diseases such as allergic asthma. Our objective
was to compare polymorphonuclear leukocytes (PMN) functions to myeloperoxidase (MPO)activity, glutathione (GSH) and
malondialdehyde (MDA) levels in PMN and determine the relationship between PMN functions and MPO activity, GSH and
MDA levels in allergic asthma patients and healthy volunteers. Also we investigated the effect of rifampicine and doxycycline
on PMN functions and MPO activity, GSH and MDA levels. PMNs were isolated from venous blood of allergic asthma patients
and healthy volunteers with ficoll-hypaque gradient centrifugation method. MPO activity was assayed with modified
o-dianisidine method. GSH levels were determined by Ellman’s and MDA levels by Beuge’s method. PMN’s phagocytic(p<0.01)
and intracellular killing activity(p<0.001) and MDA levels (p<0.001) of patients significantly decreased when compared to
healthy volunteers. Rifampicine and doxycycline have decreased both PMN functions of healthy volunteers (p< 0.05, p<0.05
respectively). Rifampicine has increased MDA levels (p<0.01) of healthy volunteers, but doxycycline has decreased MDA levels
(p<0.05) of allergic asthma patients. In conclusion, the relationship between MDA levels and PMN functions was shown. In
relationship with the disease and therapy of these patients, the decrease of PMN’s GSH levels, might bring up the usage of new
pharmacaeutical preparations which increase the MPO activity and GSH levels and decrease MDA levels in neutrophils of these
patients.
PP 188 SYNTHESIS, EVALUATION OF THE ANTIOXIDANTACTIVITY OF NEW ONO DONOR HETEROCYCLIC SCHIFF BASE AND ITS
NOVEL CU(II) COMPLEX
MEHMET EMİN HACIYUSUFOĞLU 1, MEHMET SÖNMEZ 2, İSMET BERBER 3, ZÜLBİYE ÖNAL 4
DEPARTMENT OF FOOD TECHNOLOGY, AKÇAKOCA VOCATIONAL SCHOOL, UNIVERSITY OF DÜZCE, DÜZCE,TURKEY
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE AND ARTS, GAZIANTEP UNIVERSITY, GAZIANTEP,TURKEY
3
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE AND ARTS, SINOP UNIVERSITY,SINOP,TURKEY
4
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, ERCIYES UNIVERSITY, KAYSERI,TURKEY
1
2
N donor bases known as pyrimidines and purines are two of the basic building elements of DNA; they are necessary elements
in cell programming. Also they accomplish a variety of functions in the metabolism of the cell, and without them, many cellular
functions would not be accomplished (1). These rings are known to take important role in biological systems. Therefore,
pyrimidine derived Schiff base ligands and their complexes have been extensively investigated for biological activities, including
antimalarial, antibacterial, antitumor, antiviral activities etc. in recent years (2). N donor containing Schiff bases form complexes
with metal ions by strong binding, thus these complexes have high stability. The metal(II) complexes of polydentate Schiff base
ligands of the N-aminopyrimidine type have impressive electrochemical properties and structural richness, in addition to their
potential use as a model for a number of important biological systems (3).In the study, A new heterocyclic Schiff base ligand
and its transition metal complex of the type ML2, where M= Cu(II) has been synthesized the ligand (HL) and its metal complex
we was evaluated for in vitro the antioxidant activity using DPPH activity assay
1. Chang YT, Gray NS, Rosania GR, Sutherlin DP, Kwon S, Norman TC, Sarohia R, Leost M, Meijer L, Schultz PG (1999) Synthesis
and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors. Chemistry and Biology 6: 361–375.
2. Saha N, Kar SK (1977) Chelating behavior of a new pyridylpyrazole: tris-complexes of Cu(II), Ni(II) and Co(II) perchlorates and
fluoborates with 3,5-dimethyl-1-(2’-pyridyl) pyrazole. J Inorg Nucl Chem 39: 1236–1238 3. Gülcan M, Sönmez M, Berber I (2012)
Synthesis, characterization, and antimicrobial activity of a new pyrimidine Schiff base and its Cu(II), Ni(II), Co(II), Pt(II), and Pd(II)
complexes. Turk J Chem 36: 189-200
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PP 189 SYNTHESIS AND STRUCTURE ELUCIDATION OF SOME NOVEL CHIRAL 1,2,4-TRIAZOLE-3-THIONES
EYUP BASARAN , AYSEGUL KARAKUCUK-IYIDOGAN , EMINE ELCIN ORUC-EMRE
DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
Nitrogen based heterocyclic compounds are very important in the field of medicinal chemistry. 1,2,4-triazole nucleus is associated
with diverse biological activities such as antinflammatory, antiviral, antifungal and cytotoxicity activities etc. (1-3). Taking these
observations into account in the present study, some novel chiral 1,2,4-triazoles were synthesized. Firstly, D-phenylalanine
methylester/L-phenylalanine ethylester were converted to the sulfonamide derivatives with arylsulfonyl chlorides in the
presence of triethylamine. These sulfonamides were reacted with hydrazine monohydrate to give hydrazide derivatives. Then,
hydrazide derivatives were treated with various substituted isothiocyanates to obtain new chrial thiosemicarbazide derivatives.
Finally, enantiomerically pure new chiral 1,2,4-triazole-3-thiones were prepared by cyclization of chrial thiosemicarbazides
in basic medium. The structures of all the synthesized compounds were confirmed by elemental analyses (CHNS), IR, UV-Vis,
1HNMR, 13C NMR and MS spectra. In the future, in vitro cytotoxic and antiviral activity of all compounds will be screened.
1. Mathew V, Keshavayya J, Vaidya VP, Giles D. Studies on Synthesis and Pharmacological Activities of 3,6-disubstituted-1,2,4triazolo [3,4-b]-1,3,4-thiadiazoles and Their Dihydro Analogues. Eur J Med Chem. 2007;42:823-40. 2. Kritsanida M, Mouroutsou
A, Marakos P, Pouli N, Papakonstantinou-Garoufalias S, Pannecouque C, Witvouw M, De Clercq E. Synthesis and Antiviral Activity
Evaluation of Some New 6-substituted 3-(1-adamantyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles Il Farmaco. 2002;57:253-257. 3.
Lesyk R, Vladzimirska O, Holota S, Zaprutko L, Gzella A. New 5-substituted thiazolo [3,2-b][1,2,4]triazol-6-ones: Synthesis and
Anticancer evaluation. Eur J Med Chem. 2007;42:641-648.
PP 190 ENANTIOPURE AMIDES: SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY
CANER CEVIK , EYUP BASARAN , AYSEGUL KARAKUCUK-IYIDOGAN , EMINE ELCIN ORUC-EMRE
DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
The synthesis of chiral drugs in enantiopure form is very important in synthetic organic chemistry, medicinal chemistry, natural
product chemistry and the pharmaceutical industry. Approximately half of the drugs currently in use are chiral compounds,
and about 88% of these chiral synthetic drugs are used therapeutically as racemates. Unfortunately, there are many racemic
drugs where the stereospecificity of the metabolism and/or the pharmacodynamic effects of the enantiomers is not known.
Therefore, development of new effective and selective techniques are required for the manufacture of chiral drugs. Chiral
building blocks have an important place for the production of modern pharmaceutical drugs. Chiral amines have some
advantages for drug R&D such as a highly versatile, cheap and having attractive group of chiral building blocks [1-2]. In present
work, we synthesized twelwe chiral amide derivatives in high yields by the reaction of (R)-(-)-1,2,3,4-tetrahydro-1-methylamine/
(S)-(+)- 1,2,3,4-tetrahydro-1-methylamine with various 4-substitutedbenzoyl chlorides in diethylether at room temperature.
The chemical structure of new compounds were characterized by IR, 1H NMR, 13C NMR data and elemental analysis. In future,
the in vitro cytotoxic and antiviral activity of all chiral amides will be evaluated.
[1] Laumen K, Brunella A, Graf M, Kittelmann M, Walser P, Ghisalba O. New biocatalytic approaches for the synthesis of
chiraldrugs, intermediates, and substrates, Pharmacochemistry library, 1998; 29: 17-28. [2] Nguyen L, A , He H, Pham-Huy C.
Chiraldrugs: An Overwiev, Int J Biomed Sci. Jun, 2006; 2(2): 85–100.
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PP 191 SYNTHESIS OF NOVEL CHALCONE DERIVATIVES AND INVESTIGATION OF THEIR BIOLOGICAL ACTIVITY
ZEKERIYA TURGAY SELEN 1, EMINE ELCIN ORUC-EMRE 1, EYUP BASARAN 1, AYSEGUL KARAKUCUK-IYIDOGAN 1, AYSE
KARADUMAN 2, IBRAHIM HALIL KILIC2, MEHMET OZASLAN 2
1
2
DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
DEPARTMENT OF BIOLOGY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
Chalcones, the member of α,β-unsaturated ketone, have attracted a great deal of interest due to their applications as antibacterial,
antifungal, anti-inflammatory, antitubeculosis and anticancer pharmacological agents (1-3). We synthesized different substituted
chalcone compounds, N-(4[3-(4-substitutedphenyl)prop-2-enoil]phenyl)-4-fluoro/trifluoromethylbenzamide, by using N-(4acetylphenyl)-4-fluoro/trifluoromethylbenzamide as a starting compound. The structures of these compounds were elucidated
by spectroscopic method such as UV, IR, ¹H NMR, mass and elemental analysis. In addition to that, antibacterial activity of
synthesized chalcones were investigated against 9 different bacteries (Staphylococcus aureus ATCC 25923, Staphylococcus
aureus ATCC 6538, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 700603, Staphylococcus aureus ATCC
29213, Escherichia coli ATCC 25322, Escherichia coli ATCC 35128, Escherichia coli ATCC 10799, Escherichia coli ATCC 8739) .
1. Mishra N, Arora P, Kumar B, Virendra K. Synthesis of novel 1,3-diaryl propenone derivatives and theri antimalarial activity
in vitro. Eur. J. Med. Chem. 2008; 43: 1530-1535. 2. Jin C, Liang Y, He H, Fu L. Synthesis of novel chalcone derivatives. Biomed.
Pharmacotherapy 2013; 67: 215-217. 3. Yaylı N, Mısır G, Yaşar A, Demir E, Demirdağ Z. Synthesis and antimicrobial activity of
N-alkyl substituted p-methyl (E)-3- and 4-azachalconium bromides. Turk J. Chem. 2010; 34: 219-228
PP 192 THE SYNTHESIS OF NEW HYDRAZONE DERIVATIVES FROM 4-FLUOROBENZOHYDRAZIDE
NAZIRE MERVE KARTAL 1, EMINE ELÇIN ORUC-EMRE 1, EYUP BASARAN 1, AYSEGUL KARAKUCUK-IYIDOGAN 1, SEVIM ROLLAS 2,
BEDIA KOCYIGIT-KAYMAKCIOGLU 2
1
2
DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Hydrazone is a special member of Schiff base which contents the azomethine group and it is an important organic compound
that has R2C=NNH2 general formula. Hydrazide-hydrazone derivatives exhibited broad spectrum of biological activities such
as anticonvulsant, antidepressant, antimicrobial, antitumoral, analgesic, anti-inflammatory and antitubercular activities. In
our previous work, we synthesized some hydrazide-hydrazone derivatives which were shown to exhibit high antituberculosis
activity (1). Some of these compounds showed interesting in vitro activity against Mycobacterium tuberculosis H37Rv;
especially 4-fluorobenzoic acid [((5-nitro)thiophen-2-yl)methylene]hydrazide, which showed the highest inhibitory (99%
inhibition, MIC value 3.13 µg/mL) activity. In this study, 4-fluorobenzohydrazide has been synthesized by the reaction of phenyl
4-fluorobenzoate with hydrazine monohydrate (1). This compound reacted with 4-(4-substituted phenoxy)benzaldehyde in the
presence of methanol to form N-{[4-(4-substituted phenoxy)phenyl]methylidene}-4-fluorobenzohydrazide (2). The structure of
new compounds was confirmed using IR, NMR, mass and elemental analysis. These derivatives have been screened for antiAlzheimer activity.
1. Koçyiğit-Kaymakçıoğlu B, Oruç EE, Unsalan S, Kandemirli F, Shvets N, Rollas S, Dimoglo A. Synthesis and characterization of
novel hydrazide-hydrazones and the study of their structure–antituberculosis activity. Eur J Med Chem. 2006; 41(11):1253-1261.
2. Koçyiğit-Kaymakçıoğlu B, Oruç EE, Unsalan S, Rollas S. Antituberculosis Activity of hydrazones derived from 4-fluorobenzoic
acid hydrazide. Med Chem Res. 2009;18:277-286.
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PP 193 SYNTHESIS AND CHARACTERIZATION OF NEW THIOSEMICARBAZONE DERIVATIVES DERIVED FROM
4-(DIETHOXYMETHYL)BENZALDEHYDE
MUHAMMET IBRAHIM OZSOY , EYUP BAŞARAN , AYSEGUL KARAKUCUK-IYIDOGAN , EMINE ELCIN ORUC-EMRE
DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
Thiosemicarbazones are thiourea derivatives and analogues of semicarbazones which contains a sulfur atom in place of
the oxygen atom. The biological properties of thiosemicarbazone derivatives such as antibacterial, antifungal, antimalarial,
anticancer, anti-inflammatory, anticonvulsant, antioxidant, antiviral, activities have been extensively studied over the last 50
years (1). Generally thiosemicarbazone derivatives are synthesized by condensation of the corresponding thiosemicarbazides
with aldehydes or ketones. Therefore, their biological activities depend on the parent aldehyde and ketone (2,3). In view of
the above mentioned findings, we synthesized some new thiosemicarbazone derivatives derived from 4-(diethoxymethyl)
benzaldehyde in good yields and high purity The structure of the new synthesized 1,3-thiazoline derivatives were characterizated
by using UV, IR, 1H NMR, MS spectroscopy and elemental analysis.
1. Karaküçük-İyidoğan A, Mercan Z, Oruç-Emre EE, Taşdemir D, İşler D, Kılıç İH, Özaslan M. Synthesis, Characterization, and
Biological Evaluation of Some Novel Thiosemicarbazones as Possible Antibacterial and Antioxidant agents. Phosphorus,
Sulfur, and Silicon, 2014;189:661–673. 2. Karaküçük-İyidoğan A, Taşdemir D, Oruç-Emre EE, Balzarini J. Novel Platinum(II) and
Palladium(II) Complexes of Thiosemicarbazones Derived from 5-Substitutedthiophene-2-carboxaldehydes and Their Antiviral
and Cytotoxic Activities. Eur J Med Chem 2011;46(11):5616-5624. 3. Beraldo H, Gambino D. The wide pharmacological versatility
of semicarbazones, thiosemicarba-zones and their metal complexes. Mini Rev Med Chem 2004;4: 31-39.
PP 194 SYNTHESIS OF NEW 4-THIAZOLIDINONES INCORPORATED IMIDAZO[2,1-B]THIAZOLE MOIETY AS ANTIVIRAL AGENTS
ERKAN PEHLIVAN , NURAY ULUSOY GUZELDEMIRCI
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, FACULTY OF PHARMACY, İSTANBUL UNIVERSITY
A series of 3-alkyl/aryl-2-[[[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl]hydrazono]-5-nonsubstituted/methyl4-thiazolidinones (5a-l) was synthesized by cyclization of 4-alkyl/aryl-1-[[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]
acetyl]-3-thiosemicarbazides (4a-j) with ethyl bromoacetate or ethyl 2-bromopropionate (1). Their structures were elucidated
by elemental analyses and UV, IR, 1H-NMR, 13C-NMR (APT), 13C-NMR (DEPT), HSQC and ESI-MS data. The new compounds
were evaluated against some DNA and RNA viruses in CRFK, VERO, HEL and HeLa cell cultures.
1. Habib NS, Fahmy S, El-Khawass SM, Abdel Aziem T. Novel thiazolinyl, thiazolidinoyl, thiadiazolyl and oxadiazolylbenzotriazole
derivatives with potential antiinflammatory activity and minimum ulcerogenic effect. Pharmazie 2000; 55: 900-906.
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PP 195 INVESTIGATION OF INHIBITORY EFFECTS OF 3- AND 4- ARYL COUMARIN DERIVATIVES ON ACETYLCHOLINESTERASE
ACTIVITY
MERT GURCAN KARALI 1, OZKAN DANIS 1, MUSTAFA MUHLIS ALPARSLAN 2, CIHAN GUNDUZ 1, AYSE OGAN 1
1
2
DEPARTMENT OF CHEMISTRY, FACULTY OF ARTS AND SCIENCES, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF MEDICAL BIOCHEMISTRY, FACULTY OF MEDICINE, ÇUKUROVA UNIVERSITY, ADANA, TURKEY
Alzheimers disease (AD) is a progressive, chronic, neurodegenerative disorder that is characterized by a loss of memory and
cognition, decline in language, and severe behavioral abnormalities. It is the most common form of dementia among the elderly
and it is the fourth leading cause of death in developed countries. Neuropathological evidence has shown that the decreased
levels of acetylcholine, β- amyloid senile plaques and neurofibrillary tangles formation within the brain play a crucial role in
the pathogenesis of Alzheimers disease. Accordingly, the most promising approach for the symptomatic treatment of AD is
to increase the synaptic levels of ACh in the brain by inhibiting the acetylcholinesterase (AChE) enzyme, which is primarily
responsible for its hydrolysis and termination of action. Therefore, AChE inhibitors such as galanthamine, donepezil, and tacrine
are the main drugs for the clinical management of AD. These compounds have shown to induce a modest improvement in
memory and cognitive functions. However, they don’t appear to prevent or slow down the progressive neurodegeneration.
Coumarins are naturally occurring phytochemicals in many plant species with a wide range of biological activities such as antiinflammatory, antitumor, antiviral, antimicrobial, antioxidant, antidepressant, anticancer and anticoagulant effects. The studies
have shown that naturally occurring and chemically synthesized coumarin analogs exhibit potent AChE inhibitory activity. In this
study, in order to evaluate potential AChE inhibitors, forty coumarin derivatives bearing different functionalities such as amino,
hydroxy, methoxy and acetoxy have been synthesized and confirmed on the basis of their spectral data. They were examined
for the first time for their inhibitory effect on Electrophorus electricus AChE by using acetylthiocholine iodide as substrate. Our
studies showed that 4-aryl coumarins were found to possess the highest inhibitory activity among the tested substances.
PP 196 SYNTHESIS AND STRUCTURAL ELUCIDATION OF SOME AMIDE DERIVATIVES
SEYMA ECE , EMİNE ELCIN ORUC-EMRE , EYUP BASARAN , AYSEGUL KARAKUCUK-IYIDOGAN
DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
Amide derivatives have been associated with various types of biological properties such as antitumor, anticonvulsant,
antimicrobial, analgesic and anti-inflamatory activities (1-3). In this research, 2-chloro-N-[4-(morpholin-4-yl)phenyl]acetamide
(I) was prepared by reaction of aniline with chloro acetylchloride in dioxane. This compound (I) was treated with different
aromatic or alicyclic amines such as aniline, 4-trifluoromethylaniline, morpholine to obtain N-[4-(morpholin-4-yl)phenyl]-2substituted acetamide. Synthesis of the final compounds has been caried out for the first time in this study. Physical and
chemical properties of these compounds have been confirmed by using their melting points, IR, NMR and elemental analysis
results.
1. Zhang S, Zhao Y, Liu Y, Chen D, Lan W, Zhao Q, Dong C, Xia L, Gong P. Synthesis and antitumor activities of novel 1,4-disubstituted
phthalazine derivatives. Eur J Med Chem. 2010;45: 3504-3510. 2. Khanna S, Madan M, Vangoori A, Banerjee R, Thaimattam
R, Ramesh M, Casturib SR, Pala M. Evaluation of glycolamide esters of indomethacin as potential cyclooxygenase-2 (COX-2)
inhibitors. Bioorg Med Chem 2006;14:4820-4833. 3. Ding L, Zhu J, Zheng C, Sheng C, Qi J, Liu X, Han G, Zhao J, Lv J, Zhou Y.
Synthesis and acrosin inhibitory activity of substituted 4-amino-N-(diaminomethylene) benzenesulfonamide derivatives. Bioorg
Med Chem Lett. 2011;21:6674-6677.
PP 197 SYNTHESIS AND CHARACTERIZATION OF NEW SULFONYLHYDRAZONE DERIVATIVES
MEVLUDE BETUL KOSELI , EMİNE ELCIN ORUC-EMRE , EYUP BASARAN , AYSEGUYL KARAKUCUK-IYIDOGAN
DEPARTMENT OF CHEMISTRY, FACULTY OF ART AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
It is well known that compounds containing sulfonylhydrazone group have been reported to possess antibacterial, antifungal,
antitumor and antidepressant activities (1,2). New sulfonylhydrazone derivatives bearing electron donating or electron
withdrawing substitutions were designed and synthesized from 4-fluorobenzenesulfonohydrazide. N -[[4-(4-substitutedphenoxy)
phenyl]methylidene]-4-fluorobenzohydrazides were obtained by reaction of 4-fluorobenzenesulfonohydrazide with different
aldehydes in methanol. The structure of the new compounds have been established by elemental analysis and IR, 1H-NMR and
mass spectra.
1. Hafez HN, El-Gazzar ABA . Synthesis and antitumor activity of substituted triazolo[4,3-a]pyrimidin-6-sulfonamide with an
incorporated thiazolidinone moiety. Bioorg. Med. Chem. Lett. 2009; 19: 4143–4147. 2. Navakoski de Oliveira K, Costa P, Santin JR,
Mazzambani L, Bürger C, Mora C, Nunes RJ, Souza MM. Synthesis and antidepressant-like activity evaluation of sulphonamides
and sulphonyl-hydrazones Bioorg. Med. Chem. 2011; 19: 4295–4306.
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PP 198 EFFECTS OF METHANOL EXTRACT OF MARRUBIUM CRASSIDENS BOISS ON ISCHEMIA/REPERFUSION INDUCED
ARRHYTHMIAS AND INFARCT SIZE IN THE ISOLATED RAT HEART
SEYEDEHNEGISA SEYEDTOUTOUNCHI 4, MARYAM RAMESHRAD 1, HALEH VAEZ 1, SANAZ HAMEDEYAZDAN 2, MAHDIYEH
PASHAII 3, ALIREZA GARJANI 1, FATEMEH FATHIAZAD 2
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES
3
STUDENT RESEARCH COMMITTEE, FACULTY OF PHARMACY,TABRIZ UNIVERSITY OF MEDICAL SCIENCES
4
STUDENT RESEARCH COMMITTEE, GIFTED AND TALENTED STUDENT SUPPORTING UNIT, TABRIZ UNIVERSITY OF MEDICAL
SCIENCES
1
2
The objectives of present study were phytochemical screening and study of the cardioprotective effects of the methanol extract
of Marrubium crassidens on Ischemia/Reperfusion (I/R) injuries in isolated rat heart. The leaves of plant were extracted with
methanol by maceration and subjected to colorimetry to determine its compounds. The isolated hearts were mounted on a
Langendorff apparatus then perfused during 30 min regional ischemia and 120 min reperfusion, either by modified KrebsHenseleit solution (KHBS) in control group or enriched KHBS with the extract (10, 50, and 100 µg/ml) in treatment groups.
After reperfusion, the hearts stained by Evans blue solution then incubated by triphenyltetrazolium chloride. The percentage
of infarct size was determined by Image-j software. Phytochemical screening indicated the presence of phenolic compounds
and flavonoids. The results demonstrated that the extract caused a significant reduction in the number of total ventricular
ectopic beats (100 µg/ml, p<0.05) during ischemia and reperfusion. It also significantly reduced the ventricular tachycardia
(VT) number (10µg/ml, p<0.05and 100 µg/ml, p<0.001) and duration (10 µg/ml, p<0.05) during ischemia. The VT incidence was
reduced from 100% in the control group to 20% in the treated-group with 100 µg/ml (p<0.01). The infarct size was reduced from
70.74±10.35% in the control group to 19.11±6.26 (p<0.001) and 25.27±3.89% (P<0.01) in groups treated by 10 and 50 µg/ml of
extract, respectively. The results of the study suggest that the extract has protective effects against I/R injuries in isolated rat
heart which could be related to antioxidative activities of its phenolic and flavonoids compounds.
PP 199 SUPRESSION OF DIABETIC RETINOPATHY FORMATION VIA ALPHA-AMYLASE AND GLUCOSIDASE INHIBITION
POTENTIAL OF RUMEX ACETOSELLA
NADIRE OZENVER , L. OMUR DEMIREZER
HACETTEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOGNOSY ANKARA, TURKEY
Diabetic retinopathy (DR) is the main cause of blindness in industrialised countries. The most effective medical treatment to slow
the progression of DR is glycemic control. Therefore to decrease hyperglycemia is a very significant therapeutic approach for
treating diabetes. This can be achieved through the inhibition of carbohydrate hydrolyzing enzymes such as alpha glucosidase and
alpha amylase. Alpha amylase and alpha glucosidase inhibitors can be an important strategy in the development of compounds
in the management of hyperglycemia linked to type II diabetes (1). Rumex acetosella L. (Polygonaceae) has been commonly
used for diabetes, stomach and heart diseases in traditional MEDICINE. The phytochemical studies have shown the presence
of anthraquinones, naphthalens, tannins in Rumex acetosella. The frequently occurring anthraquinone derivatives of Rumex
species are aloe-emodin, chrysophanol, emodin, physcion, rhein and their glycosides. In this study nonpolar extract of Rumex
acetosella roots were characterized with HPLC-DAD. Due to the main anthraquinone aglycones have significant interactions
with alpha amylase as a result of in silico docking study, crude standardised extract from Rumex acetosella were validated for
alpha amylase and alpha glucosidase inhibition potential. This study has provided a basis for future research about whether R.
acetosella and including compounds will have a potential to treat diabetes or not in traditional uses. 1. Kwon YI, Apostolidis E,
Shetty K. In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type 2 diabetes
and hypertension. Bioresource Technology. 2008; 99: 2981-2988.
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PP 200 BIOLOGICAL ACTIVITY OF SOME CHALCONE DERIVATIVES
YUSUF SICAK 1, BEDRIYE SEDA KURŞUN AKTAR 2, EMINE ELCIN ORUC EMRE 3, MEHMET OZTURK 1, IBRAHIM DEMIRTAS 2,
AYSEGUL KARAKUÇUK IYIDOĞAN 3
FACULTY OF PHARMACY MUGLA SITKI KOCMAN UNIVERSITY, MUGLA, TURKEY
FACULTY OF PHARMACY CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY
3
FACULTY OF PHARMACY GAZIANTEP UNIVERSTY, GAZIANTEP, TURKEY
1
2
This work is a research on antioxidant, anti-Alzheimer and urease enzyme activities of chalcones derivated from
4-morpholinoacetophenone. These derivatives have been synthesized by Claisen-Schmidt condensation of substitutedaldehyde
with 4-morpholinoacetophenone (1). The antioxidant activity of chalcone derivatives was determined as β-carotene-linoleic
acid, DPPH radical scavenging, superoxide anion radical scavenging, ABTS cation radical scavenging, and CUPRAC methods.
In vitro inhibitory activity of acetylcholinesterase and butyrylcholinesterase enzymes related with Alzheimers disease was
determined using Ellmans method (2). Also, to determine the inhibitory activity of urease was used Mobley method (3).
1. Kurşun BS. The synthesis and characterization of novel chalcone derivated from 4morfolinoacetophenone and anticancer
activity. Yüksek Lisans Tezi. 2011. 2. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric
determination of acetylcholinesterase activity. Biochemistry and Pharmacology and Behaivor. 1961; 7: 88–95. 3. Mobley HLT,
Island MD, Hausinger RP. Microbial Ureases-Significance, Regulation, and Molecular Characterization. Microbiological Reviews.
1989; 53: 85–108.
PP 201 SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY OF NOVEL THIOUREAS DERIVATED FROM
4-(4-FLUOROPHENOXY)ANILINE
INCI NEJLA YILDIZ 1, YUSUF SICAK 2, EMINE ELÇIN ORUÇ EMRE 1, MEHMET OZTURK 2, AYSEGUL KARAKUCUK IYIDOGAN 1
1
2
FACULTY OF PHARMACY GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
FACULTY OF PHARMACY MUGLA SITKI KOCMAN UNIVERSITY, MUGLA, TURKEY
Thioureas used in pharmaceutical research are an important class of compounds nitrogen and sulphur-containing. During
recent years, thiourea compounds have known many biological properties such as anti-HIV, antitubercular, analgesic, anticancer
activities (1-3). In this research; a new series of thiourea derivatives were obtained by the reaction of 4-(4-flourophenoxy)
aniline with the different isothiocyanates (3). The purity were controlled by TLC and the chemical structures of the synthesized
compounds were elucidated using UV, IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analysis. The biological
activities of synthesized thiourea derivatives have been screened as antioxidant, anti-Alzheimer activity and urease enzyme
activity.
1. Küçükgüzel I, Tatar E, Küçükgüzel ŞG, Rollas S, De Clercq. Synthesis of some novel thiourea derivatives obtained from
5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-d,hydro-3H-1,2,4-triazole-3-thiones and evaluation as antiviral/anti-HIV and antituberculosis agents. Eur. J. Med. Chem. 2008; 43(2): 381-392. 2. Mahajan A, Yeh S, Nell M, van Rensburg CJ, Chibale K. Synthesis
of new 7- chloroquinolinyl thioureas and their biological investigation as potential antimalarial and anticancer agents. Bioorg.
Med. Chem. 2007; 17: 5683-5685. 3. Kaymakçıoğlu, B.K, Rollas, S, Körceğez, E, Arıcıoğlu, F. Synthesis and biological evaluation
of new N’substitued-N’-(3,5-di/1,3,5-trimethylpyrazole-4-yl) thiourea/urea derivatives. Eur. J. Pharm. Sci. 2005; 26 : 97-103.
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PP 202 SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME NOVEL 1-(4-MORPHOLINOPHENYL)-3-(4-(4-SUBTITUTEDPHENOXY)
PHENYL)PROP-2-EN-1-ONE DERIVATIVES
YUSUF SICAK 1, MEHMET OZTURK 1, B. SEDA KURSUN AKTAR 2, IBRAHIM DEMIRTAS 2, E. ELCIN EMRE 3, AYSEGUL KARAKUCUK
IYIDOGAN 3
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCES, MUGLA SITKI KOÇMAN UNIVERSITY, MUGLA, TURKEY
DEPARTMENT OF PROPERTY PROCTECTION AND SECURITY, YAPRAKLI VOCATIONAL SCHOOL, CANKIRI KARATEKIN UNIVERSITY,
CANKIRI, TURKEY
3
DEPARTMENT OF CHEMISTRY, FACULTY OF ARTS AND SCIENCES, GAZIANTEP UNIVERSITY, GAZIANTEP, TURKEY
1
2
Searching for the therapeutic agents, novel series of 1-(4-morpholinophenyl)-3-(4-(4-subtıtutedphenoxy)phenyl)prop-2en-1-one derivatives were synthesized by using Claisen-Schmidt condensation with 1-(4-morpholinophenyl)ethanone and
4-(4-substitutedphenoxy)benzaldehyde. The in vitro antioxidant, anticholinesterase and urease inhibitory activities of newly
isolated chalcones derivatives were carried out. The antioxidant activity was determined by five complimentary assays; namely,
β-carotene-linoleic acid, DPPH radical scavenging, superoxide anion radical scavenging, ABTS cation radical scavenging, and
CUPRAC methods (1).The anticholinesterase activity was determined by using Ellmans method against acetylcholinesterase
and butyrylcholinesterase which were the chief enzymes of Alzheimers disease (2). In order to determine the urease enzyme
inhibitory activity, however, Mobley method was used (3).
1. Oztürk M, Aydoğmuş-Oztürk F, Duru ME, Topçu G. Antioxidant activity of stem and root extracts of Rhubarb (Rheum ribes):
An edible medicinal plant. Food Chemistry. 2007; 103: 623-630. 2. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new
and rapid colorimetric determination of acetylcholinesterase activity. Biochemistry and Pharmacology and Behaivor. 1961; 7:
88–95. 3. Mobley HLT, Island MD, Hausinger RP. Microbial Ureases-Significance, Regulation, and Molecular Characterization.
Microbiological Reviews. 1989; 53: 85–108.
PP 204 EFFECTS OF BENTAZONE ON LIPID PEROXIDATION AND ANTIOXIDANT SYSTEMS IN HUMAN ERYTHROCYTES IN VITRO
MAHMOUD ABUDAYYAK , SIBEL OZDEN , BUKET ALPERTUNGA , GUL OZHAN
DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, ISTANBUL UNIVERSITY
Bentazone, a benzothiadiazole herbicide, is widely used for a variety of crops including cereals, maize, peas, rice and soy beans.
The concern for human health is stil very high because bentazone is continuously monitored in environment and several studies
to evaluate its potential carcinogenic effects when chronic and high doses were administered to animals. We aimed to investigate
the possible effects of bentazone on lipid peroxidation, levels of glutathione and activities of antioxidant enzymes in human
erythrocytes in vitro. For that, erythrocyte were incubated with bentazone in different concentrations (0–50 nM) at 37 C for 1
hr. Bentazone showed significant increase in the levels of malondialdehyde (MDA) at the highest concentration in erythrocytes
as an index of lipid peroxidation. Besides, alterations in the levels of reduced glutathione (GSH) and activities of glutathione
peroxidase (GSH-Px) were observed while the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase
(GSH-Rd) were unchanged. In conclusion, findings from this study indicate that in vitro toxicity of bentazone may be associated
with oxidative stress and this work warrants further in vivo investigations.
PP 204 RESEARCHİNG OF TOCILIZUMAB EFFECT’S IN EXPERİMENTAL ALZHEIMER MODEL
ERSIN ASLAN , HATICE KUBRA ELCIOGLU , LEVENT KABASAKAL
MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL, TURKEY
Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer’s Disease (AD). It was suggested that IL-6 shows
overespression and pleiotropic activity in AD’s brain. Tocilizumab (TCZ) that is a humanized anti-human IL-6 receptor (IL-6R)
monoclonal antibody, inhibits IL-6 signal transduction. The aim of our study is to learn that the effect of Tocilizumab on AD
cognitive deficits caused by intracerebroventricular (i.c.v.) injection of streptozotocin (STZ). Male Sprague-Dawley rats were
divided into three different groups: control, STZ and TCZ+STZ. Rats that are in STZ and STZ+TCZ groups, were injected single
dosed bilaterally i.c.v STZ (3mg/kg) stereotaxically to induce experimental Alzheimer’s disease. We used single dose of i.c.v.
TCZ beginning 1 h prior to injection of STZ for 21 days. Behavioral parameters were evaluated between 15st-21st days, and
the rats were sacrificed on day 21st to examine histopathological changes. Histopathological changes were examined using
hematoxylin-eosin. Tocilizumab treatment attenuated significantly STZ induced cognitive impairment and histopathological
changes. Further studies are warranted to investigate more protective effect about Tocilizumab on AD. STZ injection caused a
significant decrease in the mean escape latency in passive avoidance and decreased improvement of performance in morris
water maze tests. Brain sections of TCZ treated rats showed decreased Aβ and IL-6 levels in the neurons and glial cells of cortical
area compared to STZ.
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PP 205 PHYTOCHEMICAL ANALYSIS AND SOIL PROPERTIES OF CERINTHE GLABRA MILLER (BORAGINACEAE)
EBRU GUL 1, AYSE SAHIN YAGLIOGLU 2, MELDA DOLARSLAN 3, HASAN SOYLEMEZ 2, IBRAHIM DEMIRTAS 2
DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, 18100, CANKIRI, TURKEY
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
3
DEPARTMENT OF BIOLOGY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, 18100 CANKIRI, TURKEY
1
2
Cerinthe glabra Miller belongs to the family Boraginaceae, the plants of family use decorative plants, spices, and useful
for the preparation of dyestuffs. Active agents of the family are mucilage derivatives (arabinose, glucose and galactose),
Pyrolizidinalkaloits (Amabilin, Supinidin, Lycopsamin, Intermedin, 7-Asetil-Lycopsamin ve 7-Asetilintermedin). Also, The family
contains tannins, saponins, resins, starches, silicic acids, vitamin C and minerals (1). C. glabra Miller is a perennial herb. However,
this plant grow Central and Southern Europe, the Balkans and the Caucasus in the World; the North and East Anatolian (Çankırı,
Kastamonu, Bitlis, Ağrı, Artvin, Tunceli and Van) in Turkey (2) . In this study, C. glabra Miller (Boraginaceae) were collected from
Çankırı. Physical and chemical soil properties of collected area are moderately alkaline (7.6-8.5 pH), sandy clay loam-clay loam
texture and unsalted soil. Species identification of the collected materials were performed. This plant were separated as leaves,
stems and roots and dried at room temperature (25 °C) in the shade. The extracts of these materials which were acetone,
chloroform, ethyl acetate and ethanol extracts were prepared, respectively. The fatty acides of acetone and chloroform extracts
by GC-MS and phenolic compounds in ethyl acetate and ethanol extracts by the HPLC-TOF/MS were performed. As a result
of GC-MS analyzes were detected 19 fatty acid, palmitic acid, linolenic acid and linoeic acid as the main component. The 16
different phenolic compounds were determined from HPLC-TOF-MS and were obtained vanillic acid, 4-hydroxybenzoic acid and
cicoric acid as the main components.
1. Baytop, T. 1999. Türkiye’de Bitkiler İle Tedavi, Nobel Tıp Kitabevleri, İstanbul. 2. Davis, P. H., 1965-1988, Flora of Turkey and
the East Aegean Islands, vol. 1-9, Edinburgh: Edinburgh UNIVERSITY Pres.
PP 206 THE PHYTOCHEMICAL ANALYSIS, ANTIPROLIFERATIVE AND CYTOTOXIC EFFECTS OF RHYTIDIADELPHUS TRIQUETRUS
(HEDW.) WARNST. MOSS EXTRACTS
MUHAMMET SAMIL YAGLIOGLU 1, GOKHAN ABAY 1, IBRAHIM DEMIRTAS 2, AYSE SAHIN YAGLIOGLU 2
1
2
DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY
Bryophyt species have been used as medicinal plant from the more than 400 years (1,2). Bryophyt species have some biological
activity such as, the antidote, antipyretic, diuretic, hair extenders, burns, jaundice, hemostasis, epilepsy, lowering blood
pressure, soothing, antimicrobial, antifungal (3). In this study, Rhytidiadelphus triquetrus moss material was collected in forest
area from Çankırı. Species identification of the collected material was performed. This moss dried at room temperature in the
shade. The extracts of the materials which were hexane, chloroform, ethyl acetate, methanol, water, water / ethyl acetate and
water / n-butanol, were prepared respectively. The fatty acids of hexane extracts by GC-MS and other phenolic compounds in
extracts by the HPLC-TOF-MS were performed. As a result of GC-MS analyzes were detected 8 compounds and arachidic acid (%
25.39), linolenic acid (% 20.70), arachidonic acid (% 17.60), 4,7,7-trimethylbicyclo[3.3.0]octan-2-one (% 14,67) and palmitic acid
(% 13,15) as the main components. As a result of HPLC-TOF-MS analyzes were determined, salicilic acid from the choloroform
extract; 4-hydroxybenzoic acid from the ethyl acetate and methanol extractc; gallic acid from water extract; quercetin and
gentisic acid from the water-ethyl acetate; gentisic acid and 4-hydroxybenzoic acid from the water-n-buthanol extract as the
main components. The obtained antiproliferative activity of all extracts were determined by BrdU ELISA method against HeLa
and C6 cells. The hexane, chloroform, ethyl acetate extracts have high antiproliferative activity. Thus, the extracts were detected
cytotoxic activities and was found to be less toxic than 5-fluorouracil used as a standard.
1. Asakawa, Y. 1990a. in eds.: R.N. Chopra and S.C. Bhatla, Biologically Active Substance from Bryophytes, Bryophyte Development:
Physiology and Biochemistry, Boston: CRC Press. 2. Asakawa, Y., Ludwiczuk, A., Nagashima, F. 2013. Phytochemical and biological
studies of bryophytes. Phytochemistry, 91; 52-80. 3. Ding, H., 1982. Zhong guo Yao Yun Bao zi Zhi Wu. Kexue Jishu Chuban She.
Shanghai, 409 p.
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PP 207 THE PHYTOCHEMICAL ANALYSIS, ANTIPROLIFERATIVE AND CYTOTOXIC EFFECTS OF TORTELLA TORTUOSA (HEDW.)
LIMPR. MOSS EXTRACTS
MUHAMMET SAMIL YAGLIOGLU 1, GOKHAN ABAY 1, IBRAHIM DEMIRTAS 2, AYSE SAHIN YAGLIOGLU 2
1
2
DEPARTMENT OF FOREST ENGINEERING, FACULTY OF FOREST, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY
DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, CANKIRI KARATEKIN UNIVERSITY, CANKIRI, TURKEY
Some bryophyt species have biological activities such as anticancer (1), antimicrobial and antifungal (2), insecticidal activity (3).
In this study, the moss Tortella tortuosa (Hedw.) Limpr. was collected in forest area from Çankırı. Species identification of the
collected material was performed. This moss dried at room temperature in the shade. The extracts of the material, hexane,
chloroform, ethyl acetate, methanol, water, water / ethyl acetate and water -n-butanol were prepared respectively. The fatty
acids of hexane extracts by GC-MS and other phenolic compounds in extracts by the HPLC-TOF-MS were performed. As a
result of GC-MS analyzes 15 compounds and Linolenic acid, methyl ester (% 52,97), Linoleic acid (% 8,53) and Palmitic acid (%
5,52) were detected as the main components. As a result of HPLC-TOF-MS analyzes, caffeic acid from the chloroform extract;
4-hydroxybenzoic acid from the ethyl acetate extract; gentisic acid and 4-hydroxybenzoic acid from methanol and water-ethyl
acetate extracts; gallic acid from water extract; gentisic acid from the water-n-buthanol extract were determined as the main
components. The antiproliferative activity of all extracts was determined by the BrdU ELISA method against HeLa and C6 cells.
The hexane, chloroform, ethyl acetate and water-ethyl acetate extracts were shown to have high antiproliferative activity. Thus,
the extracts (exceptional water-ethyl acetate extract) were found to be less toxic than 5-fluorouracil used as a standard.
1. Oztopcu Vatan, P., Kabadere, S., Uyar, R., Savaroglu, F., Kus, G. 2012. Time dependent cytotoxic role of Homalothecium
sericeum extracts on glioma. Biological Diversity and Conservation, 5(1); 1-4. 2. Savaroglu, F., Ilhan, S., Filik-Iscen, C. 2011. An
evaluation of the antimicrobial activity of some Turkish mosses, Journal of Medicinal Plants Research, 5 (14); 3286-3292. 3.
Abay, G., Karakoç, Ö. C., Tüfekçi, A. R., Koldaş, S., Demirtaş, İ. 2012. Insecticidal activity of Hypnum cupressiforme (Bryophyta)
aganist Sitophilus granarius (Coleoptera: Curculionidae), Journal of Stored Products Research, 51; 6-10.
PP 208 MITRAL RING ANNULOPLASTY IN A PATIENT WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA SUCCESSFULLY
MANAGED WITH CORTICOSTEROIDS
MURAT BULENT RABUS 1, SULE APIKOGLU-RABUS 2, MURAT SONGUR 1, ONUR YERLIKHAN 1, RAHMI ZEYBEK 1
KARTAL KOSUYOLU TRAINING AND RESEARCH HOSPITAL; CARDIOVASCULAR SURGERY DEPARTMENT
MARMARA UNIVERSITY FACULTY OF PHARMACY; CLINICAL PHARMACY DEPARTMENT
1
2
A 38 years old woman admitted to our hospital with the complaints of increasing dyspnea, ortopnea and pretibial edema. She
had been diagnosed with rheumatoid mitral regurgitation for 10 years and with idiopathic thrombocytopenic purpura for 8
years. On admittance, her platelet count was 39000/mm3. Intravenous metilprednisolon treatment was started three days
before the operation. The platelet count reached 118000/mm3 on the day of operation. She underwent a successful surgery.
The postoperative course was uneventful. The patient received postoperative thrombocyte suspension and intravenous
methylprednisolon on the postoperative first and second days. Oral prednisolon was administered as the maintenance therapy.
Platelet counts were stable throughout the preoperative, operative and early-postoperative periods. Mitral ring annuloplasty was
safely performed with no postoperative complications in a patient with idiopathic thrombocytopenic purpura, by administration
of preoperative and postoperative intravenous methylprednisolone and platelet transfusion at early-postoperative period.
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PP 209 PROTECTIVE EFFECT OF CHARD EXTRACT ON GLYCOPROTEIN COMPONENTS AND HYDROXYPROLINE LEVELS IN
DIABETIC LUNG TISSUE
OZLEM SACAN 1, ONUR ERTIK 1, YESIM IPCI 2, LEVENT KABASAKAL 2, GOKSEL SENER 2, REFIYE YANARDAG 1
ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMISTRY-34320 AVCILAR/ISTANBUL/TURKEY
MARMARA UNIVERSITY, SCHOOL OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, 34668-HAYDARPASA, ISTANBUL/
TURKEY
1
2
Chard (Beta vulgaris L. var cicla) is a popular vegetable, known for a long time for its beneficial health effects. Various reports have
demonstrated that chard has antioxidant, antiacetylcholinesterase, antidiabetic and hepatoprotective effects. Moreover, chard
exhibits mineralizing, antiseptic and choleretic activities as well as it contributes to the reinforcement of the gastric mucosa. In
the present study, the protective effect of chard on glycoprotein and hydroxyproline levels in the lung tissue of streptozotocin
(STZ) – induced diabetic rats was examined. Male, Sprague Dawley rats were used in the study. Rats were randomly divided into
three groups.Group I; Control animals given citrate buffer,Group II; Diabetic animals treated with STZ, Group III; STZ-diabetic
animals given chard extract. The chard extract was administrated by gavage technique to rats at a dose of 2 g/kg/day for 45 days
, 15 days after animals were made diabetic. Hyperglycemia was induced by as a single dose STZ (60 mg/kg), intraperitoneally.
On day 60, lungs were removed from rats and used for the analysis of glycoprotein and hydroxyproline levels. Glycoprotein
components such as hexose, hexosamine, fucose and sialic acid, and hydroxyproline levels significantly increased in lung tissues
of diabetic rats. Administration of chard significantly decreased glycoprotein components and hydroxyproline levels in the
diabetic group, indicating that chard possess a significant beneficial effect on glycoprotein components and hydroxyproline
levels. These results suggested that chard might have a significant role in alleviating lung damage in STZ diabetic rats.
PP 210 INHIBITION OF NEURAMINIDASE BY SOME CHEMICAL COMPOUNDS AND SOME PLANT EXTRACTS
ONUR ERTIK , REFIYE YANARDAG
ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMISTRY, 34320-AVCILAR, ISTANBUL/TURKEY
Neuraminidase (Sialidase, EC:3.2.1.18, NA) belongs to a class of glycosyl hydrolases that release terminal N-acetyl neuraminic
acid residues from glycoproteins, glycolipids and polysaccharides. It is known to play an important role in pathogenesis,
bacterial nutrition and cellular interaction. Neuraminidase is especially believed to play at least two critical roles in influenza
viral life cycle; the facilitation of virion progeny release; and general mobility of the virus in the respiratory tract.In order to
develop new agents to treat viral disease, significant attention has been devoted to compounds that inhibit viral adsorption
to epithelial cells, viral intrusion into cells, transcription and replication of viral genomes, viral protein expression and progeny
virus release from cells. In this study, neuraminidase inhibitory activities of some chemical compounds and some plant extracts
were investigated. Neuraminidase activity was determined using the method of Myers et al. with some modification. All plant
extracts and chemical compounds have good antineuraminidase activities. The enzyme inhibitory activity was found to increase
dose dependently. We can conclude that the examined plant extract and chemical drugs can be used in pharmaceutical industry
due to their excellent antineuraminidase activities.
PP 211 EFFECTS OF COMBINATION TREATMENT WITH AMIODARONE AND WHITE CABBAGE EXTRACT ON RAT GINGIVA AND
SALIVARY GLAND
BURCIN ALEV 1, ISMET BURCU TURKYILMAZ 2, SARP KAYA 3, SERAP AKYUZ 3, REFIYE YANARDAG 2, AYSEN YARAT 1
MARMARA UNIVERSITY, FACULTY OF DENSITY, DEPARTMENT OF BASIC MEDICAL SCIENCES, ISTANBUL,TURKEY
ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMİSTRY, ISTANBUL,TURKEY
3
MARMARA UNIVERSITY, FACULTY OF DENSITY, DEPARTMENT OF CLINICAL SCIENCES, ISTANBUL,TURKEY
1
2
Cabbage (Brassica oleracea L. var. capitata) is one of the most important vegetables grown worldwide. It provides significant
amounts of vitamins (A, C, E, K) and other photochemicals, such as glucosinates and other sulfur containing compounds which
are beneficial for human health. Numerous studies report protective effects of cabbage against many chronic diseases, several
cancer types, cardiovascular, cerebrovascular, ocular and many neurological diseases and peptic ulcers. It may protect from the
side effects of amiodarone which is used for the treatment of arrhythmias. In the literature there is no study which focuses
on the effects of these substances on oral tissues. Female Sprague-Dawley rats were randomly divided into four groups as
follows; control group receiving corn oil; cabbage extract (500 mg/kg/day) given group; amiodarone (100 mg/kg/day) given
group; amiodarone + cabbage extract (in same dose) given group. Cabbage extract and amiodarone were given by gavage to
rats for 7 days. Amiodarone was given to the animals one hour after cabbage extract administration during the experimental
period. All animals were fasted overnight and on the 8th day they were sacrificed under anesthesia. Gingiva and salivary gland
samples were taken from animals and homogenized in saline. Oxidant-antioxidant biochemical parameters were determined in
homogenized samples. Results were evaluated statistically and discussed.
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PP 212 EFFECTS OF EXERCISE AND CALORIC RESTRICTION ON METABOLIC SYNDROME INDUCED INTESTINAL OXIDATIVE
INJURY IN RATS
HAZAL IPEKCİ 1, REYHAN OZCELIK 2, BURCIN ALEV 1, UNSAL VELI USTUNDAG 1, OZAN OZCAN 1, TUGBA TUNALI-AKBAY 1, EBRU
EMEKLI-ALTURFAN 1, GOKSEL SENER 2, AYSEN YARAT 1
1
2
MARMARA UNIVERSITY FACULTY OF DENTISTRY, DEPARTMENT OF BASIC MEDICAL SCIENCES, ISTANBUL TURKEY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL, TURKEY
In the pathogenesis of the metabolic syndrome, an increase of oxidative stress may play an important role which is closely
linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of this study was to assess the
effects of exercises and caloric restriction on some small intestine oxidative stress parameters in rat with metabolic syndrome.
Fifty-six male Sprague-Dawley rats, weighing 250-350g, were divided into five groups: control, metabolic syndrome, metabolic
syndrome with exercise, metabolic syndrome with caloric restriction and metabolic syndrome with exercise and caloric
restriction. To induce metabolic syndrome 10 % fructose solution was given to rats in their drinking water for 3 months. Exercise
and caloric restriction were applied to the related groups for 3 weeks after the induction of metabolic syndrome. At the end
of the experiment all animals were fasted overnight. They were sacrificed under anesthesia. Small intestine samples were
taken from animals and homogenized in saline. Oxidant-antioxidant biochemical parameters were determined in homogenized
intestine samples. Results were evaluated statistically and discussed.
PP 213 EFFECTS OF EXERCISE AND CALORIC RESTRICTION ON AGING INDUCED INTESTINAL OXIDATIVE INJURY IN RATS
UNSAL VELI USTUNDAG 1, CAGLAR MACIT 2, BURCIN ALEV 1, HAZAL IPEKCI 1, HAZAL HAZINECI 1, EBRU EMEKLI-ALTURFAN 1,
TUGBA TUNALI-AKBAY 1, GOKSEL SENER 3, AYSEN YARAT 1
MARMARA UNIVERSITY FACULTY OF DENTISTRY, DEPARTMENT OF BASIC MEDICAL SCIENCES, ISTANBUL, TURKEY
YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL, TURKEY
3
MARMARA UNIVERSITY FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ISTANBUL, TURKEY
1
2
Aging is related with increased intestinal inflammation and elevated risk of chronic diseases such as inflammatory bowel
diseases and colon cancer. Accordingly reduced risk of these diseases has been shown in many epidemiologic studies by regular
exercise. Physical activity including regular and repetitive exercise has been shown to decrease the incidence of age-related
diseases. In this study, male 15 months old Sprague-Dawley rats, weighing 300-500g, were divided into four groups: aging, aging
with caloric restriction, aging with exercise, aging with exercise and caloric restriction. Young animals (3 months old) were used
as control group. Exercise and caloric restriction were applied to the related groups for 6 weeks.At the end of the experiment
all animals which were fasted overnight,were sacrificed under anesthesia. Small intestine samples were taken from animals
and homogenized in saline. Oxidant-antioxidant biochemical parameters were determined in homogenized intestine samples.
Results were evaluated statistically and discussed.
PP 214 SYNTHESIS AND CHARACTERIZATION OF NEW 4-SUBSTITUTED-N’-(PIPERIDIN-4-YLIDENE)
BENZENESULFONOHYDRAZIDES
NURCAN KARAMAN , EMINE ELCIN EMRE , AYSEGUL IYIDOGAN
FACULTY OF PHARMACY GAZIANTEP UNIVERSITY, ANKARA, TURKET
Sulfonylhydrazone type of compounds have been reported that they have good level of antimicrobial, anticancer and
antidepressant activity (1,2). On the basis of this knowledge, in this study a series of sulfonylhydrazones of piperidin-4-one
derivatives were synthesized. In order to obtain these compounds, sulfonyl hydrazides were reacted with ethyl 4-oxopiperidine
1-carboxylate and 2,6-diphenylpiperidin- 4-one to afford sulfonylhydrazones. Physical and chemical properties of synthesized
compounds have been characterized by utilizing their melting point, elemental analysis, IR, 1H-NMR and mass spectra results.
Acknowledgement: This study was supported by the Research Foundation of Gaziantep UNIVERSITY (Project no: FEF.11.03 ) 1.
Navakoski K., Costa P., Santin J.R., Mazzambani L., Bürger C., Mora C., Nunes R.J., Souza M.M. Synthesis and antidepressantlike activity evaluation of sulphonamides and sulphonyl-hydrazones. Bioorganic & Medicinal Chemistry. 2011; 19; 4295–4306
2. Zhang L., Yang F., Shi W., Zhang P., Li Y., Yin S. Synthesis and antigastric ulcer activity of novel 5-isoproyl-3,8-dimethylazulene
derivatives. Bioorganic & Medicinal Chemistry Letters. 2011; 21, 5722–5725
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PP 215 DRUG-INDUCED LIVER INJURY
GIZEM KAYA , SIBEL OZDEN
ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TOXICOLOGY
Drug induced liver injury Gizem Kaya, Sibel Ozden Istanbul UNIVERSITY, Faculty of Pharmacy, Department of Pharmaceutical
Toxicology, Beyazit, 34116, Istanbul-TURKEY. Drug-induced liver injury (DILI) is increasingly being recognised as a significant cause
of both acute and chronic liver disease. The most commonly implicated agents are paracetamol, antimicrobials, non-steroidal
antiinflammatory drugs, statins and isoniazid. It is seen herbal and dietary supplements cause to DILI. Drug induced-liver injury
is generally divided into intrinsic and idiosyncratic reactions. The idiosyncratic nature and poor diagnosis of DILI make this type
of reaction as major safety issue during drug development, as well as the most common cause for the withdrawal of drugs
from the pharmaceutical market. The formation of reactive metabolites during drug metabolism can lead to oxidative stress
and mitochondrial damage. The mitochondrial alterations are able to induce mild to fulminant hepatic cytolysis and steatosis.
Numerous investigations have also suggested a role for the host immune response. DILI depends on environmental, chemical,
pharmacological and genetic factors. This review manifests the potential role of reactive metabolites, mitochondrial toxicity,
host immune-response pathways and biliary transporters in the pathogenesis of DILI and also indicates risk factors for DILI.
PP 216 DETERMINATION OF ANTIOXIDANT ACTIVITY OF ASPLENIUM CETERACH SUBSP. ASPLENIUM
CENGIZ SARIKURKCU, SILA GULBAG, BASAK GOKCE
FACULTY OF PHARMACY ,SULEYMAN DEMIREL UNIVERSITY, ISPARTA, TURKEY
In this study, the antioxidant activity of ethanol and water extracts from Asplenium ceterach subsp. asplenium was studied.
The antioxidant properties of both extracts from A. ceterach subsp. asplenium were evaluated by using different antioxidant
tests; ferric reducing power, free radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and metal chelating activity
on ferrous ions (1).Total flavonoid content in the both extracts was also determined as quercetin (QEs) equivalents (1). In the
radical scavenging effect and reducing power assays, it was observed that both extracts from A. ceterach subsp. asplenium
increased with increasing concentration of the extracts and that the water extracts showed stronger DPPH scavenging activity
and reducing power rather than those of the ethanol extracts. It was found that the total flavonoid content in the ethanol and
water extracts were 15.13 and 12.34 QEs/g extract, respectively. On the basis of the results of this study, it is clear that both
extracts have powerful antioxidant activity against various antioxidant systems in vitro, moreover, this plant can be used as
easily accessible source of natural antioxidants and as a possible food supplement or in pharmaceutical applications.
1. Zengin G, Sarikurkcu C, Aktumsek A, Ceylan R, Ceylan O. A comprehensive study on phytochemical characterization of
Haplophyllum myrtifolium Boiss. endemic to Turkey and its inhibitory potential against key enzymes involved in Alzheimer, skin
diseases and type II diabetes. Ind. Crop Prod. 2014; 53: 244-251
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PP 217 THE STUDY ON THE FREQUENCY OF XENOBIOTIC-METABOLIZING ENZYME GENE POLYMORPHISMS CYP2C9 IN A
TURKISH POPULATION
SERRA VILDAN AKGUL 1, TUGCE YESIL 1, OSMAN EKINCI 3, BERNA TERZIOGLU 2, GULDEN Z. OMURTAG1, SEMRA ŞARDAŞ 1
,I.OMER BARLAS4
DEPARTMENTS OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY,
DR. SIYAMI ERSEK GOGUS KALP VE DAMAR CERRAHISI EGITIM VE ARASTIRMA HASTANESI
3
DEPARTMENTS OF ANAESTHESIOLOGY AND REANIMATION, HAYDARPASA NUMUNE TRAINING AND RESEARCH HOSPITAL,
ISTANBUL, TURKEY
4
MEDICINAL AND GENETICS, FACULTY OF MEDICINE, MERSIN UNIVERSITY, MERSIN, TURKEY
1
2
The inter-patient differences in drug response are documented to be attributable to heritable genetic variations in the nucleotide
sequence of drug-metabolizing enzymes. The identification of variant allele frequencies in specific ethnic groups is important to
individualize drug dosing and improve the therapeutics which refers to the term called pharmacogenomics. Pharmacogenomics
as a science aims at individualizing the treatment- based on the genetic makeup, to mitigate the chances of adverse drug events
and/ or to maximize the efficacy in sub-population. With clarification of exposure-response relationship, it makes it possible
to make dosing recommendations in special populations leading to approval doses/dosing regimen that were not studied in
registration trials. This study aims to detect single nucleotide polymorphism (SNP) in CYP2C9 in Turkish population. CYP2C9
metabolizes approximately 20% of clinically used drugs, including the narrow therapeutic window drugs such as warfarin,
phenytoin, etc. Extensively studied alleles are CYP2C92 and CYP2C93. However, in addition to these two alleles, other genetic
factors and an individual biological characteristics contribute to the overall drug phenotype. A major bottleneck for CYP2C9
pharmacogenomics in clinical field applications is the lack of knowledge regarding the numerous genetic polymorphisms and
their molecular functionalities. In this study, 21 subjects were studied for CYP2C92 SNP using PCR-RFLP followed by agarose
gel electrophoresis. 6 of these subjects were detected as heterozygous type while no homozygous polymorphisms have been
detected yet. In order to report the frequency of CYP2C9 polymorphism in the Turkish population, the study will be continuing
by increasing number of subjects.
PP 218 SAFETY CONCERNS OF BIOSIMILARS IN TURKEY
SERRA VILDAN AKGUL , SEVCAN GUL AKGUN , GULDEN Z. OMURTAG, SEMRA ŞARDAŞ
DEPARTMENTS OF PHARMACEUTICAL TOXICOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Biotechnological drugs also called biopharmaceuticals can be defined as drugs can be produced either in living organism or
by biological processes. Biosimilar medicinal products needed to be regulated by guideline. In Turkey the guideline for these
kinds of products have been prepared and released in August 2008. It was aimed to define number and status of biosimilar
products in this study. There are 167 authorised biotechnological drugs are available in Turkey. Derivative blood products have
higher ratio in therapeutic index classes of biosimilars, approximately as 27%. Antineoplastics and immunomodulating agents
follow them with 25% share. Clinical safety of biosimilar medicinal products must be monitored closely on an ongoing basis
during the post approval phase including continuing risk-benefit assessment. The biosimilar applicant must provide the Ministry
of Health Drug and Medical Device Agency of Turkey with a risk management and pharmacovigilance programme with its
application. The most critical safety concern about biopharmaceuticals (also biosimilars) is immunogenicity. In this poster,
the pharmacovigilance risk minimization activities required by the Ministry of Health Drug and Medical Devices of Turkey
will be introduced and discussed with the reqıirements of the health authorities. 1. Leyre Zuniga, Begona Calvo. Biosimilars:
pharmacovigilance and risk management. Pharmacoepidemiology and Drug Safety. 2010;b19: 661-669. 2. Kresse G. Biosimilars.
Science, status, and strategic perspective. Eur J Pharm Biopharm. 2009; 72: 479-486.
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PP 219 COMPARATIVE IN-VITRO EFFICACIES OF VARIOUS ANTIPSEUDOMONAL ANTIBIOTICS BASED CATHETER LOCK
SOLUTIONS ON ERADICATION OF PSEUDOMONAS AERUGINOSA BIOFILMS
BERNA OZBEK CELIK , EMEL MATARACI KARA
ISTANBUL UNIVERSITY FACULTY OF PHARMACY DEPT. OF PHARMACEUTICAL MICROBIOLOGY
Antibiotic lock technique (ALT) may be an adjunct therapy in treating catheter-related infections. The aim of this study was to
determine the in-vitro stability and efficacy of colistin, meropenem and levofloxacin alone or in combination with clarithromycin
or heparin lock solutions against biofilm embedded Pseudomonas aeruginosa strains. The efficacy of antibiotic lock solutions
was tested in an in- vitro catheter biofilm model against P. aeruginosa isolated from catheter-related bacteremia. We observed
that the use of meropenem, levofloxacin or colistin as a lock solution had potent bactericidal effects and could be prevented
bacterial regrowth at 96 or 72h, respectively. When the tested antibiotics were used in combination with clarithromycin, the
combinations were significantly more effective and rapid in eliminating P. aeruginosa colonization in biofilm than each of the
antibiotics were used alone. Moreover, tested antibiotics in combination with heparin were not significantly different for
killing effect against PA-1 and PA-27853 compared with that of each antibiotics alone. Tested catheter lock solutions may have
promising adjuvants for treating infections caused by P. aeruginosa.
PP 220 INHIBITION OF ALDOSE REDUCTASE AND MONOAMINE OXIDASE BY SOME PLANT EXTRACTS
BEYHAN KARA KISLA , REFIYE YANARDAG
ISTANBUL UNIVERSITY, FACULTY OF ENGINEERING, DEPARTMENT OF CHEMISTRY, ISTANBUL/ TURKEY
Aldose reductase (ALR) belongs to aldo-keto reductases super family. It is the first and the rate limiting enzyme in the polyol
pathway where it reduces glucose to sorbitol utilizing NADPH as a cofactor. Accumulation of sorbitol leads to osmotic swelling,
changes in membrane permeability and also oxidative stress, culminating tissue injury. Experimental animal models suggest
that the inhibition of ALR could be effective in prevention of certain diabetic complications. Monoamine oxidases (MAO) are
mitochondrial bound enzymes which metabolize neurotransmitter and dietary amines in the brain and peripheral tissues.The
monoamine oxidase inhibitors are used primarily to treat neuropsychiatric syndromes. In this study ALR and MAO inhibitory
activities of some plant extracts were investigated. All plant extracts have good ALR and MAO inhibitory activities. Enzyme
inhibitory activities were found to increase dose dependently. It may be concluded that examined plant extracts are promising
leads for the therapy of diabetes mellitus and neurological disease.
PP 221 LITHIUM INCORPORATION INTO PLGA FILMS BY THE EMULSION TECHNIQUE
BEYZA BETUL KOCAK 1, ANNA BERGSTRAND 2, ANETTE LARSSON 2
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
CHEMICAL AND BIOLOGICAL ENGINEERING, PHARMACEUTICAL TECHNOLOGY, CHALMERS UNIVERSITY OF TECHNOLOGY,
GOTHENBURG, SWEDEN
1
2
Drug-loaded biodegradable film coating for implantable medical devices may provide a better treatment by combination of
several functions within the same device which offers both a mechanical support and drug targetting at the same time (1).
Poly (lactide-co-glycolide) (PLGA) is one of the most popular biodegradable polymers which is important for pharmaceutical
applications (2). The aim of this project was to develop adequately stable emulsion formulations and produce PLGA films with
incorporated lithium salt for coating orthopedic implants that could provide controlled drug release in the human body. The
films were produced by a solvent casting method and the w/o emulsion technique was employed for drug incorporation. A
Layer by layer coating was applied on metallic screws by a spray coating method. The external and internal morphology of the
produced films was analyzed by a scanning electron microscope (SEM) and the release properties of Li+ were monitored by an
atomic absorption spectroscopy with flame emission. The emulsion stability was affected by the homogenization conditions
and by the amount of PLGA used in the formulations. Increasing homogenization rate led to more stable emulsions. Likewise an
increase in the polymer content resulted in more stable emulsions with more viscous external phase. The desired PLGA films
were only produced when the emulsions were dried under the conditions without any lid. Li+ release from PLGA films showed
clear variation depending on the molecular weight (Mw) of the PLGA that was used. The films made of PLGA with low Mw
exhibited a controlled release profile which was relatively slow and linear. However a more burst-like release profile was yielded
by the ones made of PLGA with high Mw. 1. Schmidmaier G, Wildemann B, Stemberger A, Haas NP, Raschke M. Biodegradable
poly(D,L-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res. 2001;58(4):449-455. 2.
Lakshmi SN, Cato T Laurencin. Biodegradable polymers as biomaterials. Prog Polym Sci. 2007;32: 762–798.
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PP 222 ANTIOXIDANT CAPACITY OF METHANOL EXTRACT FROM ORIGANUM HYPERICIFOLIUM AERIAL PARTS
AYGUL KOSEOGLU 1, TURGUT TASKIN 1, NARIN SADIKOGLU 2, LEYLA BITIS 1
1
2
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF PHARMACOGNOSY, FACULTY OF PHARMACY, İNÖNÜ UNIVERSITY, MALATYA, TURKEY
The genus Origanum (Lamiaceae) is represented throughout the world by 50 species and in Turkey by 22 species or 32 taxa,
21 being endemic to Turkey [1]. Origanum species have traditionally been used as a spicy additive for food instead of thyme.
This genus is rich in essential oils. The species of Origanum genus are known in Anatolia as ‘‘Yalancı kekik”, ‘‘Kekik”, Istanbul
kekiği” and ‘‘Keklik otu”. Origanum species are used as sedative, diuretic, sweater and antiseptic and also in the treatment of
gastrointestinal diseases and constipation [2]. Origanum hypericifolium O. Schwartz & P.H. Davis is an endemic species with
limited distribution and is included in the lower risk and conservation-dependent category in the red data book of Turkey [3].
The aim of this study is to reveal antioxidant capacity of extract, which is prepared by maceration in methanol from Origanum
hypericifolium aerial parts. The antioxidant capacity of methanol extract were assayed with various methods, DPPH free radical
scavenging activity, metal chelating capacity and ABTS radical cation scavenging, including total phenolic compound contents
by Folin – Ciocalteu reagent (FCR). The obtained results were compared with standard antioxidants such as Ascorbic acid, BHT
and EDTA. The methanol extract of Origanum hypericifolium aerial parts exhibited stronger DPPH free radical-scavenging (IC50:
0.147±0.03) and ABTS radical cation scavenging activity (0.56±0.017) than BHT (0.32±0.03; 1.023±0.15, respectively). It was
concluded that aerial parts of Origanum hypericifolium are beneficial to consume as spice.
References
[1]. Askun, T., Tumen, G., Satil, F., Ates, M., Food Chemistry, 2009, 116 (2009), 289–294.
[2]. Kordali, S., Cakir, A., Ozer, H., Cakmakci, R., Kesdek, M., Mete, E., Bioresource Technology, 2008, 99 (2008), 8788–8795. [3].
Celik, A., Herken, EN,, Arslan, İ,Donmez, Özel, MZ, Mercan N, Natural Product Research, 2004, 24(16),1568–1577.
PP 223 SAFETY EVALUATION OF ORAL CONTRACEPTIVES
AHMET KOC 1, HANDE SIPAHI 1, BANU UNAL 2, AHMET AYDIN 1
1
2
YEDITEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF TOXICOLOGY, 34755 ISTANBUL, TURKEY
BAYER TURK KIMYA SAN. LTD. STI., ISTANBUL, TURKEY
In recent years, unintended pregnancy rate primarily result from the lack of, incongruous or incorrect use of effective
contraceptives methods has been significantly increased. In order to reduce the risk of unintended pregnancy, appropriate
contraceptive method should be selected. Oral contraceptive pills are the most selected contraception method among women.
During the past years a huge amount of research has been undertaken to assess both risk of oral contraceptives and the
medical benefits. Use of oral contraceptives has long been known to be associated with a highly increased risk of venous
thromboembolism (VTE) that one of the more important side effect. Certain studies have shown that compared with no oral
contraceptive using, use of second generation oral contraceptives has been associated with the lower increase in VTE risk(1).
Nevertheless, massive evidence documenting various non-contraceptive health benefits of oral contraceptives has been
accumulating for many years. Many studies have been indicated that oral contraceptives are showing the reduced risk/effective
treatment maintained with low estrogens-dose formulations such as endometrial cancer, ovarian cancer and dysmenorrhea(2).
Furthermore, there are a growing body of evidence supporting reduced risk/effective treatment such as endometriosis
and benign ovarian tumors(3). Bioavailability of oral contraceptives is another important subject that interaction should be
considered because of at risk of contraceptive failure or other adverse effects. Selection of rational oral contraceptives should
be evaluated based upon women’s medical background (such as age, overweight, smoking and family history). Advantages and
disadvantages also should be taken into consideration before selection of contraceptive methods.
References:
1. Manzoli L, De Vito C, Marzuillo C, Boccia A, Villari P. Oral contraceptives and venous thromboembolism: a systematic
review and meta-analysis. Drug Saf [Internet]. 2012 Mar 1;35(3):191–205. Available from: http://www.ncbi.nlm.nih.gov/
pubmed/22283630
2. Kaunitz AM. Noncontraceptive health benefits of oral contraceptives. Rev Endocr Metab Disord [Internet]. 2002 Sep;3
(3):277–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12215722 3. Sherif K. Benefits and risks of oral contraceptives.
Am J Obstet Gynecol [Internet]. 1999 Jun;180(6 Pt 2):S343–8. Available from:http://www.ncbi.nlm.nih.gov/pubmed/10368519
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PP 224 CURRENT APPROACHES IN CALCULATION OF ROYALTY RATES FOR PHARMACEUTICAL INDUSTRY
SALIH GUMRU
DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Royalty payments can be defined as a profit sharing mechanism, in which technology licensor becomes shares from profit
generated by licensee’s efforts in commercializing the patented technology. In many deals, royalty rates are seen as a percentage
of sales or a payment per unit. However, the profitability of the products or services that incorporate the patented technology
plays a dominant role in royalty determination. Much upward pressure on royalty rates has been felt over the last two decades
in pharmaceutical industry, since it is becoming harder to discover effective and marketable new drugs and biotechnologies.
Several million dollars are discarded, in addition to endless pressure and length of more than 10 years for development of a single
product. These characteristics of pharmaceutical and biotechnological products have created a need for the “effective royalty
rates” concept to analyze and explain various deal scenarios. New approaches, such as “Analytical Approach”, “Comparable
License Transactions Analysis” and “Investment Rate of Return Analysis” have succeeded old royalty assumptions, such as “5%
of Sales Method” and “Profit Split Rule of Thumb”. In this study, by reviewing many theoretical approaches and latest royalty
calculation strategies of different companies for their brand new products, it is aimed to provide those working on it some tools
for creating a clear path through royalty rate jungle.
PP 225 A LITERATURE REVIEW: COMPARATIVE ANALYSIS OF KNOWLEDGE, ATTITUDE AND PRACTICES OF HEALTH
PROFESSIONALS TOWARDS PHARMACOVIGILANCE IN DIFFERENT COUNTRIES
OGUZHAN AYDEMIR , SALIH GUMRU
DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Although pharmacovigilance has gained attention in the last two decades, there are differences in perception about practices
in different countries. Developed countries have already solved problems about this vital health problem and created their
well-grounded pharmacovigilance systems. On the other hand, despite an increase in access to MEDICINEs, fully functional
pharmacovigilance and regulatory systems are not yet in place in low- and middle-income countries. In this study, we
performed a systematic and detailed literature review to be able to compare pharmacovigilance perception of healthcare
professionals in different countries. A better understanding of the existing regulatory and pharmacovigilance systems not only
in developed countries, but also in developing and undeveloped countries can help guide every national government and
international donors towards effective and viable pharmacovigilance systems. As a result of this awareness, US Agency for
International Development (USAID) and the US Food and Drug Administration (FDA) funded the Systems for Improved Access
to Pharmaceuticals and Services (SIAPS) Program through an interagency agreement to assess pharmacovigilance systems in
five Asian countries: Bangladesh, Cambodia, Nepal, the Philippines, and Thailand. These efforts are only for assisting countries
to protect the public from poor quality and unsafe medicines. For this purpose, we have focused on many different countries
from every corner of the globe, including Iran, Malaysia, Nepal, Nigeria, Norway, Kingdom of Saudi Arabia, Turkey and United
States of America. As a result of elaborative studies on the subject, pioneering districts on Earth may be defined to enhance
pharmacovigilance systems in developing and non-developed countries.
PP 226 EFFECTS OF DIRECT-TO-COMSUMER ADVERTISEMENT IN DRUG INDUSTRY: DEVELOPED COUNTRIES COMPARED
WITH TURKEY
SALIH GUMRU , OGUZHAN AYDEMIR
DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Direct-to-consumer pharmaceutical advertising (DTCPA) can be defined as an effort, especially by using popular media, made
by a pharmaceutical company to promote its prescription products directly to patients. USA and New Zealand are only two
countries allowing DTCPA that includes product claims. However, other countries don’t allow DTCPA at all. Canada appears to
be the third country, allowing ads that mention either the product or the indication, but not both. Efforts of pharmaceutical
industry and lobby groups have been useless to overturn bans against DTCPA in Canada and regions, such as in the European
Union (EU). Despite all of these efforts, in 2008, 22 of the 27 EU member states voted against possible legislation that would have
allowed even limited “information to patients” to be provided. While developed countries approach DTCPA applications with
hesitation, the use of a similar strategy for non-prescribed drugs has come into use in developing countries. It is accepted that
DTCA would affect health services and economy negatively in these countries. In this study, we discuss the current situation of
this marketing strategy that prevents underuse of pharmaceuticals in developed countries, but also leads to potential overuse.
The “fine tune” is always tried to be caught. We also criticize the applicability of this marketing strategy in Turkey, considered as
a developing country, compared with the situation in developed countries.
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PP 227 COMPASSIONATE USE OF MEDICINAL PRODUCTS IN DIFFERENT EUROPEAN COUNTRIES: CURRENT STATUS AND
PERSPECTIVES
SALIH GUMRU 1, ZEHRA CETIN 1, MUGE SIRVANCI YALABIK 2
1
2
DEPARTMENT OF PHARMACOLOGY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DEPARTMENT OF MEDICAL PHARMACOLOGY, FACULTY OF MEDICINE, MARMARA UNIVERSITY, ISTANBUL, TURKEY
Compassionate use refers to the use of an investigational drug outside of a clinical trial by patients with unmet medical
needs who do not meet the inclusion criteria for ongoing clinical progress. If a company decides to distribute its drug via
compassionate use program in Europe, it has to be in compliance with a patchwork of national regulations. The Regulation of
European Commission draws a frame for using these types of drugs. However, national authorities might take differential views
on compassionate use programs, especially when there is an unmet medical condition. Currently, compassionate use programs
in three major European markets (France, Germany and Spain) are subject to tight supervisory control, while regulations
are upcoming in two additional major markets (Italy and United Kingdom). Compassionate use programs in accordance with
respective national European rules not only provide companies the chance to meet ethical obligations towards patients they
suffer from an unmet medical need, but also offer the possibility of gaining access to patients before becoming marketing
authorization. In addition, companies have the opportunity to obtain clinical experience with drugs outside the controlled
environment of ongoing clinical trials. In this study, we discuss different compassionate use regulations in different European
countries. In Turkey, there is also a similar procedure, which will be explained in detail.
PP 228 ALZHEIMER AND CHEMICALS
GULSAH ARAMAN , SIBEL OZDEN
ISTANBUL UNIVERSITY FACULTY OF PHARMACY PHARMACEUTICAL TOXICOLOGY
Alzheimer is a progressive neurodegenerative disease. Its patogenesis has two neuropathological markers including senile
(amyloid) plaques and neurofibrillary tangles. Based on molecular studies it is known that the main component of senile plaques
and neurofibrillary tangles are consecutively; amyloid beta (β) and tau protein. These components form various agregates,
therefore lead to a neurodegeneration. These neurodegenerations are affected by some protective/risk factors which are genetic
factors, chemicals (heavy metals, pesticides, organochlorinated substances, medication) nutrition, age, psychosocial situation,
vascular pathways, smoking, alcohol consumption and others (such as inflammation, oxydative stress and free radical formation
etc). One particular factor is much more detailed in this review; chemical substances. The aim of this review have provide a
comprehensive overview on the medical importance of the positive (the ones who could prevent or stop the neurodegeneration
such as caffeine or ginkgo biloba extract) and the negative (the one who could accelerate the neurodegeneration such as local
anesthetics, isoflurane) relationships between some chemical substances and Alzheimer. It is important to see how chemicals
affect human on a daily basis and how people can avoid Alzheimer by taking or not these chemicals.
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PP 229 ANTIMICROBIAL ACTIVITIES OF SOME NOVEL SYNTHESIZED IMINOTHIAZOLIDINON DERIVATIVES
F. TULAY TUGCU 1, BERNA OZBEK CELIK 2, YIGIT SABRI UNLU 2, GÜL CEVAHIR OZ 2
1
2
FACULTY OF PHARMACY YILDIZ TECHNICAL UNIVERSITY
FACULTY OF PHARMACY ISTANBUL UNIVERSITY
Iminothiazolidinones and derivatives have an important place in the area of heterocyclic compounds because of their presence
in the structures of macrocyclic complex drugs, their applications in industry and usage in pharmaceutical researches due to
their biological properties (1). These heterocycles display diverse biological activities such as herbicidal, fungicidal, bactericidal
and pesticidal (2). In this study, the new synthesis iminotiyazolidinon derivatives (compounds 1-6) against six species of bacteria
and the yeast C. albicans were conducted to assess the antimicrobial activity. Disk diffussion method was used for antimicrobial
activity (3). All of the synthesized compounds were tested for antimicrobial activity using Staphylococcus aureus ATCC 6538,
Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas
aeruginosa ATCC 1539, Proteus mirabilis ATCC 14153 and Candida albicans ATCC 10231. Among the synthesized compounds
2-[(6-methylpyridin-2-yl)imino]-5-[(3-methylthiophen-2-yl)methylidene]-3-phenyl-1,3-thiazolidin-4-one (compound 5) was
found the most active derivative at an MIC value of 39.06 mg/L against C. albicans ATCC 1023. The obtained data reported that
compounds (1-4 and 6) were able to inhibit the growth of the selected micro-organisms in vitro showing MIC values between
156.25-625 mg/L. None of the compounds exhibited any activity against Klebsiella pneumoniae while all the compounds
showed microbial effect against Staphylococcus aureus ATCC 6538.
1. Bonde C.G., Gaikwad N.J. Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinones
as antimicrobial agents. Bioorg. Med. Chem. 2004; 12:2151-2161 2. Singh S.P, Parmar S.S, Raman K, Stenberg V.I. Chemistry and
biological activity of thiazolidinones. Chem. Rev. 1981; 81:175-203. 3. Koca M, Servi S, Kirilmis C, Ahmedzade M, Kazaz C, Özbek
B, Ötük G. Synthesis and antimicrobial activity of some novel derivatives of benzofuran: part 1. Synthesis and antimicrobial
activity of benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl) ketoxime derivatives. European J. Of Med. Chem. 2005; 40:13511358.
PP 230 EVALUATION OF CYTOTOXIC AND GENOTOXIC EFFECTS OF SOME NOVEL SYNTHESIZED IMINOTHIAZOLIDINON
DERIVATIVES ON HELA CELL LINE (CCL2)
F. TULAY TUGCU 1, MEHMET RIFKI TOPÇUL 2, IDIL CETIN 2, YIGIT SABRI UNLU2, YUSUF CAN GERCEK 2, GUL CEVAHIR OZ 2
1
2
FACULTY OF PHARMACY YILDIZ TECHNICAL UNIVERSITY
FACULTY OF PHARMACY ISTANBUL UNIVERSITY
The thizolidinones are useful scaffold in medicinal chemistry: it can be found as a pharmacophore in a wide variety of biologically
active compounds, such as antitumorals, antibacterials, antivirals, anti-convulsant, anti-inflammatory, anti-diabetic, anti-HIV
and many other therapeutic agents (1,2). In this study, we investigated the cytotoxic and gynotoxic effects of some novel
synthesized iminothiazolidinone derivates on HeLa (3) cell line (CCL2) that originated from human cervical carcinoma. In this
direction, cell kinetics parameters of proliferation rate, mitotic index and the labeling index was used. 1, 5, 10 µM doses were
applied for 72 hours to determine the optimum dose for all compounds and was interpreted by proliferation rate analysis. The
obtained results have shown a 10 µM dose the optimum doses for all compounds. Parameters of mitotic index and labeling were
observed by during the 0-72 hours using by optimum dose. The results from all parameters have shown that used compounds
causes a significant decrease in the proliferation of HeLa cell cultures.
1. Edwards P J. Thiazolidinone derivatives targeting drug-resistant lung cancer cells. Drug Discovery Today. 2008; 13: 1107-1108.
2. Singh S.P, Parmar S.S, Raman K, Stenberg V.I. Chemistry and biological activity of thiazolidinones. Chem. Rev. 1981; 81:175203. 3. Özcan Arıcan G, Soy N. N. Effects of epirubicin and daunorubicin on cell proliferation and cell death in HeLa cells. Journal
of Cell and Molecular Biology, 2005; 4: 47-52.
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PP 231 CENTRALLY AND PERIPHERALLY MEDIATED ANTINOCICEPTIVE ACTIVITIES OF SOME 1,3,5-TRIARYL-4,5-DIHYDRO-1HPYRAZOLE DERIVATIVES
HARIKA AYDIN , UMUT IRFAN UÇEL , UMIDE DEMIR OZKAY , OZGUR DEVRIM CAN
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY
Some new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives were synthesized via the treatment of 1,3-diaryl-2-propen-1ones with phenylhydrazine hydrochloride derivatives in hot acetic acid. The antinociceptive properties of the compounds
were evaluated by hot-plate, tail-clip and acetic acid induced writhing tests in mice. Motor coordination of the animals was
evaluated in a Rota-rod model. Morphine sulphate used as a reference drug in all nociceptive tests. Statistical evaluation of
the obtained data indicated that compounds 2c, 2e, 2g, 2h, 2j, 2l, and 2m, when administrated at 100 mg/kg, increased the
reaction time of animals both in hot plate and tail clip tests. Additionally, the same compounds reduced the number of acetic
acid induced writhing behaviors. Obtained data exhibited antinociceptive effect of these compounds on supraspinal, spinal and
peripheral nociceptive pathways. Besides, in the Rota-rod tests, 2c, 2e, 2g, 2h, 2j, 2l, and 2m did not cause any change in the
motor coordination of mice, indicating that the observed antinociceptive effect is specific. These results supported the previous
papers reporting the antinociceptive potential of various pyrazoline derivative compounds.
PP 232 ANTIDEPRESSANT-LIKE ACTIVITY OF SOME AROYL PROPIONIC ACID-HYDRAZONE DERIVATIVES
FEYZA ALYU 1, HARIKA AYDIN 1, OZGUR DEVRIM CAN 1, YUSUF OZTURK 1, GULHAN TURAN-ZITOUNI 2
1
2
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKISEHIR, TURKEY
The aim of the present study was examining the effect of some 4-[4-[2-(2-(4-substituted benzylidene)hydrazinyl)-2-oxoethoxy]
phenyl]-4-oxobutanoic acid derivatives on depression, anxiety and spontaneous locomotor activity parameters of mice. In
tail suspension tests, when administrated at 50 mg/kg dose, compounds 2a, 2b, 2d, 2e, 2f, 2g and 2i in the series, caused
significant reduction in the immobility time of mice. Additionally, in modified forced swimming tests, the same compounds
decreased the immobility and increased the swimming times of mice without any change in climbing durations. Data obtain
from these two tests clearly pointed out the antidepressant-like effects of the aforementioned compounds. Exact mechanism
of the antidepressant action exhibited in the present study need to be clarified with further detailed investigations. On the
other hand, none of the compounds changed the exploratory parameters in hole-board tests or total numbers of spontaneous
locomotor activities in activity cage measurements at the applied dose. In other words, neither anxiolytic nor sedative effects
induced by the test compounds.
PP 233 ANTIHYPERALGESIC AND ANTIALLODYNIC EFFECT OF MIANSERIN ON DIABETIC NEUROPATHIC PAIN IN RATS
UMUT IRFAN UCEL , OZGUR DEVRIM CAN , UMIDE DEMIR OZKAY
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY
In this study, effects of subacute administration of mianserin on diabetic hyperalgesia and allodynia, which developed 4 weeks
after streptozotocin injection, were investigated using several experimental pain-induction methods in rats with diabetes.
Mianserin administered at 30 and 45 mg/kg doses during 7 and 14 days not only showed opioid-mediated acute anti-nociceptive
activity but also effectively improved mechanical and thermal hyperalgesia caused by diabetic neuropathy. In addition to
having an anti-hyperalgesic effect, mianserin attenuated diabetes-related mechanical and thermal allodynia. To the best of
our knowledge, this is the first study to show that the anti-hyperalgesic and anti-allodynic effects of mianserin, an atypical
anti-depressant, in the experimental diabetes model were comparable to those of the reference drug pregabalin (dose, 10
mg/kg). However, the pharmacological mechanisms underlying these anti-hyperalgesic, and anti-allodynic effects of mianserin
remain to be elucidated. The results of this study will provide a pre-clinical basis for new approaches of proper drug selection
for the treatment of neuropathic pain, which has a high incidence among diabetes patients. Nevertheless, for mianserin to be
considered an effective alternative drug for the treatment of diabetic neuropathy, it is necessary to confirm the results of this
pre-clinical study in clinical studies.
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PP 234 ANXIOLYTIC ACTIVITIES OF SOME PYRAZOLE DERIVATIVES
NAZLI TURAN , FEYZA ALYU , UMUT IRFAN UÇEL , HARIKA AYDIN , UMIDE DEMIR OZKAY , YUSUF OZTURK
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY ESKISEHIR, TURKEY
In this study, the putative effect of some pyrazole derivatives on anxiety parameters of mice was investigated using plus-maze
and hole-board methods. In plus-maze tests, the percentage of open arm entries (POAE) and the percentage of time spent on
the open arms (PTOA) were calculated for each animal. Furthermore, in hole-board test, latencies to the first head-dips, total
numbers of head-dips and holes explored were measured as criterion of anxiety. Diazepam (1 mg/kg) was used as a reference
drug for the behavioral tests. Among the tested 18 compounds 2g, 2h, 2k, and 2s significantly increased the POAE and PTOA
values in the plus maze tests. The same compounds significantly decreased the latency to the first head-dip, whereas increased
the total numbers of head-dips and holes explored. Further 2g, 2h, 2k, and 2s induce alteration neither total spontaneous
locomotor activities recorded in the activity cage, nor falling latencies measured in the Rota-Rod. Obtained data from all of
these tests pointed out the anxiolytic-like effect of these aforementioned pyrazole derivatives. The exact mechanism of action
underlying this anxiolytic-like effect should be clarified with further detailed studies.
PP 235 ANTIFUNGAL AND ACETYLCHOLINESTERASE INHIBITORY EFFECTS OF SOME TRIAZOLE DERIVATIVES
ULVIYE ACAR 1, UMIDE DEMIR OZKAY 2
1
2
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKISEHIR, TURKEY
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY
Triazole and its derivatives are interesting class of compounds, which were reported for their extensive biological effects
as antibacterial, antifungal, antitubercular, antidepressant, anti-inflammatory, anticancer, analgesic, anticonvulsant, and
insecticidal (1). It has been reported that 1,2,4-triazole based antifungal drug tebuconazole causes significant inhibition on
acetylcholine esterase level (2). In the present study some new triazole compounds were synthesized in order to investigate
their anticandidal and anticholinesterase activities. Structures of the synthesized compounds were elucidated by spectral
data and elemental analyses. Anticandidal activity tests were performed against four different fungal strains. Some of the
compounds exhibited equal anticandidal activity to reference drug fluconazole. Anticholinesterase activity of the synthesized
compounds against acetylcholinesterase (AChE) was also studied. However, enzyme inhibitory effects of the tested compounds
were evaluated as insignificant.
Reference
1. Sahin D, Bayrak H, Demirbaş A, Demirbaş N, Alpay-Karaoğlu Ş, Design and synthesis of new 1,2,4-triazole derivatives
containing morpholine moiety as antimicrobial agents. 2012;36:411-426. 2. Kolesarova V, Sinko G, Sivikova K, Dianovsky J, In
vitro inhibition of blood cholinesterase activities from cattle by triazole fungicides, Caryologia 2013;66:346-350.
PP 236 DESIGN, SYNTHESIS AND BIOLOGICVAL EVALUATION OF SOME PIPERAZINEDITHIOCARBAMATE DERIVATIVES AS
ACETYLCHOLINESTERASE INHIBITORS
ULVIYE ACAR 1, UMIDE DEMIR OZKAY 2
1
2
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKISEHIR, TURKEY
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKISEHIR, TURKEY
Carbamate derivatives are inhibitors of acetylcholinesterase through carbamoylation of the esteratic site of the enzyme.They are
subsequently reversed upon decarbamoylation (1). The compounds which bear dithiocarbamate moiety, considered as bioisoster
of carbamate, may be shown as potential anticholinesterases. Thus, in this study we designed and synthesized new piperazine
based dithiocarbamate derivatives to investigate their inhibitory profile on acetylcholinesterase and butrylcholinesterase
enzymes. Structures of the final compounds were confirmed by 1H-NMR, IR, MS spectroscopic methods and elemental analyses.
In the series, the compound 2f was found as the most active derivative against both of the cholinesterases.
1. Becker RE, Moriearty P, Unni L. The second generation of cholinesterase inhibitors: Clinical and pharmacological effects. In
Becker, Giacobini E,editors. Cholinergic basis for Alzheimer’s therapy. Boston: Birkhauser, 1991:263-296
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PP 237 SYNTHESIS OF SOME NOVEL DITHIOCARBAMATE DERIVATIVES AS ACETYLCHOLINESTERASE INHIBITORS
BEGUM NURPELIN SAGLIK 1, UMIDE DEMIR OZKAY 2
1
2
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKIŞEHIR, TURKEY
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY,ESKIŞEHIR, TURKEY
Carbamates as pyridostigmine, rivastigmine, and physostigmine constitue a class of ChE inhibitors. However, carbamates have
a relatively short duration of action and limited penetration to blood brain barrier (1). Therefore, bioisosteric replacement
of carbamate moiety with dithiocarbamate moiety may be rational to gain new anticholinesterases. Prompted from these
observations, some new dithiocarbamate derivatives were synthesized in the present study. Structures of the target compounds
were elucidated by spectroscopic methods. Tested compounds showed enzyme inhibitory effects to different extents. Especially,
activity of the piperidine containing compounds was better than other derivatives in the series.
1. Lieske CN, Gepp, RT, Clark JH, Meyer HG, Blumbergs P, Tseng CC. Anticholinesterase activity of potential therapeutic
5-(1,3,3-trimethylindolinyl) carbamates. J Enzyme Inhib. 1991;5:215-223.
PP 238 SYNTHESIS OF SOME 6-NITROBENZOTHIAZOLE DERIVATIVES AND INVESTIGATION OF THEIR INHIBITORY ACTIVITY
ON MAO ENZMES
BEGUM NURPELIN SAGLIK 1, YUSUF OZKAY 1, UMIDE DEMIR OZKAY 2
1
2
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, ESKIŞEHIR, TURKEY
ANADOLU UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOLOGY, ESKIŞEHIR, TURKEY
Monoamine oxidases are important drug targets for the treatment of some neurological disorders. 6-Nitrobenzothiazole
derivatives were reported as MAO-B inhibitors in recent study (1). Hence, in this study we synthesized some novel
6-nitrobenzothiazole derivatives to investigate their potency on MAO-A and MAO-B enzymes. Structures of the synthesized
compounds were confirmed by NMR, MS and IR spectral data. Inhibitory, activity of the synthesized compounds against MAO-A
and MAO-B enzymes were investigated by an in vitro flurometric method (2). Compound 3e showed significant MAO-B inhibitory
activity. Some of the compound also displayed good inhibition profile to MAO-A enzyme.
1. Tripathi RK, Goshain O, Ayyannan SR. Design, synthesis, in vitro MAO-B inhibitory evaluation, and computational studies of
some 6-nitrobenzothiazole-derived semicarbazones. ChemMedChem. 2013;8(3):462-474. 2. Matsumoto T, Suzuki O, Furuta
T, Asai M, Kurokawa Y, Nimura Y, Katsumata Y, Takahashi I. A sensitive fluorometric assay for serum monoamine oxidase with
kynuramine as substrate. Clin. Biochem. 1985;18(2):126-129.
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PP 239 DESIGN, SYNTHESIS AND MOLECULAR MODELING STUDIES ON NOVEL FLUOROQUINOLONES AS POTENTIAL DNA
GYRASE INHIBITORS
NECLA KULABAS , ASLI DEMIRCI, ILKAY KUCUKGUZEL
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
DNA Gyrase is an essential enzyme that maintains the supercoils in DNA and has become an important drug target for
antibacterial and anticancer chemotherapy. DNA Gyrase, which is a subtype of Topoisomerase enzyme family, is composed of two
heterodimeric subunits, GyrA and GyrB. While GyrA helps in DNA binding, GyrB is responsible for ATPase activity. Fluoroquinolones
(FQs), possessing DNA Gyrase inhibition, have been used as antibacterial agents since 1960s. These agents specifically bind
GyrA domain of DNA Gyrase [1-3]. For this purpose, substituted aryl/heteroaryl/alkyl amines as starting compounds were
converted to 2-chloro-N-(aryl/heteroaryl/alkyl)acetamide derivatives by using α-chloroacetyl chloride. Equimolar amounts of
2-chloro-N-(aryl/heteroaryl/alkyl)acetamide derivatives and selected FQ containing antibacterial agents were reacted to yield
the target compounds. Following the isolation process, the crude products were crystallized from appropriate solvents. Purity
of the synthesized compounds was checked by HPLC and their structures were confirmed by IR, 1H-NMR, 13C-NMR and mass
spectral data besides elemental analysis. Molecular docking studies concerning the synthesized compounds were performed to
simulate potential inhibition of DNA Gyrase. Studies on calculation of binding energy (Ebind=kcal/mol) between Staphylococcus
aureus DNA Gyrase as receptor (PDB code: 2XCT) and synthesized compounds as ligands. DSV, Chimera and MGLTools were
used to prepare data before docking. Gasteiger charges were assigned to the substrate and the ligands. Receptor-ligand docking
was performed using AutoDock Vina [4].
References
[1] Shen LL, Mitscher LA, Sharma PN, ODonnel1 TJ, Chu DWT, Cooper CS, Rosen T, Pernett AG. Mechanism of inhibition of DNA
Gyrase by quinolone antibacterials: A cooperative drug-DNA binding model. Biochem. 28, 3886-3894, 1989.
[2] Khodursky AB, Nicholas R. The Mechanism of inhibition of Topoisomerase IV by quinolone antibacterials. J. Biol. Chem. 273,
27668–27677, 1998.
[3] Ostrov D, Hernández Prada J, Corsino PE, Finton KA, Le N, Rowe TC. Discovery of novel DNA gyrase inhibitors by highthroughput virtual screening. ACC. 51, 10, 3688-98, 2007.
[4] Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient
optimization and multithreading. J. Comput. Chem. 30, 31(2), 455-461, 2010.
PP 240 SYNTHESIS AND ANTITUBERCULOSIS EVALUATION OF 1,2,4-TRIAZOLE DERIVATIVES CARRYING THIOACETIC AMIDE
STRUCTURE
NECLA KULABAS 1, ESRA TATAR 1, ILKAY KUÇUKGUZEL 1, SINEM OKTEM OKULLU 2, NIHAN UNUBOL 2, TANIL KOCAGOZ 2
1
2
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
ACIBADEM UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL MICROBIOLOGY
Tuberculosis (TB) is still a very serious chronic infection disease, which caused by several species of mycobacteria. Although
tuberculosis is not a serious cause of death in countries where the disease control efforts, especially with the spread of AIDS,
is an increase in the incidence of tuberculosis.The need for novel, more effective drugs to improve TB control is evident.
Treatment of active disease needs to be shortened, simplified, and should not interfere with the administration of antiretroviral
agents. Among azoles, 1,2,4-triazoles nucleus that is one of the active components present in many standard drugs, is known
to increase the pharmacological activity of the molecules and have been reported to exhibit antibacterial, antifungal, antiviral,
antiinflammatory and antituberculosis activities. In addition to compounds possessing a thioacetic ester or amide function
displayed significant activity against M. Tuberculosis [1-5]. According to our synthesis procedure ring cyclization of the
thiosemicarbazides led to the corresponding triazoles and the linkers were obtained by condensing appropriate anilines with
chloroacetyl chloride; then these two fragments were reacted in DMF in the presence of K2CO3 in order to gain the desired
target compounds with potential antitubercular activities. Structures and purity of the synthesized target compounds were
confirmed by the use of their IR, 1H-/13C-NMR and mass spectral data; besides TLC, HPLC-UV/DAD and elemental analysis.
Antituberculosis activity has been viewed by broth dilution method for Minimum Inhibitory Concentration (MIC).
[1] Küçükgüzel İ, Tatar E, Küçükgüzel ŞG, Rollas S, De Clercq E. Synthesis of some novel thiourea derivatives obtained from
5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones and evaluation as antiviral/anti-HIV and antituberculosis agents. Eur J Med Chem. 2008; 43(2): 381–392. [
2-Küçükgüzel İ, Küçükgüzel ŞG, Rollas S, Kiraz M. Some
3-thioxo/alkylthio-1,2,4-triazoles with a substituted thiourea moiety as possible antimycobacterials. Bioorg Med Chem Lett.
2001; 11(13): 1703–1707. [3] Ananthan S, Faaleolea ER, Goldman RC, Hobrath JV, Kwong CD, Laughon BE, Maddry J, Mehta
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A, Rasmussen L, Reynolds RC, Secrist J, Shindo N, Showe DN, Sosa MI, Suling WJ, White EL. High-Throughput Screening for
Inhibitors of Mycobacterium Tuberculosis H37Rv. Tuberculosis. 2009; 89(5): 334-353.
4- Demirbas A, Şahin D, Demirbas N, Alpay Karaoglu Ş. Synthesis of some new 1,3,4-thiadiazol-2-ylmethyl-1,2,4-triazole
derivatives and investigation of their antimicrobial activities. Eur J Med Chem.2009;44(7):2896–2903.
5- Kravchenko MA, Verbitskiy EV, Medvinskiy ID, Rusinov GL, Charushin VN. Synthesis and antituberculosis activity of novel
5-styryl-4-(hetero)aryl-pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and SN reactions. Bioorg Med
Chem Lett.2014;24:3118-3120.
PP 241 PROTECTIVE EFFECT OF CARNITINE AGAINST ACRYLAMIDE-INDUCED TOXICITY IN RATS
HULYA SAHIN 1, SEZGIN AYDEMIR 1, MERAL YUKSEL 2, NAZIYE OZKAN 3, NUSRET ERDOGAN 3, GULDEN Z. OMURTAG 1
DEPARTMENT OF TOXICOLOGY, SCHOOL OF PHARMACY, MARMARA UNIVERSITY, İSTANBUL, TURKEY
DEPARTMENT OF MEDICAL LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA
UNIVERSITY, İSTANBUL, TURKEY
3
DEPARTMENT OF PATHOLOGY LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES,
MARMARA UNIVERSITY, İSTANBUL, TURKEY
1
2
Acrylamide (ACR) is a high-production vinyl compound whose polymeric form is used in oil industry, paper, plastics and textiles.
The same compound is generated in many common foods during cooking at high temperatures. Carnitine, plays an important role
in the transport of long-chain fatty acids through the mitochondrial membrane for their beta-oxidation, and in ATP production
in peripheral tissues. The purpose of the study is conducted for determine the effect of carnitine on acrylamide induced tissue
injury in rats. Sprague-Dawley rats were included in the study. ACR was given i.p. at a dose of 40 mg/kg/day and carnitine for
a dose of 100 mg/kg/day, for 10 days. Control group received SF injection. After the time rats were sacrified and brain, liver
and lung tissues were removed. For free radical determination luminol (selective for hydroxyl radical, hydrogen peroxide and
hypochlorous acid) and lucigenin (selective for superoxide radical) enhanced chemiluminescence (CL) measurements were
used. Histopathological examination, malondialdehyde (MDA; a lipid peroxidation product) and glutathione (GSH) levels were
examined. In ACR group luminol enhanced CL results were higher in liver tissues; lucigenin enhanced CL measurements were
increased in liver, lung and brain tissues, with respect to their control groups. Carnitine treatments reduce ACR induced free
radical release in all tissue groups, significantly. MDA levels confirmed the increased lipid peroxidation in ACR induced groups,
with respect to controls. Whereas carnitine treatment, reduces MDA levels, and increases GSH formation, which is decreased
with ACR toxicity. In conclusion, treatment with carnitine of ACR induced toxicity has been found to reverse some oxidative
stress parameters in brain, liver and lung tissues.
PP 242 THE EFFECT OF PELARGONIUM SIDOISES EXTRACT (UMCA®) ON ACRYLAMIDE INDUCED TOXICITY IN RATS
SEZGIN AYDEMIR 1, HULYA SAHIN 1, NAZIYE OZKAN 2, MERAL YUKSEL 3, NUSRET ERDOGAN 2, GULDEN Z. OMURTAG 1
DEPARTMENT OF TOXICOLOGY, SCHOOL OF PHARMACY, MARMARA UNIVERSITY, HAYDARPAŞA-İSTANBUL, TURKEY
DEPARTMENT OF PATHOLOGY LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES,
MARMARA UNIVERSITY, HAYDARPAŞA-İSTANBUL, TURKEY
3
DEPARTMENT OF MEDICAL LABORATORY TECHNICIANSHIP, VOCATIONAL SCHOOL OF HEALTH RELATED SERVICES, MARMARA
UNIVERSITY, HAYDARPAŞA-İSTANBUL, TURKEY
1
2
Acrylamide (ACR) is a water-soluble, vinyl monomer used in preparing polymers and copolymers containing polar functional
groups. Exposure to monomeric ACR has the potential for cytotoxic and genotoxic effects by decreasing oxidative defense
system. Pelargonium sidoises extract, (UMCA®), is available for treatment of upper respiratory tract infections. The aim of
this study is to determine the effects on oxidative stress parameters of Pelargonium sidoises extract on acrylamide-induced
liver, lung and kidney injury. Female Sprague-Dawley rats were included in the study. ACR was given at a dose of 40 mg/kg/
day. ACR-UMCA group received additionally 100 mg/kg/day UMCA®. Controls were injected saline at the same dose. After 10
days their liver, lung and kidney tissues were removed and the degree of oxidative stress was measured by glutathione (GSH),
malondialdehyde (MDA), luminol and lucigenin enhanced chemiluminescence (CL) methods. Additionally histopathological
observations were analyzed. Liver, lung and kidney MDA levels in ACR induced group are significantly higher than control group.
Because, GSH levels are significantly lower in ACR induced liver and kidney tissues, with respect to control tissues. But GSH levels
in lung tissues were not changed. UMCA® treatment reduces MDA levels and increased GSH levels, significantly. Additionally,
luminol (which is specific for .OH, H2O2, HOCl) enhanced CL levels were significantly increased in ACR induced liver tissues with
respect to control (15.8±4.2 vs. 6.3±2.5 rlu; p<0.001), and treatment with UMCA® reduced the free radical release, significantly
(9.4±2.9 rlu; p<0.01). Lucigenin enhanced CL measurements, which is selective for superoxide radical, were increased in ACR
induced lung and kidney tissues, which is reversed by UMCA® treatment, significantly. Histopathological observations show
cellular degeneration in tissues of ACR group. UMCA® treatment reduced the degeneration, slightly. In conclusion, ACR induced
toxicity in rats increases oxidative stress which results with increased MDA, reduced antioxidative capacity, and increased free
radical release in liver, lung and kidney. UMCA® treatment was protective against oxidative stress in tissues after ACR toxicity.
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PP 243 CONTROLLED PORE GLASS BASED IMMUNOSORBENT SURFACE FACILITATES THE THEOPHYLLINE MEASUREMENT
TUGBA TUNALI-AKBAY , HAZAL IPEKCI, AYSEN YARAT
MARMARA UNIVERSITY, FACULTY OF DENTISTRY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
Theophylline, also known as 1,3-dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases. In
determining theophylline toxicity or in monitoring the treatment of theophylline, theophylline determination is made by
expensive methods. The aim of this study is to facilitate the measurement of low concentrations of theophylline in cow’s milk.
Determination of theophylline in biological media such as milk, in order to avoid background interference, the extraction step
should be added. In the present study, an immunosorbent surface which facilitates the theophylline measurement without
extraction step has been developed. For this purpose protein-A controlled pore glass (CPG) matrix was used. Theophylline
antibody was immobilized to the protein A-controlled pore glass matrix for generating an immunosorbent surface. This step
helps to concentrate theophylline in the solution for the theophylline determination by colorimetric method. All results were
evaluated statistically and discussed.
This study was supported by a grant from Scientific Research Project Department of Marmara UNIVERSITY (Projects No:
SAG-B-130511-0122).
PP 244 IMMUNOSORBENT SURFACE REMOVES COTININE FROM MILK
TUGBA TUNALI-AKBAY 1, MEHMET V. KAHRAMAN 2, NILHAN APOHAN 2, HAZAL IPEKCI 1, BURCU OKTAY 2
1
2
MARMARA UNIVERSITY, FACULTY OF DENTISTRY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
MARMARA UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF ORGANIC CHEMISTRY, İSTANBUL, TURKEY
Breastfeeding is the best way of food intake in the early child hood. The adverse effects of maternal cigarette smoking on
postnatal development of infant have been well documented. Cotinine is an alkaloid found in tobacco and is also a metabolite
of nicotine. It is used as a biomarker for exposure to tobacco smoke. Similarly to nicotine, cotinine binds to, activates, and
desensitizes neuronal nicotinic acetylcholine receptors, though at much lower potency in comparison. Nicotine itself in tobacco
smoke truly exits body in a matter of hours ahead of breast feeding; cotinine delays much further. Therefore, the aim of this
study is to remove cotinine from milk by using an immunosorbent featured surface. For this purpose cotinine antibody was
immobilized to the nanofiber surface and immunosorbent surface was developed. A total of 10 fresh cow’s milk samples were
used. Cotinine was added to cow’s milk in different concentrations. Binding efficiency of cotinine to immunosorbent surface
was measured by using ELISA method. Binding percentages were evaluated statistically and discussed.
This study was supported by TUBITAK with the project numbered “SBAG112S138”.
PP 245 REMOVAL OF FLUOXETINE FROM MILK BY USING IMMUNOSORBENT FEATURED SURFACE
TUGBA TUNALI-AKBAY 1, MEHMET V. KAHRAMAN 2, NILHAN APOHAN 2, BURCU OKTAY 2, HAZAL IPEKCI 1
1
2
MARMARA UNIVERSITY, FACULTY OF DENTISTRY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
MARMARA UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF ORGANIC CHEMISTRY, İSTANBUL, TURKEY
Fluoxetine is one of the most used drug for reducing the postpartum depression either doctor’s advice or previous experiences
of mother’s. Maternal fluoxetine usage adversely affect the infant’s health. It increases crying, vomiting, diarrhea, colic and
decreases sleep of infants. Women who are maintained on therapeutic doses of fluoxetine are recommended to discontinue
breast-feeding their infants if they wish to breast-feed. Maternal fluoxetine therapy carries risks for nursing infants, but
untreated depression is also risky for mothers and infants. The aim of this study is to remove fluoxetine from milk by using
an immunosorbent featured surface. For this purpose fluoxetine antibody was immobilized to the nanofiber surface and
immunosorbent surface was developed. A total of 10 fresh cow’s milk samples were used. Fluoxetine was added to cow’s milk
in different concentrations. Binding efficiencies of fluoxetine to immunosorbent surface was measured by using ELISA method.
Binding percentages were evaluated statistically and discussed.
This study was supported by TUBITAK with the project numbered “SBAG112S138”.
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PP 246 OPTIMIZATION AND EVALUATION OF CLARITHROMYCIN FLOATING TABLETS USING EXPERIMENTAL MIXTURE DESING
TIMUCIN UGURLU , UGUR KARACICEK , ERKAN RAYAMAN
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, ISTANBUL, TURKEY
The purpose of the study was to prepare and evaluate clarithromycin (CLA) floating tablets using experimental mixture design
for treatment of Helicobacter pylori provided by prolonged gastric residence time and controlled plasma level. Ten different
formulations were generated based on different molecular weight of hypromellose (HPMC K100, K4M, K15M) by using simplex
lattice design (a sub-class of mixture design) with Minitab 16 software. Sodium bicarbonate and anhydrous citric acid were
used as gas generating agents. Tablets were prepared by wet granulation technique. All of the process variables were fixed.
Results of cumulative drug release at 8th h (CDR 8th) were statistically analyzed to get optimized formulation (OF). Optimized
formulation, which gave floating lag time lower than 15 s and total floating time more than 10 h, was analyzed and compared
with target for CDR 8th (80%). A good agreement was shown between predicted and actual values of CDR 8 th with a variation
lower than 1%. The activity of clarithromycin contained optimized formula against H. pylori were quantified using well diffusion
agar assay. Diameters of inhibition zones vs. log10 clarithromycin concentrations were plotted in order to obtain a standard
curve and clarithromycin activity.
PP 247 THE IMPACT OF PLATELET FUNCTIONS AND INFLAMMATORY STATUS ON THE SEVERITY OF PREECLAMPSIA
SADIK SAHIN 2, OZLEM BINGOL OZAKPINAR 1, MUSTAFA EROGLU 2, AYSIN TULUNAY 3, ENVER CIRACI 1, FIKRIYE URAS 1, SERMIN
TETIK 1
DEPARTMENT OF BIOCHEMİSTRY, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
ZEYNEP KAMIL WOMEN AND CHILDREN DISEASES TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY.
3
DEPARTMENT OF IMMUNOLOGY, FACULTY OF MEDICINE, MARMARA UNIVERSITY, ISTANBUL, TURKEY.
1
2
To find out whether there is a correlation between the extent of platelet activation and inflammation and the severity of
preeclampsia in the third trimester of pregnancy. Forty-one women with preeclampsia (n=23 severe, n=18 mild) and 80
normotensive pregnant women were included in the study. Their blood samples were obtained and IL-8 and IL-10 levels
measured by an enzyme-linked immunosorbent assay. Basal CD61 and CD62P expressions on CD41 positive platelets were
analyzed with the use of flow-cytometry. Platelet aggregation was induced by adenosine diphosphate and determined by
aggregometry. CD62P expression was increased in severely preeclamptic women and the platelet aggregation was decreased in
both mildly and severely preeclamptic women in comparison with normotensive pregnant women. However, CD61 expression
was similar among the groups. An enhanced inflammatory response was seen in severely preeclamptic women demonstrated
by increased levels of IL-8 and decreased levels of IL-10. However, the intensity of platelet activation did not correlate directly
with the change in plasma levels of IL-8 and IL-10 in preeclamptic women. Platelets may have a role in the inflammatory
response in preeclampsia. However, the severity of inflammation is found to be independent from the intensity of platelet
activation in preeclamptic women. This seems to be related to mechanisms causing alterations of cytokine levels such as IL-8
and IL-10, rather than platelet activation.
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PP 248 GG POLYMORPHISM OF PLATELET GLYCOPROTEIN IIB ITGA2B GENE INCREASES THE MAGNITUDE OF INTERLEUKIN-6
RELEASE AFTER CARDIOPULMONARY BYPASS
KORAY AK 1, SAMET ERGUN 2, HILAL ALTINOZ 4, ENVER CIRACI 2, OYA UYGUNER 5, SELIM ISBIR 1, SINAN ARSAN 1, SERMIN TETIK 2
MARMARA UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF CARDIOVASCULAR SURGERY
MARMARA UNIVERSITY, HEALTH SCIENCES INSTITUTE DEPARTMENT OF BIOCHEMISTRY
3
TAKSIM EDUCATION AND RESEARCH HOSPITAL PATHOLOGY DIVISION
4
ISTANBUL SÜREYYAPASA THORACIC DISEASE AND THORACIC SURGERY EDUCATION AND RESEARCH HOSPITAL
5
ISTANBUL UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICAL GENETICS
6
CYPRUS INTERNATIONAL UNIVERSITY, LEFKOSA, CYPRUS
1
2
Cardiopulmonary bypass induces a systemic inflammatory response which is thought to be a significant cause of postoperative
organ dysfunction and mortality. In this study we aimed to investigate the effect of glycoprotein IIb ITGA2B gene polymorphism
on the magnitude of the inflammatory response after cardiac surgery. Twenty patients (study group, n=20) undergoing coronary
artery bypass grafting were included. Blood samples were taken at the three different times for analyses of Interleukin 6,
Interleukin 10 and Nuclear Factor Kappa B by ELISA (t1: before operation, t2:10 minutes after removal of aortic cross clamping
and t3: 24 hours after operation. Glycoprotein IIb ITGA2B receptor polymorphism was studied in patients and 27 healthy
volunteers by polymerase chain reaction. Perioperative organ dysfunction was evaluated by cardiac surgery scorring (CASUS)
system. There was no perioperative mortality. The mean ages of the patients and controls were 67.45±12.30 and 51,38±7,03
years old. In the study group, 35% (n=7) revealed TT, 45% (n=9) TG and 20% (n=4) GG polymorphism of Glycoprotein IIb. The
allele frequencies of the study group were similar to the controls (33,3%, n=9 revealed TT, 55,5 %, n=15 TG and 11,3%, n=3 GG).
There was no significant difference in terms of genetic polymorphism (p>0.05). Postoperative day 1 and day 2 CASUS scores
were similar among the three polymorphisms. In the study group, patients with GG allele had significantly higher interleukin
6 levels 24 hours after operation than the others (for TT allele 316,14±22, 10 pg/ml, TG allele 318, 12±14,50pg/ml and GG
338,14±22.20pg/ml) (p<0.05). Our results reveal that GG allele of Glycoprotein IIb ITGA2B gene has a significant role in the
magnitude of the inflammatory response seen after cardiac surgery with cardiopulmonary bypass.
PP 249 BIOLOGICAL ACTIVITIES OF AERIAL PARTS OF CENTAUREA SALICIFOLIA
ALI SEN 1, BURCAK GURBUZ 2, OZLEM BINGOL OZAKPINAR 3, SUKRAN KULTUR 4, UMRAN SOYOGUL GURER 2, FIKRIYE URAS 3,
LEYLA BITIS 1
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOGNOSY, ISTANBUL, TURKEY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, ISTANBUL, TURKEY
3
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
4
ISTANBUL UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACETICAL BOTANY, ISTANBUL, TURKEY
1
2
In this study, we reported, for the first time to our knowledge, biological activities of hexane, chloroform and aqueous
methanol fractions of methanol extract obtained from the aerial parts of Centaurea salicifolia Bieb. ex Willd. Antibacterial
activity was assessed by agar well diffusion and microdilution methods while antiproliferative activity was measured against
five human cancer cell lines (A549: lung adenocarcinoma, Hela; cervix adenocarcinoma, HT-29: colon adenocarcinoma, MCF7; breast adenocarcinoma, PC-3; prostate adenocarcinoma) using MTT assay (1,2). Aqueous methanol extract exhibited weak
antimicrobial activity with MIC of 7750.8 µg/ml, 15501.6 µg/ml, 1937.7 µg/ml against Staphylococcus aureus, Staphylococcus
epidermidis and Pseudomonas aeruginosa. Hexane and chloroform extracts showed antimicrobial activity in the range of
1164.06 - 582.03 µg/ml against Staphylococcus aureus and Staphylococcus epidermidis. Antiproliferative activity indicates that
chloroform extract exhibited strong activity with IC50 values of 21,66; 15,89 and 6,9 µg/ml against HT-29, MCF-7 and PC-3,
respectively. The same extract showed good antiproliferative activity with IC50 values of 70,03 and 76,73 µg/ml against A549
and HeLa, respectively. The results show that active extracts are good candidates for further activity-guided fractionation in the
search for new active antimicrobial and antitumor compounds.
References
1. Sen A, Gurbuz B, Gurer US, Bulut G, Bitis L. Flavonoids and Biological Activities of Centaurea stenolepis. Chemistry of Natural
Compounds, 2014; 50(1): 128-129.
2. Csapi B, Hajdú Z, Zupkó I, Berenyi A, Forgo P, Szabo P, Hohmann J. Bioactivity-guided isolation of antiproliferative compounds
from Centaurea arenaria, Phytotherapy Research, 2010; 24: 1664–1669
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PP 250 AN ASSESSMENT OF ANTIPROLIFERATIVE AND CYTOTOXIC ACTIVITY OF ESSENTIAL OIL OF CHAEROPHYLLUM
AROMATICUM AGAINST NORMAL AND TUMOR CELL LINES
ALI SEN 1, OZLEM BINGOL OZAKPINAR 2, AHMET DOGAN 3, FIKRIYE URAS 2, LEYLA BITIS 1
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACOGNOSY, ISTANBUL, TURKEY
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, ISTANBUL, TURKEY
3
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL BOTANY, ISTANBUL, TURKEY
1
2
Chaerophyllum aromaticum L. (Syn. C. byzantinum Boiss.) is one of the 16 species of the genus Chaerophyllum (Apiaceae)
growing wild in Turkey. This species, which is known as Mendek in Giresun province, is used as digestive by people in cooked
food. In this study, the antiproliferative and cytotoxic activities of essential oil of Chaerophyllum aromaticum on normal (NIH)
and cancer (K562, PC-3, MCF-7, HeLa, A549, HT-29) cell lines have been investigated for the first time by the MTT method. In a
previous study ıt was revealed that major components in essential oil of aerial parts of Chaerophyllum aromaticum collected in
Greece were cis-Ocimene (23.98 %) and α-terpinolene (12.18 %). In an another study although it was reported that α-terpinolene
has antiproliferative activity against brain tumour cells, there isn’t any study about effect of cytotoxic or antiproliferative of
Ocimene. The current study we have found that essential oil of Chaerophyllum aromaticum does not exhibit any cytotoxic and
antiproliferative activity at 100 µg/ml concentration against all the human cell lines. This result is similar to the work of Lone
et al. (2014) who reported essential oil of leaves of Senecio graciliflorus, the main compound were identified as cis-ocimene
(24.14 %), had no cytotoxic activity on A-549, PC-3 cancer cell lines. However, to definitely decide activity essential oil of
Chaerophyllum aromaticum, the composition and activity on different cell lines of essential oil of this plant originated in Turkey
is to be also planned to investigate in our further studies. When considered ethnobotanical use of this plant, It would safely
consume by people because this plant had no cytotoxic effect on normal cell line.
PP 251 CHITOSAN HYDROGEL FOR DERMAL GENE DELIVERY
SUNA OZBAS-TURAN, JULIDE AKBUGA
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTİCAL BİOTECHNOLOGY, HAYDARPAŞAİSTANBUL, TURKEY
The skin is an attractive and the largest organ for local and systemic drug applications. Skin gene therapy is a new approach
with great potential because the accessibility and the possibility to the modified area. In present study, chitosan hydrogels were
investigated for nucleic acid delivery into the skin.
In our study, chitosan hydrogel was prepared for dermal gene delivery and physico-chemical properties and in vitro/in vivo
transfection characteristics of hydrogel formulations were investigated. Chitosan could form pH-sensitive hydrogels by
addition of PEG 400. The highest swelling values were obtained at pH 3.5 buffer. The concentrations of chitosan, PEG 400 and
glutaraldehyde affected the water uptake and swelling of chitosan:PEG hydrogels (p<0.05). The release of pDNA from hydrogels
was monitored over 40 hours. Mouse fibroblastic NIH 3T3 cell line and primary human dermal fibroblasts were used for in vitro
transfection studies. Transfection efficiency of formulation was monitored by measuring of β-galactosidase activity expressed
by β-Gal reporter plasmid. In vitro b-gal production was obtained with the chitosan-PEG 400 (1:0.25) hydrogels. Baby and adult
Sprague–Dawley rats were used for in vivo transfection studies. By using enzyme assays and histological techniques, it was
shown that the reporter gene expression in dermis and hypodermis layers of skin sustained for 7 days. Highest b-gal amount
was measured at 3. days after transfection.
As a result, high b-gal expression was obtained with DNA-chitosan hydrogels in the in vitro and in vivo studies. Chitosan-based
delivery systems including hydrogels, can be efficiently used for DNA transfer through the skin.
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PP 252 ILLNESS PERCEPTION AND DIABETES SELF CARE ACTIVITIES IN PATIENTS WITH TYPE II DIABETES MELLITUS AT
COMMUNITY PHARMACY SETTING
HARUN DOGRUSEVER1, BETUL OKUYAN2, MESUT SANCAR2, H. KUBRA ELCIOGLU1
DEPARTMENT OF PHARMACOLOGY, MARMARA UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY
DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY
1
2
The aim of the study is to determine illness perception and diabetes self care activities in patients with type II diabetes mellitus
at community pharmacy setting. This study was conducted at two community pharmacies located in Istanbul and Sakarya. The
patients were eligible if they came to community pharmacy with any reason, accepted to participate after informed about study,
were 18 years old or older, and diagnosed with type 2 diabetes mellitus. The self care activities of patients with type 2 diabetes
mellitus were measured by “The Summary of Diabetes Self-Care Activities” (1), was scored between 0-7 according to how
many times patients’ performed diabetes self-care activities (diet, exercise, blood glucose testing, foot care, and medication
utilisation) over the past 7 days. The illness perception of patients was assessed by “Brief Illness Perception Questinnaire”
(2), was scored between 0-80 and a higher score represented a more threatening point of view for the illness. Eighty patients
(mean of age: 56.20±8.67 years old; male/female 35/45) were included the present study. When evaluating patients’ recent
haemoglobin A1C level, which was gathered in sixty-three patients, only twenty- three patients’ haemoglobin A1C levels were
equal and less than 6.50%. Of them, 17.50% used alone metformin, 26.25% used sulfonylurea plus metformin combination, and
16.25% used metformin and insulin combination for management of diabetes. The median scores (interquartile 25-75) of the
self care activities in the patients were calculated as 7 (7-7) for general diet, 7 (6-7) for specific diet, 5 (3-6) for exercises, 4 (3-6)
for blood glucose testing, 3 (2-5) for foot care and 7 (6-7) for medication utilization. The median overall scores for brief illness
perceptions questionnaire was 41 (36-48). According to patients’ belief, the most common factors that caused their illness were
hereditary, diet or eating habits, and stress, respectively. As a conclusion, the diabetic patients’ illness perception and self-care
activities should be also assessed to improve diabetic patients’ therapeutic outcomes.
1. Kav S, Akman A, Dogan N, Tarakci Z, Bulut Y, Hanoglu Z. Turkish validity and reliability of the summary of diabetes self-care
activities measure for patients with type-2 diabetes mellitus. J Clin Nurs. 2010;19(19-20)2933-5.
2. Broadbent E, Petrie KJ, Main J, Weinman J. The brief illness perception questionnaire. J Psychosom Res. 2006 Jun;60(6):631-7.
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PP 253 DETERMINANTION OF MEDICATION UTILIZATION AND ILLNESS PERCEPTION AMONG PATIENTS WITH II DIABATES
MELLITUS
H.KUBRA ELCIOGLU1, BETUL ÇAGLAYAN1, ALI CAGRI DEMIREL1, OGUZHAN DEYNELI2, MESUT SANCAR3, BETUL OKUYAN3
DEPARTMENT OF PHARMACOLOGY, MARMARA UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY
DIVISION OF ENDOCRINOLOGY AND METABOLISM, MARMARA UNIVERSITY, FACULTY OF MEDICINE, ISTANBUL, TURKEY
3
DEPARTMENT OF CLINICAL PHARMACY, MARMARA UNIVERSITY, FACULTY OF PHARMACY, ISTANBUL, TURKEY
1
2
The aim of the study is to determine medication utilization and illness perception among patients with type II diabetes mellitus.
This cross sectional study was conducted in outpatient clinic of a research and training hospital between April 01 and April 30,
2013. Patients type 2 diabetes mellitus admitted to outpatient clinic with any reason during the present study were eligible if
they were 18 years or older, utilized at least one medication for treatment of diabetes during at least 4 weeks, and accepted to
participate to the present study. Medication utilization was assessed by medication taking self care component of The Summary
of Diabetes Self-Care Activities (1), was scored between 0-7 according to how many times patients’ took their medication
recommended for diabetes over the past 7 days. The illness perception of patients was assessed by ‘Brief Illness Perception
Questionnaire’ (2), was consist of eight dimension scored between 0-10. A hundred and four patients (mean of age: 55.7±12.7
years old; male/female 40/64) were included the present study. When evaluating patients’ recent haemoglobin A1C level,
haemoglobin A1C levels were equal and less than 6.5% in 33.7% of them. Duration of diabetes was more than five years in
55.6% of them. The common utilized medications for treatment of diabetes were metformin (62.5%), insulin (51.9%), and
sulfonylurea (24.0%). Besides medication for treatment of diabetes; it was also observed that statin (25.0%), aspirin (21.2%),
and angiotensin II receptor blockers (18.3%) were also prescribed among study patients. Of them, 7.7% was utilized dietary
supplements. Medication taking self-care activities in the patients were calculated as 7 (7-7). When assessed illness perception;
the median scores (interquartile 25-75) of each dimensions of illness perception were 7 (5-8) for consequences, 10 (10-10)
for timeline, 6 (3-8) for personal control, 8 (5.2-10) treatment control, 7 (4-8) for identity, 6 (2.2-8) for illness concern, 10 (810) for coherence, 7 (4-9) for emotional representation. According to patients’ belief, the most common factors that caused
their illness were hereditary, stress and ageing, respectively. Although the moderate illness perception and high medication
adherence determined among patients with type II diabetes mellitus in the present study, poor therapeutic outcomes have
been observed according to their haemoglobin A1C levels.
1. Kav S, Akman A, Dogan N, Tarakci Z, Bulut Y, Hanoglu Z. Turkish validity and reliability of the summary of diabetes self-care
activities measure for patients with type-2 diabetes mellitus. J Clin Nurs. 2010;19(19-20)2933-5.
2. Broadbent E, Petrie KJ, Main J, Weinman J. The brief illness perception questionnaire. J Psychosom Res. 2006 Jun;60(6):631-7.
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PP 254 TISSUE FACTOR EXPRESSION OF ADIPOSE TISSUE IN OBESITY
USTUNDAG, EMEKLI-ALTURFAN1, KESKIN 2, SUTCU2, YIGITBASI 3, EMEKLI3
MARMARA UNIVERSITY, FACULTY OF DENTISTRY, DEPARTMENT OF BIOCHEMISTRY
MEDIPOL UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY
2
MEDIPOL UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF PLASTIC SURGERY
3
MEDIPOL UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF BIOCHEMISTRY
1
2
Tissue factor (TF) has both procoagulant signaling activities. TF has been associated with many biochemical events including
haemostasis, thrombosis, inflammation, angiogenesis and cancer. Recently the expression of TF has been demonstrated in
adipose tissue of leptin-deficient (ob/ob) mice. In obese patients altered expression of some haemostatic parameters such as
fibrinogen and Factor VII have been shown. This may contribute to the coronary artery disease or other metabolic diseases
such as diabetes. The aim of this study is to investigate the expression of TF in the adipose tissue of a patient with obesity. TF
expression was determined immunohistochemically on formalin fixed paraffin-embedded adipose tissues that were obtained
during the liposuction procedure. The images were then obtained with the microscope fitted with a digital camera and TF expression was evaluated and discussed.
PP 255 NEW DIFLUNISAL HYDRAZONES AND THIAZOLIDINONES AS ANTI-HCV AND ANTIMICROBIAL AGENTS
SEVIL SENKARDES1, SINEM OKTEM OKULLU2, TANIL KOCAGOZ2, NEERJA KAUSHIK-BASU3, DINESH MANVAR3, AMARTYA BASU3
S.GUNIZ KUCUKGUZEL1
MARMARA UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, HAYDARPASA ISTANBUL,
TURKEY
2
ACIBADEM UNIVERSITY, FACULTY OF MEDICINE,DEPARTMENT OF MEDICAL MICROBIOLOGY,
ISTANBUL, TURKEY
3
RUTGERS-NEW JERSEY MEDICAL SCHOOL, DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BİOLOGY NEWARK, NEW JERSEY, USA
1
Hydrazide-hydrazones have been demonstrated to possess biological activities (1,2). 4-Thiazolidinone derivatives are known
to possess biological activities (3). In addition, 2¢,4¢-difluoro-4-hydroxybiphenyl-3-carboxylic acid [2-(2-fluorophenyl)4-thiazolidinone-3-yl]amide exhibited an IC50 value of 48 mM against HCV NS5B RdRp (4). These observations led us to
synthesize novel diflunisal hydrazide-hydrazones and 4-thiazolidinones and to investigate their possible antimicrobial and antiHCV activities (5,6). Thus, these derivatives showed moderate antimicrobial activity and excellent anti-HCV activity.
References:
(1) Rollas S, Küçükgüzel ŞG. Biological activities of hydrazone derivatives. Molecules. 2007; 12: 1910-1939.
(2) Aydın S, Kaushik-Basu N, Arora P, Basu A, Nichols DB, Talele TT, Akkurt M, Çelik İ, Büyükgüngor O, Küçükgüzel ŞG. Microwave
assisted synthesis of some novel flurbiprofen hydrazidehydrazones as anti-HCV NS5B and anticancer agents. Marmara Pharm
J. 2013; 17: 26-34.
(3) Tripathi AC, Gupta SJ, Fatima GN, Sonar PK, Verma A, Saraf SK. 4-Thiazolidinones: the advances continue… Eur J Med Chem.
2014; 72: 52-77.
(4) Kaushik-Basu N, Bopda-Waffo A, Talele TT, Basu A, Chen Y, Küçükgüzel ŞG. 4-Thiazolidinones: A novel class of hepatitis C virus
NS5B polymerase inhibitors. Front Biosci. 2008; 13: 3857-3868.
(5) Aydın S, Bingöl Özakpınar Ö, Özsavcı D, Çevik Ö, Şener A, Şahin F, Küçükgüzel Ş.G. “Synthesis and Anticancer Activity Of
Diflunisal Hydrazide-Hydrazones As Apoptosis Inducing Agents” International Symposium on Drug Research&Development,
2013, Antalya. P-45.
(6) Aydın S, Bingöl Özakpınar Ö, Özsavcı D, Çevik Ö, Şener A, Küçükgüzel Ş.G. “Synthesis Of New Diflunisal Thiazolidinones As
Potential Pro-Apoptosis and Anticancer Effects” 50th International Conference on Medicinal Chemistry, 2014, Rouen, FRANCE.
Acknowledgments: This research was supported by TUBITAK, Project Number: 112S013. The authors are grateful to Dr. Jürgen
Gross for obtaining HR-EI/FAB mass spectra of the compounds.
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PP2 56 THERAPEUTIC DRUG MONITORING IN PEDIATRIC PATIENTS TREATED WITH ANTI-TUBERCULOSIS MEDICATIONS:
PRELIMINARY STUDY
BETUL OKUYAN1 , MESUT SANCAR1, NAZAN DALGIC2, SEVGI KARAKUS3, ERKAN CAKIR4, LEVENT MIDYAT5, UFUK ERENBERK4,
FIKRET VEHBI IZZETTIN1, SEVIM ROLLAS3, BEDIA KAYMAKCIOGLU3
CLINICAL PHARMACY DEPARTMENT, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
DIVISION OF PEDIATRIC INFECTIOUS DISEASES, SISLI ETFAL TRAINING AND RESEARCH HOSPITAL, ISTANBUL, TURKEY
3
PHARMACEUTICAL CHEMISTRY DEPARTMENT, FACULTY OF PHARMACY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
4
DEPARTMENT OF PEDIATRIC PULMONOLOGY, BEZMIALEM VAKIF UNIVERSITY, ISTANBUL, TURKEY
5
DEPARTMENT OF PEDIATRIC PULMONOLOGY, SUREYYAPASA CHEST DISEASES AND THORACIC SURGERY TRAINING AND
INVESTIGATION HOSPITAL, ISTANBUL, TURKEY
1
2
There is a growing concern according to results of a few recently published data about a low therapeutic serum concentration
of anti-tuberculosis medications in pediatric patients with tuberculosis when compared with adult patients with tuberculosis,
which resulted in poor therapeutic outcomes in pediatric patients. The aim of the study is to determine therapeutic serum
concentration of isoniazid, rifampicin and pyrazinamide in pediatric patients treated with standard primary anti-tuberculosis
medications (the combination of isoniazid, rifampicin, ethambutol, and pyrazinamide) by using a high performance liquid
chromatography (HPLC) in different periods during treatment and to investigate association between therapeutic outcome
such as medication adherence and therapeutic serum concentration of medications. Patients were eligible for the present
study; if they were 14 years old or younger, diagnosed with pulmonary and extra pulmonary tuberculosis and started treatment
with standard primary anti- tuberculosis medications and provided consent form from their parents. The serum sample has
been collected at baseline (0 h) and 1.5, 3, 4.5 and 6 hours after giving the first dose of anti-tuberculosis drugs on the first day.
The serum sample has been also taken before and 3 hours after anti-tuberculosis therapy on the fourth day and fourth months
of treatment to determine medication adherence during management of tuberculosis. Therapeutic serum concentrations of
isoniazid, rifampicin and pyrazinamide have been assayed by previously described HPLC method (1). The appropriateness of
HPLC method that previously developed in adult patients with tuberculosis (1) has been also established for the pediatric
patients according the results thus far obtained. It has been still continued to determine serum concentration of medications
in pediatric patients.
1. Unsalan S, Sancar M, Bekce B, Clark P, Karagoz T, Izzettin FV, Rollas S. Therapeutic Isoniazid, Pyrazinamide and Rifampicin
Monitoring Using High Performance Liquid Chromatography in Tuberculosis Patients. Chromotographia. 2005; 61: 595-598.
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2014 IMPPS-4 International Congress Sponsors
www.msd.com.tr
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-192-
Thanks For Contributions
*Alphabetically Listed
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-194-
INDEX
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A
ABDERRHAMANE SENATOR 132
ABDULMONEM GOBASSA 88
ABDURRAHIM ELOUZI 156
ABOLFAZL BARZEGAR 120
ACHOURI MOHAMED YACINE 114, 126
ADEM ONAL 135, 136
A. DENIZ DURU 27
ADILE CEVIKBAS 122, 160
ADILE SERKI 155
ADNAN AYDIN 141
AFSANEH FARJAMI 58
AFZAL MUHAMMAD 145
AGOULNIK IU 53
AHMED KABOUCHE 72
AHMET AYDIN 39, 79, 175
AHMET DOGAN 187
AHMET HACIMUFTUOGLU 153
AHMET KOC 175
AHMET OZDEMIR 119
AHMET OZER SEHIRLI 160
AHMET TARIK BAYKAL 117
AICHA BOURATOUA 72
AILAR NAKHLBAND 129
AIMAN ABBAS 106
AIRY GRAS 29
AKGUL YESILADA 43
AKIN DAYAN 159
ALAA MASHINA 88
ALI CAGRI DEMIREL 189
ALI ESFAHANI 62
ALI OSMAN ATAC 33
ALIREZA GARJANI 129, 130, 133, 139, 165
ALIREZA SHAFAATI 133
ALI SEN 155, 186, 187
ALLEG ABDELATIF OUSSAMA 114
ALPER OKYAR 46
AMARTYA BASU 63, 190
AMEL AMRANI 146
AMEL CHENAFA 92, 93
ANDRé LEBERT 62, 134
ANETTE LARSSON 174
ANIL TALAS 82
ANNA BERGSTRAND 174
ANNE-LAURE CHARLES 92
ANNE-MARIE MAURER 113, 114
ANTONIO VENTOSA 56, 76, 77
A. SEZA BASTUG 137
A. SIBEL OZKAN 136
ASLI CULDUZ 67, 155
ASLI DEMIRCI 182
ASLIGUL KENDIRCI 39
ASLIHAN DAGDEMIR 134, 62
ASMA BEN AHMED 88
A. SUHA YALCIN 27
ATILA ABDULLAHI 107
AYFER TOZAN-BECEREN 104, 105
AYGUL KOSEOGLU 175
AYHAN SAVASER 136
AYKUT OZGUR 91
AYLIN SEPICI DINCEL 64
AYSEGUL IYIDOGAN 171
AYSEGUL KARAKUCUK IYIDOGAN 166, 161, 162, 164, 143,
167
AYSEGUL PRINCAL 72
AYSE KARADUMAN 162
AYSEN GARGILI 31
AYSEN KURT CUCU 116
AYSEN YARAT 170, 171, 184
AYSE OGAN 56, 104, 164
AYSE SAHIN YAGLIOGLU 135, 136, 96, 97, 98, 99, 168, 169
AYSE TARBIN JANNUZZI 145
AYSIN TULUNAY 59, 64, 185
AYSU SELCUK 81, 84, 85, 86
AYTEN CELEBI KESKIN 150
AZHAR HUSSAIN 44
AZIME BERNA OZCELIK 131, 150
AZIN JAHANGIRI 123, 124
AZIN YAGHMAEIAN 123
AZIZE SENER 80, 102, 116, 81
B
BAHAR GOKER 116, 117
BAHRAM KAZEMI 134
BAKI CHEKIB ARSLANE 88
BANU UNAL 175
BASAK GOKCE 172
BEDIA KOCYIGIT-KAYMAKCIOGLU 162
BEDRIYE SEDA KURSUN AKTAR 143, 166
BEGUM NURPELIN SAGLIK 181
BEHZAD MOKHTARE 152, 153
BELGIN SUSLEYICI DUMAN 141
BERNA OZBEK CELIK 174, 178
BERNARD GENY 92
BERNA TERZIOGLU 173
BERRA KILIC 83
BERRIN OZCELIK 81
BETUL CAGLAYAN 189
BETUL DORTUNC 61, 128, 151
BETUL FEYZA ULUSOY 114
BETUL KARADEMIR 41
BETUL OKUYAN 33, 81, 82, 83, 84, 85, 86, 87, 188, 189
BETUL SARIKAYA 105
BEYHAN KARA KISLA 174
BEYZA BETUL KOCAK 174
BEZHAN CHANKVETADZE 20
BHARGAV A. PATEL 63
BILAL YILMAZ 153, 154
BILGE KAAN AKCAY 153, 154
BINGOL-OZAKPINAR O 53
B. IREM OMURTAG KORKMAZ 46
BORA BASKAK 109
BORTE AGRAP 96
BOUAMRA DALILA 88
BOUCHEBOUR ABDELHAMID 88
BOUDGHENE STAMBOULI YASMINE 115
BOURICHE HAMAMA 125
B. SEDA KURSUN AKTAR 167
BUGRA SOYKUT 79
BUKET ALPERTUNGA 95, 145, 167
BURCAK GURBUZ 186, 122
BURCIN ALEV 170, 171
BURCU BEKTASOGLU 25
BURCU OKTAY 184
BURKHARD HORSTKOTTE 65
-196-
C
CAFER ADIGUZEL 113
CAFER ADIGUZEL 64
CAGLAR DEMIRBAG 115, 140, 110
CAGLAR MACIT 171
CAMERON ALEXANDER 61, 128
CAN AKPOLAT 77
CANAN ATALAY 157
CANAN HASCICEK 136
CANER CEVIK 161
CANSU AKBULUT 148, 149
CAROLINE FELIX 73
CARSTEN T. WOTJAK 22
CEM FICICIOGLU 74
CEM KOCAK 52
CENGIZ SARIKURKCU 172
CEYDA TUBA SENGEL-TURK 136
CIGDEM KASPAR 67
CIHAN GUNDUZ 164, 104
CIHAN ONDER 94
CLAUDIA DEUS 63
CRISTANI MARIATERESA 88
CRISTINA SáNCHEZ-PORRO 56, 76, 77
D
DALIBOR ŠATíNSKý 65
DALI YAHIA 115
DAMLA ANBAR 104
DANILO MILARDI 60
DAVOUD ASGARI 132
DENIZ CIKLA YILMAZ 137
DENIZ GURANLIOGLU 29
DERYA KOC 105
DERYA OZSAVCI 80, 102, 116, 105
DERYUGINA EI 53
DILAY YAVUZ 85, 86
DILEK BILGIC ALKAYA 116
DILEK HEPERKAN 45
DILEK YAZICI 159
DILSAD HERKILOGLU 58
DILVIN GUNEY 64
DINESH MANVAR 63, 190
DJAHIDA ELGOUTNI 93
DJAMILA ZAMA 63, 146
DJEBLI NOUREDDINE 115
DOLUNAY SAKAR 120
DOMINIQUE BERNARD-GALLON 62, 134
DUYGU GUNES 99
DUYGU TASKIN 143
E
EBRAHIM RAZZAZI-FAZELI 25
EBRU AKTAS 136
EBRU EMEKLI-ALTURFAN 171
EBRU GUL 96, 97, 98, 99, 168
EBRU OZDEMIR NATH 144
EBRU TURKOZ ACAR 111
EDA KIYMAZ 98
E. ELCIN EMRE 167
EFE DOGUKAN DINCEL 85, 86
ELIF CAGLAYAN 71
ELIF CALISKAN SALIHI 127
ELNAZ MEHDIZADEH AGHDAM 120
EMEKLI 190
EMEKLI-ALTURFAN 190
EMEL EKSIOGLU-DEMIRALP 64
EMEL MATARACI KARA 174
EMHEMMED ELGALLAL 88
EMINE AKALIN URUSAK 152
EMINE ALARCIN 110
EMINE ELCIN ORUC EMRE 143, 166, 161, 162, 163, 164, 171
EMINE SALVA 41
EMINE VURAL GENC 56
EMRAH OZAKAR 153, 154
EMRE DOLEN 137
ENDER VOLKAN 36, 57, 90
ENGIN CELEP 64
ENGIN KILIC 87
ENVER CIRACI 59, 186, 185
ERDEM BUYUKBINGOL 33
ERDEM YESILADA 20, 64
ERGUVAN TUBA OZEL KIZIL 109
ERKAN PEHLIVAN 163
ERKAN RAYAMAN 160, 185
ERLIASA BAMI 83, 86, 87
ERSIN ASLAN 167
ERTAN TUZLACI 93, 94, 155
ESIN YILMAZ 75
ESRA TATAR 63, 73, 74, 182
EYUP BASARAN 161, 162, 163, 164
F
FADILA BENAYACHE 63, 146
FARANAK SALMANNEJAD 133
FARNAZ MONAJJEMZADEH 124
FARZAD KOBARFARD 126
FATEMEH FATHIAZAD 130, 139, 165
FATIH AVCI 97
FATIH METE 159
FATMA GUMUS 131, 150
FERDA ESER 97, 135, 136
FERDA NUR ALPASLAN 33
FERIHA ERCAN 86, 87
FERZAN LERMIOGLU ERCIYAS 96
FEYZA ALYU 179, 180
FEYZA ARICIOGLU 22
FIGEN ESIN KAYHAN 148, 149
FIKRET VEHBI IZZETTIN 43, 82, 83, 84, 86, 87, 158, 159, 157,
81
FIKRIYE URAS 23, 58, 59, 64, 113, 114, 186, 187, 185
FILIZ ARIOZ OZDEMIR 66
FILIZ BAKAR 131, 136, 130
FILIZ MERICLI 24
FIROZ ANWAR 145
FRANCISCO FERNANDEZ TRILLO 61
FRATANTONIO DEBORAH 88
FRéDéRIQUE PENAULT-LLORCA 134, 62
F. TULAY TUGCU 178
FUNDA PEPEDIL 64
G
GAëLLE JUDES 62, 134
GARY WALSH 18
GAURAV GUPTA 145
GINESTA SERRASOLSES 29
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GINESTRA GIOVANNA 88
GISELLA ALFONSINO 60
GIZEM BULUT 30, 93, 94, 155
GIZEM CAKIR 63, 143
GIZEM KAYA 172
GOKCEHAN GULTEKIN 158
GOKCEN YASAYAN 61, 128
GOKHAN ABAY 168, 169
GOKNIL PELIN COSKUN 66
GOKSEL SENER 170, 171, 151
GONCA COMERT ATALAY 83
GONCAGUL HAKLAR 48
GOZDE EGEMEN 80
GOZDE YESILYAPRAK 157, 158
GULACTI TOPCU 24
GUL BAKTIR 34
GULBIKE DEMIREL 90
GULBIN ERDOGAN 116, 137
GUL CEVAHIR OZ 178
GULDEN CELIK 74
GULDEN ZEHRA OMURTAG 159, 183, 104, 105, 173
GULDEREN KARAKUS 59, 119, 120
GULER YALCIN 26, 115, 140
GULGUN TINAZ 35
GULHAN TURAN-ZITOUNI 179, 119
GULLU KAYMAK 148, 149
GULNAZ NURAL BEKIROGLU 122
GUL OZHAN 95, 147, 167, 145
GULSAH ARAMAN 177
GULSAH KARAKAYA 81
GULSEN AKALIN CIFTCI 89, 118, 119
GULTEN TASDELEN 111
GUNSELI CANSU ASKIN 159
GURKAN GUR 90
H
HADI VALIZADEH 78, 132, 138, 155
HAJER ALBORAWY 88
HALEH HAMEDIFAR 19
HALEH VAEZ 129, 133, 139, 165
HALE KOME 83
HALE ZERRIN TOKLU 95
HALIDE EDIP TEMEL 89, 118, 119
HALIL AKSOY 102, 116
HALIL IBRAHIM ULUSOY 95
HALISE DEVRIMCI OZGUVEN 109
HALISE INCI GUL 91, 92
HAMAMA BOURICHE 132
HAMID REZA HEIDARI 134
HAMID SORAYA 129
HANA SKLENářOVá 65
HANDE SIPAHI 67, 79, 175
HARIKA AYDIN 179, 180
HARIKA EYLUL ESMER 148, 149
HARTMANN R. W 35
HARUN DOGRUSEVER 188
HARZALLAH DAOUD 88
HASAN KILICGUN 57
HASAN KIRMIZIBEKMEZ 111
HASAN SECEN 91
HASAN SOYLEMEZ 168
HASAN TOLGA OZCAM 70
HATICE IKRA DUMLU 84
HATICE KAPLAN CAN 119
HATICE OZDEMIR 109
HATICE SECINTI 91
HAYAT ONYUKSEL 18
HAYDAR SUR 49
HAZAL HAZINECI 171
HAZAL IPEKCI 171, 184
H. BIROL COTUK 27
HIKMET AKPINAR 99, 100, 101
HILAL ALTINOZ 186
HILAL BARDAKCI 111
HIROSHI SAKAGAMI 91
H. KUBRA ELCIOGLU 188,167, 189
HODGSON MC 53
HOSSEIN NADERI-MANESH 134
HOSSEIN NAZEMIEH 139
HULYA SAHIN 154, 183
I
I.BANU AYCA 107, 108
IBRAHIM DEMIRTAS 96, 97, 98, 168, 135, 136, 166, 135, 143,
99, 168
IBRAHIM HALIL KILIC 162
IDIL CETIN 178
ILHAN YARGIC 21
ILKAY KUCUKGUZEL 63, 73, 74, 182, 182
IMANE SEDIRI 92
IMRAN KAZMI 145
INCI NEJLA YILDIZ 166
IPEK CELIK 85, 86
IRAJ ASVADI 62
IREM GIRGIN 84
IRFAN YALCINKAYA 122
ISIK KAYGUSUZ 64
ISMAHAN DJEBBAR 92
ISMET BERBER 160
ISMET BURCU TURKYILMAZ 170
IVANA ŠRáMKOVá 65
IZAROUKEN ASSIA 115
J
JALEH BARAR 132
JOAN VALLÈS 29
JOHANNES P. MAGNUSSON 128
JUDY DELP 95
JULIDE AKBUGA 187
J.W.FOPPE VAN MIL 32
K
KAAN KUCUKOGLU 91, 92
KADA SEOUSSEN 125
KADIR TURAN 71, 72
KAMBIZ GILANI 126
KERIM ALPINAR 30, 144
KESKIN 190
KEVIN STRANG 95
KHOSRO ADIBKIA 123, 124
KORAY AK 186
KUBILAY GUCLU 25
KUBRA ULUSOY 76
KUTAY KOROGLU 86, 87
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L
LAAYA SAADAT 139
LALE TURKGELDI 58
LAOUICHA SALIHA 125
LARDJAM ABDERRAHMENE 115
LEILA BARGHI 132
LEILA BELFARHI 146
LEMAN CELIK SUREN 79
LEVENT KABASAKAL 167, 170
LEYLA ACIK 150
LEYLA BITIS 155, 156, 186, 187, 175
LEYLA YURTTAS 89, 118
LIEVE NAESENS 73
LINA HAMMAD 106
LIN D 53
LINDA AOUAD 92
LIVIA BASILE 60
L. OMUR DEMIREZER 165
LOPEZ SM 53
LUKáš ZAHáLKA 65
LUTFI BEHCET 135
M
MAHDIYEH PASHAII 139, 165
MAHMOUD ABUDAYYAK 95, 167
MAHMOUD MOSADDEGH 142
MAI KHANFAR 94, 151
MAJID MAHDAVI 60
MARINA MILENKOVIC 70
MARJOLAINE NGOLLO 62
MARTYN C. DAVIES 61, 128
MARYAM RAMESHRAD 129, 130, 133, 139, 165
MATTEO PAPPALARDO 60
MAUREEN ECHEGUT 134
MAZID RYM 115
MECIT CALISKAN 82
MEHLIKA DILEK ALTINTOP 119
MEHMET ALI ACAR 83
MEHMET ALI AKYUZ 77
MEHMET EMIN HACIYUSUFOGLU 160
MEHMET EMRAH YAMAN 65
MEHMET GUMUSTAS 136
MEHMET HURSITOGLU 159
MEHMET MAHRAMANLIOGLU 127
MEHMET OZASLAN 162
MEHMET OZTURK 143, 166, 167
MEHMET RIFKI TOPCUL 178
MEHMET SONMEZ 160
MEHMET TEVFIK DORAK 23
MEHMET V. KAHRAMAN 184
MEHMET ZAFER GOREN 61
MELDA DOLARSLAN 136
MELDA DOLARSLAN 96, 97, 98, 99, 168
MELIHA KOLDEMIR GUNDUZ 141
MELTEM CETIN 152, 153, 154
MERAL BIRBIR 56, 74, 75, 76, 77
MERAL YUKSEL 64, 183
MERI KOLUACIK 67
MERT GURCAN KARALI 164
MERT ULGEN 47
MERVE ARICI 147
MERVE KASAP 112
MERVE SUZAN ZEDEN 57, 90
MESBAH LAHOUEL 72, 73
MESSAOUDI DALILA 125
MESUT SANCAR 81, 82, 83, 84, 85, 86, 87, 188, 189
MEVLUDE BETUL KOSELI 164
MEVLUT ALBAYRAK 65
MICHAEL DELP 95
MICHELA PADOVANI 45
MINA ISLAMBULCHILAR 62
MINE SENYILDIZ 147
MOHAMED ADIL SELKA 114
MOHAMED EL ATTUG 88
MOHAMED MIHOUB ZERROUG 132
MOHAMMAD BARZEGAR JALALI 123
MOHAMMAD REZA KHOSHAYAND 126
MOHAMMAD REZA RASHIDI 60
MOHAMMADREZA SATTARI 62
MOHAMMAD SAEID HEJAZI 60, 120
MOHAMMED CHAREHSAZ 79
MONTSE PARADA 29
MONTSE RIGAT 29
MORANDO SOFFRITTI 45
MOULAI MOHAMED CHERIF LOUAZZANI 114
MUGE SIRVANCI YALABIK 177
MUHAMMET IBRAHIM OZSOY 163
MUHAMMET SAMIL YAGLIOGLU 168, 169
MUJDE ERYILMAZ 90
MURAT BULENT RABUS 169
MURAT SONGUR 169
MURAT SUKUROGLU 92
MURAT TEMIRTURK 96
MURSID PEKIN 137
MUSTAFA BENER 25
MUSTAFA BULUT 104
MUSTAFA EROGLU 59, 185, 58
MUSTAFA GUL 92
MUSTAFA MUHLIS ALPARSLAN 164, 104
MUSTAFA OZYUREK 25
MUSTAPHA CHELGHOUM 93
MUTAZ SHEIKH SALEM 151
MUTLU AYTEMIR 81
MYRON A. MEHLMAN 51
N
NADIRE OZENVER 165
NAFIZ ONCU CAN 113
NARIN SADIKOGLU 175, 113
NASRIN MALEKI-DIZAJI 129, 130
NASTARAN NAFISSI-VARCHEH 133
NAZAN DENIZ YON ERTUG 148, 149
NAZILA JAFARI AGHDAM 123
NAZIRE MERVE KARTAL 162
NAZIYE OZKAN 58, 114, 154, 183
NAZLI GUL ALTINDIS 80, 81
NAZLI POURMOHAMMAD 121
NAZLI SENCAN 49, 67, 155
NAZLI TURAN 180
N. BUKET AKSU 36
NEBAHAT AKDEMIR 104
NECLA KULABAS 182
NEERJA KAUSHIK-BASU 190, 63
NEFISE OZLEN SAHIN 79
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NEGISA SEYEDTOUTOUNCHI 139
NESE ERDINC 138, 115
NESE ERIZ 58
NET DAS-EVCIMEN 136
NEVIN TUZCU 119
NIHAL TUMER 47, 95
NIHAN UNUBOL 74, 182
NILHAN APOHAN 184
NIMET EMEL LULECI 78
NOSTRO ANTONIA 88
NURAY ULUSOY GUZELDEMIRCI 163
NUR BAKIR 141
NURCAN KARAMAN 171
NUR MELEK CETIN 120
NURTEN ALTANLAR 90
NURTEN OZSOY 152
NUSRET ERDOGAN 154, 183
R
O
S
OGUZHAN AYDEMIR 176
OGUZHAN DEYNELI 189
ONUR DEMIRTAS 140
ONUR ERDEM 79
ONUR ERTIK 170
ONUR SENOL 65
ONUR YERLIKHAN 169
ORHAN ATES 153
OSMAN EKINCI 173
OUAHIBA BENAISSA 146
OUASSILA TOUAFEK 72
OYA KERIMOGLU 42, 110, 151
OYA UYGUNER 186
OZAN OZCAN 171
OZER SEHIRLI 151
OZGE CEVIK 80, 99, 100, 101, 102, 103, 116, 117, 122, 81
OZGE DOGAN 80, 81
OZGE KIZILKALE YILDIRIM 74
OZGUR DEVRIM CAN 112, 179
OZKAN DANIS 104, 164
OZLEM BINGOL OZAKPINAR 58, 59, 82, 86, 87, 113, 114, 186,
187, 185, 105
OZLEM ERDAS 33
OZLEM OZAKPINAR 102, 116
OZLEM SACAN 170
OZLEM TUGCE CILINGIR 100, 101, 102, 103
SADIK SAHIN 58, 59, 114, 185
SAEEDEH GHAFARI 109
SAEED GHANBARZADEH 78
SAEED SALARI 122
SAFIYE SAG ERDEM 77
SAHAR BEHZAD 142
SAKINA ZERIZER 72
SALIHA LAOUICHA 132
SALIH GUMRU 176, 177
SALVATORE GUCCIONE 28, 60
SAMET ERGUN 186
SAMIR BENAYACHE 63, 146
SANAM ARAMI 60
SANAZ HAMEDEYAZDAN 130, 165
SANDRA HABABEH 151
SARFRAZ AHMAD 40
SARP KAYA 170
SA. SOLTANI 142
SAYEH MOSTAFIDI 155
SCOTT HULTGREN 36, 57
SECKIN YATKIN 93
SEDA UNSALAN 48
SEDA YALDIZ 73
SEDA YILMAZ 104
SEHER KARSLI-CEPPIOGLU 62, 134, 78, 110
SEHKAR OKTAY 95
SEHMUS ISIK 108
SEIFEDDINE REKKAB 73
SELCUK KABAN 153, 154
SELIM ISBIR 186
SELIN KOKEN 98
SELKA MOHAMMED ADIL 126
SEMA BIRLER 19
SEMA DEMIRCI CEKIC 25
SEMANUR DENIZ 82
SEMRA SARDAS 159, 104, 105, 173
SEMRA UTKU 150
SENA F. SEZEN 34
SENATOR ABDERRAHAMANE 125
SEONKYEONG YANG 84, 85, 86
SERAP AKYUZ 170
SERAP AYAZ SEYHAN 115, 140
SERAP KARADERI 116
SEREF DEMIRAYAK 89
SERKAN KOLDAS 135
P
PARIZAD GHAREBAGHI 148
PARVIN ZAKERI-MILANI 78, 138, 155
PAULO OLIVEIRA 63
PAYAL GHOSH 95
PELIN CIKLA-SUZGUN 105
PENBE CAGATAY 141
PERVIN RAYAMAN 160
PETR SOLICH 65
PHILIP SCARPACE 95
PINAR ATA 82
PINAR AY 28
PINAR CAGLAYAN 56, 75, 76, 77
PINAR SINEM OMURTAG 104
POOYA NOORIZADEH 124
PRADEEP VELAUTHAM 88
PROFESSOR DOCTOR HER ROYAL HIGHNESS PRINCESS
CHULABHORN 18
RABIA OBA 99, 100, 101, 102, 103
RABIA SENA TURKER 93
RAHMI ZEYBEK 169
RAHSAN ILIKCI SAGKAN 131
RAMAZAN MAMMADOV 111
RANIA HAMED 106
REFIK DEMIRTUNC 159, 81, 160
REFIYE YANARDAG 170, 174
RENGUL CETIN-ATALAY 92
RESAT APAK 25
REYHAN OZCELIK 171
REZA ABOOFAZELI 133
RONAK SALEHIAN 130
RUKIYE SEVINC OZAKAR 152, 153, 154
RUPA GUHAMAZUMDER 63
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SERMIN TETIK 59, 186, 185
SERRA VILDAN AKGUL 173
S. ESIN CELIK 25
SEVCAN GUL AKGUN 173
SEVDA SUZGEC-SELCUK 152
SEVGI KARAKUS 74
SEVILAY CENGIZ 111, 112
SEVIL SENKARDES 190
SEVIM KARABULUT 137
SEVIM ROLLAS 162
SEVINC SAHBAZ 128, 151, 61
SEYDA GUL ALAGOZ 160
SEYED ALIREZA MORTAZAVI 126
SEYEDEHNEGISA SEYEDTOUTOUNCHI 165
SEZGIN AYDEMIR 154, 183
S.GUNIZ KUCUKGUZEL 190, 74, 105
SHAHRIAR PAYAB 123, 124
SHAMIM SAHRANAVARD 108, 109
SHEIDA SHARBATI 121
SIBEL OZDEN 27, 147, 167, 172, 177
SIDIKA SUNGUR 143
SIDNEY J. STOHS 43, 44
SIHEM HAFDI 93
SILA GULBAG 172
SINAN ARSAN 186
SINAN SUZEN 109
SINASI UNAL 107
SINEM GOKTURK 70, 138
SINEM OKTEM OKULLU 190, 74, 182
SOMAIEH SOLTANI 58
SOMAYEH ESMAEILI 108, 109
SOUMIA LASSED 63, 146
S. SOLTANI 142
STEPHANIE ALLEN 61, 128
SUAREZ E 53
SUHAIR AL-NIMRY 94
SUKRAN KULTUR 186, 144
SUKRAN YILMAZ 150
SULE APIKOGLU-RABUS 66, 157, 158, 159, 169
SULE CETINEL 100, 101, 102, 103, 151
SULE IBISOGLU 71
SULEYMAN ATALAY 83
SULEYMAN OK 94
SULEYMAN SEYHAN 140
SUMRU SOZER KARADAGLI 96
SUNA OZBAS-TURAN 187
SUREYYA OLGEN 130, 131
SUTCU 190
T
TAIBE ARSOY 150
TAIBI BEN HADDA 73
TANAJI T. TALELE 63
TANIL KOCAGOZ 190, 74, 182
TARBIN JANNUZZI 95
TAYEBEH GHARI 126
TERESA GARNATJE 29
TIMUCIN UGURLU 38, 185
TOUMI HOUARI 115
TUFAN GUNES 82
TUGBA TUNALI-AKBAY 171, 184
TUGCE COSAR 98
TUGCE KOC 78
TUGCE SAY 85, 86
TUGCE YESIL 173
TULIN TUGLULAR 64
TUNC AKKOC 40
TURGUT SEKERLER 86, 87, 114
TURGUT TASKIN 155, 175
TURKAN YURDUN 78, 137
U
UGUR KARACICEK 185
UGUR MUSABAK 131
ULVIYE ACAR 180
UMIDE DEMIR OZKAY 113, 179, 180, 181
UMIT SALAN 104
UMRAN SOYOGUL GURER 186, 122
UMUT IRFAN UCEL 179, 180
UNSAL VELI USTUNDAG 171
URAS F 53
USTUNDAG 190
V
VILDAN ENISOGLU ATALAY 77
VOLKAN SIRINOGLU 107
W
WANG Y 53
WILLIAM W. AU 30
Y
YADOLLAH AZARMI 139
YALCIN OZKAN 136
YASAR BIRBIR 56, 75, 76, 77
YASAR KESKIN 78
YASEMIN OZTURK 74
YASEMIN YAZAN 29
YESIM GUROL 74
YESIM IPCI 170
YIGITBASI 190
YIGIT SABRI UNLU 178
YILMAZ CAPAN 42
YOSRA BARATLI 92
YOUSEF JAVADZADEH 124
YUCEL KADIOGLU 65
YUSUF CAN GERCEK 178
YUSUF OZKAY 113, 181
YUSUF OZTURK 179, 180
YUSUF SICAK 143, 166, 167
YUSUF TUTAR 91
YVES-JEAN BIGNON 134, 62
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Z
ZAFER ASIM KAPLANCIKLI 89
ZAFER ASIM KAPLANCIKLI 119
ZAHIA KABOUCHE 72, 73
ZARIFE NIGAR ODEMIR 101,151,100
ZARIFE N. OZDEMIR KUMRAL 86, 87
ZEHRA AYDINLI 85, 86
ZEHRA CETIN 177
ZEHRA ILKE MERIC 156
ZEHRA KIPRITCI 74
ZEKERIYA TURGAY SELEN 162
ZERRIN GUNGOR 79
ZERROUG MOHAMED MIHOUB 125
ZEYNEP CIRAKLI 86, 87
ZIBA ESLAMBOULCHILAR 138
ZOHREH SANAAT 62
ZUHAL KILIC-KURT 131, 130
ZUHAL UCKUN 109, 110
ZULBIYE ONAL 160
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