Download FHMS Festival of Research 2008 Booklet

Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Contents
Page
Foreword
2
Festival of Research Programme
3
Abstracts for Hot Topic Talks
5
Abstracts for Oral Presentations
14
Abstracts for Poster Presentations
16
Sponsors’ Pages
68
Index of Presenting Authors
84
Front Cover: by Anna Tanczos
For more information about research within FHMS please contact:
Professor Ian Kitchen,
Deputy Dean (Research and Enterprise),
Faculty of Health and Medical Sciences,
University of Surrey,
Guildford,
Surrey
GU2 7XH
[email protected]
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Foreword
It gives me great pleasure to welcome you all to the first Festival of Research in the Faculty of Health
& Medical Sciences, FHMS. It is nearly a year since FHMS was formed from the merging of the
three academic Schools working in the health and medical sciences fields. Since the formation of the
Faculty, we have been building on the research synergies which existed across the three merging
Schools, to create cross-cutting interdisciplinary themes of critical mass to provide a focus for crossFaculty and inter-Faculty research collaborations. Biomedical research (RAE UoA 12) is focused on
eight themes: Sleep and Chronobiology, Cancer, Cardiovascular, Systems Biology, Pharmacology &
Toxicology, Infectious Diseases, Diabetes, Obesity & Metabolism, Materials & Nanoscience. We are
seeking to strengthen the translational element of the research in each theme. Research in Health Care
(RAE UoA 7) is focused on four strategic areas of Clinical Practice, Healthcare Workforce
Development, Patient Safety and Health Ergonomics. We have established a Public and
Environmental Health theme that bridges the health care and biomedical research activities of the
Faculty and we envisage expansion of this cross-cutting activity.
Key research areas continue to go from strength to strength. A multidisciplinary team of academics
led by the Surrey Sleep Research Centre has secured a £1.4 M grant from the Biotechnology &
Biological Sciences Research Council to study the genetic factors affecting sleep patterns and a
further large grant in this area is imminent. In the renewable energy field, two grants have been
awarded by the Engineering & Physical Sciences Research Council to Chemical Sciences academics
for the study of new materials. Research in the field of diabetes is also being supported by grants
from Diabetes UK and the British Heart Foundation.
We are proud that the achievements of both staff and students have been recognised by external
bodies. Julia Percival, a final year PhD student in the Chemical Sciences Division was awarded the
Roy Prize for best talk at a Royal Society of Chemistry Solid State Chemistry Group meeting. Dr
Nayazi Halal, who graduated with an MSc in Occupational Health and Safety in December 2006 has
been awarded the Shaikh Rashid Award for Scientific Distinction in the United Arab Emirates in
recognition of the excellent work accomplished during his Master degree. The Association for the
Study of Obesity has this year awarded Dr Denise Robertson of Nutritional Sciences Division the
'Young Achiever' award and Catia Martins has won the 'Student Researcher' award. Dr Derek
Stevenson of the Biochemical Sciences Division was awarded the Royal Society of Chemistry silver
medal in Analytical Separation Methods. Prof Karen Bryan of the Division of Health & Social Care
has been invited to chair the Action Research Network developed in the region by the Care Services
Improvement Partnership to promote collaboration between researchers, clinicians and service
managers to improve health and social care services for Older People in the South East. At the 2008
Annual Congress of the British Toxicology Society, Professors Peter Goldfarb and Gordon Gibson
were jointly awarded the Society's prestigious Paton Prize for their contribution to toxicology in the
UK over the last 20 years. We were deeply saddened by the untimely death of Gordon in May this
year.
Teaching provision is also given a high priority within the Faculty. In the 2008 Good University
Guide, our undergraduate food science programme was rated 1st, nursing 4th and our bioscience
programmes 5th in the UK.
The Festival today showcases the breadth and quality of research being performed within the Faculty.
There is a series of “Hot Topic” talks representing some of the cross cutting research themes within
the Faculty, along with four short presentations from junior researchers and over 100 poster
presentations. We are delighted to have two distinguished external speakers giving the Keynote
Address and the Festival Lecture. On behalf of all my colleagues I welcome you and hope that you
enjoy the day!
Professor John Hay
Dean of the Faculty of Health and Medical Sciences
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Faculty of Health and Medical Sciences
Festival of Research
FHMS Festival of Research Programme
Austin Pearce Building
Friday 4th July, 2008
9 am to 5 pm
9:00 – 9:10
Introductions and welcome: Vice Chancellor Professor Chris Snowdon
9:10 – 9:50
Keynote Lecture: Professor Martin Bennett
University of Cambridge
“Death, Old age and DNA damage in vascular disease”
9:50 – 10:05
10:05 – 10:20
10:20 – 10:35
10:35 – 10:50
Hot topic in Cancer: Dr Nicola Annels
Hot topic in Systems Biology: Professor Johnjoe McFadden
Hot topic in Infectious Diseases: Dr Lisa Roberts
Hot topic in Pharmacology & Toxicology: Professor Chris Fry
10:50 – 11:20 Morning Coffee
11:20 – 11:35
11:35 – 11:50
11:50 – 12:05
12:05 – 12:20
12:20 – 12:35
12:35 – 12:50
Hot topic in Cardiovascular Disease: Professor Gordon Ferns
Hot topic in Materials & Nanosciences: Dr John Varcoe
Hot topic in Health Care Practice: Dr Helen Allan
Hot topic in Diabetes, Obesity & Metabolism: Dr Denise Robertson
Hot topic in Sleep & Chronobiology: Dr Jonathan Johnston
Hot topic in Public & Environmental Health: Dr Nicola Christie
12:50 – 2:50
Lunch and Poster Session (AP3+4)
2:50 – 3:50
Selected oral presentations
3:50 – 4:20
Afternoon tea
4:20 – 5:00
Festival Lecture: Professor Sir Colin Berry
Emeritus Professor of Morbid Anatomy, University of London
“Don’t Eat or Drink, and Live Forever”
5:00 -
Festival conclusion and prizes: Professor John Hay
Followed by wine reception
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4th July 2008
Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Abstracts for Hot Topic Talks
Hot topic in Cancer
The role of NFAT/FOXP3 interaction as a target for overcoming immune suppression in cancer
Dr Nicola E Annels, Shadi Bokaee, Mick Denyer, Richard Morgan, Hardev Pandha
Oncology Group, Postgraduate Medical School, University of Surrey
Immunotherapy is a promising approach to the treatment of various types of cancer. Although peptide
or dendritic cell-based vaccines can induce antigen-specific immune responses, objective clinical
responses remain infrequent and transient. One major explanation for this tumour escape is the
immunosuppressive environment created by the tumour cells in cancer patients. A key part of this
suppression is mediated by a subset of T cells known as T regulatory cells (Tregs) that can block an
effective anti-tumour immune response. Increased levels of Tregs have been reported in patients with
different types of cancers in both the tumour microenvironment and in the peripheral blood. However,
to date there are few clinical options available for abrogating this population of cells. We have
developed a peptide (HWFT) that blocks the interaction between the Treg specific transcription factor,
FOXP3 and its co-factor NFAT. HWFT triggers apoptosis specifically in Tregs, whilst sparing other
types of immune cells including B-cells and activated T-cells, and thus represents a more specific and
potentially less toxic method for ablating Tregs and relieving immune suppression than any other
current treatment.
The efficacy of HWFT will be further studied in two mouse models of cancer, with particular regard
to its ability to ablate T regulatory cells in tumours and to cause tumour shrinkage, either alone or in
combination with other immune therapies. These models will also be used to assess key
pharmaceutical properties of HWFT including its half life in serum and its distribution in organs and
in the tumour. Additionally, we will also assess the toxicity of HWFT, establishing the MTD and
monitoring adverse events in the immune system and organs. The pre-clinical development of HWFT
will hopefully lead to a safe and effective intervention for a range of different cancers as a
combination therapy with vaccines or other treatment modalities.
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Systems Biology
From genome to metabolism: what does the TB bacillus eat
Professor Johnjoe McFadden
An impediment to the rational development of novel drugs against tuberculosis (TB) is a general
paucity of knowledge concerning the metabolism of Mycobacterium tuberculosis, particularly during
infection. A particular problem is presented by the state of persistence when the organism grows very
slowly and is relatively resistant to most drugs. We need to develop more effective treatment for TB
and for this purpose we need to understand its state during persistence. One of the outstanding
questions is the identity of the substrates that the TB bacillus consumes when growing inside the host.
In order to address this question we utilized genome-scale metabolic modelling approaches. GSMNTB, a genome-scale metabolic model of M. tuberculosis, was constructed in which all the metabolic
steps that the organism is presumed to be capable of is modelled as mathematical system. The model
is able to perform simulations of the growth and physiology of the TB bacillus in different
environments, including the host. Flux balance analysis (FBA) was used to calculate substrate
consumption rates, which were shown to correspond closely to experimentally-determined values.
Predictions of gene essentiality were also made by FBA simulation and were compared with global
mutagenesis data for in vitro-grown M. tuberculosis. A prediction accuracy of 78% was obtained.
Known drug targets were predicted to be essential by the model. The model demonstrated a potential
role for the enzyme isocitrate lyase during the slow growth of mycobacteria and this hypothesis was
experimentally verified. The model thereby provides a means to examine the metabolic flexibility of
bacterium, predict the phenotype of mutants, and identify new drug targets. We are currently using the
model to explore the in vivo phenotype of the TB bacillus.
References
D Beste, T. Hooper, G. S. Stewart, B. Bonde, C. Avignone-Rossa, M. Bushell, P. R. Wheeler, S.
Klamt, A. M. Kierzek, and J. J. McFadden. GSMN-TB: a web-based genome scale network model of
Mycobacterium tuberculosis metabolism. Genome Biol 8:R89, 2007.
D. J. Beste, E. Laing, B. Bonde, C. Avignone-Rossa, M. E. Bushell, and J. J. McFadden.
Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of
mycobacteria to survival inside the macrophage. J.Bacteriol. 189:3969-3976, 2007.
D. J. Beste, J. Peters, T. Hooper, C. Avignone-Rossa, M. E. Bushell, and J. McFadden. Compiling a
molecular inventory for Mycobacterium bovis BCG at two growth rates: evidence for growth ratemediated regulation of ribosome biosynthesis and lipid metabolism. J.Bacteriol. 187 (5):1677-1684,
2005.
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Infectious Diseases
It’s all in the translation: understanding and exploiting novel mechanisms of viral protein
synthesis
Dr Lisa Roberts
A major interest of my lab is the study of novel mechanisms viruses use to synthesise their proteins
and the exploitation of these mechanisms either in the design of effective antivirals or in biotech
protein expression systems. When viruses infect cells they must ensure they “take over” the cellular
protein synthesis machinery to make new virus proteins, at the expense of the cell’s own proteins.
Some viruses have adopted novel ways to do this. For example, picornaviruses, such as poliovirus or
foot-and-mouth disease virus, contain a structure within their genome called an internal ribosome
entry site (IRES) that binds the ribosome and directs viral protein production. We and others have
made significant progress in understanding the structure and function of these RNA elements and
during this work we discovered a novel insect virus element with potential utility in protein
expression systems − this is currently being evaluated commercially in a number of protein expression
systems.
This talk will be focussed on our more recent research on caliciviruses. Caliciviruses are responsible
for many important human and animal diseases. For example, noroviruses are the main cause of nonbacterial gastroenteritis worldwide and outbreaks are a major public health problem. Norovirus
infections are commonly known as “winter vomiting disease” and outbreaks are often seen in
hospitals, schools, cruise ships, military camps and nursing homes. Symptoms include projectile
vomiting, diarrhoea and stomach cramps. In the UK alone, it is estimated that outbreaks of norovirus
infection cost the NHS around £100 million per year. Despite the impact of calicivirus infections on
society, relatively little is known about the molecular mechanisms of virus replication and how we
can exploit this information to design effective ways of preventing and controlling outbreaks.
We have recently shown that caliciviruses appear to use a novel method of translation initiation not
found in any other animal RNA virus. This is dependent on a protein found on the viral RNA (VPg),
which binds to translation initiation factor eIF4E and directs ribosome recruitment to the viral RNA.
We are currently further defining the molecular interactions of the viral RNA with cellular proteins
and the role of these interactions in virus replication. The molecular dissection of the role of initiation
factors and other RNA-binding proteins in calicivirus translation will not only characterise a new
paradigm in translation initiation but may lead to the identification of potential targets that can be
used to control these economically important viruses.
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Pharmacology & Toxicology
Sensations from the bladder – controlling incontinence
Professor Christopher Fry
Postgraduate Medical School
Overactive bladder (OAB) syndrome is an extremely common condition in the community, affecting
people of all ages. Because of its embarrassing nature it is very much under-reported and the clinical
management is far from satisfactory. In recent years research has focussed on the physiological basis
of how we perceive when the bladder is full, and if this process is altered in patients with overactive
bladders.
When the bladder wall is stretched - as when the bladder
stretch
fills - the epithelial lining (urothelium) releases a number
of agents that can act as transmitters. These include
Urothelium
ATP
acetylcholine (Ach) and ATP. It is hypothesised that these
mucosa
transmitters can both:
Suburothelium
nerves
Ach
i excite local nerves in the suburothelium and hence
convey a sensation of bladder fullness to the central
nervous system;
ii influence directly the contractile state of the smooth
Detrusor
muscle (detrusor) in the bladder wall.
smooth
Several conditions associated with OAB, such as interstitial
muscle
cystitis, injuries to the central nervous system and ageing
itself, are accompanied by an increased release of these
transmitters.
Many questions remain to be answered, and is the subject of our investigations:
• What is the mechanism whereby bladder stretch results in transmitter release?
• What are the particular roles of ATP and Ach when they are released from the bladder?
• Can we understand the action of agents useful in alleviating OAB, such as Botulinum Toxin?
• What are the mechanisms whereby sensory nerves are activated following transmitter release?
• Does the urothelium influence directly detrusor smooth muscle activity, and if so how?
• Is detrusor muscle function itself altered in the overactive bladder?
For example:
100 µM ATP
30 mN.mm-2
0.2
nA
2+
2 min
300 [Ca ]
nM
200
100
UTP
-mucosa
100 s
ATP excites certain cells that are closely
associated with sensory nerve fibres by
generating an ion current (upper trace)
and a rise of the intracellular [Ca2+].
Carb
UTP
10 µM
Carb
1 µM
+mucosa
Detrusor samples without an intact mucosa are functionally
quiescent and agents (UTP) that excite (sub)urothelial cells are
ineffective. With an intact mucosa spontaneous activity is
present, increased by UTP. Carbachol tests muscle integrity.
With the collaboration local hospital Trusts we are collecting human samples from patients with and
without OAB to test our hypothesis
The research team at Surrey includes Dr Changhao Wu and Dr Gui-Ping Sui
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Cardiovascular Disease
Periadventitial delivery of anti-EGF receptor antibody inhibits neointimal thickening and
macrophage accumulation in balloon injured carotid artery of the cholesterol-fed rabbit
Shahida Shafia and Gordon Fernsa,b
Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH.
b
The Royal Surrey County Hospital, Guildford, Surrey GU2 7XX
a
Background: The accumulation of intimal monocytes, and their differentiation into macrophages are
the early events in native atherogenesis and the accelerated atherosclerosis associated with
angioplasty and stenting. We have recently reported that receptor for epidermal growth factor (EGF)
is expressed on the surface of rabbit peripheral blood monocytes and on human macrophages within
atherosclerotic lesions, but the role of this receptor in atherosclerosis and restenosis has not yet been
determined.
Objective: We aimed to assess the role of EGFR in the accumulation of monocyte/macrophage within
the neointima that forms following balloon catheter injury in a rabbit model of restenosis using
specific monoclonal antibody anti-EGFR (ICR62).
Methods: Intimal lesion formation was induced by balloon catheter injury of the right common
carotid artery of male NZW rabbits fed a cholesterol-enriched diet (2%) for 2 weeks. Immediately
after the injury, a collar was placed around the common carotid artery for periadventitial delivery of
ICR62 (n=7), isotype matched control antibody (n = 6) or saline (n = 8) to the injured arterial wall.
Two weeks later, the injured carotid arteries were excised, fixed, embedded and than sectioned (5 μm)
for morphometry, using image analysis software and immunohistochemistry.
Results: The anti-EGFR antibody caused a significant reduction in neointimal macrophage
accumulation compared with the controls receiving either isotype matched antibody or saline alone
(360 ± 47 mm2, mean ± SEM, vs. 437 ± 75 mm2 and 716 ± 69 mm2; P < 0.02 and P < 0.001,
respectively). Moreover, the ratio of intimal: medial area in anti-EGFR treated carotids (0.20 ± 0.02)
decreased by as much as 83% compared with saline control (1.36 ± 0.13); this reduction was highly
significant (p<0.0005). The marked reduction in neointimal thickening was associated with 76%
decrease in the formation of the intima area [0.34 ± 0.13 (n=8) vs. 1.42 ± 0.22 mm2, (n=8)].
Integrated plasma cholesterol levels remained similar in all 3 groups of rabbits.
Conclusion: Thus, the local delivery of anti-EGFR antibody resulted in a significant reduction in
balloon-induced intimal thickening and monocyte/macrophage recruitment within carotid
atherosclerotic lesions in cholesterol-fed rabbits. These findings suggest that (i) the EGFR plays an
important role in the development of early atherosclerotic lesions and that (ii) the monoclonal
antibody against these receptors may be useful for the treatment of post-angioplasty restenosis and
vessel wall thickening after vascular manipulations.
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Materials & Nanosciences
Research into Clean or Portable Energy Generation Technologies
Dr John Varcoe
Chemical Sciences and Biological Sciences Division
This hot topic talk will outline the more than £1million funded energy related research that is being
conducted in the Faculty. This research includes multidisciplinary national and international
collaborative projects involving microbial science, enzymology, polymers, solid state chemistry,
molecular modeling, electrochemistry, metallic and non–metallic nano–catalysts, and high
performance carbon materials, including multiwall carbon nanotubes.
Applications of the technologies being developed include:
1. Chemical Fuel Cells [clean energy from hydrogen, carbon (glycerol / methane / alcohols),
nitrogen (ammonia) and boron compounds (borohydride)]
2. Lithium Batteries
3. Microbial Fuel Cells (treatment of wastewaters with simultaneous electricity generation)
4. Enzyme Fuel Cells (selective biocatalysts)
5. Supercapacitors for high power energy storage
The research highlighted will include Surrey’s low alkaline anion–exchange membrane fuel cell
technologies, materials for high temperature fuel cells, microbial fuel cells fed with sludge from
human wastewater treatment plants and sulfate rich wastewaters, a solid state polymer fuel cell
containing a laccase enzyme, and lithium battery and supercapacitor materials.
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Health Care Practice
For whose benefit? Staff’s views on meeting targets and providing care for people with long
term complex conditions in new primary care organisations
Helen Allan, Paula Reed and Pam Smith, CRNME, DHSC
Government policy has recently encouraged health services to work closely and in some cases merge
with local authority social services in order to improve the quality and co-ordination of care,
particularly for vulnerable groups such as people with long term or chronic conditions. However,
there is little known about how professionals, such as general practitioners, social workers and
community nurses, feel about the organisations they work in and the ways in which they are
encouraged to do a good job.
The aims were to find out from these professional groups, their own personal and emotional responses
to working in a team, for their employing organisation, as well as their views on performance and
providing care for people with long term complex conditions.
A two year study across three Primary Care Trusts (PCTs) and integrated Local Authority sites
(including Surrey). The study had three phases. In the first phase we used in-depth qualitative
interviews to investigate how the organisations across the three sites managed the support and care of
people with long-term complex conditions. During this time we established Service User Reference
Groups (SURG). These groups developed ‘stories’ which illustrated successful and unsuccessful care
of people with complex physical and mental health problems. In the second phase of the study we
interviewed health and social care professionals to determine their personal experiences of working in
the organisation, how they consider they are encouraged to do a good job and how these factors
impact on the care they are able to provide. The final phase of the study will involve the analysis of
the information that has been collected providing answers for our research question and providing
organisations with ‘frameworks of good practice’ for the future. This paper presents some key
findings from the 19 interviews with a range of health and social care staff.
Data from the SURG group in phase one showed that users with chronic, complex, mental and
physical needs experienced, at times, unsuccessful care. There was a sense of confusion related to a
misunderstanding of the new structures in primary care and a lack of coherent service delivery often
made worse by a perceived lack of time with the same professional. In Phase two, we found that:
• Staff’s main concerns centred on the reconfiguring of the PCT. They were concerned with
how services were delivered, in particular, the location of teams and formation of new teams
across disciplines and new models of services, and who delivered the services and on the
impact on their working lives.
• There was uncertainty and confusion around the nature of risk and differences in attitudes to
risk across teams and within professions.
• Staff felt that their relationships with users were compromised by constraints on time and
reduced access. They had doubts as to whether self care was feasible for users with complex
needs in primary care.
• Staff suggested that the purpose of the re-organisation of primary care may have more to do
with reducing hospital admissions than improving user experience and that the purpose of
governance may be to improve surveillance rather than make systems and processes
transparent.
Given these data, it appears that the priority in this re-organisation has been to focus on measurable
health outcomes, in line with the productivity agenda in the NHS. For those people with chronic
debilitating long term conditions who necessitate complex care maintained over long periods, the only
measurable quality indicator is reduced hospital admissions. This indicator does not capture the
reality of their experiences because they do not get better and require care over their lifetimes.
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Diabetes, Obesity & Metabolism
Is resistant starch a potential treatment for insulin resistance?
Denise Robertson, John Wright, Jo Batt, David-Russell Jones & Margot Umpleby
Diabetes and Endocrinology, Postgraduate Medical School, University of Surrey
The development of tissue insulin resistance is a well-established step in the pathogenesis of type 2
diabetes (T2DM), linking T2DM to co-morbidities such as hypertension, cardiovascular disease,
stroke and obesity. Improving this underlying tissue IR and thus preventing the development of overt
T2DM therefore remains the preferable long-term strategy. Preliminary work in healthy subjects has
demonstrated that consumption of 30 g/day resistant starch (a form of insoluble dietary fibre)
compared to placebo for 4 weeks increased tissue insulin sensitivity via changes in adipose tissue
metabolism. In this follow-up study the effects of RS consumption are being assessed in subjects with
insulin resistance (EGIR criteria).
Fourteen insulin resistant subjects have been recruited and to date 8 subjects (fasting insulin 60 - 156
pmol/l; age 25 - 70 years; 2F/5M) have completed this randomized crossover study consuming 40
g/day RS for 8 weeks compared to placebo. At the end of each intervention period, subjects
underwent both a two-step hyperinsulinaemic-euglycaemic clamp (to measure whole-body insulin
sensitivity and sensitivity of adipose tissue lipolysis) and a meal tolerance test with arterio-venous
sampling across forearm muscle, measurement of forearm blood flow by venous occlusion
plethysmography and adipose tissue and muscle biopsies for the analysis of key genes. Results are
presented for the 8 completed subjects.
Clamp study; following RS there was an increase in insulin sensitivity at both low and high insulin
doses (63 and 25 % increase) and enhanced suppression of adipose tissue lipolysis.
Meal Tolerance Test; following RS there was a mean 11% increase in the glucose flux into forearm
muscle (P=0.043), but no difference in the uptake of fatty acids. Forearm blood flow (FBF) differed
between the 2 treatments (P=0.037).
Other; both supplements were well tolerated and there was no change in the habitual food intake.
Diastolic blood pressure fell from a mean 81 to 77 mmHg (P=0.74) despite no change in BMI.
This project is still underway with funding until July 2010 although these early preliminary results
indicate beneficial effects of RS on both tissue insulin sensitivity and vascular function, important risk
factors for type 2 diabetes and cardiovascular disease. Further analysis will be undertaken to
determine both the peripheral and hepatic insulin resistance, in addition to inflammatory markers and
plasma mediators of endothelial function. Biopsies will be analysed to look for changes at the
molecular level which underpin improvements in clinical end-points
This research is funded by Diabetes UK
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Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Sleep & Chronobiology
Fat’s got rhythm: unmasking the circadian regulation of lipid metabolism
Dr Jonathan Johnston
Circadian rhythms are endogenously controlled events that occur with a frequency of approximately
24-hours. Such rhythms are widespread throughout mammalian biology and interact with diverse
processes including behaviour, neuronal activity, cell division, hormone secretion and metabolism.
Over the past ten years, identification of key molecular components of circadian rhythms, coupled
with technological advances in cell biology, have ensured the rapid evolution of the field. Arguably
the most important development during this time has been the identification of circadian clocks in
most tissues throughout the body. As a result, the current model of mammalian rhythms describes a
‘circadian timing system’, in which clocks present within individual tissues interact in a complex
network. Major challenges are now to identify how these clocks control local aspects of physiology
and relate to disease states.
One of the research projects in my laboratory is to define the circadian regulation of adipocytes, the
main cells present within fat tissue. This talk will outline the physiological and genetic links between
circadian rhythms and fat biology, highlighting our own current and future work. It is expected that
this line of research will provide novel insights into fat metabolism and related pathophysiology,
including obesity, type 2 diabetes mellitus and cardiovascular disease.
12
Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Hot topic in Public & Environmental Health
Health Inequalities and Road Traffic Injury
Dr Nicola Christie
Robens Centre for Public Health
Road traffic injuries are a major cause of health inequalities and a leading cause of death before the
age of 40. Children from the lowest social class are over 5 times more likely to be killed as
pedestrians compared to their counterparts in the highest social class. In 2004, the Department for
Transport commissioned the Neighbourhood Road Safety Initiative – to tackle the high risk of road
traffic injury experienced by disadvantaged communities. To support this initiative quantitative
surveys have been conducted among 5000 children and 2000 adults and focus groups involving 88
parents from the most deprived communities in England. The research aimed to examine why
children are exposed to risk in these areas. The findings suggest deprived communities face a high
level of environmental risk. They live in inner city areas where road layouts give rise to high traffic
volumes and vehicle speeds. They also report illegal parking as many of the areas where they live are
old and built before mass car ownership. Parents report the constant local menace of antisocial
behaviour by young drivers and riders joyriding at speed. Families in these communities are less
likely to own a car and more likely to walk and therefore socioeconomic factors o increase exposure
to environmental risk as vulnerable road users. Parents feel there areas lack safe and secure public
spaces for children because parks and recreation grounds are inaccessible, have poor facilities and
are often inhabited by people drinking alcohol or taking drugs and as a result are littered with broken
glass and syringes. Parents reported that they cannot afford for their children to go to clubs and
activities after school and feel there is a lack of information about facilities for children. Children
want to be out with their friends so often played out in the streets close to home. The community
proposed solutions to improve safety including engineering to reduce vehicle speed, greater police
enforcement, more accessible and affordable facilities for children and, safe and secure public spaces
for children to interact with their friends and the environment. The findings show that a holistic
systems approach is required to fully understand sources of risk that impact on a community‘s health
and these need to be tackled through community based multi-agency approaches.
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Faculty of Health and Medical Sciences
4th July 2008
Festival of Research
Abstracts for Oral Presentations
No. 1
Title
Authors
Group
Abstract
THE PHOP REGULON OF STREPTOMYCES COELICOLOR, IDENTIFICATION USING
CHIP-ON-CHIP AND GENE EXPRESSION ANALYSIS
Nick Allenby, Emma Laing, Giselda Bucca, Andrzej Kierzek and Colin Smith
Microbial Sciences, Systems Biology
Streptomycetes are Gram-positive soil dwelling, filamentous bacteria which undergo complex
differentiation to form mycelium, aerial hyphae and spores. During nutrient limitation they
produce diverse secondary metabolites such as toxins, pigments, plant growth factors and
antibiotics.
During phosphate limitation the regulator PhoP induces genes which help to reduce this limitation.
Also there are clear links with secondary metabolite production. A PhoP-null mutant overexpresses the antibiotics actinorhodin and undecylprodigiosin, while high levels of phosphate in
the growth media abolish all antibiotic production. This link between primary and secondary
metabolism is both scientifically and commercially important.
Chromatin immunoprecipitation (ChIP) is a powerful method to measure protein–DNA
interactions in vivo, and it can be applied on a genomic scale with microarray technology (ChIPon-chip). Here we describe the combined approaches of both gene expression profiling and ChIPon-chip analysis to identify genes belonging to the PhoP regulon of S. coelicolor. Our ChIP-onchip analysis has shown that PhoP binds to key regulators involved in antibiotic production and to
many genes involved in the recovery and transport of phosphate from organic sources.
No. 2
Title
Authors
Group
Abstract
NEW DITERPENOIDS FROM CROTON SYLVATICUS AND CROTON
PSEUDOPULCHELLUS (EUPHORBIACEAE) AND ANTIPLASMODIAL SCREENING
OF ENT-KAURENOIC ACID
Moses K. Langat1, Dulcie A. Mulholland1, 2 and Neil R. Crouch2, 3
1
Chemical Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford
2
School of Chemistry, University of KwaZulu-Natal, Durban, South Africa
3
Ethnobotany Unit, South African National Biodiversity Institute, Durban, South Africa
Phytochemical analysis of the Croton genus has yielded the following: one new 19-norclerodane
diterpenoid, sylvaticinol (1), the known nor-cyclofarnesene sesquiterpenoid, 3-hydroxy-3-((Z)-4hydroxy-but-1-enyl)-2, 2, 4-trimethyl-cyclohexanone (2), not reported previously from the genus
Croton, and other known clerodane diterpenoids from C. sylvaticus, whose root bark has been
reported to be used for the treatment of tuberculosis,1 and two new ent-kaurenoic acid derivatives,
11β, 17-dihydroxy ent-kauren-19-oic acid (3), 14β-hydroxy ent-kauren-19-oic acid (4), entkaurenoic acid (5) and other known ent-kauranes from C. pseudopulchellus used as an antiviral, an
antitussive and to treat asthma and syphilitic sores2. The structures were established on the basis of
NMR, FTIR and MS analysis. Ent-kaurenoic acid and three extracts from the stem of C.
pseudopulchellus were tested against the CQS D10 strain of P.falciparum. The results showed that
ent-kaurenoic acid and the extracts tested were inactive against the parasite.
H
O
O
H
O
H
O
O
O
1
HO
H
H
H
OH
OH
H
H
H
HO
H
H
H
OH
2
O
OH
3
O
OH
4
O
OH
Acknowledgement
We are grateful to Prof. Smith, P., Department of Medicine, Univ. of Cape Town, South Africa for the
antiplasmodial screening.
References
1
Taylor, J. L. S., et al. 2003. Environ. Mol. Mutagen. 42, 144-54.2 Prozesky, E.A., et al. I. 2001. J.
Ethnopharmacol. 76, 239-45.
14
5
Faculty of Health and Medical Sciences
No. 3
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
PREVENTION OF UNPLANNED PREGNANCY IN WOMEN WITH TYPE 1 OR TYPE 2
DIABETES MELLITUS
Jill Shawe, Professor P A Smith & Professor I Robbins
Health and Social Care
Diabetes mellitus is a common disorder complicating pregnancy and affects 1 in 250 women in
the UK (CEMACH 2007). Unplanned pregnancy can present major health risks to both a woman
with diabetes and her fetus (CEMACH 2005). Poor glycaemic control at conception and
throughout pregnancy can accelerate the complications of diabetes and lead to severe obstetric
complications. Macintosh et al (2006) found a fivefold increased risk of stillbirth, a threefold
increased risk of perinatal mortality and a twofold increased risk of fetal congenital anomaly. In
spite of the risks, less than half of women with diabetes plan their pregnancies (Holing et al 1998,
CEMACH 2007).
An extended case study after Burawoy (1998) was undertaken with the aim of understanding the
case ‘Prevention of Unplanned Pregnancy in Women with Type 1 or Type 2 Diabetes Mellitus’.
The study was in three sequential phases each informing the next phase; a Database study using
the General Practice Research Database; a Questionnaire study; and Semi structured interviews
with Women with Diabetes and the Health Professionals involved in their care.
The findings are presented in relation to diabetes care, planning for pregnancy and contraception
for women with diabetes. Findings show that there appear to be many psychosocial perspectives
and beliefs involved in why women with diabetes do not plan their pregnancies. The study has
highlighted significant variation in prescribing and use of contraception in women with type 1 and
type 2 diabetes in comparison to those without diabetes. Recommendations are made for clinical
practice and future research in three areas of Professional Patient Relationships and Models of
Care; Use of Contraception; and Education and Training issues.
No. 4
Title
Authors
Group
Abstract
THE ROLE OF THE Per3 GENE AND PACEMAKER FUNCTION IN CIRCADIAN
ORGANISATION OF BEHAVIOUR IN MICE
Daan R van der Veen, Ying Chen & Simon N Archer
Sleep and chronobiology theme, Pharmacology and toxicology theme
Light entrained 24-hour rhythms in behaviour and physiology are seen in most mammals and are
driven by the biological clock in the suprachiasmatic nucleus in the hypothalamus (SCN), which
receives direct input from the eyes. The SCN consists of individual ‘pacer’ cells in which a
molecular loop of transcription and translation of clock genes generates ~24-hour rhythms, and it
has now been shown that almost all mammalian cells are capable of generating circadian rhythms.
The SCN ‘pacer’ cells generate circadian output rhythms directed at target regions involved in
physiology and behaviour, and also non-light entrainable peripheral oscillators. Within the SCN,
‘core’ rhythm generating, and ‘shell’ output subdivisions are recognised.
One of the genes involved in the molecular feedback loop is Period3 (Per3). A polymorphism in
human PER3 associates with diurnal preference, sleep pressure, and cognitive performance. In
Per3 knockout C57BL/6 mice, we find that circadian period of non-entrained, free-running
behaviour is affected in a light-dependant manner, which has not been noted before when studied
in a 129/sv background. The light dependency of this effect gives clues to the functioning of PER3
within the cellular molecular clock and its role in sleep and circadian rhythms.
GABAB1 receptors are found both presynaptically (GABAB1a) on the light input pathway of the
‘core’ SCN, and postsynaptically (GABAB1b) on the ‘shell’ output cells of the SCN. Because of
this localisation within the SCN, pre- and postsynaptic GABAB1 receptors in the SCN are
hypothesised to be involved in integrating light information into the SCN, and communication
between individual ‘pacer’ cells, respectively. Using the GABAB1a and GABAB1b receptor isoform
knockout mice, we measured the effect of the absence of these receptors on circadian entrainment
and free-running activity rhythms in mice. A number of differences were found, including freerunning period length, and the strength of circadian organisation of behaviour, indicating different
roles for the two GABAB1 isoforms in pacemaker function of the SCN.
15
Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Poster Abstracts
No. 5
Title
Authors
Group
Abstract
EFFECTS ON MALE RATS OF DIETS CONTAINING PERFLUOROOCTANOIC ACID
AND PERFLUORODECANOIC ACID ALONE OR IN COMBINATION.
Howarth, J.A., Price, S.C. and Hinton R.H. on behalf of the MSc Toxicology Class 2007
Division of Biochemical Sciences; Pharmacology and Toxicology Theme
Perfluoro carboxylic acids such as perfluorooctanoic acid (PFOA) and perfluorodecanoic acid
(PFDA) are widely used as surface treatment agents. In short term studies in rats and mice
administration of PFOA or PFDA in low doses results in peroxisome proliferation and the other
effects expected for peroxisome proliferators. In lifetime studies PFOA, like other peroxisome
proliferators, causes an increase in tumours of the liver but it is generally accepted on the basis of
epidemiology of the fibrate family of drugs that classic peroxisome proliferators pose no risk to
humans. PFOA and PFDA at low doses are typical peroxisome proliferators with the exception
that they cause increased fat in the liver and at higher doses PFDA produces TCDD-like effects.
The poster shows the results of a short term study set up to investigate this question. Groups of 5
male Wistar albino rats were fed for 2 weeks with either control diet, diet containing 0.004% w/w
of PFOA, 0.00125 % w/w of PFDA or diets containing both 0.004% PFOA and 0.00125% of
PFDA. Addition of either PFDA or PFOA to the diet did not affect the general health of the
animals or their body weight gain but animals offered diet containing both compounds gained
weight normally for six days but thereafter showed little weight gain although they remained
healthy with no fall in food intake and only a slight fall in water consumption. Biochemical and
histological examination of the hepatic effects showed:
a) that combinations of PFOA and PFDA can produce TCDD-like changes at doses where the
single compound has no effect
b) that the effects of the two compounds on peroxisomal enzymes was additive but the effect on
serum lipids of single compounds was the same as a combination
c) a lack of change in EROD indicating that the TCDD-like effects were not Ah receptor driven
d) a lack of change in G6Pase indicates that the lipid accumulation is not due to liver damage.
No. 6
Title
Authors
Group
Abstract
MECHANISMS OF MNV-1 ENDOCYTOSIS
Andreas Gerondopoulos, Paul Monaghan, Terry Jackson, Lisa O. Roberts
Division of Microbial Sciences; Infectious Diseases Research Theme
Caliciviruses are single-stranded positive sense RNA viruses. Feline calicivirus (FCV) causes cat
flu and noroviruses are responsible for outbreaks of human gastroenteritis, often seen on cruise
ships and in hospitals. A murine form of norovirus (MNV-1) has also been recently identified and
as this grows well in tissue culture, is an excellent model for the human noroviruses which are
difficult to culture. Although we know more and more about the replication mechanism of these
viruses, we know very little about how these viruses bind to and enter cells. It has recently been
shown that FCV binds to the receptor junctional adhesion molecule A (JAM-A) on the surface of
cells in culture and uses a clathrin-dependent mechanism of endocytosis to enter cells. We are
investigating the mechanism of endocytosis of MNV-1. Firstly, we have used a number of
pharmacological inhibitors of endocytosis (Methyl-β-Cyclodextrin, Nocodazole, Concanamycin A
and Progesterone/Nystatin) to identify the pathway of endocytosis used by MNV-1.
Secondly, we are using dominant negative inhibitors of proteins involved in endocytosis (Cav-1,
Rabs, AP180c) to study their effect on MNV-1 entry. Our results suggest that MNV-1 is likely
endocytosed via a cholesterol-dependent non-clathrin, non-caveolin dependent pathway.
16
Faculty of Health and Medical Sciences
No. 7
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
BEHAVIOURAL URINARY MANAGEMENT FOR PROSTATE SYMPTOMS: A PHASE
II TRIAL FOR TESTING FEASIBILITY OF A SELF-MANAGEMENT INTERVENTION
FOLLOWING PROSTATE RADIOTHERAPY
*S. Faithfull, **V. Khoo, *J.Cockle-Hearne
* Health Care Practice, Division of Health and Social Care, University of Surrey
** Royal Marsden Hospital
Background: Survivorship is becoming a significant aspect of prostate cancer. With up to fifty
percent of men experiencing urinary side effects at some time during their disease or following
treatment there is a growing need to address symptom management in order to reduce the impact
on quality of life. Self-management interventions incorporating cognitive and behavioural
elements have been shown to have success in reducing men’s symptoms following surgery but
there has been little focus on symptoms following radiotherapy.
Objectives: This study developed a self-management intervention for urinary symptoms as a
result of radiotherapy treatment and subsequently assessed feasibility and patient acceptability.
Influencing factors for providing successful outcomes and implementation were explored.
Method: A quasi-experimental, pre-post design was used. Men were screened for extent of urinary
symptoms between three and eighteen months post radiotherapy. Twenty-two men were recruited
from a population of 71 eligible men and fifteen men completed the programme. The intervention
was delivered over seven weeks and comprised three individual sessions and one group session
with a nurse specialist. Both cognitive and behavioural elements were used covering pelvic floor
muscle exercise and bladder retraining which were supplemented by patient education and coping
strategies in the form of problem solving and goal setting techniques. Men were assessed for
symptoms, concerns and coping confidence before the commencement of the intervention and
again after four months of follow up.
Results: Men reported significant improvement in perceived urinary symptoms (p<0.005) and this
was reinforced by improvements in actual volume (p<.05) and frequency (p<.005). Also the data
showed decreases in emotional distress (p<.05) and problems associated with urinary symptoms
(p<.05). These findings suggest that the intervention had a positive impact on quality of life.
Conclusions: The intervention is feasible to be incorporated into routine clinical practice and
further research in an RCT would be valuable in proving its effectiveness over time.
No. 8
Title
Authors
Group
Abstract
ADDRESSING THE SPEECH, LANGUAGE AND COMMUNICATION NEEDS OF
YOUNG OFFENDERS
Karen Bryan
Division of Health and Social Care. Health Care Practice Theme
Bryan et al (2007) showed that at least 60% of juvenile offenders (aged 14-17 years) have below
average language abilities for their age. These difficulties with language impact negatively on the
young person’s ability to access education and offender prevention provision. A case study of
speech and language therapy provision for one offender is outlined. A summary of how to address
this issue is provided. This proposal was the basis of an invited submission to the Bercow Review
of Services for Children & Young People (aged 0-19) with Speech, Language or Communication
needs (2008).
17
Faculty of Health and Medical Sciences
No. 9
Title
Authors
Group
Abstract
No. 10
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
PROMOTING COMMUNICATION FOR PEOPLE WITH DEMENTIA
Karen Bryan working in partnership with Sussex Healthcare
Division of Health and Social Care. Health Care Practice Theme
This project developed and evaluated a sustainable care home workforce initiative to enhance
communication with people who have dementia. Staff in two homes received a training
programme developed from the evidence base in the literature. Staff were then supported to
become ‘Communication Links’ (CLs). The CL role was then developed with the staff to enable
them to promote communication within their care homes. The CL initiative was evaluated using
questionnaires and a pre and post video evaluation of care practices.
SLEEP IN PAINFUL DIABETIC PERIPHERAL NEUROPATHY: SUBJECTIVE
MEASURES AND ACTIGRAPHY ANALYSIS
Gribble L, Korimbocus A, Middleton B, Gouni R, Kerr D, Coppini DV, Boyle J
Sleep and Chronobiology
Introduction: Patients with painful diabetic peripheral neuropathy (DPN) invariably report poor
sleep due to nocturnal exacerbations of their symptoms. Studies have shown a relationship
between pain and poor sleep exists, but no studies have compared subjective sleep with actigraphy
in this patient population.
Methods: 27 patients (15 male and 12 female with a mean age of 62.9 SD ± 8.9) have completed
the baseline period (D1 – 8 placebo run-in) of a study investigating sleep and pain in patients with
DPN. Measures included wrist actigraphy, subjective assessment of quality of sleep (QOS),
subjective number of awakenings (sNAW) and the subjective pain severity and pain interference
scores taken from the brief pain inventory short-form (BPI). Patients wore actiwatches from
medical screening to end of study and completed the sleep assessments and BPI daily from the
start of the placebo period to the end of study.
Results: Pain severity was associated with an increased perception of interference on sleep r =
0.54 (p ≤0.01) and a significant reduction in QOS r = 0.40 (p ≤0.05). Subjective NAW was
associated with QOS r = 0.49 (p ≤0.01) suggesting painful neuropathy fragments sleep reducing
sleep quality.
Actigraphy scores showed good inter-correlation, although there was little correlation between
actigraphy and subjective measures of sleep and pain. Only QOS correlated with mean wake bout
time r = 0.44 (p ≤0.05) suggesting that increased wake bout time worsens subjective QOS.
Conclusion: Subjective measures show a relationship between pain and sleep with QOS
decreasing with higher levels of pain severity and pain interference. Actigraphy did not correlate
with subjective measures of pain, but there was some correlation with QOS. Our preliminary data
highlight the importance of subjective measurements as markers of disturbed sleep, and suggest
that painful DPN both fragments and reduces the quality of sleep.
18
Faculty of Health and Medical Sciences
No. 11
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
MOLECULAR SIMULATION OF THERMOSET POLYMERS
S. Hall, I. Hamerton, B. Howlin
Materials and Nanoscience; Chemistry Division.
Three dimensional molecular modeling (Figure 1) is used to study the physical and mechanical
properties of thermosetting polymers. Calculations are carried out in house using the commercial
software package Materials Studio1 and also on the supercomputers at the Rutherford Appleton
Laboratory using an allocation of time under an EPSRC grant2. The properties of interest are the
Young’s Modulus of Elasticity, the Bulk Modulus and the glass transition temperature (Tg). The
latter is simulated by running molecular dynamics simulations at simulated temperatures from 0400°C, in steps of 5 - 10°C and plotting the change in volume versus temperature. The point where
the volume increases markedly, i.e. reflecting the region in which main chain motion of the
polymer occurs, is the glass transition temperature (Figure 2).
Figure 1
Figure 2
References
1) Accelrys Limited, 334 Cambridge Science Park, Cambridge CB4 0WN
1. S. Hall, B.Howlin* and I. Hamerton, EPSRC, 35,000 CPU Hours on RAL, March 2008February2009. “Computer Simulation of Polymers and Proteins”.
No. 12
Title
Authors
Group
Abstract
NICOTINIC ACETYLCHOLINE RECEPTOR EXPRESSION AND FUNCTION IN THE
ADENOSINE A2A RECEPTOR KNOCKOUT MOUSE
Athanasios Metaxas, Ream Al-Hasani, Joshua Foster, Susanna Hourani, Ian Kitchen,
Ying Chen
Pharmacology and Toxicology Theme; Biochemical Sciences Division.
Adenosine A2A receptor knockout (KO) mice exhibited reduced nicotine-induced conditioned
place preference and dopamine release in the nucleus accumbens (NAc) in vivo. To unravel the
mechanisms underlying the altered reward properties of nicotine in the A2A KO mouse, we
examined nicotinic receptor expression and function in the brains of naïve A2A KO CD1 mice.
Cytisine-sensitive and A85380-resistant [125I]epibatidine binding, and [125I]α-bungarotoxin
autoradiography were used to label α4β2*, α3β4* and α7 nicotinic acetylcholine receptors
(nAChRs), respectively. We found no differences between A2A KO and wild type (WT) mice in
any of the brain regions examined, including the ventral tegmentum (VTA) and NAc. Nicotineinduced increases of VTA dopaminergic (DA) neuronal firing were recorded in midbrain slices
and again, no differences were found between the two genotypes.
The A2A receptors have been reported to co-localize and functionally interact with DA D2
receptors. DA D1 and D2 receptor autoradiography showed no change in the mesolimbic regions
of the A2A KO mouse. However, D2 receptor modulation of VTA DA neuronal activity was
reduced in the KO mice after a prolonged exposure to the D2 agonist quinpirole. In conclusion, no
significant changes in nicotinic and DA receptor expression were detected in the A2A KO mice, but
an altered DA D2 receptor function in the VTA DA neurons may be responsible for the reduced
reward response to nicotine in the A2A KO mice.
19
Faculty of Health and Medical Sciences
No. 13
Title
Authors
Group
Abstract
No. 14
Title
Authors
Group
Abstract
4th July 2008
Festival of Research
USING A PROTEOMIC-BASED APPROACH TO INVESTIGATE THE ATHERO GENIC
EFFECTS OF APOB-100-DERIVED PEPTIDES
Sama M. Attiyah, Ernesto Oviedo-Orta
Microbial Sciences; FHMS
Atherosclerosis is a condition in which irregular deposits of fatty material develop within the walls
of medium-sized and large arteries, leading to reduced or blocked blood flow. Lymphocytes,
monocytes, macrophages and dendritic cells are present within atherosclerotic plaques at all stages
of its development. Macrophages present blood-borne or intra-plaque antigens in the form of
peptides to T lymphocytes on major histocompatibility (MHC) class II molecules. Antigen
presentation leads to lymphocyte activation and proliferation within the arterial wall. Lipoproteins
(especially LDL), collagen and heat shock proteins are among the many antigens that can trigger
this kind of immune responses. The main aim of my study is to identify novel MHC class II
associated peptides derived from apo-B-100 (the main protein component of LDL particles) using
liquid chromatography mass spectrometry (LC-MS). I used an acid elution method to extract
peptides from MHC membrane complexes presented by control & n-LDL or ox-LDL treated cells.
Peptide samples were analysed using LC-MS. I first carried out a set of preliminary experiments to
find the best conditions for LC-MS analysis using control peptides and then these conditions were
applied to the identification of peptides eluted from cultured cells. I was able to identify six
peptides derived from JY cells and four peptides from J774.2 cells (both untreated cells) but not
from n-LDL or ox-LDL treated cells. This result indicates that the acid elution method can be used
to identify MHC-associated peptides. Future work will concentrate in to finding better conditions
to maximise peptide elution and to assay their effect on atherosclerotic plaque development in vivo
using an animal model of the disease.
CALIX(n)ARENE (n=4,5) RECEPTORS AND THEIR CATION HOSTING PROPERTIES
Tomas Matsufuji, Katherine Zegarra-Fernandez and Angela F. Danil de Namor
Division of Chemical Sciences; Materials and Nanosciences Theme; Thermochemistry lab
Calix[n]arenes are cyclophanes arranged in a cup-shaped array that
have been extensively studied1. Although enormous amount of
investigations were performed on these macrocycles, there are still
many properties such as the thermodynamic parameters of
complexation that need to be studied in order to have a better
understanding of these receptors2-4.
Complexation studies and thermodynamic parameters for L1 and
L25 (Fig. 1) have been investigated using 1H NMR, conductometric
and calorimetric studies for the interaction of these ligands with
mono and bivalent metal cations in acetonitrile and methanol at
298.15 K. The information gathered from these studies will help
assess the importance of the pre-organization that the macrocycles
undergo in different media, the effect of solvation and the factors
controlling their selective behaviour for metal cations as a result of
modifying the number of binding sites of the receptor.
Acknowledgement: The authors thank the European Commission
(Contract INCO CT 2004-509159) for financial support.
*
*
O
O
N
n =4,5
Fig. 1. Tetrakis
[tetraacetamide] oxy}p-tertbutylcalix[4]arene and
{pentakis [pentaacetamide]oxy}
p-tert-butyl calix[5]arene
References
1. C.D. Gutsche, B. Dhawan, K.H. No, R. Muthukrishnan, J. Am. Chem. Soc., 1981, 103, 3782
2. A.F. Danil de Namor, R. M. Cleverly and M.L. Zapata-Ormachea, Chem. Rev, 1998, 98, 2495
3. A. Danil de Namor, “Thermodynamics of Calixarene-ion interactions”, Calixarenes 2001, Kluwer
Academic Publishers, Dordrecht, Netherlands, 2001.
4. A.F. Danil de Namor, K. Baron, S. Chahine, O. Jafou, J. Phys. Chem. A, 2004, 108(6), 1082.
5. Katherine Zegarra, PhD Thesis, University of Surrey, 2007.
20
Faculty of Health and Medical Sciences
No. 15
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
DO SHORT CHAIN FATTY ACIDS HAVE AN ANTI-INFLAMMATORY, AND
VASCULAR PROTECTIVE, EFFECT ON ENDOTHELIAL CELLS?
Nicola Muirhead, M M’Shahidi, R Al’Mushtaq, Dr J Lodge, Professor Gary Frost, Dr K
Bodman-Smith
Cardiovascular Theme; Divisions of Nutritional and Microbial Sciences
Cardiovascular disease (CVD) is one of the major causes of mortality and morbidity in the UK.
There is growing epidemiological evidence for an inverse relationship between diets high in whole
grains and CVD risk. However, the mechanism underlying this relationship remains unknown.
Currently we are carrying out human nutrition intervention trials involving whole grains and
supporting these with cellular models of whole grain intervention. By treating primary human
abdominal aortic endothelial cells with fermentation breakdown products of whole grains, Short
Chain Fatty Acids, we hope to investigate the relationship at the cellular level. Endpoints include
endothelial cell products such as von Willebrand Factor, Tumour Necrosis Factor alpha,
Interleukin 8, Tissue Plasminogen Activator 1 and Nitric Oxide, factors associated with systemic
inflammation, a condition implicated in CVD initiation and progression. Currently we are at the
stage of analysing samples and we hope to have the results for each end point in the near future.
No. 16
Title
Authors
Group
Abstract
SPECTRAL COMPOSITION OF DAILY LIGHT EXPOSURE IN YOUNG ADULTS IN
SUMMER AND WINTER
Thorne HC, Jones KH, Archer SN, Dijk DJ
Surrey Sleep Research Centre, Sleep and Chronobiology Theme
Introduction: Circadian photo-entrainment is mediated in part by intrinsically photosensitive
retinal ganglion cells that express the photopigment melanopsin. The spectral sensitivity of
melanopsin is greatest for blue light at 480 nm. However, at present, there is little information on
the time course of the spectral composition of light to which people are exposed over the 24-h
period and any seasonal variation thereof.
Methods: 24 subjects aged 18-29 years, 23.8 ± 3.8 years (mean ± SD), with mean body mass
index (BMI) 22.1 ± 2.3 kg/m2 participated during the winter months (Nov-Dec), whilst 5 subjects
aged 24-28 years, 27.2 ± 0.6 years, BMI 21.3 ± 0.5 kg/m2 participated in the summer months
(Apr-Jun). Subjects wore actiwatch RGB monitors (Cambridge Neurotechnology) for 7 days.
These monitors measure activity, light exposure in the blue, green and red spectral regions, in
addition to normal broad spectrum white light, with a two minute resolution. Subjects also
completed daily sleep diaries to verify the timing of sleep and wakefulness.
Results: Analysis of the relative contribution of blue light to overall light exposure demonstrated a
significant variation with time of day (P<0.05). Light during the 9.00-15.00h period was relatively
blue light enriched (41.0 ± 0.1%, mean ± SEM), whereas during the evening during 18.00-23.00h
the contribution of blue light was less (30.1 ± 1.7%). Analysis of light exposure during summer
and winter demonstrated that subjects studied in summer were exposed to higher white light levels
compared to those studied in winter (P<0.002). This difference was particularly pronounced
between 15.00-20.00h. For this time interval those subjects studied in the summer were exposed to
a significantly higher percentage of blue wavelength light between 16.00-20.00h, 40.2 ± 1.5%
compared to winter 31.0 ± 1.2% (P<0.05).
Conclusions: The present data show that in addition to overall light exposure, the spectral
composition of light varies with time of day and with season. These variations may contribute to
inter-individual and seasonal changes in entrainment and its disorders.
21
Faculty of Health and Medical Sciences
No. 17
Title
Authors
Group
Abstract
No. 18
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
SPaCE: SUPPORTING PALLIATIVE RADIOTHERAPY CARE WITH
E-TECHNOLOGY
Professor Sara Faithfull, Dr Wendy Knibb, Claire Potter
Division of Health and Social Care; Health Care Practice Theme
The delivery of healthcare is changing rapidly and is driven partially by rising incidences of
chronic disease and the associated costs of patient care. With the trend for the growth of consumer
led expenditure on healthcare, the government is encouraging the patient to take more direct
control and involvement in their healthcare. Developments in modern technology can potentially
smooth this transition of change by addressing these issues via e-technology. In cancer care, as in
other disease areas, e-technology is increasingly being used to obtain accurate and reliable selfreported symptom information and tailored symptom management. Lung cancer is the most
common cause of death from cancer in the European Union as it has one of the lowest survival
outcomes of any cancer. Symptom management is therefore fundamental with this disease due to
its rapid progression with significant morbidity. In this study using e-technology, a compact
handheld telehealth monitor (HealthHUB™), patients respond to a series of questions to assess
their current health and psychosocial status. This monitor provides a simple one-touch, easy to use
self-assessment tool that can define patient orientated outcomes of palliative treatment. Following
the analysis of the pilot project a pre and post quasi-experimental design has been implemented.
Aims of the experiment are to evaluate the extent that the HealthHUB™ supports patients and
their carers at home post radiotherapy whilst evaluating the clinical acceptability and reliability of
the technological device within existing workforce models.
THE ACUTE EFFECTS OF A PROPIONATE-RICH SOURDOUGH BREAD ON
APPETITE AND SATIETY
J. Darzi, G.S. Frost, M.D. Robertson
Division of Nutritional Sciences, Faculty of Health and Medical Sciences
There is evidence indicate a role for short chain fatty acids (e.g. propionate, acetate) produced
during colonic fermentation of non-digestible carbohydrates in regulating appetite.
In this randomised single-blind crossover study, twenty healthy participants (9 male, 11 female)
aged 25.1 [SD 4.6] years identified as unrestrained eaters consumed a breakfast based either on
sourdough or placebo bread. Participants were asked to complete Visual Analogue Scales (VAS)
to rate taste and palatability. Effects on appetite were subjectively assessed at baseline and every
30 minutes post-prandially using VAS, and were quantitatively assessed by providing an ad
libitum pasta meal 3 hours post-prandially. The glycaemic and insulinaemic response was
monitored with regular blood sampling via an indwelling cannula. Participants returned at least
one week later to consume the other bread.
No significant effects of the sourdough bread were found on subjective appetite ratings, except the
desire to eat something sweet (p=0.024 two-way repeated measures ANOVA). Furthermore mean
intake of the ad libitum pasta meal 3 hours following the sourdough breakfast (531 [SD 163]g) did
not differ when compared to the placebo breakfast (527 [SD 188]g). However, while no significant
differences in plasma glucose response were found, plasma insulin appeared to change differently
over time with a trend approaching significance (p=0.061) when analysed by two-way repeated
measures ANOVA.
The results suggest including propionate-rich sourdough bread as part of breakfast does not
acutely influence subsequent appetite or glycaemic response, and may even slow down insulin
clearance. This is contrary to previously reported data in which bread with added propionate led to
significantly higher satiety ratings and reduced glycaemic and insulinaemic responses as compared
to placebo.1 However unlike the present study, the bread was significantly less acceptable than
placebo and effects on actual intake were not assessed.
References: 1. Liljeberg et al (1995) Journal of Nutrition, 125: 1503-1511.
22
Faculty of Health and Medical Sciences
No. 19
Title
Authors
Group
Festival of Research
4th July 2008
T CATION RECOGNITION BY 4, 6, 8,10,12,16,18,22,24 - DIETHYL THIOPHOSPHATETETRA-TERT-BUTYLCALIX [4] RESORCINARENE-25, 26, 27, 28-TETROL ITLE
Nwanyinnaya Nwogu & Angela F. Danil de Namor
Division of Chemical Sciences; Materials and Nanosciences Theme; Thermochemistry lab
Abstract
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Environmental pollutants have always been a source
of concern for everybody. Some metal cations and
anions are toxic to our health and are not good for the
environment so they need to be removed. These
species affect our health and agricultural products.
This research targets mercury removal from our
environment and aims to assess quantitatively the
complexing properties of diethyl thiophosphate
resorcarene for this metal cation using a variety of
techniques (1H NMR, conductometry, atomic
absorption and calorimetry) (1, 2). The crystal structure
of the resorcarene receptor (3) will be presented.
O
Fig.1; 4,6,10,12,16,18,22,24-Diethyl thiophosphate
–tetra-tert-butyl calix[4]resorcinarene-25, 26, 27,
28-tetrol
References:
1 A. F. Danil de Namor, J. Chaaban, O. Piro and E. Castellano, J. Phy Chem. B, 2006, 110, 2442-.
2 W. B. Aparicio Aragόn: PhD Thesis,University of Surrey, 2005.
3 Calixarenes 2001, Eds Z. Asfari, V. Böhmer, J. Harrowfield and J. Vicens: Ed. Kluwer
Academic Publishers 2001.
No. 20
Title
Authors
Group
Abstract
FUNCTIONALIZATION OF CARBON NANOTUBES FOR GENE BIODELIVERY
Vanesa Sanz Beltran, Vera Neves, Elena Heister, Ravi Silva, Helen Coley, Johnjoe Mcfadden
Advanced Technology Institute, PGMS and Microbial Sciences
A comparative study on the non-covalent functionalization of CNTs for gene delivery is presented.
In order to bind plasmid DNA, the study was performed with cationic surfactants that can
effectively bind negatively charged DNA. Tests were carried out with single-walled, doublewalled and multi-walled carbon nanotubes in order to compare their solubilization properties. We
proposed also a new delivery system based on the use of RNA-wrapped single-walled carbon
nanotubes complexed with a cationic protein-luciferase plasmid (pGL3) adduct. Protamine was
selected as a cationic protein as it contains a nuclear localization signal which enhances the
expression of the transfected gene. This system was optimized using the luciferase reporter gene,
which can be used to screen a variety of protocols with a simple luminescence assay in a 96 well
plate, an advantage that other systems (e.g Green Fluorescent Protein) do not share.
Reference:
Jeynes, J. C. G., Mendoza, E., Chow, D. C. S., Watts, P. C. R., McFadden, J., and Silva, S. R. P.
Generation of chemically unmodified pure single-walled carbon nanotubes by solubilizaing with
RNA and treatment with ribonuclease A. Advanced Materials 18 (12) 1598 2006.
23
Faculty of Health and Medical Sciences
No. 21
Title
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Abstract
No. 22
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
COMPOSITION AND ANTIOXIDANT PROPERTIES OF THYME AND THYMBRA
Dara Jamil, Jonathan E. Brown, Dan Driscoll and Nazlin K. Howell
Division of Nutritional Sciences
Herbs like thyme (Thymus syriacus) and thymbra (Thymbra spicata), that grow wild in KurdistanIraq may be safer antioxidants compared with synthetic compounds. Volatile oils (VO) of whole
leaves and flowers were hydro-distilled. The VO yield of thymbra and thyme was significantly
(p<0.05) higher (4.1 % & 3.75 %, respectively) in samples grown at higher altitudes (1400 m)
compared to lower altitudes (670 m; 2.75 ± 0.15 % & 2.5 ± 0.15 %, respectively). The VOs were
analysed by GC and GC-MS and for Thymus syriacus the main components (in %) were thymol
(74.1), carvacrol (9.0), p-cymene (5.3), borneol (2.4), γ-terpinene (2.0) and β-caryophyllene (1.7).
Thymbra spicata VO contained mainly carvacrol (74.0), γ-terpinene (10.7), p-cymene (7.5), βcaryophyllene (1.6), α-terpinene (1.5). The antioxidant properties of the VOs of thyme and
thymbra were tested using sunflower oil oxidized under ultra-violet radiation (254 nm) for up to
24 h. VOs at 0.5 % and 1 % prevented peroxide formation (iodometric method) by 68 % and 57 %
for thyme and by 46 % and 43 % for thymbra compared to 0.025 % BHT (51 %), after 3 h.
Thyme, thymol, thymbra and carvacrol inhibited MDA (TBARS) formation by 77.0, 77.0, 72.0
and 72.0 %, respectively, against a 52.0 % inhibition by BHT confirming their superior
antioxidant activity compared with BHT, which was most effective at 3 h.
THERAPISTS’ AND CLIENTS’ PERCEPTIONS OF USING CORE-NET AND ARM-5 IN
THE NHS
Gisela Unsworth, Professor Helen Cowie, Dr Anita Green
Health and Social Care
Aims: Previous research evidence (Lambert et al. 2003) suggests that when routine outcome
measuring with feedback and an alliance measure is used in therapy with clients it may increase
their motivation which may improve attendance rates, clinical outcomes and increased efficiency
of services. This purely qualitative study elicited the perceptions and experiences of both
therapists and clients in the use of outcome measurement (CORE-Net) where instant visual
feedback was given on a computer and the use of an alliance measure (ARM-5) at each therapy
session for session tracking.
Methodology: A purposive sample of convenience was used with in a primary care setting (PCC)
and an employee counselling service (OH) in the NHS. Data were collected with focus groups at
two time points, one to one semi-structured interviews and diaries. All interviews were been
analysed inductively using a general inductive approach following data management with Nvivo 7
and the process diaries using qualitative conventional content analysis.
Results: Analysis revealed differences in therapists' perspectives at the two time points as well as
differences between client and therapist perspectives. The findings are discussed in the light of
previous research. Implications for practice and training are discussed.
References:
Lambert M.J., Whipple J.L., Hawkins E.J., Vermeersch D.A., Nielson S.L. and Smart D.W.
(2003) Is it Time for Clinicians to Routinely Track Patient Outcome? A Meta-Analysis. Clinical
Psychology, 10, 288-301.
24
Faculty of Health and Medical Sciences
No. 23
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
GABAB RECEPTOR ISOFORMS DIFFERENTIALLY MODULATE THE CA1 FIELD
EPSPS (FEPSPS) IN THE HIPPOCAMPAL SLICES
I.Vinogradova, Y.Chen
Division of Biochemical Sciences; Pharmacology and Toxicology Theme
Activation of metabotropic GABAB receptors modulates synaptic transmission at both pre- and
post-synaptic sites. Recently, in the GABAB1a-/- or GABAB1b-/- mice, the 1a and 1b isoforms were
found to localize differentially on the presynaptic glutamateric terminals and postsynaptic sites,
respectively (Vigot et al., 2006). The aims of the present study were to investigate the modulation
of CA1 fEPSPs by the selective activation of GABAB receptor isoforms in the 1a-/- and 1b-/- mice
and the modulation of GABAB receptor isoforms by the positive allosteric modulator CGP7930.
fEPSPs from a number of positions in the CA1 stratum radiatum were recorded in response to
paired stimuli (15 ms interval, 30-60 µA intensity and 0.2 ms duration) using an MED64 probe
with a 100 µm inter-electrode distance. The fEPSPs recorded in slices from the mutant and wildtype (WT) mice showed no significant differences. GABAB receptor activation by baclofen
suppressed the fEPSP initial slope and amplitude in the WT and 1b-/- mice but not in 1a-/- mice.
The depression of the fEPSP by baclofen was accompanied by a large increase in the paired-pulse
facilitation. Treatment of the slices with CGP7930 did not affect fEPSP parameters, as it has been
shown in the rat hippocampal slices previously (Chen et al, 2006). In the presence of CGP7930,
the fEPSP from 1a-/- mice remain insensitive to baclofen, but in WT and 1b-/- mice, baclofeninduced modulation of the fEPSP and the paired-pulse ratio was altered. The results showed that
the GABAB1a but not the GABAB1b receptor subtype is important in modulating the CA1 fEPSPs
in the hippocampal slices, agreeing with a presynaptic localization of the 1a receptor isoform. The
GABAB positive allosteric modulator CGP7930 may exert differential effects on the two receptor
isoforms.
Acknowledgement: This work is supported by the BBSRC.
No. 24
Title
Authors
Group
Abstract
CARBOHYDRATE BIOAVAILABILITY IN VITRO AND IN VIVO
Muneera Al-Mssallem, Dan Driscoll, Gary Frost and Jonathan Brown
Division of Nutritional Sciences
Dietary carbohydrates (CHO) are digested and absorbed at different rates and extents in the human
digestive tract. This feature can have an impact on the management of diabetes. The concept of
glycaemic index (GI) was introduced to facilitate the understanding of the impact of different
foods on blood glucose levels. Nevertheless, it is evident that the results obtained for GI can vary
for an individual food and foods with the same GI can produce different insulinaemic responses.
As a result an in vitro measurement of dietary CHO digestion has been developed (Englyst et al.,
1999) and two terms related to glucose release from CHOs have been introduced, namely, slowly
available glucose (SAG) and rapidly available glucose (RAG). The latter of which has been shown
to be a reliable predictor of glycaemic response in vivo. The work presented covers the
development of the in vitro assay and the determination of RAG and SAG in six different foods
using both a colorimetric determination and a high performance liquid chromatography method.
The work revealed that the two methods gave similar results and clear differences in RAG and
SAG were apparent between the different foods.
25
Faculty of Health and Medical Sciences
No. 25
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
EPIGENETIC REGULATION OF SELENIUM-RESPONSIVE GENES IN PROSTATE
CANCER
B. Bekaert, M.L. Cooper, E. Laing, G. Bucca, C. Smith, F.R. Green, M.P. Rayman
Divisions of Biochemical, Nutritional and Microbial Sciences
Background: The mammalian selenoproteome is composed of 25 selenoproteins and evidence is
accumulating to suggest an important role for several of these proteins in cancer.
Hypermethylation of gene promoters i.e. the addition of methyl groups to the 5-C position of
cytosine-guanine dinucleotides (CpG), is responsible for the down regulation of gene expression.
This epigenetic modification has been shown to occur in a large number of genes in several
complex diseases and most likely has a significant role in the aetiology of cancer. The silencing of
antioxidant selenoprotein genes through hypermethylation could promote oxidative stress,
resulting in cellular damage, widely accepted as being important in carcinogenesis.
Methods: Whole genome expression microarray technology and promoter tiling arrays were
combined to identify genes both regulated by Se and 5-aza-2’-deoxycytidine (5-AZA), in prostate
cell lines and tissues.
Results: Several selenoprotein genes were found to have altered their expression after treatment
with 5-AZA and/or Se indicating that DNA methylation could influence selenoprotein expression
and that demethylation can restore the selenium-responsiveness of some genes. The expression
profiles and DNA methylation patterns were validated and investigated using Q-RT-PCR and
pyrosequencing, respectively, and found to correlate precisely with the microarray results.
Conclusion: Using gene expression microarray technology we have identified hypermethylated
Se-responsive genes in prostate cancer by correlating gene expression with promoter methylation,
and its response to Se. Genome-wide analysis of promoter methylation in normal and cancerous
prostate cell lines and tissues is currently being investigated using Methylated DNA
ImmunoPrecipitation (MeDIP) in combination with high-resolution whole genome promoter tiling
arrays to identify hyper and hypo- methylated promoters. These experiments will improve our
understanding of the role of Se and DNA methylation in cancer.
No. 26
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Abstract
SURVIVAL OF MYCOBACTERIUM BOVIS IN PROTOZOA
Cornelia Mardare, Frans de Leij and Jeremy W Dale
Microbial Sciences Division, University of Surrey
Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB) in cattle and wildlife.
The persistence of BTB in herds in the UK and Ireland could be caused partly by protozoa offering
M. bovis an environmental reservoir and protection against disinfection. We tested the long-term
survival of M. bovis strains in the protozoa Acanthamoeba castellanii and
Tetrahymena pyriformis. Using the Ziehl-Neelsen staining technique we could show that M. bovis
is ingested by protozoa. M. bovis survived significantly longer in T. pyriformis than in
A. castellanii which reduced the number of mycobacteria over a period of 160 days. The survival
time differed significantly between the tested M. bovis strains as well as between the protozoa. The
survival time of the avirulent M. bovis BCG was significantly shorter than that of the virulent
M. bovis strains. The survival of M. bovis in A. castellanii and T. pyriformis suggests that protozoa
might protect M. bovis from environmental stress and might serve as a transmission vector for
BTB.
26
Faculty of Health and Medical Sciences
No. 27
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
NOX2 MODULATION OF CELL CYCLE INHIBITORY MOLECULE, P21CIP1
EXPRESSION IN ENDOTHELIAL CELLS
Lampson Fan, Vinoj George, Gavin Brooks and Jian-Mei Li
Cardiovascular Theme; Division of Biochemical Sciences
The abilities of endothelial cells (EC) to proliferate, to be quiescent and to undergo apoptosis
during remodeling are important determinants relating to angiogenesis, wound healing and many
cardiovascular diseases. EC express constitutively an NADPH oxidase, which is a major source of
superoxide production. The catalytic subunit of NADPH oxidase has several isoforms (Nox1-5).
However, their individual roles in endothelial function remain unknown. In this study, we
investigated the role of Nox2 in nutrient deprivation-induced cell cycle arrest and apoptosis.
In proliferating human dermal microvascular EC (HMEC1), Nox2 mRNA expression was low, but
was upregulated 24h after starvation and increased to 8±3.5-fold at 36h of starvation as detected
by quantitative real-time PCR. Accompanying the upregulation of Nox2, there was a 2.28±0.18fold increase in O2.- production detected by tiron (O2-. scavenger)-inhibitable lucigeninchemiluminescence; a dramatic induction of p21cip1 and p53 protein expression detected by
immunoblotting; cell cycle arrest and the onset of cell apoptosis detected by propidium-iodide
FACS analysis (all P<0.05). All these changes were inhibited significantly by adding apocynin (a
NADPH oxidase inhibitor), or by in vitro deletion of Nox2 expression using full-length antisense
Nox2 cDNA, or in coronary microvascular EC isolated from Nox2 knockout mice. In Nox2
knockout cells, neither O2.- production nor the p21cip1 and p53 expressions were increased
significantly after 36h of starvation and only 0.46% of cells were apoptotic compared to ~12%
found in wild-type controls. In conclusion, Nox2 is involved in the modulation of p21cip1 and p53
expression and endothelial cell cycle regulation.
No. 28
Title
Authors
Group
Abstract
AN INQUIRY INTO THE ATTITUDE OF MOTHERS TOWARDS BREAST-FEEDING
IN SAUDI ARABIA
Al-Madani M.M., Vydelingum V. and. Lawrence J. M
Division of Health and Social Care, Faculty of Health and Medical Sciences, University of Surrey
Introduction: The advantages of breast-feeding for both infants and mothers are widely
documented. The decreased rate of breast-feeding in Saudi Arabia noted in various studies has
highlighted the need for more investigation. This study reports the adaptation of the Iowa Infant
Feeding Attitude Scale (IIFAS), for use in Saudi Arabia.
Method: Cross sectional study were conducted to study the Saudi pregnant women attitudes
toward breast-feeding. The modified Iowa Infant Feeding Attitude Scale (IIFAS) used and tested
for its reliability band validity in Saudi Arabia.
Results: Women age in this study range between 18 to 45 years old with an average of 27.7. 77%
of pregnant women had previously had a child and 29% were pregnant for the first time. The
majority of women had high school education (40.6%) and 6.9% were illiterate. 90% (N=160) of
Saudi women intended to breast-feed and there were no differences between primipara and
multipara women regarding their intention to breast-feed. Although there is no statistically
significant relationship between the mothers’ intentions to breast feed and the number of
deliveries, the primipara women intended to breast feed more than multipara women. Interestingly
91% of illiterate women intended to breast-feed whereas only 84% of university level educated
women intended to breast-feed.
Conclusion: We concluded that there were no differences between primipara and multipara
women regarding their intention to breast-feed. There was no statistical significance between
women’s attitudes and demographic variables. The women’s parity was the only variable that has
statistical significance when compared with attitudinal scale
27
Faculty of Health and Medical Sciences
No. 29
Title
Authors
Group
Festival of Research
4th July 2008
SEQUESTRATION OF METAL CATIONS WITH CALIXARENES DERIVATIVES
Nadim Mahmoud Hourani and Angela F.Danil De Namor
Division of Chemical Sciences; Materials and Nanosciences Theme; Thermochemistry lab
Abstract
2
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Heavy metal ion removal from water has been the subject of
extensive technological research and recovering processes.
Calixarene’s recognition of metals has been studied for the
treatment of aqueous streams contaminated with heavy metals2.
An investigation was performed over a calixarene derivative in the
supramolecular field. 1HNMR, conductimetric and calorimetric
studies of 5,11,17,23-tetra-ter-butyl-25-27-bis(ethoxy carbonyl
methoxy)-26,28-bis(2-ethoxy methoxy) calix(4)arene (figure)
were carried out. The results showed that this receptor interacts
with various metal cations.
References:
1. Angela F. Danil de Namor, Maria A. Pugliese, Alberto R. Casal, Walther B. Aparicio-Aragon,
Oscar E. Piro, Eduardo E. Castellano, Physical Chemistry Chemical Physics, 2004, 6, 3286.
2. Thesis of Walter Benigno Aparicio Arago’n, January 2005.
No. 30
Title
Authors
Group
Abstract
CYPROTERONE ACETATE REPRESSES THE HUMAN KARYOPHERIN α2 (KPNA2)
PROMOTER BY ANTAGONISM OF THE GLUCOCORTICOID RECEPTOR (GR)
Manraj S. Cheema, G. Gordon Gibson, Nick J. Plant and Kathryn E. Plant
Biochemical Sciences Division; Pharmacology and Toxicology Theme; Centre for Toxicology
Many toxicological responses involve changes in gene expression mediated by the ligandactivated transcription factors, and the nuclear translocation of these factors is vital for their
activity, which is mediated by karyopherins α, a family of adaptor proteins which link specific
cargos to the nuclear import machinery. Our previous observations have suggested that
karyopherin α is responsive to xenobiotic provocation, including a number of classical nuclear
receptor ligands albeit not much is actually known about the regulation of this gene family.
We have previously identified and cloned a well conserved 2.6kb region immediately upstream
and including the first exon of the human KPNA2 into a secretory alkaline phosphatase reporter
vector (pSEAP2-basic). This clone was then transfected into HuH7 cell line and dosed with
varying concentration of xenobiotics (cyproterone acetate, 1-100μM; rifampicin, 50μM;
dexamethasone, 50μM; hydrocortisone, 50μM) along with appropriate vehicle control. SEAP
expression was measured and normalised to the pre-dose reading and expressed as percentage of
vehicle prior to one-way ANOVA with Bonferroni post-hoc analysis.
Prior in silico analysis revealed putative PXR and GR binding site within the human KPNA2
promoter. To demonstrate the validity of the PXR site, we have used cognate ligands of PXR,
rifampicin and CPA. While CPA inhibited SEAP expression with an EC50 of 46μM ±1.15,
rifampicin had no effect. Since CPA is also reported as a GR antagonist, we examined this as a
possible mechanism by which it regulates the human KPNA2 promoter using two GR agonists,
dexamethasone and hydrocortisone, both of which significantly induced SEAP reporter gene
expression. Our data suggests that the human KPNA2 promoter is regulated, at least in part, by the
GR. Further experiments to confirm this mechanism are currently being addressed.
28
Faculty of Health and Medical Sciences
No. 31
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
THE HUMAN KARYOPHERIN α2 (KPNA2) PROMOTER IS RESPONSIVE TO
OXIDATIVE STRESS
Manraj S. Cheema, G. Gordon Gibson, Nick J. Plant and Kathryn E. Plant
Biochemical Sciences Division; Pharmacology and Toxicology Theme; Centre for Toxicology
Upon xenobiotic exposure, the conveyance of external signals into cellular responses that involve
changes in gene expression requires the nuclear translocation of ligand-activated transcription
factors which is mediated by members of the karyopherin family of nuclear transporters, mainly
karyopherin α that acts as a molecular bridge linking these cargoes to karyopherin β which then
moves the complex into the nucleus. Our previous work have suggested that members of the rat
karyopherin α are responsive to exogenous stimuli, although not much of work have been focused
in understanding the transcriptional regulation of this gene family.
The identification and cloning of a well conserved 2.6kb region upstream and including the first
exon of human KPNA2 was previously undertaken. The reporter plasmid (pSEAP2-hKPNA2)
produced was then transfected into HuH7 cell line and dosed with various xenobiotics (Wy14,643, 50μM; clofibrate, 50μM; β-naphthoflavone, β-NF, 1-100μM or hydroquinone, 1-100μM)
or appropriate vehicle controls. Secretory alkaline phosphatase (SEAP) expression was measured
and following normalisation to the pre-dose readings, results were expressed as percentage of
vehicle control prior to one-way ANOVA and Bonferroni pot-hoc analysis.
Previous in silico analysis identified putative PPARα binding sites within the human KPNA2
promoter and we have shown that while PPAR ligand clofibrate has no effect, Wy-14,643
exhibited a profound inhibition of SEAP expression. This may be due to the fact that at high levels
Wy-14,643 causes oxidative stress. We investigate this as a possible mechanism by carrying out
dose response study on a known inducer of oxidative stress; hydroquinone that showed an
inhibition with an EC50 of 15μM ± 1.23. It is known that hydroquinone interacts with either Nrf2
or AhR and to further verify this interaction, we used a well reported sole agonist of AhR; β-NF
that showed no effect. In addition, putative Nrf2 (ARE) binding site was also revealed within the
promoter. The data suggests that the human KPNA2 promoter is sensitive to oxidative stress and is
primarily mediated via Nrf2; however, further experiments to validate this mechanism are
currently ongoing.
No. 32
Title
Authors
Group
Abstract
HEPATITIS C VIRUS-LIKE INTERNAL RIBOSOME ENTRY SITE (IRES) ELEMENTS
WITHIN PICORNAVIRUS GENOMES
Margaret M Carter, Mehran Bakhshesh, Zarmwa Gomwalk and Lisa O Roberts.
Microbial Sciences Division
Initiation of protein synthesis on picornavirus RNA is directed by a cap-independent mechanism
termed internal initiation. This is dependent on an internal ribosome entry site (IRES) element
within the 5’ untranslated region of the genome. We and others have recently shown that some
newly identified members of the picornavirus family possess a novel IRES element within their
genome, an IRES that shows a striking resemblance to those from a distinct virus family, the
flaviviruses (e.g hepatitis C virus). This suggests that genetic exchange between two virus families
has occurred. Our aim is to define the structure and function of critical regions of these new
picornavirus IRES elements in both translation and replication. Seneca Valley virus (SVV) is a
newly characterised picornavirus recently isolated from pigs in the USA. Intriguingly, SVV
displays oncolytic activity against tumour cells with neuroendocrine features, but it does not affect
normal human cells. SVV is currently in Phase I clinical trials for potential therapeutic application
in small cell lung carcinomas. We have recently shown that the SVV IRES is strikingly similar in
function and predicted structure to the classical swine fever virus IRES, so SVV also possesses a
flavivirus-like IRES element. Our studies are key to understanding how these important and
understudied picornaviruses replicate, but also have a wider impact on the study of other viruses
such as hepatitis C virus. Results will also aid in the design of potential common antiviral targets
for use in veterinary medicine and pharmaceutical development.
29
Faculty of Health and Medical Sciences
No. 33
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
A MICROBIAL FUEL CELL FOR SULFUR POLLUTANTS REMOVAL
Feng Zhaoa, Nelli Rahunenb, John R Varcoea, Amreesh Chandraa, Alexander J. Robertsa,
Claudio Avignone-Rossab, Alfred E. Thumserc, Robert C.T. Sladea
a
Chemical Sciences, bMicrobial Sciences and cBiochemical Sciences Divisions
Materials and Nanosciences Research Theme
Waste treatment and electricity generation are both key issues for sustainable modern societies.
Microbial fuel cells (MFCs) are attracting increased attention, driven by the demands for clean and
renewable energy resources, especially for their potential to directly recover electricity from waste
and wastewater.
Sulfur pollutants (sulfate, sulfite, thiosulfate and sulfide) are commonly found in wastewaters,
which are generated by many processes such as animal husbandry, mining, food processing, the
pharmaceutical industry, dye and detergent manufactures, pulp and paper wastewater etc.
Numerous adverse effects from sulfur pollution are already known: they are one of primary
sources of acid rain; they destroy aquatic ecosystem; toxic acidic gas raise serious health risks, and
can be corrosive to metals and concrete etc.
In this study, a lactate-fed MFC was evaluated for sulfur pollutants removal from artificial
wastewater; this system used activated carbon cloth-carbon fibre veil composite anode, airbreathing cathode and the sulfate-reducing bacterium Desulfovibrio desulfuricans used for sulfate,
sulfite and thiosulfate reduction. The results showed that most of the sulfate, sulfite, thiosulfate,
and sulfide were removed from wastewater by MFC operation. It provides a technological tool for
sustainable energy generation with the additionally economic and efficient wastewater treatment
for removal of sulfur pollutants.
Email: [email protected]; [email protected]
No. 34
Title
Authors
Group
Abstract
HIGHER GPx ACTIVITY IN PHYSICALLY ACTIVE ADOLESENT FEMALES IN
COMPARISON TO HEALTHY SEDENTARY CONTROLS.
E. Alshammari1, J.A. Nurmi-Lawton1, S. Shafi1, S.A. Lanham-New1 and G.A.A. Ferns2
1
Faculty of Health and Medical Sciences, 2Post Graduate Medical School, University of Surrey.
Production of reactive oxygen species (ROS) from osteoclasts is a normal physiological function,
which may alter the rate of bone remodelling when associated with other risk factors. The first aim
of this study was to assess the levels of serum glutathione poroxidais (GPx) activity in adolescent
active and inactive girls and to determine the effects of age, body mass index (BMI) and dietary
intake on GPx. The second aim was to investigate if there was an association between GPx and
bone health. Subjects for the current study were part of a three-year longitudinal investigation on
exercise and peak bone mass (PBM) development in 78 healthy subjects, comprising 38
competitive gymnasts and 40 healthy sedentary adolescent females, aged 8-17 years, as published
previously (Nurmi-Lawton et al. 2004)1. GPx was measured using standard methods: 100ul of
assay buffer, 20ul serum samples, 20ul sample buffer, 20ul of GPx standard (1:50), then 50ul of
Co-substrate. The reaction was initiated by the addition of 20ul of hydroperoxides. Finally, the
plate was shaken and read immediately using a plate reader (GenesisV3.05) at absorption of
wavelength 340 nm for 3 min at 25 0C. The results showed that serum GPx was statistically
significantly higher in healthy competitive gymnasts (n=38) compared to the healthy sedentary
adolescent females (n=40) (157±11.1 versus 126±8.8). No associations were found between serum
GPx and bone mineral density (BMD) in either the active gymnast group or the healthy controls.
Further analysis is currently underway to look at antioxidant nutrition status and markers of bone
health in these age groups to determine further the potential effect of GPx activity on bone.
)
Nurmi-Lawton, J. A., A. D. Baxter-Jones, et al. (2004). "Evidence of sustained skeletal benefits from impactloading exercise in young females: a 3-year longitudinal study." J Bone Miner Res 19(2): 314-22.
30
Faculty of Health and Medical Sciences
No. 35
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
IMMUNOMODULATORY PROPERTIES OF APOB-100 DERIVED PEPTIDES ON
DENDRITIC CELLS AND T-LYMPHOCYTES
Natalia Milioti, Alexandra Bermudez-Fajardo, Guinilla Fredrickson, Jan Nilsson, and
Ernesto Oviedo-Orta
Division of Microbial Sciences, Cardiovascular research theme
Background and aims: ApoB-100-derived peptides are known to play a key role in atheroprotective immune responses. However, their effect on cellular immunity has not been yet
reported. This work aims to characterise the immunomodulatory properties of these peptides on
dendritic cells (DCs) and naïve T-lymphocytes in vitro.
Methods: We used bone marrow progenitor cells from male apoE-/- mice to generate DCs after
incubation with rmGM-CSF and rmIL-4. DCs were incubated with increasing concentrations of
peptides (P2, P45 and P210) for 12 or 48 hours. Expression of CD11b, CD11c, CD4, CD8, CD40,
CD86 and MHC class II by DCs was assessed by flow cytometry. Proliferation of syngeneic and
allogeneic T lymphocytes driven by peptide-loaded DCs was studied using a commercial kit.
Results and conclusions: P2 up-regulated the expression of CD40 and CD86 while P45 had the
opposite effect. P210 significantly increased the expression of CD11c (a DC differentiation
marker). P2, P45 and P210 up-regulated the expression of MHC-II. Non-peptide loaded DCs were
mainly CD11chighCD11bhighCD8-CD4- compatible with tolerogenic DCs. Treatment with apo-Bderived peptides didn’t alter this phenotype as compared with ox-LDL treated cells. There was no
proliferation of allogeneic naïve CD4+T lymphocytes in response to the peptide –loaded DCs as
compared to controls. Conversely, the peptides halted the proliferation of syngeneic T cells
induced by oxLDL-loaded DCs.
Conclusions: Our results suggest that P2, P45 and P210 induce tolerogenic properties on
immature DCs and therefore are able to inhibit syngenic and allogenic with T proliferation. This
effect is peptide dose-dependent. Further studies are needed to reveal the mechanisms involved in
peptide-induced DCs tolerogenicity and its effect on atherosclerosis development.
No. 36
Title
Authors
Group
Abstract
PHYLOGENETIC ANALYSIS OF THE ATP-BINDING CASSETTE SUPERFAMILY
Ciaran Fisher1, Tanya Coleman2 and Nick Plant1
1
Biochemical Sciences Division; Pharmacology and Toxicology Theme; Centre for Toxicology
2
DMPK, AstraZeneca, Alderley Park, SK10 4TF
The ready availability of genomic data for an ever increasing number of diverse species, coupled
with accessible tools to analyse this data, offers the opportunity to study the evolution of important
gene families. The ATP-binding cassette (ABC) superfamily of genes encodes 48 proteins in
humans which are divided into 7 subfamilies. These subfamilies are represented, to a greater or
lesser degree, in all eukaryotic genomes. ABC proteins are also expressed in prokaryotic genomes,
accounting for 5% of the Escherichia coli genome. Of these 7 subfamilies, 5 encode for membrane
exporter proteins with an extensive and diverse range of substrate specificities. These exporters
have a key role in protecting organisms from xenobiotic exposure and can significantly contribute
to multiple drug resistance. Using reference sequence data, phylogenetic trees have been generated
over an extended evolutionary distance representing each of the 7 subfamilies, providing an
insight into the relationship between orthologues and how they have evolved over time. This
could provide clues as to the significance of these proteins in species differences and inter
individual variability in response to xenobiotics, important information in both drug development
and safety testing.
Key References
Dean, M., Annilo, T., 2005. Evolution of the ATP-binding cassette (ABC) transporter superfamily
in vertebrates. Annual Reviews in Genomics and Human Genetics 6, 123-142
Gillet, J. P., Efferth, T., Remacle, J., 2007. Chemotherapy-induced resitance by ATP-binding
cassette transporter genes. Biochimica et Biophysica Acta 1775, 237-262
31
Faculty of Health and Medical Sciences
No. 37
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
REMOVAL OF PHOSPHATE FROM WASTE WATER USING MODIFIED SILICATES
Rasha Khalife and Angela F. Danil de Namor
Division of Chemical Sciences; Materials and Nanosciences Theme; Thermochemistry lab
The presence of phosphate in the industrial waste water is a major problem because of
eutrophication. For this reason many processes have been used and developed over the years to
remove it from the ecosystem.
The aim of this work is to design and synthesize new decontaminating agents for the removal of
phosphates from water. In doing so silicates are used as solid supports due to their high specific
surface area and mechanical stability. Thus silicates have been modified with chelating groups
selective for phosphates.
Factors such as optimum mass, capacity of the material, pH of the solution, temperature and the
kinetics of the extraction process were investigated.
The results have shown that these materials have a high capacity to remove phosphates and are
easily recyclable. These properties are key parameters for developing a new technological
approach for the efficient removal of this polluting ion from water.
Acknowledgements: The authors thank the European Commission for the financial support
provided under the contract INCO-CT-2004-509159
No. 38
Title
Authors
Group
Abstract
THE ACUTE EFFECTS OF RESISTANT STARCH ON APPETITE AND SATIETY
Caroline Bodinham, Prof Gary Frost, Dr Denise Robertson
Division of Nutritional Sciences
Aim: To investigate the effects of 24 hour supplementation with resistant starch (RS) on appetite
compared to a placebo (rapidly digestible starch).
Methods: On separate occasions at least 1 week apart, 20 young, healthy adults males consumed
either 48g RS or an energy and carbohydrate matched placebo as part of standardised breakfast
and lunch meals. Subjective measures of appetite and blood samples were taken every 30 minutes
for the 7 hour intervention period, after which food intake was quantified by an ad libitum test
meal. Subjects were then able to consume food and drink freely for the remainder of the day which
was recorded in diet diaries to obtain overall 24 hour intake. Bowel diaries were completed on the
day of the study and the following day to monitor tolerance of the supplements.
Results: Following the RS supplement there was a significantly lower intake at both the ad
libitum test meal (1242kcal v 1328kcal p=0.033) and over the 24 hour period (2977kcal v
3292kcal p=0.051) compared to the placebo. However, this was not accompanied by differences in
the subjective appetite ratings. The supplements were reported to be well tolerated. Postprandial
plasma glucose levels were not significantly different between supplements; however, there was a
significantly lower insulin response with the RS compared to the placebo (p=0.029). C-peptide
levels were not significantly different between the supplements, but the C-peptide to insulin ratio
was significantly higher with the RS supplement (6.69 v 6.13 p=0.059).
Conclusion: The significantly lower energy intakes seen with the RS supplement could have
beneficial implications in the management of obesity. The lower insulin response, which was
accompanied by a relatively similar glucose response, would suggest a beneficial role of resistant
starch in the postprandial insulin response, especially in insulin clearance, as suggested by the
higher C-peptide to insulin ratio. Further studies are required to determine the mechanisms for the
effect on appetite and the insulin response, to establish if the effect on energy intake can be
maintained long term, and to confirm if this effect is seen in other population groups.
32
Faculty of Health and Medical Sciences
No. 39
Title
Festival of Research
4th July 2008
ROLE OF ADENOSINE A2A RECEPTOR IN THE REGULATION OF ANGIOTENSIN II INDUCED
ENDOTHELIAL CELL OXIDATIVE STRESS AND DYSFUNCTION
Authors
Group
Sapna Thakur, Susanna Hourani, Jian-Mei Li
Biochemical Sciences Division; Cardiovascular Research Theme
Abstract
The adenosine A2A receptor (A2AR) has been found to be largely expressed in vascular endothelial
cells and involved in the regulation of endothelial function. Endothelial cells express constitutively
an NADPH oxidase, which generates reactive oxygen species (ROS) and participates in cellular
redox-signalling. The activity of endothelial NADPH oxidase can be activated by angiotensin II
(Ang II), resulting in endothelial oxidative stress and dysfunction. In this study, we investigated
the role and the mechanisms of A2AR in the regulation of Ang II-induced endothelial ROS
production by NADPH oxidase, using a mouse microvascular endothelial cell line (SVEC 4-10)
(in vitro) and aortic sections from mice (ex vivo) (n=3 for all experiments).
Quantitative real-time PCR showed a significant (p<0.05) 2 fold increase in A2AR mRNA
expression in SVEC 4-10 treated with 100 nM Ang II for 30 minutes. In additon, lucigenin (5
μM)-chemiluminescence assay demonstrated a significant (p<0.01) decrease (26±5%) in ROS
production in SVEC 4-10 cells treated for 30 min with a specific A2AR antagonist (SCH 58261,
100 nM). Treatment of the cells with Ang II (100 nM, 30 min.) significantly increased (119±5%)
ROS production (p≤0.001), which could be significantly reduced to the basal level in the presence
of SCH 58261 (100 nM) (p≤0.01). Ang II-induced ROS production could be inhibited by tiron (a
specific O2- scavenger) and apocynin (an NADPH oxidase inhibitor) suggesting that the enzymatic
source of ROS generation was NADPH-oxidase. Finally we examined ERK1/2 activation in aortic
vessels obtained from mice (CD1, male, 10 weeks old) killed by schedule 1 procedure 90 min after
intraperitoneal injection of SCH 58261 (10 mg/kg body weight). High ERK1/2 phosphorylation
was found in aortic sections treated with Ang II. Compared to control sections there was reduced
ERK1/2 phosphorylation in sections from SCH 58261 treated mice. These results indicate that the
A2AR plays a role in promoting endothelium NADPH oxidase activation, as SCH 58261 inhibits
endothelial ROS production. Understanding the underlying mechanism of A2AR and Ang II
interactions will further broaden our knowledge of their involvement in the production of ROS
that results in oxidative stress contributing to vascular damage in cardiovascular disease.
No. 40
Title
Authors
Group
Abstract
A COMPARISON OF THE BIOTRANSFORMATION OF (–)-EPICATECHIN AND
PROCYANIDIN B2 BY HUMAN COLONIC BACTERIA
Stavroula Stoupi1, Gary Williamson2, J. Warren Drynan3, Jonathan Brown1 and Mike
Clifford1
1
Nutritional Sciences, FHMS, University of Surrey, Guildford GU2 7XH, Surrey, UK
2
Procter Department of Food Science, University of Leeds, LS2 9JT, UK
3
Chemical Sciences, FHMS, University of Surrey Guildford GU2 7XH, Surrey, UK
A standard in vitro colon model was used to investigate and compare the biotransformation of (–)epicatechin and procyanidin B2. The batch culture system used was freshly collected crude
human flora. Qualitative analysis via LC-ESI-MSn revealed a range of metabolites of which the
most abundant were dihydroxy phenyl propan-2-ols, dihyhydroxy phenylvalerolactones,
hydroxyphenylpropionic and hydroxyphenylacetic acid, monohydroxylated at the para position, as
well as phenylacetic acids. Twelve metabolites were identified, of which ten were fully
characterised via LC-ESI-MSn with negative-polarity ionisation. Ten metabolic intermediates
were quantified and construction of the metabolic profile was carried out after 48 hours of
incubation. Quantitative analysis via LC-ESI-MSn showed the accelerated disappearance of both
substrates after 11 hours of incubation accompanied by a simultaneous increase in metabolic
transformation-products. This is the first such study to compare pure procyanidin B2 with its
associated monomer, (−)-epicatechin (2, 3-cis stereochemistry) as a substrate for human
microflora.
33
Faculty of Health and Medical Sciences
No. 41
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
THE EFFECT OF IMMUNIZATION WITH APOB-100-DERIVED PEPTIDES ON THE
PROLIFERATION AND FUNCTIONAL STATUS OF REGULATORY T CELLS.
Chrysoulla Pierides†, Alexandra Bermudez-Fajardo†, Gunilla N. Fredrikson‡, Jan Nilsson‡
and Ernesto Oviedo-Orta†
† Cardiovascular Theme; Division of Microbial Sciences, FHMS, University of Surrey
‡ Experimental Cardiovascular Research, CRC, Lund University, Malmö, Sweden
The onset and development of atherosclerosis, a chronic inflammatory disease with an
autoimmune component, is promoted by T-cell mediated immune responses against antigens such
as oxidized low density lipoprotein (oxLDL). Regulatory T cells have been shown to be involved
in modulating inflammation leading to atherosclerosis. This study seeks to investigate the effect of
immunization with anti-atherogenic apoB-100-derived peptides (P2, P45 and P210) on the
proliferation and functional properties of regulatory T cells. Peptides were conjugated to BSA and
used to immunise apoE-/- mice (one initial injection followed by 2 booster doses at 2-weeks
intervals). Naïve spleenocytes, from non immunized, as well as apoE-/- mice immunized with BSA
and PBS were used as control groups. Upon termination, spleenocytes were used to assess the
expression of T-lymphocytes and Treg cell markers (CD4 or CD8, CD25, FoxP3 or CD127) by
flow cytometry. Pre-immunisation serum samples and serum samples upon termination were used
to determine the pro- (IFN-γ) or anti-inflammatory (IL-10) cytokine secretion profile induced by
the treatment, using commercially available cytokine ELISA kits, and levels of IgG1 and IgG2a.
Our data shows that apoB-100-derived peptides induce Treg cells proliferation in apoE-/- mice,
particularly P2 and P45. These were significantly higher when compared to all three control
groups, implying that the peptides induce proliferation of Treg cells and hence promote a Th2,
anti-inflammatory response.
This study shows for the first time that vaccination can be used to specifically modulate T-cell
mediated pro-inflammatory and pro-atherogenic responses and provides new hopes for the
development of preventive strategies.
No. 42
Title
Authors
Group
Abstract
IN SILICO MODELLING OF TRANSPORTER MEDIATED XENOBIOTIC FLUX
THROUGH CELLS
Samantha Forster1, Steve Hood2 and Nick Plant1
1
Biochemical Sciences Division; Pharmacology and Toxicology Theme; Centre for Toxicology
2
DMPK, GlaxoSmithKline, Ware, SG12 0DP
Drug transporters are being increasingly recognized, alongside phase I and II metabolic enzymes,
as important drivers in the pharmaco- and toxico- kinetic characteristics of therapeutic agents. In
many cases cellular access, determined by drug transporters, must be considered in order to better
predict drug disposition in vivo (Kim 2002). The aim of this research is to generate an in silico
model of cellular response to stimuli, using a whole-cell approach to investigate system dynamics.
An initial step in the development of such an in silico model is the generation of the base structure:
We utilise CellDesigner™, a graphical front-end for the SBML programming language, allowing
us to create a structure for potential interactions (reactions) between drugs and cellular
components (species). These models can then be populated with published literature data for each
species (quantitative data) and reaction (kinetic data), allowing construction of a first stage model.
We have created one such model, based upon the life-cycle of the Pgp substrate Rhodamine-123.
Following construction of preliminary models it is necessary to populate missing data points, thus
allowing simulation of the final model. Quantitative transcript and protein expression data for
OATP1B1, MRP2 and P-gp in Huh7 cells has been generated, demonstrating low protein
expression of OATP1B1 and MRP2, but high expression levels of P-gp. In addition, confocal
microscopy has shown that the fluorescent MRP2 substrate CDF is not exported efficiently from
Huh7 cells, due to insufficient cell polarity and lack of canaliculi formation. Taken together these
data suggest that Huh7 cells represent a poor model liver system to study transport kinetics for
these transporters. Future work will comprise the generation of kinetic information in MDCK II
cells over-expressing cloned human transporters and the examination of further in vitro human
hepatocyte systems.
34
Faculty of Health and Medical Sciences
No. 43
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
CARBON NANOTUBES INSIDE CANCER CELLS FOR GENE DELIVERY AND
THERAPY
Vera Neves, Ravi Silva, Helen Coley, Johnjoe Mcfadden
Advanced Technology Institute, PGMS and Microbial Sciences
The targeting of genes in cancer cells to stop tumour growth and kill the cancer cells has emerged
as a promising approach for cancer therapy. The key challenges for the application of this kind of
approach are largely dependent on the development of suitable delivery systems. None of the
current transfection vectors are ideal, mainly because they often provoke immune responses.
Recently, Carbon nanotubes (CNT) have been shown to transverse cellular membranes and shuttle
biological molecules, including DNA, siRNA, and proteins into cancer cells. The main advantages
of CNT compared with other delivery agents are their biocompatibility, large surface area, stability
and flexibility.
Our current work is focused around developing an in vitro model to examine the feasibility of this
approach using functionalized, RNA wrapped CNTs as a means of delivering gene therapy. We
will then use this as a basis for further in vivo work using animal tumour models with
characterised genotypes (e.g. mutated p53 etc) to validate this approach. Cultured HeLa cells
(human cervical carcinoma cells) have been exposed to single-walled carbon nanotubes (SWNTs)
functionalized non-covalently with RNA – (SWNT-RNA) and polypeptides. First, the
functionalized SWNT were characterized using AFM and Raman spectroscopy. Then, uptake of
SWNT-RNA by cells was confirmed by Raman spectroscopy, which was also used to demonstrate
that the SWNT-RNA were taken up by HeLa cells in a time dependent manner. Preliminary
studies of gene delivery were carried out, where AcGFP gene, encoding green fluorescent protein
(GFP) from Aequorea coerulescens, was used as a model to show SWNT uptake and efficient
gene expression. In order to optimize gene expression several methods of functionalization are
investigated with the future aim of using SWNT for gene silencing experiments.
No. 44
Title
Authors
Group
Abstract
NOVEL MECHANISM OF PROTEIN SYNTHESIS ON CALICIVIRUS mRNA
Elizabeth Royall, Subhan Sa Sayed, Ian G Goodfellow, Yasmin Chaudhry
and Lisa O Roberts
Microbial Sciences Division; Infectious Diseases Theme
Caliciviruses cause important diseases of humans and animals. For example, norovirus (NV) is
responsible for outbreaks of gastroenteritis in man, and feline calicivirus (FCV) usually causes an
upper respiratory tract infection in cats though virulent strains are emerging that cause serious
systemic disease. Cytoplasmic mRNAs are capped at their 5′ end and the first step in translation is
the binding of the initiation factor eIF4F to the 5′ cap structure. eIF4F is known as the capbinding complex and is made up of three proteins: eIF4E binds the cap directly; eIF4A is an RNA
helicase; and the largest of the three proteins, eIF4G, acts as a "scaffolding" and bridges the
ribosome to the mRNA via eIF3. Calicivirus mRNAs do not possess a 5′ cap structure to direct
translation of their mRNA, instead, we have shown that translation is dependent on the presence of
a protein covalently linked to the 5′ end of the viral genome (VPg). We have previously
demonstrated a direct interaction of calicivirus VPg with the cap-binding protein eIF4E and have
gone on to show that the VPg protein acts as a novel proteinaceous “cap-substitute”. We are now
carrying out further analysis of the exact requirements for components of the eIF4F complex for
translation initiation on FCV and MNV mRNAs. To identify the VPg-binding site on eIF4E we
have made a panel of eIF4E mutants and are currently examining their ability to function in
calicivirus translation. In order to assess the requirement for eIF4A, we have previously shown
that a specific inhibitor of this factor inhibits calicivirus translation in vitro. We have now
developed a system to knock down eIF4A expression in CRFK cells using siRNA, and have
shown that this leads to an inhibition of virus replication. Finally, we have previously shown that
cleavage of eIF4G inhibits FCV, but not MNV, translation. We are therefore analysing the
minimal fragments of this protein that can function in calicivirus translation. The ultimate aim of
this work is to dissect the mechanism of translation initiation on calicivirus RNA and in doing so,
identify specific targets for potential antiviral therapies for this group of economically important
viruses .
35
Faculty of Health and Medical Sciences
No. 45
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
MESOPOROUS HYBRID MATERIALS FOR A CLEAN ENVIRONMENT
Abdelaziz El Gamouz and Angela. F. Danil de Namor
Division of Chemical Sciences; Materials and Nanosciences Theme; Thermochemistry lab
Mesoporous materials have attracted great attention since their discovery due to their wide range
of applications as catalysts1 adsorbents2, molecular recognition devices3 and their use in separation
processes4. These well organised materials are characterised by a large BET surface area, high
porosity, controlled pore size and ordered pore arrangements5. It is in the basis of these properties
that these materials are able to interact with guest species through static or covalent bonding
interactions.
This work describes i) the synthesis and characterization of an hexagonal mesoporous silica
(HMS), the heterogeneous methodology used for the hybridisation of the composite material and
the functionalization of the silanol groups of the mesoporous ii) the removal of polluting
compounds (gallic and tannic acids) from aqueous solutions by the new modified mesoporous
materials.
Acknowledgement: The authors thank the European Union for financial support under contract
INCO-CT-2004-509159 and 509153.
References:
1. R. Nava , J. Morales, G. Alonso , C. Ornelas , B. Pawelec , J.L.G. Fierro, Appl.ied. Catalysis A:
General (2007) 321 58–70
2. P. Punyapalakul, S. Takizaw, wat. re s. (2006) 40 3177 – 3184
3. T. Takei, O. Houshito, Y. Yonesaki, N. Kumada, N. Kinomura, J. So. Sta.t. Chem. (2007) 180
1180–1187
4. Peter M. Price, James H. Clark and Duncan J. Macquarie, J. Chem. Soc, Dalton Trans. (2000),
101-110.
5. M. R. Jamali, Y. Assadi, F. Shemirani, M. S. Niasari, Talanta (2007)71 1524–1529.
No. 46
Title
Authors
Group
Abstract
OPTIMIZED REMOVAL OF XYLENOL ORANGE IN WASTEWATER USING A
MESOPOROUS SILICA
Xiaolu Bi, Abdelaziz El Gamouz, Angela. F. Danil de Namor
Division of Chemical Sciences; Materials and Nanosciences Theme; Thermochemistry lab
Dyes are used to impact colors to materials and are essential for textile manufacturing, scientific
research, as well as people’s daily life. Both the synthesis of dyes and the coloring process involve
several steps which generate wastage continuing hazardous chemicals. Most of these wastes are
difficult to biodegrade due to their complex aromatic molecular structure and synthetic origin.
Improvement of pollution treatment measures, such as the extraction of dyes from wastewater can
yield both economic and environmental benefits.
Furthermore, mesostructure materials have attracted a great interest because of their wide pore
opening and narrow pore size distribution of the channels which can provide a confined space for
intrapore inclusion chemistry as host.
Despite many applications and
environmental concerns on dyes, little
quantitative work has been carried out to
determine the factors influencing their
extraction. The aim of this work is to
investigate the optimum conditions for the
extraction of xylenol orange by using a
mesoporous silica. The process has been
optimized by investigating the effect of
mass, pH, temperature, kinetic as well as
the optimum capacity.
Acknowledgement: The authors thank the European Union for financial support under contract
Inco-CT-2004-509159 and 509153.
36
Faculty of Health and Medical Sciences
No. 47
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
SUBJECTIVE AND ACTIGRAPHIC SLEEP IN OLDER PEOPLE WITH CONTROL
AND ‘BLUE-ENRICHED’ WHITE LIGHT
Katharina A. Lederle, Benita Middleton, Tracey L. Sletten, Victoria L. Revell, Debra J.
Skene
Sleep and Chronobiology Theme
Short wavelength blue light is most effective in influencing non-image-forming responses to light
e.g. shifting circadian rhythms. The effect of ‘blue-enriched’ white light (colour temperature 17
K) compared to control white light (4 K) on subjective and actigraphic sleep in older people (≥ 60
years) with self-reported sleep problems (PSQI > 5) was measured in the current study.
During an 11-week trial (randomised, crossover design) involving 2 light treatment periods (each
for 3 weeks) and 2 washout periods, healthy participants (n = 12; mean ± SD 65.3 ± 4.0 years; 7F,
5M) were exposed to both light conditions in their own homes. Light was administered for 2 h in
the morning and 2 h in the evening during the light treatment weeks. For the entire study period
participants kept daily sleep diaries and wore an actiwatch-L (AWL), an activity and light monitor.
Subjective and objective sleep parameters derived from the sleep diaries and AWLs have been
analysed using repeated measures one-way ANOVA. Subjective sleep efficiency improved
significantly, sleep latency reduced and wake-up time advanced compared to baseline (p < 0.05)
during and after both light conditions. Objective sleep efficiency improved significantly during
the 17 K light (p < 0.05); nocturnal wake time was reduced during both light conditions (p < 0.05)
compared to baseline (4 K) or washout (17 K).
Thus both lights had some significant beneficial effects on sleep when compared to baseline and
washout periods. However, there were no significant differences in any sleep parameter between
the two light conditions.
Supported by Marie Curie RTN grant (MCRTN-CT-2004-512362); funded by the Cross-Council
New Dynamics of Ageing (NDA) initiative (Grant number RES-339-25-0009).
No. 48
Title
Authors
Group
Abstract
DETERMINATION OF TRACE ELEMENTS IN HUMAN HAIR FROM KARBALA,
IRAQ
B. A. Joda & N. I. Ward
Chemical Sciences, FHMS, University of Surrey
This study describes the effect of cigarette smoking and diet program on trace elements
concentrations in human hair (scalp and axillar) of more than 100 human individuals by atomic
absorption flame spectroscopy (Ca, Mg, Fe, Na) and inductively coupled plasma mass
spectrometry (ICP-MS) for Co, Cu, Cd, Cr, Mn, Mo. Ni, Se, V and Zn. Many of these elements
are found or used at very low concentrations within the human body and some have a significant
role in terms of the essential body processes and values outside of “normal” levels can lead to a
number of health disorders. All of the samples were collected in Karbala, Iraq from a human
population consisting of smokers, non-smokers and passive-smokers, who are of various ages. In
contrast, samples were collected from Iraqi individuals who have lived in the UK for a long time
to compare their elemental levels with residents who live in Iraq. The data will report
methodological developments to optimize the required hair sample mass and dilution volumes for
elemental quantification, methods of sample digestion and analytical validation (use of certified
reference materials and inter-analytical method comparison).
37
Faculty of Health and Medical Sciences
No. 49
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
DIFFERENTIAL TRANSCRIPTIONAL REGULATION OF NUCLEAR IMPORT GENE
KARYOPHERIN α3 BY NUCLEAR RECEPTORS
Supaporn Yimthaing, G. Gordon Gibson, Nick J. Plant, Kathryn E. Plant
Biochemical Sciences Division; Pharmacology and Toxicology Theme; Centre for Toxicology
Karyopherin α (KPNA) consists a family of soluble nuclear receptors that mediated the transport
of macromolecules into the nucleus to maintain key cellular process. However, experimental data
to explain the transcriptional regulation of KPNA genes has not to date be obtained. To resolve
this issue, this study has been designed to investigate nuclear-receptor mediate transcriptional
regulation of human KPNA3 gene which was transcribed at the highest level in adult liver. In
silico analysis was performed to locate well conserved regions upstream of the first exon of the
human, rat and mouse. Approximately 2 kb proximal promoter was identified as functionally
conserved region which contains putative binding sites for nuclear receptors including PPARα,
HNF4α, CAR, and VDR.
The initially study has been focused on ligands for PPARα, HNF4α, CAR, and VDR. The results
from our regulation study in the human hepatoma cell line Huh-7 showed that human KPNA3
gene expression was markedly suppressed by Wy-14643, and 1α,25(OH)2D3 in presence of
PPARα and VDR, respectively. In contrast to Wy-14643, clofibrate, which is also PPARα ligand,
had no significantly effect in human KPNA-α3 gene expression. Similarly, CAR ligand
(Phenobarbital), and HNF4α ligand (palmitoyl CoA) did not significantly alter human KPNA3
gene expression. From these results, it would be suggested that the expression of human KPNA-α3
gene might be substrate-specific and that PPARα and VDR may mediate inhibition of human
KPNA3 gene expression by Wy-14643 and 1α, 25(OH)2D3 at transcriptional level which may play
important role in regulation of nuclear transport in the liver.
No. 50
Title
Authors
Group
Abstract
EFFECT OF TOTAL SLEEP DEPRIVATION ON POSTPRANDIAL PLASMA
GLUCOSE, TRIACYLGLYCEROL AND NON-ESTERIFIED FATTY ACID
CONCENTRATIONS IN SHIFT WORKERS AND NON-SHIFT WORKERS
Sophie M.T. Wehrens, Shelagh M. Hampton and Debra J. Skene
Sleep and Chronobiology, Faculty of Health and Medical Sciences
Epidemiological studies have shown that sleep deprived individuals are at higher risk of
cardiovascular disease, accompanied by changes in blood glucose, triacylglycerol (TAG) and nonesterified fatty acid (NEFA) concentrations. However, these changes have not been investigated in
response to total sleep deprivation in laboratory conditions. The aim of the present study was to
investigate the effects of one night of total sleep deprivation (TSD), a recovery nap and recovery
sleep on postprandial metabolism under controlled conditions. The responses of shift workers and
non-shift workers were compared.
Six shift workers (33.5±7.8yrs (mean±SD), body mass index (BMI): 28.2±3.7kg/m2, waist-hip
ratio (WHR): 0.93±0.03cm; shift work history ≥5yrs) were matched with 6 non-shift workers
(31.5±5.4yrs, BMI: 25.1±1.3kg/m2, WHR: 0.91±0.04cm; shift work history <6months). After an
adaptation and baseline night (equal to habitual sleep), volunteers were kept awake for 36.5h,
followed by a nap (4h), recovery sleep and another 16h awake in the laboratory (all in dim light,
<8 lux, interventions relative to wake up time, body posture and food controlled between days).
Blood samples were taken prior to and after a standard breakfast (7.3% protein, 40% fat, 52.7%
carbohydrates, 991kcal) on the baseline day, after TSD and after recovery sleep. Plasma glucose,
TAG and NEFA concentrations were measured by automatic analysis with Ilab650.
Preliminary analysis by repeated-measures ANOVA (within subjects factors: time and day)
showed a significant day*group interaction for postprandial glucose responses (F(2,9)= 4.7;
P<0.05). Higher glucose levels (P<0.05) were observed after recovery sleep in non-shift workers
but not in shift workers. There was also a significant effect of day on postprandial TAG responses
(F(2,9)= 4.2; P<0.05) with higher TAG levels after recovery sleep compared to TSD. However, no
effect of day was observed in postprandial NEFA responses.
Supported by EU grant MCRTN-CT-2004-512362
38
Faculty of Health and Medical Sciences
No. 51
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
FELINE CALICIVIRUS ISOLATED FROM CATS WITH VIRULENT SYSTEMIC
DISEASE APPEARS TO DELAY RATHER THAN INDUCE APOPTOSIS IN VITRO.
Ben Brennan, George.E.N Kass and Lisa O. Roberts
Microbial Sciences Division; Infectious Diseases Theme
Caliciviruses are responsible for many important diseases of man and animals yet we still know
relatively little about the molecular mechanisms of pathogenesis, especially the events involved in
cell damage. Noroviruses cause gastroenteritis or “projectile vomiting” in humans and outbreaks
are often seen in hospitals, cruise ships and in military camps, while feline calicivirus (FCV)
causes cat ‘flu’. Our previous work has shown that FCV-F9 infection of cells induces apoptosis.
Furthermore, we have shown that apoptosis proceeds through the mitochondrial pathway,
involving bax translocation to the mitochondria, cytochrome c release and a drop in mitochondrial
membrane potential.
More recently there have been reports of FCV strains associated with acute lethal virulent
systemic disease (VSD) within cats. In attempting to ascertain why these strains have such
devastating effects upon infection we have examined the molecular mechanism of apoptosis
induced by one particular strain of calicivirus, UKOS A. The UKOS A strain was isolated from
the first reported outbreak of VSD within the United Kingdom.
We have discovered that the UKOS A strain delays apoptosis, rather than inducing it as the F9
strain does. We have demonstrated this delay through the use of phosphatidyl serine translocation
and caspase-3 activation assays. The translocation of cytochrome c from the mitrochondria to the
cytosol is also delayed. Finally, we have examined the viral titres and cellular morphology of
infected cells and found that the UKOS A-infected cells display cytopathic effect earlier than F9
infected cells, despite the apparent delay in apoptosis.
We therefore propose that the delay in apoptosis affected by UKOS A allows the virus to replicate
to higher titres within the infected cells and this could in part explain the increased virulence of
this strain of FCV.
No. 52
Title
Authors
Group
Abstract
ERGONOMICS OF THE MEDICATION ROUND IN CARE HOMES
Paul Wadsworth, Peter Buckle, Rosemary Lim, Janet Anderson
Public Health Theme
Medication errors are a potential cause of concern for care home residents. This study considered
the ergonomics issues relating to the medication round. The research sought to establish i) the
frequency of interruptions during the medication round ii) the source of interruptions (e.g. staff,
residents, visitors) iii) the nature/purpose of these interruptions iv) the ergonomics issues that
should be addressed to enhance safe administration. A sample of sixteen homes was selected as
representative of the range of size (number of residents) and type (residential and/or nursing) of
care homes across the UK Assessments were made through observations, interviews and task
analysis. In many regards, the medication round system adopted in care homes mirrors that found
in most acute hospital ward settings. However, it differs most notably from this system in the
availability of appropriately trained health care professionals within the immediate system.
Most medication rounds were interrupted by other tasks with up to 12 interruptions per hour
occurring. The source of these was, most often, other staff. The physical design of the trolley and
care home environment were also areas of concern. A Systematic Human Error Reduction and
Prediction Approach (SHERPA) analysis revealed a number of tasks where errors are likely to
occur. Recommendations are made for further investigation and some possible solutions are
advanced for evaluation.
39
Faculty of Health and Medical Sciences
No. 53
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
SYSTEMS APPROACHES IN HEALTHCARE: PATIENT SAFETY CASE STUDIES
INVOLVING COGNITIVE WORK ANALYSIS (CWA)
Peter Buckle, Janet Anderson and Rosemary Lim
Public Health Theme
It is generally agreed by human factors specialists that there is a need to undertake systems
approaches to the analysis of healthcare settings if improvements in patient safety are to be
achieved. The difficulty lies is identifying an appropriate means of achieving this. This paper
considers how Cognitive work analysis (CWA) contributes to a systems approach to patient safety.
This paper provides an overview of the use of CWA in several areas of health care where patient
safety concerns are known to exist. This approach has identified some specific advantages over
other methods including: Practical and logical identification of systems boundaries;
Identification of systems ‘values’ with the added potential of then enabling further study as to
how these are prioritised; Systematic and auditable identification of physical components in the
system and scope for information sources to be exhaustively listed; Identification of missing
elements that might be required to fulfil the required system objectives; Ability to help identify
where a health care system might fail (currently being linked to studies of the use of prospective
hazard analysis); the scope to identify training needs, particularly with reference to patient safety
and to assist in understanding how and where to make recommendations for system
improvements.
The paper will describe these aspects of CWA application in a number of healthcare contexts,
including those involving medication errors.
No. 54
Title
Authors
Group
Abstract
DOES C-REACTIVE PROTEIN MEDIATE ACTIVATION OF DENDRITIC CELLS
DURING INFECTION WITH NEISSERIA MENINGITIDIS
Jenson J.S, Casey R, McFadden J & Bodman-Smith K.
Division of Microbial Sciences; Infections Diseases Theme.
Infection with Neisseria meningitidis in humans can cause both meningitis and septicaemia which
may lead to endotoxic shock, gangrene, organ and neurological damage as a result of an overactivated inflammatory response. There is no effective vaccine for group B strains which are the
most common in the UK.
The prototypic acute phase reactant in humans: C-reactive protein (CRP), increases in serum
concentration by up to 1000 fold during inflammatory responses, and, as a powerful opsonin,
binds to a variety of phosophorylated and carbohydrate structures present on the surface of several
microorganisms and apoptotic cells. CRP has been reported to induce the secretion of both proand anti-inflammatory cytokines from leukocytes, which may affect ongoing inflammation and
downstream acquired immune effector mechanisms.
The Dendritic cell (DC) is the prototypic professional antigen presenting cell. We aim to
investigate the effect of CRP on human dendritic cell responses to N. meningitides. Our studies
have shown that purified CRP binds pathogenic strains of N. meningitidis via pili-associated
phosporylcholine in a concentration- and calcium-dependent manner and that this binding
increases uptake by human macrophages and neutrophils. Preliminary data from our group using
Fluorescence Activated Cell Scanning (FACS) and confocal microscopy has shown that CRPopsonisation of meningococci results in a significant increase in the uptake of meningococci by
human DCs. We have also investigated the effect of CRP-mediated uptake of N.meningitidis on
expression of DC maturation and costimulatory markers. The results from this study suggests that
CRP may be able to modulate DC activation and thereby affect immune responses to
meningococci which may lead to development of novel therapeutic strategies.
40
Faculty of Health and Medical Sciences
No. 55
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
ABERRANT CA2+ OSCILLATIONS UNDERLIE HUMAN DETRUSOR MUSCLE
OVERACTIVITY
Sui G, Fry CH and Wu C
PGMS; Toxicology & Pharmacology
Introduction: Overactive bladder syndrome (OAB) is highly prevalent and costly, but its
pathogenesis remains unclear; in particular, the origin of involuntary muscle activity. Hyperactive
smooth muscle activity could form an important functional substrate for myogenic overactivity.
However its determinant, intracellular Ca2+, has never been examined in pathologically overactive
human bladders. Our aims are: to test the hypothesis that spontaneous intracellular Ca2+
oscillations are increased in human detrusor smooth muscle from overactive bladders; and to
elucidate the cellular mechanisms underlying such activity.
Methods: Intracellular Ca2+ and electrical activity were measured in smooth muscle cells from
patients with overactive or stable bladder, using epifluorescence microscopy and voltage-clamp.
Results: Basal cytoplasmic Ca2+ was elevated in cells from overactive bladders. Unprovoked,
spontaneous rises of Ca2+ were also identified, reminiscent of involuntary detrusor contractions,
and associated with cell shortening. They were Ca2+-dependent, sensitive to L-type Ca2+ channel
antagonist verapamil and also attenuated by blocking SR Ca2+ reuptake with thapsigargin. The
fraction of spontaneously active cells was higher in cells from overactive bladders and the overall
magnitude of spontaneous Ca2+ increases was also greater. Spontaneous action potentials or
depolarising oscillations associated with Ca2+ rises were also observed; with a higher percentage of
cells from idiopathic OAB, but not in neurogenic OAB. Inhibition of T-type Ca2+ channel by low
concentrations of NiCl2 attenuated both spontaneous electrical and Ca2+ activation.
Conclusions: Spontaneous, autonomous cellular activity - Ca2+ and membrane potential
oscillations, originates in detrusor smooth muscle from human bladders, mediated by extracellular
Ca2+ influx and intracellular release, and facilitated by T-type Ca2+ channels. Such activity
underlies muscle contraction and defective Ca2+ activation contributes to upregulated contractile
activity in overactive bladders.
No. 56
Title
Authors
Group
Abstract
DESIGN OF A NEW CATALYTIC PHOSPHATE PROTECTING GROUP FOR DNA
SYNTHESIS
Bharatheeban Skandarajah and Dmitry A. Stetsenko*
Division of Chemical Sciences, Materials and Nanosciences Theme
There are two phosphate protecting groups, 11,2 and 2,3 that are able to catalyse phosphodiester
bond formation in DNA synthesis. However, 1 requires harsh conditions for its deprotection,2 the
use of 2 may lead to side-reactions,3 and both require complex multi-step synthesis.
It seems very interesting to see if 1-methylimidazol-2-ylmethyl group 3 can be a novel catalytic
phosphate protecting group that would be simpler, less expensive and yet more reactive.
1. Froehler, B. C., and Matteucci, M. D., J. Am. Chem. Soc. 1985, 107, 278.
2. Sproat, B. S.; Rider, P.; Beijer, B., Nucleic Acids Res. 1986, 14, 1811.
3. Efimov, V. A.; Buryakova, A. A.; Dubey, I. Y.; et al., Nucleic Acids Res. 1986, 14, 6525.
41
Faculty of Health and Medical Sciences
No. 57
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
MECHANISM OF ACTION OF OLIGOMYCINS ON ATP SYNTHASE
R. Green, B. Howlin, A. Thumser, D.C. Povey, R.A. Palmer and J. Saldanha
Chemical and Analytical Sciences
The solution of the single crystal x-ray structures of oligomycins A, B and C by our collaborators
(Palmer and Saldanha) has enabled the use of the actual three dimensional structures as probes to
computationally dock into a model of E.coli ATP synthase, which was built by protein homology
modelling. The protein model as built did not have a suitable pocket for the oligomycins to bind,
so an induced fit energy minimization method was used to locate it. This pocket provides; 1) a
mechanism for the inhibition of ATP synthase by oligomycins, 2) interactions are found between
amino acid residues known to be involved in oligomycin binding from experimental data with the
bound oligomycins, 3) calculated values of the inhibition constants (Ki) of the oligomycins that
compare with experimentally measured values.
Figures ATP synthases (as indicated) and oligomycin binding site (in Yellow).
No. 58
Title
Authors
Group
Abstract
CONSTRUCTION OF AN ISOTOPOMER MODEL OF CENTRAL METABOLISM IN
MYCOBACTERIUM TUBERCULOSIS AND USE OF THE MODEL TO ANALYZE 13CSUBSTRATE LABELING EXPERIMENTS TO ESTIMATE INTERNAL FLUXES IN
MYCOBACTERIUM TUBERCULOSIS
Bhushan Bonde, Dany Beste, Nick Kruger, George Ratcliff, Andrzej Kierzek, Nathaniel
Hawkins, Jane Ward, Michael Beale, Johnjoe McFadden.
Microbial Sciences Division
In the recent years, estimating the steady state in-vivo reaction fluxes using 13C labeled
experiments has become a popular technique. The estimation of reaction fluxes in the central
metabolism of the slow growing M. tuberculosis (Mtb) will help in understanding the biology of
the persistent Mtb and facilitate the tuberculosis (TB) drug discovery.
In the present study, the central metabolic pathway (Glycolysis, pentose phosphate, TCA and
glyoxylate shunt) based model of TB was constructed from the previously developed genome
scale model of M. tuberculosis with the addition of the detailed atom transitions for each reaction.
Continuous slow growing Mtb cells were cultivated in the chemostat and 20% 13C uniformly
labeled glycerol was fed to obtain the isotopic labeling profile. The carbon positional labeling
pattern of the amino acids isolated from Mtb cell was estimated using Mass Spectroscopy. The
13C-FLUX and in-house developed (PyFlux) software tools were used for data handling and
simulations. Monte carlo and genetic algorithm method was used to obtain the estimated best fit
fluxes.
The estimated fluxes suggest that an alternative novel flux mode is present in TB which utilizes
the glyoxylate shunt and the anaplerotic pathway in Mtb.
42
Faculty of Health and Medical Sciences
No. 59
Title
Authors
Group
Abstract
No. 60
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
TEMPORAL AND LIGAND DEPENDENT SUB-CELLULAR LOCALIZATION OF THE
NUCLEAR RECEPTORS PXR, VDR, PPARα AND RXRα IN HUMAN LIVER AND
INTESTINAL CELL LINES
Ellen Wiedemann, Kate Plant, Nick Plant, G. Gordon Gibson and Peter Goldfarb
Biochemical Sciences Division; Pharmacology and Toxicology Theme; Centre for Toxicology
Nuclear receptors play an important role in signal transmission allowing coordination of
transcriptome responses to xenobiotic exposure as well as maintaining tissue homeostasis. The
intracellular localization of nuclear receptors is central to their function but for many of the
nuclear receptors the current data is equivocal regarding this localization. We have transiently
transfected human liver (Huh7) and intestinal (Caco-2) cells with GFP-coupled nuclear receptors
and quantified their intracellular localization in the presence or absence of exogenous ligand. In
both cell lines, VDR was located predominantly in the cytoplasm in the absence of exogenous
ligand, translocating into the nucleus following addition of ligand to the culture medium. In
contrast, without ligand only around 30% of the tagged PXR, PPARα and RXRα molecules were
found in the cytoplasm of the Huh7 cells, translocating almost entirely into the nucleus upon
ligand activation. In Caco-2 cells, the nuclear localization of PXR, PPARα and RXRα in the
absence of exogenous ligand was even more pronounced. The extent to which the localization of
tagged receptors expressed from transfected constructs truly reflects that of their endogenously
expressed counterparts remains to be determined. We are currently investigating how modulation
of transgene expression may affect the nuclear vs. cytoplasmic pool sizes and how this may impact
upon nuclear receptor activation of target genes.
THE ABILITY OF SHORT WAVELENGTH LIGHT TO SHIFT HUMAN CIRCADIAN
RHYTHMS
Katrin Ackermann, Tracey Sletten, Vikki Revell, Simon Archer, and Debra J. Skene
Sleep and Chronobiology
Environmental light is the most important cue responsible for the entrainment of the internal
circadian clock to the 24 h day. Short wavelength (blue) light is most effective at influencing both
acute and circadian responses to light. Ageing is accompanied by changes in the lens that reduce
the transmission of light, particularly short wavelengths, and may impair non-image forming light
responses in older individuals. The primary aim of the current study was to assess whether the
phase shifting response to short wavelength light was reduced in older individuals using the
plasma melatonin rhythms as a marker of the central circadian clock. In addition, we also wanted
to assess whether circadian rhythms in clock gene expression in blood exhibited comparable phase
shifts and could be used as an additional, reliable phase marker in future studies.
Eleven young (23.0 ± 2.9 years) and 15 older (65.8 ± 5.0 years) healthy males participated in two
laboratory sessions that included a 2 h intermittent monochromatic light pulse (~6x1013
photons/cm2/sec), individually timed to begin 8.5 h after their DLMO determined in a prior visit.
Subjects were exposed to short wavelength light (456 nm) in one session and medium wavelength
light (548 nm) in another. Frequent blood samples (30 – 60 min) were taken on the pre-stimulus
and post-stimulus nights for measurement of plasma melatonin and clock gene analysis. For clock
gene analysis, RNA was extracted from whole blood cells and reverse transcribed for real-time
PCR. Relative quantification of gene expression was performed for the clock gene PER3, using
GAPDH as the house-keeping gene.
Here we present preliminary data on PER3 expression in young subjects stimulated with short
wavelength blue light. This light was effective at phase advancing the plasma melatonin rhythm.
The PER3 data appear to reveal similar phase shifts, but more subjects need to be analysed before
any firm conclusions can be made.
Supported by Marie Curie RTN grant (MCRTN-CT-2004-512362) and the 6th Framework project
EUCLOCK (018741).
43
Faculty of Health and Medical Sciences
No. 61
Title
Authors
Group
Abstract
No. 62
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
DECREASE OF D2 RECEPTOR BINDING BUT INCREASE IN D2 STIMULATED G
PROTEIN ACTIVATION AND DOPAMINE TRANSPORTER BINDING IN BRAINS OF
MICE TREATED WITH A CHRONIC ESCALATING DOSE “BINGE” COCAINE
ADMINISTRATION PARADIGM
A. Bailey, J.H. Yoo, T. McGee, I. Kitchen
Division of Biochemistry; Pharmacology and Toxicology Theme
Understanding the neurobiology of the transition from initial drug use to excessive drug use has
been a challenge in the field of drug addiction. In this study, we examined the effect of chronic
“binge” escalating dose cocaine administration, which mimics human compulsive drug use, on
behavioural responses and the dopaminergic system of mice. Male C57BL/6J mice were injected
with saline or cocaine (3x15 mg/kg/day for 4 days, 3x20 mg/kg/day for 4 days, 3x25 mg/kg/day
for 4 days and 3x30 mg/kg/day for 2 days), three times daily at 1 h intervals in an escalating dose
paradigm for 14 days. Locomotor and stereotypy activity was measured and quantitative
autoradiographic mapping of D1 and D2 dopamine receptors and DAT as well as D2-stimulated
[35S]GTPγS binding was performed in the brains of mice treated with this escalating dose “binge”
cocaine administration paradigm. An initial sensitisation to the locomotor effects of cocaine
followed by a dose dependent increase in the duration of the locomotor effect of cocaine was
observed. Sensitisation to the stereotypy effect of cocaine and an increase in cocaine-induced
stereotypy score was observed with an increase in cocaine dose from 3x20 to 3x25 mg/kg/day.
There was a significant decrease in D2 dopamine receptor density, but an increase in D2 stimulated
G- protein activity and DAT density in the striatum of chronic “binge” escalating dose cocaine
treated mice. Our results document that chronic “binge” escalating dose cocaine treatment triggers
profound behavioural and neurochemical changes in the dopaminergic system which might
underlie the transition from drug use to compulsive drug use associated with addiction, which is a
process of escalation.
PERSISTENT REGION SPECIFIC UPREGULATION OF mGLuR5 BINDING IN
BRAINS OF MORPHINE WITHDRAWN MICE
A. Bailey, E. Martignoni, I. Kitchen
Division of Biochemistry; Pharmacology and Toxicology Theme
Evidence shows that the mGluR5 receptor plays an important role in opiate addiction. To
determine whether morphine or acute withdrawal from morphine alters mGluR5 density, we
carried out quantitative autoradiographic mapping of the mGluR5 receptor labelled with[3H]MPEP
in brains of mice treated with chronic morphine and of mice acutely withdrawn from morphine.
Male C57BL/6J mice were injected with saline or morphine (20 x 2 mg/kg/day on days 1 and 2,
40 x 2 mg/kg/day on days 3 and 4, 80 x 2 mg/kg/day on days 5 and 6 and 100 x 2 mg/kg/day for
days 7 and 8) at 8 h intervals. For the withdrawal group the mice received the same dose of
morphine for 7 days and then received an injection of saline on day 8. A significant increase in
[3H]MPEP binding was seen in the anterior olfactory nucleus, nucleus accumbens, olfactory
tubercle and motor cortex of morphine withdrawn and morphine-treated mice. An increase in
[3H]MPEP binding was observed in the caudate putamen, the diagonal band, CA1, CA2 and CA3,
dentate gyrus and basolateral amygdala of morphine treated, but not withdrawn mice. This is the
first study to show alterations in mGluR5 density after chronic morphine treatment which persists
after withdrawal in some regions.
44
Faculty of Health and Medical Sciences
No. 63
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
IS THERE A ROLE FOR C-REACTIVE PROTEIN IN ENDOTHELIAL CELL
ACTIVATION AND THE ATHEROGENIC PROCESS?
Minoo Shahidi, Nishad Panchal, Sarah Wright, Clementine Adams, Ernesto Oviedo-Orta
and Kikki Bodman-Smith
Microbial Sciences, Faculty of Health and Medical Sciences
Cardiovascular disease is an inflammatory disorder in which cells of the immune system and their
products play a major role. C-reactive protein (CRP) is an inflammatory, acute phase protein
with well documented roles as a powerful opsonin aiding host resistance to infection by a variety
of microorganisms. Recently CRP has been hailed as a potent cardiovascular disease risk factor
with reported effects on endothelial cell activation. Controversy has arisen over these reports as
contaminating endotoxin and the preservative sodium azide have been suggested to be responsible
for many of the effects described. The role of CRP in the development of atherosclerotic plaques,
therefore, remains unclear.
In prelimiary studies undertaken by our group, we have analysed the expression of a range of
endothelial cell activation markers (such as ICAM-1, PECAM-1, VCAM-1 and von Willebrand
factor) and the CRP receptor (FγRI) by the endothelial-like cell line EAhy 926 and on human
abdominal aortic endothelial cells in the presence of highly purified and exhaustively dialysed
CRP using FACs analyses. Our results, demonstrate that several previously reported activation
markers are not increased by the addition of highly purified CRP to in vitro cultures (such as
ICAM-1), but that expression of the putative receptor for CRP (FcγRI) is increased in these
cultures.
In conclusion, there is a need for focussed investigations into the effects of CRP on human arterial
endothelial cells from primary cultures and the effect of CRP on arterial neo-intima formation in
more physiologically relevant tissues.
No. 64
Title
Authors
Group
Abstract
IMPACT OF PAINFUL DIABETIC PERIPHERAL NEUROPATHY ON SLEEP
ARCHITECTURE USING POLYSOMNOGRAPHY
M. Eriksson, L.Gribble, R. Gouni, D. Kerr, D.V. Coppini, J. Boyle
Division of Biochemical Sciences: Diabetes and Endocrinology Theme
INTRODUCTION: Up to approximately 60 % of all diabetes patients develop neuropathy during
the course of their illness, and 30% of these will also experience varying degrees of neuropathic
pain, or so called painful diabetic peripheral neuropathy (DPN). Diabetic neuropathic pain is
typically more severe at night, and depending on its quality and severity, is likely to have some
impact on patients’ sleep, leading to both physical and psychological complications.
METHOD: Sleep architecture and pain interference for 27 (M = 15, F = 12, mean age of 62.8, ±
8.9) diabetic patients with painful peripheral neuropathy was studied. Overnight sleep was
measured between 23.00h to 07.00h using polysomnography (PSG) and subjective sleep was
assessed using sleep diaries. Pain severity and interference was measured by using the short form
brief pain inventory (BPI).
RESULTS: The BPI showed that pain had most impact on sleep and there was a correlation
between years since neuropathy diagnosis and pain interference on sleep (p < 0.05). 85% of
patients reported that their pain interfered with their sleep, with 31% having substantial
interference (defined as BPI score of ≥ 5). Increased pain interference correlated with increased
duration of stage 1 (r = 0.74, p < 0.01) and increased PSG number of awakenings (NAW) (r =
0.48, p = 0.017). In addition, pain interference on sleep correlated significantly with subjective
quality of sleep (sQOS) (r = 0.47, p < 0.05). All results are based on partial correlations for both
age and gender.
CONCLUSION: These preliminary data provide objective evidence that DPN interferes with
PSG measures of sleep. Higher pain interference is associated with increased NAW and duration
of stage 1 sleep, and reduced quality of sleep suggesting that DPN is associated with fragmented
and lighter sleep.
45
Faculty of Health and Medical Sciences
No. 65
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
ENCOUNTERING INFERTILITY: HOW RELIGIOUS AND SPIRITUAL BELIEFS
AFFECT WOMEN’S CHALLENGE TO ACCEPT SELF AS INFERTILE
Robab Latifnejad Roudsari, Helen T. Allan, Pam A. Smith
Division of Health & Social Care
Awareness of inability to conceive is an emotional crisis and like a disaster for the majority of
infertile women. This study explored how infertile women’s religious and spiritual beliefs affected
their confrontation with infertility. The design was a feminist grounded theory study on 40 infertile
women affiliated to different denominations of Christianity and Islam who were interviewed in
one Iranian and two UK fertility clinics. Data were collected through semi structured in-depth
interviews and analyzed using grounded theory.
The emerged categories embraced abrupt and subsequent appraising of infertility and challenging
for acceptance which were encompassed in the core category of relying on a higher being. Abrupt
appraising was presented as disbelief, uncertainty, and questioning. Subsequent appraising was
associated with more searching and probing to find out the cause of the illness and reappraising
the meaning of infertility. Challenging for acceptance was demonstrated as being in limbo, feeling
of difference and trying to accept self as infertile. We argue that religious participants using a
religious/spiritual meaning-making framework tried to reappraise their illness spiritually and
trusting a higher power went through various stages which made them capable to encounter
infertility peacefully.
No. 66
Title
Authors
Group
Abstract
CATION RECOGNITION BY A PARTIALLY SUBSTITUTED LOWER RIM
CALIX[4]ARENE
Tomasz S. Pawłowski, and Angela F. Danil de Namor
Division of Chemical Sciences; Materials and Nanosciences Theme; Thermochemistry lab
Calixarene chemistry is a relatively new field [1]. The intensive interest this kind of macrocycles
results from their versatile behaviour, the possibility of upper and lower rim functionalization and
their wide range of applications [2, 3]. Calixarenes and their different derivatives have shown
interesting complexing properties with ionic species [4, 5].
O
OH
S
N
2
The complexation ability of a partially substituted lower rim of
calix[4]arene (5,11,17,23-tetra-tert-butyl[25,27-bis(diethylthiocarbamoyl)oxy]calix[4]arene) (Fig. 1.) for monovalent (alkali
and Ag+) and bivalent (alkaline earth and heavy-metal) cations has
been investigated through 1H NMR, conductometry, potentiometry
and calorimetry in various solvents (acetonitrile, MeCN, dimethyl
sulfoxide, DMSO and N,N-dimethylformamide, DMF). 1H NMR
studies in CD3CN, d7-DMF and d6-DMSO show that in these
solvents ligand possesses high selectivity for mercury (Hg2+) and
silver (Ag+).
Fig. 1. 5,11,17,23-tetra-tert-butyl[25,27-bis(diethyl-thiocarbamoyl)oxy]calix[4]arene.
Acknowledgment. The authors thank the Polish Ministry of Science and Higher Education for the financial
support provided under Contract Nr 14/MOB/2007/0.
[1] Gutsche, C. D.; Muthukrishnan, R. J. Org. Chem. 1978, 43, 4905.
[2] Gutsche, C. D. Calixarenes. Monographs in Supramolecular Chemistry; Stoddart, J. F., Ed.; Royal
Society of Chemistry, 1989.
[3] Calixarenes. A versatile Class of Macrocyclic Compounds; Vicens, J., Böhmer, V., Eds.; Kluwer Acadeic
Publishers: Dordrecht, The Netherlands, 1991.
[4] Dhawan, B. D.; Chen, S. I.; Gutsche, C. D. Makromol. Chem. 1987, 188, 921.
[5] Danil de Namor, A. F.; Cleverley, R. M. and Zapata-Ormachea, M. L. Chem. Rev. 1998, 98, 7, 2495.
46
Faculty of Health and Medical Sciences
No. 67
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
SERUM INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-1 (IGFBP-1): AN
IMPROVEMENT OVER HOMA AND QUICKI IN THE ASSESSMENT OF INSULIN
SENSITIVITY SCREENING FOR NON-DIABETIC SUBJECTS
A. Borai*, C. Livingstone†, H. Zarif‡, G. Ferns*
*Centre for Clinical Science & Measurement, FHMS, University of Surrey
†Royal Surrey County Hospital, Dept of Clinical Biochemistry.
‡
King Khalid National Guard Hospital, Saudi Arabia, Jeddah.
Objective: To compare fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) and
indices of insulin sensitivity with the standard frequently-sampled intravenous glucose tolerance
test (FSIGT) and to evaluate its reproducibility.
Research design and methods: Insulin sensitivity was assessed by FSIGT, IGFBP-1,
homeostasis model assessment 2 (HOMA2-IR), quantitative insulin check index (QUICKI) and
fasting plasma insulin (FPI) in 52 subjects across a range of glucose tolerances: 22 normal glucose
tolerance (NGT), 9 impaired fasting glucose (IFG), 10 impaired glucose tolerance (IGT) and 11
subjects with type 2 diabetes.
Results: In 22 subjects with normal glucose tolerance, Si correlated more strongly with IGFBP-1
(r = 0.78) than HOMA2-IR (r = - 0.56), QUICKI (r = 0.61) or FPI (r = -0.56). The intra-individual
reproducibility for IGFBP-1 (%CV) was 20.9%, 29.5%, 33.1% and 48.0% in subjects with NGT,
IFG, IGT, and type 2 diabetes respectively. IGFBP-1 measured four times in the fasting state at 5
minute intervals yielded CVs for the respective categories of 8.2%, 16.1%, 29.2% and 13.8%.
Conclusions: Fasting serum IGFBP-1 concentration correlated well with other surrogate measures
of insulin sensitivity and it could be used as a potent and simple biomarker for epidemiological
screening of insulin sensitivity in subjects with normal glucose tolerance.
No. 68
Title
Authors
Group
Abstract
A COMPARATIVE STUDY OF INSULIN RESISTANCE BETWEEN SAUDI AND
CAUCASIAN POPULATIONS ACROSS A RANGE OF GLYCAEMIC CATEGORIES
USING IGFBP-1 AND OTHER INDICES
A. Borai*, C. Livingstone†, H. Zarif ‡,S. Mehta†, G. Ferns*
*Centre for Clinical Science & Measurement, FHMS, University of Surrey
†Royal Surrey County Hospital, Dept of Clinical Biochemistry
‡
King Khalid National Guard Hospital, Department of Pathology, Saudi Arabia, Jeddah
Objective: To compare insulin sensitivity between Saudi and Caucasian populations in subjects
across a range of glucose tolerance using a variety of indices.
Methods and materials: Subjects with normal glucose tolerance (NGT; n = 24), impaired fasting
glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 12), type 2 diabetes (DM; n = 13 )
were recruited who were distributed evenly between two populations, Saudi ( n = 33) and
Caucasian (n = 28). Insulin sensitivity was assessed using FSIVGTT and other simple indices
techniques.
Results: In NGT subjects, fasting IGFBP-1, 2hr IGFBP-1, insulin sensitivity (Si), Dia BP and
HbA1c were significantly different between the two populations (p < 0.004, p < 0.05, p < 0.01, p <
0.001 and p <0.01 respectively) indicating greater insulin resistance in the Saudi subjects. Across a
combined glucose tolerance categories, type 2 diabetes was significantly different with NGT only
in QUICKI, ISI-gly and Belfiore index (p<0.05, p<0.05 and p<0.001 respectively).
Conclusions: Saudi NGT subjects appear to be more insulin resistant than Caucasian NGT
subjects. Our data indicate that IGFBP-1 can be used as a simple marker to estimate insulin
resistance in subjects with NGT in different populations. Levels of insulin, IGFBP-1 and most of
other simple fasting derived indices must be interpreted carefully in subjects with type 2 diabetes.
47
Faculty of Health and Medical Sciences
No. 69
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
EFFECT OF PARTICLE SIZE ON THE MOBILISATION AND ACCUMULATION OF
HEAVY METALS IN STORMWATER DRAINAGE SEDIMENTS WITHIN A WETLAND
DRAINAGE SYSTEM OF THE LONDON ORBITAL (M25) MOTORWAY
A Patel, J O’Reilly, N I Ward
1
ICP-MS Facility, Chemical Sciences, Faculty of Health and Medical Sciences, University of
Surrey, Guildford, Surrey, GU2 7XH, UK
The London Orbital (M25) motorway has the highest traffic densities and potential traffic flow
problems of any motorway in the United Kingdom. Several motorway stormwater drainage
systems have been studied since the 1980s in terms of the chemical (heavy metals, cations/anions
and polycyclic aromatic hydrocarbons) levels in stormwaters, pond and drainage sediments, and
wetland pond vegetation [1]. In 2008, it is proposed that the junction 5 to 6 section of the M25 is
to be widened to four lanes each direction with an associated increase in the traffic volume,
especially heavy goods vehicles. An evaluation was made in the winter 2007 to assess the
chemical loading of heavy metals as a function of particle size in drainage sediments of a wetland
stormwater pond system. The mobilisation and accumulation of heavy metals (Cd, Cu, Zn, Mn,
Sb, V and Cr) is strongly influenced by storm events, stormwater flows and residence times,
especially in the silt trap, balancing pond wetland and outflow pond. Sediment samples were
separated into particle sizes ranging from <50 to >200 µm. Heavy metals levels for specific
particle sizes were significantly influenced by the sampling location (functional influence of the
drainage system), depth profile and influence of storm events.
[1] Hares RJ, Ward NI, (2004) Sediment accumulation in newly constructed vegetative treatment
facilities along a new major road. Sci Tot Environ 334-335, 473-79.
Supported by Marie Curie RTN grant (MCRTN-CT-2004-512362) and the 6th Framework project
EUCLOCK (018741).
No. 70
Title
Authors
Group
Abstract
THE USE OF HIGH DENSITY MICROARRAYS TO INVESTIGATE SEQUENCES
DIFFERENCES BETWEEN TWO CLOSELY RELATED STREPTOMYCES SPECIES
Lewis, R.A., Allenby N.E.E. and Smith, C.P.
Microbial Sciences
Recently the Surrey Functional Genomics Laboratory (SFGL), in collaboration with Oxford Gene
Technologies (OGT), have developed an ink-jet in situ synthesized (IJISS) high density
microarray for Streptomyces coelicolor. Each array comprises 105K unique 60bp probes spaced
every 135bp covering coding, and non-coding, regions. Here we report the use of such a
microarray in a comparative genome hybridiszation (CGH) experiment, and the identification of
sequence differences between NRPS genes(CDAPSI) in the calcium dependant antibiotic (CDA)
biosynthetic gene clusters in the evolutionary closely related species S. coelicolor and S. lividans.
The results indicate that the adenylation domain of Module 4 of the S. lividans CDAPSI gene
possesses a mosaic/hybrid/ recombinant sequence, with respect to the S. coelicolor sequence. In
addition to providing a fascinating insight into the evolutionary history of CDAPSI these results
demonstrate the power of high density microarrays to discriminate between very similar
sequences.
48
Faculty of Health and Medical Sciences
No. 71
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
StropE, THE STREPTOMYCES OPERON PREDICTION SERVER
Laing E, Verlade G, Smith CP and Hubbard SJ
Division of Microbial Sciences; Systems Biology Theme
Before complete networks can be constructed for systems biology level studies it is necessary to
understand all the components of that network. Transcriptional regulation networks are comprised
of hierarchies of regulation complexity, which, given a certain stimulus, are invoked by:
Stimulon → Regulon → Operon → Gene/Chromosome topology. Thus, for the construction of a
complete transcriptional regulation network each level of the hierarchy needs to be considered. In
this work it is the operon level that is being investigated.
We have previously described how an operon can be predicted and what information
(function/regulation) that the structure of the unit carries (Laing et al, 2006, 2007, 2008 and
manuscript in preparation). However, the dynamicity of operons, how their regulation patterns
change under certain conditions, is a parameter that as yet has been difficult to explore given the
availability of public Streptomyces microarray experiments.
The Streptomyces operon prediction server, StropE, is the first web-tool (for any organism) that
allows the viewing of predicted/known operons and their expression in terms of polarity (Laing et
al, 2006) and their respective gene neighbourhood utilizing selected microarray experiments, using
either publicly available (pre-loaded or loaded from StreptoBASE,www.streptobase.org) or the
users own data (private). Here, the utility of StropE and the information that is available through
this site (strep-microarray.sbs.surrey.ac.uk/stropE.html) is presented.
References:
Laing E, Mersinias V, Smith CP, Hubbard SJ. In preparation.
Laing E, Sidhu K, Hubbard SJ. BMC Genomics 2008 9(1):79.
Laing E. Phd thesis, University of Manchester 2007.
Laing E, Mersinias V, Smith CP, Hubbard SJ. Genome Biology 2006 7(6):R46.
No. 72
Title
Authors
Group
Abstract
ISOLATION OF ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORY
PEPTIDES FROM ATLANTIC MACKEREL (SCOMBER SCOMBRUS)
Chitundu Kasase and Nazlin K Howell
Division of Nutritional Sciences
Atlantic Mackerel (Scomber scombrus) fish protein was hydrolyzed with pepsin and pancreatine
and further fractionated into two fractions (3-5 kDa and 2 kDa) using membrane ultrafiltration.
Angiotensin I converting enzyme (ACE) inhibitory activities of the fractionated hydrolysates were
investigated, and the fraction that exhibited the highest ACE inhibitory activity was further
purified using gel filtration chromatographic method. The activity of ACE in the presence of an
inhibitor (protein fractions) was measured through the hydrolysis of the substrate hippurylhistidyl-leucine (HHL) by ACE to give hippuric acid (HA) and the HA determined by a HPLC
method. Under these assay conditions, calibration curve of HA showed linearity over the
concentration range of 0.4 – 1.8 μg (R2 = 0.9707). The recovery of HA was 96.0% in the
concentration range 0.2 – 1μM. The ACE inhibitory activity of the 3-5 kDa, 2kDa fractions and
captopril (control) determined by the validated HPLC method were found to be 18.8, 68.1 and
83.1% respectively. When the MFPH 2kDa was further fractionated by gel filtration, the fraction
with the highest ACE activity gave an IC50 of 3.15 mg/ml compared to that of captopril (0.014
μM). The gel filtration peptide fraction is being further purified by chromatographic techniques to
identify the most potent ACE inhibitory fraction by LC-MS.
49
Faculty of Health and Medical Sciences
No. 73
Title
Authors
Group
Abstract
No. 74
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
INTERACTION OF BOG BILBERRY EXTRACT WITH WHEY PROTEINS
Nan Zheng and Nazlin K Howell
Division of Nutritional Sciences
Bog bilberry (Vaccinium uliginosum) grows abundantly in the Daxinganling area, North East
China, and contains a large concentration of anthocyanins (350 mg/100 g). Anthocyanins are
reported to have a beneficial effect on health, including improved vision and reduction in the risk
of cancer and cardiovascular diseases. The objective of this study was to determine the
composition of a commercial bog bilberry extract and to investigate the effect of this extract on
proteins that may be present in food products. The interaction of 2% (w/v) bog bilberry extract
with 15% (w/v) whey proteins in distilled water pH 7, was investigated by differential scanning
calorimetry (DSC) and small and large deformation rheology. The addition of bog bilberry extract
decreased the thermal stability of whey proteins as indicated by a lower denaturation temperature
and enthalpy by DSC. Gelation properties of whey proteins increased in the presence of bog
bilberry extract using large deformation rheology. In addition the G' and G" (viscous and elastic
modulus) values of bog bilberry extract treated whey proteins was also higher, confirming an
increase in gel strength and a more extensive cross-linked gel network than with whey protein
alone. Bog bilberry can be used to enhance the organoleptic and nutritional quality of food
products.
L-GLUTAMATE-INDUCED HT22 CELL DEATH DOES NOT INVOLVE CELL CYCLE
ARREST
Mohammad Hawat, Codou Mbow, George E.N. Kass.
Biochemical Sciences Division; Pharmacology and Toxicology Theme; Centre for Toxicology
Acute cerebral ischemic injury results in increased L-glutamate release that can cause cell death
via L-glutamate receptor- and non-receptor-mediated mechanisms. We have recently shown that
L-glutamate induces a caspase-independent form of apoptosis that is dependent on calcium and
calpains. Recently, the activation and re-expression of cell cycle has been observed as a common
mechanism leading to neuronal loss in the brain of patients affected by neurodegenerative
disorder. Also many studies find that cell cycle activation is companied with DNA damage. In
contrast, many inducers of apoptosis cause cell cycle arrest. In the present study, we investigated
the effect of glutamate on the cell cycle in HT22 hippocampal neurons.
Cell cycle in HT22 cell line was investigated by flow cytometric analysis of propidium iodide (PI)
staining and bromodeoxyuridine (BrdU) incorporation. The results showed that the inducer of
apoptosis staurosporine caused an increase in the cell number in G2, and ultimately caused G2/M
phase arrest in HT22 cells. In contrast, treatment with L-glutamate at 3 and 5 mM did not affect
the cell cycle in HT22. These findings led to conclude that glutamate-induced death of HT22
cells does not involve cell cycle arrest.
Contact: [email protected]
50
Faculty of Health and Medical Sciences
No. 75
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
THE EFFECT OF RIMONABANT ON RESTING ENERGY EXPENDITURE, INSULIN
SENSITIVITY AND BODY COMPOSITION
Ivana Sarac, Katharine Backhouse, Fariba Shojaee-Moradie, Denise Robertson, Mike
Stolinski, Margot Umpleby
Postgraduate Medical School; Diabetes, Obesity and Metabolism Theme
Aim: To investigate in obese subjects the direct (weight-loss independent) metabolic effects of an
endocannabinoid CB1 blocker, Rimonabant.
Methodology: In an ongoing clinical trial 32 obese (BMI 30-35) Caucasian post-menopausal
women, aged 50-65 are being randomised into 2 groups. Following a 4 week run-in-period for
both groups, group 1 (n=16) receive rimonabant (20mg/d) for 13 weeks with energy intake
matched for their measured energy expenditure. Group 2 (n=16) receive dietary intervention for 13
weeks to achieve the same weight loss as group 1. The following are measured at baseline and
after 12 weeks of the interventions: body weight, waist circumference, resting energy expenditure
(by indirect calorimetry); insulin sensitivity (by euglycaemic hyperinsulinaemic clamp);
circulating levels of leptin and adiponectin.
Results: Preliminary results from the first 4 subjects on Rimonabant treatment to complete the
trial show there was no statistical difference in total energy intake before and during the treatment
(1857±220 vs. 1917±200 Kcal/kg/day, p=0.125) (mean±SD). Body weight loss was 3.1±1.0kg
(3.5±1.1% of baseline body weight) (p=0.009), accompanied by 5.2±2.4% decrease in waist
circumference (p=0.059) and 33.5±10.3 % improvement in insulin sensitivity (p=0.039). There
was no significant change in resting energy expenditure (16.58±1.13 vs. 16.95±0.46 Kcal/kg).
Leptin levels decreased by 14.2±5.2% (p<0.001) and adiponectin levels increased by 12.2±18.49%
(NS).
Conclusion: Rimonabant treatment for 12 weeks (without energy intake reduction and change in
resting energy expenditure) led to a reduction in body weight and waist circumference and an
improvement in insulin sensitivity, which might translate to a lowered risk for cardiovascular
disease and diabetes in obese subjects.
No. 76
Title
Authors
Group
Abstract
CONSECUTION TOWARDS PROTEOMICS OF NON-ALCOHOLIC FATTY LIVER
DISEASE
J. Bernadette Moore, Gemma Shay and Waqar Azim
Nutritional Sciences Division
First described less than 30 years ago, non-alcoholic fatty liver disease (NAFLD) is now the most
common reason for referral to hepatology clinics. The hepatic consequence of obesity and the
metabolic syndrome, worldwide NAFLD incidence has dramatically increased in concert with
obesity and prevalence is now estimated at 20-30% of the UK population. A disease spectrum,
NAFLD progresses from the relatively benign steatosis to non-alcoholic steatohepatitis (NASH)
which can lead to fibrosis, cirrhosis and end stage liver disease. Identifying and monitoring the
25% of NAFLD patients that will develop progressive NASH is a critical, clinical challenge
because liver biopsy, the diagnostic gold standard, is associated with significant morbidities and
mortality. We aim to use proteomics as a tool to both identify clinical biomarkers of disease
progression in plasma from NAFLD patients and to characterize mechanisms of progression using
in vitro and in vivo models. Isobaric tags and multidimensional protein separation strategies will
be used upstream of LC-MS/MS to quantitatively identify protein changes between NAFLD
patient and treatment groups. An in vitro model of NASH, the palmitic acid treatment of HuH7
human hepatocytes, is being used to optimize proteomic methodologies prior to the use of patient
samples. While it is established that high doses of palmitate causes lipid accumulation and
apoptosis in hepatocytes we are interested in identifying initial protein changes in HuH7 cells prior
to frank apoptosis. We will present initial data characterizing the dose response to palmitate
treatment of HuH7 cells and discuss our approach to analyzing the plasma proteomes of NAFLD
patients.
51
Faculty of Health and Medical Sciences
No. 77
Title
Authors
Group
Abstract
No. 78
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
A NOVEL CLOCK HAPLOTYPE IS ASSOCIATED WITH DIURNAL PREFERENCE IN
EUROPEANS
Brian E Cade, Simon N Archer, Krishna Veeramah, Mark G Thomas, and Malcolm von
Schantz
Sleep and Chronobiology Theme, Faculty of Health and Medical Sciences
CLOCK 3111 (rs1801260 C) has been associated with diurnal preference (DP) in some
populations, though not in others, possibly due to age, population differences in linkage
disequilibrium (LD) between rs1801260 and a causative factor, or environmental effects. This
study examines these possibilities using HapMap European (CEU) and East Asian (JPT+CHB)
data alongside a gene-wide association study of DP using a UK sample of 80 intermediate (INT),
extreme eveningness (EVE) and morningness (MORN) individuals. CLOCK has robust LD within
HapMap across the entire gene. HapMap haplotypes with rs1801260 C have highly similar LD in
all populations. The most common 19-SNP EVE haplotype (18.1% EVE, 9.4% MORN) is
independent of rs1801260 C. A unique 6-SNP subset haplotype is significantly associated with DP
(INT+MORN+EVE, QTL Beta=-8.825, p=0.003), and is specific to younger participants (<40yo
p=0.004, 40+yo p=0.953). Interestingly, 53.8% of INT individuals carry the haplotype along with
rs2070062 G (a SNP in complete LD with rs1801260), compared to EVE 12.7% and MORN 7.5%
frequencies. This suggests that the haplotype and rs1801260 C combined may be important in the
maintenance of normal DP in this UK population. This haplotype is consistent with a single
HapMap CEU haplotype (13% of CEU), which in turn has one difference to the most common
JPT+CHB haplotype (49%) in 162 SNPs. CLOCK is a possible candidate for balancing selection
based on high Tajima's D values and supported by a genome-wide screening (CEU rank = 0.997).
A CLAY MINERAL EARTH AS POTENTIAL SCAVENGERS OF ORGANIC AND
INORGANIC AQUEOUS POLLUTANTS
Uday F. Al-Karam, Amar H. Al-Dujaili, Angela F. Danil de Namor1, Adel O. Sharif2
1. Division of Chemical Sciences; Materials and Nanosciences Theme; Thermochemistry lab
2. Center for Osmosis Research & Application, Chemical & Process Engineering
The presence of organic and heavy metals in water has been a major concern for many years
because of their toxicity towards aquatic life, human beings and the environment. The rapidly
deteriorating water quality in many of the Iraqi water resources is a serious problem that threatens
to accentuate rapidly and could be irrevocably damaging unless drastic and effective measures are
expeditiously instituted. Because of the extreme stresses to which the water resources of Iraq have
been subjected, (especially in the last three decades) water, whether for domestic, industrial or
agricultural use, is heavily polluted by organic and heavy metal pollutants.
Several processes have been used and developed over the years to remove organic and metal
cations from water: chemical precipitation[1], solvent extraction[2], membrane processes, etc[3].
Due to the high cost of these methods, naturally occurring materials have been explored. Clays are
widely applied in many fields of Science and Technology due to their local availability, technical
feasibility and cost effectiveness.
The aim of this work is to study the feasibility of using a naturally occurring clay mineral for the
removal of phenol and lead from water. A mineralogical and physicochemical characterization of
this material by different techniques (X-ray Diffraction and X-ray Florescence Spectrometry) was
carried out. Batch equilibrium experiments demonstrated the ability of this material for fast
removal of these pollutants. Factors such as pH, temperature on the extraction process were
investigated.
Acknowledgement: The authors thank the Republic of Iraq, Ministry of Higher Education for financial
support
References:
1- D.Bhattacharyya, D.A. Jumanwan, G. Sun, K. Schwitzebel, AIChE Symposium Series, Water-1980,
77(209), 1981,31.
2- G.S.Logsdop, J.M. Symons, J. Am Water Work Assoc. 1973, 65 (8), 544.
3- S.L Daniels, AIChE Symposium Series Water- 1975, 71 (151), 1975, 265.
52
Faculty of Health and Medical Sciences
No. 79
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
VALIDATION OF PULSE WAVE VELOCITY AS A MARKER OF ARTERIAL
STIFFNESS
Laura Tripkovic, Dr. Kathryn Hart, Dr. John Lodge
Division of Nutritional Sciences
Arterial stiffness is an indication of structural and functional changes to the endothelium caused by
factors such as aging or hypertension-related damage. Pulse Wave Velocity (PWV), is a noninvasive, highly-reproducible technique used to assess the degree of large artery stiffness, and has
been proven to be an independent marker of CVD risk. The aim of this study is to determine the
intra-individual variability and establish predictive markers of PWV within a healthy population
group to inform its use in research and clinical practice.
PWV was performed on 22 males, aged 21-56yrs. All participants were normotensive, with BMI
18.7-33.5kg/m2. Prior to attending, all participants consumed a standard meal the previous night
and then fasted for 12 hours. Following a standardised operating procedure, PWV measurements
(peripheral (pPWV) and central (cPWV)) were recorded in duplicate within one session for each
participant.
Intra-individual variation for pPWV and cPWV, expressed as Coefficients of Variation, were
found to be 8.4% and 5.9% respectively. Only age was predictive for pPWV, accounting for 32%
of the variance (P=0.002), whilst a model incorporating age, diastolic and systolic blood pressure
accounted for 72% of the variance in cPWV (P<0.001). Younger volunteers (21-30yrs) were
found to have significantly lower pPWV (7.0±1.31m/s, p>0.05) and cPWV (5.7±0.74m/s,
p>0.001) recordings than the older males (31-56yrs) of 8.8±1.14m/s (pPWV) and 8.5±2.19m/s
(cPWV).
The results show relatively low intra-individual variation and an apparent relationship between
blood pressure and cPWV, which supports current literature. This technique is being extensively
used within a variety of nutrition intervention studies to further investigate the potential
relationships with other validated markers of CVD risk. Ongoing research will evaluate possible
limiting factors that may affect PWV to establish its optimum use within the classical research
setting.
No. 80
Title
Authors
Group
Abstract
ChIP-ON-CHIP ANALYSIS OF TRANSCRIPTION FACTOR BINDING IN
STREPTOMYCES COELICOLOR: VALIDATION USING HSPR REPRESSOR
G. Bucca¹, E. Laing¹, V. Mersinias³, N. Allenby¹, D. Hurd², M. Harrison² and C.P.Smith¹
Microbial Sciences
High density intergenic arrays of the Streptomyces coelicolor genome have been designed in
collaboration with Oxford Gene Technology Ltd. These are in situ ink jet synthesized arrays which
comprise 22.000 60 mer oligos designed to maximally cover the intergenic regions (with an
average spacing of 110 bp). As a first step in array validation, we used antibodies against a well
studied transcriptional repressor controlling the transcription of the dnaK operon, Lon protease and
ClpB molecular chaperone genes. Chromatin immunoprecipitation was carried out with
S.coelicolor cultures which have been treated with formaldeyde in order to cross link the proteins
to their DNA targets. HspR-specific polyclonal antibodies have been added to the chromation and
after de-crosslinking, the bound DNA was labelled with Cy3-dCTP and cohybridized with Cy5dCTP labelled total chromation on the intergenic arrays. The results show a clear enrichment in
known HspR binding sites and reveal some putative previously unidentified targets.We have also
developed a more versatile Streptomyces coelicolor microarray, in which both the intergenic and
coding regions are covered (represented by 44.000 probes with an average distance between
probes of ca 195 bp). With these arrays we were able to repeat and extend our findings on genome
wide HspR binding and we were able to superimpose on the chIP-on-chip data the corresponding
expression data. The results show a nice correlation between HspR binding and corresponding
expression of the respective HspR targets and reveal stable RNA genes that are also putative HspR
targets.
53
Faculty of Health and Medical Sciences
No. 81
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
THE REMOVAL OF LEAD AND COPPER FROM AQUEOUS SOLUTION BY
GRANULAR ACTIVATED CARBON IN BATCH AND FIXED BED PROCEDURES
Jenan A. Al-Najar, Abbas H. Sulaymon, Angela F. Danil de Namor1, Adel O. Sharif2.
1
Thermochemistry Laboratory, Chemical Science (FHMS) , University of Surrey
2
Center for Osmoses Research & Application, Chemical and Process Engineering
Heavy metals are among the most toxic contaminants of surface and water. Since most heavy
metal compounds are non-degradable into nontoxic end products, these concentrations must be
reduced to acceptable levels before being discharged into the environment. Otherwise these could
e pose a serious threat to public health and/or affect the quality of potable water (1).
The effect of metals and their compounds on humans, animals and plants, are quite varied.
According to the World Health Organization and the International Programme on Chemical Safety
(2), (3) the most toxic metals are magnesium, iron, cobalt, nickel, copper, zinc, cadmium, mercury
and lead.
Adsorption of Pb(II) and Cu(II) onto granular activated carbon DARACO 20-40 mesh has been
investigated. From the batch experiments, adsorption isotherms were produced and the kinetics of
the adsorption process was assessed. It was found that this material removes Pb(II) more
efficiently than Cu(II). The adsorption data we fitted using both, the Langmuir and the Freundlich
isotherms. The kinetics of the adsorption process shows the effect of the contact time on the
uptake of metal ions. It was found that the adsorption for each element reaches a maximum after
300 min. The fixed bed method was used to determine the experimental breakthrough curve for
each element. The effect of flow rate, height of bed and initial metal concentration was
investigated.
Acknowledgement: The authors thank the Republic of Iraq, Ministry of High Education for
financial support
References:
1. Aslam, M.M., Hassan, I., Malik, M. and Matin, A., 2004, "Removal of copper from industrial
effluent by adsorption with economical variable material", Electronic J. of Environment,
Agriculture and Food Chemistry EJEAFChe, 3 (2), pp.658-664
2. WHO, 1984, World Health Organization, Geneva Guidelines for Drinking Water Quality, 1984
3. IPCS, 1988, International Programme on Chemical Safety Environmental Health Criteria World
Health Organization Geneva
No. 82
Title
Authors
Group
Abstract
SOCIAL DETERMINANTS IN THE CONTEXT OF SEEKING DIAGNOSIS OF
PROSTATE CANCER
Dr. Ali Taghipour, Dr. Vasso Vydelingum, Prof. Sara Faithfull
Division of Health & Social Care
Background and objective: Little is known about men’s social perspectives when they make a
decision for diagnosis of prostate cancer. This study was carried out to understand the social
determinant of prostate cancer in the process of seeking diagnosis.
Method: Using grounded theory with theoretical perspective of social constructionism, twelve
men who had experienced prostate cancer were interviewed face to face.
Results: The findings showed that seeking diagnosis in men with prostate cancer was complicated
by some social factors like reluctance to accept the label of prostate cancer, masculinity, genderrelated complications of the illness and as a result spoiled identity. These issues were logically
unrelated to the medical issues but had dramatic influence on the patients’ decision-making to
follow the diagnosis. However, receiving support from family especially wife and also trusted
family physicians helped men to make an appropriate decision for detection of the illness.
Conclusion: The findings of this study suggest that men’s perceptions on the social factors of the
illness had a significant influence on delay or acceleration in seeking diagnosis of prostate cancer.
54
Faculty of Health and Medical Sciences
No. 83
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
IMPACT OF PROSTATE CANCER EXPERIENCES ON MEN’S PERCEPTIONS FOR
EARLY DETECTION: A QUALITATIVE STUDY
Dr. Ali Taghipour, Dr. Vasso Vydelingum, Prof. Sara Faithfull
Division of Health & Social Care
Background: Illness period of prostate cancer does not begin when the man first comes into
contact with the physician, clinic, or hospital. There is a significant period of decision-making and
self-therapy between wellness and disease periods. Little is known of patients’ perception and
experiences about their illness and why they often delay in seeking help.
Method: Using GT, this study focused on Iranian men’s perceptions and experiences about the
detection of prostate cancer. Using a semi-structured face-to-face interview guide, twelve men
who had experienced prostate cancer were interviewed. Through the process of obtaining data, the
investigator jointly collected, coded, and analyzed the data. The selection of participants was
continued until data saturation.
Results: Findings of this study showed that the symptoms experienced and therapy consequences
considerably influenced the participants’ perceptions. The men felt that medical interventions
were focused on the biological aspects rather than psychosocial concerns of the illness. The
participant attempted to minimize the therapeutic side effects. However, they did not recommend
detection of the illness without a realistic understanding of post treatment complications.
Conclusion: By arguing that men’s experiences and perceptions should be considered in the
process of decision-making for any medical intervention.
No. 84
Title
Authors
Group
Abstract
ARSENIC SPECIATION IN WATER SAMPLES USING SOLID PHASE EXTRACTION –
LINK TO ARSENIC POISONING IN HUMANS
J. O'Reilly, M. Watts and N. I. Ward
Chemical Sciences
In recent years arsenic (As) has become a major concern in terms of its toxicological effects on
humans and the environment. Studies are needed to help identify and quantify the levels of As
that preside in the environment, particularly the more toxic As3+ species. Development of a fieldbased method utilising disposable Bond Elut SPE cartridges incorporating strong cation exchange
(SCX) and strong anion exchange (SAX) phases for the determination of As3+, As5+, DMA and
MMA has been employed for waters (well, river, tap and bottled). This methodology enables the
separation and preservation of As species in the field with subsequent elution and analysis in the
laboratory. Each fraction is analysed by ICP-MS for total As, with correction for the polyatomic
40
Ar35Cl+ and validation using CRM’s and inter-laboratory comparison data. Separation of As
using the cartridges was confirmed by RP-HPLC-ICP-MS.
The field-based method was employed on waters from various rural areas of Argentina (La Pampa,
Santiago del Estero and San Juan), where total As levels have been reported to be as high as 8000
µg/l (1). High levels of naturally occurring As in groundwater in Argentina have been further
affected through extensive mining of gold in areas such as San Juan.
In La Pampa As levels in well water are over 700 µg/l (WHO level for drinking water is 10 µg/l
As). Contaminated well waters provide a possible uptake of As into the local populace, potentially
leading to chronic As poisoning. Therefore studies have been carried out on human and animal
samples to establish a link between the natural As levels and the current state of health. Human
health in regions like La Pampa and Santiago del Estero have reported many cases of skin legions,
pigmentation changes, hyperkeratosis and various forms of cancer associated with the
consumption of this water.
55
Faculty of Health and Medical Sciences
No. 85
Title
Authors
Group
Abstract
No. 86
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
MEASUREMENT OF POSTPRANDIAL TRIGLYCERIDE KINETICS IN BOTH
ENDOGENOUS AND EXOGENOUS LIPOPROTEINS USING STABLE ISOTOPES
F. Sun, M. Stolinski, F. Shojaee-Moradie, M. Umpleby
Diabetes and Endocrinology, Postgraduate Medical School
Abnormally elevated postprandial triglycerides (TG) are a feature of metabolic syndrome and type
2 diabetes and are predictive of an increased risk of cardiovascular disease. The cause is poorly
understood due to the lack of selective and sensitive methods to accurately quantify the kinetics of
postprandial exogenous (chylomicrons) and endogenous (VLDL) triglyceride-rich lipoproteins. In
this study postprandial TG kinetics were measured in healthy subjects using a novel method to
separate exogenous and endogenous lipoproteins. Six healthy volunteers (2M,4F), age
36.8±3.9yr, BMI 24.4±1.1kg/m2 (mean±SEM) were studied on 2 occasions in random order 1]
after an overnight fast and 2] during a continuous feeding protocol with 6 liquid meals (486kcal,
11% carbohydrate, 88% fat) given every 2h. In both studies a bolus injection of [2H5]-glycerol was
administered to label TG. Sf>60 and Sf 20-60 lipoprotein fractions were separated by sequential
ultracentrifugation. Endogenous and exogenous particles were isolated using a novel
immunoaffinity method (Protein G coupled to three monoclonal antibodies specific for apoB1004G3, 5E11 and Bsol16) which allowed complete separation of apoB100 and apoB48 containing
lipoproteins. TG was extracted from the purified particles and glycerol enrichment measured by
gas chromatography mass spectrometry. TG fractional catabolic rate (FCR) was calculated using
a mathematical model of the exogenous and endogenous TG pathways. Plasma TG
concentrations were 0.88±0.11mmol/L in the fasted study and 1.47±0.20mmol/L in the fed study.
There were no differences in VLDL1 and VLDL2 TG FCR between the fasted and fed studies
(VLDL1, 43.8±15.3 vs 52.2±14.1 pools/day; VLDL2, 26.8±4.4 vs 20.4±2.1 pools/day). In the fed
study chylomicron TG FCR (48.0±18.5 pools/day) was not different from VLDL1 FCR but small
chylomicron TG FCR (12.7±1.9 pools/day) was significantly lower than VLDL2 FCR (p=0.022).
Feeding did not change the clearance rate of VLDL1 and VLDL2 in healthy subjects. Although
chylomicrons are cleared at the same rate as VLDL1 the clearance of small chylomicrons (the
same density as VLDL2) is lower than the clearance of VLDL2.
PSYCHOSOCIAL ASPECTS OF THE EARLY DETECTION OF PROSTATE CANCER
IN IRANIAN MEN
Dr. Ali Taghipour, Dr. Vasso Vydelingum, Prof. Sara Faithfull
Division of Health & Social Care
Background and objective: Despite significant progress in prostate cancer research over the last
two decades, screening of the disease has remained controversial. From a psychosocial
perspective, little is known of patients’ beliefs about their illness and why they often delay in
seeking diagnosis. The purpose of this qualitative study was to understand the psychosocial
aspects of the early detection of prostate cancer.
Method: This study used a grounded theory approach with the theoretical perspective of social
constructionism. A purposive sampling of twelve men from public and private sector hospitals
who had received therapy were interviewed face to face in Persian using a semi-structured
interview guide. Interviews were audiotaped, transcribed in full translated into English and then
analyzed.
Results: Findings of this study showed that the illness symptoms and therapy consequences
considerably influenced the participants’ perceptions. They chose hiding as a strategy for
symptoms management. Choosing this strategy may be related to embarrassment, normalization,
and minimization of the illness problems. The finding also showed that masculinity and doctorpatient relationship were the most important barriers for making decision, but family support and
trusted physicians were the major factors to facilitate the decision-making for the illness detection.
Conclusion: The findings recommended that the early detection of prostate cancer need a model
based on both biomedical and psychosocial aspects.
56
Faculty of Health and Medical Sciences
No. 87
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
REDUCED RISK OF SEVERE HYPOGLYCAEMIA IN TYPE 2 DIABETES AFTER
STARTING ON ANALOGUE COMPARED WITH HUMAN INSULIN: A COHORT
STUDY USING THE UK GENERAL PRACTICE RESEARCH DATABASE
Annie Hutchison, David Russell-Jones, Victoria Hordern, Corinne S de Vries
Postgraduate Medical School
Recent years have seen rapidly increasing use of analogue insulins, the withdrawal of many
animal insulins and greater emphasis on maintaining near-normal glycaemia. Given these
changes, clinical differences between human and analogue insulin in the risk of severe
hypoglycaemic events remain of clinical interest.
The UK General Practice Research Database was used to compare the risk of serious
hypoglycaemic events requiring emergency medical intervention (e.g. diabetic coma) in new
users of human or analogue insulin among adults with Type 2 diabetes. Survival analysis
using Cox proportional hazards with recurrent events was used to derive hazard ratios by
insulin type.
11,813 "new" insulin users were identified, of whom 1,005 had one or more serious
hypoglycaemic events. We found an adjusted 28% (HR 0.72; [CI95] 0.62-0.84, p<0.001)
reduction in the risk of serious hypoglycaemic events in users of analogue insulin compared
with users of human insulin. Matched analysis using a propensity score showed a reduction
of 26% (HR 0.74; CI95 0.60-0.91, p<0.001) for analogue insulin users compared with users
of human insulin. Sensitivity analyses did not materially change these risk estimates.
This observational study based on general practice data suggests there are clinical benefits
associated with the choice of analogue over human insulins for patients with Type 2 diabetes
No. 88
Title
Authors
Group
Abstract
IDENTIFICATION OF A CIRCADIAN CLOCK IN ADIPOCYTES
Daniella Otway, Gary Frost, Jonathan Johnston
Biochemical Sciences: Sleep and Chronobiology Theme
Since the 1980s, obesity has become an increasing global problem. With our modern 24-hour
society, prevalence of obesity has been linked to disruption of the circadian clock, an internal
mechanism that drives daily rhythms of physiology. The molecular oscillator underlying these
rhythms has been discovered in most body tissues. Furthermore, recent studies strongly suggest a
role for clock gene involvement in adipose (fat tissue) biology, including metabolism. Many
adipose derived hormones (adipokines) are also rhythmic in the plasma. However, adipose tissue
is extremely heterogeneous and it is therefore unclear whether published rhythms represent an
endogenous clock within the key endocrine cells present within adipose tissue, namely the
adipocytes. Moreover, all studies to date have analysed tissue biopsies, which have been under the
control of multiple external neuronal and humoral signalling pathways. We have tested the
hypothesis that murine 3T3-L1 adipocyte cells possess a functional circadian clock. Firstly, we
characterised the differentiation of 3T3-L1 adipocytes from their precursor cell line, examining
molecular markers of the differentiation process, and studying lipid accumulation. Next, we
demonstrated the presence of clock gene expression in both pre-adipocytes and differentiated cells
using reverse transcriptase PCR. Serum pulse methodology was then used to induce rhythmic
clock gene expression in both pre- and post-differentiated adipocyte cell populations, followed by
quantitative real time PCR analysis of clock genes and adipokine expression. Medium was also
collected and assayed for leptin secretion. These data show, for the first time, that 3T3-L1 preadipocytes and adipocytes contain a circadian clock, and that leptin is rhythmically released from
adipocytes. This work will now be extended to assess whether the adipocyte molecular clock is
disrupted in human diabetic patients.
57
Faculty of Health and Medical Sciences
No. 89
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
EVALUATION OF “BLUE ENRICHED” LIGHT ON SLEEP AND ACTIVITY IN CARE
HOME RESIDENTS: METHODOLOGY
Peter L Morgan, Benita B Middleton, Debra J Skene
Sleep and Chronobiology
The light dark cycle is a major time cue (zeitgeber) that entrains human physiology to the 24 hour
day. Photic information is perceived by cells in the retina which transmit a signal that reaches cells
within the suprachiasmatic nuclei (SCN), the central circadian oscillator. The SCN generate
circadian rhythms in a number of biological parameters, such as melatonin and cortisol secretion.
Circadian phase shifting and suppression of melatonin synthesis has been shown to be most
sensitive to short wavelength blue light, approx. 460 nm.
With advancing age, alterations in the eye, the circadian system and the sleep-wake cycle occur
which can result in sleep problems and decreased daytime functioning. One approach to this issue
has been the use of bright white light therapy which has been shown to have some benefits for
sleep in the elderly.
The aim of the study is to assess the effectiveness of a novel lighting condition (‘blue-enriched’
white light) compared to a control dim white light, in improving sleep quality and daytime
alertness and performance in elderly people living in care homes. A 12 week randomised cross
over design will be carried out in 6 care homes in total, where the two light intervention periods
will last 4 weeks each, with a 4 week washout period after each “blue-enriched” light period. The
lights will be attached to wall and ceiling fittings in communal areas regularly used by residents.
Residents will participate by completing a range of tasks depending on their ability. Daytime
social interaction and napping, subjective sleepiness, mental state and depression will be
monitored in all residents. More able residents will wear light and activity monitors (Actiwatches)
to determine actigraphic sleep parameters and daytime activity in tandem with subjective sleep
diaries. Measures of daytime vigilance will also be taken in this group.
Funded by the Cross-Council New Dynamics of Ageing (NDA) initiative (Grant number RES339-25-0009)
No. 90
Title
Authors
Group
Abstract
PREPARATION AND EVALUATION OF NOVEL BIOCIDAL N-HALAMINE
MODIFIED SILICA GELS FOR STERILIZATION APPLICATIONS
Abd El-Shafey I Ahmeda, John N Haya, Michael E Bushellb, John N Wardellb and Gabriel
Cavallia
Chemical Sciencesa and Microbial Sciencesb, Faculty of Health and Medical Sciences
Novel modified silica gels as biocidal agents were prepared by reacting uramil with 2-Cyanofunctionalized silica gel and 3-(Isocyanato)propyl-functionalized silica gel, (200-400 mesh). The
resulting heterocyclic modified silica gels were halogenated (chlorinated, brominated and
iodinated). The structures of the biocidal N-halamine modified silica gels (NHMS) were studied
using FT-IR spectroscopy, solid 13CNMR spectroscopy and SEM. The biological activity of
NHMS against Gram-positive and Gram-negative was studied using an agar plate method and by
determining the effect of NHMS on bacterial viability. One of the chlorinated heterocyclic
modified silica gels succeeded in achieving a 3 log reduction in viability in 7 hours for E. coli and
similarly, a 4 log reduction in 7 hours for S. aureus. The iodinated derivatives showed a more
powerful biological activity than the brominated and the chlorinated forms. Stability of the
halogens attached to the heterocyclic ring on the silica was improved, and the number of halogen
ions per repeating unit increased compared with similar modified silicas available in the market.
Preparing NHMS with this particle size, 200-400 mesh, supports its use in water filters and other
sterilization purposes.
58
Faculty of Health and Medical Sciences
No. 91
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
DEVELOPMENT OF A METHOD TO MEASURE HIGH DENSITY LIPOPROTEIN
(HDL) KINETICS USING STABLE ISOTOPES
X.Li, M.Stolinski, M. Umpleby
Diabetes and Endocrinology / PGMS, University of Surrey
Apolipoprotein A-I (apoA-I), the main protein in HDL is secreted by the liver and intestine and
acquires lipids to form nascent preβ-HDL. After addition of lipids from peripheral tissues
spherical αHDL is formed. Current understanding of HDL kinetics is limited due to an inability to
measure the kinetics of preβ-HDL. Traditionally, HDL is separated by ultracentrifugation
(1.063<d<1.21g/ml), which can damage the integrity of HDL particles and lead to dissociation of
apoA-I. In addition, preβ-HDL cannot be recovered in this density range.
The aim of this study was to develop methods to determine the kinetics of apo-A1 in α-HDL and
preβ-HDL following isotopic labelling. A novel technique to isolate apoA-I from α-HDL and
preβ-HDL has been developed and optimised. Four healthy subjects were given a 9h infusion of
1-13C-leucine with hourly blood sampling. Plasma α-HDL and preβ-HDL were separated by
agarose gel electrophoresis. Lipoproteins were extracted from the bands and apo-A1 isolated by
SDS-PAGE. The isotopic enrichment of apoA-I was measured by Gas chromatography mass
spectrometry. Results indicate that α−HDL and preβ−HDL kinetics can be measured by this
methodology. Using this technique it may be possible to determine the mechanism of the decrease
in HDL cholesterol in type 2 diabetes and metabolic syndrome.
No. 92
Title
Authors
Group
Abstract
ROLE OF GABAB RECEPTOR ISOFORMS IN THE CONTROL OF HIPPOCAMPAL
ACTIVITY
Joshua David Foster, Ian Kitchen, Ying Chen
Pharmacology and Toxicology Theme, Division of Biochemical Sciences
Medial temporal lobe epilepsy is one of the most prevalent types of epilepsy and is characterised
by seizures originating from hippocampus. Seizures are proposed to result from an increase in
excitation or the loss of inhibition within the hippocampus. Gamma-aminobutyric acid (GABA)
and its receptors form the major inhibitory system in the central nervous system and are implicated
in the control of seizure activity. GABA activates the ionotropic (GABAA) and metabotropic
(GABAB) receptors, resulting in fast and slow synaptic inhibitions respectively. Reduction in the
GABAA receptor mediated inhibition induces seizures, whereas the activation and inhibition of
GABAB receptors has both anti- and pro-seizure activities. The GABAB receptor has two receptor
subtypes GABAB(1a, 2) and GABAB(1b, 2), which have been shown to be expressed at different
synaptic locations. No subtype specific pharmacological agents currently exist, however isoformselective knockout mice, GABAB1a -/- and GABAB1b -/-, have been generated.
We propose that the two GABAB receptor subtypes will have separate roles in the control of
seizure activity within the hippocampus. Distribution of the isoforms within mouse brain tissue
will be investigated using immunohistochemical staining for the GABAB receptor. Seizure activity
will be chemically induced in hippocampal slices from the GABAB1a -/- and GABAB1b -/- mice and
recorded using a multi-electrode electrophysiological technique. GABAB pharmacological agents
will be used to investigate the ability of the individual subunit to modulate hippocampal seizure
activity.
59
Faculty of Health and Medical Sciences
No. 93
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
RELIGION AND SPIRITUALITY AS MEDIATING FACTORS IN ADJUSTING
MARITAL RELATIONSHIPS IN INFERTILE WOMEN
Robab Latifnejad Roudsari, Helen T. Allan, Pam A. Smith
Division of Health & Social Care
Despite growing body of the literature regarding marital adjustment of infertile women, there is no
study to address the role of religious and spiritual beliefs in adjusting marital relationships in
infertile women. This study explored how religion and spirituality can be as mediating factors in
adjusting marital relationships in this population. For this reason a group of 40 infertile women
affiliated to different denominations of Christianity and Islam were interviewed. The design was a
feminist grounded theory study including semi structured in-depth interviews. Data were collected
in one Iranian and two UK fertility clinics and analyzed using grounded theory.
Religious infertile women tried by establishing a divine relationship and going through the
following phases to adjust their marital relationships: being optimistic and positive, having
supportive relationships, being grateful and appreciated for their marital life, offering spiritual
sympathy and adopting religious role models. These strategies aided them to be more
understanding, sympathetic and gentle to each other and maintain a family cohesion. We argue
that awareness of these approaches help health professionals to offer religious and spiritual coping
strategies to infertile women which can help adjusting their marital relationships.
No. 94
Title
Authors
Group
Abstract
INFERTILE WOMEN’S EXPECTATIONS FROM HEALTH PROFESSIONALS
CONCERNING THEIR SPIRITUAL NEEDS
Robab Latifnejad Roudsari, Helen T. Allan, Pam A. Smith
Division of Health & Social Care
Many patients would like their caregivers to discuss their spiritual beliefs. This study has explored
infertile women’s expectations from health professionals in the context of spiritual care. For this
purpose 30 volunteer infertile women affiliated to different denominations of Christianity and
Islam and also seven infertile women with no formal religion were interviewed. Participants were
recruited in one Iranian and two UK fertility clinics. Data were collected through in-depth
interviews and analyzed using grounded theory.
Findings showed that both religious and non-religious participants expected health professionals to
be honest, sincere, understanding and sympathetic. They criticized depersonalization and
approaching people like “numbers” and not human beings. Religious participants had extra
expectations like addressing their spirituality and undertaking religious rituals before the treatment
procedures. They believed that attending to religious and spiritual issues would be peaceful,
encouraging and not only make the experience satisfying and pleasant but also would have longterm impact on their psychological well-being. We argue that the multidisciplinary team who
approach infertile women should be attentive to all dimensions of the patients and treat them as a
whole person with all physical, social, emotional and spiritual needs.
60
Faculty of Health and Medical Sciences
No. 95
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
ENQUIRY BASED LEARNING - EDUCATIONAL TORNADOS WITHOUT THE
DAMAGE
Allison Wiseman, Jacqueline A England
Health and Social Care; Health Care Practice
Spiral curricula have long been seen as one of the best ways of developing knowledge, giving
students the opportunity to regularly revisiting topics to develop their knowledge and enhance
their understanding of subjects related to their professional role. An example of this would be the
basic anatomy and physiology required to understand human body processes that is then
developed to include the effect of the disease process and treatment regimes used. However, the
spiral is normally uni-dimensional. With a tornado effect the spiral takes on a three dimensional
form and can enhance the way students perceive new knowledge and process it to enhance their
learning.
This paper explores current theories of learning and contextualises the authors’ perceptions of
links between these and the ‘tornado effect’ that learning can have. It will demonstrate how the
learning experience, if truly meaningful, can be likened to a tornado effect on student nurses
knowledge and their ability to apply this knowledge to the practice of caring for their clients.
An associated benefit of this approach is the enhancement of key transferable skills, viewed as
essential in today’s’ health care, such as communication, team working, information literacy,
leadership, time management and evidence based practice.
Student evaluations relating to the development of enquiry based learning have been collected
from 3 consecutive cohorts of second year adult nursing students over a one year period. These
evaluations and the reported student perceptions are utilised to illustrate these theoretical concepts
and links to the practice situation.
Crabtree H 2003 Improving student learning using an enquiry based approach Extract of conference
proceedings from Education in a changing environment 17th- 18th September 2003
Lusardi M , Levangie P, Fein B 2002 A problem based learning approach to facilitate evidence based
practice in entry level health professional education Journal of Prosthetics and Orthotists 14, 2: 40-50
Palmer S 2002 Enquiry based learning can maximise the students potential Psychology learning and teaching
2, 2: 82-86
No. 96
Title
Authors
Group
Abstract
CALCINEURIN SLOWS CONDUCTION VELOCITY IN GUINEA PIG LEFT
VENTRICULAR PAPILLARY MUSCLE
Rita Jabr, Nicolas S Peters and Christopher H Fry
PGMS, Cardiovascular & Pharmacology and Toxicology Themes
Gap junction (GJ) conductance is one of the major determinants of conduction velocity (CV) in
the heart. An alteration in GJ phosphorylation state could modulate CV and may contribute to
ventricular arrhythmias. In ventricular hypertrophy and fibrillation, an increase in the activity of
Ca2+ /calmodulin dependent protein phosphatase 2B; calcineurin (CaN) has been documented. It is
unknown if CaN mediates ventricular arrhythmias induced by sustained elevation of intracellular
Ca2+ ([Ca2+]i). The aim of this study was to investigate the contribution of CaN to conduction
delay after a rise of [Ca2+]i. Guinea-pig papillary muscles were superfused with Tyrode’s solution
(pH 7.40;37oC), tied to an isometric force transducer and point-stimulated with an extracellular
stimulating electrode. Intracellular microelectrodes at known distances, d, from the stimulating
electrode recorded the conduction delay, t, and CV was calculated as d/t. Superfusion with a
29mM Na solution to raise [Ca2+]i reversibly reduced CV by 66 [58,74]%. Addition of the CaN
inhibitor, cyclosporine A (CsA;10 µM), had no significant effect on CV under control conditions
(102 [100,106]% control), but significantly attenuated the low-Na induced reduction of CV (80
[77,83]% of control. We propose that the reduction of CV caused by a rise in [Ca2+]i is in part due
to activation of CaN and evident by partial amelioration of slowing by CsA. We hypothesise that
dephosphorylation of connexin proteins underlies this action.
61
Faculty of Health and Medical Sciences
No. 97
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
METHODS FOR PREVENTING BARIUM SULPHATE SCALING IN RESERVOIRS
Sarah A. E. Abdulla, Paul A. Sermon And Ian R. Collins
Chemical Sciences Division; Materials and Nanosciences Theme
Barium sulphate (BaSO4) scaling is formed during the secondary stage of oil recovery from the
north sea. When sea water is pumped into the reservoir (containing formation water) to maintain
pressure. As a result a white insoluble slurry (BaSO4) blocking the pipelines is formed. A
sequence of work has been taking place to form barium sulphate colloids and microemulsions
using surfactants1, stober silica2 and aluminium oxide hydroxide3 (see Figure 1). Amounts of
barium ions not precipitated were measured in stober silica and aluminium oxide hydroxide
(AlOOH) using a barium electrode and ICP-MS.
a
b
c
d
e
Fig. 1 TEM images of BaSO4 a) colloid in ethanol water, b) microemulsion in poly oxyethylene4- dodecyl ether, c) colloid in stober silica and d) aluminium oxide hydroxide. E) SEM image of
BaSO4 in AlOOH
References
1) S. A. E. Abdulla, P. A. Sermon, M. Worsely and I. Colloins, J. Amer. Cer. Soc, under press.
2) W. Stöber, A. Fink, J. Coll. Intr. Sci. 26, 62-69, 1968.
3) R. Petrovic, S. Milonjic, V. Jokanovic, Lj. Kostic-Gvozdenovic, I. Petrovic-Prelevic, Dj.
Janackovic, Powder, Tech. 133, 185-189, 2003.
No. 98
Title
Authors
Group
Abstract
ABSENCE OF CASPASES IN A PACLITAXEL-RESISTANT BREAST CANCER CELL
LINE
Ghada Ajabnoor, Patricia Macanas-Pirard, Christine Shotton, Helen M Coley*
Post Graduate Medical School; Cancer Research Theme
Anticancer drug resistance occurs as a result of altered response to cytotoxic insult, particularly via
inhibition or inactivation of apoptosis (programmed cell death type I, PCDI), and plays a major
role in tumour development and progression. An alternative form of cell death – non-apoptotic or
autophagic cell death (PCDII) has recently emerged as a factor contributing to the cytotoxic
response of cancer cells. We studied in vitro cell death in a drug resistant model MCF-7 human
breast cancer cells with acquired resistance (c. 20-fold) to paclitaxel termed MCF-7TaxR. It has
been reported in the literature that the absence of caspase-3 in parent MCF-7 cell line (due to
chromosome deletion) may explain why this cell line recruits apoptotic and autophagic cell death
following cytotoxic insult. Induction of apoptosis was examined by flow cytometry analysis using
Annexin-V assay by treating MCF-7, MCF-7TaxR and MB-231 (caspase-proficient) breast cancer
cells as a control with 0.5 µM staurosporine together with the pan-caspase inhibitor Z-VAD (100
µM ). Results showed the ability of staurosporine to induce apoptosis in breast cancer cells was of
the order: MB-231>>MCF-7>> MCF-7TaxR. Western blot analysis revealed an absence of
caspase-7 in MCF-7TaxR. The oligo GEArray® human apoptosis microarray analysis confirmed
the absences of caspase-7 and caspase-9 genes in MCF-7TaxR cells and their presence in MCF-7
cells. Hence, we have tried to look for the presence of autophagic cell death in our MCF-7TaxR
model. Flow cytometry analysis using Acridine Orange assay to detect the presence of autophagic
cell death (PCDII) prior 1µM staurosporine and 5uM bafilomycin (autophagy inhibitor) showed
evidence of autophagic cell death in MCF-7TaxR cells. Collectively, these finding indicate for the
first time the lack of involvement of caspase mediated cell death in a drug-resistant cancer cell line
in the presence of retained drug sensitivity due to alternative cell death mechanisms.
62
Faculty of Health and Medical Sciences
No. 99
Title
Authors
Group
Abstract
No. 100
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
EFFECT OF ROSEMARY ON THE PROTEIN STRUCTURE AND FUNCTIONAL
PROPERTIES OF CHICKEN MUSCLE PROTEINS
Norizah Mohd Sarbon, Farah Badii and Nazlin K Howell
Division of Nutritional Sciences
The aim was to assess changes in muscle protein structure and functional properties during frozen
storage of chicken breast muscle, in the presence and absence of rosemary extract as antioxidant.
Changes in muscle proteins were measured by the protein extractability, rheology, differential
scanning calorimetry (DSC) and FT-Raman spectroscopy. Lipid oxidation was measured by
peroxide value and malondialdehyde formation (thiobarbituric acid reactive substances). Protein
extractability of chicken muscle decreased markedly during frozen storage, but was higher in the
presence of 500 ppm rosemary extract. Dynamic rheological properties (G') and (G") increased on
frozen storage due to protein denaturation and cross-linking However, addition of rosemary at 250
ppm reduced toughness of chicken muscle. Further, rosemary extracts especially at 500 ppm
significantly reduced malondialdehyde formation. Protein conformational changes and
denaturation were confirmed by a decrease in alpha helix, tryptophan and the tyrosine doublet
ratio (830/850 cm-1) of Raman spectra during frozen storage; these changes were minimised by
treatment with rosemary extract.
ELECTROPHYSIOLOGICAL PROPERTIES OF HUMAN MYOCARDIUM FROM
PATIENTS WITH HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY
CH Fry, R Gray, WG McKenna, P Dhillon, R Jabr
PGMS, Cardiovascular theme
Introduction: Hypertrophic cardiomyopathy is associated with increased risk of myocardial dysfunction and sudden death. We measured, in vitro, the electromechanical properties of obstructive
human HCM tissue (HOCM) to understand the cellular basis of these clinical manifestations.
Methods: Myocardial strips were prepared from 16 myectomy biopsies. Data were compared to
samples from patients with mitral stenosis (MS) as control myocardium. Isometric tension and
intracellular potentials were recorded in superfused preparations, and separate measurement of gap
junction resistance was estimated from impedance measurements of the muscle. Gap junction
proteins (connexin43) was estimated by Western blot.
Results: HOCM samples failed to increase contractile performance with an increase of heart rate.
Compared to control myocardium contraction duration was increased, mirrored by action potential
(AP) prolongation. HOCM tissue was also less sensitive to β-agonists compared to control and
lacked the characteristic shortening of the AP associated with the catecholamine. AP conduction
(CV) was slower and gap junction resistivity greater in HOCM than MS tissue; with a negative
association between Cx43 protein quantity and gap junction resistivity. Clinical ECG and in vitro
data correlated with respect to corrected QT interval vs APD95 and QRS complex time vs CV.
Conclusions: These observations provide a physiological basis of electromechanical dysfunction
seen in patients with HOCM and provide a means for therapeutic manipulation of the heart.
63
Faculty of Health and Medical Sciences
No. 101
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
SEX AND AGE EFFECTS UPON SLEEP EEG TOPOGRAPHY
Stephen Emegbo1,2, Stuart Peters1, Derk-Jan Dijk1,2.
1
Surrey Clinical Research Centre, Faculty of Health and Medical Sciences, University of Surrey
2
Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey.
Topographic changes in sleep EEG have been reported previously by age. Although changes in
spectral composition have also been independently observed between sexes, the level of
interaction is yet to be evaluated.
Aim/Objectives: To assess the effect of sex within 4 age bands upon electroencephalogram (EEG)
activity in 3 topographic bands during NREM sleep.
Methods: Sleep EEG from healthy subjects aged 20-29yr (21F/36M), 30-49yr (18F/24M), 5067yr (28F/15M) and 68+yr (25F/14M) were included in this analysis. Log transformed power
spectra in frequency bins from 1.0 to 32.0 Hz were observed from 3 midline derivations (Fz, Cz &
Oz) and referenced to the left-mastoid region (A1). A correlated errors model was used to evaluate
the level interaction between the group factors (sex & age) and within-factors (midline derivations
and EEG frequency), with significance set at <0.05.
Results: Tests of fixed-effects revealed significance effects by topography (<0.0001) up to
32.0Hz. Both age and sex revealed significance up to 8.0Hz, with intermittent differences up to
21.0Hz by age and 32.0Hz by sex. Consolidated differences were observed in both
age*topography and topography*sex interactions up to 15.0Hz, while age*sex interactions only
revealed significance at 1.0 and 13.0Hz. The age*sex*topography interaction only found
significance in the 10.0Hz frequency bin. Further inspection of least squared means identified
significant differences in EEG power from 1.0 to 9.0 Hz frequency bins for all age bands. With
increasing frequency, significant effects were maintained in the older age bands, with effects more
pronounced in anterior to posterior derivations (Fz>Cz>Oz) for each frequency band.
Conclusions: These results are consistent with previous research and provide strong indications
towards the effect of both sex and aging upon spectral EEG composition. Furthermore, these
findings suggest that the sex differences in EEG frequency are “global” up to 9.0Hz irrespective of
age and topography, whilst age-related attenuation in frequencies above 9.0 Hz may by a
topographically posterior event.
No. 102
Title
Authors
Group
Abstract
SYNTHESIS OF BUILDING BLOCKS FOR DNA NANOSTRUCTURES
Adnan Jamil and Dmitry A. Stetsenko*
Division of Chemical Sciences, Materials and Nanosciences Theme
DNA has emerged recently not only as the most important molecule for molecular biology but also
as a promising material for nanotechnology, e.g. for nanoarchitectures, molecular computing and
nanodevices.1,2
The objective of this project is the synthesis of bipyridine and biquinoline building blocks shown
above for potential biocatalytic and photochemical application in DNA bionanotechnology.
1. Wengel, J. Org. Biomol. Chem. 2004, 2, 277.
2. Ito, Y. and Fukusaki, E. J. Mol. Cat. B: Enzym. 2004, 28, 155.
64
Faculty of Health and Medical Sciences
No. 103
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
A BIOCOMPATIBILITY STUDY INVESTIGATING THE APPLICATION OF
HYDROGEL-BASED MOLECULAR IMPRINTED POLYMERS IN PLASMA AND
SERUM
Quan Phan1, Azadeh Namvar2, Mir Hassan Moosavy2, Derek Stevenson, Keith Warriner2
and Subrayal Reddy1
1
Chemical Sciences Division, Faculty of Health and Medical Sciences, University of Surrey
2
Department of Food Science, University of Guelph, Guelph, Ontario. N1G 2W1, Canada
The design and synthesis of molecularly imprinted polymers (MIP) has been around for many
years, since Linus Pauling’s early theory in the 1940’s suggesting serum proteins actually
assembled around template antigen molecules (Pauling and Cambell 1942). Although MI
technology has been around for decades, the application of MIPs in real biological conditions e.g
in plasma samples has still not been greatly investigated. This study investigates the potential
application of Hydrogel-based MIPs in real biological conditions using BHb specific MIPs for
BHb detection in plasma and serum. A rebinding study into staphylococcus aureus enterotoxin B
(SEB) was also done in order to see if MIPs can be used to detect harmful food toxins that can be
potentially found in blood.
Experimental: BHb MIPs were created using an optimised protocol from Hawkins et al 2005
using polyacrylamide hydrogels. BHb samples were then added to varying concentrations of
plasma and serum in de-ionized water, and rebinding studies for the detection of BHb were carried
out. SEB MIPs were also created using polyacrylamide, and separate rebinding studies carried out.
Results were acquired using spectrophotometry.
Results: Results for BHb MIPs used in the plasma and serum study were referenced on rebinding
studies performed on BHb MIPs for BHb before any interferent was introduced. When BHb MIPs
were reloaded in the presence of neat plasma and serum a 28.99% and 28.64% protein recovery
was obtained respectively. Dilutions of the interferents in DI water showed more promising results
with 85-100% protein recovery. SEB MIPs showed low protein template recovery with 54.1%
rebinding efficiency, though ongoing work in this area is being carried out in order to produce an
optimised HydroMIP.
References:
Pauling, L. & Campbell, D. 1942, Science, vol. 76, pp. 211-220.
Hawkins, D. 2005, Investigation of hydrogel based molecularly imprinted polymers (HydroMIPs)
for protein recognition, Ph.D. thesis, University of Surrey
No. 104
Title
Authors
Group
Abstract
THE EFFECT OF ASHPHALTENE CONTENT ON WATER IN OIL EMULSION
STABILITY
Chris Jones and Prof. P Sermon
Division of Chemical Sciences
Ashphaltene fractions were extracted from Milne Point (Alaskan North Slope) crude oil and added
to a simulated crude oil in varying quantities. These were emulsified with water and the stability of
the emulsions created was measured over time.
Identical amounts of Deionised water were added and mixed under the same conditions.
Resolution of water from the emulsion was measured over time. A Conductivity probe was used to
determine whether the continuous phase of the emulsion was water or oil.
Finally a Cryo-SEM Microscope was used to analyse the droplet size and distribution of the
emulsion droplets.
65
Faculty of Health and Medical Sciences
No. 105
Title
Authors
Group
Abstract
No. 106
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
A STUDY OF WEIGHT LOSS MAINTENANCE USING EMAIL SUPPORT
Denise Thomas, Judy Lawrence and Vasso Vydelingum
Division of Health and Social Care, Doctorate of Clinical Practice (05 Cohort) & Portsmouth
Hospitals NHS Trust
The study centred on people who had lost weight through a dietitian led NHS outpatient clinic.
At reaching a clinically effective weight loss of >5% initial weight, individuals who had access to
email were recruited into a randomised controlled trial. All participants were given individual
dietary and exercise plans and taught how to manage their weight within a 4 Kg weight band. The
intervention arm of the study received 6 months of weekly email messages based on weight
management information. At each month participants in the intervention arm received a personal
email message to ask what their monthly weight was. The control arm of the study received no
email contact. At 6 months each participant completed an exit interview to assess the outcome of
the study.
At entry to the study period the percentage weight lost, was similar for the two groups, whilst at
the end of the 6 month study period there was a significant difference between the two groups (p=
0.03). The control group had on average maintained only 7% of their weight loss from their
original weight whereas the intervention group showed a mean percentage weight loss of >10%.
There was also a difference in maintenance of overall weight loss with the control group
significantly less likely (11.4 vs 7.8kg) to maintain their overall weight loss (p=0.05). In both
intervention and control groups’ the consumption of fruit and vegetables and episodes of activity
lasting 15 minutes per day were correlated with maintaining weight loss.
The study shows the beneficial effects of using email, which provides a means to reach large
numbers of people simultaneously, can support people in behaviour change.
CIRCADIAN BEHAVIOUR IN MOUSE GABAB1 RECEPTOR ISOFORMS KNOCKOUTS
Daan R van der Veen, Asha Cummins, Simon N Archer & Ying Chen
Sleep and chronobiology theme, Pharmacology and toxicology theme
Within the major light entrainable clock in the suprachiasmatic nuclei of the hypothalamus,
multiple subdivisions can be made. One way is to subdivide the SCN into a light input or ‘core’
subdivision and output subdivision, the ‘shell’. The ‘core’ receives light information perceived by
the eye in the ventrolateral part of the SCN as a glutamate signal from the retinohypothalamic tract
(RHT). The ‘shell’ serves as the output of the dorsomedial SCN, abundantly expressing
vasopressin projections to SCN target regions. In the SCN, GABAB1 receptors are found both
presynaptically (GABAB1a) on the membranes of the RHT and postsynaptically (GABAB1b) on the
vasopressinergic cells of the ‘shell’.
It has been shown that activation of GABAB receptors decreases the response of the RHT and
attenuates light induced phase shifts. Because of the distinct localization of the presynaptic
inhibitory GABAB1a receptor isoform, we hypothesize that that is an effect of this specific isoform.
What the role of the GABAB1b receptor isoform in the SCN is unknown, but could be involved in
cellular communication between individual pacemaker cells.
Using the newly availably GABAB1a and GABAB1b receptor isoform knockout mice, we measured
the effect of the absence of these receptors on circadian entrainment and free running activity
rhythms in mice. Running wheel activity was acquired both under light-dark and under continuous
conditions. A number of differences were found. Notably, we see that mice carrying the GABAB1a
isoform knockout show a higher tendency to go arrhythmic while mice carrying the GABAB1b
isoform knockouts show longer free-running periods. These results indicate that GABAB1 a and b
receptor isoform have different functions indeed, being involved in light entrainment and SCN
rhythm generation respectively.
66
Faculty of Health and Medical Sciences
No. 107
Title
Authors
Group
Abstract
Festival of Research
4th July 2008
CIRCADIAN RESPONSES TO LIGHT IN PER3 KNOCKOUT MICE
Daan R van der Veen & Simon N Archer
Sleep and Chronobiology Theme
Circadian rhythms in behaviour and physiology are driven by internal, autonomic circadian
pacemakers. The main circadian, light entrainable pacemaker is located in the suprachiasmatic
nuclei of the hypothalamus and consists of approximately 10.000 pacer cells in mice. At the
molecular level, a feedback loop of transcriptional activator and repressor clock genes generates a
circadian rhythm with an intrinsic period close to 24 hours and one of the clock genes in the
negative loop is the Period 3 (Per3) gene.
The intrinsic circadian period of humans and other vertebrates varies considerably. Such a
difference in intrinsic period may be involved in diurnal preference and affect circadian
entrainment. A polymorphism in human PER3 associates with diurnal preference, sleep pressure,
and cognitive performance1. In mice, the Per3 knockout phenotype shows a 30 minute shortening
of the intrinsic circadian period (in the 129/sv background)1. This murine Per3 knockout is
perceived as a mild or subtle circadian clock mutant in comparison to mutations in other circadian
clock genes.
Aiming at a better understanding of the contribution of the Per3 gene in sleep and chronobiology,
we are now looking more closely at the Per3 knockout mouse. Using our newly established, stateof-the-art rodent facilities, we have started to look at the dynamics of circadian rhythms and
entrainment in the Per3 knockout. We find that, in a C57Bl/6 background, the shortening of
intrinsic period in running wheel activity in knockouts is dependent on ambient light levels in
constant light conditions, and almost absent in constant darkness. Period length increases with
increasing light, but in the Per3 knockout mice this increase is significantly less compared to wildtypes.
1
No. 108
Title
Authors
Group
Abstract
Viola et al., 2007
2
Shearman et al., 2000
STRAIN DIFFERENCE BETWEEN C57BL/6 AND CD1 MICE IN CONDITIONED
PLACE PREFERENCE AND REINSTATEMENT TO MORPHINE
R. Al-Hasani, A. Bailey, S.M.O. Hourani, I. Kitchen
Division of biochemical sciences, pharmacology and toxicology theme
We compared morphine-induced conditioned place preference, looking at conditioning, extinction
and reinstatement, in C57BL/6 and CD1 mice. The mice were conditioned to morphine (10mg/kg,
s.c.) for 4 days followed by a period of extinction with saline injections. A reinstating dose of
morphine (5mg/kg s.c.) was injected on the final day. In CD1 mice there was no reliable
significant difference in preference for the morphine-paired chamber between pre- and postconditioning, so extinction and reinstatement could not be studied. This lack of conditioning was
also observed in cocaine-treated CD1 mice. In C57BL/6 mice, however there was a significant
increase in the time spent in the morphine-paired chamber post-conditioning in comparison to preconditioning (P<0.001). There was also a significant increase in the time spent in the drug-paired
chamber following reinstatement in comparison to both post-conditioning (P<0.001) and postextinction (P<0.001). These results show marked differences in sensitivity to the rewarding effects
of morphine between CD1 and C57BL/6 mice.
This work was supported by a MRC studentship, the EC (LSHM-CT-2004-005166) and the BPS.
67
Faculty of Health and Medical Sciences
Festival of Research
4th July 2008
Presenting Authors
Name
Abdulla, SAE
Ackermann, K
Ahmed, AI
Ajabnoor, G
Al-Hasani, R
Al-Karam, UF
Allenby, N
Al-Madani, MM
Al-Mssallem, M
Al-Najar, JA
Alshammari, E
Attiyah, S
Bailey, A
Bekaert, B
Bodinham, C
Bonde, BK
Borai, A
Brennan, B
Bryan, K
Bucca, G
Buckle, P
Cade, B
Carter, MM
Cheema, MS
Cockle-Hearne, J
Darzi, J
El Gamouz, A
Emegbo, S
Eriksson, M
Fisher, C
Forster, S
Foster, JD
Fry, CH
George, V
Gerondopoulos, A
Green, R
Gribble, L
Hall, S
Hawat, M
Hourani, NM
Hutchison, A
Jabr, R
Jamil, A
Jamil, D
Jenson, JS
Joda, BA
Jones, C
Kasase, C
Abstract
97
60
90
98
108
78
1
28
24
81
34
13
61, 62
25
38
58
67, 68
51
8, 9
80
52, 53
77
32
30, 31
7
18
45, 46
101
64
36
42
92
100
27
6
57
10
11
74
29
87
96
102
21
54
48
104
72
Name
Khalife, R
Laing, E
Langat, MK
Latifnejad Roudsari, R
Lederle, K
Lewis, RA
Li, X
Mardare, C
Matsufuji, T
Metaxas, A
Milioti, N
Mohd Sarbon, N
Moore, JB
Morgan, PL
MSc Tox class 2007
Muirhead, N
Neves, V
Nwogu, N
O'Reilly, J
Otway, D
Patel, A
Pawlowski, T
Phan, Q
Pierides, C
Potter, C
Royall, E
Sanz Beltran, V
Sarac, I
Shahidi, M
Shawe, J
Skandarajah, B
Stoupi, S
Sun, F
Taghipour, A
Thakur, S
Thomas, D
Thorne, HC
Tripkovic, L
Unsworth, G
van der Veen, DR
Vinogradova, I
Wehrens
Wiedemann, E
Wiseman, A
Wu, C
Yimthaing, S
Zhao, F
Zheng, N
84
Abstract
37
71
2
65, 93, 94
47
70
91
26
14
12
35
99
76
89
5
15
43
19
84
88
69
66
103
41
17
44
20
75
63
3
56
40
85
82, 83, 86
39
105
16
79
22
4, 106, 107
23
50
59
95
55
49
33
73