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5th China International Silver Conference Presentation Nanotechnology Discovers Universal Pathogen Solution: Uniform Picoscalar Oligodynamic Silver Hydrosol (UPOSH) © 2006 by Immunogenic Research Foundation (IMREF). Dr. John W. Apsley, II, Executive Director 7327 Silent Creek Ave., SE Snoqualmie, WA 98065 www.imref.org Presentation Goals Nanotechnology’s Historical Impact Upon Silver In Medicine. Understanding Nanoscalar And Subnanoscalar Silver As A Universal Pathogen Solution. Reviewing The Medical Applications of uniform picoscalar oligodynamic silver hydrosol or UPOSH. Future Research Objectives & Needs. Silver Overview Silver-based drugs are the most documented universal, broad-spectrum antimicrobial agents in modern history. Over 700 viral, bacterial, fungal and protozoan pathogens are documented to succumb to silver-based drugs. No other single antimicrobial agent competes with silver’s proven track record of safety and broad-spectrum application. With the rise of antibiotic-resistant bacteria, highly advanced silver hydrosols (i.e., silver in water) are reemerging as primary antimicrobial agents because there are no valid drug resistant strains to silver. Silver hydrosol is the best candidate to thwart bacterial or viral epidemics and pandemics. Silver Overview Continued Silver compounds have been used as medicine since the late 1800’s and has been well-received as an effective treatment against a wide variety of infections by millions of individuals across the Globe. Silver is a natural mineral in the same class as zinc, chromium, cobalt, copper, iron, magnesium, molybdenum, vanadium and zinc which are important for health maintenance. Humans naturally ingest from 22 to 300 mcg of silver per day from natural sources in food and water. There is evidence that silver is a natural and vital component of our immune system and that low tissue levels associated with a dietary deficiency may result in a relatively weakened immune system, making one more prone to infection. J. Nutr. 1940,19:579-592 Clinical Practice of Alternative Medicine, 2001 The Journal of bone and Joint Surgery, 1978 Clin Orthop, 1977 Antimicrobial Agents and Chemotherapy, 1976 5th China International Silver Conference Presentation History of Silver Hydrosol in Medicine History of Silver Hydrosol in Medicine Carey Lea (1891) announces the creation of the first silver hydrosol. Carl Nageli (1893) first defined the oligodynamic effect (from the Greek oligos = few, and dynamis = power; originally oligodynamisch) as the power of extremely small concentration of metal ions (e.g., silver and copper) to exert potent biocidal actions. The Lancet (1912 & 1918) and the British Medical Journal (1917) report stunning results utilizing silver hydrosols. Goetz (1940) clarifies that oligodynamic silver is only applicable to low concentrations of silver ions (Ag+). Contrarily, microcidal actions of heavy metal salts can only derive from high concentrations. This clarifies why heavy metal salts are poisonous. Rentz, Journal of Nutritional & Environmental Medicine, 2003 History of Silver Hydrosol in Medicine Cont. Pilcher and Sollmann (1923), Goetz (1940) and Russell et al. (1994) rated the therapeusis and bioactivity of all silver based drugs according to their respective silver ion content. Historically, Electrargol and Colsargen (circa 1910 – 1940) were effective silver hydrosols used to control acute and critical infections. A nanotechnology breakthrough in the USA (1997 – 2006) creates the first commercially available uniform picoscalar oligodynamic silver hydrosol (UPOSH) exceedingly a 95% bioactivity level. All previously measured silver based drugs were found to contain less than 20% bioactivity, with the exception of the caustic agent silver nitrate (+ 60% bioactive), which is unsuitable for intravenous administration. The Journal of Laboratory and Clinical Medicine, 1923 Prog Med Chem, 1994 Medical Properties of Silver There are distinct silver-based drugs: (1) silver-salts, (2) silver-proteins, (3) colloidal silver & Silver Hydrosol (a subset of colloidal silver). Silver hydrosols may contain very small particles which are not uniform in size (0.8-200.0 nm) that may remain suspended in water without forming an ionic solution. Uniform picoscalar silver hydrosol contains suspended uniform colloidal silver particles in ultra-pure water typically 0.8nm in size, endowing exponential surface area and surface energy to the silver). In dramatic contrast, a solution of silver-salt is one in which the ions of silver remain dissolved in water, which endows exponentially less therapeutic activity and can be toxic at high doses. For example, in addition to being exponentially less active than uniform picoscalar silver hydrosol, silver salts and silver proteins are excreted much more slowly than the smaller silver hydrosol particles and can accumulate in tissues. Medical Properties of Silver Cont. Oligodynamic silver ions destroy bacteria, viruses and other germs by at least three key ways that lead to permanent inactivation (denaturing) of essential bacterial protein and DNA without harming host tissues via: Disrupting a germ’s outer membrane proteins; Inactivation of bacterial enzymes; Inhibition of bacterial replication via DNA binding. J Biomed Mater Res, 2000 Antimicrob Agents Chemother,1976 Nanotechnology’s Impact The therapeutic powers of suspended silver depends upon four physical attributes of the silver: 1) 2) 3) 4) Particle size (Surface area & energy); Particle concentration (Therapeutic Index); Particle charge (Oligodynamic quality); Particle Shape (Catalytic activity). Nanotechnology’s Impact Cont. The smaller the colloidal silver particle, the more therapeutic activity. Typical commercial products posses a non-uniform average colloidal particle size ranging from 200nm to 20nm. Currently, the most advanced nanotechnologies are unable to make particles below 1nm with one exception. This one exception has created the World’s first uniform picoscalar oligodynamic silver hydrosol (i.e., ≤ 0.8nm average particle sizes). According to the United Kingdom’s Royal Society and Royal Academy of Engineering, such picoscalar particles would exhibit vast quantum energy dynamics of exponential power. Such exponential power translates into an unprecedented historical impact for medicine. Journal of Nutritional & Environmental Medicine, 2003 University of Miami Nanoscience and Nanotechnologies, July 2004 Nanotechnology’s Impact Cont. Nanotechnology. 2005;16:2346-53. The Bactericidal Effect of Silver Nanoparticles Jose R Morones, Jose Luis Elechiguerra, Alejandra Camacho, et al. Abstract Nanotechnology is expected to open new avenues to fight and prevent disease using atomic scale tailoring of materials. Among the most promising nanomaterials with antibacterial properties are metallic nanoparticles, which exhibit increased chemical activity due to their large surface volume ratios and crystallographic surface structure. The study of bactericidal nanomaterials is particularly timely considering the recent increase of new resistant strains of bacteria to the most potent antibiotics. This has promoted research in the well known activity of silver ions and silver-based compounds, including silver nanoparticles. The present work studies the effect of silver nanoparticles in the range of 1-100 nm on Gram-negative bacteria using high annular dark field (HAADF) scanning transmission electron microscopy (STEM). Our results indicate that the bactericidal properties of the nanoparticles are size dependent, since the only nanoparticles that present a direct interaction with the bacteria preferentially have a diameter of ~ 1-10 nm. Nanotechnology’s Impact Cont. J Nanobiotechnology. 2005; 3: 6. Interaction of Silver Nanoparticles with HIV-1 Jose Luis Elechiguerra, et al. Abstract The interaction of nanoparticles with biomolecules and microorganisms is an expanding field of research. Within this field, an area that has been largely unexplored is the interaction of metal nanoparticles with viruses. In this work, we demonstrate that silver nanoparticles undergo a size-dependent interaction with HIV-1, with nanoparticles exclusively in the range of 1–10 nm attached to the virus. The regular spatial arrangement of the attached nanoparticles, the center-to-center distance between nanoparticles, and the fact that the exposed sulfur-bearing residues of the glycoprotein knobs would be attractive sites for nanoparticle interaction suggest that silver nanoparticles interact with the HIV-1 virus via preferential binding to the gp120 glycoprotein knobs. Due to this interaction, silver nanoparticles inhibit the virus from binding to host cells, as demonstrated in vitro. Nanotechnological Breakthrough Uniform oligodynamic picoscalar silver hydrosol (UPOSH) reflects the following physical chemistry attributes: Uniform picoscalar ≤ 1 nm silver clusters Oligodynamic silver content ≥ 95% Particle Diffusion Coefficient 10-5cm2/sec for optimal absorption & target adsorption A near neutral pH of 6.7 20 to 25 ppm silver concentration per cc No anion present, silver and water only Sterile, hypotonic, pyrogen-free water base Stable when stored as directed for 5 years IMREF White Paper 1001: Speciations and Oligodynamics of Silver-Based Drugs © 2006 Immunogenic Research Foundation, Inc. UPOSH Particle Uniformity UPOSH Transmission Electron Micrograph 100,000x Magnification (Univ. of Miami) UPOSH Uniformity UPOSH & Large Nanoscalar Silver UPOSH & Small Nanoscalar Silver Schematic of Coronavirus Juxtaposed With UPOSH: For Every Atom of Virus, There Will Be One Silver Particle Present To Enable Complete Viral Destruction Broad Spectrum Efficacy of Oligodynamic Silver Oligodynamic silver is by definition non-toxic to higher life forms, yet lethal to all lower life forms such as: Viruses; Bacteria; Fungi; Protozoa; Resistant (MDR) Pathogens; Cancer. UPOSH As Universal Pathogen Solution Bactericidal Spectrum of Oligodynamic Silver Bactericidal Spectrum of Oligodynamic Silver Achromobacter metalcaligenes Achromobacter mucosa Acinetobacter spp. (92 different strains,including former Herellea spp.) Acinetobacter anitratus Acinetobacter lwoffii Actinomyces viscous Aerobacter aerogenes Agrobacterium tumefaciens Alcaigenes faecalis Alternaria dianthi Alternaria oleracea Bactericidal Spectrum of Oligodynamic Silver Alternaria solani Amoebic dysentery Anthrax bacilli Arthrobacter globiformis Bacillus antratum (Micrococcus Acinetobacter) Bacillus cereus Bacillus megaterium Bacillus mycoides Bacillus subtillis Bacteria aertryek Bacteria danyaz Bacteria gaertner Bactericidal Spectrum of Oligodynamic Silver Bacteria pestis Bacteria pyocaneus Bacteriodes fragilis Bacterium tabacum Bordetella pertussis Borrelia burgdorferi (Lymes Disease) Brevubacteriun linens Brucella abortus Burkholderia cepacia (25416 strain) Caulobacter vibroides Citrobacter Clostridium perfringes (strains 1687, 1694) Bactericidal Spectrum of Oligodynamic Silver Corynebacterium diphtheriae Cryptococcus albicans E. polygoni Entamoeba histolytica (cysts) Enterobacter spp. (20 different strains) Enterobacter aerogenes Enterobacter cloacae Enterococci (20 different strains) Enterococcus Group D streptococcus Enterococcus faecalis Enterococcus faecium Erwinia amylovora Bactericidal Spectrum of Oligodynamic Silver Escherichia coli (20 strains) E. coli (B23 strain) E. coli (HB 101 strain) Euglena Exotoxins (i.e., exoproteins, endopeptidases, enterotoxins - bacterial or fungal) Flavobacterium spp. (IIb) F. group (IIIa) F. Aquatile F. Halmephilum Gangrene (pyemia) Gardnerella vaginalis Bactericidal Spectrum of Oligodynamic Silver Gonorrhoeal arthritis Gonorrhoeal conjunctivitis Gonorrhoeal opthalimia Gonorrhoeal Prostatitis Helicobacter pylori Hypopyon ulcer (corneal ulcers) Klebsiella Klebsiella oxytoca Klebsiella pneumoniae (over 20 different strains) Lactobacillus acidophilus Legionella pneumophila (Legionaire's Disease) Listeria monocytogenes Bactericidal Spectrum of Oligodynamic Silver Micrococcus luteus Mima Meningococcal meningitis Mycobacterium (Tuberculosis) Mycoplasma spp. Neisseria gonorrhea Paramecium spp. (Balantidium coli, Holophrya coli, Leukaphrya coli) Para-typhoid Para-typhosus A Para-typhosus B Plasmodium berghei (Malaria) Pneumococci Bactericidal Spectrum of Oligodynamic Silver Proteus spp. (20 different Indole-positive strains) Proteus mirabilis (over 20 different strains) Proteus morgani Proteus rettgeri Proteus vulgaris Providencia stuartii (20 different strains) Pseudomonas aeruginosa spp. (over 20 different strains) Ps. Fluorescens Ps. Multiphilia Ps. pycocyanea Pyorrhea alveolaris (Riggs Disease) Rickettsiae spp. (S. typhus) Bactericidal Spectrum of Oligodynamic Silver Salmonella spp. Salmonella arizona Salmonella typhimurium Shigella boydii Spore-forming bacteria (unidentified species) Staphyloclysin (denatures) Staphylococcus spp. (20 Coagulase-negative strains) Staphylococcus aureus Stapylococcus aureus (97 MRSA strains) Staphylococcus epidermidis Staphylococcus maruslene Staphylococcus pyogenea Bactericidal Spectrum of Oligodynamic Silver Staphylococcus pyogens albus Staphylococcus pyogens aureus Staphylococcus systeneriae Stenotrophomonas (Pseudomonas) maltophilia Streptococci spp. Streptococcus (Nonhemolytic) Streptococcus Group A (including β hemolytic type) Streptococcus Group D Streptococcus agalactiae (27956 strain) Streptococcus fæcalis Streptococcus faecalis (9790 strain) Streptococcus gordonii Bactericidal Spectrum of Oligodynamic Silver Streptococcus mitis Streptococcus monilla Streptococcus mutans Streptococcus mutans (GS-5 strain) Streptococcus pneumoniae Streptococcus pyogenes (over 20 different strains) Streptococcus salivarius Streptococcus sobrinus Treponema pallidum (Syphilis) Typhoid Bacillus Veillonella alcalescens Vibrio cholerae Yersinia pestis (Bubonic plague) 5th China International Silver Conference Presentation Virotoxicity of Oligodynamic Silver Metal Based Drugs, 1994 Biochemistry, 1991 Prog Med Chem, 1994 Virotoxicity of Oligodynamic Silver Adenovirus Coxsackie virus type B-3 (CB-3 strain) ECHO virus ECHO virus type 6 (EC-6 strain) Enteroviruses (bovine) Herpes Simplex Herpes zoster (shingles) HIV Influenzae (types unidentified) Influenzae A Influenzae B (Haemophilus influenzae) Virotoxicity of Oligodynamic Silver Poliovirus type 1 (Po-1) Poliovirus type 1 (Sabin strain) Pseudorabies virus Reovirus type 1 Rhinovirus type 1A Rotavirus (bovine spp.) Rubeola virus (Measles - MV, Nagahata strain) Vaccinia virus (poxviruses) Varicella-zoster virus, Variolavirus spp. (Small pox) Verruca spp. (warts) Vesicular stomatitis-Indian virus. 5th China International Silver Conference Presentation Fungicidal Spectrum of Oligodynamic Silver Metal Based Drugs, 1994 Biochemistry, 1991 Prog Med Chem, 1994 Fungicidal Spectrum of Oligodynamic Silver Actinomyces viscosus Alternaria dianthi Alternaria oleracea Alternaria solani Ascomycetes (Pneumocystis carinii) Aspergillus flavus Aspergillus fumigatus Aspergillus niger Basidiomycetes Botryobasidium solani (Rhizoctonia) Botrytis cineria Botrytis paenoiae Candida albicans Fungicidal Spectrum of Oligodynamic Silver Candida albicans II Candida glabrata Candida krusei Candida parapsilosis Candida pseudotropicalis Candida tropicalis Candida utilis Chlamydospores – Tilletia tritici Dermatophytosis spp. (Ringworm) Erwinia amylovora Erysiphe graminis (Blumeria) Fomes annosus Fungi Imperfectii Fungicidal Spectrum of Oligodynamic Silver Fusarium spp. Heterodera marioni Malassezia furfur Monilinia fructicola Mucor pusillus Ophiobolus graminis Pestalotia stellata Phlyctenular Conjunctivitis Phycomycetes Phytophthora infestans Rhizopus nigricans Saccharomyces cerevisiae Saprophytes Fungicidal Spectrum of Oligodynamic Silver Sarcina aurantiaca Sclerotinia americana Sclerotinia fructicola Septoria apii Sporosarcina ureae Tinea versicolor Torulopsis glabrata Uromyces caryophyllinus Venturia pyrina Xanthium glabaratum Yeast (unidentified species) Future Research The Immunogenic Research Foundation (IMREF) is a non-profit corporation funded by charitable donations. IMREF and its Scientific Advisory Board members are concerned with conducting world-wide clinical research on global epidemics and pandemics, including Cancer, H5N1, Hepatitis C, HIV, Lymes Disease, Multiple Sclerosis, and drugresistant super germs. Future Research Since its inception in January of 2006, IMREF has been establishing itself as the Internet’s prime facilitator for silver-based therapeutics. To date, the endowment of a world-class library covering nearly every aspect of silver in medicine has been instrumental to IMREF’s current success. With your help IMREF is positioned to become the top internationally recognized educational service and medical authority on silver in medicine. Future Research IMREF’s Board of Directors and Scientific Advisory Board members include renown clinical investigators such as: Debra Mash, PharmD; Karen Weaver, JD, RPh; Brian Clement, PhD; Deborah Metzger, MD, PhD; Dana Flavin, MD, MS; Kent Holtorf, MD; Rashid Buttar, DO; Eric Gordon, MD; Tom Lodi, MD; Jonathan Wright, MD; Steve Hines, ND; and Virginia Osborne, ND. Future Research IMREF is currently appraising silver research being conducted nationally as well as internationally. In alliance with other researchers, IMREF will educate the world and help guide HIV, HCV, Lyme, Malaria and Cancer investigations world-wide. In order to complete this mission IMREF is currently seeking up to $3,000,000.00 USD for it current fiscal year of operations. Thank you for your interest & support.