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(continued): *********** Session #5 Abstract #20. ENHANCEMENT OF IMMUNE FUNCTION IN AGING ANIMALS USING A COMPLEX PLANT CARBOHYDRATE WHICH STIMULATES MACROPHAGE SECRETION OF IMMUNOINTERACTIVE CYTOKINES D.L. Busbee, E.A. Merriam, B.D. Campbell and L.P. Flood., Department of Anatomy and Public Health, College of Veterinary Medicine, Department of Physiology, College of Medicine, Texas A & M University, College Station, Texas. A long-chain, B (1,4)-linked, acetylated polymannose (ACM, Acemannan(tm)) was used to treat mice in a tumor recovery study, and in a study of immune function across a 3 month to 17 month age-continuum. Animals transplanted subcutaneously with 106 or 107 cells of a syngeneic sarcoma (Norman Murine Sarcoma, NMS) were treated IP with ACM (1 mg/kg in sterile 0.9% NaCI). Tumor growth was monitored, with 100% of non-ACM treated animals developing large sarcomas and proceeding to a morbid state. About 40% of ACM-treated animals exhibited tumor growth followed by immune system-associated tumor regression and complete recovery. Animals which recovered from the NMS transplant could not subsequently be successfully transplanted with sarcoma cells. Mice injected IP with ACM exhibited increased peritoneal macrophage secretion of IL-1 and TNF-A. Mice, C57BL/6N, treated with ACM across an age continuum were evaluated for IL-1 (units/ml sustaining lymphocyte blastogenesis relative to units/ml of recombinant murine IL-1A) and IL-6 secretion, thymocyte blastogenesis and antibody-dependent cellular cytotoxicity (ADCC). ACM treatment increased IL-1 and IL-6 secretion in young and old animals, and initiated increased concanavalin-stimulated blastogenesis in young animals. ACM-stimulation of increased lymphocyte blastogenesis was not clearly demonstrated in cells from all age groups. Cells from 17 month old mice ACM-treated animals showed almost a 2-fold increase in concanavalin-stimulated blastogenesis over cells from non-CM-treated animals. ACM treatment was associated with increased capacity of animals to mount an effective immune system surveillance against implanted sarcoma cells. Since the mice, CFW, used in NMS tumor-implantation experiments are outbred, variability in the response to NMS with or without ACM was expected. ACM-treatment was associated with increases in peritoneal macrophage secretion of IL-1 and IL-6, and in increased capacity to initiate lymphocyte blastogenesis. The data indicate that ACM, an acetylated polymannose with an unusual B (1,4) carbohydrate linkage, serves as an effective immunostimulatory agent in mice, and suggest that it might have a use in the long-term support of immune function in anti-aging medicine. Session # 5. Abstract # 21. MECHANISMS OF IMMUNE SENESCENCE IN THE ELDERLY: IMPLICATIONS FOR THERAPY. G.D. Marshall, M.D., Ph.D., E.M. Henninger B.S., M.T. (ASCP), S.K. Agarwahl, B.A., and C.C. Cassidy, B.S., Division of Allergy & Clinical Immunology, University of Texas Houston Medical School, Houston, Texas. Increased incidence of and mortality from diseases associated with the senescence of the immune response are expected consequences of aging in humans. The exact mechanisms associated with these observations are not fully understood but include a decrease in immunocompetent cell numbers as well as function. Review of the literature suggests that the aging process is associated with decreased numbers and/or function of immunocompetent T cells. Residual T cells, both CD4+ and CD8+, tend to be of the memory (TH2) rather than naive (TH1) type. Clinical studies suggest that immune responses may be variable depending upon the underlying health of the individual as well as age. We have observed differences in mitogen- and antigen-induced blastogenesis and cytokine production from old vs young humans. This is correlated in vivo with DTH skin tests and in vitro cytokine profiles except for elevated lL-10 in elderly patients. These data suggest that healthy elderly humans produce adequate in vivo immune responses due to the expanded presence of multiple memory T cells. However, new antigen exposure (i.e. infectious, malignant, etc.) is met with an inadequate immune response (perhaps due to excess lL-10 levels) resulting in impaired immune responses and increased morbidity/mortality. Confirming this hypothesis will aid design of studies with immunomodulators that may normalize the immune responses of elderly individuals with immune dysfunctions. Session #5 Abstract # 22. CO-ENZYME Q10 AND LIFESPAN EXTENSION L. STEPHEN COLES, M.D., Ph.D., Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA and Steven B. Harris, M.D., Department of Pathology, UCLA School of Medicine, Center for the Life Sciences, Los Angeles, CA CoEnzyme Q10 (CoQ10) is a vitamin-like, naturally occurring compound found in most cells of the body as well as in many foods. CoQ10 plays a key enzymatic role in energy production within mitochondria. Mitochondria are specialized organelles which function as energetic power plants to produce adenosine triphosphate (ATP), the energetic coin of the realm within both plant and animal cells. CoQ10 has been on the market in Japan since the early 1970s, where it is used as a tonic by approximately ten percent of the adult population in that country. For the last decade or so American cardiologists have been using CoQ10 as a prescription drug (under the trade name Ubiquinone) for patients suffering from heart disease. However, since the mid-1980s, CoQ10 has been marketed as a nutrient in U.S. health food stores in capsules that range from 10 to 30 milligrams. Numerous studies have demonstrated that CoQ10 is highly effective in preventing and treating atherosclerosis, angina (heart pain), myocardial infarction (heart attack), and other cardiovascular diseases. Although its mechanism of action is currently unknown, it is speculated that it may function as certain other vitamins do as an antioxidant. Experiments with rodents have shown that CoQ10 confers significant advantage in increasing average life expectancy. However, we are disappointed to report that it does not appear to increase maximum life span. Session # 5 Abstract # 23. EARLY DETECTION OF CORONARY ARTERY DISEASE USING ULTRAFAST CT Stuart Rich, M.D., F.A.C.C., Professor of Medicine and Chief, Section of Cardiology, The University of Illinois at Chicago, School of Medicine, Chicago, IL. The high prevalence of coronary artery disease in the American population makes aggressive programs of early detection and prevention mandatory. However, the traditional methods of screening for coronary artery disease with risk factor profiling, or using exercise testing, is both too insensitive and nonspecific to accurately identify people at risk for coronary events. Furthermore, although studies on the value of lipid lowering agents as secondary prevention are convincing, the use for these same drugs as primary prevention remains controversial. A new technology, ultrafast CT, which allows the noninvasive, safe and rapid detection of coronary atherosclerosis in asymptomatic individuals holds great promise as a screening tool to identify patients at risk for coronary events in the general population. By applying proven methods for prevention of coronary atherosclerosis, it may be possible to have a major impact in reducing the clinical expression of coronary disease. Ultrafast CT holds great promise as a screening tool for the detection of coronary artery disease in the general population. Session #5 Abstract # 24. BIOMARKERS: ROLE IN DETERMINING BIOLOGICAL AGE. Frances A. Kovarik, Ph.D., Executive Director, American Academy of Anti-Aging Medicine, Chicago, IL and Vincent C. Giampapa, M.D., F.A.C.S., Director of Surgery, Plastic Surgery Center of Montclair, NJ and Assistant Clinical Professor, University of Medicine and Dentistry of New Jersey Medical Center, Newark, NJ This presentation is an overview of evaluating biomarker parameters on four levels starting with the functional parameters of the body and progressively examining biomarkers on the cellular, molecular, and chromosomal levels. The data collected by using this biomarker matrix is fed into a computer program that helps cross-correlate and analyze the data to help determine the state of aging within the tested individual. This biomarker study is a new concept presented in evaluating the aging parameters of the individual on multiple levels. The biomarker parameters are examined on four planes. Session #5 Abstract # 25 . DHEA AS A MARKER OF AGING AND A THERAPEUTIC PRINCIPAL Julian M. Whitaker, M.D., Medical Director, Whitaker Wellness Institute, Newport Beach, CA. Dehydrepiandrosterone (DHEA) is a steroid hormone produced by the adrenal gland. Synthesized from cholesterol, it is produced in larger amounts than any other adrenal steroid hormone. DHEA is both a precursor to the sex hormones and functions as a "buffer" hormone. It also has recently discovered independent functions of its own. DHEA has therapeutic potential for many medical conditions including: cardiovascular disease, diabetes, hypercholesterolema, obesity, cancer, Alzheimer's disease, memory deficits, autoimmune diseases, immune disorders including AIDS, chronic fatigue, and osteoporosis. In addition, DHEA has a decided effect on mortality, with studies showing that an increase in blood levels of DHEA sulfate is associated with a 36% reduction in mortality from any cause. An individual's innate blood levels of DHEA reach a peak in his or her mid-twenties and progressively decline from that point. Blood levels of DHEA sulfate are a marker for many degenerative diseases, including the above-mentioned conditions. Supplemental DHEA is being used clinically for these conditions, as well as for physical and psychological well-being and life extension. Doses vary but as much as 1,600 mg/day have been given for a month without side effects. A recommended initial therapeutic dose is 25 mg/day for women and 50 mg/day for men, with monitoring of blood levels every three months and adjusting the dose accordingly. The intent is to maintain levels in the average range for a young adult, regardless of the individual's age. Session # 5. Abstract # 26. LASER LIGHT FACIAL REJUVENATION. Gregory S. Keller, M.D., F.A.C.S., F.A.B.O., Keller Facial Plastic Surgery Center, Santa Barbara and Director, Laser Surgical Unit, Goleta Valley Community Hospital, Santa Barbara, CA. The full potential for laser use in facial rejuvenation has not been realized. This paper attempts to summarize the new advances in this rapidly moving field and to outline areas of laser technology that may find applications in the near future. The "hottest" area of physician and patient interest in lasers in the field of facial plastic surgery currently is "laser resurfacing" of the skin. Though iridium yag laser removal of layers of skin has been used of skin research for years, it is the new pulsed carbon dioxide lasers and new scanning systems that have made laser resurfacing of the skin practical. Because of the lasers ability to abrade at different depths that change millimeter by millimeter over the skin's surface, unwanted wrinkles can be diminished with these laser systems without the depigmentation that was associated with deeper chemical peels and dermabrasion. Aesthetic surgery with the laser has also reduced the healing time and degree of morbidity that has been associated with facelifting, blepharoplasty, and extended or composite facelifting. The preponderance of medical evidence demonstrates that the laser reduces the morbidity and recuperation time of these procedures, but physicians have been slow to adopt these techniques due to the cost of the systems and the training time required to use them. Laser hair transplantation will probably be the field of most intense interest in the next year. The field of hair transplantation is evolving toward the implantation of thousands of grafts of single, two to three, and three to five hairs. This is a tedious process and bleeding of the scalp, as well as surgeon and technician fatigue, can cause a failure of the procedure. Lasers and scanners have been developed that speed and automate the process. Troublesome bleeding that can extrude the grafts from the recipient bed is avoided. Futuristic laser uses for rejuvenation may rely on more esoteric usages. Photodynamic therapy is one such treatment modality that has been used to treat skin and other cancers. A drug is used which is selectively retained in cancerous or other tissues. A laser light that is non-thermal (of the intensity of a light bulb) is then used to catalyze a destructive process. We noticed that skin next to a tumor that was treated with PDT experienced a rejuvenation process equivalent to a chemical peel without the skin being broken. Psoriasis and vascular lesions may also be treated with photodynamic therapy. Low energy lasers for enhancing healing and lasers that specifically alter components of the cell have been used for research purposes. They may find more applications in the future. Lasers that treat varicose and telangectatic leg veins also are under development. Banquet Speaker Abstract # 27. LIFE EXTENSION NOW AND IN THE 21ST CENTURY Roy Walford, M.D., Department of Pathology, University of California at Los Angeles School of Medicine, Center for the Life Sciences, Los Angeles, CA Studies of the eight humans sealed inside the closed ecological space known as Biosphere 2, near Tucson, Arizona, provided evidence that humans on a calorie-restricted nutrient-dense diet show the same physiological changes (in cholesterol levels, fasting blood sugar, blood pressure, white blood cell counts, glycated hemoglobin, insulin and cortisol levels) as rodents on such a diet, strengthening the inference that retardation of aging and enhanced resistance to disease might also obtain in humans on such a regime. Whereas calorie-restriction may be the first method (the only one at present) used to enhance human life span, and is probably not applicable to a general population,te rpdadvances being made in gerontology suggest that other simpler methods may be forthcoming, and that the 21st century will be the cenury of "the long-living society." Session #6 Abstract # 28. NEW CONCEPTS IN DRUG DELIVERY SYSTEMS. Vincent C. Giampapa, M.D., F.A.C.S., Director of Surgery, Plastic Surgery Center of Montclair, NJ and Assistant Clinical Professor, University of Medicine and Dentistry of New Jersey Medical Center, Newark, NJ Aside from the generally known routes of administration, new delivery systems have been developed that include the use of bio-absorbable substrates which house the desired medications within them. These tubules are implanted subcutaneously. Through the use of growth factors, the blood supply is developed around the drug laden tubules. Thus the medications can be distributed to the body over long periods of time. Other systems are discussed including subcutaneous implantable pod systems. The implantable pod systems allow multiple drug deliveries at desired time sequence intervals; other drug delivery systems presented include the capsulating cell technologies. Over the last few years, new drug delivery systems have been conceptualized and developed using bio-absorbable, bio-degradable substances. Utilizing polylactic and polyglycolic acid in the tubules, drugs can be administered from these bio-absorbable tubules to the surrounding subcutaneous tissues. With the advent of these types of tubules, growth factors are applied to the surface of this system. These growth factors induce DNA neurovascularization around the tubules and enhance drug delivery. This same concept is used in the pod delivery systems that may house both encapsulated genetically altered cells or genetically produced cells in the form of a highbred organ; these cells will then deliver their normal hormonal components and permit auto-self regulation. Other uses of the pod delivery system are in the form of a percutaneous refillable reservoir. The reservoir is controlled by a microchip and an internal power source. This system allows for multiple drug deliveries of key anti-aging hormones or enzyme systems. The release of these compounds can be strategically timed making the release with biologically determined rhythms within the body to mimic the body's normal release schedules. The state of development of these tubules and their future use with anti-aging and longevity medicine, as well as degenerative diseases is discussed. Session #6 Abstract #29. ORGAN CRYOPRESERVATION Gregory M. Fahy, Ph.D., Transfusion Medicine Research Program, Naval Medical Research Institute, Bethesda, MD. A common cause of death among older individuals is organ failure. The treatment of choice for organ failure is organ replacement, but organ replacement eventually leads either to organ rejection or to death from the secondary effects of immunosuppression used to prevent rejection. These problems could be overcome by better matching, by the induction of immunological "tolerance" to the transplanted organ, or both, but these solutions can best be accomplished using longer organ storage times than can be achieved using conventional organ storage methods. By cooling organs to cryogenic temperatures, all meaningful time limits on organ storage can in principle be abolished. The problem has been to carry out this cooling in such a way that the preservation procedure itself does not kill the organ in the process. After approximately 40 years of effort in pursuit of this goal, a workable approach appears to be near at hand. The technique is called "vitrification", or preservation at very low temperatures in the absence of ice. This may be accomplished using high concentrations of chemical additives that replace water and prevent the remaining water from freezing. To date, rabbit kidneys have been able to tolerate all phases of the procedure except warming from cryogenic temperatures, but suitable warming techniques now appear to be available for testing. The successful banking of kidneys may well lead to successful banking of virtually all other organs, including non-vital organs such as hands that will be feasible to transplant given the advantages of immunological tolerance. Session #6 Abstract #30. NOVEL FIBRIN SEALANT APPLICATIONS Barry Datlof, American Red Cross, Rockville, MD Fibrin sealant, produced by mixing solutions of thrombin and fibrinogen complex to form a clot at the site of application, can be supplemented with therapeutically valuable substances such as growth factors to stimulate tissue regeneration, various hormones or drugs with diverse effects, antibiotics to inhibit bacterial growth, or growth inhibitors to slow tumor growth. The ability of fibrin sealants to adhere to moist tissue also allows localization of drug delivery; therefore, higher localized levels and lower systemic levels can be maintained. The duration of delivery may be customized to suit the application. Since fibrin sealant ultimately is degraded through normal fibrinolytic mechanisms, it can be used as a short or long-term drug delivery system for a variety of substances. The Plasma Derivatives and Molecular Biology Labs at Red Cross' Holland Laboratory are developing a number of commercial applications for supplemented fibrin sealants. Particularly promising is its use in periodontal disease treatment, vascular grafts, bone repair, ulcer and burn healing, and the delivery of cancer therapeutics. The Red Cross currently seeks licensees and joint development partners to commercialize supplemented fibrin sealants. In addition to companies with valuable supplements, the Red Cross seeks companies with expertise in formulation and testing, manufacture, and medical devices. ********* I'll send the rest tomorrow, this is quite long and is just the first half! I've also got some other info I've found recently on pesticides, drugs and pharmacology, vitamins, herbs, etc., and I'll slowly pass it all on. Wendy