free of liver toxicity and effective in bringing levels of serum T within physiological range. It may, however, result in supraphysiologicallevels of dihydrotestosterone and rarely gastrointestinal side effectsThe drug is lipid soluble and should be taken with meals. The recommended dose is 120 to 200 mg in 3 divided doses, depending onthe degree of Testosterone deficiency, body surface, obesity and clinical response.Intramuscular injections of Testosterone are usually long acting. These formulations obtain a maximum concentration at approximately72 hours after injection which slowly diminish over the ensuing 10 - 14 days. The gradual decline frequently results in a very low nadirprior to repeat injection. Parenteral androgens do not provide normal circadian patterns of serum testosterone and the injections aresomewhat uncomfortable. Levels of DHT are normal but androgen metabolites are frequently not physiological while estradiol levelsmay become excessive in some men. In the first few days after injection supraphysiological serum testosterone levels occur whichmay result, in breast tenderness or gynecomastia.Intramuscular testosterone may also be administered as unmodified aqueous testosterone in its most elemental form. This preparation,however, is rapidly absorbed and degraded, requiring frequent administration and is unsatisfactory for chronic Testosteronereplacement.More widely used preparations include the 17-hydroxyl esters of testosterone which are administered with slow release oil basedinjection vehicles.These esters, however, lack inherent androgenic activity and must be hydrolyzed to testosterone before they becomepharmacologically active. The 17-hydroxyl esters of testosterone most widely used include the short acting testosterone proprionateand the longer acting testosterone enanthate and cypionate. Testosterone propionate is rarely used clinically because of its short halflifeand requirement for every other day injection to maintain normal serum Testosterone levels. Testosterone enanthate and cypionate,however, may be administered every 10 - 21 days to maintain normal average testosterone levels. It must be acknowledged, however,that testosterone levels with these preparations surge to supraphysiological levels as high as 1400 ng/ml at approximately 72 hoursafter administrationThe decline in serum Testosterone continues over 14-21 days reaching baseline at approximately 21 days. The significant peaks andvalleys (roller-coaster effect) of serum Testosterone in patients treated with parenteral Testosterone injections may produce significantmood swings and noticeable ups and downs in libido and sexual function. These long acting Testosterone preparations are however,the most cost efficient methods for androgen replacement.Dosage is 200 -400 mg every 2 -4 weeks. 200 mg injections will maintain normal T levels for approximately two weeks while 300 mgdoses are required to maintain eugonadal range for approximately three weeks. Higher doses will not maintain Testosterone levels inthe normal range beyond the three week limit.Effects: These agents have clearly been demonstrated to improve libido, sexual function, potency, energy level, bone density andmood if these abnormalities are caused by androgen deficiency. Supraphysiological levels of serum Testosterone may result ininfertility due to suppression of FSH and LH production. Reports of sexual aggressiveness and overall aggressive behavior during peaklevels following injectable testosterone have been reported anecdotally.Careful counseling about the possibility of these mood and behavioral changes for patients undergoing short acting parenteraltestosterone therapy is essential. Long acting Intramuscular Nebido injections is more acceptable in this respect. Tan et al haverecently reported the effects of parenteral Testosterone on HDL levels in 11 men receiving 250 mg of Testosterone enanthate at fourweekly intervals. While these doses of Testosterone resulted in sub-optimal serum levels, no significant changes in plasma cholesterol,triglycerides, LDL, or HDL occurred. Injectable Testosterone has also been implicated in abnormal erythropoeisis and increasedhemoglobin levels and sometimes hypercoagulability. These changes, however, have not been demonstrated with newer transdermalpreparations. As discussed below, there is a justified concern about elevated testosterone levels in elderly men and associatedprostate specific antigen (PSA) elevations, increased prostatic size with associated obstructive symptoms and the activation of occultprostatic malignancy.While some increases in PSA and prostate specific membrane antigen (PSMA) as well as increased prostatic size have beendocumented, these changes are not statistically significantly different from untreated hypogonadal men. Similarly, PSA elevations havenot risen beyond normal clinical values.Transdermal Testosterone Therapy (TTT), a higher priced but more physiologic approach to testosterone replacement, has recentlybecome available worldwide.ANTI-AGING MEDICINETTT is available in both a scrotal and non-scrotal patches. These preparations utilize elemental Testosterone absorbed transdermallyto obtain normal serum Testosterone levels and reproduce the diurnal physiologic variations of Testosterone observed in normalhuman testosterone secretion.Patches are applied at bedtime with peak Testosterone levels achieved in the early morning and a nadir prior to patch replacement.The first patch available was a scrotal one that required weekly scrotal shaving and was difficult for some patients to apply and maintainin position for 24 hours. Patients with small rugated scrotums had difficulties with absorbing higher doses of Testosterone. The scrotalpatch, while obtaining normal physiologic Testosterone levels and normal estradiol levels, was demonstrated to have abnormally highdihydrotestosterone levels as a result of high concentrations of 5-alpha reductase in the scrotal skin. Transdermal patches are nowavailable for non-scrotal use and include the Androderm and Testoderm systems.These non-scrotal patches also maintain diurnal serum concentrations with normal estradiol and dihydrotestosterone levels. Whilemost patients can be treated with a single non-scrotal transdermal patch, some patients require more or less Testosterone replacementdepending upon deficiency and absorption characteristics. Morning Testosterone levels should be evaluated within 2 -3 weeks ofinitiating therapy to identify peak Testosterone levels.Serum evaluations of these patients should be carried out between 8 and 10 AM to determine the highest daily level of serumTestosterone produced by the patch. Because androgen levels with these systems do not increase beyond normal, it is unlikely thatthere will be detrimental changes in mood with transdermal preparations. While psychological effects have not been carefully studiedin a long term series, no cases of aggressiveness with the transdermal patch systems have been reported. Follow-up studies oftransdermal T replacement have, however, demonstrated an improvement in Testosterone levels associated with improved sexualfunction, libido, nocturnal penile tumescence (NPT) response, with maintenance of normal hematocrit, lipid profile, PSA levels, andprostatic volumes. Most common side effects of the dermal patches include the inconvenience of applying them and dermatitis,sometimes leading to significant chemical burns.Other Techniques: Numerous techniques for Testosterone delivery remain investigational. They include long acting implantablepercutaneous pellets, spheres, and microcapsules under study in Europe. These subcutaneous capsules are fused pellets ofunmodified testosterone implanted every 4 -6 months. Because these pellets require the use of a trochar or a minor surgical procedure123
to be administered, they are less appealing than other Testosterone preparations. Further development of these pellets to decreaseinvasiveness of administration and increase patient acceptance may lead to their use for long term Testosterone replacement therapy.Their longevity and difficulty in removing them if serious adverse events occur, makes the implants and microcapsules less attractivefor elderly patients.Swiss Oats & Homeopathic Preparations:A recent trial demonstrated that this helped elevate free testosterone levels in those who were deficient and the vitamins, iron & otheringredients in this food supplement restored symptoms in andropausal men by releasing Testosterone bound to SHBG. Anothersupplement from the Tribulus family was shown laboratorily to raise serum DHEA which is a precursor of testosterone.SESSION 24AAANTI AGING WORKSHOP 9 STEM CELLS9.30 am / 9h30THE USE OF STEM CELL XENO-TRANSPLANTATION AS A TREATMENT OF AGING DISEASESLA TRANSPLANTATION DE CELLULES SOUCHES COMME TRAITEMENT DES MALADIES LIÉES À L’ÂGEMICHAEL E. MOLNAR(USA)CELLULES SOUCHESWorld believes dis-information by the media that stem cell transplantation was born in U.S.A. in 2001 and that only human embryonicstem cell transplantation is the acceptable way to carry out such treatment. Physicians have been victims of the same fiction spreadby peer-reviewed medical journals.In reality animal fetal precursor stem cell transplantation was first reported at the meeting of French Academy of Sciences by Brown-Seguard in 1889. Medical historians established 1931 as the year of birth of the new medical field of cell transplantation in Switzerland.To-date 99.7% of over 5 million patients treated by stem cell transplantation in the world have been treated by animal fetal precursorstem cell transplantation without a single fatality.This treatment is safer than taking a small dose of aspirin providing stem cell transplants are prepared in accordance with regulationof U.S. FDA 'PHS Guidelines on Infectious Disease Issues in Xenotransplantation' of January 19, 2001 (Federal Register, Volume 66,Number 19, pages 8120 - 1) by a lege artis method such as that of Bio-Cellular Research Organization LLC. This method incorporatesprimary organ culture and assures that there is no need for immunosuppression following SCT treatment.In 1956 cell xeno-transplantation was crushed in U.S., and since that time there are no German medical textbooks or journals dealingwith cell xeno-transplantation available at any U.S. medical school library.In 1997 cell xeno-transplantation was nearly quashed in Germany (with a reversal in 2000 by German Supreme Court).All regulations about cell xeno-transplantation disappeared in Switzerland, country of birth for this therapy.Since SCT has always focused on treatment of incurable or no longer treatable diseases there have not been any grounds to considerSCT a dangerous competition to the existing dominance of health care by the pharmaceutical industry.Claims that only human embryonic stem cell transplantation is 'the stem cell transplantation' have been contrary to all scientific factsto-date since such therapy has been recognized for 75+ years by all cell xeno-transplantation experts as oncogenic and thus neverused in clinical practice.Animal fetal precursor stem cell transplantation has been used in clinical practice in many countries: start in Switzerland, followed byGermany, France, Italy, Spain, Netherlands, Argentina, Mexico, Costa Rica, U.S.A (until 1956), U.S.S.R., Canada, Malaysia, Thailand,Hong Kong, Indonesia No ethical problems were ever encountered and reported anywhere.The described confusion, and repeated moves to destroy such a valuable therapy, deserves clarification.This paper is an attempt to do that.ANTI-AGING MEDICINESESSION 25AAANTI AGING WORKSHOP 10 PRACTICAL SESSION ON HOW TO IMPROVE THE DIGESTIVE SYSTEM11.00 am / 11h00INTESTINAL MUCOUS MEMBRANELA MUQUEUSE INTESTINALEINTESTINAL MICROFLORALA MICROFLORE INTESTINALEMICHAEL CULP(UK)FRANCISCO GUARNER(SPAIN)SÉANCE PRATIQUE SUR L'AMÉLIORATION DU SYSTÈME DIGESTIFCHAIR: GEORGES MOUTONMARCEL ROBERFROID (BELGIUM)124The human gut is the natural habitat for a large, diverse and dynamic population of micro-organisms which over millennia have adaptedto live on the mucosal surfaces or in the lumen. The interaction between gut bacteria and their host is a symbiotic relationship mutuallybeneficial for both partners. The host provides a nutrient-rich habitat and the bacteria confer important benefits to the host. Functionsof the microbiota include nutrition (fermentation of nondigestible substrates that results in production of short chain fatty acids,absorption of ions, production of aminoacids and vitamins), protection (the barrier effect that prevents invasion by alien microbes), andimportant trophic effects on the intestinal epithelium and the immune system (development and homeostasis of local and systemicimmunity).Symbiosis between host and gut bacteria can be optimized by prebiotics. Inulin-type fructans have been shown to improve the