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ABSTRACT: Some analogues of gonadotropin-releasing hormone GnRH ; influence the in vitro proliferation of cultured human cells by complex interactions that are only partially understood. This study explored the effect of Triptorelin, a GnRH agonist, on the LNCaP and PC3 prostatic cell lines, which are, respectively, responsive and unresponsive to androgen stimulation. The toxicity and cell cycle modifications induced by the drug were investigated by FACScan analysis; the effect on cell proliferation in different culture conditions was determined by counting in a Burker chamber; and the expression of binding sites for 125I-Triptorelin was revealed by displacement experiments. PC3 cell growth was completely unaffected by Triptorelin. The drug caused a double stimulatory-inhibitory action on the growth of actively proliferating LNCaP cells, depending upon the dose and environment. A significant inhibitory effect on proliferation, ranging from 25% to 65% compared with controls, was observed at a high dose 10 4 M ; according to the culture conditions; and a proliferative effect 42% compared with controls ; was observed at a.

Some news reports have indicated shortages of the product at retail, but roche has special measures in place to ensure that tamiflu is readily available.

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Stock holder will be the World Health Organization. It can then be made available to governments at the quickest possible speed when the first human to human cases become apparent and then it can used as a part of an initial response. The stock of Tamiflu is currently 3 million courses that's been provided by the manufacturer for WHO. Not all of those are yet produced but they are going on stream in the near future. The makers of Relenza are also planning to make a donation that will soon be available. WHO is going for more stocks to be put at regional levels so that there is going to be more capacity and is looking at the procedure of dissemination of those stocks. And that is going to have a key role in helping to do the initial containment of influenza. JENKINS: Steve wants to jump in but I've got just one quick questions. If this thing hits within the next 6 months to a year, when we will not yet have the stockpiles that we want. Are we going to see a situation where the wealthy countries that have these stockpiles, Britain and France, is actually going to say we are hanging on to ours and we are not going to share it with these Asian and African countries? NABARRO: This is going to be the test of how our world works. The joint-up-ness of our world. If the countries that have stocks of Tamiflu hang on to them and there's none available for a poor country, which might be the country where the pandemic is starting, the rebound will affect the rich countries as well as the poor countries. It will be very short-sighted attitude for countries just to hang on to their stocks for their own population and not pay attention to what's happening where the pandemic is starting.

Disease. Vaccines are developed by cultivating the virus in chicken eggs, however, H5N1 attacks and kills chicken eggs, rendering efforts to cultivate it useless. The answer the scientific community has come up with to combat this problem is reverse genetics, making the H5N1 virus harmless to chicken eggs and facilitating the development of a vaccine. Scientists are also exploring other options available as Tamiflu production is limited. Research is being done to develop other drugs that might be as effective, or perhaps more effective at combating this deadly virus. The World In the wake of the spread of the H5N1 virus, the world has begun to take notice, and many countries are rushing to stockpile drugs and draft preventive measures. More funding has also been channeled towards development and research into combating this disease. Britain for example has stockpiled 14.6 million courses of Tamiflu, and has measures in place for physical prevention in the case of an outbreak. Thailand has deployed personnel to spray disinfectant on infected farms and villages. Many countries in Southeast Asia have to date culled millions of birds in an effort to stem the spread of the virus. However, it is still spreading at a frightening pace. Recently there have been reports of bird flu in birds as faraway as Germany, France and other European countries and taxol. We have demonstrated that chenodeoxycholic acid in physiological concentrations reduces sensory thresholds to rectal balloon distension. This study demonstrates that the stimulation of rectal afferents can elicit both inhibitory and excitatory responses from the unprepared proximal human colon. In contrast to this synergism in effects on rectal sensation between chemical and mechanical stimuli, these stimuli had opposing effects in terms of colonic motor responses. Rectal instillation of a physiological concentration of chenodeoxycholic acid initiates propagating sequences in the proximal unprepared colon. Balloon distension of the rectum inhibits all types of proximal colonic activity. These responses are presumed to be mediated by long colocolonic pathways. These observations are consistent with the hypothesis that a combination of chemical and mechanical rectal stimulation enhances proximal colonic propagating activity while retarding nonpropagating activity and that such a combination of responses is likely to facilitate colonic transit and defecation. The colon is responsive to stretch in vivo and in vitro 4, 28 ; . We found that rectal balloon distension suppressed both propagating and nonpropagating activity and that this response was most pronounced in the cecoascending colon. The reported observations to date are conflicting with some 16 ; showing colonic distension to have little or no effect on the elicitation of colonic propagating events in the human colon, whereas others 4 ; found balloon distension to elicit.

The hormone affects maturation of oocytes. Its action is required for optimal oocyte cytoplasm and oolemma maturation Filicori, 1999 ; . Thus, it plays a crucial role in determining the quality of oocytes Kreiner et al., 1987 ; . It has been documented that, in oestrogen-poor follicles, the quality of oocytes may be adversely affected Fishel et al., 1983; BoteroRuiz et al., 1984 ; . A good quality matured oocyte is defined as one in which the re-initiation and division of first meiotic phase is complete, and has progressed to metaphase II with completion of the accompanying cytoplasmic process essential for fertilization and early embryonic development. Fertilization rates were proved to be higher with mature oocytes Edwards et al., 1984 ; . In our study, follicular and mature oocyte numbers showed a significant negative association with the severity of the PvuII polymorphism. It is possible that this polymorphism downregulates the ER gene, interfering with the effective mediation of oestrogen and its functions, on the follicleoocyte unit. This down-regulation could vary with the severity of the polymorphism, leading to variation in follicle and oocyte numbers in each of the three polymorphic groups. In a recent study in a Greek population, two polymorphisms PvuII and BstUI in the ER- gene that were known to be associated with breast cancer and spontaneous abortion in particular were analysed in IVF patients to elucidate the role of ER- in ovulation induction and implantation Georgiou et al., 1997 ; . It was found that these polymorphisms were associated only with the ratio of follicles to oocytes and not with the number of follicles or number of oocytes. The polymorphisms appeared to affect the ovarian response by changing the final number of mature oocytes. In the present study, however, strong negative associations were found between severity of PvuII polymorphism in the ER gene, with both the follicular and mature oocyte numbers, and their ratios. A major contributing factor to the high follicular number and oocyte number in our study and their significant association with PvuII polymorphism could be due to the difference in stimulation protocol, the criteria used to select follicular size for HCG administration, and for oocyte aspiration. Difference in ethnicity of the population group studied could also play some role in contributing to the variation. Screening of this polymorphism in other populations and their responses to stimulation may have to be carried out to substantiate these findings. The ratio of mean follicle number to mean mature oocyte number was lowest in the no-polymorphism group indicating that this group had the highest number of mature oocytes per follicle. Moreover, the homozygous polymorphic group showed highest ratios with the lowest number of mature oocytes per follicle. ER polymorphisms may thus affect the ovarian response by changing the final number of mature oocytes in relation to the number of follicles. In our study, a significant negative association was also seen between follicular sizes and severity of the polymorphism. Oestrogen enhances FSH-stimulated aromatase activity, progestin and cAMP biosynthesis in cultured granulosa cells Adashi and Hsueh, 1982; Welsh et al., 1983 ; . Oestrogen receptors are present in human granulosa cells and play an 800 and tamiflu.

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