Microbicides 2004 Microbicides 200428-31 March 2004, Hilton London MetropoleThe conference42 million men, women and children worldwide were living with HIV by the end of December 2002 (source: UNAIDS), including five million newly-infected during that year alone. Another 45 million people will become infected between 2002 and 2010, unless the current transmission rates can be vastly reduced. Of the 42 million, 29.4 million live in sub-Saharan Africa and 58% of them are women. Not only are women more susceptible to HIV infection, many are powerless to insist on the use of condoms or other methods of protecting themselves. In this context, and with the knowledge that an effective HIV vaccine is unlikely to be available for several years, the need for an effective topical microbicide grows ever more urgent. 2004 should prove to be a landmark year in the field of microbicide development as the first Phase III trials of novel products are due to start – the next step along the road to making a microbicide available to the millions worldwide in desperate need of protection.The aims of the Microbicides 2004 conference are to:Report novel or innovative work in the microbicides fieldProvide updates on recent microbicides research, divided into three tracks: basic science, clinical science, and behavioural science (including public health and the microbicide marketplace)Provide a forum for the discussion of new developments in microbicide research including ethical, clinical, behavioural and methodological issuesPresent opportunities for knowledge-sharing between microbicide researchers, public-health workers and advocacy organisations.There will be an opening ceremony on the evening of Sunday 28 March at which politicians, policy makers and the international media are expected. The conference will run for a full three days, each of which will contain:Scientific overviews and presentations with plenary sessions, invited lecturers and presentations of original researchWorkshops to review issues unique to microbicides such as trial design and outcome measures, and ethical issues in the clinical trials of microbicidesPoster sessions. Focus on LondonFollowing the successful Microbicides conferences in Washington in 2000 and Antwerp in 2002, March 2004 sees the focus move to London.The venue is the Hilton Metropole Hotel, two minutes by taxi from Paddington station and the Heathrow Express, with a journey time from the airport of 15 minutes. The hotel is in walking distance of Hyde Park and London’s main shopping streets, and close to Imperial College. Accommodation will be available at the venue and other hotels in the vicinity.London in March offers a variety of diversions for out-of-conference relaxation, including sight-seeing and shopping; the arts and the theatre; and pubs, clubs and restaurants to suit every taste. Conference staff will be on hand to help delegates plan their spare time.To book your place or find out more information, e-mail info@microbicides2004.org.uk or telephone the Event Office on +44 (0) 20 7720 4411
Oral: invited speaker Oral: Track A Oral: Track B Oral: Track C Poster: Track A Poster: Track B Poster: Track C Abstract only Authors

02627_1 SAMMA, A NOVEL CONTRACEPTIVE MICROBICIDE, INDUCES cGMP-DEPENDENT INDUCTION OF ACROSOMAL LOSS

Anderson, Robert A*
Feathergill, K*, Diao, X*, Chany, C*, Waller, DP**
TOPCAD Program, *Rush Med Cntr, **Univ of IL at Chicago,Chicago, IL

SAMMA, a low molecular weight non-sulfonated oligomer, is of interest as a contraceptive microbicide because it is structurally dissimilar to sulfonated high molecular weight polymers currently in development. Understanding SAMMA-activated signal transduction pathways common to sperm and sexually transmitted microbes may lead to a more efficacious product. The present study examined the roles of several protein kinases in SAMMA-induced acrosomal loss (SAL) in human sperm. Neither 25 µg/mL genistein (protein tyrosine kinase inhibitor) nor 0.5 µM KT5720 (cAMP-dependent protein kinase inhibitor) affects SAL. However, 0.5 µM calphostin (Ca2+ -phospholipid- dependent kinase (PKC) inhibitor) inhibits SAL by 94%. Without added Ca2+, soluble guanylate cyclase activation and AL by 20 µM nitroprusside (produces nitric oxide) is unaffected by 2 µM KT5823, a cGMP-dependent protein kinase (PKG) inhibitor. With added Ca2+, KT5823 by itself induces 66% maximal AL, and inhibits SAL by approximately 82%. Further, 0.5 µM S-methyl-L- thiocitrulline (nitric oxide synthase inhibitor) has no effect on SAL. These data suggest that SAL is mediated by PKG, in turn activated by cGMP, likely produced by a receptor-linked guanylate cyclase. Although nitric oxide increases cGMP and causes AL in human sperm, it is not likely involved in SAL. PKC may be involved in SAL, but it isn’t clear if activation of PKC is due to upstream activation of phospholipase C (PLC). Our studies suggest that one of the co-products of PLC-g action (inositol trisphosphate; IP3) has little, if any involvement. This is in contrast to suggested action of IP3 in AL induced by physiological stimuli, such as oocyte zona pellucida protein (Mol Human Reprod 3: 195, 1997). The relation between PKG and PKC as mediators of SAL remains to be determined. Supported by NIH grants HD41763 and AI37940

Dr. Robert Anderson
Ob/Gyn Res, Rush Med Cntr, 1653 W. Congress Pkwy, Chicago, IL 60612
(Telephone) 312-942-5451 (Fax) 312-942-5451 (E-mail) robertan@corecomm.net