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_2 T-TYPE CA 2+ CHANNELS MEDIATE SAMMA-INDUCED HUMAN ACROSOMAL LOSS

Anderson, Robert A*
Feathergill, K*, Diao, X*, Chany, C*, Herold, B**, Cooper, M***, Waller, DP****, Zaneveld, LJD*
TOPCAD Program, *Rush Univ Med Cntr, ****Univ of IL at Chicago,Chicago, IL, **Mt. Sinai Sch. of Med, NY; ***SIU Sch of Med, Springfield, IL

Work is ongoing to understand the actions of the contraceptive microbicide, SAMMA, a novel low molecular weight carboxylated oligomer. Past work suggested that SAMMA induces acrosomal loss (AL) in human sperm by activating voltage-dependent Ca2+ channels, though probably not L-type. The present study extended observations with Ca2+ channel antagonists and examined selected Ca2+-dependent pathways. Thapsigargin (THG; releases intracellular Ca2+ stores) also induces AL; 1 µM THG causes a 93% (90% confidence limits = 84.0-98.5%) maximal AL; 10 µM nifedipine inhibits this response by 68%. 2-aminoethoxydiphenylborate (2-APB) prevents inositol triphosphate-mediated release of intracellular Ca2+. Consistent with inhibition by nifedipine of THG-induced AL and its failure to block SAMMA-induced AL, 2-APB is without effect. Diphenylhydantoin, a T-type Ca2+ channel blocker, inhibits SAMMA-induced AL (IC50 - 200 µM). Neither trifluoperazine nor calmodulin binding domain affect SAMMA-induced AL, arguing against a role of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). The data suggest that Ca2+ entry, via either L- or T-type calcium channels, causes AL. CaMKII, involved in AL caused by sustained increases in intracellular Ca2+ (Fert. Steril. (Progr Suppl): S181, 1992), isn’t important in SAMMA-induced AL. The oocyte zona pellucida (natural AL stimulus) may cause Ca2+ entry through L-type channels, activation of which are triggered by release of intracellular Ca2+ stores (Mol. Hum. Reprod. 3: 195, 1997.). Similar signalling may accompany epithelial cell infection by HSV (J Cell Biol 163: 283, 2003). SAMMA may be contraceptive and microbicidal by altering the normal Ca2+ responses to viral and sperm entry into target cells. 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