Clinical Science Workshop 3 Free session Chairpersons : P . Portegies ( Amsterdam , NL ) I . Grant ( La Jolla , USA ) 57 Pro - glutathione compounds as alternative therapeutical strategy in neuroaids

Oxidative stress seems toplay amajor role inHIV pathogenesis. It increases HIV replication through the activation of NFkappaB and is involved in neuroAIDS, particularly through increased apoptotic phenomenon. Glutathione (GSH) is the major intracellular antioxidant and its deŽciency has been correlated with HIV replication and decreased survival of HIV-infected patients. In order to counteract these deleterious processes and to potentate the efŽcacy of antiretroviral molecules in the central nervous system, new pro-GSH molecules have been synthesized and their anti-oxidant and anti-HIV activities were evaluated in vitro. I-152, a pro-drug of N-acetylcysteine (NAC) and ß-mercaptoethylamine (MEA) has shown better antioxidant and direct antiviral properties as compared with these reference molecules. I-152 increases GSH level in several cell types such as human lymphocytes, monocyte-derived and tissular macrophages, in astrocytes (also involved in free radical detoxiŽcation and neuroprotection), as well as murine cortical neurons, particularly susceptible to oxidative stress-induced apoptosis). In pathophysiological conditions inducing a GSH deŽciency i.e. HIV infection of MDM, I-152 restores the intracellular GSH level. Moreover, the antioxidant activity of I-152 is associated with anti-inammatory effects i.e. decreased TNF-alpha synthesis in macrophages and neuroprotective effects in H2O2or buthionine sulfoximine (BSO)-exposed neuronal cultures. At last, antiretroviral effects of NRTI, NNRTI and protease inhibitors is increased by co-treatment with I-152 conŽrming that pro-GSH molecules e.g. I-152 may be alternative therapeutical strategies in NeuroAIDS. 58 Detection of JC virus DNA sequences and cellular localization of viral products T-antigen and agnoprotein in oligodendrogliomas L. Del Valle,1 S. Enam,1 C. Lara,1 C. Ortiz-Hidalgo,2 C.D. Katsetos,3 K. Khalili1 1. Temple University (Philadelphia , USA) 2. American British Cowdray Hospital (Mexico City, MEX) 3. St. Christopher’s Hospital Children (Philadelphia , USA)