Digital information evolution: the AIDS Library experience.

The AIDS Library evolved out of consumer health activism in response to the need for the latest HIV information, materials, and technology. In 1998, staff implemented a microcomputer-based integrated automated library system with Web publishing capability to link catalogs, databases of Philadelphia regional services, online publications, and fact sheets. The Web site, , became "live" December 1, 1998. History leading to its development and future plans are presented.

Oxathiin carboxanilide, a potent inhibitor of human immunodeficiency virus reproduction.

Oxathiin carboxanilide (OC), NSC 615985, a compound originally synthesized as a potential fungicide, was demonstrated to be highly active in preventing human immunodeficiency virus (HIV)-induced cell killing and in inhibiting HIV reproduction. Virus-infected CD4+ lymphocytes were completely protected by 0.5 microM OC, whereas no toxicity was observed at concentrations below 50 microM OC. Production of infectious virus, viral p24 antigen, and virion reverse transcriptase were reduced by OC at concentrations that prevented viral cell killing. A variety of CD4+ T-cell lines were protected by OC from HIV cytopathicity, and OC inhibited two distinct strains of HIV-1. However, HIV-2 infections were unaffected by OC. OC had no direct effect on virions of HIV or on the enzymatic activities of HIV reverse transcriptase or HIV protease. Time-limited treatments of cells with OC before, during, or after exposure of cells to virus failed to protect cells from the eventual cytopathic effects of HIV, and OC failed to inhibit the production of virus from cells in which infection was established or from chronically infected cells. We conclude that the highly active OC has a reversible effect on some early stage of HIV-1 reproduction and cytopathicity. Pilot in vivo experiments showed that circulating concentrations of OC exceeding 1 microM could be achieved and sustained in hamsters for at least a week with no remarkable toxicological sequelae. OC represents a new class of anti-HIV agents that are promising candidates for drug development.

Preparation and antiinflammatory activity of 2- and 4-pyridones.

Several N-alkyl- and N-arylacetoacetamides have been self-condensed to form pyridones. N-Alkylacetoacetamides give 2-pyridones, while N-arylacetoacetamides give 4-pyridones. In an attempt to develop nonacidic, nonsteroidal antiinflammatory agents, the pyridones were tested in a carrageenan-induced pedal edema assay in rats. While the 2-pyridones were not active, 9 of 17 4-pyridones tested were active, and one compound (4g) had antiinflammatory efficacy in a dose-response assay (ED50 values). Most compounds were considered nontoxic by determination of approximate LD50 values in mice by a standard multidimensional observational assay.