Viremia and AIDS in rhesus macaques after intramuscular inoculation of plasmid DNA encoding full-length SIVmac239.

We have succeeded in stably maintaining the entire genome of SIVmac239 as a plasmid clone. Supercoiled proviral plasmid DNA was inoculated intramuscularly into two adult rhesus macaques and into a neonate. All three animals became viremic and seroconverted. Viral kinetics were followed prospectively by quantitative competitive reverse transcriptase polymerase chain reaction (QC-RT-PCR), measurement of proviral DNA load in peripheral blood mononuclear cells (PBMCs) by PCR, and virus isolation by cocultivation. The infant developed high virus loads and succumbed to AIDS and SIV-associated nephropathy at 10 weeks postinoculation. Both adults are still living but have progressed to AIDS; one adult has also developed severe thrombocytopenia. We conclude that infection through intramuscular inoculation of cloned plasmid DNA encoding the entire proviral genome is reproducible and will provide a useful tool for studying viral pathogenesis.

Use of prostacyclin and its analogues in the treatment of cardiovascular disease.

Prostacyclin is found in all body tissues and body fluids, and is the major metabolite of arachidonic acid in the vasculature. It is a potent vasodilator that affects both the systemic and pulmonary circulations. Prostacyclin also prevents vascular smooth muscle proliferation and inhibits platelet adhesion and aggregation. These features have made it a very attractive substance for treatment of many different cardiovascular diseases. Epoprostenol, a synthetic prostacyclin, is currently available in parenteral form for the treatment of primary pulmonary hypertension, and has been shown to be a valuable palliative therapy. The drug appears to have limited effectiveness for treating patients with congestive heart failure and coronary artery disease, but has shown some utility in patients with peripheral vascular disease, including Raynaud's phenomenon. Analogues of prostacyclin are now in clinical trials and include iloprost, a stable analogue that has been used intravenously to treat patients with peripheral vascular disease. Other parenteral formulations under investigation include taprostene, ciprostene, and UT-15. Beraprost and cicaprost, are two prostacyclin analogues that can be used in oral form, are being studied in clinical trials.