Screening of compounds with potential use in the treatment of human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) can currently be made in cell culture systems, but there is a need for relevant animal models. We have infected cynomolgus monkeys with simian immunodeficiency virus of sooty mangabey origin (SIVSM) and investigated the influence of multiplicity of infection (MOI) and the effects of three different anti-HIV compounds, 3′-azido-3′-deoxythymidine (AZT), foscarnet (PFA) and 2′,3′-dideoxycytidine (ddC) on the acute infection. To secure a maximal effect of treatment this was started 8h before challenge with SIVSM and the drugs were given subsequently every 8h for 7–9 days. The appearance of viral antigen and antibodies in serum was determined. In control animals the mean day for SIV antigen appearance was Day 5.9 post-infection, whereas in animals treated with 3 × 25 mg kg−1 day−1 of AZT and 3 × 65 mg kg−1 day−1 of PFA there were significant delays in SIV antigen appearance of 1.0 and 3.6 days, respectively. Some delay in antigen appearance was indicated in animals treated with 3 × 0.2 mg kg−1 day−1 of ddC. A delayed antibody response was only seen in animals treated with PFA. Viral infection was not prevented at the multiplicity used with any of the drugs, despite treatment prior to virus inoculation. The animal model described offers attractive features for in vivo evaluation of potential anti-HIV compounds.
Objectives The study was designed to compare effects of food deprivation (FD) and sleep deprivation (SD) on cognition during survival training. Methods In a cross-over design (n=12), the effects of FD (up to 66 hours followed by 500 kcal intake over 24 hours) and SD (up to 50 hours) on cognitive variables, blood glucose, and 3-OH-butyrate were studied. Results Food deprivation and SD impaired attention-dependent tasks. The FD impairment of simple reaction time was independent of blood glucose levels, which were normalized by a 500 kcal intake over 24 hours while the reaction time was not. Sleep deprivation and FD impaired maze-solving performance on all variables except rule breaks, which were significantly occurring after 50 hours of SD. Delayed word recall was impaired by SD for 50 hours. On the Balloon Analogue Risk Task, SD was associated with reduced risk-taking. In a gambling task, both SD for 50 hours and FD for 66 hours were associated with a tendency to make early choices when presented with consecutive choices, but the risk-taking was not affected. Conclusions Sleep deprivation has multiple cognitive effects, including attention, memory, visual-spatial ability, and risk-taking. Food deprivation had no affect on risk-taking, while the other tasks were affected in a way similar to SD but were less pronounced. The FD effects on cognition did not appear to depend on blood sugar levels. The need to sleep should be prioritized in survival situations to avoid cognitive impairment.
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