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PubMedDate not supplied

Peritoneal macrophage cholesteryl ester content as a function of plasma cholesterol in rats.

Cholesterol accumulation in macrophages that have migrated in the subintimal space leads to foam cell formation, which is believed to be one of the initiating events in atherosclerosis. In this study we investigated the effect of cholesterol feeding on peritoneal monocyte/macrophage cholesterol content and peritoneal cavity lipoprotein composition in rats. A cholesterol (2%) and cholic acid (1%) diet caused significant hypercholesterolemia in plasma, and at the same time the cholesterol content of peritoneal monocytes/macrophages was increased. At day 7, the cellular cholesteryl ester content had risen to 30.1 micrograms/mg cellular protein from a baseline value of 9.2 micrograms/mg. The unesterified cholesterol content also increased by 56%. At this time, acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was doubled, whereas neutral and acidic cholesteryl ester hydrolase activities were unchanged. Reversal to the regular chow diet after 7 days of the cholesterol-enriched diet normalized plasma cholesterol levels as well as peritoneal monocyte/macrophage cholesteryl ester content. ACAT activity also decreased toward normal levels. Analysis of the d less than 1.21 g/ml peritoneal lipoproteins isolated by ultracentrifugation revealed the presence, in both normal and hypercholesterolemic rats, of apolipoprotein A-I-rich lipid complexes with pre-beta mobility on agarose gel electrophoresis. The size of the peritoneal lipoproteins was smaller than that of plasmatic high density lipoproteins, and their chemical composition was also different from that of the major plasma lipoproteins. The cholesteryl ester content of peritoneal lipoproteins increased after feeding of the cholesterol-enriched diet. In conclusion, our results show that cholesterol feeding leads to rapid accumulation of cholesteryl esters in monocytes/macrophages. As soon as plasma cholesterol levels are returned to normal, cellular cholesterol content is also normalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

[Causality relationship of drug adverse reactions: experience in the use of HIV-protease inhibitors].

PURPOSE: To establish the exact cause and effect relationship between protease inhibitors (PIs) and adverse events. MATERIALS AND METHOD: Prospective, cohort, multicenter study on HIV-positive patients who are beginning treatment with a PI. Causal relationships are evaluated using the RUCAM algorithm. RESULTS: Since the beginning of the study 1207 patients have been enrolled. Average time of observation is 10.7 months. To date, 784 adverse events have been observed, distributed as follows: excluded 3.8%, improbable 18.5%, possible 41.3%, probable 30.1%, and highly probable 6.3%. Saquinavir shows a statistically significant difference in the rate of non-correlated events with respect to other groups. CONCLUSIONS: Over 20% of adverse events during PI treatment are shown to be non-correlated to these drugs. Saquinavir shows the highest rate of non-correlated events.

Adult↗