Elevation of serum cholesterol levels in mice by the antioxidant butylated hydroxyanisole

The food antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are structurally related to the hypocholesterolemic drug probucol. The purpose of this study was to determine if BHA can lower serum cholesterol levels as is observed with probucol. Treatment of mice with 0.75% BHA in their feed for 10 days resulted in a significant (P < or = 0.01) elevation of serum cholesterol levels. This effect contrasts with the cholesterol-lowering effect of probucol. Further, the degree of cholesterol elevation was comparable to that observed in mice administered 3% cholesterol in their feed for 7 days. The enzyme acyl CoA:cholesterol acyltransferase (ACAT) was decreased significantly (P < or = 0.01) in liver microsomes from BHA-treated mice. In contrast, hepatic microsomal ACAT activity was increased significantly (P < or = 0.01) in cholesterol-fed mice. These results suggested that the increased serum cholesterol observed in BHA-treated mice was not accompanied by an increase in hepatic cholesterol levels. Indeed, hepatic microsomal cholesterol levels were reduced in BHA-treated mice, but were increased significantly (P < or = 0.01) in cholesterol-fed mice. These results demonstrate that the common food additive BHA elevates serum cholesterol levels by a mechanism that apparently involves the decreased uptake of cholesterol by the liver.     

Influence of HIV-related immunodeficiency on the histopathology of chronic hepatitis C

OBJECTIVE: There is substantial evidence demonstrating the aggravating effect of human immunodeficiency virus (HIV) infection on the progression of chronic hepatitis C virus (HCV) infection. There is however, little data on the affect of certain factors which could affect liver pathology findings in patients with concomitant HIV infection such as the duration of HIV infection or T-cell subpopulation counts. We examined pathology findings in patients with concomitant HIV and HCV infections to determine the impact of immunodepression. PATIENTS AND METHODS: We reviewed liver pathology data collected in patients with concomitant HIV and HCV infections grouping patients according to severity of the liver pathology: group 1 = cirrhosis or active hepatitis; group 2 = minimally active hepatitis or histologically normal liver. Transparietal liver biopsies were obtained for the work-up of viral hepatitis or because of long-term unexplained fever or suspected lymphoma. Epidemiological and biological data were obtained from medical files. The duration of the liver disease was estimated from the date of exposure to risk of immunodepression as determined by the peripheral CD4+ and CD8+ counts. All pathology specimens were read by two pathologists who established the Knodell score for each patient. RESULTS: Fifty patients were included: 23 were classed in group 1 and 28 in group 2. The Knodell score was significantly different between the two groups, 11 +/- 4 and 4 +/- 3 respectively (p < 0.0001). Disease duration was similar for the two groups: mean 8 years. Mean CD4+ count was significantly higher in group 1: 312/mm3 versus 110/mm3 for group 2 (p = 0.0057); as was the mean CD8+ count (758/mm3 versus 360/mm3, p = 0.0013). For the entire study population, there was a significantly negative correlation (p < 0.05) between the Knodell score and the CD4+ count (r = 0.31) and for the CD8+ count (r = 0.41). CONCLUSION: HCV-related liver pathology in patients co-infected with HIV depends on the level of immunodepression. CD8+ counts are better correlated with pathology findings than with CD4+ counts.     

Design of an isolated pig heart preparation for positron emission tomography and magnetic resonance imaging

RATIONALE AND OBJECTIVES: Validation of new positron emission tomography (PET) tracers or magnetic (MR) imaging contrast agents is based on isolated rodent heart preparations. The use of larger animals could provide a more direct validation using the devices used for humans. METHODS: An isolated pig heart preparation has been developed and adapted to the technical constraints of whole body PET and MR imaging. This preparation could be used either in the Langendorff or working mode after selective cannulation of both coronary arteries. RESULTS: The authors showed that quantification of regional kinetics of PET tracers was possible using this preparation by measuring fluorine-18-labeled deoxyglycose (18FDG) kinetics in remote and ischemic territories. Experiments using MR imaging contrast agents, for myocardial perfusion, demonstrated the ability of this preparation to accurately validate these contrast agents over a wide range of flow rates. CONCLUSIONS: An isolated pig heart preparation could be developed to fulfill the constraints of PET and MR imaging, and proved useful for the study of the distribution of different tracers or contrast media developed for functional cardiac imaging in humans.