Suppression of experimental atherosclerosis in rabbits by interferon-inducing agents.

The effects of two chemically different interferon inducers on the suppression of atherosclerosis were studied in rabbits fed an atherogenic chow diet. One group (10 rabbits per group) was fed normal rabbit chow, and three groups were fed an atherogenic chow. One of the latter groups received the atherogenic feeding alone; the other two were treated with either polyinosinic-polycytidylic acid (poly I:C) or 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP). Neither of the drugs reduced significantly the hypercholesterolemia induced by the feeding. However, both poly I:C and ABPP treatment significantly reduced the percent area of the aortic intimal surface lesions, stained for lipid with Sudan IV, compared with that in untreated rabbits fed atherogenic chow. Microscopic sections of typical aortic plaques showed that both drug treatments significantly reduced the size and number of intimal lipid deposits compared with those observed in the aortas of untreated animals. Chemical analysis for cholesterol and collagen content revealed that interferon-inducing agents significantly reduced cholesterol deposits in the aorta, with little effect on fibrous protein deposition. The results indicate that two unrelated interferon-inducing drugs suppressed atherogenesis without reducing serum cholesterol and low density lipoprotein levels. Whether the protection against atherosclerosis is exerted by endogenous interferon production remains to be determined.

Mediation of depression by perceptions of defeat and entrapment in high-stress mothers.

Previous studies have demonstrated a causal role of stress in depression, and an association between depression and perceptions of defeat and entrapment. The present study was conducted to determine whether perceptions of defeat/entrapment mediate the relationship between stress and depression. Seventy-six mothers of children attending specialist educational provision for a range of special needs completed the Parenting Stress Index-Short Form (PSI-SF), Defeat and Entrapment Scales, the Beck Depression Inventory (BDI), and the Fawcett-Clark Pleasure Capacity Scale (FCPCS). Relative to population norms, respondents reported very high levels of stress, moderately high levels of defeat/entrapment, mild depression, and very low hedonic capacities. Most of these measures were more extreme in younger mothers and those with a prior history of depression. FCPCS scores were correlated negatively with stress, after controlling for levels of defeat/entrapment, but were not correlated with BDI scores, suggesting that the FCPCS may be an unsuitable instrument for use in the present participant population. Significant positive correlations were found between all measures of stress, defeat/entrapment and depression. After controlling for PSI-SF scores, correlations between BDI and defeat/entrapment scores remained highly significant. However, after controlling for defeat/entrapment, correlations between BDI and PSI-SF scores were non-significant. Hence, perceptions of defeat/entrapment mediate the relationship between stress and depression. This relationship was confirmed formally using regression analysis. Because respondents reported high levels of stress in contrast to mild levels of depression, a causal link can be inferred, running from stress via defeat/entrapment to depression.

Management of obstructed biliary endoprostheses.

In five patients with bile duct obstruction, a previously inserted endoprosthesis became occluded. After repeat percutaneous biliary drainage, the prostheses were mechanically unclogged, removed, or removed and replaced. No patient required surgery, and no prosthesis reoccluded. We discuss technique for deoccluding and, if necessary, removing and replacing obstructed stents.

Suppression of aortic atherosclerosis in cholesterol-fed rabbits by purified rabbit interferon.

The effectiveness of rabbit interferon in suppressing atherosclerosis was evaluated in rabbits fed a diet containing 1% cholesterol. Ten male New Zealand White rabbits received intramuscular injections of 1 million units of interferon twice a week, while a control group of 10 rabbits received injections of buffer. Both groups had average serum cholesterol levels of over 2000 mg/dl during the 8-week experimental period. Interferon treatment resulted in no significant hypolipidemic effect or changes in lipoprotein composition. Atherosclerotic lesions in aortas were quantified both macroscopically and microscopically. Interferon treatment decreased the grossly visible lesion area significantly from 25 +/- 4% to 8 +/- 1% (mean +/- SEM, p less than 0.005) compared to the untreated group. Microscopic analysis of serial cross-sections of aortic segments revealed significant (p less than 0.01) reductions in both lesion size and frequency in the interferon-treated group. Electron microscopy also showed that interferon treatment reduced the pathological effects of cholesterol feeding. Tissue analysis showed that total aortic cholesterol was reduced by 28% by interferon treatment, while the aortic phospholipid concentration was increased by 25%. The possibility exists that the interferon preparation used contained other biological response modifiers and that the observed effects may be totally unrelated with interferon. These results suggest that the mechanism of atherosclerosis suppression in these cholesterol-fed rabbits is not related to the lowering of serum cholesterol but may be associated with inhibition of lesion initiation.

Effect of high fat and high sucrose feeding on lipogenesis by isolated rat intestinal cells.

Lipid synthesis was studied in intestinal mucosal cells isolated from rats fed a high fat or a high sucrose diet. The cells actively incorporated 14C(1)-labeled free fatty acids into glycerolipids [( 1-14C]acetate was utilized for both fatty acid and cholesterol synthesis), while [14C(U)]glucose label was found in cholesterol and in the glycerol moiety of glycerolipids, but not in fatty acids. Sucrose feeding resulted in increased acetate incorporation into cholesterol, but not into fatty acids while the high fat diet markedly depressed the incorporation of acetate. In contrast, fat feeding increased both glucose and fatty acid incorporation into glycerolipids, as well as glucose incorporation into cholesterol. Using the incorporation of glucose into lipid glycerol as an estimate of the phosphatidic acid pathway, it was found that this pathway was stimulated by both fat and carbohydrate feeding. The results suggest that differences in the regulation of cholesterol and glycerolipid synthesis in the intestine compared with adipose tissue and liver may relate to the role of intestine in synthesizing lipoproteins for lipid transport.

Common bile duct obstruction: assessment by transcholecystic cholangiography.

Percutaneous transcholecystic cholangiography was performed in 20 patients. Fifteen patients had normal-sized bile ducts on sonograms and computed tomographic scans, and five had partial common bile duct obstruction. Gallbladder pressures were measured in 14 patients. In all cases the intrahepatic and extrahepatic bile ducts were well visualized. Only one clinically significant complication, bile peritonitis, occurred, and it was relieved by inserting a cholecystostomy catheter. Techniques as well as the potential indications for transcholecystic cholangiography are discussed. The authors believe the transcholecystic approach is a useful alternative to transhepatic cholangiography.