[Clinical studies on the isolation of Clastridium difficile--13 cases].
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Biomedical subjects
Publications and source records attributed to T Ide.
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The effect of clofibrate on the production of ketone bodies and the secretion of lipids was examined in the isolated rat liver. Feeding of clofibrate (0.3% in the diet) for a week caused the liver enlargement. The drug increased ketone body production and conversely decreased the secretion of triglyceride and cholesterol in the perfused liver, in particular when oleate was provided to the perfusion medium. Fractionation of the liver perfusate at the density of 1.006 g/ml showed that changes in the rate of lipid secretion were largely due to the modification of the rate of very low density lipoprotein secretion. These observations indicated that the enhancement of fatty acid oxidation by clofibrate resulted in the concomitant decrease in the flux of free fatty acid into triglyceride synthesis and subsequent formation and secretion of triglyceride-rich lipoproteins in the liver. Measurement of activities of enzymes involved in hepatic cholesterogenesis proved that the alteration of the rate of hepatic cholesterogenesis might not be a factor responsible for the hypocholesterolemic action of clofibrate.
The effects of diet types on microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the intestinal villus and crypt cells isolated by scraping were studied in rats. The jejunoileal gradient for the reductase specific activity, a phenomenon usually observable in rats fed a commercial non-purified diet, disappeared when sucrose- or glucose-enriched semipurified diets were ingested. Feeding these semipurified diets resulted in a significant increase in reductase activity in jejunal villi and crypts with a concomitant decrease in that of the ileal populations. Neutral detergent fiber prepared from the non-purified diet, but not cellulose powder, when included to semipurified diets at the levels equivalent to those in the non-purified diet, eliminated the ileojejunal gradient, reductase activity was virtually the same in the proximal and distal portions of the intestine or the distribution pattern resembled that shown in rats fed a non-purified diet. Potato and corn starches replaced for sucrose in a low-fiber semipurified diet were also effective for elimination of the gradient, but wheat starch was less effective in the respect. It is clear that intestinal sterogenesis via HMG-CoA reductase is specifically regulated by the complex interplay of dietary components, in particular carbohydrate sources.
Isolated livers from rats fed soybean protein isolate and casein or amino acid mixtures simulating these proteins were perfused for 4 hours with Krebs-Henseleit buffer containing 0.15% glucose and 25% human red blood cells. Feeding soybean protein as compared with casein resulted in a significant reduction of the secretion of cholesterol, triglyceride and apo A-I. The results agreed well with the responses of serum counterparts reported previously. When amino acid mixture diets were fed, however, no such difference could be demonstrated, though the soy-type amino acid mixture had also been shown to decrease serum cholesterol and apo A-I. The production rate of total ketone bodies was the same, but the ratio of beta-hydroxybutyrate:acetoacetate was significantly higher in rats fed plant protein. The perfusate glucose tended to be higher on soybean protein. These differences were less clear on feeding amino acid mixtures. Neither the rate of bile flow nor the concentration of biliary bile acids and cholesterol were influenced by the type of dietary protein. These observations led us to conclude that soybean protein exerts the cholesterol-lowering action primarily through the regulation of hepatic contribution. The data also suggested that the protein-dependent difference in the concentration of serum cholesterol and apo A-I might not be explained thoroughly by the difference in the amino acid profile alone.
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Effects of dietary cholesterol, beta-sitosterol and cholestyramine on hepatic HMG-CoA reductase activity and sterogenesis were examined in male rats refed different types and amounts of fats for 3 days after fasting 2 days. Safflower oil (10%) decreased reductase and sterogenic activities more than saturated fat or low fat. Reductase activity and sterogenesis decreased as dietary cholesterol increased; this was not influenced by the type of dietary fat. Although cholesterol as low as 0.01% depressed these activities, more cholesterol was required to deposit cholesterol in the livcreased cholesterol excretion as neutral steroids but failed to enhance reductase and sterogenic activities. In contrast, cholestyramine increased these activities to approximately the same level irrespective of the type and amount of dietary fat. Hepatic cholesterol decreased only in rats refed saturated fat; neutral or acidic steroid excretion was greatest in this group. Hepatic cholesterol and enterohepatically circulating cholesterol may not be critical factors in regulating HMG-CoA reductase in fasted-refed rats. Rather, the quantity of bile acids fluxed to the liver appears to influence the reductase activity in this situation. However, analyses of fecal acidic steroids provided no evidence for a relationship between HMG-CoA reductase activity, bile acid metabolism and dietary fat.
The distribution of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat small intestine was modified by the type of the diets. The reductase activity in rats fed a commercial non-purified diet (rat chow) was markedly higher in the ileum than in the jejunum, while this pattern was reversed in animals fed a purified diet. Feeding a fat-containing purified diet, in comparison with a fat-free diet, resulted in a significant increase in the activity of the villous reductase. In rats fed a purified diet, the synthesis of digitonin precipitable sterols from [1-14C]acetate in vivo was considerably higher in rats fed a purified diet than in the animals fed a non-purified diet. Although responses to various measurements were not always consistent, the observation that the type of the diet modifies specifically the intra- and inter-tissue distribution of cholesterol synthesizing activity in the intestine strongly stresses the necessity of appropriate sectioning of the tissues, particularly in comparative studies. Also, comparisons of the sterogenesis of the small bowel and liver denote the possibility that intestinal contribution to endogenous cholesterol synthesis is considerably greater than previously estimated, even in the absence of dietary cholesterol.