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Biomedical subjects

M T Subbiah

Publications and source records attributed to M T Subbiah.

At least 127 records · Page 7Linked to original sources

Effect of estrogens on the concentration and composition of arterial sterols and steryl esters in male white carneau pigeons.

The effect of short-term (6 months) administration of conjugated equine estrogen (Premarin) on content and composition of the aortic sterols in male shite Carneau pigeons while they were on a cholesterol-free grain diet was investigated. Estrogen treatment resulted in a 38% increase (P less than 0.05) in free sterol concentration, with a 28.8% concomitant decrease (P less than 0.05) in the percent of cholesteryl esters. The total sterol concentration remained unchanged. This finding suggests that estrogens might influence the synthetic or hydrolytic (or both) processes that control the concentration of cholesteryl esters in the aorta. Fatty acid composition of steryl esters did not change significantly. The cholesterol content of plasma showed a mild reduction (14%) whereas the triglycerides increased significantly (30%).

Animals↗

Effect of prostaglandins E1 and F1alpha on the activities of cholesteryl ester synthetase and cholesteryl ester hydrolases of pigeon aorta in vitro.

The in vitro effects of prostaglandins E1 and F1alpha on the activity of cholesteryl ester synthetase and cholesteryl ester hydrolase activities of the pigeon aorta were examined. It was found that prostaglandin E1 markedly inhibited the cholesteryl ester hydrolase activity in the supernatant fraction and slightly inhibited the cholesteryl ester synthetase activity. Prostaglandin F1alpha, however, modestly stimulated the cholesteryl ester hydrolase activity both in the microsomal and in the supernatant fraction of the aorta. These observations strongly warrant further studies on the role of prostaglandins in atherogenesis.

Animals↗

Effect of estrogens on the acitivities of cholesteryl ester synthetase and cholesteryl ester hydrolases in pigeon aorta.

This study is the first to report the effect of conjugated equine estrogens on the acitivity of cholesteryl ester synthetase and cholesteryl ester hydrolases in the aorta. In spontaneously atherosclerosis-susceptible White Carneau pigeons, estrogens significantly decreased (P less 0.01) the activity of cholesteryl ester synthetase and increased (P less than 0.01) the cholesteryl ester hydrolase activity in the microsomal fraction of the aorta. There was no effect on the cholesteryl ester hydrolase activity in the supernatant fraction. The inhibition of cholesteryl ester synthesis and the stimulation of cholesteryl ester hydrolase might be responsible for the decreased content of cholesteryl esters noted in pigeon aorta after estrogen treatment.

Acyltransferases↗

Sterol and bile acid metabolism during development. 1. Studies on the gallbladder and intestinal bile acids of newborn and fetal rabbit.

Bile acid composition and content in the intestine and gallbladder of newborn and fetal rabbits were investigated. Unlike the circumstances in adult rabbits, the bile acids were conjugated with both taurine and glycine. The major bile acids of the fetus and newborn rabbit were cholic acid, chenodeoxycholic acid, and deoxycholic acid. This is different from the known bile acid composition of adult rabbits, in which deoxycholic acid is the major bile acid (greater than 80%). The proportion of chenodeoxycholic acid was higher in the fetal than in the newborn tissues. The total bile acid pool in the newborn was higher than in the fetus. In the fetus, large proportions of bile acids (60.9%) were associated with the gallbladder fraction, whereas in the newborn the bulk of the bile acids were found with the intestinal fraction (64.4%).

Animals↗

Sterol and bile acid metabolism during development: 2. Identification of 3beta-hydroxy-5-cholenoic acid (an intermediate in alternate pathway of bile acid synthesis) in newborn and fetal guinea pig.

3beta-hydroxy-5-cholenoic acid was found in the bile and feces of newborn and fetal guinea pigs. The identity of this compound was confirmed by gas chromatography and mass spectrometry. This finding suggests that the formation of chenodeoxycholic acid through 3beta-hydroxy-5-cholenoic acid is intermediate in the early life of guinea pigs. Thus, it provides a useful model for studying the details of regulatory factors and significance of this pathway. This study also revealed that, unlike the adult guinea pig, the newborn guinea pig has significant amounts of glycine conjugates of bile acid.

Animals↗

Smooth muscle cells of intimal cushions and the localization of atherosclerotic lesions.

Atherosclerosis results from a precise sequence of endothelial interaction with platelets or thrombocytes and mononuclear cells, uptake of specific lipoproteins, cholesteryl ester removal, production of collagen, elastin ad proteoglycans by activated smooth muscle cells. Thus, both the filtration hypothesis and the thrombogenic hypothesis for the pathogenesis of atherosclerosis appear to be correct.

Animals↗

Effect of long-term administration of estrogens on the subcellular distribution of cholesterol and the activity of rate-limiting enzymes of cholesterol biosynthesis and degradation in pigeon liver.

To determine the mechanism of the hypocholesteremic effect of estrogens noted in pigeon, studies were done on the subcellular distribution of cholesterol and the activity of beta-hydroxy-beta-methylglutaryl CoA reductase (HMG-CoA reductase) and and cholesterol 7alpha-hydroxylase in pigeon liver after long-term (6 months) estrogen administration. Estrogens significantly reduced free cholesterol concentration in microsomes and mitochondrial fraction. The concentration of cholesteryl ester was reduced in the supernatant fraction. The activity of HMG-CoA reductase was significantly reduced in the estrogen-treated birds, while cholesterol 7alpha-hydroxylase activity showed no changes. Thus, the hypocholesteremic effect of estrogen noted in pigeons could be mainly due to the inhibition of cholesterol biosynthesis in the liver.

Animals↗

Concentration changes of bile acids in sequential segments of pigeon intestine and their relation to bile acid absorption.

Changes in the concentration of bile acids in sequential segments of pigeon intestine were measured. It was found that the jejunum has the highest concentration of bile acids. When the ratio of bile acids to beta-sitosterol (a non-absorbable dietary marker) was examined in contents of various segments, it was found that the ratio showed a marked decrease (86.6%) from the upper to lower jejunum while the subsequent changes in other segments were not as striking. This indicates that the jejunum is the major site of bile acid absorption in the pigeon, unlike in mammals, where the ileum has been shown to be the major site of bile acid absorption. This notion was confirmed by studies of the effect of ileal bypass in these pigeons. This surgical procedure did not significantly change the fecal excretion of bile acids or neutral sterols indicating that the jejunum is capable of maintaining a normal enterohepatic circulation of bile acids in the absence of the ileum in the pigeons.

Animals↗

Effect of dietary restriction on plasma cholesterol and cholesterol excretion in the White Carneau pigeon.

The effect of short-term dietary restriction on plasma cholesterol and cholesterol balance was examined in young While Carneau pigeons. Dietary restriction of 1 month increased plasma cholesterol significantly and subsequently decreased to initial levels at 3 months. The fecal excretion of neutral sterols was significantly reduced (P less than 0.001) at both 1 and 3 months following dietary restriction, while the fecal excretion of bile acids showed no significant changes.

Animals↗

On the cholesteryl ester hydrolase activity in the microsomal and supernatant fractions of pigeon aorta.

Cholesteryl ester hydrolase activity was measured in the microsomal and supernatant fractions of the aorta of atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons while on their normal cholesterol-free diets. Enzyme activities from both fractions showed fatty acid specificities for the hydrolysis of different cholesteryl esters in the following decreasing order: Linoleate greater than oleate greater than palmitate. At 9 months of age (the period of lipid accumulation) the microsomal enzyme activity in the Show Racer breed was significantly higher (P less than 0.001) than in the White Carneau breed, while the supernatant enzyme was slightly higher (P less than 0.05) in the White Carneaux at this age. In older birds (3 years of age) these differences in enzyme activities disappeared.

Aging↗

Plasma lipoprotein profile and composition in White Carneau and Show Racer breeds of pigeons.

Plasma lipoprotein profile and composition in atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons were investigated while consuming a regular pigeon chow diet free of cholesterol. Plasma was studied by analytical and preparative ultracentrifugation and paper electrophoresis. Lipid composition of each lipoprotein was determined by combined TLC-GLC techniques. The major plasma lipoprotein of both breeds was high density lipoprotein (HDL) with some low density lipoprotein (LDL) and no very low density lipoprotein (VLDL). Cholesterol was mainly found in the HDL in both breeds (71.7%), and no difference was noticed in the total cholesterol content of whole plasma or in various lipoproteins. The LDL fraction in White Carneaux showed a significantly lower (P less than 0.05) percentage of cholesterol esters compared with Show Racers (58.63 +/- 4.9 in White Carneaux vs. 72.12 +/- 2.1 in Show Racers). In LDL, the percentage of the triglyceride concentration in White Carneaux was significantly lower (P less than 0.01) than that of Show Racers while the percentage of protein content in White Carneaux was higher than in Show Racers. No significant differences were observed in fatty acid composition of steryl esters phospholipids, and triglycerides in the lipoprotein fractions of the two breeds. These studies show important differences in the cholesterol esters, protein, and triglyceride content of LDL in the atherosclerosis-susceptible breed of pigeons.

Animals↗

Estimation of bile acid excretion in man: comparison of isotopic turnover and fecal excretion methods.

Bile acid excretion was studied in 9 human subjects simultaneously by the Lindstedt (Lindstedt, S. 1957. Acta Physiol. Scand. 40:1-9) isotopic turnovermethod and by fecal chemical analysis during a balance study. The identities of the fecal bile acids were confirmed by combined gas-liquid chromatography/mass spectrometry. Under the steady state conditions of the patient studies, bile acid excretion values obtained by fecal analysis were lower (by 18.1 to 44.2%) than the values obtained by the isotopic turnover method. This difference persisted even in those patients given [14C]chenodeoxycholic acid instead of [3H]chenodeoxycholic acid. The fecal excretion values were similar when calculated using either beta-sitosterol or chromium sesquioxide as fecal flow markers. The fecal excretion values during the earlier part of the isotopic study were higher than those during the latter part of the study. The lower values of bile acid excretion obtained from fecal analysis could not be explained by the loss of bile acids as sulfate conjugates or by losses due to bile acid degradation in the intestine. This study suggests that bile acid turnover is consistently higher than bile acid excretion under experimental conditions. It is recommended that the data obtained from the isotopic turnover method should not be compared with fecal excretion data.

Adult↗

Studies concerning the hypercholesterolemia of pregnancy: cholesterol catabolism and excretion during late pregnancy in the rat.

To investigate the mechanism of hypercholesterolemia noted in pregnancy, cholesterol catabolism and excretion was investigated during late pregnancy in the rat. Pregnancy was associated with an increase in plasma cholesterol and a decrease in the concentration of both cholesterol and bile acids in bile (with no difference in bile flows). The appearance of injected 4-C14-cholesterol in the bile of pregnant females was less than that of virgin females with a significant decrease in the bile acid fraction. The cholic/chenodeoxycholic acid ratio of newly formed C14 bile acids in pregnant rat bile was lower than in the bile of virgin female rats. Surprisingly, cholesterol balance studies failed to reveal any difference in the fecal excretion of neutral sterols or bile acids between virgin and pregnant female rats. The hypercholesterolemia of pregnancy could be partially due to the decrease in biliary cholesterol and bile acid excretion. The lack of difference in fecal cholesterol excretion is perhaps due to the operation of compensatory absorption mechanisms in the intestine which needs further investigation.

Animals↗