PubMed Health⌕ Search

Biomedical subjects

B J Kudchodkar

Publications and source records attributed to B J Kudchodkar.

At least 37 records · Page 2Linked to original sources
PubMed1983

Effect of positively charged sphingomyelin liposomes on cholesterol metabolism of cells in culture.

When cultured human skin fibroblasts were incubated at 37 degrees C with sonically dispersed positively charged sphingomyelin liposomes, sphingomyelin accumulated within the cell. This resulted in stimulation of cholesterol synthesis by increasing 3-hydroxy-3-methylglutaryl Coenzyme A reductase activity. Activation was rapid and was not due to the efflux of cell cholesterol or to cell growth and proliferation. Neither low density lipoprotein cholesterol nor nonlipoprotein cholesterol could suppress the sphingomyelin-induced cholesterol synthesis or activate the acyl-CoA cholesterol acyltransferase, despite an increase in cell cholesterol content. In contrast, the response to 7-ketocholesterol or 26-hydroxycholesterol was not impaired. The effect of sphingomyelin on cholesterol synthesis was temporary and reversible. Twenty-four hours after removal of sphingomyelin, cholesterol synthesis returned to normal and could be suppressed by LDL. Accumulation of sphingomyelin in the cell decreased lysosomal cholesteryl ester hydrolase but had no effect on the microsomal cholesteryl ester hydrolase. These results suggest that accumulation of sphingomyelin in the cell markedly affects cellular cholesterol homeostasis. Resultant accumulation of cholesteryl esters in the presence of extracellular cholesterol could be relevant to atherogenesis.

Cells, Cultured↗
PubMed1981

The effect of hydrocortisone on cholesterol metabolism of cultured human skin fibroblasts.

Hydrocortisone in physiologic concentrations resulted in a reduction in sterol synthesis by cultured normal human skin fibroblasts. These changes were observed when [14C]acetate, [14C]octanoic acid and 3H2O were used as precursors. However, the incorporation of [3H]mevalonic acid lactone into digitonin-precipitable sterols was not affected by hydrocortisone, suggesting that hydrocortisone inhibits sterol synthesis at a site prior to the formation of mevalonic acid. In contrast, the activity of hydroxymethylglutaryl-CoA reductase was stimulated several-fold by the hormone. Thus, the inhibitory effect of hydrocortisone on the cholesterol synthetic pathway may be on hydroxymethylglutaryl-CoA synthase.

Acetates↗
PubMed1981

Receptor-dependent uptake of human chylomicron remnants by cultured skin fibroblasts.

Human chylomicrons were isolated from plasma from a subject with familial hypertriglyceridemia and converted to chylomicron remnants by incubation with postheparin plasma. The interaction of these apolipoprotein E-containing, cholesterol-rich human chylomicron remnants with cultured skin fibroblasts was studied. Chylomicron remnants were internalized by skin fibroblasts as a unit, mainly via the low density lipoprotein (LDL)-receptor pathway, resulting in increased cell cholesterol content. After entering the fibroblast, chylomicron remnants stimulated cholesterol esterification, suppressed 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and down-regulated LDL receptor activity similar to the action of LDL. As a function of increasing lipolysis, remnant particles were progressively more effectively taken up by skin fibroblasts, despite a decrease in the apolipoprotein E content per lipoprotein particle. Remnant particles produced after hydrolysis of 70 to 80% of chylomicron triglyceride increased cell cholesterol content to an amount nearly identical to that observed with LDL when the two lipoproteins were incubated at an equal cholesterol concentration. However, when incubated on the basis of equal particle number, chylomicron remnants were 2 to 3 times more effective than LDL in delivering cholesterol to the cells. These results suggest that chylomicron remnants play a role in the regulation of postabsorptive cholesterol homeostasis in nonhepatic cells, and possibly in the pathogenesis of atherosclerosis.

Biological Transport↗
PubMed1980

Plasma high density lipoproteins and coronary artery disease.

Plasma lipid samples and other atherosclerosis risk factors were related to presence of extent of coronary artery disease (CAD) in 102 consecutive patients undergoing coronary angiography. Thirty-six were without CAD and 66 had angiographically documented CAD. In CAD, high density lipoprotein (HDL) cholesterol was lower and total cholesterol and low density lipoprotein cholesterol were higher than in subjects without CAD. Further, HDL was inversely related to extent of CAD (number of major obstructed vessels). Moreover, decreased HDL was the single most important determinant of CAD among all atherosclerosis risk factors (more so in females than in males). In addition, reduced plasma enzymatic activity of lecithin:cholesterol acyltransferase (LCAT) correlated with the presence and extent of angiographically shown CAD. These findings document the protective effect of elevated plasma HDL against coronary obstructive disease and suggest this salutary action may be related to LCAT mobilization of cholesterol from atherosclerotic lesions.

Arteriosclerosis↗
PubMed1978

A reappraisal of the mechanisms of hypocholesterolemic action of therapeutic agents.

The most commonly used methods to study the mechanisms of hypocholesterolemic action of therapeutic agents generally determine the turnover of total (exchangeable) cholesterol pools in the body. This approach is based on the view that whatever increases the total load of cholesterol in the body will increase the levels of plasma cholesterol, and vice versa. Despite the importance of this assumption it has never been tested, and there is no evidence to indicate that it is valid under all conditions. This "overload" hypothesis dates from the times before the importance of plasma lipoproteins was recognized and their role in the transport of lipids was well understood. However, it is becoming increasingly clear that the levels of plasma cholesterol are determined more directly by the "transport" of cholesterol into and out of plasma compartment by lipoproteins than by the synthesis, absorption and elimination of cholesterol from the total body pools. Any effects that the latter parameters of cholesterol metabolism have on the levels of plasma cholesterol must be mediated through changes in synthesis and the subsequent metabolism of plasma lipoproteins. In other words, in any equation relating changes in the levels of plasma cholesterol to the changes in synthesis, absorption and elimination of cholesterol from the body pools we must consider the "transport" of cholesterol by lipoproteins and their metabolism.

Animals↗
PubMed1977

Effects of acute caloric restriction on cholesterol metabolism in man.

The effects of acute caloric restriction on cholesterol balance and kinetics of plasma cholesterol specific activity were investigated in five hyperlipemic subjects with varying degrees of obesity. Caloric restriction decreased plasma triglycerides by 41 +/- 12%, plasma cholesterol by 11 +/- 9%, and the ratio of esterified to free cholesterol by 12 +/- 7+. Immediately on institution of caloric restriction there appeared to be an influx of tissue cholesterol into plasma and a reduction in endogenous synthesis of cholesterol. The cholesterol balance decreased from 1,469 +/- 441 to 1,212 +/- 349 mg/day and the rate of decay of plasma cholesterol specific activity decreased 62 +/- 3%. The effect of caloric restriction on hepatic synthesis of bile acids was also very prompt. The total fecal bile acids were reduced immediately by 36 +/- 7%. Because the effect on fecal excretion of deoxycholic acid was greater than that on fecal lithocholic acid, it was suggested that hepatic synthesis of cholic acid was reduced more than the synthesis of chenodeoxycholic acid. Caloric restriction did not cause any change in the percentage of absorption of dietary cholesterol (40 +/- 2% versus 42 +/- 3%). These observations are in accord with our model relating cholesterol metabolism with the metabolism of plasma lipoproteins in man.

Adult↗
PubMed1976

Turnover of plasma cholesteryl esters and its relationship to other parameters of lipid metabolism in man.

Studies on plasma cholesteryl esters were made in 32 normal and hyperlipidaemic subjects in an attempt to elucidate further the metabolic relationships between cholesterol and other plasma lipids and lipoproteins. Fractional and net turnover rates of plasma cholesteryl esters were measured using two independent (in vivo and in vitro) methods, both of which determined the prevailing activity of plasma lecithin: cholesterol acyltransferase in the ambiance of the patients own plasma. The results obtained by the two methods were in excellent agreement. The turnover rates of plasma cholesteryl esters in hypertriglyceridaemic patients were significantly greater than in patients with only hypercholesterolaemia and in those with normal plasma lipids. In agreement with these observations, the esterified to free cholesterol ratios in hypertriglyceridaemic patients were significantly greater than in those with normal plasma triglycerides. Patients who had only hypercholesterolaemia had normal esterified to free cholesterol ratios. The rates of esterification of plasma free cholesterol correlated well with triglyceride concentrations as well as with the net turnover of plasma triglycerides and also with the turnover or synthesis of endogenous cholesterol. Since the turnover of plasma triglycerides in most patients with modest to moderate hypertriglyceridaemia reflects the turnover of their plasma very low density lipoproteins, it is suggested that it is the turnover of these lipoproteins which correlates with the hepatic synthesis of cholesterol and with the esterification of plasma cholesteryl esters.

Adult↗
PubMed1976

Plasma cholesteryl esters turnover in man: comparison of in vivo and in vitro methods.

The rate of formation of plasma cholesteryl esters was determined by both in vivo and in vitro methods in 15 subjects. In vivo production of plasma cholesteryl esters was calculated from the specific activity slopes of plasma free and esterified cholesterol after an intravenous injection of [3H] mevalonic acid or [3H] cholesterol incorporated in plasma lipoproteins. In vitro production of cholesteryl esters was estimated by measuring lecithin:cholesterol acyltransferase activity in plasma. Lecithin:cholesterol acyltransferase was estimated by incubating the subjects' own plasma for 1 h at 37 degrees C. The plasma sample used for incubation was collected 2 h after the injection of radioactive precursor (when radioactivity of esterified cholesterol was very low relative to that in free cholesterol and the specific activity of free cholesterol in all of the major plasma lipoprotein classes was identical). The mean value for the production of plasma cholesteryl esters obtained by in vivo method was 126.2 +/- 41.9 mg/h, and it was not significantly different from the mean of 110.5 +/- 25.5 mg/h calculated from the results of in vitro method. The values obtained by the two methods in all 15 subjects had an excellent correlation (r = 0.93). It was found that in normotriglyceridemic subjects the values obtained by the two methods wwere essentially identical, but in hypertriglyceridemic subjects the values obtained by the in vitro method were consistently somewhat lower than the obtained by the in vivo method.

Cholesterol↗
PubMed1976

Absorption of dietary beta-sitosterol in laying hens and its incorporation into the egg.

Studies were undertaken to determine the dietary beta-sitosterol absorption in laying hens and its incorporation into the egg. Hens were divided into four groups and fed a commercial low-fat laying diet. Group 1 served as controls; the diet of group 2 was supplemented with 10% corn oil; group 3 with 4% plant sterols (emulsion in carboxymethylcellulose); group 4 with 10% corn oil and 4% plant sterols. The daily beta-sitosterol intake of hens in groups 1, 2, 3 and 4 was 0.036 g 0.095 g, 2 g and 2.56 g, respectively. After consuming the diets for 30 to 40 days, cholesterol and beta-sitosterol contents of the eggs were estimated by gas liquid chromatographic and mass spectrometric methods. Feeding corn oil with and without plant sterols increased cholesterol content of the eggs, while feeding plant sterols alone had no effect on egg cholesterol levels. The beta-sitosterol content of eggs from groups 1 and 2 was similar (60-66 mug/g yolk) and feeding plant sterols increased the beta-sitosterol content to a very small extent (82-90 mug/g yolk). Studies on the dietary beta-sitosterol and cholesterol absorption indicated that there was very little absorption of beta-sitosterol. In control hens, beta-sitosterol absorption was about 7% compared to 81% cholesterol absorption. Plant sterols feeding did not affect the beta-sitosterol absorption but reduced cholesterol absorption by 40%. Feeding corn oil alone did not affect cholesterol absorption. Failure to detect any significant amount of beta-sitosterol in these hens. At the peak radioactivity deposition in the eggs, only 2% of the absorbed beta-sitosterol radioactivity was found in the eggs of group 4 compared to 5% found in group 1, while cholesterol radiioactivity was nearly 4 to 5 times in both groups. These data suggested that laying hens synthesized specific lipoproteins for deposition in yolk.

Absorption↗
PubMed1975

Effect of cholestyramine on tissue pools of cholesterol a preliminary report.

Four Type II Hyperlipoproteinemic subjects were investigated before and after treatment with cholestyramine. Plasma cholesterol was significantly reduced (365 plus or minus 23 vs 273 plus or minus 34 mg/100 ml) and triglycerides significantly increased (149 plus or minus 55 vs 181 plus or minus 59 mg/100 ml) on cholestyramine treatment. The daily turnover of cholesterol, as determined by the method of Goodman and Nobel, was nearly doubled by the treatment (0.813 plus or minus 0.11 vs 1.595 plus or minus 0.176 g). Although previous workers have already suggested that cholestyramine does not decrease tissue cholesterol pools, we observed a significant increase in tissue pools in each of the three subjects given cholestyramine alone (10.1 plus or minus 1.4 vs 16.2 plus or minus 6.9 g) for Pool A - EXCLUDING PLASMA; AND 27.2 PLUS OR MINUS 4.6 VS 43.7 PLUS OR MINUS 6.4 G FOR Pool B). Treatment for the fourth subject consisted of a combination of cholestyramine and clofibrate. This combination appeared to prevent increases in the size of Pool B and in the size and production rate of Pool A. These preliminary observations suggest that the hypocholesterolemic effect of cholestyramine may be enhanced and its effects on tissue cholesterol prevented by giving it in combination with other agents such as clofibrate.

Adult↗