Biomedical subjects
S Balasubramaniam
Publications and source records attributed to S Balasubramaniam.
Unsuspected tension pneumothorax as a hidden cause of unsuccessful resuscitation.
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Low density lipoprotein metabolism in the normal to moderately elevated range of plasma cholesterol: comparisons with familial hypercholesterolemia.
Low density lipoprotein (LDL) metabolism was investigated using a pulse injection of 125I-labeled LDL in 20 subjects who did not have familial hypercholesterolemia (FH) (plasma cholesterol 160-297 mg/dl) and in 9 subjects who did have heterozygous FH (plasma cholesterol 273-501 mg/dl). Subjects were also injected with 131I-labeled LDL chemically modified with cyclohexanedione. This technique permitted a calculation of the amount of apoLDL removed via receptor-mediated and receptor-independent pathways. In subjects without FH, 40% (range 25-49%) of LDL was cleared via receptor-mediated pathways and in subjects with FH this figure was 22% (range 3-33%). In nonfamilial hypercholesterolemia there was clear evidence of defective removal of LDL via receptor-independent pathways in association with some overproduction of apoLDL. In heterozygous FH there was evidence of defective removal of LDL via receptor-mediated pathways, while some subjects also showed evidence of overproduction of apoLDL. It is suggested that LDL catabolism via receptor-independent pathways plays a major role in regulating plasma cholesterol levels in the normal to moderately elevated range.
Regulation of neutral cholesterol esterase and acyl-CoA : cholesterol acyltransferase in the rat adrenal gland.
The activities of neutral cholesterol esterase and acyl-CoA : cholesterol acyltransferase in rat adrenal gland were measured at various time intervals over 24 h. The activity of cholesterol esterase displayed diurnal rhythm, with a major peak at the onset of darkness coinciding with the peak in the diurnal rhythm of plasma corticosterone concentration. The activity of acyl-CoA : cholesterol acyltransferase also exhibited a characteristic diurnal rhythm, with the minimum activity occurring 3 h after the onset of darkness. The profile of the rhythm exhibited by the activity of the esterifying enzyme was similar to the mirror image of the pattern of diurnal rhythm in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. Microsomal non-esterified cholesterol showed a gradual decline with a significant decrease in concentration at the onset of darkness, thus suggesting that diurnal removal of cholesterol in the environment of the esterifying enzyme and hydroxymethylglutaryl-CoA reductase leads to such diurnal decrease or increase in the activities of these two enzymes. Acute administration of corticotropin led to a 3-fold increase in the activity of cholesterol esterase, a 50% decrease in the activity of acyl-CoA : cholesterol acyltransferase and a 2-fold increase in the activity of hydroxymethylglutaryl-CoA reductase. Corticotropin administration also resulted in a significant decrease in microsomal non-esterified cholesterol and increase in plasma corticosterone concentration. These observations suggest that corticotropin plays an important part in generating the diurnal rhythm in the activities of the three enzymes.
Long-term treatment of hypercholesterolaemia with a new palatable formulation of guar gum.
Nineteen patients with primary hypercholesterolaemia previously stabilized on diet alone were treated with a new formulation of guar gum (6g t.d.s. with meals) in a placebo-controlled, single-blind study. Seventeen patients completed 3 months treatment without serious side effects, while 2 patients withdrew immediately because of severe diarrhoea. Thirteen patients have completed 12 months treatment with guar gum. There have been no significant changes in safety parameters. Plasma cholesterol was reduced by a significant 15% during the first 3 months of treatment (7.9 +/- 0.8 vs 6.7 +/- 1.0 mmol/l, P less than 0.001) and this effect has been sustained for 12 months. The fall in plasma cholesterol was associated with a significant 20% fall in LDL cholesterol, but with no change in HDL cholesterol. Plasma triglycerides did not change significantly. Percentage cholesterol absorption was reduced by guar gum in 4/5 normal subjects examined.
Complications in the prehospital use of nitroglycerin.
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Use of calcium in brady-asystolic arrest.
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Evaluation of ceftizoxime in acute peritonitis.
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Long-term treatment with slow release oxprenolol alone, or in combination with other drugs: effects on blood pressure, lipoproteins and exercise performance.
Twenty-eight patients with mild essential hypertension were treated with placebo for six weeks and then with active medication for a further 32 weeks. Twelve patients were well-controlled with 160-320 mg/day of slow release oxprenolol alone, 12 required oxprenolol and chlorthalidone, and four also required hydrallazine. beta-adrenergic blockade reduced the basal level of plasma free fatty acid (FFA) by 41%. A sub-maximal exercise test reduced the level of FFA by 34% during placebo treatment. The same exercise test during beta-blockade reduced the already lowered basal FFA level by a further 45%. Only female subjects experienced exercise-induced leg fatigue during beta-blockade. They always had higher FFA levels than males, but the relative changes in FFA concentration were similar in both sexes. Exercise testing induced a 52 mmHg rise in systolic blood pressure, but this was reduced to only 14 mmHg during treatment. Patients controlled on oxprenolol alone showed no significant change in plasma lipid and lipoprotein levels. Those patients ultimately requiring combination drug therapy experienced a statistically significant rise in plasma triglycerides and a significant fall in high density lipoprotein cholesterol. The biological importance of these changes is uncertain.
Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase and of acyl-CoA--cholesterol acyltransferase by the transfer of non-esterified cholesterol to rat liver microsomal vesicles.
The incubation of rat liver microsomal fraction with a serum preparation followed by the re-isolation of the microsomal membranes has resulted in an increase in the concentration of non-esterified cholesterol, a considerable decrease in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase and in an increase in the activity of acyl-CoA-cholesterol acyltransferase in the treated microsomal preparation. These effects were related to the concentration of serum in the incubation mixture and to the duration of the incubation. The transfer of non-esterified cholesterol was specific in that the content of protein and the total phospholipids were similar in the original microsomal fraction and the serum-treated microsomal preparation. The incubation of the microsomal fraction with lipoprotein-deficient serum or with no serum resulted in both cases in small changes in the non-esterified cholesterol, the esterified cholesterol and the total phospholipid content in the treated preparations compared with these concentrations in the original microsomal fraction, whereas the activity of acyl-CoA-cholesterol acyltransferase and of 3-hydroxy-3-methylglutaryl-CoA reductase was similar in the lipoprotein-deficient-serum-treated and the buffer-treated microsomal preparations. The activity of 3-hydroxy-3-methylglutaryl-CoA reductase was lower and the activity of acyl-CoA-cholesterol acyltransferase was higher in the lipoprotein-deficient-serum-treated and the buffer-treated microsomal preparations as compared with these activities in the original microsomal fraction. However, the serum-treated microsomal preparation had considerably lower activity of 3-hydroxy-3-methylglutaryl-CoA reductase and considerably higher activity of acyl-CoA-cholesterol acyltransferase than these activities in buffer-treated and in lipoprotein-deficient-serum-treated microsomal preparations.
Efficacy of skull radiography.
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Analytical fractionation of human liver microsomal fractions: localization of cholesterol and of the enzymes relevant to its metabolism.
1. The submicrosomal distribution of three enzymes concerned in cholesterol metabolism, and of free and esterified cholesterol, was determined in human liver by analytical isopycnic centrifugation on sucrose gradients. 2. The distribution profile and median density of acyl-CoA:cholesterol O-acyltransferase was similar to that of RNA, showing that this enzyme is confined largely to the ribosome-rich membranes of the endoplasmic reticulum. The distribution profiles and median densities of 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-mono-oxygenase showed that both enzymes are confined to the smooth, ribosome-poor, endoplasmic reticulum. 3. Most of the free cholesterol in the microsomal preparations was present in smooth membranes from the Golgi apparatus and in vesicles from plasma-membrane fragments. The distribution of esterified cholesterol was multimodal and extended throughout the whole gradient.
On the mechanism of plasma cholesterol reduction in the rat given probucol.
1. The effects of the cholesterol-lowering drug probucol on lipoprotein metabolism and on the key enzymes that regulate hepatic cholesterol metabolism in the rat were studied. 2. Probucol given for 2 weeks was accompanied by a significant reduction in plasma concentrations of low-density and high-density lipoproteins (LDL,HDL). The fractional catabolic rates of the apolipoproteins of HDL and LDL (apoHDL, apoLDL) were not affected by probucol, although the absolute rates of catabolism of both the apolipoproteins were significantly reduced. 3. The activities of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) reductase and cholesterol 7 alpha-mono-oxygenase, as well as the rate of hepatic sterol synthesis, were unchanged during the first 2 weeks of probucol. More prolonged probucol led to inhibition of the activity of these enzymes and reduction in sterol synthesis, although the liver cellular content of cholesterol significantly increased. 4. It is postulated that a principal mode of action of the drug is to reduce the rate of lipoprotein synthesis.
Trauma centers: an idea whose time has come.
Major trauma is a preventable entity. Illustrations are used to discuss the differences between major trauma centers. Requirements for a trauma center are enumerated and the impact of residency training programs is discussed relative to trauma care. The development of trauma centers is examined and reference is made to Boyd's article on trauma centers. Priorities to develop a National Trauma System as well as educational programs are explained. Finally, a discussion of the teaching of advanced trauma life supports (ATLS) is presented.The ongoing need for the development of trauma centers is detailed.
On the mechanism of regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase and of acyl coenzyme A:cholesterol acyltransferase by dietary fat.
The activity and the kinetic properties of hydroxymethylglutaryl-CoA reductase and of acyl-CoA:cholesterol acyltransferase in the liver microsomal fraction have been compared between rats fed on either unsaturated or on saturated fat. When rats wre fed for 12h on a compounded diet containing either safflower seed oil or tristearin the composition of the fatty acyl chains of the microsomal phospholipids was shown to be relatively more unsaturated in the rats that received the unsaturated fat. The activity of hydroxymethylglutaryl-CoA reductase in the microsomal fraction was considerably reduced in rats fed on compounded diet containing unsaturated fat whereas this dietary condition resulted in a considerable increase in the activity of acyl-CoA:cholesterol acyltransferase. Similar effects were observed after feeding rats for 12 h on a commercial diet supplemented with either safflower seed oil or with tristearin. The addition of 2% cholesterol to the fat-supplemented diets resulted in both cases in a decrease in hydroxymethylglutaryl-CoA reductase and an increse in acyl-CoA:cholesterol acyltransferase activity as compared with the corresponding values from the rats fed on the fat-supplemented diets with no cholesterol. The Arrhenius plots of hydroxymethylgutaryl-CoA reductase in the microsomal fraction from rats fed on fat-supplemented commercial diet for 12 h showed breaks in the activation energy at 29.6 degrees C for the preparations from rats fed on tristearin and 28 degrees C for those from rats fed on safflower seed oil. The activation energy of the enzyme was lower above and higher below the break for the preparations from rat fed on the unsaturated fat-supplemented diet. Similar differences were obtained from the comparison of the Arrhenius plots in the preparations from rats fed on saturated fat and those in the preparations from rats fed on unsaturated fat when the diet was compounded and given to the animals for 36 h. The addition of 2% cholesterol to the commercial diet supplemented with either saturated or unsaturated fat resulted in Arrhenius plots with a constant activation energy between 37 and 22 degrees C for the enzyme in microsomal preparations from both groups of rats. The apparent Km value for hydroxymethylglutaryl-CoA was lower for the reductase in microsomal preparations from rats fed on the unsaturated fat as compared with that for the enzyme in microsomal preparations from rats fed on saturated fat. There was also a decrease in the apparent Km value for oleic acid for the acyltransferase from rats fed on unsaturated fat as compared with that for the enzyme in the microsomal preparation from the rats fed on saturated fat. The results of the present study are consistent with higher concentration of free cholesterol in endoplasmic reticular membrane in the environment of the reductase and that of acyltransferase following the administration of dietary unsaturated fat as compared with that following the administation of saturated fat.
Myoglobinuric acute renal failure in phencyclidine overdose: report of observations in eight cases.
Eight cases of myoglobinuric acute renal failure that developed following exposure to phencyclidine were seen in the emergency department of the Martin Luther King Jr. General Hospital during a period of 36 months. All eight survived with complete recovery of renal function. Dialysis was necessary in three patients. Acute renal failure is an uncommon complication of phencyclidine abuse.
Studies on medicinal plants of Sri Lanka. III. Pharmacologically important alkaloids of some sida species.
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