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Biomedical subjects

B Radhakrishnamurthy

Publications and source records attributed to B Radhakrishnamurthy.

At least 109 records · Page 6Linked to original sources

Serum alpha-lipoprotein responses to variations in dietary cholesterol, protein and carbohydrate in different non-human primate species.

Serum alpha-lipoprotein responses to variations in dietary cholesterol, protein, and carbohydrate were studied in different nonhuman primate species. Chimpanzee, rhesus, green, patas, squirrel and spider monkeys all showed significant interspecies differences in serum total cholesterol responses to 1.84 mg/kcal exogenous cholesterol. Dietary cholesterol significantly increased the alpha-lipoprotein cholesterol in all species except rhesus and chimpanzee. Among these species, there was no relationship between the basal serum lipoprotein profile and subsequent lipoprotein responses to dietary cholesterol. Although the level of dietary protein at 6%, 12%, and 37% of calories had no appreciable main effect on serum total cholesterol in spider monkeys, very low protein diet (6% of calories) produced a significant elevation in alpha-lipoprotein cholesterol. Serum alpha-lipoprotein responses to exogenous cholesterol (1.84 mg/kcal) was highest for the very low protein diet and lowest for low protein diet (12% of calories). Diets with high sucrose (76.5% of calories) and low saturated fat (12.5% of calories) containing no added cholesterol were tested in squirrel and spider monkeys and produced a consistent serum total cholesterol response; the alpha-lipoprotein response was significantly higher in squirrel monkeys than in spider monkeys. The above findings have implications in experimentally induced and comparative atherogenesis.

Animals↗

Collagenase-solubilized lipoprotein--glycosaminoglycan complexes of human aortic fibrous plaque lesions.

The interaction of lipoproteins and arterial connective tissue macromolecules was studied using human atherosclerotic plaque tissues. After extraction with 0.15 M NaCl, the tissues were repeatedly digested with collagenase followed by elastase. The collagenase-solubilized lipoprotein--GAG complexes were isolated by gel-filtration and ultracentrifugation and analyzed for lipids, GAG and protein. While extraction by 0.15 M NaCl released only about 13% of the total cholesterol from the tissues, subsequent digestions by collagenase and elastase yielded 60% and 17% cholesterol, respectively. Both 0.15 M NaCl and collagenase treatment released equal amounts of GAG and accounted for 84% of the total GAG. Immunologically, lipoproteins resembled serum apoB-containing lipoproteins. Bio-Gel A-50m column chromatography of collagenase-extracted materials gave a single peak which contained lipoproteins of 1.006 and 1.063 floating densities, GAG and hydroxyproline. Hyaluronic acid (HA) and chondroitin 6-sulfate were identified; HA was the major GAG. Although the precise nature of the interaction of arterial connective tissue components with lipoproteins is not completely understood, isolation of such complexes indicates the importance of these macromolecules in sequestration of lipoproteins.

Aorta↗

Varied effects of dietary sucrose and cholesterol on serum lipids, lipoproteins and apolipoproteins in rhesus monkeys.

Serum lipid, lipoproteins, apolipoproteins and plasma insulin and glucose were studied in rhesus monkeys (Macaca mulatta) fed high sucrose diets (69%, w/w), with and without added cholesterol. When compared to basal diet, a high sucrose diet with no added cholesterol fed for 6 weeks increased serum total cholesterol and triglycerides by factors of 1.2 and 2.8, respectively. Cholesterol supplementation of sucrose diets increased the serum total cholesterol levels by a factor of 2.2 and decreased the serum triglycerides by 0.47. The serum cholesterol response to experimental diets was reflected predominantly in beta-lipoprotein and to a lesser extent in alpha-lipoprotein. Sucrose diets without cholesterol enriched the beta- and pre-beta-lipoproteins with triglycerides and protein at the expense of cholesterol. On the same diet, the protein content of alpha-lipoprotein increased at the expense of cholesterol and triglycerides. In contrast, dietary cholesterol decreased the triglyceride content and increased the cholesterol content of all the lipoprotein classes. Sucrose feeding seems to increase ApoB more than non-ApoB proteins. The proportion of ApoC-II relative to ApcoC-III increased in each animal on a sucrose diet; exogenous cholesterol further increased this trend. While sucrose diet decreased ApoA-I/ApoA-II ratios, cholesterol supplementation reversed this trend. Dietary sucrose increased the plasma glucose, insulin, and insulin-glucose ratios. The addition of cholesterol also tended to decrease plasma glucose and insulin levels. These observations indicate varied responses of serum lipoproteins and apoproteins to dietary sucrose with and without cholesterol supplementation.

Animals↗

The effect of various dietary regimens and cholestyramine on aortic glycosaminoglycans during regression of atherosclerotic lesions in rhesus monkeys.

The effect of various diets on the aortic glycosaminoglycan (GAG) composition was studied in rhesus monkeys. Aortas were obtained from monkeys fed diets containing cholesterol and comparative fats including coconut oil--butter and peanut oil and with and without cholestyramine. Additional groups in each experiment were placed on regression diets of low-fat, low-cholesterol with and without cholestyramine. Further, an atherogenic diet of coconut oil--butter was alternated every 2 months with a diet enriched with corn oil. GAG isolated from intima and media--adventitia indicated slight variations in the concentration of total GAG among different dietary groups but major differences in the concentration of individual GAG. The concentrations of hyaluronic acid and heparan sulfate were generally greater in aortas of monkeys fed corn oil diets than in those fed coconut oil--butter or peanut oil diets. The concentration of dermatan suulfate generally decreased during regression of lesions induced by the saturated fat--cholesterol diet. Furthermore, the aortas of monkeys with lesions from feeding peanut oil showed higher levels of dermatan sulfate and lower levels of chondroitin 4-sulfate than the saturated fat-fed groups. The addition of cholestyramine enhanced the effects of regression. These observations show that the composition of GAG of the arterial wall can be influenced by various dietary programs and that GAG play a role in induction and regression of experimental atherosclerotic lesions.

Animals↗

Connective tissue composition of aortas from non-human primates. A comparative study.

Connective tissue composition of aortas from several non-human primate species has been studied in an effort to relate collagen, elastin, ang glycosaminoglycan (GAG) content to species susceptibility to atherosclerosis. Among the species studied the baboon contained the highest content of GAG in the aorta. While the distribution of individual GAG varied from species to species, heparan sulfate (HS) was the highest GAG in aortas from most of the species. The ratio of HS to chondroitin sulfates (CS) plus dermatan sulfate (DS) was lowest in the baboon, a species relatively less susceptible to atherosclerosis, and highest in the squirrel monkey, a very susceptible primate. If a relationship exists between HS to CS + DS ratio in the aorta and atherosclerosis, the primates can be arranged in the following decreasing order of susceptibility: squirrel, chimpanzee, stump-tailed, rhesus, African green, patas, baboon. In studies of other connective tissue components, the proportion of total collagen to elastin was found lowest in the baboon. Such observations emphasize the importance of connective tissue in the pathogenesis of atherosclerosis.

Animals↗

Studies of glycosaminoglycan composition and biologic activity of Vessel, a hypolipidemic agent.

Heparin-like glycosaminoglycans (GAG) were isolated from commerical Vessel and their biologic properties studied. Vessel was found to be a mixture of chondroitin sulfates, dermatan sulfate and heparin-like GAG. Chondroitin sulfates and dermatan sulfate in Vessel were hydrolyzed by chondroitinase ABC and the residual Vessel was fractionated on a Dowex-1 Cl- column eluting with a stepwise-increasing concentration of NaCl (1.2--4.0 M). The major fractions eluted at 1.6 M and 1.8 M NaCl were tentatively identified by chemical analysis as heparin-like GAG with somewhat lower sulfate content than standard heparin. Both fractions had lipoprotein lipase-releasing activity and anticoagulant activity similar to heparin, but 1.6 M NaCl fraction had a third of the anticoagulant activity of standard heparin. The 1.8 M NaCl fraction complexed with serum lipoproteins similarly to heparin. In preliminary studies cholesterol-fed rabbits treated with Vessel exhibited somewhat less atherosclerosis than controls.

Animals↗

Synergistic effects of dietary carbohydrate and cholesterol on serum lipids and lipoproteins in squirrel and spider monkeys.

Serum lipid and lipoprotein responses to diets with a high level of simple carbohydrate (69% w/w sucrose) and a low level of saturated fat (5% w/w butter-coconut oil, polyunsaturated/saturated fatty acid ratio 0.03) containing 0, 0.1, and 1.0 mg/kcal added cholesterol was studied in five squirrel (Saimiri sciurea) monkeys. Variations in response produced by altering the nature of dietary carbohydrate (sucrose versus dextrin) and the fat (polyunsaturated/saturated fatty acid ratio, 0.03 versus 1.5) in the above diets were studied in three groups (five per group) of spider monkeys (Ateles sp.). In the absence of exogenous cholesterol, feeding a sucrose-saturated fat diet for 6 weeks produced a consistent increase in serum cholesterol in both species and an increase in serum triglycerides only in squirrel monkeys. Exogenous cholesterol had a remarkable synergistic effect on the high carbohydrate diet in increasing the serum cholesterol and had a suppressing effect on serum triglycerides in both species. Polyunsaturated fat reduced the hypercholesterolemic effect of sucrose with or without exogenous cholesterol. Dextrin diets resulted in lower serum cholesterol responses than sucrose diets when the diets contained 0 or 0.1 mg/kcal added cholesterol. Serum cholesterol response was reflected in beta- and alpha-lipoproteins. These results emphasize the varied response of serum lipids and lipoproteins to dietary changes in carbohydrate, fat, and cholesterol that might have a bearing on experimental atherosclerosis.

Animals↗

Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species.

1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis.

Animals↗

Phylogenetic variability of serum lipids and lipoproteins in non-human primates fed diets with different contents of dietary cholesterol.

The response of serum lipids and lipoproteins to different levels of dietary cholesterol (0.05% to 1.5% w/w) was measured in six nonhuman primate species. Relative response of serum cholesterol in different species, measured in terms of response, index, varied with dietary cholesterol concentration. The overall response for the different diets allowed ranking of the species as follows: Squirrel is greater than green is greater then spider is approximately thesus is approximately patas is greater than chimpanzee The serum cholesterol response was reflected not only in an increase in beta + pre-beta-lipoprotein cholesterol but also in alpha-lipoprotein cholesterol, with significant differences among species in the amount of cholesterol transported in the lipoprotein classes.

Animals↗

Serum lipid and lipoprotein responses of six nonhuman primate species to dietary changes in cholesterol levels.

The response of serum lipids and lipoproteins to different levels of cholesterol in the diet was studied in chimpanzee (Pan troglodytes), rhesus (Macaca mulatta), green (Cercopithecus aethiops), patas (Erythrocebus patas), squirrel (Saimiri sciurea) and spider (Ateles sp.) monkeys. Five animals of each species were fed increasing amounts of dietary cholesterol (0.05% to 1.5% W/W) for 3-week periods; between each experimental diet, the animals were fed a basal diet without cholesterol for a similar period. Serum cholesterol response of different species measured in terms of response index (area under the time-concentration curve above basal value) varied with the dietary cholesterol content and showed a significant interspecies difference at 0.5% dietary cholesterol (1.8 mg/kcal) level. The overall response for the different diets allowed ranking of the species as follows: squirrel greater than green greater than spider approximately equal to rhesus approximately equal to patas greater than chimpanzee. The serum lipoprotein response was reflected not only in an increase in beta-lipoprotein but also in alpha-liprotein with significant differences among species in the amount of cholesterol transported in the lipoprotein classes. Challenging the animals with dietary cholesterol seems to be an essential step for determining inter- and intraspecies differences.

Animals↗

Serum-free and protein-bound sugars and cardiovascular complications in diabetes mellitus.

Free and protein-bound serum sugars and serum lipids were analyzed in 65 adult diabetic patients, 10 age-matched controls, and 24 male medical students for correlation of carbohydrate changes with the extent of retinal, renal, and cardiovascular disease. In diabetic sera, both protein-bound sugars and free mannose, fucose, and hexosamine were significantly elevated; free galactose and inositol were elevated in some diabetic patients, and essentially undetectable in sera from controls. Serum triglycerides and pre-beta-lipoproteins were also elevated in diabetics, but alpha-lipoproteins decreased. Although no specific relationships were observed with the extent of retinal and renal disease, bivariate analyses by Pearson coefficients of correlation showed correlations between levels of serum-free mannose and systolic blood pressure, free hexosamine and duration of diabetes, and serum protein-bound fucose and age. Serum triglycerides and pre-beta-lipoprotein levels correlated with insulin therapy. These are preliminary leads of laboratory studies related to carbohydrate macromolecular changes which might aid in a better understanding of the cardiovascular complications associated with diabetes.

Adult↗