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Biomedical subjects

C Sharma

Publications and source records attributed to C Sharma.

At least 55 records · Page 3Linked to original sources

Effect of dietary carbohydrate type on lipoprotein lipase, hepatic lipase, and lecithin:cholesterol acyltransferase activities in cynomolgus monkeys.

The effects of dietary sucrose and starch with and without exogenous cholesterol on postheparin plasma lipoprotein lipase (PHLA) and hepatic lipase (HLA) were studied in cynomolgus monkeys. Serum triglyceride levels were higher in sucrose-fed animals than starch and exogenous cholesterol lowered serum triglyceride levels when added to sucrose diet but not starch diets. Sucrose markedly increased insulin levels, more so than starch; however, dietary cholesterol lowered insulin levels in sucrose diet but increased the levels in starch diet. PHLA activity was increased two- to threefold greater in sucrose than in starch diets. Exogenous cholesterol lowered PHLA activity in sucrose diet but increased PHLA activity in starch diet. HLA activity was increased with sucrose more than starch. Lecithin:cholesterol acyltransferase (LCAT) activity was significantly higher in sucrose diets than in the starch diet. Addition of cholesterol to either of these diets lowered the LCAT activity. These results indicate that PHLA, HLA, and LCAT activities not only are affected by the nature of carbohydrates, but also are related to triglyceride metabolism. The interaction of carbohydrates and cholesterol in the diet by influencing these selected enzymes plays an integrated role in lipoprotein particle interconversion processes.

Animals↗

Serum apolipoproteins A-I and B in 2,854 children from a biracial community: Bogalusa Heart Study.

Serum apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B) profiles were examined in 2,854 children, 5 to 17 years of age, from a total biracial community. Black boys had higher apo A-I levels than white boys (P less than .001), whereas girls showed no such race-related difference. Black-white difference in apo A-I persisted among boys with similar triglyceride levels provided that triglyceride levels were high. The ratio of high-density lipoprotein cholesterol (HDL-C)/apo A-I was higher in black than in white children, irrespective of sex (P less than .001). Only black children showed sex-related differences for apo A-I (boys greater than girls, P less than .05). Sex-related differences were seen in white children for HDL-C/apo A-I ratio (boys greater than girls, P less than .001) and in children of both races for apoB (girls greater than boys, P less than .01). Age-related changes were more apparent for apo A-I and HDL-C/apo A-I ratio than for apo B. A progressive decrease in apo A-I was noted during sexual maturation only in white boys. The magnitude of inverse association of apo B to HDL-C was less strong in black children (P less than .01). Although apo A-I was inversely correlated with very low-density lipoprotein cholesterol and triglycerides in white children, no association was noted in black children. These findings are indicative of intrinsic metabolic differences among the race-sex groups, resulting in variability in lipoprotein composition and levels and atherogenic potential.

Adolescent↗

Glycoprotein biosynthesis during inflammation in normal and streptozotocin-induced diabetic rats.

Extracellular glycoproteins play an important role in wound healing; yet little is known about glycoprotein biosynthesis and its regulation by insulin in inflammation. Using [1-14C] fucose as a marker, glycoprotein biosynthesis was studied in carrageenan-induced granuloma from diabetic and control rats. Fucose incorporation into glycoproteins was followed for 24 h after an intraperitoneal injection of the label. Radioactivity in trichloroacetic acid precipitable serum glycoproteins and saline-soluble and insoluble glycoproteins was assessed in five-, seven-, and ten-day-old granuloma tissues. Fucose incorporation was higher in soluble glycoproteins (P less than 0.01) at all points in controls than in diabetic granulomas, and peak incorporation was reached in both groups on the seventh day. Incorporation of fucose into insoluble glycoproteins was higher in normals on the seventh day than in diabetics. Liver-, kidney-, and intestine-soluble glycoproteins showed a maximum incorporation on the seventh day, but no difference was noted between diabetic and normal rats. Incorporation of fucose in insoluble glycoproteins showed a gradual decline with the age of granuloma in all tissues from both groups, with the exception of the kidney. In the kidney, fucosylation of insoluble glycoproteins was decreased (P less than 0.01) in diabetics compared to controls. These results indicate an active phase of biosynthesis, with an increase in glycosylation during inflammation that is probably insulin dependent.

Animals↗

Metabolic epidemiology of colon cancer: fecal mutagens in healthy subjects from rural Kuopio and urban Helsinki, Finland.

Fecal mutagenic activity and dietary pattern of rural and urban Finnish population groups with distinct risk for the development of colon cancer were studied in a low-risk population in rural Kuopio and an intermediate-risk population in urban Helsinki. The average daily intake of protein and fat was the same in the two groups but the frequency of consumption of whole-grain cereals and whole-grain bread, as well as the amount of fiber from the bread were higher in Kuopio as compared to Helsinki. Fecal samples collected for 2 days were incubated under anaerobic conditions at 37 degrees C for 96 h, extracted with hexane: peroxide-free diethyl ether, partially purified on a silica Sep-Pak cartridge, and assayed for mutagenic activity using the Salmonella typhimurium/mammalian microsome system. The fecal mutagenic activity was observed with the tester strains TA98 and TA100 with and without microsomal activation in both the population groups. The percentage of samples showing fecal mutagenic ratio greater than 3 with TA98 and TA100 with microsomal activation, was higher in volunteers from Helsinki than in Kuopio.

Adult↗

Effect of Japanese seaweed (Laminaria angustata) extracts on the mutagenicity of 7,12-dimethylbenz[a]anthracene, a breast carcinogen, and of 3,2'-dimethyl-4-aminobiphenyl, a colon and breast carcinogen.

Animal model studies suggest that diets containing Laminaria angustata, a brown seaweed commonly eaten in Japan, inhibit breast carcinogenesis. In order to identify the compound(s) in the seaweed responsible for tumor-inhibiting activity, we used Ames/mammalian microsome assay system to determine the antimutagenic (or anticarcinogenic) effect of various solvents and water extracts of Laminaria angustata. The antimutagenic effects of acetone, ether, chloroform, chloroform + methanol, hot water and cold water extracts on the mutagenicity induced by 7,12-dimethylbenz[a]anthracene (DMBA), a breast carcinogen, and 3,2'-dimethyl-4-aminobiphenyl (DMAB), a colon and breast carcinogen, was studied using the Salmonella typhimurium strains TA98 and TA100. All extracts were nonmutagenic in both bacterial tester strains. The addition of 10-100 mg solvent extracts of seaweed/plate greatly inhibited DMAB-induced mutagenicity in both tester strains (80-96% inhibition) and DMBA-induced mutagenicity in TA100 (about 82%), whereas hot and cold water extracts produced a moderate inhibition in a dose-related manner in both strains.

9,10-Dimethyl-1,2-benzanthracene↗

Fecal mutagens from subjects consuming a mixed-western diet.

Because of potential significance of fecal mutagens (presumptive carcinogens) in the pathogenesis of colon cancer, feces from 99 healthy subjects from the New York metropolitan area were studied. The diet histories indicate that all participants were consuming a mixed-western diet which is high in total fat and low in fiber. Fecal samples that were incubated under anaerobic conditions at 37 degrees C for 96 h or frozen without incubation, were extracted with hexane: peroxide-free diethyl ether (1:1), partially purified on a silica Sep-pak cartridge and assayed for mutagenicity using the Salmonella typhimurium/mammalian microsome system. Aliquots of fecal samples incubated anaerobically showed a higher frequency of mutagenic activity (per cent samples showing activity) in strains TA98 and TA100 with and without microsomal (S9) activation. In addition, the mutagens requiring S9 activation, were more frequently inactivated when the fecal samples were frozen immediately after defecation and transported to the laboratory. Compared with hexane: ether, extraction of fecal samples with acetone increased the mutagenic activity mostly with TA98 with S9 activation. The HPLC fractionation of hexane: ether extract with methanol: water gradient using reverse phase C-18 column and UV detector at 254 nm indicated that the mutagenic activity (TA98 with S9 activation) is concentrated in several peaks. This is the first demonstration of HPLC profile of fecal samples that are active in TA98 with S9 activation. HPLC profile of fecal extracts and mutagenic activity of these extracts in strains TA98 and TA100 suggest the presence of several types of mutagens in the feces of healthy subjects consuming a high-fat, low-fiber mixed-western diet.

Biotransformation↗

Serum lecithin:cholesterol acyltransferase activities of cynomolgus monkeys fed different carbohydrate diets.

Although serum lecithin:cholesterol acyltransferase (LCAT) activity is known to be modulated by nutritional factors, little is known about the effects of dietary carbohydrate on this enzyme. Therefore, LCAT activities were assessed in cynomolgus monkeys fed diets for 6 weeks on 4 diets containing 77% of calories as sucrose or starch and cholesterol at 0 and 1 mg/kcal. Three different assay conditions were used in order to measure the overall LCAT activity and to differentiate enzyme activity from the effect of serum substrate and end-product lipoprotein alterations by diet on this enzyme. Molar rate of serum total LCAT activity was higher in sucrose than starch diets (P less than 0.01). Use of sera from sucrose-fed animals, either as substrate or enzyme source, increased the fractional rate of cholesterol esterification (P less than 0.01). Exogenous cholesterol lowered serum total LCAT activity only in sucrose diet (P less than 0.01). Use of sera from sucrose + cholesterol-fed animals as substrate significantly lowered the fractional rate of cholesterol esterification (P less than 0.01); whereas no such alterations were noted when this serum was used as enzyme source. The differential effect of starch and sucrose diets on LCAT activity suggests that the nature of dietary carbohydrates may affect LCAT activity in association with triglyceride metabolism by altering the amount of enzyme in terms of its activity and/or the nature of substrate and cholesterol ester acceptor lipoproteins.

Animals↗

Effect of micronutrients, antioxidants and related compounds on the mutagenicity of 3,2'-dimethyl-4-aminobiphenyl, a colon and breast carcinogen.

The possible antimutagenic effects of butylated hydroxytoluene (BHT), ethoxyquin, disulfiram, indole-3-carbinol, indole-3-acetonitrile, sodium selenite and alpha-tocopherol on 3,2'-dimethyl-4-aminobiphenyl-induced mutagenicity were studied using the Ames Salmonella/mammalian microsome assay system with strains TA98 and TA100. All seven compounds were nonmutagenic in both bacterial tester strains. The addition of or 50-250 micrograms of sodium selenite, 5-50 mg of alpha-tocopherol or 50-250 microgram of BHT per plate inhibited DMAB-induced mutagenicity in TA98 and/or TA100. Ethoxyquin, disulfiram and indole-3-carbinol increased DMAB-induced mutagenicity in TA100, whereas these compounds had little or no effect in TA98-3-acetonitrile had very little effect in either strain.

Aminobiphenyl Compounds↗

The role of intestinal microflora in the metabolic reduction of 1-nitropyrene to 1-aminopyrene in conventional and germfree rats and in humans.

1-Nitropyrene (100 mg/kg body wt.) was administered by gavage to conventional and germfree Fischer 344 rats. 1-Aminopyrene was detected in the feces of conventional rats (5-6% of the dose) but not in the feces of germfree rats. Conjugates of 1-aminopyrene were not detected in the feces of germfree rats and neither 1-aminopyrene nor its conjugates were found in the urine of either conventional or germfree rats. Since reduction of 1-nitropyrene to 1-aminopyrene is an activation process, the results indicate that intestinal microflora are important in the metabolic activation of 1-nitropyrene in vivo in the rat. Human intestinal microflora also reduced 1-nitropyrene to 1-aminopyrene.

Anaerobiosis↗

Effect of butylated hydroxytoluene and butylated hydroxyanisole on the mutagenicity of 3,2'-dimethyl-4-aminobiphenyl.

This study was undertaken to investigate the possible antimutagenic effects of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on 3,2'-dimethyl-4-aminobiphenyl (DMAB)-induced mutagenicity, using the Ames Salmonella/mammalian microsome system. The addition of 100-250 micrograms of BHT or 25-500 micrograms of BHA/plate was found to inhibit DMAB-induced mutagenicity in Salmonella strains TA 98 and TA 100. In TA 100, the mutagenicity was further inhibited with the addition of S9 prepared from the livers of rats fed a 0.6% BHT diet as compared to S9 from the animals fed a diet containing no BHT.

Aminobiphenyl Compounds↗

Longitudinal changes of serum lipid and apoB levels in a newborn-infant cohort.

Longitudinal changes in serum apoB levels in relation to serum lipid levels were determined in a subset (n = 30) of a newborn-infant cohort selected from infants (n = 440) of Bogalusa, Louisiana who were born between January 1, 1974 and June 30, 1975. Serum total cholesterol, triglycerides, beta + pre-beta-lipoprotein cholesterol and apoB levels were measured at birth, 6 mo, 1 yr, 2 yr, and 3 yr of age. The mean +/- SD, mg/dl, levels of these variables increased dramatically (p less than 0.0005) from birth to 6 mo (Total cholesterol: 65.0 +/- 15.7 versus 136.3 +/- 27.4; triglycerides: 32.9 +/- 18.9 versus 82.3 +/- 28.9; beta + pre-beta-lipoprotein cholesterol: 31.8 +/- 9.1 versus 87.3 +/- 25.7; apoB: 20.8 +/- 5.3 versus 49.0 +/- 13.5). On the other hand, the ratio of apoB to beta + pre-beta-lipoprotein cholesterol at birth was significantly higher than at 6 months of age (0.69 +/- 0.24 versus 0.58 +/- 0.12, p less than 0.0005). None of the variables changed significantly between 6 mo and 3 yr of age except the increase in serum total cholesterol level from yr 2 to yr 3 (142.6 +/- 26.6 versus 156.4 +/- 23,0, p less than 0.01). A high intra-child year to year correlation for serum apoB was noted beginning at 6 mo of age (r = 0.67, p less than 0.0001); while the apoB levels were proportional to beta + pre-beta-lipoprotein cholesterol levels in some children, others had varied levels of apoB in relation to cholesterol carried by this apoprotein. The fact that apoB levels persist beginning at 6 mo of age and that we are beginning to observe interindividual differences in levels of cholesterol carried by this apoprotein may have clinical implications for coronary artery disease.

Apolipoproteins↗

Metabolic epidemiology of large bowel cancer. Fecal mutagens in high- and low-risk population for colon cancer. A preliminary report.

Because of potential significance of fecal mutagens in the pathogenesis of colon cancer, the dietary pattern and fecal mutagens of 3 populations with distinct risk for the development of colon cancer, a high-risk population in New York Metropolitan area (non-Seventh-Day Adventists), a low-risk population of vegetarian Seventh-Day Adventists in New York Metropolitan area and a low-risk population in rural Kuopio, Finland were studied. The average daily intake of protein was the same in the 3 groups, but the sources were different, a greater portion coming from meat in the New York non-Seventh-Day Adventists and from vegetables in Seventh-Day Adventists. The intake of fat was lower in Seventh-Day Adventists and higher in Kuopio and in New York non-Seventh-Day Adventists. The intake of dietary fiber was high in Kuopio compared to other groups. Fecal samples collected for 2 days were freeze-dried extracted with peroxide-free diethyl ether, partially purified on a silica-gel column and assayed for mutagenicity using the Salmonella/mammalian microsome mutagenicity test. The mutagenic activity was observed with Salmonella typhimurium tester strain TA98 without microsomal activation and with TA100 with and without microsomal activation in high-risk subjects from New York consuming a high-fat, high-meat diet. The incidence of fecal mutagen activity was higher in volunteers from New York consuming a high-fat, high-meat diet compared to low-risk rural Kuopio population. None of the vegetarian Seventh-Day Adventists showed any mutagenic activity.

Adult↗