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Biomedical subjects

S A Tepper

Publications and source records attributed to S A Tepper.

At least 19 recordsLinked to original sources

Influence of acarbose (a glucosidase inhibitor) on experimental atherosclerosis in the rabbit.

Acarbose, a complex oligosaccharide of microbial origin, was added at levels of 100, 200 or 400 mg/kg to an atherogenic diet fed to New Zealand White rabbits. The rabbits consumed 75 g/day of each diet, thus the daily intake of Acarbose was 7.5, 15 and 30 mg. Rabbits fed 30 mg/day of Acarbose showed reduced levels of plasma cholesterol, intermediate density lipoprotein (IDL) and low density lipoprotein (LDL). Aortic sudanophilia was inhibited by 23% in rabbits fed 7.5 mg/day of Acarbose and by 43% in rabbits fed 15 or 30 mg/day. Acarbose had been shown previously to lower serum cholesterol and triglyceride levels in rats and mice. Our studies demonstrate that it also inhibits atherogenesis in rabbits fed 0.2% cholesterol.

Acarbose

Experimental atherosclerosis in rabbits fed cholesterol-free diets. 13. Interaction of proteins and fat.

The atherogenic and cholesterolemic effects of animal protein vis-a-vis plant protein are well documented. Virtually all the studies were carried out using diets high in saturated fat, such as coconut oil. In order to determine if the same effects were seen with less saturated fat, we have compared atherogenic effects of an animal protein (casein) with those of a plant protein (soybean protein isolate) fed with partially hydrogenated soybean oil (PHS) (iodine value 72) or soybean oil (iodine value 134) as part of a cholesterol-free semipurified diet. After 6 months only rabbits fed casein-PHS exhibited elevated levels of plasma and liver cholesterol and triglycerides and atherosclerosis. Rabbits fed soy protein-PHS had slightly higher plasma cholesterol and triglycerides than did those fed soy protein and soybean oil, but values in both groups were in the normal range. The different effects of animal and plant protein on lipidemia and atherosclerosis can be influenced by dietary fat and appear to be dependent on fat saturation.

Animals

Dietary fiber supplements: effects on serum and liver lipids and on liver phospholipid composition in rats.

Rats (6 per group) were fed semipurified diets containing either particulate fibers (alfalfa, 10%; cellulose, 10%; bran, 10%), a soluble ionic fiber (pectin 5%), soluble, nonionic fibers (guar gum, 5%; Metamucil, 10%), a mixed fiber preparation (Fibyrax, 10%, or an insoluble, ionic bile acid-binding resin (cholestyramine, 2%). The control group was fed the unsupplemented diet. The feeding period, during which diet and water were provided ad libitum, was 28 days. Compared with the control group, serum total cholesterol levels were increased by more than 10% in rats fed alfalfa and decreased by more than 10% in rats fed cellulose, guar gum, Fibyrax and cholestyramine. There were no significant differences in percentage of plasma HDL cholesterol. Serum triglycerides were elevated in the groups fed alfalfa, pectin, guar gum or Fibyrax and reduced in the group fed Metamucil. Plasma phospholipids were elevated in rats fed alfalfa or bran, unaffected in rats fed pectin or Metamucil and reduced in the other groups. Liver total cholesterol was elevated in all groups but those fed wheat bran and cholestyramine. The percentage of liver cholesterol present as ester was elevated in every group except that fed cholestyramine. Liver triglycerides were reduced in rats fed guar gum or Metamucil and elevated in those fed alfalfa. Liver phospholipids were lowered in the group fed cellulose. Liver phospholipids were fractionated by thin layer chromatography to give phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (Sph), lysophosphatidylcholine (LPC) and phosphatidylinositol plus phosphatidylserine (PI + PS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Flordipine, a calcium channel blocker, which does not influence lipidemia or atherosclerosis in cholesterol-fed rabbits.

Data relating to the effects of calcium channel blockers on experimental atherosclerosis in rabbits are inconsistent with most studies finding no effect on either serum lipids or atherosclerosis. We have administered flordipine (5, 15 or 45 mg/kg/day) for 10 weeks to rabbits fed 1% cholesterol and 4% corn oil. At no level of treatment was there an effect on serum or liver lipids or on aortic sudanophilia.

Animals

Dietary fiber and intestinal adaptation: effects on lipid absorption and lymphatic transport in the rat.

Adult male rats fed defined diets containing various fiber supplements or cholestyramine for 4 wk were surgically provided with lymphatic drainage catheters and starved overnight. After duodenal administration of a standard lipid test emulsion, absorption rates and lipoprotein distributions of cholesterol and oleic acid were determined. Prefeeding diets containing cellulose or alfalfa had no significant effect on oleic acid absorption. Diets containing pectin, guar gum, metamucil, mixed fibers (Fibyrax), or cholestyramine caused decreased lymphatic recovery in the initial period; except for the metamucil diet, no decrease was caused in the 24-h recovery, suggesting delayed but not impaired absorption. Fatty acid distribution among lipoproteins and chylomicron size were not altered by diet. All supplements caused a significant reduction in cholesterol absorption during the initial period, and cholesterol absorption remained depressed in animals prefed pectin, guar gum, mixed fibers, metamucil, and cholestyramine.

Animals

Influence of soy protein or casein on pre-established atherosclerosis in rabbits.

Atherosclerosis was established in rabbits by feeding 1% cholesterol and 4% corn oil for two months. The rabbits were placed into five groups of equal average cholesterol level (2876 mg/dl) one of which was autopsied. The four remaining groups were placed on commercial ration (CR), CR plus 4% corn oil, or semipurified diets containing 14% coconut oil and 25% soy protein or casein. After two months, serum cholesterol levels in CR, CR plus corn oil, soy and casein groups had fallen by 91, 80, 81, and 64%, respectively. Aortic sudanophilia (%) in these four groups had increased by 106, 213, 238, and 25%, respectively. The findings confirm earlier observations that rabbit atherosclerosis does not regress when the atherogenic stimulus is removed.

Animals

Influence of dietary fiber on lipids and aortic composition of vervet monkeys.

A semipurified, cholesterol-free diet containing 40% carbohydrate can produce aortic sudanophilia or aortic atherosclerosis in vervet monkeys (Cercopithecus aethiops pygerethrus) depending on the particular carbohydrate fed. Four groups of vervet monkeys (three males and three females per group) were fed semipurified diets containing lactose. Two of the groups were also fed 15% cellulose (C) or 15% cellulose plus 0.1% cholesterol (CC); the two other groups were fed 15% pectin (P) or 15% pectin plus 0.1% cholesterol (PC). The average serum total cholesterol and low density lipoprotein cholesterol levels over the entire feeding period (mg/dl +/- SEM) were, for C, 156 +/- 14 and 95 +/- 5; for P, 173 +/- 15 and 112 +/- 8; for CC, 187 +/- 27 and 122 +/- 21; and for PC, 155 +/- 11 and 108 +/- 7. Cholesterol levels at autopsy (mg/dl +/- SEM) were, for C, 103 +/- 6; for P, 108 +/- 16; for CC, 92 +/- 9; and for PC, 106 +/- 7. Aortic sudanophilia (percentage of area) was, for C, 5.9 +/- 2.7; for P, 13.5 +/- 9.4; for CC, 5.3 +/- 2.1; and for PC, 21.6 +/- 10.3. Dietary pectin led to more severe sudanophilia (increased by 129% in the absence of cholesterol and by 308% in its presence) than did cellulose. Analysis of aortic glycosaminoglycans (GAG) revealed that dermatan sulfate levels fell in both cholesterol-fed groups, and chondroitin sulfate fell in aortas of group CC. Heparan sulfate levels were unaffected by cholesterol feeding. Hexuronic acid, galactosamine and hexosamine levels were elevated in the pectin-fed monkeys, but levels were unaffected by dietary cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of casein and soy protein on hepatic and serum lipids and lipoprotein lipid distributions in the rat.

Rats fed a semipurified diet containing casein developed higher levels of circulating triglycerides and cholesterol than animals fed a soy protein-containing diet. The increased serum lipid levels in non-fasted rats were associated largely with the d less than 1.006 g/ml lipoprotein particles (e.g. chylomicrons or very low density-like lipoproteins). In addition, casein-fed rats exhibited higher levels of circulating insulin and depressed hepatic 7 alpha-hydroxylase levels compared to soy-fed rats. Supplementation of the casein diet with arginine, to give an arginine/lysine ratio comparable to that in the soy diet, resulted in a reduction of d less than 1.006 g/ml lipids, a reduction in serum insulin levels and an elevation in hepatic 7 alpha-hydroxylase activity. Supplementation of the soy diet with lysine also resulted in modification of these parameters toward those observed with casein diets, albeit the effects were less dramatic. The results suggest that the hyperlipidemia associated with feeding casein-based diet is associated with decreased rates of clearance of chylomicron-like lipoproteins and their component triglycerides and cholesterol. Furthermore, this is largely prevented by addition of arginine to diets containing casein as the sole protein source.

Animals

Effect of pectin and cellulose on formation and regression of gallstones in hamsters.

Male Syrian hamsters were fed a lithogenic diet containing 7% cellulose or 4.2% pectin. After 50 days, pectin was 76% and cellulose 64% less lithogenic than the control diet. Hamsters fed the control diet for 50 days were maintained on that diet for another 50 days or fed diets containing cellulose or pectin. There was a 52% increase in gallstone incidence in hamsters continued on the control diet and a 9% increase in those on cellulose. Pectin promoted regression of gallstones (by 52%).

Animals

Experimental atherosclerosis in rabbits fed cholesterol-free diets. Part 12. Comparison of peanut and olive oils.

The atherogenicity of peanut oil is well established as is the fact that the structure of the component triglycerides of peanut oil influences its atherogenicity. This study was carried out to determine if the relative saturation of peanut oil was partly responsible for the observed effects. Rabbits were fed a semipurified, cholesterol-free diet containing 14% of North American peanut oil (iodine value, 100), South American peanut oil (iodine value, 110) or olive oil (iodine value, 83) for 8 months. Rabbits fed olive oil exhibited higher levels of serum and liver lipids than did the two peanut oil-fed groups but significantly lower levels of aortic atherosclerosis. The findings confirm earlier observations that the structure of a fat can have an affect on its atherosclerogenic potential that is independent of its level of unsaturation.

Animals

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Relationship of diet to serum lipids.

Serum cholesterol, high-density lipoprotein cholesterol, and triglycerides of three groups of Seventh-day Adventists (SDAs)--true vegetarians, lacto-ovo vegetarians, and nonvegetarians--and the general population were measured and related to age, sex, and diet. True vegetarian SDAs had the lowest cholesterol levels while cholesterol levels of the other three groups were similar. Triglyceride levels were highest in the true vegetarian SDAs and lowest in general population. Cholesterol levels rose with increasing age while percentage of high-density lipoprotein cholesterol fell. Female SDAs in all three dietary groups had higher cholesterol levels than males. In all four groups percentage of high-density lipoprotein cholesterol was higher in females than in males. In the male subjects, cholesterol levels varied linearly and inversely with carbohydrate intake. Protein and fat intake in true vegetarian SDAs and lacto-ovo vegetarian SDA groups were lower than in the nonvegetarian SDA and general population groups. The differences in protein and fat intake were reflected in elevations in serum cholesterol levels. In the female subjects, cholesterol levels were also inversely correlated with carbohydrate intake but not as distinctly as in the males. True vegetarian SDA females ingested less protein and fat than the other three groups and exhibited lower serum cholesterol levels. Cholesterol levels in lacto-ovo vegetarian SDA, nonvegetarian SDA, and general population female subjects were similar and did not reflect differences in protein or fat intake. The true vegetarian dietary lifestyle resulted in lowest cholesterol levels, however, if it was breeched to the least extent, cholesterol levels rose. Thus, intake of skim, low fat, or whole milk resulted in similar serum cholesterol levels as did low or high egg consumption.

Adult

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Binding of bile salts to dietary residues.

The binding of glycocholic and glycochenodeoxycholic acids to dried defatted residues of homogenized diets consumed by four dietary groups has been measured. The four groups were true vegetarian Seventh-day Adventists (SDA), lacto-ovo vegetarian SDA, nonvegetarian SDA, and the general population. Glycocholic acid was bound to the same extent (7 to 9%) by all four dietary residues. The true vegetarian SDA residues bound significantly more glycochenodeoxycholic acid than those of either lacto-ovo vegetarian SDA (p less than 0.001) or nonvegetarian SDA (p less than 0.001). The general population residue bound significantly more glycochenodeoxycholic acid than did those of nonvegetarian SDA (p less than 0.001). Binding of glycochenodeoxycholic acid was significantly correlated with dietary neutral detergent fiber (p less than 0.001), hemicellulose (p less than 0.01) and cellulose (p = 0.01). There was no correlation between the binding of glycochenodeoxycholic acid and dietary lignin, pectin, or cutin.

Adult

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Comparison of serum hexosaminidase levels.

Elevated levels of serum hexosaminidase (beta-2-acetamido-2-deoxy-D-glucoside; N-acetamidodeoxy-D-glucohydrolase, EC 3.2.1.30)(HEX) have been found in patients with cancer. In view of the reported low levels of colon cancer among Seventh-day Adventists (SDA) we determined levels of total HEX, and its heat-labile (HEX-A) and heat-stable (HEX-B) isozymes in vegetarian SDA, lacto-ovo vegetarian SDA, nonvegetarian SDA, and the general public. Lowest levels of total HEX and highest percentage of HEX-B were found in vegetarian SDA. The levels in the other three groups were comparable, and these differences were seen at all age levels. Female subjects exhibited significantly lower total HEX levels than the males but the percentage of HEX-B was the same.

Adult

Serum hexosaminidase as a possible biomarker for human cancer.

The levels of total serum hexosaminidase and of its heat stable isozyme (beta-hexosaminidase) were determined in the sera of subjects bearing ovarian and other female genital cancers and of control subjects. The assays were carried out on a double blind basis. Total hexosaminidase levels were significantly elevated in sera of subjects with female genital cancers and in subjects with ovarian cancer. Levels of beta-hexosaminidase were elevated in all subjects with genital cancer. The hexosaminidase assay may be a convenient biomarker for human cancer since earlier studies have shown that total and beta-hexosaminidase levels are elevated in sera of most cancer patients studied.

Female

Influence of dehydroepiandrosterone (DHEA) on cholesterol metabolism in rats.

Wistar rats were fed semipurified diets containing 0.5% of dehydroepiandrosterone (DHEA) for 14 days. DHEA feeding resulted in weight loss and slight liver enlargement. It did not affect serum triglyceride levels but increased serum cholesterol levels. Liver triglyceride levels of DHEA-fed rats were significantly lower than in controls. DHEA inhibited cholesterol absorption. Liver slices from DHEA-fed rats incorporated more acetate into cholesterol than controls; there were no differences in conversion of mevalonate.

Animals

Modification of dimethylhydrazine-induced carcinogenesis in rats by dietary cholesterol.

Diets capable of affecting serum cholesterol levels were examined for effects on tumorigenesis in male Fischer 344 rats given 1,2-dimethylhydrazine dihydrochloride (DMH). Four regimens were used: Group A was maintained on a semipurified diet; Group B was maintained on the same diet with cholesterol and bile salts added; Group C was fed the cholesterol and bile salt diet and then switched to the semipurified diet; and Group D was fed the cholesterol and bile salt diet and then placed on a semipurified diet containing bile salts. Six months after DMH administration, Group B and D exhibited similar tumor incidence (77% and 83%, respectively) and yield (2.3 and 2.4 tumors/tumor-bearing rat). These yields were significantly greater than those seen in Group A (70% incidence and 1.4 tumors/tumor-bearing rat) or Group C (52% incidence and 1.7 tumors/tumor-bearing rat). Tumors in Groups B and D were larger in size and closer to the rectum than those seen in the other groups. In each of Groups A, C, and D, approximately 26% of the tumors were malignant; in Group B, 42% were malignant. Colonic epithelial cell kinetics in rats from Groups C and D not given DMH were determined using autoradiographic study of [3H]thymidine incorporation. Group D showed enhanced cell proliferation and expansion of the crypt cell population. These results suggest that dietary bile salts increase cell turnover and frequency of tumors, and that the addition of cholesterol to a cocarcinogenic diet can be associated with a significantly higher percentage of invasive tumors.

1,2-Dimethylhydrazine

Influence of beclobrate and eniclobrate on cholesterol metabolism in rats.

Two new hypocholesterolemic compounds, ethyl-(+/-)-2-[[alpha-(p-chlorophenyl)-p-tolyl]-oxy]-2-methylbutyrate (Sgd 24 774, beclobrate) and the 3-pyridinylmethyl ester (eniclobrate), have been studied in normocholesterolemic rats. The two compounds are hepatomegalic and they lower serum and liver cholesterol levels but raise liver triglyceride levels. They also reduce the percentage of esterified cholesterol present in the serum. Beclobrate enhances hepatic HMG-CoA reductase activity but does not affect cholesterol-7 alpha hydroxylase. Eniclobrate, on the other hand, increases activity of the hydroxylase but not of HMG-CoA reductase. Neither compound affects cholesterol absorption.

Animals