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Biomedical subjects

D Kritchevsky

Publications and source records attributed to D Kritchevsky.

At least 145 records · Page 8Linked to original sources

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↗

Effect of trans-unsaturated fats on experimental atherosclerosis in vervet monkeys.

Vervet monkeys ( Ceropithecus aethiops pygerethrus ) were placed on semipurified diets containing 14% fat of which 3.2 or 6.0% was present as trans-unsaturated fatty acid (t-FA). Two groups were fed the high and low levels of t-FA for a year and two others were fed t-FA for 6 months and then returned to the control diet for 6 months more. One other group was fed the control diet for a year. The control diet contained 14% fat which was a mixture of 72% olive oil and 28% corn oil. There were no significant differences in weight gain. Monkeys fed 6% t-FA or control diets for one year had lowest liver weights. Serum cholesterol and triglycerides in monkeys fed 3.2% t-FA for one year were 134 and 55 mg/dl, respectively; in monkeys returned to control diet after 6 months on 6% t-FA the values were 146 and 50 g/dl. Serum and triglyceride levels for the other 3 groups were 166 +/- 2 and 70 +/- 2 mg/dl. Liver cholesterol levels ranged from 4.0 mg/g (3.2% t-FA) to 4.7 mg/g (control) and 4.8 mg/g (6% t-FA). Lecithin:cholesterol acyltransferase (LCAT) activity was 59.0 microM/h for controls and ranged from 52.4 microM/h (3.2% t-FA) to 73.4 microM/h (6% t-FA). Cholesterol synthesis by liver slices was not affected by diet when the substrate was acetate. When mevalonate was used, the monkeys fed either level of t-FA for 12 months exhibited greatly reduced (about 80%) cholesterogenesis. The levels of t-FA in serum and liver reflected the amount in the diet. After being returned to control diet levels of t-FA in serum and liver of monkeys (fed 3.2% t-FA) fell by 97 and 94%, respectively, and those in serum and liver of monkeys fed 6% t-FA fell by 65 and 91%. There were no significant differences in aortic atherosclerosis or arteriosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Influence of hypocholesterolemic drugs on aortic cholesterol esterase in rabbits.

We have studied the influence of three hypocholesterolemic drugs (Fenofibrate, Pirinixil and Probucol) on aortic cholesterol esterase (E.C.3.1.1.13) activity in cholesterol-fed rabbits. After three weeks, cholesterol-fed controls exhibited a 28% increase in cholesteryl ester synthetase activity (S) and a 13% decrease in cholesteryl ester hydrolase activity (H) giving a 47% increase in S/H ratio. None of the drugs influenced cholesterol-induced synthetase activity, but fenofibrate treatment increased hydrolase activity resulting in a fall in the S/H ratio to the level observed in rabbits fed corn oil but no cholesterol. The other two hypocholesterolemic agents did not affect the aortic S/H ratio.

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↗

Effect of soy protein and casein intake on intestinal absorption and lymphatic transport of cholesterol and oleic acid.

Rats were fed for 4 wk on defined diets containing either casein or soy as the protein source, or diets in which the lysine/arginine ratios were modified by addition of arginine to casein, and lysine to the soy diet. During this period, weight gains and food intakes were comparable in the four dietary groups. Animals were subjected to cannulation of the left thoracic lymphatic duct, and after an overnight fast, were given a single intragastric dose of a lipid emulsion containing oleic acid and cholesterol. The overall 24-h recoveries of cholesterol and fatty acid in lymph were similar in the four groups, as were the distribution of lipids among the major lipid fractions and lipoprotein classes of thoracic duct lymph. However, analysis of timed lymph collections indicated that absorption of lipids was more rapid in casein-fed rats than in those fed soy protein. Furthermore, addition of arginine to the casein diet resulted in a slowed rate of lipid absorption, and addition of lysine to the soy diet markedly increased the rate of lipid absorption.

Animals↗

Comparison of dietary carbohydrates for promotion of DMBA-induced mammary tumorigenesis in rats.

Epidemiologic studies have suggested that sugar consumption is correlated with risk of breast cancer. We tested this possibility using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor rat model. Rats were fed diets containing one of three carbohydrates: sucrose, lactose, or corn starch. Tumor yields were similar in the groups fed sucrose and corn starch but significantly lower in the animals fed lactose. Consumption of starch was associated with the most palpable tumors which weighed significantly more than tumors from the other groups. These data indicate significant effects on promotion of mammary tumorigenesis by dietary carbohydrates.

9,10-Dimethyl-1,2-benzanthracene↗

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↗

Dietary fat versus caloric content in initiation and promotion of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats.

Enhancement of mammary tumor formation by dietary fat may be mediated via increased caloric intake. Three experiments were performed to study this relationship in 7,12-dimethyl-benz(a)anthracene (DMBA)-treated female Sprague-Dawley rats: (a) high- or low-fat isocaloric diets were fed in a crossover design; (b) low-fat, high-calorie and high-fat, low-calorie diets were fed in a crossover design; (c) pair-fed rats were restricted to 60% of the calories of controls with ad libitum access to food beginning 10 days after DMBA administration. The pair-fed rats received daily 60% of calories, the same level of fiber, and 115% more fat than did rats fed ad libitum. Tumor yield but not tumor incidence was greater in rats fed high-fat rather than low-fat isocaloric diets prior to initiation of tumorigenesis. A low-fat, high-calorie diet led to more tumor incidence and yield than was associated with feeding of a high-fat, low-calorie diet. Caloric restriction (although with concomitant intake of more fat) led to complete inhibition of tumor formation. These results indicate that both high-fat and high-calorie diets exhibit cocarginogenic, not merely promotional, properties. Caloric intake may be a greater determinant than dietary fat of a tumor-enhancing regimen. Finally, restriction of caloric intake during promotion markedly suppresses tumor formation, despite the increased fat content of the restricted diet, suggesting a permissive role for calories in tumor formation. The possibility remains that alterations in levels of other dietary components could also have contributed to the observed effects.

9,10-Dimethyl-1,2-benzanthracene↗

Early morphological changes in the endothelium of a peripheral artery of rabbits fed an atherogenic diet.

The effect of an atherogenic diet on the endothelium of the central artery of the rabbit ear was studied by scanning and transmission electron microscopy. Examination of the inner surface of the artery after only 5 weeks on the diet revealed morphological changes including irregularly shaped cells, breaks at intercellular junctions, swelling of the membrane over the central part of the cells, and occasional holes in the cells. By 9 weeks more severe damage was seen including lifting off of cells and some holes. In addition, arrays of dark spots were seen by scanning electron microscopy in some cells in arteries of rabbits fed the diet for 5 to 9 weeks. The dark spots may correspond to abnormally large vacuoles seen inside endothelial cells by transmission electron microscopy. The central ear artery and aorta of some rabbits were tested for their ability to convert arachidonic acid into prostacyclin and thromboxane A2 by radioimmunoassay of the stable metabolites 6-keto-prostaglandin F1 alpha and thromboxane B2. The vessels from rabbits fed the atherogenic diet did not differ from vessels of rabbits on the control diet in their production of either metabolite.

6-Ketoprostaglandin F1 alpha↗

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↗

Gallstone formation in hamsters: effect of varying animal and vegetable protein levels.

The lithogenic diet routinely used for production of gallstones in hamsters contains 20% casein. It has previously been shown that replacement of casein by soy protein significantly decreases gallstone formation. In this study hamsters were fed a lithogenic diet containing casein (C), soy isolate (S), C/S 3:1, C/S 1:1, and C/S 1:3. The percentages of hamsters with gallstones on these five diets were: 44, 12, 38, 23, and 15. Biliary cholesterol levels and lithogenic index both decreased significantly with increasing levels of soy protein. Dilution of casein with soy protein progressively decreases lithogenicity.

Animal Feed↗