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Biomedical subjects

D Kritchevsky

Publications and source records attributed to D Kritchevsky.

At least 127 records · Page 7Linked to original sources

Calories, fat and cancer.

The experiments reported are part of our effort to dissociate the tumor-enhancing effects of dietary fat and high caloric intake. Rats either were fed ad libitum diets containing 4% corn oil or their calories were restricted by 40% and their diets contained 13.1% corn oil. Incidence of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors was 80% in rats fed ad libitum and 20% in those fed the calorie-restricted diets. Incidence of 1,2-dimethylhydrazine (DMH)-induced colon tumors was 100% in rats fed ad libitum and 53% in those whose caloric intake was restricted by 40%. The tumor yield (tumors per tumor-bearing rat) was significantly lower in rats on caloric restriction. In another series, rats were fed diets containing 5, 15 or 20% corn oil ad libitum or were fed calorie-restricted (by 25%) diets which provided 20 or 26.6% corn oil (therefore, the same absolute amount of fat was consumed in each of the pair-fed groups). Tumor incidence and tumor yield in the two calorie-restricted groups were similar to those seen in the rats fed 5% fat ad libitum; tumor burden (total g of tumor) was 45-65% lower in the calorie-restricted rats. The data suggest that caloric intake is a more stringent determinant of tumor growth than fat intake.

9,10-Dimethyl-1,2-benzanthracene↗

Hypercholesterolemia and aortic glycosaminoglycans of rabbits fed semi-purified diets containing sucrose and lactose.

This study was designed to evaluate the role of dietary sucrose and lactose in a semipurified diet as initiating factors for aortic glycosaminoglycan (GAG) and lipid changes. Rabbits were fed sucrose or lactose as 40% by weight of a semi-purified, cholesterol-free diet for 10 weeks. At the end of the feeding period there was no macroscopic evidence of atherosclerosis. Sucrose-fed rabbits had significantly higher plasma cholesterol and phospholipid levels than the lactose-fed rabbits and triglyceride levels were variably elevated in the sucrose group. Analysis of plasma lipoproteins indicated that sucrose elevated VLDL and LDL when compared to lactose. Only the higher molecular weight form of apo B (apo BH) could be demonstrated when apo B components of isolated lipoproteins were analyzed. Sucrose-fed rabbits had significantly more aortic cholesterol, cholesteryl ester and phospholipid and tended to have more GAG/mg dry defatted aorta than the lactose-fed rabbits. Plasma cholesterol levels correlated with aortic lipids and in the sucrose group, aortic cholesteryl ester and cholesterol were strongly correlated with aortic GAG particularly hyaluronic acid. Results suggest that the semi-purified diet alters aortic GAG composition but in order for the initiation of cholesterol accumulation a significant increase in plasma lipoprotein cholesterol is necessary.

Animals↗

Effects of fatty acid esters of cheno- and ursodeoxycholic acids on gallstone formation in hamsters.

Fatty acid esters (at the 7 position) of chenodeoxycholic (CDCA) and ursodeoxycholic (UDCA) acids have been tested for their effects on formation and dissolution of gallstones in hamsters. The free bile acids were fed at a level of 0.2% of the diet and esters were fed at equimolar levels. The earlier finding that CDCA does not affect gallstone formation in hamsters fed the Dam and Christensen diet were confirmed. The acetic, butyric and lauric acid esters of CDCA had a very slight inhibitory effect on lithogenesis but CDCA 7 oleate and linoleate completely inhibited gallstone formation. UDCA and its 7 oleate inhibited both formation and progression of gallstones. The observed effects are probably a function of the form of the bile acid and not of the esterifying acid. The observation that ethyl oleate has a slight litholytic effect suggests that the acid moiety of the ester may exert a slight influence.

Animals↗

Novel derivatives of 3 alpha,7 alpha-dihydroxy-5 beta-cholan-24-oic acid (chenodeoxycholic acid) and 3 alpha,7 beta-dihydroxy-5 beta-cholan-24-oic acid (ursodeoxycholic acid).

Several 7-acyl cheno- and ursodeoxycholic acids were obtained in good yields starting from the corresponding cheno- and ursodeoxycholic acids, by a diacylation-selective hydrolysis procedure. A superior method for the synthesis of the 7-oleyl derivatives, by a selective acylation procedure, is also presented.

Chemical Phenomena↗

The Western diet: an examination of its relationship with chronic disease.

Diet is a component in the etiology of the two major causes of death in the United States, namely, cardiovascular disease and cancer. During the last decade, various organizations have suggested that we alter the "typical" American diet in order to decrease the incidence of these diseases even though both diseases are indisputably of multiple etiology. An implication behind these recommendations is that individuals will increase their longevity by changing their diets. The burden of proof falls on those proposing changes to the diet that such alterations will be safe and effective. In spite of our often indicted diet, mortality from heart disease and stroke continue to fall and deaths from diet-related cancers are static or dropping. Longevity in the U.S. is exceeded by only five countries, whose populations consume a diet similar to ours in four, and that in the fifth is approaching ours. While low-fat high-fiber diets probably have some beneficial effect vis-a-vis chronic diseases, it is likely that other risk factors contribute more to the total risk of disease. Therefore, it is illogical to expect dietary manipulation to offset significantly other concurrent risks such as heredity, tobacco use, hypertension, and obesity. Individuals who are at high risk for specific diseases should modify their diets to minimize this particular risk factor. Most Americans can safely reduce their intake of total calories, fat, sugar, and salt. Although this can be achieved most readily on a population basis by following a form of "prudent" diet, it is premature to promise medical benefits to individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Diseases↗

The influence of diet and dimethylhydrazine on the small and large intestine of vervet monkeys.

The morphological features of the intestine in monkeys on various diets with and without carcinogen were studied. Seventy adult female vervet monkeys were divided into seven treatment groups. Four groups received a Western high-fat low fibre diet (WD); two a Prudent low-fat higher fibre diet (PD) and one a control low-fat high fibre diet (CD). Three groups (2 WD, I PD) received dimethylhydrazine 10 mg/kg intramuscularly at 14 days intervals. After 18 months, monkeys of two groups on the WD were transferred to the PD and 30 months later all were terminated. Small and large intestine were examined macroscopically, histologically with morphometry, histochemically for acid and neutral, sialo- and sulphomucins and enzyme-histochemically for mucosal gamma-glutamyltranspeptidase (GGT) activity. Large intestines in all other than CD, particularly in WD-treated animals were dilated, thin walled, less corrugated and contained more residual contents. Diverticulosis was found to be mostly associated with WD. Apparently histologically normal colonic mucosa showed changed mucin secretion, predominantly in WD groups, and also GGT activity in all but CD groups. Changes which could be associated with pre-malignancy occurred predominantly but not exclusively in carcinogen treated animals. Within 4 years of feeding to monkeys, diets used by affluent western man caused distinct changes suggestive of the development of intestinal diseases such as megacolon, diverticulosis and cancer. Feeding a prudent diet resulted in only a mild reduction of these signs, whereas they were absent in a usual monkey diet that was much lower in animal products and refined carbohydrates.

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↗

Increased atherosclerosis in rabbits immunized with endothelial cells.

Rabbits maintained on normal ration or cholesterol-supplemented diet were immunized with homogenates of endothelial cells grown in cultures that were derived from either bovine or human aorta. Minimal aortic lesions were found in all groups of rabbits fed regular diet; microscopically, differences were seen that manifested as medial lesions in controls and intimal lesions in animals immunized with endothelial cells. Aortic atherosclerosis was significantly increased in the immunized, cholesterol-fed animals over that in controls. This difference was more pronounced in the abdominal aorta where the area with lesions in immunized rabbits was 4-7 times that of controls; atherosclerosis of the thoracic aorta was 2.5-5 times greater in the immunized animals (P less than 0.001 for both segments). Increased atherosclerosis was observed despite a significant reduction in plasma cholesterol in the immunized rabbits (770 +/- 119 mg/dl) compared to controls (1595 +/- 225 mg/dl) (P less than 0.001). Immunization with endothelial cells elicited strong cell-mediated and humoral responses as determined by dermal delayed hypersensitivity and solid-phase immunoradiometric tests, respectively. Cross-reactivity in both assays was found against human and bovine cells. Enhancement of atherosclerosis appears to depend not on induction of immune complexes but on specific antibodies and cell-mediated reactions.

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↗

Morphological disruption of colonic mucosa by free or cholestyramine-bound bile acids.

In order to assess the effects of free or resin-bound bile acids on colonic topography, adult rats were surgically provided with an indwelling infusion catheter in the proximal cecum, which exited at the neck behind the head. Conscious, unrestrained rats were allowed chow ad libitum and were administered 1 ml of an infusion mixture twice daily for five days. The infusion mixtures included either carrier saline, 100 mg cholestyramine, 165 mumol mixed bile acids, or the bile acids bound to cholestyramine. Additional groups of rats were fed defined diets with and without 2% cholestyramine. Compared to fed controls, colonic infusions of saline had little effect on colon topography. Infusions of 100 mg of cholestyramine in saline twice each day did cause some apparent damage to surface morphology of the colon, but not to the extent observed during feeding of the resin as 2% of the diet. In contrast, extensive surface damage of the colon was observed by twice daily infusions of either 165 mumol of an equimolar mixture of cholic, deoxycholic, and chenodeoxycholic acids, or by the bile acids mixed previously with the ion-exchange resin. The data suggest that topographical damage of the colon observed during feeding of bile acid-sequestering resins is in large part due to increased concentrations of either bound or unbound bile acids in the large bowel.

Animal Feed↗

The absorption and transport of dietary cholesterol in the presence of peanut oil or randomized peanut oil.

Peanut oil has been shown to be unexpectedly atherogenic for cholesterol-fed rats, rabbits and rhesus monkeys. However, randomization (rearrangement of fatty acids to random distribution) of peanut oil significantly reduced its atherogenicity for rabbits and monkeys. This study was conducted to investigate whether the absorption and transport of dietary cholesterol was altered in the presence of peanut oil or randomized peanut oil, thereby accounting for the difference in the atherogenicity of the two diets. Intestinal lymph fistula rats were infused intraduodenally with a lipid emulsion at a rate of 3 ml/hr. The lipid emulsion contained either peanut oil (control) or randomized peanut oil (experimental) (10 mM), 14C-cholesterol (1.3 mM) and sodium taurocholate (19 mM) in phosphate-buffered saline, pH 6.4. Lymph triglyceride, cholesterol and phospholipid outputs were similar in both groups of rats during fasting and subsequently during lipid infusion. Comparable recovery of 14C-cholesterol from the intestinal lumen and the intestinal mucosa of the control and the experimental rats showed that the absorption and transport of dietary cholesterol were similar in both groups of rats. Analyses of the fatty acid of both lymph and intestinal mucosal lipid again failed to reveal a difference between the 2 groups of rats. It is concluded that the difference in the atherogenicity between the peanut oil and the randomized peanut oil is probably caused by events subsequent to the release of cholesterol containing chylomicrons and very low density lipoproteins by the small intestinal epithelial cells.

Animals↗

Effect of essential fatty acid deficiency on myelin proteins.

The effect of essential fatty acid (EFA) deficiency on rat-brain myelin proteins was studied. Rats were maintained on a lipid-free diet and compared with control rats fed the same diet supplemented with 3% corn oil. At 17 days of age, each pup was injected with [3H]leucine and rats from each group were killed over a period of 163 days. Although a large decrease occurred in the total amount of myelin protein per brain, the proportions of constituent myelin proteins remained relatively unchanged. Metabolic studies showed a decrease in the net turnover of myelin proteins analogous to that previously demonstrated for myelin phospholipid (PL).

Animals↗