Search PubMed⌕ Search

Biomedical subjects

D Kritchevsky

Publications and source records attributed to D Kritchevsky.

At least 109 records · Page 6Linked to original sources

Isolation and quantitation of lectins from vegetable oils.

The factor(s) responsible for the unexplained atherogenicity of peanut oil remain to be elucidated. To this end, we developed a technique to determine if lectin was present in the oil and to quantitate its concentration. This technique was applied to other vegetable oils including corn, soybean, and sunflower. Crude, unprocessed corn and soybean oils were also analyzed for lectin content. The crude oils contained from 858 to 2983 micrograms lectin per kg, while the refined oils contained 24 to 55 micrograms/kg of biologically active lectin. The identities of the isolated lectins were confirmed by electrophoresis on SDS-polyacrylamide gels. The biological significance of the presence of lectin in these oils remains to be determined.

Hemagglutination↗

Diets realistic for westernized people significantly effect lipoproteins, calcium, zinc, vitamins C, E, B6 and haematology in vervet monkeys.

This report describes measurements of 50 variables in adult, female, reproductively inactive Vervet monkeys during prolonged nutrition realistic for westernized people. Dietary treatments consisted of an atherogenic Western diet (WD) and a prudent Western diet (PD). Ingredients were normal foods for man and no extra cholesterol was added. Fortification of both diets with vitamin C after cooking was necessary to prevent deficiency. Randomised groups of Vervet monkeys received either the PD or WD for 47 months, while a third group was fed WD for 20 months and then PD for 27 months (WD-PD). Before the dietary treatments nourishment was by a high carbohydrate diet (HCD) and baseline and reference values (RV) apply to this nutritional status. Plasma total cholesterol (mg/dl) was increased from 147 (HCD) to 174 (PD) and 376 (WD). Individual cholesterolaemio response ranged from mild to severe and was stable (PD and WD). Dietary reversal (WD-PD) reduced cholesterolaemia promptly. Statistically significant increases in calcium, zinc and vitamin E and decreased vitamin B6 were associated with the WD relative to the PD (in serum and plasma). Two cholesterol metabolising microsomal enzymes in liver were notably increased and one unchanged (WD). There were no dietary effects on triglycerides, vitamin A and glucose in plasma; insulin, glucagon, electrolytes, copper, magnesium or enzymes reflecting liver, muscle or brain cell damage in serum. Red blood cells, platelets and directly associated parameters increased (WD), haemoglobin was the same and haemoglobin per red cell decreased. Bleeding time was not affected. Bivariate correlations across the diets confirmed that Western nutrition promoted inherent individual susceptibility to cholesterolaemia. There were notable differences from RVs in total cholesterol, calcium, packed cell volume and haemoglobin, which emphasise excesses and deficiencies of the WD and PD.

Animal Nutritional Physiological Phenomena↗

Promotion and regression of atherosclerosis in vervet monkeys by diets realistic for westernized people.

We have described and measured aortic and arterial atherosclerosis in adult female Vervet monkeys (n = 61) after application of dietary treatments for 47 months. The diets were compounded entirely of normal food items for westernized people, with no extra cholesterol added. A 'Western' diet (WD), known to induce hypercholesterolaemia, was found to be atherogenic in aortas and some arteries. A more 'prudent' diet (PD) induced much less lipid infiltration into aortic intimas and was not associated with serious atherosclerotic changes. However, when this PD was used as a treatment for 27 months, following 20 months of nutrition by the WD, minimal regression of cholesterol crystals and non-lipid components of atherosclerotic plaque was detected. There was no significant coronary artery or myocardial disease in these adult females after 47 months of feeding on the WD whereas males do develop coronary atherosclerosis and myocardial fibrosis. For this model the PD would be more effective in preventing atherosclerosis than treating advanced lesions. We believe this is the first time that the pathology of atherosclerosis promoted by realistic diets has been modelled in adult females of this species.

Animal Nutritional Physiological Phenomena↗

Seasonal variation of serum lipids in the vervet monkey.

Seasonal variation of serum lipids has been observed in man, primates and other species. We are presenting data on serum lipid variation in Vervet monkeys (Cercopithecus aethiops). The monkeys (54 males, 33 females) were fed control diets (commercial pellets, fruit, vegetables) and data were pooled and grouped by season. Data having been obtained in South Africa, the seasons were: summer (December, January, February); fall (March, April, May); winter (June, July, August); and spring (September, October, November). Data presented are based on multiple samplings. Total serum cholesterol (mg/dl) and beta-lipoprotein cholesterol (mg/dl) varied significantly with season, peak values being observed in the fall months. Triglyceride and alpha-lipoprotein cholesterol levels showed seasonal variation which was not statistically significant. However, when data were analyzed by weight group (less than 3.3 kg; 3.3-4.3 kg; 4.4-5.3 kg; greater than 5.4 kg) only triglyceride and alpha-lipoprotein levels varied significantly with season. Significant interactions between diet, sex, weight, and season have also been observed. These observations can be used in planning future studies.

Animals↗

Influence of N,N'-(1,11-undecandiyl) bis (2,3-dihydro-2-methyl-1H-indole-1-carboxamide) (BAY 02752) on gallstone formation and regression in hamsters.

A new hypolipidemic drug (BAY 02752) when added to a lithogenic hamster diet at dosages of 1000 and 500 mg per kg of diet significantly (p less than 0.005) inhibited gallstone formation. When BAY 02752 was fed to hamsters with pre-established gallstones, it inhibited progression (p=0.052) of the stones and appeared to promote dissolution.

Animals↗

A comparison of the effects of soya-bean protein and casein on bile composition, cholelithiasis and serum lipoprotein lipids in the vervet monkey (Cercopithecus aethiops).

1. Two groups of vervet monkeys (Cercopithecus aethiops) were fed on high-cholesterol diets which differed only with respect to the protein source. In one group casein was the only protein source, while the other group received only soya-bean protein. 2. Samples of blood, bile and liver biopsy material were collected at the commencement of the study and at 3-monthly intervals until termination 12 months later. 3. At the end of the experimental period all the animals (n 19) had high plasma cholesterol levels and had developed pigment gallstones, the compositions and weights of which were not related to the protein source or to plasma cholesterol levels. Gallstone weight was related to the presence of acidic and sulphated mucins in gallbladder mucosa. We were also unable to confirm the hypocholesterolaemic effect of soya-bean protein which has been demonstrated previously in rhesus monkeys and hamsters. Bile composition and plasma lipids did not differ significantly between the casein-fed and soya-bean fed animals. Lithogenic index was below 1 for both groups and did not differ significantly between the two groups. 4. No significant difference was found in the severity of cholelithiasis between the casein-fed and the soya-bean-fed animals.

Animals↗

Dietary fiber supplementation and fecal bile acids, neutral steroids and divalent cations in rats.

Young adult rats were fed ad libitum for 4 wk on defined diets containing either no fiber, 10% levels of insoluble fiber sources [cellulose, wheat bran, alfalfa, mixed fibers (Fibyrax)], 5% levels of soluble fiber sources [pectin, guar gum, psyllium (Metamucil)] or 2% cholestyramine (Questran), a bile acid sequestrant. Fecal samples were obtained from paired rats over a 3-d period, were analyzed for neutral and acidic steroid levels and compositions and, together with the food, were assayed for divalent cations (Ca2+, Mg2+, Fe2+ and Zn2+). Animals in all groups were in balance for divalent cations, and there appeared to be no relationship between the extent of cation balance and the type of fiber fed. All insoluble fiber diets and the guar gum and psyllium diets resulted in significantly higher daily fecal mass and, in general, resulted in significant dilution of total fecal steroids. With the insoluble fibers, there was a general dilution of fecal neutral steroids, which was not apparent with the soluble fibers or cholestyramine. In addition, except for the pectin- and mixed fiber-containing diets, there was reduced bacterial conversion of the primary bile acids to secondary bile acids or metabolites.

Animals↗

Inhibition of cholesterol synthesis.

Efforts to find inhibitors of cholesterol synthesis, which might act as hypocholesterolemic agents, have been going on for over 30 yr. One difficulty with this approach is that we are dealing with an integral metabolite rather than a foreign substance. It is thought that the ideal place for inhibition of synthesis would be a water-soluble intermediate between hydroxymethylglutaryl coenzyme A (HMG CoA) and squalene. Several inhibitors of cholesterol synthesis that acted in later stages showed an increase of a new steroid in the blood that usually accumulated at the stage of inhibition. A few of these compounds have also been shown to be teratogenic for rats. Currently there is a new generation of inhibitors whose site of action is at HMG CoA reductase. Fortunately, at this writing no serious side effects have been reported.

Animals↗

Reduction of colonic carcinogenesis by wheat bran independent of fecal bile acid concentration.

It has been reported previously that populations with a decreased concentration of fecal bile acids have a lower incidence of colon cancer. We examined the importance of fecal bile acid dilution by wheat bran (WB) in inhibiting colonic tumorigenesis in an experimental animal model. Male F344 rats received oral doses of the colon carcinogen 1,2-dimethylhydrazine [CAS: 540-73-8] and were assigned randomly to groups fed one of four semipurified diets for 26 weeks. The diets were fiber-free (FF), 10% WB, FF + bile salts, or WB + bile salts. The amount of bile salts added was adjusted to produce a fecal bile acid concentration in the group fed WB + bile salts equal to that found in the FF groups. Fecal bile acid concentrations at 12 and 24 weeks in the WB + bile salts group were similar to those in the FF group. Gross and microscopic findings at necropsy revealed a reduced total number and multiplicity of colon tumors in both bran-fed groups. Although the fecal bile acid concentrations of the FF and WB + bile salts groups were equal, the latter showed a significant reduction in tumor yield.

1,2-Dimethylhydrazine↗

Dietary fibre and lipid metabolism.

The influence of dietary fibre on lipid metabolism can be assessed at several levels. In animal studies it is possible to investigate the effects of fibre on serum and tissue lipid levels, on lipid absorption and excretion and, in specific instances, on experimental atherosclerosis. In man we are limited to examination of blood lipid and lipoprotein levels and on patterns of lipid excretion. Ershoff and his co-workers (eg) were among the first to demonstrate beneficial effects of fibre on serum and liver cholesterol levels in cholesterol-fed rats. They also showed that not all that we call fibre is hypocholesterolaemic. Cellulose, for instance, caused increases in liver cholesterol levels in rats. Cellulose also leads to increased levels of carcass cholesterol. Experiments in chickens, rabbits and monkeys have shown cellulose to exert the least beneficial effect on atherosclerosis or aortic sudanophilia. In man the insoluble fibres such as bran or cellulose are not hypocholesterolaemic, whereas soluble fibres such as guar gum or pectin are. The effects are also reflected in levels of high and low density lipoproteins. Studies relating to mechanism(s) of fibre action have shown that fibre may increase cholesterol and bile acid excretion and, in some cases, may affect faecal bile acid composition. Fibres have been shown to bind bile acids in vitro, the extent of binding being a function of both the type of fibre used and the type of bile acid or bile salt being studied. Fibre has also been shown to bind other lipids. Fibre also influences the rate of cholesterol absorption. To date most results can be classified according to the type of fibre used, ie soluble or insoluble; ionic or non-ionic. Our added understanding of modes of action of fibre will depend on better ability to relate structure to function.

Animals↗

The influence of diet and dimethylhydrazine on the large intestine of vervet monkeys: scanning and transmission electron microscope studies.

The study was designed to identify diet and carcinogen-dependent ultrastructural changes in the epithelium of macroscopically normal colonic mucosa in primates. Seventy adult female vervet monkeys were divided into seven equal treatment groups. Four 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, 1 PD) received dimethylhydrazine intramuscularly at 14 day intervals. After 18 months, monkeys of two groups on the WD were transferred to the PD (WD----PD) and 30 months later all were killed. Mucosae of caecum, colon transversum and rectum were examined by scanning and transmission electron microscopy and showed close similarity to that of humans. Rectal mucosae showed increased surface goblet cell secretory activity, mucin production and microvillar changes related to WD and WD----PD. The enhancing effect of a carcinogen on ultrastructural changes such as cellular pleomorphism, cytoplasmic interbridging, nuclear and nucleolar irregularities and appearance of argentaffin cells in the free surface epithelium were noted predominantly in high-fat treated animals. Such changes observed in the upper part of crypt, orifice and free surface epithelium can be characteristic for precancerous change and could be utilised practically in the detection of precursor lesions of the colon.

Animals↗

Diet, nutrition, and cancer. The role of fiber.

The mechanisms by which dietary fiber could inhibit development of colon cancer include effects on fecal weight and transit time, adsorption of bile acids, dilution of colonic contents, production of short chain fatty acids (products of fiber fermentation), inhibition of dehydroxylation of bile acids, and regulation of energy intake. Review of the literature suggests that effects on fecal weight and transit time and adsorption of bile acids are not likely mechanisms. Since concentration of bile acids is lower in feces of less susceptible populations, dilution of colonic contents may contribute to fiber effects. High colonic pH is associated with promotion of cancer and production of short chain fatty acids would counteract this effect. Animals maintained on calorie-restricted diets exhibit fewer spontaneous or experimentally induced tumors. Regulation of energy intake by fiber may contribute towards reduction of colon cancer incidence in man especially when caloric content is low from infancy.

Adsorption↗

Dietary fiber and human cancer: critique of the literature.

The relationship between dietary fiber consumption and risk of gastrointestinal cancer in humans is examined using representative studies of several types: international and intranational correlations, case-control analyses, metabolic investigations, cohort studies, and migrant studies. The strongest statistical association between diet and cancer is found in international studies in which numerous environmental variables differ. Studies on smaller groups within a single culture have not given strong support to the findings of international comparisons. Colon cancer rates within regions of the U.S. and other countries vary with sufficient magnitude that diet is unlikely to account for more than a minor proportion of risk. The evidence that a diet containing fiber-rich foods reduces risk of colon cancer must be considered tentative. Foods high in starch and fiber are statistically associated with a high rate of stomach cancer. Examination of the combined rates of colon and gastric cancer shows that the U.S. risk is low relative to countries in which a diet higher in fiber is consumed. It would be premature to suggest that a high fiber diet will confer protection against gastrointestinal cancer.

Colonic Neoplasms↗

Influence of caloric intake on experimental carcinogenesis: a review.

The effect of caloric intake on tumor growth has been recognized for over 70 years. Inhibition of tumor growth depends primarily on the extent of caloric restriction, but tumor type, animal strain, and dietary composition all exert some influence. Caloric restriction is most effective when maintained during both initiation and promotion, but if limited to one of these phases, restriction during promotion appears to be the more effective modality. The types of tumor that have been studied include spontaneous mammary and lung tumors as well as tumors induced by organ-specific carcinogens or irradiation with ultraviolet light. Numerous investigators have studied the effects of fat, and a diet low in calories but high in fat is generally significantly more effective in inhibiting carcinogenesis than is a diet high in calories but low in fat. Mice fed high fat, low calorie diets exhibited 48% fewer chemically induced skin tumors and 61% fewer tumors induced by ultraviolet irradiation than did mice fed low fat, high calorie diets. Mice fed a diet containing 2% fat exhibited a 66% incidence of skin tumors, whereas mice fed an isocaloric diet containing 61% fat showed a 78% incidence. Rats whose diet was restricted in calories by 40% exhibited no mammary tumors (coconut oil as primary dietary fat) or 75% fewer tumors (corn oil as dietary fat) compared to ad libitum-fed controls; they also exhibited 47% fewer colonic tumors. The mechanism by which caloric restriction exerts its tumor-inhibiting effects remains to be elucidated.

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↗