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Biomedical subjects

D Kritchevsky

Publications and source records attributed to D Kritchevsky.

At least 73 records · Page 4Linked to original sources
PubMed1991

Dietary fat and experimental atherosclerosis.

This paper reviews studies relating to the effects of fat unsaturation and fatty acid composition on the development of experimental atherosclerosis in rabbits. The results derived from the feeding of various fats are similar whether one feeds cholesterol or an atherogenic, cholesterol-free semipurified diet. In general, the severity of atherosclerosis is inversely related to the level of fat unsaturation. Two exceptions are cocoa butter which is much less atherogenic than expected, most probably due to its high content of stearic acid, and peanut oil, while relatively unsaturated, is surprisingly atherogenic for rats, rabbits and monkeys. This latter effect is not related to the level (6%) of long-chain saturated fatty acids (arachidic, behenic, lignoceric) present in peanut oil, but rather to its triglyceride structure. Randomization of peanut oil, which modifies its triglyceride structure, significantly reduces its atherogenicity.

Animals↗
PubMed1991

The role of calories and caloric restriction in carcinogenesis.

Studies in mice and rats show that caloric restriction (CR) without malnutrition lowers the incidence of most spontaneous and induced tumors and delays their onsets. The maximum life spans of rodents and other experimental animals (e.g., fish, spiders, water fleas) are extended by CR. The molecular events that underlie these outcomes remain unelucidated. Although epidemiologic studies have not usually examined the relationship between caloric intake and cancer incidence, recent findings suggest a positive association for certain cancers such as colorectal, breast, and stomach. It is apparent that future studies of diet and cancer in humans must seriously assess the role of calories and energy balance as well as their interaction with the effects of specific nutrients.

Animals↗
PubMed1990

Steady-state mRNA expression for growth factors in DMBA-induced rat mammary tumors.

Steady-state mRNA levels were examined for insulin-like growth factors (IGF) I and II, transforming growth factor alpha (TGF alpha) and its receptor and the epidermal growth factor (EGF) receptor in mammary tumors induced by DMBA in rats. An abundant 4.8 kb TGF alpha transcript was identified in all tumors, along with a 7.5-8.0 kb IGF-I transcript. A presumptive 2.9 kb IGF-II transcript was also identified in all tumors. Northern analyses and receptor autophosphorylation studies failed to detect EGF receptors in any mammary tumors. These findings suggest the potential for autocrine or paracrine influences of IGF-I and IGF-II in this tumor model and a possible paracrine influence of TGF alpha in tumor-induced neovascularization.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Nutrition and breast cancer.

International comparisons have provided striking correlations between fat consumption and risk of breast cancer, but these comparisons do not often consider variations in life style. Case-control studies carried out in several countries showed no real association between fat intake and breast cancer. There is some evidence that vitamin A or carotenoid intake may exert a protective effect. Alcohol intake, on the other hand, seems to be positively associated with breast cancer risk. Elevated body weight, body mass, stature, and frame size have been found to be associated as risk factors for breast cancer in women. Animal studies found that caloric restriction inhibits growth of spontaneous and induced mammary tumors, an observation that held up even when the calorie-restricted animals ingest more fat than the ad-libitum-fed controls. College women who exercise have a lower incidence of breast cancer than their more sedentary classmates. Exercise is another means of reducing caloric availability.

Animals↗
PubMed1990

Fiber and cancer.

The role of dietary fiber in colon cancer is still not clear. Ecological studies suggested a protective role for high fiber intake, but more recent analysis shows similar intakes of dietary fiber in populations with high or low incidence of colon cancer. Case-control studies generally do not support a protective role for fiber. The data suggest that the effects of fiber must be considered in the context of the total diet and interactions of dietary components. A role for levels of energy intake is not excluded.

Bile Acids and Salts↗
PubMed1990

A comparison of absorption of glycerol tristearate and glycerol trioleate by rat small intestine.

Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri[9,10 (n)-3H]oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl [1,3-14C]tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Protein and atherosclerosis.

In general, protein of animal origin is more cholesterolemic and atherogenic than plant protein. The addition of single amino acids to the protein can influence cholesterolemia and atherogenicity, by either increasing or decreasing these conditions. The lysine to arginine ratio, which is higher in animal than in plant proteins, may be a factor in cholesterolemia. The results may be explained in part by the findings that lipid absorption is elevated in rabbits or rats fed animal proteins as is turnover time. Animals fed soy protein excrete more neutral and acidic steroids, and have increased activity of hepatic HMG CoA reductase and cholesterol 7 alpha-hydroxylase. Animal protein may exert its hypercholesterolemic effect by mechanisms which include increased absorption of cholesterol and decreased turnover.

Animals↗
PubMed1990

Influence of caloric restriction and exercise on tumorigenesis in rats.

Underfeeding or caloric restriction have been shown to inhibit the growth of spontaneous, transplanted, or chemically induced tumors in rats and mice. At 40% caloric restriction, growth of 7,12-dimethylbenz(a)anthracene-induced mammary and 1,2-dimethylhydrazine-induced colonic tumors is inhibited significantly even when the restricted diet contains twice as much fat as the control diet. Some inhibitory effects become evident even at 10% caloric restriction. In studies involving high fat diets, we find that rats receiving 20% fat ad libitum exhibit significantly higher 7,12-dimethylbenz(a)anthracene-induced mammary tumor incidence, multiplicity, and weight than rats ingesting the same amount of fat daily, but in a diet containing 25% fewer calories. In a study of intermittent ad libitum and restrictive feedings, chemically induced tumorigenicity varies inversely with feed efficiency. Exercise has also been shown to inhibit tumor growth. Sedentary rats fed ad libitum have a 108% higher incidence of 1,2-dimethylhydrazine-induced colon tumors than rats fed ad libitum but subjected to vigorous treadmill exercise. Caloric flux (either reduced intake or increased outflow) appears to reduce tumorigenicity in rodents.

1,2-Dimethylhydrazine↗
PubMed1990

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↗
PubMed1989

Caloric restriction and 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in rats: alterations in circulating insulin, insulin-like growth factors I and II, and epidermal growth factor.

Caloric restriction (CR) inhibits many neoplastic diseases in rodents, yet the biochemical mechanism(s) for these effects are poorly understood. We have examined the effects of ad libitum (AL) feeding with 25 or 40% CR on the promotion of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in virgin female Sprague-Dawley rats. Further, we have also studied the influence of chronic CR on temporal alterations in circulating insulin, insulin-like growth factor I/somatomedin C, insulin-like growth factor II/multiplication-stimulating activity, and epidermal growth factor levels at 0, 1, 3, 5, 11, and 20 weeks in carcinogen- and vehicle-treated animals. Tumor incidence and multiplicity were markedly inhibited (P less than 0.05) with increasing CR. Fasting serum insulin-like growth factor I/somatomedin C levels exhibited a significant acute decline with CR at 1 and 3 weeks, but were comparable to AL-fed controls throughout the remainder of the 5-month study, despite continued differences in weight gain between AL and CR rats. Levels of insulin-like growth factor II/multiplication-stimulating activity exhibited no discernible pattern in relation to CR. Serum insulin levels showed age-dependent increases, but were affected by increasing CR at all time points. Insulin levels were significantly (P less than 0.05) reduced in 40% CR rats from 3 weeks onward compared to controls, while 25% CR resulted in nonsignificant (P less than 0.07) reductions throughout the study. No significant differences in growth factor levels were observed between 7,12-dimethylbenz(a)anthracene- and vehicle-treated rats. Circulating epidermal growth factor was not detectable in any treatment group regardless of the nature or duration of the dietary regimen, time of blood collection, or subsequent tumor-bearing status. These data suggest that decreased serum insulin-like growth factor I/somatomedin C and insulin levels with CR and their complex interactions in vivo may play a role in the inhibition of mammary tumor promotion by CR.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Growth factor binding to 7,12-dimethylbenz(a)anthracene-induced mammary tumors from rats subject to chronic caloric restriction.

Caloric restriction (CR) inhibits tumorigenesis in rodents. To understand the basis for this effect the binding of insulin, insulin-like growth factor I/somatomedin C (IGF-I/Sm-C), insulin-like growth factor II/multiplication stimulating activity (IGF-II/MSA), and epidermal growth factor were examined to membrane preparations of 7,12-dimethylbenz(a)anthracene-induced mammary adenocarcinomas and several normal tissues from female Sprague-Dawley rats. Animals were fed ad libitum (AL) or 25% and 40% calorically restricted diets. Large, palpable (LP) and small, less than or equal to 100 mg, nonpalpable (SNP) tumors were evaluated. Growth factor binding to tumors was differentially affected by CR. IGF-I/Sm-C binding was comparable for AL-LP, AL-SNP, and 25% CR-LP tumors, but elevated in 25% CR-SNP tumors. Scatchard analysis revealed high and low affinity IGF-I/Sm-C binding sites, with AL-SNP and 25% CR-SNP tumors exhibiting similar levels of high affinity sites and at a greater concentration than AL-LP and 25% CR-LP tumors. Insulin binding to mammary tumors was low, i.e., 8- to 13-fold lower than IGF-I/Sm-C binding. The 25% CR-LP and SNP tumors bound 2- to 5-fold more insulin than corresponding AL-LP and SNP tumors. Binding of IGF-II/MSA to these tumor preparations was high, approximately 11- to 25-fold greater than insulin binding, and was unaffected by CR or tumor size. The binding of epidermal growth factor was not detected in any tumor preparations. Receptor binding studies were confirmed with covalent cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Normal tissues exhibited tissue- and growth factor-specific alterations in binding with host CR. Thus, alterations in growth factor binding were not tumor specific, but were less pronounced than in mammary tumors. These findings suggest alterations in IGF-I/Sm-C and insulin binding properties to tumors in relation to CR and tumor size may contribute, in part, to the inhibitory effects of CR on tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Inhibition of DMBA-induced mammary tumorigenesis by caloric restriction in rats fed high-fat diets.

Most previous studies on the inhibiting effect of caloric restriction during promotion of DMBA-induced mammary carcinogenesis have used low to moderate levels of dietary fat, i.e., about 4 to 14% by weight. The current study was designed to test whether a moderate degree of caloric restriction, 25%, would inhibit tumor growth in rats fed the equivalent of 20% dietary fat which approximates human consumption in affluent countries. Rats were fed diets ad libitum that contained 5, 15 or 20% corn oil. Groups of rats were pair-fed to the last 2 groups, but subjected to a 25% caloric restriction. These groups were fed 20 or 26.7% corn oil so that absolute fat intake in the paired groups was identical. Significant inhibition of tumor incidence, tumor weight, tumor burden, body fat deposition, and fasting serum insulin were observed in the 2 calorically restricted groups. We conclude that moderate caloric restriction is significantly more effective in inhibiting tumor growth than is the promoting effect of diets high in fat. Total body weight, body fat and serum insulin concentrations may be better correlates of risk of developing mammary tumors than is dietary fat.

3-Hydroxybutyric Acid↗
PubMed1989

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↗
PubMed1989

Influence of dietary cis and trans fats on DMH-induced colon tumors, steroid excretion, and eicosanoid production in rats prone to colon cancer.

The effect of geometrical isomerism of dietary fats on colon tumorigenesis was studied in male and female rats of a strain prone to colon cancer (Wistar-Furth-Osaka). The rats were fed purified diets containing either partially hydrogenated corn oil (trans fat) or high-oleic safflower (cis fat) at the 5% level for one week and received a single oral dose of 1,2-dimethylhydrazine. The difference in the fatty acid composition of dietary fats was confined solely to the geometry of octadecenoate. An appropriate level of linoleic acid (2% of total energy) was supplied. After about 60 weeks, neither fat-type nor sex-dependent differences in the incidence of colon and small intestinal tumors was observed. The fecal excretion of neutral but not acidic steroids was higher in male rats fed the trans fat than in those fed the cis fat, but the composition remained almost unchanged. Aortic production of prostacyclin and the plasma concentration of thromboxane B2 were not influenced by dietary fats, although these were significantly higher in females, irregardless of the fat source. Thus, trans fat behaved much like the cis fat in various parameters, except for steroid excretion.

Animals↗
PubMed1989

Response of mammary tumors to caloric restriction for different time periods during the promotion phase.

Rats treated with 7,12-dimethylbenz[a]anthracene were subjected to 25% caloric restriction for varying times during the promotion/progression phase of mammary tumorigenesis. Caloric restriction was inhibitory to a statistically significant extent when it was maintained for the entire four-month study or only during the first or last two months. Restriction for the first month with subsequent ad libitum feeding led to rapid weight gain with concomitant appearance of tumors. These data indicate that caloric restriction can be instituted late in the tumorigenic process with an acute response of tumor growth to caloric intake or body weight.

9,10-Dimethyl-1,2-benzanthracene↗