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Biomedical subjects

D Kritchevsky

Publications and source records attributed to D Kritchevsky.

At least 181 records · Page 10Linked to original sources

Age-strain interrelations in lipid metabolism of rats.

Various aspects of lipid metabolism were compared in Fisher 344 (F) and Sprague-Dawley (SD) rats aged 2, 6, 12, 18 and 24 months. The analyses included free and total cholesterol of serum and liver, LCAT, hepatic HMG-CoA reductase, cholesterol 7 alpha-hydroxylase, fatty acid synthetase, acetyl CoA carboxylase and cholesterol synthesis from acetate or mevalonate. The body weight of SD rats increases with age whereas that of F rats plateaus at 9-12 months. Liver and aorta cholesterol levels were comparable for the 2 strains. Serum cholesterol varied but was usually lower in F rats. HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities were not significantly different. Cholesterol synthesis from acetate was significantly higher only in 2-month-old F rats; synthesis from mevalonate was similar at each level. Acetyl CoA carboxylase and fatty acid synthetase activity were generally higher in F rats at every age level. The major difference between F and SD rats is in their pattern of weight gain with age. Differences in lipid metabolism are most marked between the young (2-month) rats.

Aging↗

Experimental atherosclerosis in rabbits fed cholesterol-free diets. Part 9. Beef protein and textured vegetable protein.

Rabbits were fed a semipurified diet containing 40% sucrose, 25% protein, 15% fiber and 14% tallow. The proteins fed were beef (B), textured vegetable protein (TVP) and casein (C). One diet contained beef-TVP (1 : 1) and in another a soy carbohydrate fraction, spent flakes, was added to the diet; it provided 2.2% protein and 10.5% fiber. TVP provided 6.4% soluble carbohydrate and 10.5% fiber. The diets were fed from 8 months. Diets containing beef protein or casein gave significantly higher serum cholesterol levels and atherosclerosis and significantly lower serum HDL-cholesterol than did the other 3 diets. The beef-TVP (1 : 1) diet gave low serum cholesterol (67% below beef) levels and atherosclerosis (47% below beef). This effect is probably due to the protein. The diet containing spent flakes gave low serum cholesterol levels (44% below beef) and atherosclerosis (45% below beef). This effect is attributed to the different fiber. The lowest serum cholesterol levels and least severe atherosclerosis were observed in the rabbits fed TVP.

Animals↗

Serum cholesterol and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis.

Diet-induced changes in serum cholesterol levels and their relationship to mammary carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) were studied in female Sprague-Dawley rats. DMBA was given to rats subjected to 3 dietary treatments: (1) a semipurified, cholesterol-free diet (SP); (2) the same diet with 1.5% cholesterol and 0.5% bile salts added (CB); (3) diet CB, until administration of DMBA and then switched to diet SP. Tumor yield per rat was increased in rats fed diet CB, but incidence and tumor size were similar among all 3 groups. Rats maintained on diet SP alone had a higher percentage of histologically benign tumors. Hypercholesterolemia of dietary origin appears to enhance slightly chemical carcinogenesis in this model.

9,10-Dimethyl-1,2-benzanthracene↗

Effect of chronic intake of dietary fibers on the ultrastructural topography of rat jejunum and colon: a scanning electron microscopy study.

This report is an attempt to quantitate the observable topographical characteristics of small and large intestine after a specific dietary regimen under well-defined states of lipid absorption and metabolism. Alfalfa, white wheat bran, cellulose, and pectin were fed for 6 wk at a level of 15 g/100 g diet to four groups of rats (12 rats per dietary group). A 5th control group was maintained on Purina Rat Chow. Three animals from each group were blind-coded for morphological assessment. After anesthesia, the jejunum and mid-colon were removed and processed for scanning electron microscopy. Beginning with the mildest mucosal surface changes, the observed order in terms of increasing severity is bran less than cellulose less than pectin less than alfalfa. Our observations suggest that altered rates of cell loss in intestinal tract cytokinetics may be occurring with particular feeding patterns and should be considered as a possible mechanism in the nutritional consequences of dietary fiber intake.

Animals↗

Effects of tomato pomace and mixed-vegetable pomace on serum and liver cholesterol in rats.

The effects of tomato pomace and mixed-vegetable pomace, vegetable processing by-products, on serum and liver cholesterol were compared against pectin, wheat bran, cellulose, and lignin. Male Sprague-Dawley rats (100 g) were fed high sucrose, semi-purified diets containing basal (0), 5% or 10% of the fiber source and either 0, 0.5% cholesterol or 0.5% cholesterol + 0.125% sodium cholate. After 28 days, there were highly significant differences (P less than 0.001) in serum and liver cholesterols due to fiber source, dietary cholesterol and the interaction. The effect of fiber source level was significant (P less than 0.05) for liver cholesterol only. Pectin groups had serum and liver cholesterol levels lower (P less than 0.05) than the others. At the 10% level, tomato pomace, wheat bran and lignin (Indulin AT) groups had serum cholesterols higher (P less than 0.05) than basal; the mixed-vegetable pomace and cellulose groups were not different from basal. Liver cholesterols of tomato pomace, mixed-vegetable pomace, wheat bran and lignin groups were not different at the 10% level, but were higher than the pectin, cellulose and basal groups (P less than 0.05). In a second experiment, serum cholesterols of rats fed pectin were lower (P less than 0.05) than for those fed cellulose or two types of lignin (Indulin AT, Reax 27).

Animals↗

Ultrastructural modifications of intestinal and colonic mucosa induced by free or bound bile acids.

There is substantial evidence that bile acids may enhance the colon tumorigenesis induced by chemical carcinogens and that agents stimulating increased bile acid excretion may show similar promoting or enhancing activity. To test the premise that these agents might modify topographical ultrastructure of the small intestine and colon in the absence of carcinogens, rats were fed for 6 weeks on chemically defined diets containing 2% levels of three commercial bile acid sequestrants or 15% levels of wheat brain, cellulose, pectin, or alfalfa. Major qualitative and quantitative deviations from normal morphology were observed with each of the three sequestrants. Similar but less dramatic modifications occurred with diets containing alfalfa or pectin, both of which either "bind" bile acids in vitro or result in increased bile acid excretion. Bran and cellulose which neither "bind" bile acids nor increase their fecal excretion, were without significant effects on intestinal or colonic morphology. The morphological deviations observed with bile acid sequestrants were shown to be a direct response to free or bound bile acids by comparing the morphological modifications resulting from daily intracolonic infusions of free bile acids, sequestrant-bound bile acids, or the sequestrant alone.

Animals↗

Sitosterol.

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Animals↗

[Pharmacology of fenofibrate (author's transl)].

Fenofibrate is one of several compounds with substituted-2-phenoxy-isobutyric acids and esters. In ageing rats receiving a hyperlipidaemic diet or injections of triton, fenofibrate lowers blood lipids as much as, or more than other antilipaemic agents. It is active in man against the main types (IIa, IIb and IV) of hyperlipoproteinaemia (HLP), and this activity is sustained throughout treatment (20 months in one study). In comparative studies, the effects of fenofibrate (400 mg/day) on the lipoprotein fractions tested were superior to those of clofibrate (2 g/day) and slightly superior to those of gemfibrosil (800 mg/day) and bezafibrate (600 mg/day). The drug also enhanced the lipid-lowering effects of colestipol. In doses of 300 mg/day fenofibrate produced a significant 13-15% decrease in apoprotein B with a concomitant 19-28% increase in apoprotein A. Fenofibrate was also found to normalize platelet aggregation in patients with type IIb HLP. In animals fenofibrate is excreted in equal amounts in the urine and faeces; in man, urinary excretion predominates (85-90%). The serum half-life curve is diphasic, with a rapid (5 hours) slope and a slow (17 hours) slope. In a 10-day study conducted on 10 volunteers serum levels of fenofibric acid remained remarkably constant, indicating lack of accumulation. New data on the mode of action are needed to further differentiate fenofibrate from clofibrate.

Animals↗

Effect of bile salt-binding resins on the morphology of rat jejunum and colon. A scanning electron microscopy study.

One mechanism suggested to account for the hypocholesteremic effect of dietary fibers is their ability to sequester bile salts. Since bile salts have been found to alter intestinal structure, the morphological effects of several commonly used, xenobiotic, bile salt-binding agents was investigated. Wistar rats were fed a purified stock diet, ad libitum, for 6 weeks containing either 2% cholestyramine, 2% colestipol, or 2% DEAE-Sephadex. The bile salt-binding capacity of these substances was tested in vitro using taurocholate and glycocholate. The effect of in vivo feeding of the resins was to evoke ultrastructural topographical deviations from control appearance in both jejunal and colonic mucosae. Colonic cell injury was more severe than that observed in the jejunum of both colestipol- and DEAE-Sephadex-fed animals while the reverse was true for the rats fed cholestyramine. The degree of distortion in each condition was positively correlated with the extent of bile salt-binding capability in vitro. The rank order of both effects in terms of increasing severity was DEAE-Sephadex less than colestipol less than cholestyramine.

Animals↗

Dietary fibers: V. Binding of bile salts, phospholipids and cholesterol from mixed micelles by bile acid sequestrants and dietary fibers.

Mixed micelles were prepared containing combinations of either taurocholate or taurochenodeoxycholate, monoolein, oleic acid, dioleylphosphatidylcholine (lecithin) and cholesterol. These were incubated with commercial bile-acid-sequestering resins, cholestyramine and DEAE-Sephadex, or various dietary fibers and fiber components including wheat bran, cellulose, alfalfa, lignin and 2 viscosity grades of guar gum. Binding was determined as the difference between the radioactivity of each micellar component added and that recovered in the centrifugal supernatant after incubation. In general, the extent of bile salt sequestration was characteristic and reproducible for each bile salt, and was largely unaffected by the presence of one or more additional components of the micellar mixture, including the other bile salt. Cholestyramine bound 81-92% of the bile salts and 86-99% of the phospholipid and cholesterol present in micelles. DEAE-Sephadex sequestered only 49% of the taurocholate and 84% of the taurochenodeoxycholate, but completely removed all of the phospholipid and cholesterol from micelles containing either bile salt. Among the dietary fibers, guar gum of either viscosity bound between 20-38% of each micellar component, whereas lignin, alfalfa, wheat bran and cellulose were progressively less effective in sequestration of individual components of mixed micelles. The extent of sequestration of micellar components by these resins and fibers is reasonably correlated with the effects of these same materials on lymphatic absorption of lipids and to their suggested hypocholesteremic properties.

Bile Acids and Salts↗

Clofibrate, pirinixil (BR 931) and WY-14,643 do not affect body cholesterol in Sprague-Dawley rats.

Cholesterol levels in plasma and different tissues were determined in Sprague-Dawley male rats, on standard and cholesterol-cholic acid enriched diets, after short term treatment with the absorbable hypolipidemic agents, clofibrate, WY-14,643 and Pirinixil (BR 931). The objective of the study was to evaluate the mode of action of these drugs in decreasing plasma cholesterol, be it by increased tissue mobilization, or by redistribution from plasma to tissues. After one or two weeks on a standard diet, none of the three agents significantly affected total body cholesterol stores. In spite of the liver enlargement induced by all three, in no case was total liver cholesterol significantly raised. Only clofibrate significantly increased colonic cholesterol concentrations. On a cholesterol-cholic acid regimen, some cholesterol mobilization was noted with all three drugs. However, only Pirinixil significantly reduced total liver cholesterol as well as the estimated total body cholesterol. A parallel effect of diet and drugs on plasma and body cholesterol pools is not constantly observed. In the examined rat model, clofibrate and two chemically unrelated compounds with a probably similar mechanism of action, markedly reduce plasma cholesterol levels while not affecting or decreasing total body cholesterol stores.

Animals↗