Cholesterol and hormone levels in sera of juvenile female rhesus monkeys.
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Biomedical subjects
Publications and source records attributed to D Kritchevsky.
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The activity of N-acetyl hexosaminidase (beta-2-acetamido-2-deoxy-D-glucoside:N-acetamido-deoxyglucohydrolase, E.C. 3.2.1.30) was significantly greater in sera of patients with solid malignant tumors than in sera of healthy volunteers or of patients with nonmalignant ailments. The increased activity was found in the two major isozymes, hexosaminidase A and hexosaminidase B, but the increase in the latter isozyme was more prominent than in the former. Measurement of the levels of the hexosaminidase isozymes may provide an ancillary diagnostic test for malignancy.
We describe a method for determining free and total cholesterol in extracts of rat-liver lipids by use of a cholesterol esterase/cholesterol oxidase enzymatic kit (Boehringer Mannheim Corp). The lipids are solubilized (as micelles) directly into the aqueous reagent mixture. Results of the enzymatic method correlate well with those obtained by an acid/ferric chloride assay of digitonin precipitates of the extracts. The enzymatic assay of free and total cholesterol in tissue offers advantages of simplicity over previously used methods.
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In studies of hydrolysis and synthesis of cholesterol esters by aortic enzymes, conventional methods (aside from isotope methodology) are too insensitive to measure reaction products when few aortas are used. High-performance thin-layer chromatography coupled with spectrodensitometry of plates charred after spraying with a cupric acetate-phosphoric acid reagent permitted quantitation of 10-ng amounts of cholesterol, cholesterol oleate oleate, and oleic acid. Linear calibration curves were obtained after spectrodensitometry of chromatograms containing 10-200 ng of lipid. The results were verified by radioassay.
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The influence of (--)-hydroxycitrate, a potent competitive inhibitor of adenosine triphosphate (ATP) citrate lyase, on serum triglyceride and cholesterol levels, and in vitro and in vivo rates of hepatic fatty acid and chloesterol synthesis was investigated in normal and hyperlipidemic rat model systems. (--)-Hydroxycitrate reduced equivalently the biosynthesis of triglycerides, phospholipids, cholesterol, diglycerides, cholesteryl esters, and free fatty acids in isolated liver cells. In vivo hepatic rates of fatty acid and cholesterol synthesis determined in meal-fed normolipidemic rats were suppressed significantly by the oral administration of (--)-hydroxycitrate for 6 hr, when control animals exhibited maximal rates of lipid synthesis; serum triglyceride and cholesterol levels were significantly reduced by (--)-hydroxycitrate. In two hypertriglyceridemic models-the genetically obese Zucker rat and the fructose-treated rat-elevated triglyceride levels were due, in part, to enhance hepatic rates of fatty acid synthesis. (--)-Hydroxycitrate significantly reduced the hypertriglyceridemia and hyperlipogensisi in both models. the marked hypertriglyceridemia exhibited by the triton-treated rat was only minimally due to increased hepatic lipogenesis;(--)-hydroxycitrate significantly inhibited both serum triglyceride levels and lipogenesis in this model.
Several of a series of linoleic acid amides have been reported to inhibit cholesterol-induced atherosclerosis in rabbits. The three amides which have been studied to the greatest extent are (in order of increasing activity) N-cyclohexyl linoleamide (AC23), N(alpha methylbenzyl) linoleamide (AC223), and N[aplha-phenyl-beta-(p-tolyl)ethyl] linoeamide (AC 485). We have found AC223 to inhibit cholesterol absorption in rats and to slightly inhibit exogenous but not endogenous cholesteremia in rabbits. In a fiber-free diet, AC223 reduces serum cholesterol and liver triglyceride levels. Rats were also fed a basal semipurified diet with and without AC223. Fecal excretion of labeled exogenous (as [ (14)C] cholesterol) or endogenous (as [14 C] mevalonolactone) steroid was 44 and 43% higher in drug treated groups. The mechanism of hypocholesteremic action of the linoleamides appears to involve inhibition of cholesterol absorption.
The statistical correlation between elevated serum cholesterol levels and increased risk of coronary heart disease has channeled thinking towards regarding dietary fat and cholesterol as the principal causes of hypercholesteremia. Since 1909 there have been a number of changes in nutrient availability in the United States. Protein availability is unchanged but the ratio of animal to vegetable protein rose from 1.06 in 1909 to 2.37 in 1972. Fat availability has risen by 26% with the ratio of animal to vegetable fat falling from 4.88 in 1909 to 1.64 in 1972. A review of available data indicates that amount and type of protein may affect cholesteremia and atherosclerosis in experimental animals. Soy protein is less cholesteremic than casein but the extent of difference can be affected by the type of carbohydrate. In a semipurified, cholesterol-free diet, saturated fat exerts an atherogenic effect but unsaturated fat does not. No atherogenicity is evident when saturated fat is added to laboratory ration. In the semipurified diet, fructose is more atherogenic than glucose, and casein is more atherogenic then soy protein. The latter difference can be virtually eliminated if alfalfa replaces cellulose as the dietary fiber. The data suggest that all elements of the diet interact and can affect cholesteremia and atherosclerosis. These effects must be considered in the planning of dietary intervention trials.
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Randomized lard and butter oil were conpared with native lard and butter oil for their effects on cholesterol-induced atherosclerosis in rabbits. In each experiment there was also a group fed corn oil. The diets contained 2% cholesterol and 6% fat and were fed for eight weeks. Randomization of either butter or lard had virtually no effect as regards their atherogenic potential when fed as part of a diet containing 2% cholesterol. The corn oil-containing diet was less atherogenic than any of the other fats.
Rabbits were maintained for 10 months on a semipurified, cholesterol-free atherogenic regimen. All diets contained sucrose (40%) and hydrogenated coconut oil (14%). The protein (25%) was either casein or soya protein and the fiber (15%) was either wheat straw, alfalfa, or cellulose. Within either protein group the order for induction of cholesteremia was cellulose=wheat straw greater than alfalfa. For atherogenesis, the effect was cellulose greater than wheat straw greater than alfalfa Soya-wheat straw or soya-cellulose diets were less cholesteremic and atherogenic than their casein counterparts. When alfalfa was the fiber, the two types of protein were almost equivalent. Our results show that casein may be more cholesteremic and atherogenic than soya protein under certain conditions (cellulose or wheat straw as fiber) but the addition of alfalfa to the diet renders the two proteins equivalent.
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Analyses of serum lipids of children with cystic fibrosis (CF) have indicated a deficiency in essential fatty acids (EFA). In view of a report that intravenous administration of soybean oil emulsions normalized sweat sodium values in CF children, we studied the effects of orally administered essential fatty acids (as corn oil) for one year. Some improvement was noted in all patients, but no one consistent factor predominated. However, arachidonic acid, which was found only in trace amounts or was absent in sera of all children with CF before the clinical trial, was increased significantly in the sera after the oral administration of EFA for one year. Other findings included a significant decrease in sweat sodium and T3 in most patients.
There is evidence that type of diet may affect the course of chemical carcinogenesis. In experiments with acetylaminofluorene, rats maintained on stock diet exhibit fewer tumors than do rats fed semi-purified diets. Rats fed stock diet augmented with high levels of sodium cyclamate (2.5-10%), amaranth (5%) or Tween (15%) showed normal weight gain, whereas addition of these toxicants to a fiber-free basal diet caused severely restricted weight gain and decreased survival. The latter effect can be overcome by addition of 10% pectin, alfalfa or cellulose to the basal diet. On the other hand, mice fed a fiber-free diet survived pneumococcal infection better than did mice fed modified stock diets. The mechanism(s) by which fiber affects carcinogenicity or toxicity are unelucidated. The effect of fiber and other aspects of diet on drug action is an area of research that should be developed.
The in vitro binding of sodium taurocholate to various cereal products was determined. Maize meal bound significantly more bile salt than maize rice or samp and significantly less than minitmeal or minitsamp.