Dietary linoleic acid, accumulation of arachidonic acid in tissue lipids and production of TXB2 and PGI2 in the cardiovascular system.
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Biomedical subjects
Publications and source records attributed to E Agradi.
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The efficacy of the total substitution of animal proteins with a textured soybean protein in hypercholesterolemic individuals was assayed in 42 in-patients and 18 out-patients. The in-patients studied followed one of three different crossover protocols: in protocol A, the soybean diet was compared with a standard low lipid diet; protocol B compared two soybean diets, one with added cholesterol, one without; and protocol C compared a soybean diet containing a high P/S fatty acid ratio to one with a low P/S ratio. In all three protocols, the soybean regimen provided valid and reproducible hypocholesterolemic effects that were not modified by the addition of cholesterol. P/S variations appeared, however, to modify the final effect: soybean definitely had a decreased effectiveness with a low P/S (0.1) regimen. The overall plasma cholesterol changes in the 42 in-patients after 3 weeks on the different soybean diet protocols was -20%. Patients with type IIA and IIB hypercholesterolemia provided almost equivalent results, whereas patients with mixed phenotypes (IIB-III) appeared somewhat more sensitive to the dietary effect. Cholesterol decreased mostly in the low density lipoprotein fraction, but some very low density lipoprotein changes were also noted upon variation of the P/S ratio. The out-patients studied provided less satisfactory results. possibly due to the difficulty of adequately complying with the diet. These studies indicate that treatment with the soybean diet is an effective regimen for inducing a significant cholesterol reduction in type II patients refractory to standard low lipid regimens.
Semisynthetic diets containing 8% by weight of either corn oil or butter were fed to male New Zealand rabbits for three weeks. The plasma cholesterol values were determined, the threshold concentrations for aggregation of platelet rich plasmas were measured for collagen and Na arachidonate, and the conversion of 14C arachidonic acid to thromboxane B2 and hydroxy fatty acids (HETE and HHT) at 10, 20 and 40 microM substrate concentrations were studied. The thresholds for arachidonate induced aggregation were lower and the amplitudes of collagen induced aggregations were greater in the butter fed than in the corn oil fed rabbits. Conversions of arachidonic acid to thromboxane B2 but not to hydroxy fatty acids were greater in the butter fed rabbits at 10 and 20 microM substrate. The observed changes were accompanied by only slight modifications of plasma cholesterol levels.
A soybean textured protein induced a 14% decrease of plasma-cholesterol levels after two weeks and 21% after three when substituted for animal proteins in a group of 20 patients with type-II hyperlipoproteinaemia. Comparison of soybean diet with a standard low-lipid diet in the same patients, according to a cross-over protocol, indicated that this hypocholesterolaemic effect was not due to differences in the lipid composition of the two diets. The hypothesis that a soy protein has a hypocholesterolaemic action per se is supported by the results of a subsequent experiment in 8 type-II patients in whom the addition of cholesterol (500 mg/day) to soy protein did not modify the hypocholesterolaemic response.
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Limited trypsinization of the fatty acid synthetase multienzyme complex from rat mammary gland results in the release of a protein, molecular weight 32,000, with thioesterase activity. The other components of the multienzyme complex--the acyl carrier protein, acetyl and malonyl transferases, condensing enzyme, keto reductase, dehydrase and enoyl reductase--are not affected and remain associated with the complex. The thioesterase can be isolated by ammonium sulfate precipitation and gel filtration. Extensive trypsinization of fatty acid synthetase multienzyme complex results in a loss of thioesterase activity, probably due to cleavage of the thioesterase component into inactive peptides. However, the molecular weight and specific activity of the thioesterase isolated after limited trypsinization is relatively unaffected by the severity of the conditions of proteolysis. Both the thioesterase and the residual trypsinized complex react with antibodies produced against the native multienzyme. The results demonstrate that mild trypsinization can be used to release the thioesterase component of the multienzyme with little perturbation of either the thioesterase or the other components of the complex.
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