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Biomedical subjects

M M Mathias

Publications and source records attributed to M M Mathias.

7 recordsLinked to original sources

Copper-marginal and copper-deficient diets decrease aortic prostacyclin production and copper-dependent superoxide dismutase activity, and increase aortic lipid peroxidation in rats.

Agonist challenged aortic prostacyclin production was examined in copper-adequate, -marginal and -deficient rats fed AIN-based diets providing 6.7, 1.7 and 0.8 micrograms Cu/g, respectively. Aortic rings were incubated in Krebs-Henseleit salts, 10 mmol/L HEPES buffer, pH 7.4, 95%:5% O2:CO2, 37 degrees C, and equilibrated for 1 h. Equilibrated rings were challenged with buffer (basal), 273.0 nmol/L thrombin and angiotensin II at 84.6 pmol/L and 846.0 pmol/L. Prostacyclin production, determined at 10 minutes by RIA as 6-keto prostaglandin F1 alpha, in basal and 84.6 pmol/L angiotensin II ring incubations was significantly reduced by 28 to 48% in copper-deficient rats. With thrombin or 846.0 pmol/L angiotensin II prostacyclin production was significantly reduced by 18 to 55% in copper-marginal and copper-deficient rats. Copper-dependent superoxide dismutase activity was significantly depressed by 30 and 57% in aortae of copper-marginal and copper-deficient rats. Lipid peroxidation, estimated by the thiobarbituric acid test, was significantly increased by 85% in copper-deficient rats, with a nonsignificant 40% increase in aortae from copper-marginal rats. The results suggest that the decreases in aortic prostacyclin production in aortae from both copper-deficient and copper-marginal rats are associated, in a dose-dependent manner, with copper-dependent superoxide dismutase depression and increases in aortic lipid peroxidation.

Analysis of Variance

Studies of women eating diets with different fatty acid composition. III. Fatty acids and prostaglandin synthesis by platelets and cultured human endothelial cells.

The aim of this study was to determine how plasma fatty acids (FA) of subjects eating either a diet designed to match the US diet consumed in 1974 in fat content and composition in accord with the HANES I survey (US74) or a diet modified to meet the US Dietary Goal Recommendations (MOD) are altered, and how the changes affect platelet thromboxane (TXB2) synthesis, and prostacyclin (PGI2) and prostaglandin E2 (PGE2) synthesis by cultured human endothelial cells. Following a period of recorded self-selected diets, 10 women ate the US74 diet for 4 weeks, changing to the MOD diet for the next 4 weeks (sequence 1), and 10 ate the MOD diet followed by the US74 diet (sequence 2). Plasma triglycerides, free FA, platelet FA composition, and red blood cell phospholipids responded to the change from self-selected to controlled diets, but differences in responses were not seen between US74 and MOD diets. Red blood cell total FA did not respond to dietary changes. Under collagen but not thrombin stimulation, platelet TXB2 synthesis was correlated with platelet arachidonate concentration but not serum cholesterol. Endothelial cells were isolated from umbilical cord veins and incubated for 72 hours with a 20% medium of the women's plasma. In sequence 1 (high saturated FA to high polyunsaturated fatty acids), but not in 2 (reverse order), plasma from subjects eating the MOD diet decreased (p less than 0.05) basal and thrombin-stimulated PGI2 and PGE2 synthesis by the cells. These cells had a higher content of linoleic acid than cells from subjects eating the US74 diet. Thus, our study suggests that an increase in the intake of linoleic acid from 4.8 to 7.6 en% decreases PGI2 and PGE2 synthesis by human endothelial cells, and supplementation of the diet with linoleic acid has a longer period of effectiveness than its decrease in the diet.

Adult

Calcium, collagen dose, gender and fasting affect the response of rat platelet thromboxane formation to extremes in dietary linoleate.

Platelet thromboxane synthesis in response to supplemental linoleate in the diet has been very inconsistent. The objective of this study was to investigate potential confounding factors known to affect platelet thromboxane synthesis. Citrated whole blood was recalcified with varying Ca2+ concentrations and challenged with low or high dose collagen preparations to induce extreme ranges of thromboxane synthesis from endogenous arachidonate pools by rat platelets. Male and female weanling rats were fed 0.0, 1.0 or 23 energy percent linoleate for 11 to 13 weeks. Fasting tended to enhance thromboxane synthesis. Both fasted and fed females showed slightly faster rates of thromboxane synthesis than males. Essential fatty acid deficiency depressed (P less than 0.01) thromboxane synthesis; the degree of this depression was inversely related to the level of recalcification (68% for 0.0 mM Ca2+, 36% for 2.5 mM Ca2+ and 20% for 5.0 mM Ca2+) when challenged with the high dose collagen. Essential fatty acid deficiency depressed platelet phospholipid arachidonate concentration 26%. Only blood from fed females stimulated with a mild challenge responded to excess dietary linoleate, and a 62% (not statistically significant) depression in TX synthesis was observed and this was associated with a decrease in platelet phospholipid arachidonate concentration.

Animals

The relationship of dietary fats to prostaglandin biosynthesis.

The direct and indirect evidence that the fatty acid composition of dietary fat is involved in the regulation of prostaglandin biosynthesis was reviewed. Direct evidence included effects of essential fatty acid deficiencies and excesses on endogenous tissue levels and production rates of prostaglandins by several tissues. Indirect evidence included lipolytic, platelet aggregatory, hypertensive, inflammatory and immune responses. In general, composition of dietary fat did not affect prostaglandin biosynthesis unless a biochemical essential fatty acid deficiency was induced or the linoleate to saturated fatty acids ratio of the dietary fat was greater than 5. Most results were interpreted in light of changing fatty acid composition; however, very few direct measurements have been made.

Adipose Tissue

Prostaglandin production and lipolysis in isolated rat adipocytes as affected by dietary fat.

The influence of dietary fat on prostaglandin production and lipolysis was tested in basal and norepinephrine stimulated adipocytes isolated from the epididymal fat pads of fasted rats. Seven diets varying in fat calories and polyunsaturation were utilized. No basal differences were noted for prostaglandin E2 production or lipolysis. Norepinephrine stimulated prostaglandin E2 and F2alpha production was significantly (P less than 0.01) increased with greater polyunsaturation of fat, but not by increased fat calories. Norepinephrine stimulated lipolysis was depressed by an increase in fat calories but was unaffected by the degree of polyunsaturation of fat. This is in vitro evidence against the concept that prostaglandins play a feedback regulator role in fat cell lipolysis since no correlation could be made between the two parameters.

Adipose Tissue

Dietary fat type and ambient oxygen tension influence pulmonary prostaglandin synthetic potential.

Chronic hyperoxia produces pathological changes in lung which can be fatal. With an interest in delineating dietary factors which might affect the pulmonary response to hyperoxia, we fed rats a semi-synthetic diet containing polyunsaturated fatty acids (PUFA) as either 5% or 78% of the fat complement. The rats were exposed to pure oxygen at one atmosphere. Half the animals in each diet group were injected with aspirin during the hyperoxic exposure. Radioimmunoassay of lung prostaglandins (PG) F2alpha, E2 and E1 were performed at 0, 24, 48 and 72 hours. The major findings were: (1) Feeding the high PUFA diet elevated lung PG synthetic potential tenfold over that of low PUFA-fed animals. There was no effect of diet on mortality. (2) Hyperoxia significantly increased F2alpha-synthetic potential during the first 24 hours of hyperoxia and moderately increased the synthetic potential of E2 and E1. (3) Aspirin significantly depressed synthetic potential of all three PG prior to oxygen exposure but its effect was overcome during hyperoxia. Aspirin-injected rats showed 80% mortality in oxygen vs. 50% for saline controls.

Animals

Linoleate enrichment of diet and prostaglandin metabolism in rats.

Evidence that biosynthesis of prostaglandins (PG) in tissues of animals deficient in essential fatty acids is dependent on the availability of their precursors has been demonstrated. The purpose of this study was to determine the following: (1) effects of dietary linoleate enrichment on PG biosynthesis in rats; (2) effects of exogenous PGE2 and dietary linoleate on plasma free fatty acids and serum cholesterol in fed and fasted rats. Rats were fed three different concentrations of dietary linoleate as beef tallow, hydrogenated vegetable fat, or corn oil. The concentrations of PGE1 and PGF2a measured by radioimmunoassay were higher in rats fed the fed the beef tallow diet independent of energy status. A decrease in the concentration of PG between fasted and fed rats receiving hydrogenated vegetable fat is discussed in respect to the possible influence of trans isomers of unsaturated fatty acids on the biosynthesis of PG. There were significant effects of fasting on serum cholesterol concentration regardless of diet and significant interactions among effects of PGE2, fasting, and diet, suggesting regulatory effects of PGE2 on serum cholesterol concentration. The increase in plasma free fatty acids associated with fasting was prevented by PGE2 for all diets, but had the most marked effect on rats fed hydrogenated vegetable fat.

Animal Nutritional Physiological Phenomena