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Biomedical subjects

S Renaud

Publications and source records attributed to S Renaud.

At least 91 records · Page 5Linked to original sources

Effects of dietary linoleic acid on rat platelet ADP-induced aggregation and binding of 125I-fibrinogen.

Platelets from rats fed a diet high in linoleic acid (6%) bound increased amounts of fibrinogen on stimulation with ADP, compared to those from rats fed diets with low (2%) or no linoleic acid. However, this increased fibrinogen binding was associated with a decrease in platelet aggregation induced by ADP. Changes in the linoleic acid concentration in platelet membranes may cause changes in this relationship.

Adenosine Diphosphate↗

The effect of oral contraceptives on rat platelet membrane glycoproteins.

Female rats were administered oral contraceptives and the levels of sialic acid on platelet membrane and granule glycoproteins were compared to controls using a sialic acid assay and a fluorescein-conjugated wheat germ agglutinin binding assay and also by measuring the binding of 125I-labelled wheat germ agglutinin to glycoprotein bands from platelets separated by polyacrylamide electrophoresis. The contraceptive-treated rats showed increased levels of glycoprotein sialylation which may partly explain the altered physiological function of the platelets.

Animals↗

Effects of oral contraceptives, or lanosterol, on ADP-induced aggregation and binding of 125I-fibrinogen to rat platelets.

The aggregation to ADP and the binding of 125I-fibrinogen to platelets from rats treated with oral contraceptives or normal platelets treated in vitro with lanosterol were compared to their respective controls. Both types of platelets showed a significant increase in ADP-induced aggregation and in binding of fibrinogen, indicating that the effect of oral contraceptives could be partly due to increased levels of lanosterol in platelet membrane.

Adenosine Diphosphate↗

A sensitive method for the routine determination of plasma nicotine by flame ionization gas-liquid chromatography.

A gas chromatographic procedure for the analysis of nicotine in plasma, which uses quinoline as an internal standard, is reported. The nicotine is extracted with diethyl ether, concentrated without any evaporation, thus avoiding losses, and analyzed without derivatization. The recovery is 83.2 +/- 6.1% (n = 6). Although the analysis is carried out with a classical flame ionization detector, the detection limit is 0.1 ng/ml. Linearity is observed up to 100 ng/ml. The results of the precision analysis performed in the working range indicate a good reproducibility: a coefficient of variation of 5.2% is obtained for within-run analysis and 10.5 to 4.5% for nicotine values from 2.9 to 19.1 ng/ml for day analysis. Since a single run (the limitative step) lasts less than 15 min this improved procedure allows a great number of samples to be processed per day.

Animals↗

Vitamin E prevents the platelet abnormalities induced by estrogen in rat.

Platelet lipid biosynthesis in relation to aggregation has been studied in female rats treated with ethynylestradiol and fed laboratory chow or a vitamin E-deficient diet. In both normal and vitamin E-deficient rats, administration of ethynylestradiol highly significantly (p less than .001) increased the biosynthesis of total lipids but mostly of lanosterol (+ dihydrolanosterol) by thirteen-fold in normal rats and by nine-fold in vitamin E-deficient rats. The increased lipid synthesis was associated with a higher response of platelets to thrombin-induced aggregation. Concomitant administration of alpha-tocopherol acetate in both normal and vitamin E-deficient rats depressed markedly the enhanced lipid synthesis and aggregation induced by estrogen. Administration of ethynylestradiol lowered considerably the level of vitamin E in plasma but not in platelets. Treatment by tocopherol partly corrected the low plasma level of vitamin E resulting from estrogen administration. In vitro addition of lanosterol to platelets highly significantly increased the response of platelets to thrombin- and ADP-induced aggregation. This hyperaggregability was almost entirely inhibited by preincubation of platelets with tocopherol acetate. In the present in vivo and in vitro studies, alpha-tocopherol was able to neutralize most of the adverse effects of estrogen on blood platelets.

Animals↗

Lipoxygenase activity of intact human platelets.

The oxygenation by lipoxygenase of different icosaenoic and docosaenoic acids by intact human platelets was studied. The HPLC analysis of the hydroxy compound (s) derived from icosaenoic acids showed that the 12-derivatives predominate. The increase of the fatty acid concentration markedly enhanced their oxygenation except for icosapentaenoic acid. The conversion of this acid into its hydroxy derivative rose in the presence of arachidonic acid, probably through both its cyclo-oxygenase and lipoxygenase product formation. Since 12-hydroxy-icosaenoic acids are modulators of PGH2-induced platelet aggregation, we conclude that the interactions between polyunsaturated fatty acids during their oxygenation by platelet lipoxygenase could be relevant to the regulating activity of dietary fatty acids.

Blood Platelets↗

Platelet function after cigarette smoking in relation to nicotine and carbon monoxide.

In two sets of experiments involving 10 smokers, we followed the acute effect of inhaling smoke from cigarettes with five different nicotine yields (0.07 to 1.44 mg) on platelet function in relation to blood levels of carboxyhemoglobin and nicotine. Blood was drawn from fasted subjects who had not smoked for 10 hr before and after smoking one cigarette. Depending on the cigarette, the increase in platelet aggregation to thrombin, adenosine diphosphate, collagen, and epinephrine 10 min after smoking ranged from 0% to approximately 80% for the cigarettes with the higher nicotine yields. Blood nicotine levels increased from 112% to 644%. Clotting activity of platelet-rich plasma (PRP) and platelets rose by 16% with the cigarettes with the highest nicotine contents. Platelet activity correlated with blood nicotine levels but not with carboxyhemoglobin levels. Nicotine diluted in saline solution and added in vitro to PRP from six other subjects 2 min before the aggregation or clotting test at levels after smoking (10 and 20 ng/ml) induced a rise in platelet reactivity of the same order as that after smoking cigarettes. Data suggest that in some cigarettes, nornicotine and substances contained in tar may contribute to the effect of cigarette smoking on platelets.

Adenosine Diphosphate↗

Platelets during alimentary hyperlipaemia induced by cream and cod liver oil.

Healthy male subjects were given 100 g lipids as cream or cod liver oil. They were examined before and during alimentary hyperlipaemia. Cream increased platelet coagulant activity in plasma and reduced it in washed platelets. Both meals increased platelet sensitivity to thrombin and collagen. Cod liver oil reduced the uptake of arachidonic acid (AA) in platelets. Washed platelets prelabelled with [14C]-AA increased radioactivity 10-fold in free fatty acids (FFA) by exposure to thrombin [2 U (10(9) platelets)-1] for 20 s. This increase was augmented by cod liver oil. Phosphatidylethanolamine and phosphatidylcholine were the most significant donors of AA during thrombin stimulation. By exposure of prelabelled washed platelets to thrombin [0.3 U (10(9) platelets)-1] for 4 min the percentage distribution of [14C]-AA increased after cod liver oil in FFA plus the products of AA metabolism formed by the cyclooxygenase and lipoxygenase pathways. This study indicates that intake of a meal rich in lipids induces acute disturbances in platelets that may favour thrombosis. These effects were observed after intake of both saturated and polyunsaturated fatty acids.

Adult↗

Influence of sex and dietary fats on platelet lipid biosynthesis in rat.

The platelet biosynthesis of total lipids, lipid fractions and fatty acids was determined by incorporation of [14C]acetate in normal and castrated rats of both sexes. Comparison was made between animals fed laboratory chow alone, and animals receiving, in addition, for 4 days by stomach tube a saturated (cream) or polyunsaturated (sunflower seed oil) fat. In male rats, the polyunsaturated fat increased slightly the total platelet lipid biosynthesis. The saturated fat drastically reduced it by 43% in comparison to the polyunsaturated fat-fed animals. Normal female rats did not exhibit a similar difference in the platelet lipid synthesis. However, the inhibitory effect of saturated fat on lipid synthesis could be observed in castrated females, although it was less pronounced (27% reduction) than in castrated or normal males (43%). Administration to castrated males of estradiol for 1 month almost completely inhibited the difference induced by the feeding of the different fats in the lipid platelet synthesis of male rats. This difference in the platelet lipid biosynthesis between male and female rats, normal and castrated, was observed mostly in the phospholipid (especially phosphatidylcholine), monoacylglycerol and triacylglycerol fractions and affected primarily the synthesis of the three main saturated fatty acids, 14:0, 16:0 and 18:0. Thus, it seems that, in rat, the short-term administration of a saturated fat induces drastic changes in the platelet lipid biosynthesis, but only in males. The protection observed in females appears to be essentially dependent upon estrogens.

Acetates↗

Potentiating effect of 5,8,11-eicosatrienoic acid on human platelet aggregation.

5,8,11-Eicosatrienoic acid (20:3 omega 9), a fatty acid increased in the platelet phospholipids of man and animals fed saturated fats, was either added to human platelets simultaneously with the aggregating agents, or incorporated into the platelet phospholipids by preincubation. 20:3 omega 9 markedly increased the response of platelets to all aggregating agents tested when added simultaneously with the agent, but solely to thrombin and ionophore, after incorporation into the platelet phospholipids. The potentiating effects of 20:3 omega 9 on thrombin aggregation do not appear to be related to prostaglandin formation, but rather to the production of a monohydroxy derivative through the lipoxygenase pathway.

8,11,14-Eicosatrienoic Acid↗

Protective effects of dietary calcium and magnesium on platelet function and atherosclerosis in rabbits fed saturated fat.

Male rabbits were fed for 6 months a purified diet rich in fat (45% of calories), mostly saturated (butter) containing per 100 g either 354 mg of calcium and 46 mg of magnesium (group I), 948 mg of calcium and 46 mg of magnesium (group II), or 354 mg of calcium and 356 mg of magnesium (group III). In group II, fed the additional calcium, significant (P less than 0.001) changes were observed; i.e. prolongation of clotting time (platelet clotting activity), decrease in platelet aggregation to thrombin, and in the concentration of the plasma total cholesterol, with a less significant (P less than 0.05) decrease in plasma triglycerides. A significant (P less than 0.01) decrease in the ratio monoemes/18:2 in the plasma cholesterol esters but not in the plasma or platelet phospholipids was also found in these rabbits. In relation to their lower activity, platelets from group II exhibited a significant increase in 22:4n-6 (phospholipids) and in the ratio cholesterol/phospholipids, both significantly correlated with the platelet function tests. In this same group, the excretion of fecal lipids and saturated fatty acid 18:0 was increased by 4.3-fold and 7.6-fold, respectively. The severity of atherosclerosis and the accumulation of cholesterol in the aorta were significantly lower in group II, while the plasma level of calcium was similar to that of group I. In group III, fed additional magnesium, results were similar to those of group II, but less significant.

Animals↗

Oral contraceptive and Platelet lipid biosynthesis in female rats: dose-response relationship.

Female rats were treated with different doses of an oral contraceptive (ethinyl estradiol + lynestrenol) and lipid biosynthesis was studied in blood platelets by acetate incorporation into different fractions separated by thin layer chromatography. A marked increase in lipid biosynthesis was observed, especially in the sterol fractions (cholesterol and lanosterol-dihydrolanosterol). It was dose-dependent, observed after a lag-phase, maximal in 3 days and normalized in 8 days. Thus, the oral contraceptive studied here appears to modify platelet lipid biosynthesis for the entire life of the platelets.

Acetates↗

Biosynthesis of platelet lipids in relation to aggregation in women using oral contraceptives.

The platelet lipid biosynthesis in relation to platelet aggregation and lipemia was studied by 14C-acetate and mevalonate incorporation into platelets of seventeen women without medication and of eighteen women using a low estrogen oral contraceptive. The lipid biosynthesis was significantly increased by 59% (mevalonate) and 38% (acetate) in women on oral contraceptives. From mevalonate, lipid synthesis was increased mostly in the lanosterol-dihydrolanosterol fraction (p less than .01). From acetate, lipid synthesis was significantly enhanced in all the lipid classes. In the oral contraceptive group, the response of platelets to thrombin aggregation was only slightly higher, but HDL-cholesterol was significantly lower. However, in the women using oral contraceptives, the percentage of abnormal values in HDL-cholesterol, thrombin-aggregation and acetate incorporation into lanosterol was similar. Thus, more than 40% of the women studied here, using low estrogen oral contraceptives, presented an increase in platelet lipid biosynthesis, especially in the lanosterol-dihydrolanosterol fraction, which was significantly correlated (p less than .05) with the response of their platelets to thrombin-induced aggregation.

Adult↗

Comparative beneficial effects on platelet functions and atherosclerosis of dietary linoleic and gamma-linolenic acids in the rabbit.

Male rabbits (10 weeks old) were fed, for 20 weeks, purified diets rich in fat (45% of calories) containing saturated fats (butter), polyunsaturated fats (evening primrose oil + butter or sunflower oil + butter) for 20 weeks. Linoleic acid represented respectively 3.6, 33 and 34% of the dietary fatty acids, while gamma-linolenic acid was present (4.4%) solely in the second group. A significant increase in di-homo-gamma-linolenic acid in plasma, platelets and aorta was noted only in the animals fed evening primrose oil. Despite this, the results of the platelet aggregation to thrombin and ADP, the recalcification plasma-clotting time (platelet-rich plasma) and the severity of atherosclerosis were not significantly different from those observed in the group fed sunflower oil. In contrast, in comparison to the butter-fed animals, the two groups fed the polyunsaturated fats showed remarkable improvements in the clotting time (P less than 0.01) and in the severity of atherosclerotic lesions (evening primrose oil P less than 0.001; sunflower oil P less than 0.05). However, the response to thrombin-induced aggregation was significantly decreased (P less than 0.05) only in the evening primrose oil-fed animals. In these long-term studies in young rabbits, dietary gamma-linolenic acid did not seem to have marked beneficial effects, additional to those induced by linoleic acid, on platelet functions or on atherosclerosis.

Adenosine Diphosphate↗

Platelet functions in relation to diet and serum lipids in British farmers.

Coagulation and platelet aggregation induced by thrombin, ADP, adrenaline, and collagen were studied in three contrasted groups, each of 20 to 22 middle-aged male farmers. Serum lipids were similar in the three groups. In the west of Scotland group, however, platelet reactivity was significantly greater than in the east of Scotland. This was associated with a dietary intake, evaluated by three different techniques, higher in saturated fat but also lower in polyunsaturated fat and alcohol. Platelet function in the southern England group also correlated with dietary fats and in addition inversely with calcium intake. On an individual basis in the 63 farmers, all the platelet function tests were significantly correlated with the intake of saturated fat regulated by that of calcium and alcohol. The dietary effects on platelets appear to be mediated by the fatty acid composition of plasma lipids and of platelet phospholipids. In that fraction, the fatty acids 20:3 omega 9, 22:3 omega 9 and 20:4 were the most closely related to the platelet function tests. the trienoic acid 20:3 omega 9, identified with essential fatty acid deficiency, was also correlated with the intake of saturated fat and calcium. In this study, platelet functions were more dependent upon the dietary factors associated with coronary heart disease such as saturated fats, calcium, and alcohol than upon serum lipids.

Blood Coagulation↗