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Biomedical subjects

S Renaud

Publications and source records attributed to S Renaud.

At least 73 records · Page 4Linked to original sources
PubMed1991

Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study.

The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men (2,398) aged 49-66 years at the time of study. Platelet aggregation induced by collagen, thrombin, and ADP was measured in fasting blood samples and was related to prevalent angina, past myocardial infarction, and electrocardiographic evidence of ischemic heart disease. A number of subjects had taken aspirin, other nonsteroidal anti-inflammatory drugs, or other drugs affecting platelet aggregation 7 days before blood sample collection; after the exclusion of these subjects, data were available for 1,811 men. No relations were demonstrated with angina, but significant relations were shown between past myocardial infarctions and electrocardiographic evidence of ischemia and ADP-induced aggregation (both primary and secondary) and between electrocardiographic evidence of ischemia and thrombin-induced aggregation. The strongest relation indicated more than a twofold increase in the odds of a past myocardial infarction in subjects of the highest fifth of ADP-induced primary platelet aggregation compared with the lowest fifth. No significant relations were detected with collagen-induced aggregation. Accounting for a number of possible confounding factors had a relatively small impact on the relations between platelet aggregation and ischemic heart disease. Other evidence, including the well-established effect of aspirin on reducing the incidence of ischemic heart disease, indicates that the relations we describe are unlikely to be simply an effect of IHD on platelets.

Aged↗
PubMed1991

Effects of PP-56 and vitamin E on platelet hyperaggregability, fatty acid abnormalities, and clinical manifestations in streptozocin-induced diabetic rats.

The effects of vitamin E and D-myo-inositol 1,2,6-trisphosphate (PP-56) were investigated in long-term studies in streptozocin-induced diabetic rats fed a purified diet with 33% lipids and a polyunsaturated-to -saturated fatty acid ratio of 1. A supplement of vitamin E decreased plasma triglycerides, platelet lipid biosynthesis, some of the delta 6- and delta 5-desaturase abnormalities, and urine ketone bodies but did not affect the response of platelets to aggregation. PP-56 completely normalized the platelet reactivity to ADP and thrombin. This was accompanied by normalization of platelet lipid biosynthesis and diabetes-induced abnormalities in delta 6- and delta 5-desaturases. PP-56 treatment also reduced the mortality rate and to a certain extent urinary ketone bodies. The protective effect of PP-56 on platelet aggregation and mortality rate were dose related. PP-56, a molecule derived from phytic acid, seems to exert potent protective effects on some of the manifestations associated with diabetes in rats.

Adenosine Diphosphate↗
PubMed1990

The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: evidence from the Caerphilly Collaborative Heart Disease Study.

This epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet "function" as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemic heart disease in a general population of 49-66 year men at increased risk. Adenosine diphosphate (ADP) induced platelet aggregation in platelet rich plasma (PRP) at a constant platelet count and also the whole blood platelet count and red cell (RBC) count were strongly and independently related to ADP-induced platelet impedance changes. Both platelet count and platelet aggregation in PRP assessed by changes in optical density were directly related to increasing platelet "sensitivity" as measured by impedance changes in whole blood but RBC count was inversely related. Positive independent relationships between platelet impedance changes and plasma viscosity and fibrinogen were markedly attenuated when platelet count was taken into account, but this finding does not discount a role for these factors in platelet aggregation. No relationship was noted between white blood cell (WBC) count and platelet impedance changes; however, a significant inverse relationship was noted with platelet aggregation in PRP. These findings indicate that laboratory-based experimental findings can be observed in population based studies, and that these haematological factors may be important indicators of ischaemic disease in the population.

Adenosine Diphosphate↗
PubMed1990

Inhibition of coronary artery thrombosis by SIN-1, a donor of nitric oxide.

Molsidomine and its metabolite, SIN-1, a donor of nitric oxide, are potent coronary vasodilator and anti-ischemic agents. Recently, SIN-1 and nitric oxide have also been shown to inhibit platelet adhesion and aggregation in vitro. The present study in dogs was designed to evaluate the in vivo antithrombotic properties of SIN-1. Coronary intimal damage and stenosis are known to induce coronary cyclic flow variations that reflect platelet thrombus formation followed by disaggregation and embolization (Folts preparation). This model of coronary artery thrombosis appears to simulate the combination of some of the factors contributing to unstable angina and myocardial infarction in human. SIN-1 infusion (10 micrograms/kg/min) significantly reduced the frequency of cyclic flow variations: 4.9 +/- 6.2/h vs. 14 +/- 4.6/h (before treatment, p less than 0.03, n = 6). Results were similar to those obtained with aspirin (5 mg/kg, bolus i.v.: 1.5 +/- 0.6/h vs. 11.7 +/- 3/h, p less than 0.03, n = 5) whereas saline had no effect (17.8 +/- 2.2/h vs. 19.3 +/- 2.4/h, n = 5). As expected, blood pressure was decreased only in the SIN-1 group: 56.2 +/- 7.8 vs. 87.3 +/- 9.3 mm Hg (p less than 0.02) (mean arterial blood pressure). The present results suggest that the well-documented anti-ischemic properties of SIN-1 could be partly due to its antithrombotic activity, clearly demonstrated with the model of coronary thrombosis used here in the dog.

Animals↗
PubMed1989

Dietary lipids and their relation to ischaemic heart disease: from epidemiology to prevention.

From the Seven Countries Study and recent statistics from WHO and the OECD, it is clear that saturated fats, mainly dairy fats, are closely associated with the mortality rate from ischaemic heart disease (IHD). Consumption of alcohol, especially wine, but not polyunsaturated fats, seem to offer protection. Racial and other environmental factors do not seem to be confounding factors for that relationship as evaluated by studies in migrants, Japanese to USA, Southern Europeans to Australia, and in vegetarians in California. By contrast, very few trials using dietary polyunsaturated/saturated (P/S) ratios from 1.5-2.5 vs 0.4-0.7 have really prevented coronary death by diet modification. The only successful trial had a P/S ratio of 0.7. High P/S ratio increases platelet reactivity. Recent studies indicate that thrombosis and platelets play a more prominent role in IHD than expected. To decrease platelet activity and prevent IHD, a P/S ratio of 0.4-0.7 should be preferred.

Coronary Disease↗
PubMed1988

Platelets and aging. II--Plasma lipoproteins and fatty acid profiles.

Lipid composition of both plasma and platelets were investigated in sixteen old (78-94 years) and eight young (25-35 years) subjects. No age-related change was noted in plasma total and HDL cholesterol whereas a slightly increase of triglycerides was observed in the elderly population. Level of apo AI tended to decrease while apo AII decreased significantly in the elderly. These results led to a higher apo AI/apo AII ratio in elder subjects. However, no difference was detected in the level of apo B. In contrast, several modifications appeared in fatty acid composition of plasma lipids. Primarily, monounsaturated fatty acids content was increased while level of linoleic acid (and arachidonic acid in phospholipids) decreased in each class of plasma lipids of elderly subjects. In platelets from the elderly, we found an enhancement of monounsaturated fatty acids in phosphatidyl-inositol (PI), -ethanolamine (PE) and -choline (PC). The decrease of linoleic acid was detected in PC while the reduction of AA was noted in PE. These results indicate that modifications of fatty acid composition in both plasma and platelet lipids appeared with aging. They might be linked to the enhanced platelet activation in vivo observed in elderly people.

Adult↗
PubMed1987

Influence of vitamin E administration on platelet functions in hormonal contraceptive users.

Platelet functions (aggregation, clotting activity), platelet lipid biosynthesis, sterol composition and phospholipid fatty acids were studied in relation to plasma lipids and fatty acids as well as dietary habits at day 5 and 21 of the menstrual cycle in 30 women having used hormonal contraceptive for several years. The women were studied again on day 21 of the second cycle after they had taken for two months 200 mg vitamin E per day in addition to the contraceptive. At day 21 (after 3 weeks of hormonal contraceptive) as compared to day 5, there was a significant increase in the clotting activity of platelets and the response to ADP-induced aggregation concomitant with a decrease in plasma vitamin E. After vitamin E administration, platelet activity at day 21 was markedly decreased, being similar to the activity at day 5, with a significant increase in the level of vitamin E in plasma and platelets. The high response of platelets to aggregation in women using contraceptives does not seem to be associated with the intake of saturated fat but rather with that of 18:2. The aggregation to thrombin was mostly related to lanosterol biosynthesis and the aggregation to ADP to platelet cholesterol, but not to plasma lipids or apoproteins. The present pilot study suggests that the platelet hyperactivity of long-term hormonal contraceptive users might be dependent upon a low level of platelet alpha-tocopherol which can be rapidly overcome by giving a supplement of vitamin E.

Adult↗
PubMed1986

Nutrients, platelet function and composition in nine groups of French and British farmers.

In 260 male farmers (40-45 years) divided into 9 groups from different areas in France and Britain, coagulation, platelet aggregation, lipemia, fatty acids from plasma lipids and platelet phospholipids were determined in relation to the food intake evaluated by recall, weighing and chemical analysis of the diet. The clotting activity of platelets and their response to thrombin aggregation was significantly correlated on an individual basis with the intake of saturated fatty acids both in subsamples as well as in the whole study. Serum cholesterol was also significantly correlated with saturated fats but only on a group basis or on the totality of the study. Calcium, linolenic acid and alcohol in the diet were inversely related to certain platelet functions. Linoleic acid was inversely related to serum cholesterol and triglycerides. Dietary saturated fats were associated, with an increase in the platelet phospholipids not in saturated fatty acids but in 20:3 (n-9), known to promote platelet aggregation to thrombin, with a decrease in platelet cholesterol, also apparently regulating platelet functions. The present studies indicate that dietary saturated fats, calcium (hard water) and alcohol, influence platelet behaviour in a way strictly parallel to their known effect on coronary heart disease.

Adenosine Diphosphate↗
PubMed1986

Influence of long-term diet modification on platelet function and composition in Moselle farmers.

Platelet function and composition, lipemia, and dietary habits were evaluated yearly in 98 male farmers from Moselle (East of France) before and after decreasing, in half of them, dietary saturated fats from 16.2% to 9.9% of calories (P/S from 0.32 to 0.97). One year after these dietary changes, cholesterol and triglycerides decreased by approximately 10%, platelet aggregation to thrombin by 81%, and their clotting activity by 30%. However, ADP aggregation was enhanced by 54%. At 2 yr the P/S was decreased to 0.7 and diet also modified in controls, with 18:2 being increased mostly in one group (P/S = 0.81) and 18:3 in another (P/S = 0.59). In both groups, the main platelet function tests were significantly depressed 1 yr later. Considering the whole study, the intake of saturated fat was mostly correlated (group and individual) with platelet aggregation to thrombin, platelet clotting activity, and 20:3 (n-9) in plasma and platelet lipids.

Adenosine Diphosphate↗
PubMed1985

Effect of dietary (n--3) fatty acids on platelet function and lipid metabolism in rats.

Six groups of rats were fed diets containing 40% (by weight) lipids, mostly as saturated fatty acids (from 78 to 90%), with a basic amount of linoleic acid (18:2) (1.9%). In four groups, 5% of the saturated fats were substituted with an oil (vegetable: corn, rapeseed; or fish: cod liver, maxepa) and in one group 0.6% of the saturated fats was replaced by eicosapentaenoic acid ethyl ester. The diets supplied different amounts of 18:2 (1.9 to 10%), 18:3 (0.2 to 1.2%), 20:5 (n--3) (eicosapentaenoic acid) (0 to 1.3%) and 22:6(n--3) (0 to 1.6%). After 3-8 months on diets, platelet aggregation, plasma and platelet cholesterol, fatty acids and incorporation of [14C]acetate and [14C]arachidonate into platelet lipids were investigated. The three diets supplying eicosapentaenoic acid (1.3%) induced an approximately 80-fold increase in this fatty acid in plasma and platelet phospholipids, mainly at the expense of arachidonic acid. This was associated with an increase of the incorporation of arachidonic acid into platelet PE and PS. The incorporation of acetate in the (n--3) fatty-acid-fed animals was markedly increased into 22:5 and 22:6(n--3) at the expense of 22:4(n--6). Platelet aggregation induced by ADP was similar in the six groups. The response to thrombin was lower in animals fed corn and maxepa oils. Collagen aggregation tended to be lower in the fish-oil groups. Platelet aggregation to collagen was significantly negatively correlated to the level of eicosapentaenoic acid in platelet phospholipids, while the aggregation to thrombin was related to the level of 20:3(n--9). In the present study in rat, the (n--3) fatty acids added in small amounts to a saturated fat diet over a period of several months induced drastic changes in platelet lipid metabolism and composition without comparable effects on platelet behaviour.

Acetates↗
PubMed1985

Prostaglandin E2-like activity of 20:3n-9 platelet lipoxygenase end-product.

5,8,11-Icosatrienoic acid (20:3n-9), a fatty acid associated with platelet hyperactivity, was oxygenated by platelet lipoxygenase. The end-product of this pathway was purified by high-performance liquid chromatography (HPLC) and characterized as 12-hydroxy-5,8,10-icosatrienoic acid [12-OH-20:3(5,8,10)] by capillary gas-liquid mass spectrometry. When tested upon platelet aggregation, 12-OH-20:3(5,8,10) exhibited a biphasic effect. At low concentrations (below 5 X 10(-7) M) it potentiated aggregation but inhibited it at higher levels, a pattern similar to that obtained with prostaglandin E2. However, since the amounts of 12-OH-20:3(5,8,10) generated under thrombin stimulation are in the range of concentrations with potentiating effects, it seems that the 12-OH derivative is responsible for the hyperaggrebility of 20:3n-9-rich platelets.

8,11,14-Eicosatrienoic Acid↗
PubMed1985

Effect of smoking and dietary saturated fats on platelet functions in Scottish farmers.

Coagulation and platelet aggregation to thrombin and adrenaline, before and 10 min after smoking one high nicotine cigarette, were studied in 40 healthy male farmers (40 to 45 years) from the South-West and North-East of Scotland. These tests were conducted in association with detailed dietary studies. In the West group the intake of dairy fats, saturated fats and P/S ratio as well as most of the platelet function tests estimated were significantly higher than in the East group. Serum cholesterol (total and HDL) was similar in the two regions, while triglycerides were lower in the West. Smoking one cigarette considerably enhanced the platelet functions in both areas but the increases were more marked in the West group. The increase in the response of platelets to smoking was additive to that apparently induced by the intake of saturated fat in such a way the response of platelets to thrombin and epinephrine after smoking one cigarette in the West was approximately four times this obtained before smoking (or in a non-smoker) in the East. These additive effects of cigarette and saturated fat might be relevant to the reported higher incidence of coronary heart disease in the West of Scotland.

Adult↗
PubMed1984

Effects of dietary lipids on behaviour, lipid biosynthesis and lipid composition, in rat platelets.

Rats of either sex were fed for 18 and 34 weeks respectively diets containing 40% (by weight) lipids with polyunsaturated fatty acids representing 1.34% or 13.2% of total calories. Platelet reactivity to thrombin, platelet fatty acid composition and incorporation of [14C]acetate into platelet lipids were investigated. Diets rich in saturated fatty acids markedly increased platelet sensitivity to thrombin. The concentration of 20:3 and 22:3 of the (n - 9) series and of 20:3 and 22:5 of the (n - 6) series were increased at the expense of 18:2 and 22:4 of the (n - 6) family in platelet lipids. 20:4 (n - 6) was unchanged. The fatty acid changes were more pronounced in male rats and after 34 weeks. [14C]Acetate incorporation into total platelet lipids and particularly into choline phosphoglycerides and ceramides was lower in animals fed saturated fats. This diet reduced the synthesis of 16:0 and of 22:4(n - 6) in platelet total fatty acids, while that of 22:3(n - 9) was markedly enhanced. This study showed that long-term feeding of high-saturated-low-polyunsaturated fat diets in rats induced marked changes in platelet lipid synthesis and composition, in both sexes. The lipid synthesis modification appears to be more pronounced in males than in females. The changes in the fatty acids 20:3(n - 9), 22:3(n - 9) and 22:4(n - 6) appeared to be closely related to platelet behaviour. The balance between the content and synthesis of these last fatty acids might be of significance for the effect of diet on thrombogenesis.

Acetates↗