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Biomedical subjects

M Lagarde

Publications and source records attributed to M Lagarde.

At least 235 records · Page 13Linked to original sources
PubMed1984

Fatty acid composition in native and cultured human endothelial cells.

Endothelial cells from human umbilical veins were isolated by collagenase treatment. Cells were cultured in the presence of either 20% fetal bovine serum (FBS) or 20% human serum (HS). At confluency, endothelial cell lipids were labeled with tracer concentrations of tritiated arachidonic acid, then extracted and separated into lipid subclasses by thin layer chromatography. The fatty acid composition of each lipid class was determined by glass capillary gas-liquid chromatography analysis and compared to that of cells freshly isolated from the cord (NC cells). The fatty acid compositions differed only in phospholipids. Polyunsaturated fatty acids (PFAs), arachidonic, and linoleic acids were depleted in FBS cell phospholipids and replaced by both stearic and oleic acids. No significant difference could be observed between NC cell and HS cell phospholipids. We conclude that PFAs might be decreased in FBS cells because of the relative paucity of PFAs in FBS as compared to HS. It seems therefore more convenient to cultivate endothelial cells in the presence of HS, especially in respect to their phospholipid content of arachidonic acid, which is the physiological reservoir for prostacyclin synthesis.

Animals↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

Uptake and effect on arachidonic acid oxygenation of some icosaenoic acids in human platelets.

8,11,14-icosatrienoic (DHLA), 5,8,11,14,17-icosapentaenoic (EPA) acids (the monoenoic and trienoic prostaglandin precursors, respectively) and 5,8,11-icosatrienoic acid (20:3n-9) were pre-coated onto albumin and then incorporated into platelet lipids. Around 80% of the total incorporation concerned their acylation into phospholipids and a few percentage was oxygenated through the cyclooxygenase and/or lipoxygenase pathways, simulating therefore the in vivo situation. Such modified platelets normally oxygenated exogenous arachidonic acid (AA) while (only when enriched with DHLA or EPA) they produced less oxygenated derivatives of AA under thrombin stimulation. This indicates that endogenous AA liberation was decreased in both DHLA and EPA-rich platelets, which might be related to the formation of inhibitory prostaglandins from these polyunsaturated fatty acids.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1984

Effect of molsidomine, an anti-anginal drug, on arachidonic acid metabolism in human platelets.

Sin-1, an active metabolite of molsidomine which antagonizes platelet aggregation, was tested upon the oxygenation of arachidonic acid (AA) in these cells. While Sin-1 did not affect the formation of oxygenated derivatives of exogenous AA, it decreased markedly that of endogenous AA when platelets were triggered with thrombin or the calcium ionophore A23187. These results indicate that Sin-1 is an inhibitor of the liberation of AA from platelet phospholipids presumably by inhibiting phospholipase activity itself.

Antihypertensive Agents↗
PubMed1983

Stereospecific inhibition of PGH2-induced platelet aggregation by lipoxygenase products of icosaenoic acids.

Mono-hydroxylated fatty acids were prepared from the three prostaglandin precursors (20:3, 20:4 and 20:5) through the platelet 12-lipoxygenase or the soybean 15-lipoxygenase and were purified by HPLC. The inhibition of PGH2-induced human platelet aggregation by these hydroxy derivatives was compared. Other hydroxy derivatives of arachidonic acid of physiological importance were also tested in that respect. We have found that 12- or 15- hydroxy-icosaenoic acids are the most potent inhibitors. As compared to 12- or 15-hydroxy -20:4 (12- or 15-HETE), 5-HETE was about three fold less potent. We have also found that leukotriene B4 (5S, 12R-diHETE) is completely devoid of inhibitory activity while its isomer 5S, 12S-diHETE shares the activity of every mono-hydroxy-icosaenoic acids which are also S derivatives. We conclude that hydroxy derivatives of icosaenoic acids can inhibit PGH2-induced platelet aggregation by structural analogy and that they need a S configuration. These findings point out a possible negative feed back modulation of platelet aggregation by the lipoxygenase products of arachidonic acid and other icosaenoic acids which can arise in platelets subsequently to dietary manipulations.

Arachidonic Acids↗
PubMed1983

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↗
PubMed1983

Plasma lipoproteins and fatty acid composition after "minipill".

A study of the effect of a low-dose oral contraceptive, Adepal (ethinyl estradiol and levonorgestrel, 30 and 150 micrograms on the 5th to 12th, 40 and 200 micrograms on the 13th to 28th, respectively) on the blood lipids, lipoproteins and fatty acid composition has been conducted on 13 young women before and after six months of treatment. All together, total cholesterol concentration did not vary; however, the high cholesterol values decreased whereas the low cholesterol values increased with the pill. Triglyceride levels increased significantly (p less than 0.001). High density lipoprotein (HDL)-cholesterol decreased clearly (p less than 0.001) regardless of the cholesterol value at the beginning; low and very low density lipoprotein (LDL + VLDL)-cholesterol increased slightly, as well as the apoprotein B (Apo B) concentration (p less than 0.05). The lipoprotein electrophoresis showed intermediate bands (IDL) in 5/12 of the women after treatment. The three major classes of lipoprotein showed some variations in the fatty acid composition after the oral contraceptive; in any lipid class from any lipoprotein, the linoleic (18: 1 omega 6), arachidonic (20: 4 omega 6) and eicosapentaenoic (20: 5 omega 3) acids decreased whereas the palmitic (16: 0) and oleic (18: 1 omega 9) acids increased. Our results suggest that a low-dose contraceptive like Adepal produces, nevertheless, some significative modifications of plasma lipids and lipoproteins.

Adult↗
PubMed1982

Interactions between prostaglandin precursors during their oxygenation by human platelets.

The oxygenation through the prostaglandin synthase complex and the lipoxygenase pathways of the three prostaglandin precursors was investigated in human platelets. These precursors (dihomogammalinolenic (8,11,14-eicosatrienoic; 20:3 (8,11,14)), arachidonic (5,8,11,14-eicosatetraenoic; 20:4 (5,8,11,14)) and 5,8,11,14,17-eicosapentaenoic (20:5 (5,8,11,14,17)) acids) were used alone or simultaneously. We have found that 20:4 (5,8,11,14) increases the oxygenation of 20:3 (8,11,14) by the prostaglandin synthase complex while 20:5 (5,8,11,14,17) decreases the oxygenation of 20:4 (5,8,11,14) by the same enzyme complex. On the other hand, the utilization of 20:5 (5,8,11,14,17) by the prostaglandin synthase complex and the lipoxygenase was markedly enhanced in the presence of 20:3 (8,11,14), 20:4 (5,8,11,14) or both. Besides, the increased concentrations of 20:5 (5,8,11,14,17) failed to enhance its oxygenation to such an extent while the addition of 20:3 (8,11,14) or 20:4 (5,8,11,14) allows the marked potentiation of the 20:5 (5,8,11,14,17) oxygenation at any concentration. This indicates that, to be efficient, the utilization of 20:5 (5,8,11,14,17) by platelet oxygenases needs the presence of 20:3 (8,11,14), 20:4 (5,8,11,14) or their derivatives. In addition, using small concentrations of each prostaglandin precursor close to concentrations presumably released from platelet phospholipids during aggregation, all show the same tendencies. We conclude that the interactions we have observed between prostaglandin precursors during their oxygenation by human platelets could be of primary importance to explain the modifications of platelet reactivity reported after dietary manipulations.

8,11,14-Eicosatrienoic Acid↗
PubMed1982

The phospholipid and fatty acid composition of human platelet surface and intracellular membranes isolated by high voltage free flow electrophoresis.

Human platelets were labeled with tracer doses of [14C]arachidonic acid, then fractionated into mixed membranes which are separated into intracellular membranes and two different domains of surface membranes by high voltage free flow electrophoresis. Each subfraction was analyzed for its phospholipid content. Glycerophospholipids were separated by high performance liquid chromatography and their fatty acids analyzed by glass capillary gas chromatography. Intracellular membranes appeared substantially depleted in sphingomyelin, while enrichment of this phospholipid was seen in surface membranes. PC and PI were more enriched in intracellular membranes than in the surface membranes and the contrary was observed for PE. On the other hand, the pattern of the phospholipid labeling by [14C]arachidonate followed closely the glycerophospholipid profiles of the membrane subfractions, but the specific radioactivity of PI was higher than of PC, which itself was higher than that of PE. Moreover, the endogenous content of arachidonic acid accentuates these tendencies. The percentage of arachidonate in PE was higher in the surface membranes than in the intracellular membranes and the contrary was observed for arachidonyl-PC and PI. These differences were compensated for by certain saturated and monounsaturated fatty acids present in the composition profiles. These findings are discussed in relation to the membrane localization of lipases involved in the liberation of arachidonic acid for prostanoid synthesis.

Blood Platelets↗
PubMed1981

Chemoimmunotherapy with levamisole in acute lymphoblastic leukemia.

Patients with acute lymphoblastic leukemia (ALL) who were in two consecutive protocols and in complete remission (CR) with maintenance therapy, were randomized to receive or not receive levamisole. A total of 15 of 55 low-risk patients of protocol 10-LLA-72 with levamisole had relapses, compared with 25 of 54 not receiving levamisole; 67 and 49%, respectively, remain in CR at 48 months (P less than 0.025). In protocol 1-LLA-76, 14 of 91 low-risk patients on levamisole and 25 of 93 patients receiving levamisole had relapses; 78 and 61%, respectively, remain in CR at 36 months (P less than 0.05). Seventeen of 39 high-risk patients (children with a leukocyte count higher than 50,000 and adults) receiving levamisole had relapses compared with 37 of 61 not on levamisole. The DNCB skin test showed at 18 and 24 months a 74 and 85% positivity in the levamisole groups vs. a 38 and 35% positivity in the control group (P less than 0.025). We conclude that levamisole prolongs the duration of CR and survival in low-risk patients with ALL.

Adolescent↗