Different utilization of arachidonic and dihomogammalinolenic acids by human platelet prostaglandin synthetase.
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Biomedical subjects
Publications and source records attributed to M Dechavanne.
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Cyclic AMP first decreased in wahed platelets after the addition of 0.1 IU thrombin/ml and then increased progressively. Platelets pre-incubated with acetylsalicylic acid showed only a decrease of cyclic AMP upon addition of thrombin. Furthermore, two patients with defective prostaglandin synthesis had always reduced cyclic AMP whether their platelets were pre-incubated with acetylsalicylic acid or not. Thus, if prostaglandin synthesis is inhibited the level of cyclic AMP decreased and did not increase with time.
Platelets prostaglandin cyclic endoperoxides after collagen stimulation were measured in 7 patients with arterial thrombosis, 4 patients with recurrent deep venous thrombosis and 27 patients before undergoing total hip replacement. Patients with post-surgical D.V.T. synthetized more platelet cyclic-endoperoxides compared to those with no D.V.T. COULD BE DIVIDED INTO 2 SUBGROUPS : GROUP I with platelet cyclic endoperoxides and group II with higher cyclic-endoperoxides synthesis. Also, there was a higher ratio of platelet cyclic endoperoxides in patients with arterial thrombosis and in 2 patients with recurrent venous thrombosis and shortened platelet survival time. Thus, a greater synthesis of platelet prostaglandin cyclic, endoperoxides was formed in a number of patients with thrombosis.
The association of thrombocytopenia, macrothrombocytopathia, nephritis and deafness is rare. Reported here is a new case of this triple association. The clinical course, the nephropathologic findings and the bilateral neurologic hearing loss were similar to those already reported, with a slowly progressive impairment of renal function accompanied by a persistent proteinuria. The platelet diameters were increased. These macroplatelets contained granules of normal structure but with an irregular distribution in the cytoplasm. In other areas the cytoplasm was rich in surface connected system. The survival of these platelets and their contraction were normal. Their aggregation and excretion in response to collagen, adenosine diphosphate and thrombin, and the values of platelet factor 3 activity were all decreased. The degranulation defect, also present, was observed in the absence of a decrease in intracellular cyclic adenosine 5'-monophosphate (AMP) suggesting a relationship between these two findings.
In four patients, platelet aggregation with arachidonate was absent but was normal with "Labile Aggregation Stimulating Substance". ADP (10muM) aggregation was always reversible; collagen aggregation was absent and those induced by thrombin and ristocetin were normal. Collagen did not induce 14C-serotonin release but there was some release with thrombin. There was no thromboxan B2 synthesis in these platelets. Two patients showed hereditary hemostasis defect and the others acquired cyclo-oxygenase deficiency.
The intracellular level of cyclic AMP and PGE1 in platelets of 19 patients before and on the third day after surgery was measured. Among these 19 patients, 11 developed venous thrombosis in the legs early after surgery. We found no correlation between the occurrence of thrombosis and the initial level of cyclic AMP of PGE1. Nevertheless, after surgery the mean values of cyclic AMP or PGE1 in both the groups with or without thrombosis were significantly decreased. For PGE1 levels statistical analysis of variance showed a significant difference between the individual variations, pointing out an "individual factor".
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In a prospective randomised trial, three groups of 20 patients each were compared. A first group served as a control, a second group received dipyridamole and acetylsalicylic acid and a third group received low doses of heparin. The incidence of deep vein thrombosis determined by the 125I-fibrinogen test was 40% in the first group, 50% in the second group, and 5% in the third group. The differences between the heparin group and the two other groups are statistically significant. No wound complication and no haematoma at the injection site occurred.
A stereological model, which provides quantitative information on the morphology of the platelet release reaction as isolated from platelet aggregation, was developed for the human platelets separated from blood by Mustard's procedure. Three morphologically defined spaces (granules, surface-connected canalicular system S.C.S., cytoplasm) were used to characterize platelet degranulation (with the variation of the volume density of the granules) and contraction (with the variation of the volume density of both granules and S.C.S.). This model was applied to the evaluation of ultrastructural changes associated with the thrombin-induced release reaction. Degranulation and contraction were associated in the platelets which had been allowed to release for 1,5 and 150 sec. Under conditions of the study, prostaglandins E1 (10(-7) M) inhibited both degranulation and contraction (p less than 0,001). Aspirin (10(-4) M) only inhibited contraction (p less than 0.01) and dibutyryl-AMPc (10(-4)) only inhibited granulation (p less than 0,001).
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