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Populations that consume a diet rich in marine lipids may have a lower risk of atherosclerotic disease. Fish oil contains the N-3 polyunsaturated fatty acid eicosapentaenoate, and the biosynthesis of thromboxanes and prostacyclins from eicosapentaenoate (thromboxane A3 and prostaglandin I3), rather than from the usual precursor arachidonate (thromboxane A2(More)
The capacity of platelets to generate thromboxane A2, reflected by measurement of serum thromboxane B2 (TxB2), greatly exceeds the systemic production of thromboxane in vivo. Thus, it is possible that substantial but incomplete inhibition of thromboxane formation ex vivo would still allow marked augmentation of thromboxane production in vivo. To address(More)
Although thromboxane A2 is a potent platelet agonist and vasoconstrictor in vitro, our knowledge of its pathophysiologic importance in human disease is limited. To facilitate the elucidation of its role in vivo, we sought to define a human syndrome in which pharmacologic interventions designed to inhibit the biosynthesis or biologic actions of thromboxane(More)
Thromboxane A2, the predominant cyclo-oxygenase product of arachidonic acid in platelets, is a potent vasoconstrictor and platelet agonist. Analysis of urinary metabolites by gas chromatography and mass spectrometry is a specific non-invasive method of measuring the biosynthesis of thromboxane that avoids the problem of platelet activation ex vivo.(More)
The pathogenesis of atherosclerosis, a major cause of age-related mortality, remains poorly understood. Although platelets and their products, including thromboxane A2, may be of importance in this process, little is known about eicosenoid biosynthesis and platelet function with increasing age. In order to address the hypothesis that platelet activation(More)
Although other mechanisms may be contributory, the antithrombotic properties of aspirin derive predominantly from its platelet-inhibitory effects. These are mediated via irreversible acetylation of platelet cyclo-oxygenase with subsequent blockade of platelet thromboxane synthesis. Long term administration of doses of aspirin as low as 20mg daily depresses(More)
Renal failure occurs in about 50% of cases of myeloma and may be a presenting feature of the disease. It is known to be a poor prognostic sign, with median survival of 13 months (MRC, 1984) or less (Cavo, 1986) compared to 30-36 months for myeloma as a whole (Editorial, 1988). In about half the patients renal failure is reversible following initial(More)
Selective inhibitors of thromboxane synthase have two theoretical advantages over inhibitors of the cyclooxygenase enzyme as potential antithrombotic compounds. First, they do not prevent formation of prostacyclin, a platelet-inhibitory, vasodilator compound, coincident with inhibiting thromboxane biosynthesis. Second, the prostaglandin endoperoxide(More)
A sensitive gas chromatography-mass spectrometric method was used to measure the generation in whole blood of leukotriene B4 (LTB4), a potent stimulator of neutrophil chemotaxis, in eight patients with chronic granulocytic leukaemia (CGL) and 12 healthy controls. LTB4 was detectable in unstimulated samples from all the patients (mean 194 (70 SEM) pg/ml),(More)