2-3-dinor-6-ketoprostaglandin-f1alpha and Acute-Disease

Heavy binge drinking may trigger the onset of embolic stroke and acute myocardial infarction, but the underlying mechanisms are unclear. The effects of binge drinking on the hemostatic system and its circadian variation have not been investigated. We investigated the effects of an acute intake of a large dose of alcohol (1.5 g/kg).. Twelve healthy, nonsmoking men participated in sessions where they were served ethanol in fruit juice or served fruit juice alone and, lying in a supine position, were followed up for 12 to 24 hours. The treatments were randomized and separated from each other by a 1-week washout period. Blood and urine were collected for hemostatic measurements.. The urinary excretion of the platelet thromboxane A(2) metabolite 2, 3-dinor-thromboxane B(2) was significantly (P<0.05) greater during the night after an evening intake of alcohol than during the control night. A smaller increase was observed during the daytime after an intake of alcohol in the morning. The effects on the endothelial prostacyclin metabolite 2,3-dinor-6-ketoprostaglandin F(1alpha) excretion were negligible. A 7-fold increase in plasminogen activator inhibitor 1 activity was observed after both morning (P<0. 05) and evening (P<0.01) intakes of alcohol.. This is the first study to suggest that acute ingestion of a relatively large but tolerable dose of alcohol transiently enhances thromboxane-mediated platelet activation. The observations also demonstrate alcohol-induced changes in the normal circadian periodicity of the hemostatic system in subjects not accustomed to consumption of alcohol.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Alcoholic Intoxication; Biomarkers; Circadian Rhythm; Creatinine; Cross-Over Studies; Disease Susceptibility; Drug Administration Schedule; Ethanol; Fibrinolysis; Hemorheology; Hemostasis; Humans; Male; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Platelet Activation; Platelet Aggregation; Stroke; Supine Position; Thromboxane B2

The use of cyclooxygenase-2 (COX-2) inhibitors has been reported to be associated with detrimental vascular events. The aim of our study was to evaluate the role of COX-2 activity in the control of human vascular tone under inflammatory conditions.. Using organ bath experiments, the contraction induced by norepinephrine (NE), U46619, acetylcholine, and KCl was performed on isolated human internal mammary arteries (IMA) cultured in the presence or absence of both interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS) with or without endothelium. Under these conditions the COX (cyclooxygenase) isoforms were detected by immunohistochemistry and western blot, and the prostaglandins (PG) and thromboxane (Tx) released were measured using an enzyme immunoassay kit. A significant decrease in the maximal effect induced by NE but not by other stimuli was observed in the IL-1beta- and LPS-treated preparations after 6 and 24 h of culture (-19 +/- 6 and -25 +/- 4%, respectively), an effect that was endothelium independent. Under this inflammatory condition, the COX-2 inhibitors DFU (1 micromol/L), DuP-697 (0.5 micromol/L), and Etoricoxib (1 micromol/L) markedly restored and increased the vascular reactivity to NE. These alterations were not observed with SC-560 (1 micromol/L), a selective COX-1 inhibitor. In addition, the COX-1 isoform was always detected and the COX-2 isoform was only found in human IMA exposed for 6 or 24 h under inflammatory conditions. The COX-2 induction was accompanied by an increase in PGE(2) (prostaglandin E(2)) and PGI(2) (prostaglandin I(2)) release in the culture medium (approximately 2.5-fold) but not with an increase in TxA(2) (thromboxane A(2)) release.. These observations suggest that the inhibition of COX-2 directly potentiates the human vascular tone induced by NE under inflammatory conditions.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Aged; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Endothelium, Vascular; Female; Humans; Inflammation; Interleukin-1beta; Lipopolysaccharides; Male; Middle Aged; Norepinephrine; Organ Culture Techniques; Thromboxane B2; Vasoconstriction

Elevated levels of 11-dehydrothromboxane B2 (11-dehydro-TXB2) excreted in urine have been observed in acute ischemic stroke. This marker of platelet activation has not been investigated in patients with acute spontaneous intracerebral hemorrhage (ICH).. We examined 43 patients with spontaneous ICH and 23 controls. Urinary excretion rates of 11-dehydro-TXB2, 2,3-dinor-thromboxane B2 (2,3 dinor-TXB2) and 2,3-dinor-6-ketoprostaglandin F(1alpha) (2,3-dinor-PGF(1alpha)) during the first week and at 3 months after ICH were compared between patients who had or had not used aspirin and controls.. On admission, ICH patients without aspirin use had significantly higher urinary levels of 11-dehydro-TXB2 (p<0.001), 2,3-dinor-TXB2 (p<0.001) and 2,3-dinor-PGF(1alpha) (p=0.019) than controls. Aspirin users had significantly lower urinary levels of these metabolites than nonusers. The metabolite levels of aspirin users on admission did not significantly differ from those of controls. The differences between aspirin users and nonusers leveled off during the following 3-5 days, however, as the blocking effect of aspirin on the production of TXA2 and PGI2 ceased. Three months after ICH, the metabolite excretion levels in all the patients were similar to those in nonusers of aspirin on admission. On admission, aspirin users had longer bleeding times (p=0.032) than nonusers, but aspirin use did not associate with impaired recovery or hematoma enlargement.. Urinary excretion levels of 11-dehydro-TXB2, 2,3-dinor-TXB2 and 2,3-dinor-PGF1alpha were higher in patients with acute ICH than in controls. The levels in aspirin users were equally low as in controls but rose to the levels of the other patients within a few days. The metabolite levels remained high 3 months after ICH in all patients. Prior use of aspirin did not seem to cause hematoma enlargement.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Aged; Aspirin; Bleeding Time; Blood Coagulation; Cerebral Hemorrhage; Epoprostenol; Female; Humans; Male; Middle Aged; Prospective Studies; Regression Analysis; Thromboxane A2; Thromboxane B2

Systemic prostacyclin and thromboxane A2 production in rat experimental acute pancreatitis has been evaluated by measuring the urinary excretion of the 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2, respectively. Acute pancreatitis was induced by intraductal administration of 4.5% sodium taurocholate (0.1 ml/100 mg body weight) and intravenous cerulein perfusion (5 micrograms/kg/hr) for 6 hr, respectively. Urinary excretion of 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2 were much more important in sodium taurocholate- than in cerulein-induced acute pancreatitis. These data confirm an altered prostacyclin and thromboxane metabolism occurring in experimental acute pancreatitis. Phospholipase A2 activity and the effect of gabexate mesilate on the arachidonate metabolism were also evaluated.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Amylases; Animals; Ceruletide; Epoprostenol; Gabexate; Lipase; Male; Pancreatitis; Phospholipases A; Phospholipases A2; Rats; Rats, Sprague-Dawley; Taurocholic Acid; Thromboxane A2; Thromboxane B2