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Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stoke, or cardiovascular death in patients at high risk for cardiovascular events

"Among aspirin-treated patients at high risk of cardiovascular events, persistent thromboxane generation predicts the risk of the composite outcome of myocardial infarction, stroke, or cardiovascular death, independent of other cardiovascular risk factors."

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Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events.

"In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B2 levels identify patients who are relatively resistant to aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block in vivo thromboxane production or activity."

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Effects of smoking cessation and nicotine substitution on systemic eicosanoid production in man

"This study investigated the effects of smoking cessation with and without nicotine substitution on the excretion of major urinary metabolites of thromboxane A2 and prostacyclin; 11-dehydrothromboxane B2 and 2, 3-dinor-6ketoprostaglandin F1 alpha, respectively, as well as on the excretion of leukotriene E4 in man."

"The fact that eicosanoid production remains at pre-cessation levels in volunteers who quit smoking but use nicotine substitution may be involved in the risk of cardiovascular complications reported during nicotine replacement therapy."

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Urinary 11-dehydro-thromboxane B2 and coagulation activation markers measured within 24 h of human acute ischemic stroke

"The aim of this study was to determine the extent of change in platelet and coagulation markers in the acute phase of ischemic stroke and to assess the utility of marker mesurement in stroke subtype classification.  Urinary 11-dehydro-thromboxane B2 (11-deTXB2), a marker of in vivo platelet activation, and markers of coagulation activation, including prothrombin fragment 1 +2 (F1 + 2), thrombin-antithrombin complex (TAT) and fibrinogen, were measured in 25 patients with ischemic stoke within 24 h of onset symptoms. Eight patients taking aspirin at the time of the stroke had signficantly lower 11-dTXB2 values than patients not taking aspirin (964 vs. 4,314 pg/mg of creatinine P=0.0007).  Stroke patients not taking aspirin had significantly higher 11-dTXB2 concentration than age-matched controls (4,314 vs. 1,788 pg/mg of creatinine; P= 0.0006)."

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Correlation between the clinical effects of seratrodast and the level of 11-dehydrothromboxane B2 in urine/sputum in bronchial asthma patients

"An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2.  The compound has a bicyclic oxaneoxetane structure.  It is a potent inducer of platelet aggregation and causes vasoconstriction.  It is the principal component of rabbit aorta contracting substance ORCS)."

"These results suggest that bronchial asthma patients with high urinary 11-DHTXB2 levels could markedly respond to Seratrodast treatment. ”

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Diabetes mellitus, hypercholesterolemia, and hypertension but not vascular disease per se are associated with persistent platelet activation in vivo

"Previous studies relating increased thromboxane (TX) biosynthesis to cardiovascular risk factors do not answer the question whether platelet activation is merely a consequence of more prevalent atherosclerotic lesions or reflects the influence of metabolic and hemodynamic disturbances on platelet biochemistry and function."

"The occurrence of large-vessel peripheral arterial disease per se is not a trigger of platelet activation in vivo.  Rather, the rate of TXA2 biosynthesis appears to reflect the influence of coexisting disorders such as diabetes mellitus, hypercholesterolemia, and hypertension on platelet biochemistry and function.  Enhanced TXA2 biosynthesis may represent a common link between such diverse risk factors and the thrombotic complications of peripheral arterial disease."

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Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease

“The urinary excretion of 11-dehydro-TxB2 was significantly higher in patients with COPD than in control subjects. Moreover, 11-dehydro-TxB2 excretion was inversely related with arterial oxygen tension.”

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Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia

"Thromboxane A2 (TXA2) biosynthesis is enhanced in the majority of patients with type lla hypercholesterolemia.  Because simbastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) was previously shown to reduce platelet aggregation and TXB2 production ex vivo, we investigated TXA2 biosynthesis and platelet function in 24 patients with type ll hypercholesterolemia randomized to receive in a double-blind fashion simvastatin (20mg/d) or placebo for 3 months.  The urinary excretion of 11-dehydro-TXb2, largely a reflection of platelet TXA2 production in vivo, was measured by a previously validated radioimmunoassay technique.  Blood lipid levels and urinary 11-dehydo-TXB2 excretion were significantly (p<.001) reduced by simvastatin.  In contrast, placebo-treated patients did not show any statistically signficant changes in either blood lipids or 11-dehydro-TXB2 excretion."

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Risk factors for carotid atherosclerosis and platelet activation

"In the 24 patients in whom the plaque score was measured, multivariate analysis indicated a significant positive correlation between urinary excretion of 11-dehydrothromboxane B2 and plaque score, age, smoking and hypercholestermia.  Our results indicate the risk factors such as age, hypercholestermia, atherosclerosis and smoking activate platelets in vivo to develop carotid atherosclerosis."

"Multivariate analysis indicated a significant positive correlation between urinary excretion of 11-dehydrothromboxane B2 and plaque score, age, smoking and hypercholesteremia."

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Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking

“Cigarette smoking increased the urinary excretion of 11-dehydrothromboxane B2 (reflecting thromboxane A2 generation).”

“Cigarette smoking was also associated with higher levels of fibrinogen in plasma.”

“Cigarette smoking and transdermal nicotine treatment were both associated with a higher white blood cell count compared with the placebo patch.”

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