Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma level of 11-dehydrothromboxane B2 (11-dehydroTXB2) is free from artifactual increase during blood sampling, and it can be reliable indicator of TXA2 production in vivo. We have estimated plasma 11-dehydroTXB2 in patients with ischemic stroke. Subjects studied were 29 patients with cerebral thrombosis (62 +/- 9 years old) and 41 healthy controls (61 +/- 7 years old). Plasma 11-dehydroTXB2 and TXB2 were determined by radioimmunoassay. Plasma 11-dehydroTXB2 levels in patients and controls were 5.4 +/- 2.5 and 1.8 +/- 0.9 pg ml, respectively, and the difference was significant (p less than 0.001). Plasma TXB2 also was higher in patients than in controls: 401 +/- 61 vs 311 +/- 51 pg/ml (p less than 0.05). However, the 11-dehydroTXB2 was found to be a more effective parameter to distinguish between stroke patients and controls. Estimation of plasma 11-dehydroTXB2 levels is a reliable method to detect platelet hyperfunction in stroke patients.
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PMID:Plasma 11-dehydrothromboxane B2: a reliable indicator of platelet hyperfunction in patients with ischemic stroke. 201 5

The effects of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) on tracheal secretion were compared in 6 anesthetized dogs. Using a double-balloon endotracheal catheter, 5 ml of saline was instilled into an isolated tracheal segment during HFOV and CMV for 10 min respectively. Two eicosanoids, 15-hydroxyeicosatetraenoic acid (15-HETE) and 11-dehydrothromboxane B2 (11-dehydro-TXB2) were measured by radioimmunoassay in each sample. HFOV (stroke volume: 6 ml/kg, f: 10 Hz, bias flow: 5 l/min) and CMV (stroke volume: 12 ml/kg, f: 15/min) were performed in random sequence and achieved comparable gas exchange. The concentration of 15-HETE in tracheal fluid during HFOV (87 +/- 67 pg/ml) was decreased to less than half of that during CMV (286 +/- 184 pg/ml, P less than 0.05), while there was no significant change of 11-dehydro-TXB2 either in tracheal fluid or in plasma. This reduction of 15-HETE was tended to be enhanced by vagotomy (HFOV: 42 +/- 14, CMV: 120 +/- 103 pg/ml) with the concentration ratio of CMV/HFOV remaining unchanged. HFOV may provide hitherto unrecognized advantage over CMV by reducing airway secretion of 15-HETE, a potent inflammatory mediator.
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PMID:Reduction of 15-hydroxyeicosatetraenoic acid (15-HETE) in tracheal fluid by high frequency oscillatory ventilation. 240 21

Moderate regular alcohol intake has been found to be associated with a decreased risk for coronary heart disease and stroke. We investigated the effects of acute intake of red wine (60 g ethanol) and a standard dinner under controlled conditions on haemostatic factors. Shear-induced platelet aggregation (SIPA) decreased after the intake of alcohol irrespective of whether the subjects were fasting or not, and also after the intake of food. The intake of alcohol inhibited the postprandial increase of von Willebrand factor multimers. Plasma levels of plasminogen activator inhibitor 1 activity (PAI-1) and serum triglycerides were increased by alcohol. Excretion of the platelet thromboxane A(2) metabolites 11-dehydrothromboxane B(2) and 2,3-dinorthromboxane B(2), as well as the endothelial prostacyclin metabolite 2, 3-dinor-6-ketoprostaglandin F(1)alpha, into urine was not influenced by either alcohol or food. We conclude that eating a dinner together with red wine has no untoward effect on SIPA and that the decrease of SIPA is not specific for alcohol.
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PMID:Effects of alcohol and the evening meal on shear-induced platelet aggregation and urinary excretion of prostanoids. 1109 67

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 measurement in stroke subtype classification. Urinary 11-dehydro-thromboxane B(2) (11-dTXB2), 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 stroke within 24 h of onset of symptoms. Marker levels in patients with ischemic stroke were compared with those in 19 age-matched controls who had not taken aspirin for at least 2 weeks before sampling and 25 healthy controls. Median marker levels were significantly increased in stroke over those in age-matched controls for fibrinogen (344 vs. 289 mg/dl; P=0.030), F1+2 (1.40 vs. 0.80 nmol/l; P=0.003), and TAT (6.65 vs. 2.20 microg/l; P<0.0001). Median marker levels for seven patients with cardioembolic stroke and 18 with non-cardioembolic stroke were not significantly different for any marker test. Eight patients taking aspirin at the time of the stroke had significantly lower 11-dTXB2 values than patients not taking aspirin (964 vs. 4,314 pg/mg of creatinine; P=0.007). 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=0.006). Coagulation and platelet activation markers are increased in the acute phase of stroke regardless of the clinical mechanism. This finding suggests that the markers may not be useful for predicting clinical subtype of ischemic stroke in the acute phase.
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PMID:Urinary 11-dehydro-thromboxane B(2) and coagulation activation markers measured within 24 h of human acute ischemic stroke. 1168 46

From previous studies, the prevalence of aspirin nonresponders is 5.5-45% in patients with various cardiovascular diseases. Those who have aspirin nonresponders have a greater risk of clinically cardiovascular events. The purpose of the study was to look for the prevalence, associated factors and the outcomes of aspirin nonresponders among patients with ischaemic stroke. Patients with ischaemic stroke who were treated during January 2011-August 2011 were included. Urine 11-dehydro-thromboxane B2 (dTXB2) was measured to determine the response to aspirin in patients. The demographics and vascular risk factors were compared between patients who were classified as aspirin responders or aspirin nonresponders. The outcomes of the study were favourable outcome, cardiovascular events and mortality. There were 182 patients included during the study period: 128 patients with an acute ischaemic stroke and 54 patients with a stable ischaemic stroke. Ninety patients (49.5%) were found to be aspirin nonresponders. Multivariate analysis revealed that stroke presentation (acute stroke) was the only factor associated with aspirin nonresponders [odds ratio (OR) 2.38, 95% confidence interval (CI) 1.193-4.746, P = 0.014]. With a mean follow-up time of 16 months, aspirin nonresponders had a less favourable outcome (54 vs. 83%, OR 0.24; 95% CI 0.11-0.51, P < 0.001), marginally higher cardiovascular events (11 vs. 2%, OR 4.48; 95% CI 0.92-21.37, P = 0.045) and higher mortality (12 vs. 1%, OR 10.52; 95% CI 1.3-85.28, P = 0.007). The prevalence of aspirin nonresponders was rather high in Thai patients with ischaemic stroke. Aspirin nonresponders had a less favourable outcome, higher cardiovascular events and death rate.
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PMID:Aspirin nonresponders in patients with ischaemic stroke. 2342 55

Eicosanoids may play a role in ischemic stroke. However, the associations of variants in cyclooxygenase (COX) pathway genes and interaction among these variants with carotid plaque vulnerability are not fully understood. In present study, twelve variants in COX pathway genes were examined using matrix-assisted laser desorption ionization time-of-flight mass spectrometry method in 396 patients with ischemic stroke and 291 controls. Platelet aggregation, platelet-leukocyte aggregates, and urine 11-dehydrothromboxane B2 (11-dTxB2) were also measured. According to the results of carotid high-resolution B-mode ultrasound, the patients were stratified into the following groups [i.e., non-carotid plaque and carotid plaque. The carotid plaque was further classified into subgroups of echolucent plaque (ELP) and echogenic plaque (EGP)]. Additionally, gene-gene interactions were analyzed to assess whether there was any interactive role for assessed variants in affecting carotid plaque vulnerability, platelet activation and 11-dTxB2 levels. There were no significant differences in the frequencies of genotypes of the twelve variants between patients and controls. Among 396 patients, 294 cases (74.2%) had carotid plaques (106 had ELP, 188 had EGP). Frequency of PTGS2 rs20417CC, TXAS1 rs2267679TT, TXAS1 rs41708TT, PTGIS rs5602CC, and TXA2R rs1131882TT genotype was significantly higher in patients with plaque compared with patients without plaque, or in patients with ELP compared with patients with EGP. 11-dTxB2 levels, platelet aggregation and platelet-leukocyte aggregates were significantly higher in patients with ELP compared with patients without plaque or with EGP. Multivariate logistic regression analysis revealed that PTGS2 rs20417CC, TXA2R rs1131882TT, and high-risk interaction among variants in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were independently associated with the risk of ELP after adjusting for confounding variables. The variants in COX pathway genes and the high-risk interactions among variants in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were associated with high 11-dTxB2 and platelet activation, and independently associated with the risk of carotid plaque vulnerability. These variants might be potential markers for plaque instability.
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PMID:Genetic variants of PTGS2, TXA2R and TXAS1 are associated with carotid plaque vulnerability, platelet activation and TXA2 levels in ischemic stroke patients. 2870 3

Since increased cholesterol levels are crucial in determining the development of atheroma, their reduction represents a mainstay in primary and secondary cardiovascular prevention. The most recent spectacular advancement in cholesterol-lowering therapy is represented by proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors. Although their benefit over currently available treatments has been ascribed primarily to their strong low-density lipoprotein (LDL)-cholesterol reducing action, several clues suggest that PCSK9 inhibitors may also influence platelet function and blood coagulation. PCSK9 knockout mice develop less venous and arterial thrombosis and show reduced in vivo platelet activation upon arterial injury. In patients with acute coronary syndromes (ACSs) treated with P2Y12 inhibitors, a direct association between PCSK9 serum levels and residual platelet reactivity was found. A direct correlation between urinary excretion of 11-dehydro-thromboxane-B2, a marker of in vivo platelet activation, and circulating PCSK9 levels was reported in patients with atrial fibrillation. Moreover, recombinant human PCSK9 added in vitro to human platelets potentiated activation induced by weak agonists. Finally, blood clotting factor VIII (FVIII), which is associated with stroke and ACS risk, is cleared from the circulation by members of the LDL receptor (LDLR) family. Given that PCSK9 degrades LDLR, it is conceivable that PCSK9 inhibitors by enhancing the expression of LDLR may slightly decrease circulating FVIII, in this way contributing to the prevention of cardiovascular events. This review aims to discuss the possible and hypothetical interactions between PCSK9 and the haemostatic system and to examine the possible pleiotropic effects of PCSK9 inhibitors in cardiovascular prevention.
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PMID:PCSK9 in Haemostasis and Thrombosis: Possible Pleiotropic Effects of PCSK9 Inhibitors in Cardiovascular Prevention. 3060 18