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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia/reperfusion (I/R), a phenomenon that is associated with conditions such as organ transplantation, trauma, vascular disease, and stroke, involves the recruitment of activated and adherent leukocytes that subsequently mediate tissue injury. Endothelial cell adhesion molecules such as P-selectin mediate I/R-induced leukocyte recruitment and allow the adherent leukocytes to damage the vascular wall and parenchymal cells. This study examines the influence of dypiridamole (persantine) on hemorrhagic shock (H/S)-induced P-selectin expression. H/S was induced in C57BL/6 mice by withdrawing blood to drop the mean arterial blood pressure to 30 to 35 mm Hg for 45 minutes. The mice were resuscitated by infusing the shed blood and Ringer's lactate (50% shed blood volume). In vivo P-selectin expression was determined using a dual monoclonal antibody technique in the heart, lung, liver, kidneys, stomach, small bowel, and colon of a control group, a hemorrhagic shock group, and a hemorrhagic shock group that was pretreated with Persantine (Boehringer, Ingelheim, Ingelheim, Germany). H/S significantly (P < 0.01) increased P-selectin expression in all regional vascular beds of untreated mice. Persantine treatment largely prevented the H/S-induced P-selectin expression in the same vascular beds. Persantine significantly attenuates the upregulation of P-selectin in the hemorrhagic shock model.
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PMID:Persantine attenuates hemorrhagic shock-induced P-selectin expression. 1114 78

Platelet activation seems to play a critical role in a number of vascular diseases, including stroke. The aim of our study was whole-blood flow cytometry evaluation of platelet activation markers: P-selectin (CD62), glycoprotein-53 (CD63) and platelet-derived microparticle in vivo in patients with acute cerebral infarction. We investigated 50 patients (29 men and 21 women, mean age 67.8) with acute cerebral infarction. Parameters of platelet activation were measured on the 1st, 3rd and 7th day after stroke onset. Comparisons were made with 20 control patients matched age. Compared to controls (1.6 +/- 0.7%) the stroke patients showed higher expression of CD62 on the 1st (2.6 +/- 1.4%), 3rd (3.5 +/- 2.3%) and 7th (3.0 +/- 2.0%) day after stroke onset. The differences were statistically significant on all days (p < 0.05). Compared to controls (1.5 +/- 0.6%) the stroke patients had also higher expression of CD63 on the 1st (1.9 +/- 0.6%), 3rd (2.0 +/- 0.6%) day and they showed higher level of platelet-derived microparticles on the 3rd (13.0 +/- 3.0%) day after stroke onset. The differences were statistically significant (p < 0.05). Elevated expression of CD62, CD63 and platelet-derived microparticles level indicate platelet activation during the acute phase of ischaemic stroke. Flow cytometry is a useful tool for in vivo assessment of platelet activation.
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PMID:[Blood platelet activation markers in patients with acute cerebral infarction during the earliest stage of the disease--evaluation using flow cytometry methods]. 1125 75

Platelet membrane glycoprotein polymorphisms are candidate risk factors for thrombosis, but epidemiological data are conflicting. Thus, demonstration of a genotype-dependent alteration in function is desirable to resolve these inconsistencies. We investigated in vivo platelet activation in acute thrombosis and related this to platelet genotype. Frequencies of the 1b and 2b alleles of the HPA 1a/1b and HPA 2a/2b platelet glycoprotein polymorphisms were determined in 150 (52 men/98 women, mean age 58.3 years) patients with atherothrombotic stroke, and the influence of genotype on markers of platelet activation was assessed. Platelet P-selectin (CD62P) expression and fibrinogen binding was measured using whole blood flow cytometry within 24 h of stroke and 3 months later in 77 patients who provided a repeat blood sample. Results were compared with matched controls. Neither the 1b allele [allele frequency 0.11 vs. 0.13, odds ratio (OR) confidence interval (CI) 0.8 (0.5-1.3)] nor the 2b allele [0.09 vs. 0.07, OR (CI) 1.4 (0.8-2.4)] was significantly over-represented in patients. Increased numbers of activated platelets were found following stroke (acute mean P-selectin expression 0.64% vs. control 0.35%, P < 0.001; acute mean fibrinogen binding 1.6% vs. control 0.9%, P < 0.001). Activation persisted in the convalescent phase (P < 0.001 and P = 0.005 vs. controls for P-selectin and fibrinogen respectively). Expression of P-selectin and fibrinogen was not influenced by either the HPA 1a/1b genotype (P > 0.95 for each marker, Scheffe's test) or the 2a/2b genotype (P > 0.95 for each). Although persisting platelet activation is seen in atherothrombotic stroke, it is independent of HPA 1a/1b and 2a/2b genotypes. These data suggest an underlying prothrombotic state, but do not support the polymorphisms studied as risk factors for thrombotic stroke in this population.
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PMID:In vivo platelet activation in atherothrombotic stroke is not determined by polymorphisms of human platelet glycoprotein IIIa or Ib. 1126 63

Cigarette smoking is accepted to be one of the major factors which increase the risk of coronary artery disease, peripheral vascular disease and stroke. A number of studies have been carried out on the acute and chronic effects of tobacco smoking on platelet activation. An enhancing effect of high nicotine cigarette smoking on platelet aggregation has been reported. Since platelet receptors are involved in the final stage of platelet aggregation, the intention of this study was to investigate platelet receptors in acute and chronic smokers before and after smoking. Nineteen chronic smokers, 18 acute smokers and 18 healthy non-smoking controls were included in the present study. Platelet aggregation was carried out using ristocetin, adenosine diphosphate (ADP) and collagen both before and after smoking in acute and chronic smokers. Flow cytometric studies of platelets were carried out utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen antibody in unstimulated and ADP-stimulated platelets, FITC-labelled anti-GP IIb/IIa antibody, FITC-labelled anti-GP Ib/IX antibody and FITC-labelled P-selectin antibody. The intensity of fluorescence was graded into three groups and expressed in arbitrary units. The interesting data generated in the present work is that in vivo platelet activation occurs immediately after smoking a cigarette which is detected by using FITC-labelled anti-human fibrinogen antibody binding to platelet and by P-selectin expression. It is also quite evident from the present study that a significant number of circulating platelets are in the activated state in chronic smokers. Therefore this study suggests that smoking-induced platelet activation may be an important contributory mechanism for acute coronary events in smokers.
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PMID:Changes in platelet glycoprotein receptors after smoking--a flow cytometric study. 1128 26

In vitro studies have suggested that losartan interacts with the thromboxane (TxA2)/ prostaglandin H2 (PGH2) receptor in human platelets, reducing TxA2-dependent platelet activation. The aim of this study was to evaluate the effect of different angiotensin II type 1 receptor antagonists in stroke-prone spontaneously hypertensive rats (SHRSP). The level of platelet activation was assessed by determining P-selectin expression in platelets by flow cytometry. The ex vivo adhesion of platelets was also analyzed. The number of platelets that expressed P-selectin in SPSHR was significantly increased (% P-selectin expression: WKY 4 +/- 0, 4%; SHRSP 15.5 +/- 0, 8% [n = 8], p < 0.05). In SHRSP receiving losartan (20 mg/kg body weight per day) the percentage of platelets expressing P-selectin fell to levels close to that observed in WKY. The number of platelets from SHRSP treated with valsartan and candesartan (20 mg/kg body weight per day for 14 days) that expressed P-selectin was not significantly different from those from untreated SPRHR. Only losartan treatment reduced ex vivo platelet adhesion to a synthetic surface. The antiplatelet effect of losartan does not appear to be related to the level of blood pressure reduction. In ex vivo experiments, losartan significantly reduced the binding of the radiolabeled TxA2 agonist U46619 to platelets obtained from SHRSP in a dose-dependent manner. Treatment with losartan reduced the number of activated platelets in SHRSP independently of its blood pressure effects. TxA2-receptor blockade is proposed as a mechanism by which losartan can prevent platelet activation.
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PMID:Inhibition of platelet activation in stroke-prone spontaneously hypertensive rats: comparison of losartan, candesartan, and valsartan. 1130 Jun 53

Multiple factors are involved in thrombus formation and require complex and highly therapeutic strategies. Platelet activation plays a critical role in the genesis of acute coronary syndromes involving not only platelets but also endothelial cells, leucocytes and erythrocytes. Angiotensin II (Ang II) is a vasoconstrictor that could participate in the thrombotic process. Platelets also express Ang II AT1 type receptors on their surface. Losartan is a non-peptidic inhibitor of AT1 receptors. It has been demonstrated that losartan reduced platelet aggregation induced by the thromboxane A2 (TXA2) analogue U46619. This effect was not observed with the losartan metabolite EXP 3174. The effect of losartan was assessed in binding studies in which losartan competitively inhibited the binding of [3H]U46619 to platelets in a dose-dependent manner. Irbesartan also inhibits the TXA2 receptor in platelets, an effect that was not obtained with the active form of candesartan, CV11974, and with valsartan. These results suggest that the structural requirements necessary to antagonize the TXA2/PGH2 platelet receptor may be different from those involved in AT1 receptor antagonism. The in vivo relevance of the in vitro findings has been confirmed by the fact that in vivo administration of losartan decreases P-selectin expression in platelets obtained from stroke-prone spontaneously hypertensive rats.
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PMID:Angiotensin II AT(1) receptor antagonists and platelet activation. 1136 20

Recently, clinical depression has been identified as an independent risk factor for increased mortality in patients following acute coronary events. Although the underlying mechanisms of this link remain uncertain, increased platelet activity has been suggested but never proven as the mechanism responsible for this association. Sertraline hydrochloride is a selective serotonin reuptake inhibitor (SSRI), and is an effective antidepressant agent. Its major liver metabolite, N-desmethylsertraline (NDMS), is known to be neurologically inactive. We assessed the in vitro effects of escalating concentrations of sertraline and NDMS on human platelets by aggregometry in plasma and whole blood, by expression of major surface receptors with flow cytometry in washed cells and in the whole blood, and quantitatively by various platelet function analysers in healthy volunteers and patients with coronary artery disease. Pretreatment of blood samples with sertraline and NDMS resulted in a dose-dependent inhibition of platelet-rich plasma aggregation induced by 5 microM ADP (P =, 0.002), by 10 microM ADP (P = 0.0017), by collagen (P = 0.008), and by thrombin (P = 0.026). Whole blood platelet aggregability was also significantly reduced when induced by 20 microM ADP (P = 0.006), and by collagen (P = 0.01). Surface expression of CD9 (P = 0.004), GP Ib (P = 0.0001), GP IIb/IIIa (P = 0.007), VLA-2 (P = 0.01), P-selectin (P = 0.02), and PECAM-1 (P = 0.01), but not the vitronectin receptor, was also reduced in sertraline and NDMS pretreated washed platelets. Whole blood flow cytometry revealed significant inhibition of GP IIb/IIIa (P = 0.008), and P-selectin expression (P = 0.0001) in NDMS treated samples. Closure time was delayed for the collagen-ADP cartridge (P = 0.009), and for the collagen-epinephrin cartridge (P = 0.01), indicating platelet inhibition in whole blood under high shear conditions. Rapid platelet-function assay revealed a decreased (P = 0.002) ability of platelets to agglutinate fibrinogen-coated beads, suggesting GP IIb/IIIa inhibition. Both sertraline, and its neurologically inactive metabolite NDMS, exhibited significant dose-dependent inhibition of human platelets. The documented anti-platelet effects of sertraline and NDMS may be directly related to the mortality benefits of SSRIs after ischemic events including myocardial infarction and stroke.
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PMID:Platelet inhibition by sertraline and N-desmethylsertraline: a possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. 1139 37

While the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke and myocardial infarction) are paradoxically thrombotic rather than haemorrhagic. To investigate abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial dysfunction (von Willebrand factor), platelet activation (soluble P-selectin) and thrombogenesis (plasminogen activator inhibitor and fibrin D-dimer) in stroke and the effects of concurrent hypertension, we studied 86 consecutive patients (58 male, 28 female) aged < 75 years (mean age +/- SD, 64.2 +/- 9.2 years) with acute stroke (ictus < 12 h). Baseline blood tests on admission were compared with 46 'hospital controls' (patients with uncomplicated essential hypertension; mean age +/- SD, 65.9 +/- 3.8 years) and 24 healthy normotensive controls (mean age +/- SD, 65 +/- 14.0 years). Further comparisons were made between stroke patients with hypertension (systolic blood pressure > 160 mmHg and/or diastolic > 90 mmHg) on admission and those without hypertension. Mean plasma viscosity (one-way analysis of variance, P = 0.026) and fibrinogen levels (P = 0.016) were significantly higher in stroke patients and hospital controls, when compared with healthy controls. The von Willebrand factor, plasminogen activator inhibitor soluble P-selectin and fibrin D-dimer levels were highest in the acute stroke patients, intermediate in hospital controls and lowest in healthy controls (all P < or = 0.001). There were no significant differences in measured indices of haemorheology, endothelial dysfunction and thrombogenesis between the three stroke pathological subtypes (ischaemic/thrombotic, haemorrhagic or transient ischaemic attack). There were also no significant differences in the measured parameters for stroke patients with or without systolic blood pressure > 160 mmHg or diastolic blood pressures > 90 mmHg using clinical (manual) readings or mean daytime or night-time ambulatory blood pressure monitoring recordings. There were no statistically significant differences between the measured parameters on admission and at 3 months follow-up in 26 patients (all P = not significant). Plasma viscosity was significantly correlated with mean daytime systolic blood pressure (r = 0.314, P = 0.021) and mean night-time systolic blood pressure (r = 0.309, P = 0.025). This study of hypertension and haemostasis in acute stroke has demonstrated clear abnormalities of haemorheology, endothelial dysfunction, platelet activation and thrombogenesis, which do not appear to be affected by the height of the blood pressure or the presence of hypertension. This is despite the known hypercoagulable state found in hypertension and the relationship of haemostatic abnormalities to vascular complications.
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PMID:Abnormal haemorheology, endothelial function and thrombogenesis in relation to hypertension in acute (ictus < 12 h) stroke patients: the West Birmingham Stroke Project. 1146 15

Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation. We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling. PARP-1 was also required for p65-mediated transcriptional activation. PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells. Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants. However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains. Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50. Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65. Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
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PMID:The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function. 1159 Jan 48

We determined the percentages of fibrinogen-bound and P-selectin-expressed platelets in whole blood using flow cytometry in 254 patients with various cerebral infarction subtypes, as well as in 30 age-matched controls. Patients with atherothrombotic stroke showed significant increases in both fibrinogen-bound and P-selectin-expressed platelets. Patients with lacunar stroke also showed significant increases in both of them, but the percentage of P-selectin expression was significantly lower than that in atherothrombotic stroke. Patients with cardioembolic stroke showed a significant increase in P-selectin-expressed platelets without any increase in fibrinogen-bound platelets. Platelet fibrinogen binding and P-selectin expression were significantly lower in patients treated with ticlopidine but not with aspirin than in those not treated with any antiplatelet agent, and were lowest in those treated with both ticlopidine and aspirin. Our findings suggest that expression of adhesion molecules on platelet membrane surface differs among the patients with subtypes of ischemic stroke and differs among the types of antiplatelet regimens.
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PMID:Measurement of platelet fibrinogen binding and p-selectin expression by flow cytometry in patients with cerebral infarction. 1167 62


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