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)

Results of different studies conducted over the past 2 decades on the relationship between oral contraceptive (OC) use and venous thromboembolism, stroke, and myocardial infarct are summarized. The possibility that OCs would increase the risk of venous thrombosis was 1st raised by a case reported in 1961, and has been confirmed by at least 9 retrospective and 4 prospective studies in the UK, US, and Scandinavia. An increased risk of venous thrombosis has been confirmed only among women currently using OCs and possibly among those stopping use within 1-2 weeks. The risk is unrelated to duration of use, although few data are available on women using OCs continuously for more than 3 years. The proof of a relationship between risk of venous thrombosis and estrogen content is convincing, although an association with progestin content has also been suggested. Evidence is beginning to accumulate for an association between smoking and venous thrombosis in OC users and nonusers alike. British prospective studies have indicated a risk of death from venous thrombosis in OC users of 2-3/100,000 users/year during the 1970s, but modern low-dose formulations, better patient selection, and better surveillance have probably reduced the risk further. The evidence of a relationship between OC use and cerebral hemorrhage is only moderately convincing, with any increased risk unlikely to be more than 2-fold. The data regarding cerebral thrombosis are more consistent and convincing; they demonstrate a positive association of risk of cerebral thrombosis with both the estrogen and progestin content of OCs. Past as well as current users may be at increased risk, but data on the effect of duration of use are lacking. At least 9 retrospective and 2 prospective studies have established the significance of the risk of myocardial infarct in OC users. Risk of myocardial infarct may be related to both estrogen and progestin content, and appears to be limited to current users. Little evidence has been found of a relationship to duration of use. Strong evidence exists of a relationship between OC use and other risk factors for myocardial infarct, including smoking and hypertension. Very few deaths were observed from this cause in women under 35 in the 1970s. As with venous thrombosis, the mortality risks of stroke and myocardial infarct have probably declined appreciably in the past few years. OCs have been implicated in blood pressure elevations as well as a series of cardiovascular problems such as Budd-Chiari syndrome, occlusion of arteries in the intestines and extremities, and hemolytic uremic syndrome. The few available published studies suggest that administration of estrogens to peri- or postmenopausal women does not entail a cardiovascular risk.
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PMID:[Vascular disease and hormonal treatment--epidemiology]. 1228 Jan 97

The established indication for Tc99m apcitide scintigraphy is for detecting deep venous thrombosis. However, due to its mechanism of binding to GP IIb/IIIa receptors on activated platelets, it can be used to image acute cerebral thrombosis. I report a patient with an acute ischaemic stroke, with right leg swelling, referred for Tc99m apcitide scintigraphy to show of deep venous thrombosis. There was no abnormal uptake in the legs but there was in the left parieto-occipital region. This correlated with the clinical and CT data, indicating an acute ischaemic stroke in this area.
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PMID:Detection of acute cerebral ischaemia with Tc-99m apcitide scintigraphy. 1238 29

The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)
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PMID:[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs]. 1457 69

In this study, we investigated the association of G protein beta3 subunit gene (GNB 3) C825T polymorphism with ischaemic stroke and its subtypes in the Chinese Han population in a large case-control study. A total of 990 ischemic stroke patients and 1124 controls were recruited from six medical centres in China. Genotype was determined by polymerase chain reaction and restriction fragment length polymorphism (RFLP) assay. Logistic regression analysis was performed to identify the independent risk factors for stroke. The frequency of 825T carriers is significantly higher in cerebral thrombosis in male subjects (OR=1.35, 95% CI, 1.01-1.82, P=0.046). After further adjustment with traditional risk factors to stroke, the association is not significant. In conclusion, the GNB3 825T allele is not an independent risk factor to ischaemic stroke in the Chinese population.
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PMID:The 825C/T polymorphism of G-protein beta3 subunit gene and risk of ischaemic stroke. 1592 Apr 55

D-dimer measurement is commonly included in the diagnostic workup of patients with suspected acute symptomatic deep venous thrombosis and pulmonary embolism. As a haemostatic marker, it could be theoretically useful in other thromboembolic disorders, such as acute cerebrovascular events. In this review we summarize published literature on D-dimer testing in acute ischemic stroke and cerebral sinus and venous thrombosis (CSVT), discussing possible clinical diagnostic and therapeutical applications. In ischemic stroke, mounting evidence suggests a possible role of D-dimer in the acute diagnosis of ischemic stroke subtypes, especially in identifying tromboembolic and lacunar stroke. Its prognostic role still remains unclear, due to conflicting data. D-dimer could be also an useful screening test for excluding CSVT in patients presenting with acute headache, making the presence of cerebral thrombosis unlikely with low plasma levels. In this clinical setting sensitivity and negative predictive value are comparable to that reported in the diagnosis of acute thromboembolic disease. However, more studies are needed to confirm these recent findings as well as management studies to correctly introduce D-dimer measurement in clinical daily practice of ischemic stroke and CSVT.
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PMID:D-dimer testing in ischemic stroke and cerebral sinus and venous thrombosis. 1630 60

Ten cases of lacunar infarction, 10 cases of nonlacunar cerebral thrombosis, and 8 healthy controls who did not have risk factors of cerebrovascular diseases were studied. Subcortical cystic infarctions with a diameter of less than 1.5 cm were classified as lacunar infarction and the other cerebral thrombosis were classified as nonlacunar cerebral thrombosis. Cerebral blood flow examination by Xenon computed tomography (CT) method was performed within 14 days after the onset of stroke. Stable Xenon was inhaled for 3 minutes and CT scan was taken once before the inhalation, 3 times during the inhalation, and 5 times in the washout phase. Regional blood flows in the infarcted area, around the infarcted area, and in the cerebral cortex and the cerebral white matter where the influence of the infarction was considered to be little were measured before and after intravenous injection of 17 mg/kg acetazolamide. In the lacunar infarction, the blood flow in the cerebral cortex where the influence of the infarction was considered to be little was decreased and the cerebrovascular dilatory reserve capacity in the cerebral cortex and the cerebral white matter was decreased. Arteriolosclerosis is considered to be the basic cause of lacunar infarction.
J Stroke Cerebrovasc Dis
PMID:Regional cerebral blood flow in lacunar infarction. 1789 85

The aim of this study was to investigate the influence of delayed Rho-kinase inhibition with fasudil on second ischemic injury in a rat cerebral thrombosis model. Cerebral ischemia was induced in rats by injecting 150 mug of sodium laurate into the left internal carotid artery on day 1. In the ischemic group, the regional cerebral blood flow (rCBF) was significantly decreased 6.5 h after the injection. Fasudil (3 mg/kg/30 min i.v. infusion) significantly increased rCBF. The viscosity of whole blood was significantly increased 48 h after the injection of sodium laurate. Fasudil (10 mg/kg, i.p.) significantly decreased blood viscosity. To clarify the therapeutic time window of fasudil, rats received their first i.p. administration of fasudil (10 mg/kg) 6 h after an injection of sodium laurate. Administration of fasudil twice daily was continued until day 4. Fasudil prevented the accumulation of neutrophils within the brain as seen from measurements taken on day 3, and improved neuronal functions and reduced the infarction area as seen on day 5. Fasudil and hydroxyfasudil, an active metabolite of fasudil, concentration-dependently inhibited phosphorylation of myosin binding subunit of myosin phosphatase in neutrophils. The present results indicate that inhibition of Rho-kinase activation with fasudil is effective for the treatment of ischemic brain damage with a wide therapeutic time window by improving hemodynamic function and preventing the inflammatory responses. These results suggest that fasudil will be a novel and efficacious approach for the treatment of acute ischemic stroke.
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PMID:Wide therapeutic time window for Rho-kinase inhibition therapy in ischemic brain damage in a rat cerebral thrombosis model. 1818 27

It has been reported that the variants of the PDE4D (phosphodiesterase 4D) gene are associated with stroke, especially with the combination of cardio-embolic and carotid stroke in the Icelandic population, but it is still very controversial as to whether PDE4D is a susceptible gene for stroke in other populations. In the present study, we tested whether the PDE4D gene variation also confers stroke risk in a Chinese population. Our hypothesis was tested in a case-control study of a Chinese population comprising 639 stroke patients (including 253 with cerebral thrombosis, 171 with lacunar infarction and 215 with intracerebral haemorrhage) and 887 healthy controls. Three SNPs (single nucleotide polymorphisms) (rs966221, rs456009 and rs2910829) in PDE4D were chosen based on the significant association with stroke reported previously in a Western population, and these were genotyped using PCR/RFLP (restriction-fragment-length polymorphism) and confirmed by sequencing. We found that only SNP83 (rs966221) was associated with stroke. Allele C of rs966221 is a risk allele, conferring an increased risk for atherothrombotic strokes [OR (odds ratio), 1.51; 95% CI (confidence interval), 1.09-2.10] independent of conventional risk factors. Haplotype analysis confirmed that haplotype G-C-C was associated with increased risk for atherothrombotic stroke (OR, 1.80; 95% CI, 1.300-2.491). Our findings support that SNP83 of PDE4D is a genetic risk factor for atherothrombotic strokes in a Chinese population.
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PMID:Phosphodiesterase 4D gene polymorphism is associated with ischaemic and haemorrhagic stroke. 1869 98

Coagulation factor (F)XI was first described as a member of the contact pathway of coagulation. However, the 'classic' theory of the extrinsic and intrinsic pathway has been revised and FXI was found to be activated by thrombin and to play a role in sustained thrombin generation and fibrinolysis inhibition. Recent studies have pointed to a disproportionate role of FXI in thrombosis and hemostasis. The observations that human congenital FXI deficiency is generally accompanied by mild and injury-related bleeding, and that experimental, provoked bleeding in animals is unaffected by FXI deficiency or FXI inhibition, suggest that the FXI amplification pathway is less important for normal hemostasis in vivo. In contrast, elevated plasma levels of FXI may contribute to human thromboembolic disease and the antithrombotic efficacy of FXI inhibition has been demonstrated in numerous animal models of arterial, venous and cerebral thrombosis. Whether severe FXI deficiency in humans protects against thromboembolic events remains unclear, although some evidence exists that the occurrence of ischemic stroke or venous thrombosis is low in severely FXI-deficient patients. Because of its distinctive function in thrombosis and hemostasis, FXI is an attractive target for the treatment and prevention of thromboembolism. A novel strategy for FXI inhibition is the use of antisense technology which has been studied in various thrombosis and bleeding animal models. The results are promising and support the concept that targeting FXI might serve as a new, effective and potentially safer alternative for the treatment of thromboembolic disease in humans.
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PMID:Coagulation factor XI as a novel target for antithrombotic treatment. 2072 68

Rho kinase (ROCK), one of the serine/threonine kinases, is involved in pathologic conditions, and its activation causes neuronal cell death. Fasudil, a selective ROCK inhibitor, has been reported to cause increased cerebral blood flow (CBF) in the ischemic brain and protect against neuronal cell death by inhibiting ROCK. Ozagrel, a thromboxane A(2) synthase inhibitor, inhibits platelet aggregation and causes vasodilatation, thereby increasing CBF in cerebral thrombosis. The present study evaluates the combination therapy of fasudil and ozagrel on focal brain ischemia induced by middle cerebral artery occlusion (MCAO) in mice. Each monotherapy of fasudil at 10 mg/kg i.p. and ozagrel at 30 mg/kg i.p. significantly reduced cerebral infarction. The combination therapy of fasudil (3 mg/kg i.p.) and ozagrel (10 mg/kg i.p.), which are noneffective doses, resulted in reduction of cerebral infarction, and the protective effect was observed up to 5 min, but not 3 h, after reperfusion. Regional CBF after MCAO and phosphorylation of endothelial nitric-oxide synthase (NOS) significantly increased in response to the combination therapy, whereas these effects were not observed with monotherapy of either drug. The protective effect of combination treatment was antagonized by the treatment of a NOS inhibitor, nitro-l-arginine methyl ester hydrochloride. These findings indicate that the combination treatment of fasudil and ozagrel exhibits additive effects for neuroprotection after MCAO. These findings indicate that the combination treatment of fasudil and ozagrel may be useful as a potential therapeutic strategy for the treatment of stroke.
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PMID:Fasudil and ozagrel in combination show neuroprotective effects on cerebral infarction after murine middle cerebral artery occlusion. 2149 51


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