Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The European and Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) is a randomised clinical trial in which patients with cerebral ischaemia of arterial origin will be randomised between oral anticoagulation (international normalized ratio (INR): 2.0-3.0), the combination of acetylsalicylic acid (in any dose between 30 and 325 mg per day) plus dipyridamole (400 mg daily) and acetylsalicylic acid only (in any dose between 30 and 325 mg per day). It is planned to enroll 4500 patients with a mean follow-up of three years. Primary outcome is the composite event of vascular death, stroke, myocardial infarction, or major bleeding complication; outcome assessment will be blinded. ESPRIT is an international, multicentre study in which 60-80 hospitals in the Netherlands and other countries in Europe and Australia will participate.
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PMID:[Prevention of vascular complications following cerebral ischemia of arterial origin; the ESPRIT trial: mild anticoagulant therapy, combination treatment with acetylsalicylic acid plus dipyridamole or treatment with acetylsalicylic acid alone?]. 956 33

Platelets have assumed a role in the development of focal cerebral ischemia by virtue of their participation in thromboemboli that may initiate stroke symptoms. Platelets are one component of the blood-vascular axis responsible for preventing hemorrhage. Activated platelets initiate hemostatic plug formation and provide a scaffolding for coagulation activation. Platelets are activated by a number of stimuli, such as exposure of the vascular subendothelium, fibrin deposition, and abnormal surfaces, e.g., atheromata. A number of observations, including the appearance of platelet thrombi on atheromata in situ, indicate that platelet physiology is relevant to stroke. In addition, certain antiplatelet agents (e.g., aspirin) significantly reduce the incidence of ischemic stroke after initial transient ischemic attacks. Aspirin, the combination of aspirin and dipyridamole, and ticlopidine have all been shown to be useful in reducing the frequency of secondary stroke events. Clopidogrel has been shown to reduce the frequency of secondary vascular ischemic events when stroke, myocardial infarction, and peripheral arterial disease are considered together. Unfortunately, all antithrombotic agents carry a potential risk for inducing symptomatic intracerebral hemorrhage during ischemic stroke. The mechanism by which this may happen with antiplatelet agents has not yet been determined. As in other areas of stroke treatment, it is the balance between efficacy in reduction of symptomatic thrombotic events and the risk for hemorrhage that will define benefit.
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PMID:The role of platelets in ischemic stroke. 974 24

Recent studies have shown that acute infections, especially of the respiratory tract, are an important risk factor for cerebral ischemia. Additionally we know that chronic dental infections may be a risk for myocardial infarction and artherosclerosis. However, the connection between stroke and dental infections has hardly been examined so far. Therefore we performed a case-control study using a standardized questionaire and examination. We investigated 66 patients consecutive to a acute cerebral ischemia/stroke and 60 age- and sex-matched nonstroke neurological patients as a control group. Dental status was determined by a so called total dental index (TDI) which reflects primarily caries, periodontitis, periapical lesions, devital and missing teeth as well as by a panoramic index (PI). Specifically, older patients with cerebrovascular ischemia tended to have a significantly worse dental status and had more severe periodontitis and periapical lesions than control subjects. A predefined poor dental status was associated with cerebrovascular ischemia independent from other vascular risk factors and social status. In conclusion, poor dental health, mainly resulting from chronic dental infections, may be associated with an increased risk for cerebrovascular ischemia. The results must now be verified in larger studies. As chronic dental infections are a common and also easily treatable factor, their identification as a risk factor for stroke would be quite important in the field of preventive medicine.
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PMID:[Odontogenic focus as the etiology of cerebral ischemia]. 988 Oct 1

Poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme that is activated by DNA strand breaks to participate in DNA repair. Excessive activation of PARP, however, can deplete tissue stores of nicotinamide adenine dinucleotide (NAD), the PARP substrate which, with the resultant depletion of ATP, leads to cell death. In many cases of CNS damage, for example vascular stroke, nitric oxide release is a key stimulus to DNA damage and PARP activation. In conditions as diverse as focal cerebral ischaemia, myocardial infarction and toxin-induced diabetes, PARP inhibitors and PARP gene deletion afford dramatic protection from tissue damage. Accordingly, PARP inhibitors could provide novel therapeutic approaches in a wide range of clinical disorders.
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PMID:Poly (ADP-ribose) polymerase, nitric oxide and cell death. 1032 3

The European and Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) is a randomised clinical trial in which patients with cerebral ischaemia of arterial origin will be randomised between oral anticoagulation (international normalized ratio (INR): 2.0-3.0), the combination of acetylsalicylic acid (in any dose between 30 and 325 mg per day) plus dipyridamole (400 mg daily) and acetylsalicylic acid only (in any dose between 30 and 325 mg per day). It is planned to enroll 4500 patients with a mean follow-up of three years. Primary outcome is the composite event of vascular death, stroke, myocardial infarction, or major bleeding complication; outcome assessment will be blinded. ESPRIT is an international, multi-center study in which 60-80 hospitals in the Netherlands and other countries in Europe and Australia will participate.
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PMID:[Secondary prevention after ischemic cerebral infarct. The ESPRIT Study: low dose anticoagulation, combined therapy with acetylsalicylic acid/dipyridamole or monotherapy with acetylsalicylic acid?]. 1035 2

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.
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PMID:[Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?]. 1036 Jan 91

Endothelial-derived nitric oxide (NO) is an important mediator of vascular function. Clinical studies indicate that HMG-CoA reductase inhibitors (statins) improve endothelial function and reduce the incidence of stroke and myocardial infarction. Treatment of human endothelial cells with statins increased the expression of endothelial NO synthase (eNOS) protein and mRNA expression. Statins increased eNOS mRNA half-life but did not change eNOS gene transcription. Inhibition of mevalonate synthesis by statins not only blocks the formation of cholesterol but also of isoprenoids. The upregulation of eNOS expression by statins was independent of cholesterol but mediated via the inhibition of the isoprenoid geranylgeraniol, whereas farnesiol had no effect on eNOS. Immunoblot analyses, (35S)-GTP gamma S-binding assays and transfection studies revealed that statins upregulate eNOS expression by blocking the geranylgeranylation of the GTPase Rho which is necessary for its membrane-associated activity. Studies with mice showed, that statin treatment upregulates eNOS expression and function independent of serum cholesterol levels. Prophylactic treatment with statins augmented cerebral blood flow and reduced cerebral infarcts in normocholesterolemic mice. These effects of statins were completely absent in eNOS-deficient mice indicating that enhanced eNOS activity by statins is the predominant mechanism by which these agents protect against cerebral injury. Our results suggest that statins provide a novel prophylactic treatment strategy for increasing blood flow and reducing brain injury during cerebral ischemia. Upregulation of eNOS by inhibiting Rho may provide a new pharmacologic target for the treatment of arteriosclerosis, pulmonary hypertension, and heart failure.
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PMID:[Regulation of endothelial NO production by Rho GTPase]. 1037 57

This review aims to summarise the value of long-term oral anticoagulant treatment in stroke prevention. Oral anticoagulation is the treatment of first choice in patients with atrial fibrillation (AF) and vascular risk factors and in AF patients with recent cerebral ischemia. The treatment also substantially reduces the risk of stroke in patients after myocardial infarction. The optimal target intensity of anticoagulation in stroke prevention is an International Normalized Ratio (INR) between 2.0 and 3.0. The treatment has been found to be hazardous at INR intensities between 3.0 and 4.5 in patients with transient ischemic attack (TIA) or minor stroke of presumed arterial origin. The value of the treatment in lower intensity in such patients still has to be established.
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PMID:Anticoagulant treatment in stroke prevention. 1052 51

BACKGROUND: We investigated the association of cigarette smoking with high-grade carotid artery stenosis in patients with ischemic stroke and transient ischemic attacks. METHODS: Prospectively collected data from 404 patients with focal brain ischemia were used for a cross-sectional study estimating the association between cigarette smoking and high-grade carotid artery stenosis (diagnosed by Doppler-ultrasound and defined as a luminal narrowing of > or = 70%). Cerebral ischemia patients with normal sonographic findings served as a comparison group. Multivariate logistic regression models were used for statistical tests to determine the association between smoking and high-grade carotid stenosis. Age, gender, hypertension, diabetes mellitus, hypercholesterolemia and co-existing heart disease (myocardial infarction, angina, heart failure) were considered potential confounders. RESULTS: High-grade carotid stenoses were found in 25% (n = 101) of the patients; 39% (n = 156) were classified as smokers. Smoking (odds ratio 3.6, 95% confidence interval [CI] 2.2 to 5.8), hypercholesterolemia (odds ratio 1.8; CI 1.1 to 2.8) and preexisting heart disease (odds ratio 1.7; CI 1.1 to 2.7) were significantly associated with carotid stenosis > or = 70%. The impact of smoking augmented with increasing degree of stenosis (odds ratio for stenoses > or = 80%: 4.3, CI 2.3 to 7.7), whereas the association with hypercholesterolemia, and co-existing heart disease decreased in strength for stenoses greater than 80%. Hypertension and diabetes mellitus were not found to be significantly with high-grade carotid artery stenoses. CONCLUSION: Smoking is an independent determinant of severe carotid artery stenosis in patients with focal cerebral ischemia.
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PMID:[In Process Citation] 1059 30

The ESPRIT trial addresses the problem that aspirin, the standard therapy for secondary prevention of vascular complications after a transient ischaemic attack (TIA) or ischaemic stroke of arterial origin, reduces the risk of serious vascular events by only about 13%. Anticoagulants may be an alternative, as these have proved highly efficacious in trials after myocardial infarction and after cerebral ischaemia with atrial fibrillation. After cerebral ischaemia of presumed arterial origin, high-intensity anticoagulation (INR 3.0-4.5) is not safe, but the value of anticoagulation with an INR between 2.0 and 3.0 is still unknown. Secondly, a recent, large trial showed that the combination of aspirin and dipyridamole prevents more major vascular events than aspirin alone, but several earlier trials did not find such an advantage. In ESPRIT, patients with a TIA or minor ischaemic stroke (Rankin grade </=3) will be randomized between oral anticoagulation (INR 2.0-3.0), the combination of dipyridamole (400 mg daily) plus aspirin (in any dose between 30 and 325 mg daily) and aspirin only. Primary outcome is the composite event 'death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction or major bleeding complication', whichever occurs first. Outcome assessment will be blinded. The recruitment of a total of 4,500 patients from more than 10 countries is planned; the mean follow-up will be 3 years.
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PMID:Design of ESPRIT: an international randomized trial for secondary prevention after non-disabling cerebral ischaemia of arterial origin. European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group. 1068 54


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