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

Platelet-dependent thrombosis and subsequent embolization are major causes of cerebral ischaemia. Beside aspirin which irreversibly blocks platelet cyclo-oxygenase, several other substances interfere in different platelet metabolic pathways and block platelet adhesion and aggregation. We found in an experimental model using non-human primates that a specific peptide inhibitor blocking GP IIb/IIIa platelet receptor which binds fibrinogen completely, prevents the retention of embolized platelet aggregates in the cerebral circulation. As thrombin may play a key role for platelet activation in vivo leech-derived hirudin, a direct thrombin inhibitor as well as activated protein C which limits thrombin production and also prevents platelet dependent thrombus formation very effective. We demonstrated in the same non-human primate model of platelet embolization that the amount of retention of platelet emboli in the vascular bed depends on the nature of the vasculature. For example, platelet emboli were cleared very quickly from brain microcirculation, whereas platelet embolization into the lower limb via the femoral artery caused a significantly longer retention of the embolized material. Such specific mechanisms may be caused by different levels of local vasodilators as PGI2 or EDRF.
 ...
PMID:Platelet thromboembolism. 801 31

Protein C and protein S deficiencies increase the risk of venous thrombosis and pulmonary embolism, but their role in arterial thrombosis or embolism is controversial. We describe cerebral ischemia in two young women in a family with inherited deficiencies of both proteins C and S and provide evidence that a combined deficiency of proteins C and S may be a high risk factor for ischemic stroke in young adults.
 ...
PMID:Deficiency of both protein C and protein S in a family with ischemic strokes in young adults. 803 22

This study was designed to evaluate the clinical value of consecutive measurements of the levels of the anticoagulation factors protein C. protein S and antithrombin III in the plasma of patients with subarachnoid haemorrhage (SAH). Sequential samples of plasma were obtained from 34 patients at days 0 to 3, 5, 8, 14, and 20 days after SAH. Their levels of protein C, protein S and antithrombin III were measured by specific immuno-assays, and the symptomatic vasospasm and clinical states of the patients were monitored. Based on the retrospective comparisons between the measured levels of the three factors and the levels in pooled plasma from normal volunteers, the time course of changes in the levels allowed the classification of the patients into five groups as follows: A, the levels of the three factors decreased suddenly at 5 days after SAH, then increased again (n = 6); B, the three factors increased continuously (n = 13); C, the three factors remained below the normal range (n = 3); D, the three factors remained within the normal range (n = 6); and E, the three factors decreased continuously (n = 6). In group A patients, temporary deficiencies in the three factors occurred that coincided with the occurrence of delayed neurological deficit (DND). Twelve patients (92%) in group B had a favourable outcome (good and moderate disability) without DND. The patients in group C had low levels of anticoagulation factors and mild DND followed by a favourable outcome. Five patients (83%) in group D had a favourable outcome. In group E, five patients (83%) had a poor outcome (severe disability and death) due to DND. When clinical outcomes were compared by patient group, the patients in group E had significantly more unfavourable outcomes than did the other groups (P < 0.01). Although the mechanism responsible for the decrease in anticoagulation factor levels remained unclear, the results suggested that the decrease in anticoagulation factors may indicate hypercoagulability and cerebral ischaemia after SAH.
 ...
PMID:Plasma levels of protein C, protein S, and antithrombin III in patients with subarachnoid haemorrhage. 908 71

We analysed the results of coagulation studies in an unselected series of young adults with acute cerebral ischaemia. Our aims were (a) to determine the prevalence of coagulation disorders among these patients, (b) to investigate the relation between the presence of coagulation abnormalities and large vessel disease or potential sources of cardiac embolism and (c) to evaluate the occurrence of thrombotic events in patients with or without coagulation disorders. One hundred and twenty consecutively admitted patients (53 men, 67 women, median age 38 years, range 15-45) who presented with acute cerebral infarction (n = 89) or a transient ischaemic attack (n = 31) were evaluated. Diagnostic studies consisted of electrocardiography, echocardiography, duplex scanning, and/or angiography. Coagulation studies included activity tests of protein S, protein C, antithrombin, plasminogen, measurement of immunoglobulin G (IgG) anticardiolipin antibodies (ACLA), and a dilute prothrombin assay. Initially, 30 patients had increased ACLA titres and 28 had an abnormal dilute prothrombin assay, suggesting lupus anticoagulant. Decreased protein S, protein C and antithrombin activity were detected in 20, 3 and 3 patients, respectively, excluding patients in whom the abnormalities could be explained by the use of medication, by pregnancy or puerperium. We detected a decreased activity of plasminogen in 5 patients. The disorders could be confirmed by a second assessment in only 2 patients with a protein S deficiency, in none of the patients with a protein C or antithrombin deficiency and in 1 patient with plasminogen deficiency. However, the abnormalities persisted in 19 of 21 patients with increased anticardiolipin IgG titres and in 9 of 20 patients with lupus anticoagulant. A confirmed coagulation disorder was not associated with stroke type or vascular risk factors, but it was more common among patients with large vessel disease (odds ratio: 3.8, 95% confidence interval (CI): 1.1-12.8). Sixteen patients had a recurrent thromboembolic event, but the risk of recurrence was not increased among patients with a confirmed coagulation disorder. Our results suggest that idiopathic coagulation disorders are found in about a quarter of young stroke patients. They are difficult to predict and probably interact with other risk factors.
 ...
PMID:Coagulation disorders in young adults with acute cerebral ischaemia. 945 24

Cerebral ischaemia in young adults is a well-recognised disease, and approximately half of the cases remain aetiologically unclear despite extensive investigations. Thrombophilias are known to cause a subset of ischaemic strokes in this population. The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population. Carriers of this gene mutation have a sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate whether the FVL mutation constitutes a risk factor for juvenile cerebral ischaemias. A total of 225 patients aged < or = 45 years at onset of cerebral ischaemia and 200 age-matched healthy controls were investigated. The overall frequency of heterozygosity for the FVL mutation did not differ significantly between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence interval (CI) 0.7-3.1]. In the subgroup of patients with cryptogenic cerebral ischaemia (n = 94), however, a significantly higher frequency of this gene defect (15.9%) was found compared with the controls (OR 3.0, CI 1.3-6.6). Further trends towards higher frequencies of the FVL mutation were found in patients with patent foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9, all not significant). In conclusion, the FVL mutation is not a risk factor for cerebral ischaemia of the young. However, our results suggest that this gene mutation plays an aetiological role in the subgroup of patients suffering from 'cryptogenic' ischaemic events.
 ...
PMID:Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients. 977 64

A possible association between anticardiolipin antibodies (ACA), which are a marker for increased risk of cerebral ischemia, and deficiency of free Protein S, a naturally occurring anticoagulant, has been suspected in some studies of ischemic stroke, particularly in young adults. In order to investigate this further, we prospectively studied all stroke patients </= 65 years of age admitted to our stroke unit during 1991-1992. A total of 66 patients with acute ischemic stroke or transient ischemic attacks (TIA) (embolic/thrombotic infarction n = 30, embolic infarction n = 13, thrombotic infarction n = 10, and TIA n = 13) were analysed for ACA, protein C and S, free protein S and antithrombin III (AT III). Traditional risk factors were scrutinized in each patient. Eight patients had some previously undetected derangement of the coagulation process; five had elevated ACA levels, four had low, free Protein S levels, and three had low AT III levels. None of the patients showed any decrease in total protein C or S levels. A striking association between the presence of ACA and free protein S deficiency was noted. All patients with free protein S deficiency had concomitant elevated ACA levels. Sixteen patients had had a previous episode of ischemic stroke/TIA or mycocardial infarction, two of them had lowered AT III levels. Thirty-four patients had one or more elevated infectious parameters but with no clear correlation to derangement of the coagulation factors. We conclude that a probable association between ACA and free protein S deficiency exist in ischemic stroke patients, and that it may have a pathogenetic importance. Copyright 1998 Lippincott Williams & Wilkins
 ...
PMID:Association between deficiency of free protein S and anticardiolipin antibodies in patients </= 65 years of age with acute ischemic stroke and TIA. 1021 Aug 79

A diagnosis of moyamoya disease was made in three children aged five, eight and 13 years (including two Turkish sisters). Clinical presentation was recurrent episodes of cerebral ischemia and stroke. CT scans and MRI showed infarcts in various distributions. Angiography revealed anterior bilateral stenosis of the circle of Willis and development of Moyamoya collateral pathways. In one case there was coagulopathy with protein C deficiency. To increase transdural collateral flow, revascularisation with encephalo-duro-arterio-synangiosis was attempted in all three children. Outcome was clinically and angiographically satisfactory and none of the children developed further neurological complications. The current state of study on Moyamoya disease is also presented.
 ...
PMID:[Moyamoya disease: advantage of early diagnosis and survival treatment. Review of three cases]. 1058 42

Inflammatory reactions mediated by cytokines are involved in the pathogenesis of acute stroke. Decrease in circulating levels of protein C (PC) and protein S (PS) induced by inflammatory cytokines has been postulated as a potential mechanism for a procoagulant tendency during acute stroke. The procoagulant state associated with impairments in natural anticoagulants may induce microvascular obstruction leading to a tissue perfusion reduction that worsens cerebral ischemia. Interleukin-6 (IL-6) regulate the synthesis of C4b-binding protein (C4BP), an acute-phase protein that also regulates PS plasma levels. We measured IL-6, C4BP, erythrocyte sedimentation rate (ESR), total and free PS and PC in 44 patients with acute ischemic stroke to determine if IL-6 decreases circulating levels of natural anticoagulants through the C4BP pathway and if these acute changes in natural anticoagulants may have clinical implications. Patients with higher levels of IL-6 had more severe neurologic deficits on admission, greater infarct size, higher levels of acute-phase reactants, and lower levels of free PS. IL-6 was significantly correlated with C4BP, ESR, and free PS levels. PC levels were also lower in the group of patients with greater IL-6, but differences were not statistically significant. No correlations were found between C4BP and natural anticoagulants. Severe neurologic deficit, greater infarct volume, atrial fibrillation, increased levels of inflammatory parameters (ESR and IL-6), and reduced levels of free PS were associated with disabling stroke at 3 months, but only neurologic severity and ESR remained as independent predictors of stroke disability on multiple regression analysis. Inflammatory reactions mediated by IL-6 during the acute phase of stroke influence the modulation of free PS. However, variations in free PS levels do not have implications for clinical outcome in stroke patients. The link between proinflammatory cytokines and free PS in the acute phase of stroke is not related to the C4BP pathway.
 ...
PMID:Interaction between interleukin-6 and the natural anticoagulant system in acute stroke. 1076 81

Hemostasis factors may influence the pathophysiology of stroke. The role of brain hemostasis in ischemic hypertensive brain injury is not known. We studied ischemic injury in spontaneously hypertensive rats in relation to cerebrovascular fibrin deposition and activity of different hemostasis factors in brain microcirculation. In spontaneously hypertensive rats subjected to transient middle cerebral artery occlusion versus normotensive Wistar-Kyoto (W-K) rats, infarct and edema volumes were increased by 6.1-fold (P < 0.001) and 5.8-fold (P < 0.001), respectively, the cerebral blood flow (CBF) reduced during middle cerebral artery occlusion (MCAO) by 55% (P < 0.01), motor neurologic score increased by 6.9-fold (P < 0.01), and cerebrovascular fibrin deposition increased by 6.8-fold (P < 0.01). Under basal conditions, brain capillary protein C activation and tissue plasminogen activator activity were reduced in spontaneously hypertensive rats compared with Wistar-Kyoto rats by 11.8-fold (P < 0.001) and 5.1-fold (P < 0.001), respectively, and the plasminogen activator inhibitor-1 antigen and tissue factor activity were increased by 154-fold (P < 0.00001) and 74% (P < 0.01), respectively. We suggest that hypertension reduces antithrombotic mechanisms in brain microcirculation, which may enhance cerebrovascular fibrin deposition and microvascular obstructions during transient focal cerebral ischemia, which results in greater neuronal injury.
 ...
PMID:Brain injury and cerebrovascular fibrin deposition correlate with reduced antithrombotic brain capillary functions in a hypertensive stroke model. 1089 83

Disturbances of coagulation and fibrinolytic pathways were studied in 53 young patients with cerebral ischemia. Upon admission 26 of 53 patients had abnormality in at least one of the antithrombin-III, protein C, protein S activities or in activated protein C (APC) ratios. Three months after the first examination the majority of the previously detected abnormalities returned to normal values and the most frequent alterations were decrease in protein S activity (3 patients) and APC resistance (3 patients). Conditions resulting in impaired fibrinolysis were frequently detected upon admission. Elevation of plasminogen activator inhibitor-1, lipoprotein (a), and alpha-2-antiplasmin was present in 23, 10, and 4 cases, respectively. It is concluded that abnormalities of coagulation as well as of the fibrinolytic systems are prevalent in the acute phase of cerebral ischemia, however, the results may be significantly influenced by the disease process or the acute phase effect.
 ...
PMID:Natural coagulation inhibitor proteins in young patients with cerebral ischemia. 1172 Oct 97


1 2 3 Next >>