Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to examine the plasminogen activator (PA) induction involved in the pathogenesis of acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS), PA activity in peripheral blood lymphocytes derived from 5 ADEM and 3 MS patients was investigated. There was no PA induction in any ADEM, MS or control lymphocytes treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone. PA activity, however, in lymphocytes exposed to human interferon-gamma (HuIFN-gamma) prior to MNNG treatment was elevated during the active phase of ADEM and MS, whereas the PA induction disappeared in association with improvement of the neurologic symptoms. The PA activity was abolished by mixed treatment with HuIFN-gamma and anti-HuIFN-gamma antibody. No such PA induction by any HuIFN was observed in any normal controls or cases of other neurologic diseases. Among the cytokines tested other than HuIFN, tumor necrosis factor-alpha, in combination with MNNG, also induced PA activity in lymphocytes from ADEM and MS patients during the active phase. Thus, the PA induction observed in lymphocytes on combined treatment with MNNG and cytokines may be involved in the progression of neurologic disorders in these demyelinating diseases, and indicates the possibility of therapeutic strategies involving anticytokine usage.
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PMID:Involvement of cytokines in N-methyl-N'-nitro-N-nitrosoguanidine-induced plasminogen activator activity in acute disseminated encephalomyelitis and multiple sclerosis lymphocytes. 824 10

Approximately 80 to 90% of cerebral ischaemic events that occur within 24 hours of symptom onset are due to atherothrombotic or thromboembolic occlusions. This forms the rationale for the use of thrombolytic agents in patients with acute ischaemic stroke. Early studies determined that recanalisation occurred in approximately 21 to 72% of patients with occluded cerebral arteries after intra-arterial or intravenous administration of streptokinase, urokinase, alteplase (recombinant tissue-type plasminogen activator; rt-PA) or duteplase (a 2-chain rt-PA). Initial reports suggested that frequencies of haemorrhagic transformation and parenchymatous haematoma in the carotid territory were similar whether patients with middle cerebral artery stroke received thrombolysis via intra-arterial or intravenous administration. The Multicentre Acute Stroke Trial-Europe (MAST-E), the Australia Streptokinase (ASK), and the Multicentre Acute Stroke Trial-Italy (MAST-I) trials, which evaluated intravenous streptokinase 1.5 x 10(6) IU in patients with acute ischaemic stroke, were terminated prematurely because of excessive early mortality and symptomatic intracranial haemorrhage in streptokinase recipients compared with those treated with placebo. However, those studies had not been preceded by dose-ranging trials. Intravenous administration of alteplase 0.9 mg/kg within 3 hours [National Institute of Neurological Disorders and Stroke (NINDS) trial], or 1.1 mg/kg within 6 hours [European Cooperative Acute Stroke Study (ECASS)], of symptom onset in patients with acute ischaemic stroke resulted in an absolute 11 to 13% treatment-associated improvement in clinical measurement scales; such as the modified Rankin scale and Barthel index, compared with placebo recipients. In the ECASS trial, those results were limited to a 'target population' restricted to those who satisfied all entry criteria. In both trials, the frequency of symptomatic haemorrhage was greater in patients treated with alteplase than with placebo and reinforced the importance of careful patient selection. Strict patient selection remains central to the success of this approach.
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PMID:Thrombolytic therapy in the treatment of stroke. 936 Aug 56

Results from the two National Institute of Neurological Disorders and Stroke (NINDS) studies indicate that administration of alteplase (recombinant tissue-type plasminogen activator; rt-PA) within 3 hours of symptom onset to appropriately selected patients with acute ischaemic stroke improves patient outcome. Several factors that delay time to treatment in patients with stroke have been identified, the most important of which is probably the failure of the patient (or family member) to recognise the signs and symptoms of stroke. Once the need for help is recognised, the initial point of access to emergency medical systems should be the local emergency number (e.g. 911 in the US) rather than the family physician. Patients with suspected stroke should be evaluated and treated by a physician as soon as possible, but this will depend to some extent on the level of expertise of the attending physicians and on available resources. The NINDS-sponsored National Symposium on the Rapid Identification and Treatment of Acute Stroke has recommended ideal time goals for all hospitals that treat patients with acute stroke. These goals include 25 minutes from arrival at an emergency department to computerised tomography scan, and 60 minutes from arrival to treatment. Recommendations for enhancing the logistics of treatment for patients with stroke may involve the following: improved education programmes for at-risk populations and their families and emergency medical system personnel, identification of acute stroke as a level one emergency similar to acute myocardial infarction or trauma, and modelling of treatment algorithms accordingly, acceptance of, and commitment to, the time guidelines recommended by the National Symposium on the Rapid Identification and Treatment of Acute Stroke. Effective and safe use of alteplase will also depend on rapid access to the highest level of neurological and radiological expertise. This may require major changes in the educational curriculum of emergency department residency and ongoing continuing education programmes, and/or more intensive radiological training for neurologists and neurologists-in-training.
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PMID:Logistics in acute stroke management. 936 Aug 58

We assessed initial clinical experience with IV tissue plasminogen activator (t-PA) treatment of acute ischemic stroke in a standardized retrospective survey of hospitals with experienced acute stroke treatment systems. The incidence of symptomatic intracerebral hemorrhage (ICH) was 6% (11 of 189 patients; 95% CI 3 to 11%), similar to that in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Deviations from the NINDS protocol guidelines were identified in 30% of patients (56 of 189). The incidence of symptomatic ICH was 11% among patients with protocol deviations as compared with 4% in patients who were treated according to the NINDS protocol guidelines, suggesting that strict adherence to protocol guidelines is prudent.
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PMID:Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: a multicenter survey. The t-PA Stroke Survey Group. 1043 Apr 44

Thrombolytic therapy with t-PA for acute ischemic stroke may provide benefit in long-term outcome. This retrospective study was undertaken to evaluate appropriateness of the National Institute of Neurological Disorders and Stroke (NINDS) protocol in the emergency department (ED). All patients with appropriate International Classification of Diseases, 9th revision (ICD-9) codes indicating stroke who presented to our 387-bed trauma-I community hospital during 1997 were included in the study. Of the nearly 35,000 patients screened, 201 patients satisfied our inclusion criteria. Mean age was 73.5 +/- 13.3 years. Men were evaluated and transported to computed tomography more rapidly and older patients more slowly. Nonwhites were more likely to arrive via emergency medical services (EMS). Average time from EMS arrival at scene to ED arrival was 22.7 minutes, and from ED arrival to triage was 8.4 minutes. The most common reason for exclusion from t-PA administration was delayed presentation (n = 188); this is the most serious barrier to use of t-PA for acute ischemic stroke. Extensive public education may combat this.
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PMID:Lack of t-PA use for acute ischemic stroke in a community hospital: high incidence of exclusion criteria. 1104 42

Patients with acute ischemic stroke should be immediately transported to the nearest hospital for rapid evaluation and treatment. Intravenous t-PA within 3 hours of symptom onset is the recommended treatment for patients who meet the National Institute of Neurological Disorders and Stroke (NINDS) study eligibility criteria. Patients should be informed of the risk of symptomatic cerebral hemorrhage, and strict adherence to the NINDS study protocol is strongly recommended to optimize the risk-benefit ratio. Ischemic stroke patients who are not eligible for t-PA therapy should usually be started on aspirin. Intravenous heparin is not recommended as a standard treatment but may be considered for specific patient subgroups. Low-dose subcutaneous heparin is recommended for prophylaxis of deep vein thrombosis in immobilized patients. Management of stroke patients by a designated stroke team is recommended to facilitate prompt diagnosis and treatment and early initiation of rehabilitation therapy. We also recommend that physicians who manage patients with acute stroke maintain contact with local or regional stroke centers to facilitate referral of appropriate patients for intensive care or specialized diagnostic tests or therapies.
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PMID:Acute Ischemic Stroke. 1109 99

The publication of the positive results of the National Institute of Neurological Disorders and Stroke (NINDS) trial of alteplase (a recombinant tissue plasminogen activator; rt-PA) for acute stroke patients in 1995 and its approval by the US Food and Drug Administration as well as the American Academy of Neurology and American Heart Association increased the interest and attention of the medical community in acute stroke treatment. However, the implication of this NINDS Stroke Study and other thrombolytic trials in clinical practice remains controversial and debated. Furthermore, the recent publication of the results from the European Cooperative Acute Stroke Study II (ECASS II) and Alteplase Thrombolysis of Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) studies will feed the controversy, since the results of these two studies are disappointing and do not confirm the positive results of the NINDS Stroke Study as expected by clinicians managing patients with acute stroke. The Standard Treatment with Alteplase to Reverse Stroke (STARS) and Cleveland studies, which involved a large number of community hospitals to assess the safety profile and the benefit of rt-PA thrombolysis for acute stroke patients in clinical practice, have shown controversial results. Consequently, the issue arises of which is the more reasonable position concerning thrombolysis by alteplase, which seems to work but has not been proven yet beyond reasonable doubt? The recent publication of the results from the Prolyse in Acute Cerebral Thromboembolism (PROACT II) study has shown that intra-arterial thrombolysis with prourokinase is a benefit treatment in stroke patients with a proven middle cerebral artery occlusion within 6 h of stroke onset. Numerous trials devoted to neuroprotection against acute ischemic stroke have been prematurely stopped because of safety concerns or poor risk-benefit ratios, but some new neuroprotective drugs seem promising and are being tested in ongoing studies. The third issue under study concerns the use of antithrombotic drugs in the acute phase of stroke, particularly the new potent platelet glycoprotein IIb/IIIa antagonists such as abciximab. In this paper, we have reviewed selected recent clinical trials focusing on recent advances in acute stroke therapy.
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PMID:Recent progress in drug treatment for acute ischemic stroke. 1124 3

What is the risk of thrombolysis in patients with acute stroke who might recover without treatment? In the National Institute of Neurological Disorders and Stroke rt-PA for Acute Stroke Trial, 2.6% of patients taking placebo showed spontaneous 24-hour recovery, compared to 11.5% of recombinant tissue-type plasminogen activator (rt-PA)-treated patients (p < 0.001). There were no symptomatic ICH in the patients taking placebo; one hypertensive, rt-PA-treated patient hemorrhaged. Assuming the National Institute of Neurological Disorders and Stroke protocol is followed rigorously, patients with acute stroke rarely recover spontaneously and the thrombolytic risk is low.
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PMID:Thrombolysis in patients with transient neurologic deficits. 1173 41

Serine proteases, such as thrombin and tissue-type plasminogen activator, play an important role in brain injury after intracerebral hemorrhage and other neurologic disorders. Plasminogen activator inhibitor-1 is one of the serine protease inhibitors, or serpins. The balance between serine proteases and serpins may affect the outcome of intracerebral hemorrhage. The purpose of this study was to determine whether plasminogen activator inhibitor-1 and tissue-type plasminogen activator are upregulated after intracerebral hemorrhage and the role that thrombin plays in that induction. Plasminogen activator inhibitor-1 protein levels were upregulated after intracerebral hemorrhage. Brain plasminogen activator inhibitor-1 content also increased after thrombin infusion in a dose-dependent manner. Hirudin, a specific thrombin inhibitor, blocked the upregulation of plasminogen activator inhibitor-1 after intracerebral hemorrhage. Time courses showed that plasminogen activator inhibitor-1 levels around the hematoma peaked at the first day. Plasminogen activator inhibitor-1-positive cells were detected in the perihematomal area and the ipsilateral basal ganglia after thrombin infusion, but not in the contralateral hemisphere. Plasminogen activator inhibitor-1 messenger RNA levels were increased at 24 hours after intracerebral hemorrhage and after thrombin infusion. However, tissue-type plasminogen activator protein levels were the same in the control, whole-blood, and thrombin-infusion groups. In conclusion, intracerebral hemorrhage and thrombin infusion stimulate plasminogen activator inhibitor-1 but not tissue-type plasminogen activator production in the brain. The upregulation of plasminogen activator inhibitor-1 may be neuroprotective by limiting thrombin or other serine protease-induced toxicity.
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PMID:Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage. 1180 94

Treatment for acute ischemic stroke has for years been frustrated by lack of efficacy. Despite a plethora of seemingly promising treatments from animal research, clinical application never came to fruition. Experience seems to indicate that the only truly effective treatment is the rapid restoration of perfusion to ischemic tissue prior to frank infarction. Unfortunately, every agent designed to achieve this goal met with the same ironic limitation; the ability to dissolve clot was coupled with the risk of causing intracerebral hemorrhage. Accordingly, stroke was addressed primarily through modification of risk factors and rehabilitation of the neurological sequelae. However, following the randomized trial of intravenous tissue-type plasminogen activator (t-PA) sponsored by the National Institutes of Neurological Disorders and Stroke (NINDS) in 1995, the first proven effective therapy for acute stroke became available. The door was finally open to emergency treatment of stroke in the acute phase. Moreover, the positive results of the NINDS trial appear to be independent of age. Nevertheless, intravenous thrombolysis remains ineffective in the majority of patients treated and is withheld from an even larger population because of presentation outside of the 3-hour therapeutic window. As a result, effective therapy is not available for most patients presenting with acute stroke. Recent advancements in the evaluation and treatment of acute ischemic stroke, including intra-arterial thrombolysis, mechanical thrombolysis, and combination therapies, hold significant promise for a larger proportion of patients. New imaging technology may also improve our ability to identify patients with viable brain tissue who may derive the greatest benefit from these therapies.
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PMID:Developments in endovascular therapy for acute ischemic stroke. 1207 36


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