Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, the plasma fibrinolytic activity in 30 cases of cortical artery territory cerebral infarction (CACI) and 32 cases of perforating artery territory cerebral infarction (PACI) within 3 days after ictus, and 30 sex- and age-matched controls without cardio-cerebrovascular diseases were evaluated by a comprehensive panel of assay, including the plasma tPA activity, PAI activity, endothelial capacity of tPA release and PAI/tPA ratio. The results showed that the plasma fibrinolysis and the endothelial potential to release tPA responding to stimulation in both subtypes of the patients were significantly lower than those in the controls, which provide the theoretical basis for carrying out the thrombolytic therapy in the ischemic stroke. And the study also suggested that increased plasma PAI activity could increase the risk of AS thrombotic events with increased serum triglyceride level.
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PMID:Analysis of plasma fibrinolysis in the patients with acute cerebral infarction. 873 55

Thrombolysis is proposed for the acute treatment of cerebral infarction as it is able to recanalize occluded arteries and thus potentially restore normal perfusion of the cerebral parenchyma, but the results concerning the efficacy of this treatment are still inconclusive. However, it has been fully demonstrated that thrombolytic treatment, leads to a significant reduction in mortality, in patients with acute myocardial infarction. Data from all of the pilot studies using SK or tPA treatment in acute stroke are described in this review, which underlines the incidence of hemorrhagic transformation (hemorrhagic infart and parenchymal hematoma) and its possible correlation to clinical worsening. Pharmacological, experimental and clinical studies encourage the carrying out of large-scale clinical trials using thrombolytics in patients with acute cerebral infarction. Significant data relating to ongoing controlled clinical trials will be available in the near future; only after the analysis of these results will it be possible to confirm the efficacy of thrombolytics in acute stroke.
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PMID:Thrombolytic therapy. From myocardial to cerebral infarction. The MAST-I Group. Multicentre Acute Stroke Trial. 874 84

We report the case of a 3-year-old girl who presented with near-lethal pulmonary thrombembolism 3 weeks after an uneventful Fontan operation. Complete occlusion of the left lower lobe pulmonary artery had occurred together with a cerebral infarction. Recombinant tissue plasminogen activator (rt-Pa) was used for thrombolysis because of its short half-life and its clot-selective properties. To further minimize the systemic effects of rt-PA, local catheter-directed lysis was performed. A prolonged course of low-dose rt-PA therapy achieved complete lysis without side effects.
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PMID:Catheter-directed thrombolysis with recombinant tissue plasminogen activator for acute pulmonary embolism after fontan operation. 878 Oct 96

The acute occlusion of cerebral artery by embolism causes severe cerebral infarction. In cases with poor colateral circulation, cerebral infarction develops more severely. In these cases, quick recanalization of the occluded cerebral artery is necessary to prevent severe hemorrhagic infarction and brain edema. We report a case where interventional techniques were used to bring about quick recanalization of occluded cerebral artery. We encountered a case of a sixty-year-old male who experienced complete occlusion of the left middle cerebral artery due to an embolus. It was very hard to pass a guide wire through the embolic lesion. At first, we tried mild local fibrinolysis therapy using tissue plasminogen activator, but we could not get any recanalization. However, after mild local fibrinolysis therapy, the guide wire could be passed through the occlusion point. Secondly, we tried percutaneous transluminal angioplasty (PTA) with 2.0mm diameter angioplastic balloon using up to five atomic pressures, after which we obtained partial recanalization. Finally we achieved total recanalization of the middle cerebral artery by PTA with a 2.5mm diameter angioplastic balloon. We crushed this embolus using the angioplastic balloon with up to six atomic pressures. The point of the techniques is to press the embolus against the arterial wall. After this angioplasty, there was an occlusion of the common trunk of the posterior parietal artery and the angular artery. However there was neither massive hemorrhagic infarction nor massive brain edema on follow up CT. In the treatment of acute occlusion of the cerebral artery due to embolism, we found PTA is very effective against the embolus. In the future, we need to develop a retrieving device and a balloon that will prevent the production of small emboli during the crush process involved when bringing about recanalization using PTA.
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PMID:[A case of acute occlusion of left middle cerebral artery due to an embolus treated successfully with percutaneous transluminal angioplasty]. 893 72

Although stroke is a major cause of morbidity and mortality, it is only relatively recently that a concerted effort has been made to develop acute treatments. Thrombolytics, such as recombinant tissue plasminogen activator (rt-PA), may benefit selected patients within 3 h of cerebral infarction. CUrrently, rt-PA is only licensed for use in the United States. Many potential strategies for neuroprotection exist and are currently under investigation. Because the mechanisms of neurotoxicity involve numerous interdependent processes, it may be that the interpretation of a single site in the cascade of events is insufficient to provide effective neuroprotection. Drugs acting at several sites in the neurotoxic cascade may be more effective, and the results of Phase III studies with the novel neoroprotectant lubeluzole are anticipated.
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PMID:The rationale for new therapies in acute ischaemic stroke. 920 64

We described an autopsy case of a ruptured aneurysmal subarachnoid hemorrhage treated with endovascular embolization by interlocking detachable coils. An 85-year-old male presented with sudden onset of severe subarachnoid hemorrhage. Cerebral angiogram revealed a right internal carotid-posterior communicating artery aneurysm. Post-operative angiogram revealed complete obliteration of the aneurysm, except for its orifice. Following the embolization of the aneurysm, tissue plasminogen activator was intrathecally perfused for anti-vasospasm treatment. Follow-up angiogram showed stable obliteration of the aneurysm, and no particular findings of cerebral vasospasm. The patient had been recovering without any neurological deficits, but died from pneumonia on the 25th day after the embolization. Autopsy findings revealed the disappearance of the subarachnoid hemorrhage, and no visible finding of cerebral infarction or edema. The inner lumen of the aneurysm was occupied by a mixture of the coils and the clots. The surface of the embolized coils was directly observed through the orifice of the aneurysm without any membranous substance from the inner lumen of the internal carotid artery. This pathological finding is different from the previously reported animal models in which the surface of the embolized coils was covered with endothelial membrane 2 weeks after embolization. Further examinations are required to clarify the pathogenesis of the endothelial regrowth.
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PMID:[An autopsy case of a ruptured cerebral aneurysm treated with interlocking detachable coils]. 930 Apr 53

We assessed the incidence of hemorrhagic transformation and infarct volume after early intravenous infusion of recombinant human tissue plasminogen activator (rht-PA) in a newly developed rat cerebral embolic model. Male Wistar rats (n=60) were subjected to middle cerebral artery (MCA) occlusion by a single fibrin rich clot. One hour after embolization, rats were assigned to the following groups: (1) rht-PA treated group (n=20); (2) vehicle treated group (n=20); and (3) saline treated group (n=20). Neurological deficits, lodgement of a clot at the origin of the MCA, infarction volume and microscopic hemorrhage were measured. Animals exhibited moderate to severe neurological deficits 1 h after MCA occlusion in all groups. Administration of rht-PA significantly (P<0.05) reduced the incidence of lodgement of a clot at the origin of the MCA (30%) compared with the saline treated group (100%) and the vehicle treated group (80%). A significant (P<0.05) reduction of percent hemispheric infarct volume was detected between the saline (33.2+/-3.71%) and the rht-PA groups (19.4+/-3.3%). However, no significant difference was found in the total area of microscopic hemorrhage of the rht-PA (0.05+/-0.02 mm2), the vehicle (0.02+/-0.01 mm2), and the saline (0.03+/-0.02 mm2) treated groups. No significant difference of percent hemispheric infarct volume (P=0.08) was observed between the vehicle and the rht-PA treated groups. This study demonstrates that treatment with rht-PA reduced infarct volume without increasing intracerebral hemorrhage in rats with large cerebral infarction when treatment was initiated at 1 h of the onset of embolization.
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PMID:Early (1 h) administration of tissue plasminogen activator reduces infarct volume without increasing hemorrhagic transformation after focal cerebral embolization in rats. 980 10

The pathophysiology of ischemic neuronal cell damage has been studied extensively. Intracellular calcium ions, excitatory amino acids, nitric oxide, oxygen free radicals, proteolysis, apoptosis, and so on play important roles. There are also gene expressions following cerebral ischemia, such as the immediately early gene, heat shock protein, cytokines, adhesion molecule, and growth factor, etc. In vessels of the ischemic brain, activation of platelets, leukocytes, the coagulation cascade, and fibrin generation occur and aggravate the cerebral microcirculatory disturbance. Treatment of acute ischemic stroke must be based on the clinical type (atherothrombotic, lacunar or cardioembolic) and the time after onset. Fibrinolysis by tissue plasminogen activator (intravenous administration) is approved in the USA for patients with cerebral infarction within 3 hours after onset. Efficacy of anticoagulant therapy using heparin was not verified by the International Stroke Trial (IST). In Japan selective anti-thrombin agent (argatroban) is used in patients with atherothrombotic cerebral infarction within 48 hours after onset. Results of IST and Chinese Acute Stroke Trial (CAST) showed aspirin within 48 hours after onset of cerebral infarction reduced recurrence of ischemic stroke during the acute stage and death within 6 months.
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PMID:[Recent advances in pathophysiology and treatment of acute ischemic stroke]. 1034 38

Since the publication of the NINDS rt-PA trial in 1995, tissue plasminogen activator has been licensed for the treatment of acute cerebral infarction in the U.S. The demonstrated benefit was confirmed to patients presenting within three hours of symptom onset on adhering to study guidelines, which subsequently have formed the basis for a protocol for thrombolysis in acute stroke. The implementation of a thrombolysis programme in Ireland would require a restructuring of hospital facilities to manage acute stroke. We conducted a prospective study of 100 patients admitted to an acute stroke unit to assess the potential for intervention with t-PA under NINDS guidelines. Data was collected on stroke type. CT appearances, time of onset of stroke and laboratory parameters. Only 6% of all strokes assessed were eligible for thrombolysis and time to presentation was the major excluding factor. When time was removed as an exclusion criteria only 1/5 of all strokes were potential candidates in this best case scenario. Thrombolysis does improve outcome in cerebral infarction in a a strictly controlled setting but only 6% of our patients would currently be eligible for treatment. While this may improve with better public education regarding stroke and it's treatment, only a 1/5 of our patients would still be eligible were they all to present within 2 hours of symptoms onset.
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PMID:Potential for treatment with thrombolysis in an Irish stroke unit. 1036 96

We evaluated the efficacy of local intra-arterial fibrinolysis (LIF) used in tissue plasminogen activator (t-PA) and its indication for acute middle cerebral artery (MCA) occlusion on angiographic degree of leptomeningeal collateral flow in a series of 26 patients (mean age: 67.2 years old). The occlusion types were classified into three types: (1) M 1 proximal occlusion (N = 8) involved the lenticulostriate arteries (LSA), (2) M 1 distal occlusion (N = 6) without involvement of the LSA to M 2 bifurcation, (3) M 2-3 occlusion (N = 12). In M 1 proximal and distal type, 100% patients had complete or partial recanalization till 5.3 and 6 hours, and 91.7% recanalized in M 2-3 type within 3.96 hours from attack on the average. Small cerebral infarction post LIF showed in 50%, but had no clinical change for the worse in all types. There was 65% in excellent or good prognosis on 2 months after attack. Within the range of 600,000-2,400,000 units of t-PA (mean = 1,107,000 units), small hemorrhagic transformation were developed in 5 cases (19.2%) without influence on its outcome. It means that below 2,400,000 units t-PA for LIF were safety amounts. In patients with poor collateral flow in angiographic findings, good prognosis could be possible in 75% within 4 hours (M = 3.96 hours) recanalization on the average. We conclude that LIF used in t-PA would be efficatious in M 1 proximal occlusion within 4 hours of onset and in patients with poor collateral flow when recanalized within 4 hours after attack.
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PMID:[Clinical study of therapeutic time window of local fibrinolysis for acute middle cerebral artery occlusion]. 1051 55


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