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

All thrombolytic agents convert plasminogen to plasmin, either directly as urokinase, saruplase and alteplase or indirectly as streptokinase. In the majority of recent clinical trials with streptokinase, a high-dose (0.7 to 1.5 mega-units), brief-duration (30 to 90 minutes) drug regimen has been used. After a mean time interval of 4.2 hours from onset of pain to intravenous infusion of streptokinase, a repeat angiography performed 60 to 90 min after start of thrombolytic treatment gives a reperfusion rate of 43%, the corresponding figures for anistreplase, saruplase and alteplase are 56%, 67% and 69%. The patency rates of similar studies with the same endpoint are for streptokinase 56%, for anistreplase 77%, for urokinase 62%, for saruplase 71% and for alteplase 75%. The reduction in hospital mortality in randomized trials with intravenous streptokinase (high-dose) is in 6 large studies in a total of 23,267 randomized patients from 10.7% in the control group to 7.0% in the streptokinase group. In a mortality study involving 1,004 patients randomized to intravenous anistreplase or placebo the 30-day mortality was reduced by 47%, from 12.2% to 6.4%. A large trial in which 5,011 patients were randomized to alteplase or placebo, the 30-day mortality was 7.2% compared to 9.8% in controls, a reduction of 27% by alteplase. In another trial 721 patients were randomized to placebo or alteplase; all patients were on aspirin. The 14-day mortality was only 2.8%, 51% less than that in the control group. It is most important that the favourable impact on hospital survival is maintained at 1 year with any thrombolytic drug. Large scale trials directly comparing mortality after alteplase, streptokinase or anistreplase are being performed or in the planning phase. The risk of bleeding exists with any thrombolytic agent but intracranial bleeding is the most serious one. In a large trial on 5,011 patients with acute myocardial infarction, stroke occurred in 1.1% of alteplase treated patients compared with 1.0% in placebo treated controls. Crucial problems are residual stenosis of the coronary artery and reocclusion. Urgent angioplasty does not seem to be the right answer; more effective antithrombotic strategies still have to be developed.
 ...
PMID:[Thrombolytic therapy in acute myocardial infarct]. 219 44

The oral administration of the thrombolytic agent urokinase was studied. Its intestinal absorption was demonstrated in dogs by the observation of a prolonged urokinase activity in plasma with a concomitant lytic effect on artificial thrombi after intraduodenal administration. In situ intestine-liver perfusion experiments in dogs revealed that a plasminogen activator, distinct from the administered urokinase--thus presumed to be a tissue plasminogen activator--was liberated into the circulation in association with intestinal absorption of urokinase. Its absorption in men was demonstrated in a cross-over double blind study of oral urokinase on healthy subjects. On the basis of these results a double blind clinical trial of oral urokinase was performed on 101 patients with cerebral thrombosis. The results showed the usefulness of urokinase treatment, particularly in the early phase after the onset of stroke. The clinical effect was influenced by the plasma plasminogen level.
 ...
PMID:Oral urokinase: absorption, mechanisms of fibrinolytic enhancement and clinical effect on cerebral thrombosis. 242 93

Recognition that myocardial infarction is caused by coronary thrombosis has stimulated a search for a safe, rapidly acting, and effective thrombolytic regimen. Tissue plasminogen activator (t-PA) can provide relatively clot-selective thrombolysis, but one quarter of patients fail to achieve reperfusion, lysis speed is not optimal, and higher doses have been associated with an increased incidence of hemorrhagic stroke. We report the results of a multicenter study of pro-urokinase, a second naturally occurring plasminogen activator that has structural similarities to t-PA but has a different mechanism of action. Pro-urokinase was administered 3.9 +/- 1.1 hours after the onset of chest pain to 40 patients with acute myocardial infarction with angiographically confirmed complete coronary occlusion (TIMI grade 0). After a 90-minute intravenous infusion of pro-urokinase (4.7-9 million units, 36-69 mg) 51% (20 of 39) of the patients demonstrated reperfusion (TIMI grade 2 or 3) occurring 64.8 +/- 22.3 minutes after initiation of therapy. Fibrinogen levels fell only 10 +/- 17% from baseline, confirming the fibrin specificity of pro-urokinase. As with t-PA, however, this specificity was only relative. alpha 2-Antiplasmin decreased to 39% and plasminogen decreased to 64% of initial values. Fibrinogen degradation products increased 63% and the fibrin-specific D-dimer increased 8.7-fold. Thus, pro-urokinase produces relatively clot-selective coronary thrombolysis similar to that produced by t-PA, but the use of either pro-urokinase or t-PA alone in higher doses would be likely to produce more nonspecific effects.
 ...
PMID:Clot-selective coronary thrombolysis with pro-urokinase. 249 4

In an effort to determine the value of tissue-type plasminogen activator (TPA) in the treatment of embolic stroke, 17 rabbits were subjected to a model of embolic stroke in which 2-hour-old, tin-impregnated, autologous clots were embolized to the bifurcation of the internal carotid artery at the circle of Willis via retrograde injection into the cannulated external carotid artery. High-resolution digital subtraction radiography was used to localize clots intracranially at the carotid bifurcation. Circulation through the internal carotid artery and intracranial vessels was monitored with serial digital subtraction angiography before and after embolization and during treatment. Disappearance of the tin marker on the digital subtraction radiograph indicated dissolution of clot and was associated with reestablishment of circulation on the digital subtraction angiogram. Experimental animals were treated with human-specific recombinant TPA 30 minutes, 2 hours, or 4 hours after clot embolization. TPA was administered as an intravenous bolus of 0.5 mg/kg followed by an infusion of 1 mg/kg/h for 2 hours. Digital subtraction angiograms were performed every 30 minutes. All clots dissolved, and cerebral circulation was reestablished within 120 minutes of treatment. In control animals treated with saline, embolized clots were stable, and the internal carotid artery remained occluded. At the completion of each study, the animal was perfused with freshly prepared, buffered 2,3,5-triphenyltetrazolium chloride (TTC) for demarcation of cerebral infarction. Control animals demonstrated infarction of 50 +/- 3.6% of the ipsilateral cerebral hemisphere, with an infarct weight of 2.1 +/- 0.2 g.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Evaluation of recombinant tissue plasminogen activator in embolic stroke. 249 63

We present the case of a 42-year-old female, who suffered an embolic occlusion of the right middle cerebral artery (MCA). Recanalization was achieved with tissue plasminogen activator (t-PA) within 7 h after onset of stroke. Post-t-PA infusion angiographic and CT examinations revealed fragmentation of the thrombus and a small putaminal haemorrhage associated with early reperfusion of the MCA. No clinical deterioration was observed and complete recovery occurred within 10 days.
 ...
PMID:Putaminal haemorrhage after recanalization of an embolic MCA occlusion treated with tissue plasminogen activator. 249 2

Early fibrinolytic therapy with full molecular tissue plasminogen activator (t-PA) has been observed to be both angiographically and clinically effective when employed in animal stroke models. Preliminary clinical trials with t-PA are in progress. It is possible to refine t-PA by developing fragments or analogues of the drug. Using recombinant DNA technology in the Escherichia coli system, a t-PA analogue consisting of the catalytic fragment of t-PA and a dimer of the B fragment of staphylococcal protein A (Fb-Fb-CF) has been produced. Because this analogue has a long serum half-life of 90 minutes, we employed Fb-Fb-CF in a rabbit cerebral embolic stroke model to assess its efficacy as a reperfusion agent. When given as a bolus to 10 animals 15 minutes after embolization, Fb-Fb-CF produced angiographic cerebral reperfusion in 48 +/- 21 minutes (+/- SD), while in 8 saline-treated controls, reperfusion was not observed at 180 minutes in any animal (p less than 0.01). In another experiment reperfusion was demonstrated at 66 +/- 32 minutes in 11 animals treated with Fb-Fb-CF 90 minutes after embolization as compared with 100 +/- 25 minutes in 12 saline-treated controls (p less than 0.01). A small macroscopic hemorrhage within an infarct was seen in 1 Fb-Fb-CF-treated animal in the 15-minute experiment and in none of the controls. In the 90-minute experiment, macroscopic hemorrhagic infarction was seen in 4 Fb-Fb-CF-treated animals and in 3 controls.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effects of a new tissue plasminogen activator analogue, Fb-Fb-CF, on cerebral reperfusion in a rabbit embolic stroke model. 249 44

Thrombolytic therapy offers the promise of major therapeutic intervention in many areas as well as in the treatment of patients with acute myocardial infarction who present to the emergency department. Infusion of tissue-type plasminogen activator (tPA) during field transport has been proven safe, but optimal methods for reliably diagnosing acute myocardial infarction in the prehospital setting have yet to be delineated. A major advance would be achieved if thrombolysis were proven effective in preventing the progression of unstable angina to actual infarction. However, early studies have yielded contradictory results. The use of tPA in dissolving peripheral arterial clots appears very promising, but long-term limb survival has yet to be demonstrated. Unlike heparin, thrombolytic agents can also lyse clot in peripheral deep veins and possibly lessen the tendency toward postphlebitic syndrome. The proper dosage regimen to minimize hemorrhage has not been determined. Pulmonary emboli can be lysed by tPA. IV infusion is as effective as intrapulmonary. Significant complications can be minimized, particularly if major vessel catheterization can be avoided for diagnosis. Even after catheterization for pulmonary angiography, however, thrombolytic therapy appears quite promising. The use of thrombolytic agents for embolic-thrombotic stroke is less promising: therefore, the risk of hemorrhagic complication may not outweigh the potential benefit. Thrombolytic therapy thus offers the potential for significant impact on the practice of emergency medicine.
 ...
PMID:Future role of thrombolytic therapy in emergency medicine. 251 90

The development of fibrinolytic agents such as streptokinase and recombinant tissue type plasminogen activator (r-TPA) and other modalities of treatment in acute ischemic stroke, has raised the need for a more precise knowledge of the pathophysiology of the acute phases of ischemic stroke as it pertains to prediction of clinical outcome. In a prospective analysis, 80 patients were studied within less than 6 h from the onset of symptoms by means of a detailed protocol including clinical evaluation, cerebral computed tomography, digital angiography and ultrasound transcranial Doppler sonography. Early angiography revealed a complete arterial occlusion in 76% of cases, the majority of which were intracranial (66%). Seventy percent of the occlusions that were retested were removed within 1 week. Potential embolic sources were found in more than 80% of cases. Patients with documented intracranial occlusion and scarce or absent collateral filling at early angiography, had the worst clinical outcome (P less than 0.05), based on mortality data and the Canadian Neurological Scale. The 30-day mortality rate was 25%. Survival was significantly better (P less than 0.01) in patients with a Canadian Neurological Score on entry of greater than or equal to 6.5 than in patients with a less than 6.5 value. Our data indicate that early pathophysiological studies augment the clinical information and should be taken into account in the design and analysis of therapeutic trials of acute ischemic stroke.
 ...
PMID:Clinical and instrumental evaluation of patients with ischemic stroke within the first six hours. 267 Dec 68

Clinical experience with thrombolytics in non-coronary disorders is limited to the plasminogen activators streptokinase, urokinase and alteplase; therapeutic trials with anistreplase (APSAC) are almost, and with saruplase completely, limited to acute myocardial infarction. In terms of thrombus clearance, thrombolytic drugs are superior to heparin in patients with recent deep vein thrombosis in the pelvis or lower limbs. In aggregate, thrombi younger than 8 days are lysed in approximately 60% of patients treated with streptokinase, urokinase or alteplase. The results of studies assessing the subsequent development of the postphlebitic syndrome are conflicting, but most suggest that thrombolytic therapy can reduce symptoms of chronic venous insufficiency. Currently, the combination of systemic thrombolytic drugs followed by heparin is recommended for patients with acute major pulmonary embolism who are haemodynamically unstable. Streptokinase, urokinase and alteplase have all been shown to accelerate the lysis of pulmonary emboli and to decrease pulmonary vascular obstruction and pulmonary hypertension. Systemic venous or intrapulmonary infusions of alteplase offers the same benefit in terms of angiographic and haemodynamic improvement. A short infusion of 100 mg alteplase over 2 hours seems to be superior to a 24-hour infusion of urokinase. None of the thrombolytic trials in pulmonary embolism have been large enough to demonstrate a reduction in mortality. It is now generally accepted that, unless contraindicated, thrombolytic therapy is the front-line treatment for patients with massive pulmonary embolism and major haemodynamic disturbance. The local treatment of acute arterial occlusion in limb arteries results in rapid clearing of the artery in 67% of patients treated with streptokinase; the corresponding success rates for urokinase and alteplase are 81% and 88 to 94%, respectively. The main question appears to be the identification of patients in whom local thrombolysis is the treatment of choice, as opposed to established therapeutic modalities. Thrombolytic treatment following a major ischaemic stroke is hazardous, although clinical improvement has been noted in a minority of patients with recanalised cerebral arteries. The safety and efficacy of thrombolytic treatment remains unproven for this indication, and its use must be restricted to experimental protocols. Thrombolytic treatment in retinal artery or vein occlusion has, in practice, been abandoned.
 ...
PMID:Use of thrombolytic drugs in non-coronary disorders. 268 38

13,318 patients admitted to fifty-two coronary care units with suspected acute myocardial infarction were considered for inclusion in a double-blind study comparing recombinant tissue-type plasminogen activator (rt-PA) 100 mg plus heparin with placebo plus heparin. 8307 (62%) were excluded, mainly because their symptoms had begun more than 5 h previously, but all excluded patients were followed up at least until hospital discharge. 2516 patients were randomly allocated to rt-PA and 2495 to placebo. At one month the overall case fatality rates were 7.2% and 9.8%, respectively, a relative reduction of 26% (95% confidence interval 11-39%). 6.3% of patients given rt-PA had a bleeding complication (1.4% major) compared with 0.8% given placebo (0.4% major). However, the incidence of stroke was similar--1.1% in the rt-PA group and 1.0% in the placebo group. Subset analysis showed that patients who had a normal electrocardiogram (ECG) at the time of randomisation (17.5% of the whole trial population) had a low case fatality rate (1.6% in those given rt-PA compared with 3.0% in those given placebo). In those with an abnormal ECG at entry, rt-PA was associated with a 24.5% relative reduction in 1 month fatality (95% confidence interval 9-37%).
 ...
PMID:Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis (ASSET). 290 Sep 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>