Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In spite of equivalent clinical efficacy of various thrombolytic agents for the treatment of acute myocardial infarction there is evidence of different drug-depending influences on the haemostatic and fibrinolytic system. In the present study 40 patients with acute myocardial infarction have been investigated. 20 patients received 750,000 and 1.5 mio U streptokinase (SK), respectively, 10 patients 30 mg anisoylated plasminogen streptokinase activator complex (BRL 26921) and 10 patients a combination of 200,000 U urokinase (UK) and 4.5 mio U pro-urokinase (PUK) as a short-term intravenous treatment. Reperfusion of coronary arteries has been achieved in 70 to 100 percent. Major not fatal bleedings occurred in 2 patients. One patient died within 72 hours after beginning of the myocardial infarction. The longest duration of fibrinolytic activity was observed in the BRL 26921 group (half-disappearance time close to 2 h). It was significantly shorter in the SK groups showing a dose-dependency. Plasma concentration of fibrinogen dropped beyond normal levels following SK and BRL 26921, but not under UK/PUK. Plasma viscosity correlated with fibrinogen decrease and displayed a dose-depending relationship with the presence of SK. Haemorheological effects are suggested to be important for the clinical efficacy of thrombolytic therapy in myocardial infarction.
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PMID:Modern strategies for treatment of acute myocardial infarction: significance of haemostaseological and rheological findings. 212 76

Between October 1982 and July 1984 systemic thrombolysis was carried out in 10 patients (5 males and 5 females aged 19 to 66 years) with massive pulmonary embolism (PE). Mean thrombolytic treatment duration was 77 hours. The main fibrinolytic agent used (9 cases) was streptokinase. Sequential treatment with streptokinase and urokinase was given to 2 patients and urokinase alone to one. 5 patients received porcine plasmin additionally, and one patient BRL 26921 (streptokinase-plasminogen complex) and human plasminogen. Pulmonary arterial pressures were recorded serially. Pulmonary angiograms were obtained before, occasionally during and after thrombolysis. Pulmonary arterial pressures (systolic: p less than 0.01, diastolic: p less than 0.05, mean: p less than 0.01, paired t-test, two tailed) and pulmonary angiograms (p less than 0.001, paired t-test, two tailed) all showed significant improvement. Thrombolytic treatment had to be discontinued in two patients due to side effects. Patients with the most recent PE showed the best response. Patients with recurrent PE and preexisting pulmonary hypertension showed no improvement. In PE without deep vein thrombosis (DVT), treatment duration of up to three days seems to be appropriate. In PE with concomitant DVT the treatment should be prolonged to achieve complete lysis of thrombi.
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PMID:[Fibrinolysis therapy in massive lung embolism. Experiences in 10 patients 1982-1984]. 293

Left ventricular pump failure is today's main cause of in-hospital mortality from acute myocardial infarction and is directly dependent on infarct size. The first clinical attempts to preserve myocardium after acute infarction and to improve morbidity and prognosis by thrombolysis date from about twenty years ago. Through large multicenter studies and promising new agents, coronary thrombolysis has again attracted increased attention in the past two years. After a brief overview on the preconditions for successful thrombolysis, the efficacy, advantages, complications and problems of different thrombolytic agents and forms of administration are reviewed on the basis of the controlled studies published up to June 1986. They concern streptokinase by intracoronary and intravenous route, urokinase and the "clot specific" agents of the second generation, recombinant tissue-type plasminogen activator (rtPA) and anisoylated plasminogen streptokinase activator complex (APSAC) BRL 26921. Finally, questions that remain open even after successful thrombolysis with myocardial salvage are raised, and in particular the problem of reocclusion and postlytic treatment. In spite of justified hopes and the demonstrable feasibility of reopening a coronary artery, thrombolysis in acute myocardial infarction should not be used routinely as long as the beneficial long term effect is not definitely proven for patients, or at least for a known subgroup of patients, in terms of left ventricular function, mortality and morbidity following myocardial infarction.
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PMID:[Thrombolysis in acute myocardial infarct: prerequisites, current experiences and remaining problems]. 309 41

Fibrinolysis is a physiological process which aims at dissolving intravascular thrombi and is mediated by activation of plasminogen to plasmin. Streptokinase (SK) and urokinase (UK) are non-specific plasminogen activators. They have proved effective as thrombolytic agents, but their use is limited by the risk of haemorrhages due to systemic fibrinogenolysis. More fibrin-specific drugs have recently been developed. One is a tissue plasminogen activator (t-PA), the other is a urokinase precursor (pro-UK), also called single chain urokinase plasminogen activator (scu-PA). Genetic engineering techniques have resulted in the large-scale production of a "recombinant t-PA" (rt-PA) and a "recombinant scu-PA" (r scu-PA) for therapeutic use, notably in acute myocardial infarction. In vitro, these two drugs exhibit a thrombolytic activity that is equal to, or greater than that of SK or UK. In vivo, their fibrinogenolytic effect is less pronounced, and their thrombolytic effect greater than those of SK or UK. "Acyl-enzymes" have more recently emerged. These are inactive acylated SK-plasminogen complexes which progressively become effective in plasma after deacylation. So far, the most extensively studied of these complexes is BRL 26921 (anisoylated plasminogen streptokinase activator complex, or APSAC) which is administered by bolus intravenous injection. It is more thrombolytic than SK but produces systemic fibrinogenolysis to an equivalent degree. Injected intravenously (by infusion or bolus) during the first hours of a coronary infarction these three new thrombolytic agents have proved effective in promoting coronary reperfusion, with an early coronary patency rate of 70-75%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New thrombolytic agents in myocardial infarction]. 312 22

BRL 26921 is a new acylated streptokinase-plasminogen complex which may have a more specific local thrombolytic effect than streptokinase or urokinase. 34 patients with acute peripheral arterial occlusions were given eight hourly bolus injections of 5 mg BRL 26921 for up to 72 h. Systemic fibrinolysis was observed in all patients yet in only 24% was the occluding thrombus lysed. 44% of the patients had haemorrhagic complications and 24% suffered further thrombotic events during or soon after treatment. There was no correlation between the degree of systemic fibrinolysis produced and dissolution of the thrombi. The degree of systemic fibrinolysis did not affect the complication rate. There is no evidence from this study that BRL 26921 has a specific local thrombolytic effect.
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PMID:The systemic fibrinolytic effect of BRL 26921 during the treatment of acute peripheral arterial occlusions. 352 Sep 38

Fibrinolytic agents with higher specificity for fibrin in the thrombi and little systemic activation of the fibrinolytic system have been developed and tested in preliminary clinical trials of patients with acute myocardial infarction. The largest published experience available has been with recombinant tissue plasminogen activator, which seems to be more effective than streptokinase in lysing coronary thrombi. The acylated streptokinase-plasminogen complex BRL 26921 and pro-urokinase also gave promising preliminary results. All these agents, however, were accompanied by unexpectedly high incidence of systemic activation of the fibrinolytic system and by hemorrhagic complications with frequencies similar to those accompanying streptokinase. Hence, their superior clinical efficacy must be clearly proven before they are substituted for a more widely available and less expensive drug, such as streptokinase.
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PMID:Newer fibrinolytic agents in patients with acute myocardial infarction. 354 57

The study concerns 31 cases of parenteral fibrinolysis performed at the acute stage of myocardial infarction in 30 patients (mean age: 51.9 years), treated less than 4 hours and 15 minutes after the onset of pain. The treatment with streptokinase (80.65%), BRL 26 921 (12.90%) and urokinase (6.45%) was undertaken within a mean time of 3 hours and 17 minutes +/- 53 min. Revascularization defined by the disappearing of pain, the sudden flattening of ST with presence of Q wave, was obtained in 71 p. cent of patients before the 6th hour. The study of the CK curve shows that the enzymatic peak is reached earlier in these patients (13 hours 23 vs 19 h 42). Severe arrhythmias are rare (VF: 0%, transient AVB III: 3.2%). VAIRs were only observed in patients revascularized at an early stage (p 0.02) and in 54.5 p. cent of them. It seems to concern the largest M.Is, treated and revascularized later, regardless of the artery concerned. The syndrome bradycardia-hypotension (Bezold-Jarisch reflex) is only found in patients revascularized at an early stage (22.7 p. cent). Late VES (RR' RR-200 ms or fusion) are more frequent in patients revascularized at an early stage. These three benign rhythm disorders which do not usually require treatment, seem to be good success criteria of fibrinolysis but cannot be considered as predictive indications of myocardial protection.
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PMID:[Impact and significance of early rhythm disorders after fibrinolytic treatment of myocardial infarction]. 361 81

The role of thrombus-binding in the fibrinolytic response to the acylated streptokinase.plasminogen activator complex, BRL 26921, has been examined using human plasma clots, radiolabelled with 125I-fibrin, in vitro. When clots were briefly exposed to BRL 26921, washed and returned to homologous plasma, lysis continued for up to 3 hours and attained approximately 25% of that lysis achieved by incubating with BRL 26921 for 5 hours. This continuing lysis was potentiated by return of exposed clots to alpha 2-antiplasmin-depleted plasma, or buffer and is attributed to an initial uptake of BRL 26921 rather than the binding of exogenous plasmin that was observed for streptokinase and high concentrations of urokinase. The sustained lysis is not explained by transfer of loosely-associated surface material or by dissociation of agent from the clot with reuptake from a dilute systemic pool. The response can be attributed, at least in part, to specific fibrin binding, mediated by kringles 1-4, for a low-molecular weight plasminogen (Val442) variant was less active.
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PMID:Induction of a sustained fibrinolytic response by BRL 26921 in vitro. 389 61