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

Thrombolytic therapy is aimed at dissolving thrombi. Streptokinase (SK) and urokinase (UK) are currently used in France but their mode of action has not been completely elucidated, which renders the establishment of therapeutic protocols and the choice of doses difficult. This treatment has a certain number of contraindications which must be strictly respected. The effectiveness of SK and UK in high doses has been demonstrated, in particular in pulmonary embolism and acute arterial obstruction of the limbs, but there is a risk of haemorrhage, whilst UK in moderate doses is usually well tolerated but has yet to prove its effectiveness in randomised double blind trials. Laboratory control has been simplified but it is essential not to forget the importance of clinical monytoring. Finally, drugs have recently been used in association with thrombolytics and more particularly the administration of plasminogen or defibrinating agents before or after thrombolytics.
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PMID:[Thrombolytic treatment (theoretical basis, therapeutic protocols, monitoring)]. 3 Nov 15

Systemic streptokinase has shown its effectiveness in the treatment of recent arterial obstruction of the limbs. The haemorrhagic and embolic complications of this type of treatment nevertheless limit its indications. Streptokinase should be reserved for acute thromboses present for less than two months, and responsible for severe ischaemia without the possibility of surgical treatment. The intra-arterial administration of urokinase limits the risks of systemic fibrinolysis, though the effectiveness of the therapeutic protocols proposed has yet to be demonstrated.
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PMID:[Thrombolytic treatment of arteriopathies]. 3 Nov 19

A new method is presented for estimating the activator (plasminogen-streptokinase complex) concentration in native plasma of patients undergoing streptokinase infusion. The principle of the method is based on clot lysis time as recorded by the thromboelastograph. The test clot constituents were bovine fibrinogen, bovine plasminogen, EDTA, human plasma (with unknown activator concentrations), and thrombin. In order to obtain a standardization line, urokinase dissolved in NaCl solution was substituted for patients' plasma. Thus, each lysis time could easily be converted into urokinase equivalent (CTA-u/ml). Streptokinase and plasminogen molecules in undiluted patients' plasma were found to exist both in an activator-bound (equimolar plasminogen-streptokinase complex) and in a freely circulating form. This result is in agreement with earlier findings where the activator complex was demonstrated to be a widely dissociated complex in highly diluted plasma of patients, thus displaying an ample proportion of free streptokinase and plasminogen and molecules. Streptokinase treatment using dosage schemes of 100,000 u SK/h, and 200,000 u/h were monitored by quantitative activator, streptokinase, and plasminogen measurements. An average activator concentration of 50-100 CTA-u/ml and a SK-concentration of 7-16 u/ml were recorded during streptokinase infusion. Plasminogen values averaged 0.25%, independent of the amount of streptokinase infused. Each drop in streptokinase was accompanied by a drop in activator during the infusion, and each rise in streptokinase by a rise in activator. There was a strong correlation between streptokinase and activator concentrations in that, on the average, 1 u streptokinase equalled 8.4 CTA-u/ml activator (correlation coefficient r = 0.9) It is concluded that the activator concentration in the plasma of patients undergoing fibrinolytic treatment can easily be adjusted by regulating the hourly streptokinase influx.
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PMID:Studies on activator formation in human plasma with streptokinase. III. Investigation of activator kinetics in undiluted plasma in terms of urokinase equivalents. 13 62

We report on 10 patients with thromboembolic occlusion of the middle cerebral artery (MCA) who underwent local thrombolytic therapy. Six patients developed a MCA occlusion during long-standing interventional neuroradiological procedures, while four had a proven or suspected cardio-embolic stroke. Streptokinase or urokinase was applied by a microcatheter placed into the thrombus within six hours of clinical onset. Complete or partial revascularization was achieved in all patients. Recovery was complete in seven and partial in three of the patients. In two patients, minor haemorrhagic transformation of the infarct occurred, which did not lead to neurological deterioration. It is concluded that in a selected group of patients with MCA occlusion, local thrombolytic therapy represents a safe and effective therapy.
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PMID:Local thrombolytic therapy for thromboembolic occlusion of the middle cerebral artery. 135 78

The effects of thrombolytic therapy in acute myocardial infarction are related exclusively to coronary arterial reperfusion. This is the main factor which influences myocardial salvage, the conservation of left ventricular function and, ultimately, the reduction in mortality. From the beginning of the 80s, the patency (or reperfusion) rate was arbitrarily assesses at 90 minutes. However, arterial reperfusion is a progressive phenomenon and the patency rate in a population of acute myocardial infarctions varies with time. Depending on the thrombolytic agent and the rate of administration, the patency increases at a variable rate attaining a plateau at the 4th-6th hour, the maximal patency being obtained between the 24th to the 48th hour. Therefore, assessing patency at the 90th minute of thrombolytic therapy is an approximate and relatively inaccurate method of assessing the efficacy of a given thrombolytic agent. When evaluating a thrombolytic drug administered at a certain dosage, the rate of reperfusion and the value and precocity of the plateau phase must be taken into account. The respective performances of different thrombolytics in terms of arterial patency are comparable. Nevertheless, the rate of reperfusion with Streptokinase given at the dose of 1.5 million i.v. in 60 minutes is lower than that obtained with more recent thrombolytic drugs. Streptokinase also appears to be less active on chronic thrombi. The late patency rate after the 24th hour is over 90% with nearly all thrombolytic drugs but it would seem to be less with rt-PA because of a higher reocclusion rate associated with this particular agent. The study of reocclusion requires control coronary angiography between the 24th and 72nd hour (7th day in some studies). The prevalence of this complication is influenced by several factors, especially the severity of residual stenosis after thrombolysis and the grade of perfusion obtained after the treatment: secondary reocclusion is significantly lower with long-acting and non-fibrin specific thrombolytic agents. It is approximately 2 to 5% with APSAC, Streptokinase and pro-urokinase, and two to three times greater with rt-PA. Finally, the use of more powerful antiplatelet drugs than those currently available and of specific anti-thrombin agents could reduce the rate of secondary reocclusion. Associations of thrombolytic agents, the development of thrombolytic chimera and new thrombolytic molecules could improve the efficacy of thrombolytic therapy in terms of capacity of reperfusion and tolerance, especially with respect to haemorrhagic complications.
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PMID:[Arterial permeability, objective of thrombolytic therapy]. 153 Apr 9

The reduction in morbidity and mortality associated with thrombolytic therapy in patients with acute myocardial infarction was initially attributed to early restoration of arterial patency, salvage of ischemic myocardium, and preservation of left ventricular function. Recombinant tissue plasminogen activator (rt-PA) was initially the favored thrombolytic agent because of selected studies showing superior early patency rates. Interestingly, averaged results of studies using conventional dosing regimens show 90-min patency rates for streptokinase, rt-PA, and anisoylated plasminogen streptokinase activator complex (APSAC) to be 53%, 68%, and 72%, respectively, suggesting that previous claims exaggerated differences in early patency. More recently, it was found that administering the full 100-mg dose of rt-PA within 90 min increased 90-min patency rates to approximately 85% and that infusing rt-PA plus urokinase or streptokinase halved reocclusion rates. These results again suggest the unrealized potential of rt-PA to offer a unique clinical benefit. However, three important recent trials have challenged the concept that early patency conveys a survival benefit by showing no difference in mortality in patients treated with different thrombolytic agents. Other trials have shown survival benefit in patients in whom patency of the infarct artery was achieved in a time frame beyond that in which myocardial salvage could be expected. The "open-artery hypothesis" suggests that survival may be more dependent on improved left ventricular remodeling and healing, increased electrical stability, and better myocardial perfusion than on infarct size reduction. In an attempt to determine whether 90-min patency or 24-h patency is more predictive of survival, the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial will randomize approximately 40,000 patients to (1) streptokinase and subcutaneous heparin; (2) streptokinase and intravenous heparin; (3) front-loaded, weight-adjusted rt-PA and intravenous heparin; or (4) the combination of streptokinase and rt-PA and intravenous heparin.
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PMID:Is survival in acute myocardial infarction related to thrombolytic efficacy or the open-artery hypothesis? A controversy to be investigated with GUSTO. 155 79

A functional assay for equine plasminogen was established, using urokinase as the activator, a synthetic chromogenic substrate, a computer-assisted centrifugal analyzer, and acidified/neutralized plasma. One documented effect of plasma acidification appears to be inactivation of alpha-2-antiplasmin. Intra- and interassay precision testing yielded coefficients of variation of 4.1% (n = 10) and 5.6% (n = 26), respectively. Plasminogen was stable in equine plasma stored up to 1 week at 4 C and up to 5 months at -70 C. Plasminogen in nonacidified equine plasma was not activated by urokinase, streptokinase, tissue plasminogen activator, or tissue plasminogen activator plus soluble fibrin. Streptokinase also failed to activate plasminogen in acidified/neutralized equine plasma.
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PMID:Chromogenic assay for equine plasminogen. 169 46

The thrombolytic and systemic effects of BM 06.022 were evaluated and compared with those of alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle-2 and protease domains of human tissue plasminogen activator (t-PA) and is unglycosylated because of its expression in Escherichia coli cells. Thrombus formation in anesthetized open chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery at a high level site of obstruction. In heparinized dogs, none of six vehicle-treated animals exhibited reperfusion. Reperfusion was achieved in four of six dogs at 18.3 +/- 6 min after intravenous bolus injection of 140 kU/kg (0.24 mg/kg) of BM 06.022, whereas four of six dogs exhibited reperfusion later (p less than 0.05) at 76.5 +/- 16.1 min during infusion of 1.33 mg/kg of alteplase (0.13 mg/kg as initial bolus injection, followed by 0.66 mg/kg over 1 h and 0.53 mg/kg over 2 h). Significantly later (p less than 0.05) reperfusion than that achieved with BM 06.022 was achieved in five of six dogs at 57.8 +/- 12.1 min after intravenous injection of 0.4 U/kg of anistreplase. Streptokinase (21,000 IU/kg over 60 min) and urokinase (20,000 IU/kg as an intravenous bolus injection, followed by 20,000 IU/kg over 89 min) each induced reperfusion in three of six dogs but at 67 +/- 12 and 84.3 +/- 17.1 min (p less than 0.05 vs. BM 06.022), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of thrombolytic and systemic effects of the novel recombinant plasminogen activator BM 06.022 compared with alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. 173 72

Three thrombolytic agents are frequently used in the United States for treating patients with acute myocardial infarction: streptokinase, alteplase (tissue plasminogen activator [t-PA]), and anistreplase (anisoylated plasminogen-streptokinase activator complex [APSAC]). A fourth agent, urokinase, is occasionally used but clinical experience is considerably more limited with this agent. Streptokinase, alteplase, and anistreplase differ in a number of pharmacologic properties, which include half-life, enzymatic efficiency, and induction of platelet aggregation; these differences may be clinically important. For example, anistreplase and alteplase have high affinity for fibrin and bind to intravascular thrombi after intravenous administration, which may result in higher clot specificity. Anistreplase has the longest half-life of the 3 agents and, therefore, can be administered conveniently and quickly. Alteplase has a shorter half-life and heparin is generally a necessary adjunctive agent. These differences can be clinically significant in various settings and application of such theoretical advantages is just beginning.
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PMID:Importance of the pharmacological profile of thrombolytic agents in clinical practice. 174 49

Intravascular aggregation of platelets was evaluated in relation to the fibrinolytic system in order to assess the possibility of a "cause-effect" relationship. The spontaneous fibrinolytic activities of the plasma of male rats and of female rats at the various stages of the oestrous cycle were determined. Male rats had higher euglobulin clot lysis time (54.5 +/- 5.3 vs 29.2 +/- 3.1 min; P less than 0.05), higher fibrinogen levels (330.0 +/- 15.8 vs 231.0 +/- 31.1 mg/dl; P less than 0.025) and higher plasminogen activity (8.1 +/- 1.2 vs 6.1 +/- 1.6 plasmin units/ml; P less than 0.05) than female rats. Female rats had higher fibrinolytic index (8.8 +/- 0.8 vs 6.3 +/- 0.3 mg/dl; P less than 0.05) and plasminogen activator activity (99.1 +/- 6.0 vs 76.5 +/- 7.7 Plough units/ml; P less than 0.05) than male rats. The antiplasmin activities were the same in both sexes. During the oestrous cycle in female rats, euglobulin clot lysis time was not significantly different though it was highest during met-oestrous (34.2 +/- 3.6 min). However, pro-oestrous rats had lower fibrinogen (122.9 +/- 5.3 mg/dl; P less than 0.005), higher fibrinolytic index (10.6 +/- 0.8 mg/dl/min; P less than 0.001) and higher plasminogen activator activity (109.4 +/- 7.8 Plough units/ml; P less than 0.05) than rats from the other stages of the oestrous cycle. There were no significant differences in plasminogen content and antiplasmin activity. Using native rats, aggregatory responses to submaximal doses of adenosine diphosphate (20 micrograms/kg) were determined and correlated with the fibrinolytic data in age- and weight-matched rats (of both sexes). Aggregatory responses in all the groups of rats used correlated positively with fibrinogen levels (r = 0.8316; P less than 0.001) and negatively with plasminogen activator activity (r = -0.7839; P less than 0.05). Streptokinase (250-1000 Plough units/kg/hr) and urokinase (1000-4000 Plough units/kg/hr) produced dose-related reductions in intravascular aggregation induced by adenosine diphosphate. The streptokinase effect (but not urokinase effect) was reversed by epsilon-aminocaproic acid. Following the cessation of infusion of streptokinase and urokinase, there was a recovery of the platelets to aggregate to adenosine diphosphate. These observations suggest fibrinolytic pathway-specific effects. However, on its own, epsilon-amino-caproic acid did not affect the aggregatory responses of platelets from pro-oestrous rats. These results suggest that changes in fibrinolytic mechanisms may account for differences observed in intravascular aggregation of platelets of male and female rats and of female rats during the oestrous cycle.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationship between gender difference in intravascular aggregation of platelets and the fibrinolytic pathway in the rat. 181 61


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