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)

The efficacy of intrathrombic deposition vs. parathrombic infusion of urokinase (UK) and tissue-type plasminogen activator (t-PA) was investigated in a canine model. Gianturco coils were placed by transcatheter techniques into the iliac veins of 12 dogs. Venography obtained 48 hours later showed formation of large thrombi. After heparinization, UK (24,000-48,000 IU/ml) or t-PA (12,500-25,000 IU/ml) was spray-injected at high pressure throughout test clots every half-hour using a steel catheter with multiple side holes. Between injections, the agent was infused below the clots. The contralateral thrombi received an equivalent dose of fibrinolytic agent by continuous infusion. In six cases, plasminogen was injected into test clots prior to activator treatment. Thrombi spray-injected with either activator lysed in 64 +/- 26 minutes. Four of six thrombi treated with parathrombic urokinase infusion showed partial lysis after 133 +/- 50 minutes. After parathrombic infusion of t-PA, three clots showed complete lysis, one showed partial lysis, and two demonstrated no lysis. There was no significant difference in lysis rate between intrathrombic UK and t-PA nor did prior intrathrombic injection of plasminogen accelerate lysis. In summary, intrathrombic injection of highly concentrated UK or t-PA lysed subacute thrombi more effectively than parathrombic infusion.
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PMID:Fibrinolysis with intrathrombic injection of urokinase and tissue-type plasminogen activator. Results in a new model of subacute venous thrombosis. 310 98

A 36-year-old man with thoracic outlet syndrome, admitted to the hospital with digital ischemia from subclavian artery thrombosis and distal embolization, was given intra-arterial urokinase. Thrombus in the subclavian artery was lysed successfully and peripheral emboli were partially cleared, resulting in relief of digital symptoms. Although surgical decompression and vascular reconstruction at the thoracic outlet may be necessary, this technique provides a means of recanalizing small distal vessels.
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PMID:Treatment of a case of thromboembolism resulting from thoracic outlet syndrome with intra-arterial urokinase infusion. 335 71

The thrombolytic efficacy of defibrase (DF) and urokinase (UK) was evaluated and compared in a canine model in which left circumflex coronary artery (LCX) thrombus formation was initiated by electrical stimulation (150 UA, DC) of the arterial intimal surface via an implanted copper wire electrode. Forty-eight mongrel dogs were equally divided into 8 groups: six groups for both intravenous (iv) and intracoronary (ic) infusion of DF, UK and normal saline 30 min after complete obstruction by a LCX thrombus, the remaining two groups for iv infusion DF and UK 360 min after occlusion. Results showed that in the control groups no LCX recanalization after infusion occurred, but all the treated groups recanalized when drug infusion started 30 min after occlusion. Thrombus wet weight and infarct size were much higher in the control group. No significant differences were found between treated groups except that the recanalizing speed was fastest by ic UK with the highest occurrence rate of reperfusion arrhythmia. For 6-hour-old thrombi, DF was more effective than UK for recanalization. Thrombus wet weight and infarct size were lower in the recanalized dogs. Both agents reduced plasma plasminogen and fibrinogen significantly but serious incision bleeding was only found in the UK group. In order to study the mechanism underlying UK-induced hemorrhage, we observed the influences of UK and DF on blood coagulation factors in another 12 dogs. Results showed that DF only reduced factor 1 while UK additionally reduced coagulation factors 2, 7, 8 and 10, indicating that the non-selective depletive effect on coagulation factors may be one of the mechanisms of UK-induced hemorrhage. We conclude that both DF and UK can lyse fresh coronary thrombi, DF was more effective than UK on lysing older thrombi, considering its convenient use and less frequency of side effects, DF is therefore considered a more promising agent clinically.
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PMID:Comparison of the thrombolytic efficacy of defibrase and urokinase on canine coronary artery thrombosis and the mechanism of urokinase-induced hemorrhage. 349 37

A case of a 44 year old female with inferior vena cava thrombosis associated with cholelithiasis was reported. The patient had chest and back pain due to pulmonary embolism. Ultrasonic examination showed stone echoes in the gallbladder and thrombus echoes in the inferior vena cava (IVC) at the height from renal veins to bifurcation of iliac veins, but iliofemoral thrombosis was not found by RI angiography and venography. Anticoagulant and urokinase were administered, then pulmonary embolus disappeared and IVC thrombus reduced. IVC thrombus was removed by incision of IVC. Thrombus was white thrombus. Etiology of thrombus was not clear. IVC ligation or plication for prevention of pulmonary emboli was not carried out. Etiology, diagnosis and treatment of IVC thrombosis were also discussed.
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PMID:[A case of inferior vena cava thrombosis associated with cholelithiasis demonstrated by ultrasonic examination]. 352 16

Since thrombi continue to incorporate fibrin during lysis we tested the effect of pretreatment with ancrod, a defibrinating agent from Malaysian pit viper venom, on thrombolysis with urokinase and streptokinase. Thrombi were induced by copper-coils in the carotid arteries of the dogs, weighed after 1 hour and inserted into the femoral arteries of the same animals. They were then exposed for 15 min to iv boluses of streptokinase 10,000 U/kg, urokinase 10,000 U/kg and urokinase 25,000 U/kg with or without pretreatment with ancrod. Ancrod depleted fibrinogen within 5 min and enhanced the lytic effect of streptokinase from 25 +/- 8% to 59 +/- 13% (p less than .05), urokinase 10,000 U/kg from 16 +/- 11% to 66 +/- 18% (p less than .01) and urokinase 25,000 U/kg from 27 +/- 17% to 85 +/- 8% (p less than .001) of the initial thrombus weight. Ancrod itself did not activate plasminogen to plasmin. We conclude that ancrod enhances thrombolysis probably by depleting fibrinogen and preventing new fibrin incorporation into the thrombus during lysis.
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PMID:Ancrod enhances the thrombolytic effect of streptokinase and urokinase. 366 Mar 51

A simple venous thrombosis model in rabbits was used for the quantitative evaluation of the thrombolytic effect of human extrinsic (tissue-type) plasminogen activator as compared with urokinase.A thrombus was formed in an isolated segment of the jugular vein from a mixture of (125)I-labeled fibrinogen, whole rabbit blood, and thrombin. In order to immobilize the thrombus during lysis, it was formed around a woolen thread introduced longitudinally in the lumen of the vein. Thrombotic extension of the clot was prevented by subcutaneous injection of heparin. The extent of thrombolysis was measured as the difference between the radioactivity introduced in the clot and that recovered in the vein segment at the end of the experiment. In control animals the extent of thrombolysis was 5.6+/-1.4% (n = 5) after 6 h, 14.5+/-1.7% (n = 10) after 30 h, 16.0+/-1.5% (n = 11) after 78 h, and 48.1+/-2.7% (n = 10) after 174 h (mean+/-SEM). Extrinsic (tissue-type) plasminogen activator, highly purified from the culture fluid of a human melanoma cell line, was administered systemically or locally over a time period of 4 h and the percent thrombolysis measured 2 h after the end of the infusion. One- and two-chain extrinsic plasminogen activator had very similar thrombolytic potency. Systemic infusion resulted in a dose-dependent degree of thrombolysis. The activator-induced thrombolysis, after infusion of 100,000 IU ( congruent with1 mg protein), was approximately 75% for fresh clots, 35% for 1-d-old clots, 30% for 3-d-old clots, and 50% for 7-d-old clots. The thrombolytic activity of urokinase was more than five times lower than that of extrinsic plasminogen activator: Infusion of 500,000 IU resulted in approximately 40% lysis of fresh clots and 25% of 1-3-d-old clots, while 7-d-old clots appeared to have become resistent to urokinase. Local infusion resulted in a 5-10 times higher thrombolytic effect of both extrinsic plasminogen activator and urokinase. Thrombolysis with extrinsic plasminogen activator was not associated with systemic activation of the fibrinolytic system as evidenced by unaltered plasma levels of fibrinogen, plasminogen, and alpha(2)-antiplasmin. Systemic infusion of urokinase resulted in significant thrombolysis only at doses that were associated with disseminated plasminogen activation. Local infusion of urokinase required a 5-10-fold higher dose than extrinsic plasminogen activator to obtain a similar degree of thrombolysis, which also occurred in the absence of systemic activation of the fibrinolytic system. It is concluded that the extent of thrombolysis by extrinsic plasminogen activator is mainly determined by the dose of activator and its delivery in the vicinity of the thrombus and much less by the age of the thrombus or the molecular form of the activator. Extrinsic plasminogen activator appears to be superior to urokinase because of its higher (5-10-fold) specific thrombolytic activity and the absence of systemic activation of the fibrinolytic system, which results in defibrinogenation and a bleeding tendency.
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PMID:Thrombolysis with human extrinsic (tissue-type) plasminogen activator in rabbits with experimental jugular vein thrombosis. Effect of molecular form and dose of activator, age of the thrombus, and route of administration. 668 15

Thrombotic occlusion remains a major cause of central venous catheter removal prior to completion of therapy. Injection of a dilute solution of a potent fibrinolytic agent, urokinase or streptokinase, into the occluded Silastic central venous catheter consistently reestablishes its patency. This procedure was performed on 352 occluded silicone elastomer central venous catheters with only one failure and one minor complication. We recommend this technique for restoring patency of occluded silicone elastomer central venous catheters.
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PMID:Restoring patency of occluded central venous catheters. 735 37

Thrombotic obstruction of glomerular capillaries causes acute renal failure in patients with hemolytic-uremic syndrome (HUS). Recanalization of occluded vessels normally occurs by activation of the endogenous fibrinolytic system, mediated by plasminogen activators, which are stored and synthesized in the endothelial cells. However, endothelial injury is considered the primary event in the pathogenesis of HUS, and this may result in impaired fibrinolysis. In five children with HUS we performed a prospective study of plasminogen activator activity and two plasminogen activator antigens: tissue-type plasminogen activator and urokinase-type plasminogen activator before and after intravenous desmopressin. Plasminogen activator inhibitor type-1 antigen was also studied. In the acute stage of HUS plasminogen activating activity was low, in spite of elevated levels of total plasminogen activator antigens. This decrease of plasminogen activating activity was due to high levels of the plasminogen activator inhibitor. Improvement of fibrinolysis paralleled recovery from HUS. We conclude that decreased fibrinolysis is an important pathophysiologic feature of HUS.
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PMID:Impaired fibrinolysis in the hemolytic-uremic syndrome of childhood. 811 Aug 78

Thrombotic vascular occlusion may complicate the clinical course of many neonatal and pediatric pathologic processes. Systemic thrombolytic therapy with heparin, urokinase, or streptokinase may not be appropriate in the critically ill neonate because these agents generate a diffuse coagulopathic state. Direct surgical intervention for repair may be precluded by the small size of the vessels involved. Recombinant tissue plasminogen activator (rTPA) induces only a minimal proteolytic state while inducing thrombolysis within the local environment of the clot. We report our experience with regional rTPA infusion in four critically ill patients with venous and arterial thrombotic disorders. there were two brachial artery occlusive lesions--a neonate with iatrogenic occlusion due to a misplaced intravenous catheter and a 2-year-old child with inadvertent arterial ligation during an attempted venous cutdown. Two venous lesions consisted of a full-term neonate with renal vein/inferior vena caval thrombosis and a 32-week infant with partial superior vena caval thrombosis due to a Broviac catheter. Systemic thrombolytic therapy was contraindicated in these patients because of underlying illnesses. Pretherapy vascular evaluation included Doppler examination and angiography. The rTPA infusion was continued until there was evidence of clot lysis by ultrasound, angiogram, or venogram. Infusion rate of rTPA was adjusted according to fibrinogen levels. All three neonates responded successfully to rTPA therapy. Two neonates required only bolus administration and one responded to combined bolus and continuous infusion therapy after 58 hours. rTPA failed to reverse brachial artery occlusion in the 2-year-old child with purpura fulminans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant tissue plasminogen activator for neonatal and pediatric vascular thrombolytic therapy. 826 84

The purpose of our study was to assess the efficacy of external ultrasound to enhance in vitro thrombolysis with urokinase or streptokinase. One-hour-, 1-day-, 4-day-, and 6-day-old human blood thrombi (n = 366) were incubated in normal saline solution with three different concentrations of streptokinase (50, 250, and 2000 mu/ml) or urokinase (200, 2000, and 5000 mu/ml). Thrombi were exposed to pulsed ultrasound of 1 MHz at 1.0, 1.5 and 2.2 W/cm2 at different exposure times. The combination of ultrasound (2.2 W/cm2, 30 min) and urokinase or streptokinase enhanced lysis rate by an average of 25% compared with lysis with thrombolytic agents alone (p < 0.05). The enhancement was greater at higher ultrasound power outputs (2.2 W/cm2 > 1.5 W/cm2 > 1.0 W/cm2). At higher-power outputs there was no increase of temperature in the solution containing the thrombus. The extent of lysis was higher with longer ultrasound exposure time and with fresh thrombi. These data suggest that use of external ultrasound has the potential to increase both efficacy and rate of thrombolysis.
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PMID:Enhancement of thrombolysis by external ultrasound. 849 94


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