Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Thrombotic occlusion is a frequent complication associated with the use of central venous catheters. The purpose of this study was to evaluate the efficacy of a continuous infusion of low-dose urokinase (200 U/kg/h) in clearing catheters that had not cleared after two bolus doses of urokinase in a pediatric oncology population. Fifty-eight incidents of catheter-related occlusions (49 Hickman-type catheters/nine implantable ports) as documented by radiographic dye study occurred in 227 pediatric oncology patients with 254 central venous catheters during a 1-year period. Fourteen of 58 catheters failed to clear after two bolus instillations of urokinase (5,000 U and 10,000 U). Thirteen catheters were treated for 24 hours with urokinase, 200 U/kg/h, and one catheter with urokinase, 100 U/kg/h for 24 hours. Twelve catheters were used for study. Coagulation studies were monitored preinfusion, 12 hours into the infusion, and postinfusion. Patency was reestablished in 11/12 catheters (92%) with a mean infusion time of 28.7 hours. No coagulation abnormalities or clinical bleeding associated with the urokinase infusion occurred. Only one patient exhibited a prolonged partial thromboplastin time (greater than 150 seconds); this was associated with a heparin effect. These data indicate that low-dose urokinase may be a safe and effective means to clear occluded central venous catheters in children.
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PMID:Continuous infusion of low-dose urokinase in the treatment of central venous catheter thrombosis in infants and children. 265 25

From May 1958 to May 1987, 428 upper extremities were replanted, with an overall survival rate of 87.4 percent. With the aim of increasing the survival rate a new method was tried. Unlike conventional continuous intravenous infusion, a Teflon catheter (28 gauge) was inserted into the proximal main artery of the anastomosed artery, and a daily dose of 80 ml comprising 240,000 U of urokinase, 40 micrograms of prostaglandin E1, 10,000 U (maximum) of heparin, and low molecular weight dextran was administered by means of continuous infusion for the 10 consecutive days, during which arterial thrombosis is likely to occur. Thirteen cases (replantations and damaged digital arteries) survived without any re-operation for arterial thrombus. There were statistically significant differences (p less than 0.025) in platelet count, fibrinogen, and AT III preoperatively and three days postoperatively. There were also statistically significant differences (p less than 0.05) in prothrombin time, partial thromboplastin time, and clotting time between pre-operative measurements and those taken four and 15 hr postoperative, but those data remained within normal range. No abnormalities were present in the arteries through which the catheter was inserted, as validated by postoperative digital subtraction angiography.
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PMID:Continuous local intra-arterial infusion of anticoagulants for digit replantation and treatment of damaged arteries. 272 24

The thrombolytic efficacy of recombinant single-chain urokinase-type plasminogen activator (rscu-PA) was studied in an open-chest canine model of coronary artery thrombosis. Dogs (n = 16) were anesthetized, a left thoracotomy performed, and a two cm segment of the left circumflex coronary artery was isolated and instrumented with an electromagnetic flow probe, an intracoronary stimulation electrode, and an adjustable mechanical occluder. Anodal direct current (100 microA) was applied to the stimulation electrode until thrombosis occurred (n = 14). After 30 min of thrombotic occlusion, rscu-PA was administered intravenously. Dogs were sacrificed either 6 h after thrombolysis or 6.5 h after initiation of rscu-PA when thrombolysis did not occur. In group A (30-50 micrograms/kg bolus rscu-PA + 20-40 micrograms/kg/min infusion rscu-PA for 30 min, n = 5) thrombolysis occurred in one case (20%) and this artery reoccluded. In group B (250 micrograms/kg bolus rscu-PA + 25 micrograms/kg/min infusion rscu-PA for 30 min, n = 6) all reperfused and only one reoccluded (16.6%). In group C (200 micrograms/kg bolus rscu-PA + 100 micrograms/kg/min rscu-PA infusion for 30 min, n = 2) both reperfused and neither reoccluded. Infarct size, determined as a percentage of left ventricle, was smaller when thrombolysis was followed by persistent reperfusion (n = 7), than when reperfusion did not occur (n = 4): 16.9 +/- 3.7% vs 31.3 +/- 2.2%, respectively (mean +/- SEM, p less than 0.02). If thrombolysis was followed by reocclusion, infarct size was 27.0 +/- 10.0%. In this study thrombolysis occurred when changes in prothrombin time, partial thromboplastin time, fibrinogen and fibrin split products were suggestive of systemic finbrinogenolysis. In conclusion, effective thrombolysis with rscu-PA appears to limit infarct size and to be accompanied by evidence of systemic fibrinolysis.
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PMID:Recombinant single-chain urokinase-type plasminogen activator (rscu-PA) induces thrombolysis and systemic fibrinolysis in a canine model of coronary artery thrombosis. 313 91

Tissue fibrin deposition may be an important component of inflammatory reactions. Current evidence suggests that intraalveolar procoagulant (PC) and plasminogen activator (PA) activities may be important determinants of local fibrin turnover in lung injury. In this study, we measured the PC and PA activities in cell-free bronchoalveolar lavage fluid (BALF) obtained from 17 patients with pulmonary sarcoidosis and 12 normal volunteers. Procoagulant activity was assayed by timing clot formation in a one-stage coagulation assay, and plasminogen activator activity was determined by measuring plasminogen-dependent lysis of [125I]fibrin. Mean PC activity in the sarcoidosis group was significantly elevated (102 +/- 25 versus 31.5 +/- 8.1 tissue thromboplastin units/ml; p less than 0.002), with 6 of 17 patient values beyond the 95% confidence limits of normals. These differences were not seen when PC activity was corrected for total protein in BAL. In contrast, PA activity tended to be lower in the sarcoidosis group (0.54 +/- 0.094 versus 0.643 +/- 0.106 Plough units/ml, p less than 0.3), and this difference became significant when PA was normalized to total protein (p less than 0.001). The ratio of procoagulant activity compared to plasminogen activator (PC/PA) was greater in the patients with sarcoidosis than normals (258 +/- 54 versus 40.3 +/- 6.4; p less than 0.001). The PC/PA ratios in 14 of 17 patients exceeded the 95% confidence limits of normals. In the sarcoidosis group, the PC/PA ratio correlated weakly with the number and percentage of lymphocytes retrieved by BAL. The plasminogen activator was a urokinase by molecular weight (53 kDa) and by comparing neutralization of PA activity by antibodies against urokinase and tissue plasminogen activator. The procoagulant was particulate and functioned as a factor X activator comprised of tissue thromboplastin and factor VII. We conclude that in pulmonary sarcoidosis, abnormal expression of procoagulant and plasminogen activator activities in alveolar fluid may favor accumulation of fibrin matrix at inflammatory foci.
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PMID:Procoagulant and plasminogen activator activities of bronchoalveolar fluid in patients with pulmonary sarcoidosis. 337 Dec 78

We have investigated here the coordinate expression of both procoagulant (PCA) and fibrinolytic (FA) activity of cells from 16 human ovarian carcinoma cases. To avoid interference of contaminating host cells, we used cells isolated in primary culture from ascitic fluid or from solid tumor. The FA was determined in cellular extracts by an amidolytic assay in the presence of fibrin monomers. FA, which was plasminogen dependent in almost all of the cases, showed a wide range of activity (from less than 0.001 to 2.30 UK units/mg protein). The molecular analysis of plasminogen activator (by SDS-PAGE and fibrin autography) showed a single molecular form of 52,000 daltons, inhibited by an antibody against human urokinase. PCA, studied with a one stage clotting assay in disrupted cells, was of tissue thromboplastin type in all instance and varied from 12.0 to 1300 thromboplastin units/10(4) cells. No simple correlation was found between FA and PCA in the cellular samples studied; moreover, for neither parameter was it possible to find any changes with the staging of the disease.
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PMID:Procoagulant and fibrinolytic activity of human ovarian carcinoma cells in culture. 373 46

Dipyridamole, an inhibitor of platelet aggregation, has been shown to have beneficial effects in disorders characterized by extravascular fibrin deposition. Mononuclear phagocytes are present in extravascular sites and are capable of expressing both plasminogen activator and procoagulant activities, which suggests these cells play a central role in extravascular fibrin turnover. We therefore sought to determine whether dipyridamole affects the expression of plasminogen activator and procoagulant activities by rabbit alveolar macrophages cultured in vitro. We found that dipyridamole (10 to 100 mumol/L) caused increases in both cell-associated and released plasminogen activator activity, which reached levels of 240% (P less than .05) and 543% (P less than .01) of controls, respectively. In contrast, dipyridamole decreased the cell-associated procoagulant activity of alveolar macrophages to as little as 21.3% of controls (P less than .01). Similar effects were seen in cells cotreated with lymphokines. The procoagulant activity expressed by these cells functioned as a tissue thromboplastin. The plasminogen activator of control and treated cells was a urokinase as determined by molecular weight characteristics (50 kilodaltons) and by antibody neutralization profiles using polyclonal antibodies against human urokinase and tissue plasminogen activator. These effects of dipyridamole could not be duplicated by structurally dissimilar agents sharing some of the pharmacological actions of dipyridamole; however, two pyrimidopyrimidine compounds structurally similar to dipyridamole effectively mimicked the effects on both procoagulant and plasminogen activator activities. We conclude that dipyridamole may have antithrombotic effects by directly modulating the role of mononuclear phagocytes in fibrin turnover. Thus, dipyridamole may be useful in situations where extravascular fibrin deposition is important to the pathogenesis of tissue injury and repair.
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PMID:Dipyridamole stimulates urokinase production and suppresses procoagulant activity of rabbit alveolar macrophages: a possible mechanism of antithrombotic action. 380 75

The pathophysiology of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is briefly discussed, and the efficacy, dosage and administration, laboratory monitoring, and adverse effects of thrombolytic agents, heparin, and warfarin are reviewed. Acute therapy of DVT and PE is usually initiated with intravenous heparin; however, thrombolytic agents such as streptokinase and urokinase may be preferred in patients with massive PE or severe DVT when clot lysis rather than clot stabilization is deemed necessary. For DVT or PE, an intravenous loading dose of streptokinase or urokinase is given, followed by a continuous infusion of the drug. Therapy with streptokinase is continued for 24 hours in patients with PE and for 72 hours in those with DVT; urokinase is continued for 12 hours in patients with PE. Monitoring of blood coagulation tests during thrombolytic therapy is recommended primarily for ensuring that a lytic state is achieved. Intravenous heparin is preferred for acute treatment of DVT or PE; controversy exists regarding whether administration by continuous infusion or intermittent bolus injection is superior. Heparin dosage is usually adjusted to maintain the activated partial-thromboplastin time (APTT) ratio between 1.5 and 2.5; however, the ideal therapeutic range has never been firmly established. After acute treatment with heparin, most patients should continue to receive either warfarin or subcutaneous heparin for several months to prevent recurrent thromboembolism. Bleeding is the major adverse effect of thrombolytic agents and anticoagulants. The risk of bleeding with heparin and warfarin therapy increases with excessive prolongation of the APTT and prothrombin time (PT), respectively. Future clinical trials should further define the role of thrombolytic agents in the treatment of DVT and PE and the efficacy of less-intense warfarin therapy for pulmonary embolism or arterial thromboembolic events.
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PMID:Pathophysiology and treatment of deep-vein thrombosis and pulmonary embolism. 389 Dec

Twenty-nine patients received intracoronary thrombolytic therapy for acute myocardial infarction 3.5 +/- 1.4 hours (mean +/- standard deviation) after the onset of pain. Ten patients received urokinase (UK) and 19 patients received streptokinase (SK). Laboratory variables of the coagulation system were measured before and immediately after therapy. When comparing patients in whom coronary artery recanalization occurred vs those in whom the artery remained occluded, those in whom recanalization was achieved had greater alterations in fibrinogen, prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products and plasminogen by thrombolytic therapy than did those in whom recanalization was not achieved (p less than 0.05 for all variables). Euglobulin lysis time showed a similar but nonsignificant trend (p = 0.114). Patients who received SK showed markedly greater alterations in coagulation parameters than did patients treated with UK (p less than 0.05 for 5 of 6 variables measured) and had a much higher incidence of successful thrombolysis (74% for SK, 20% for UK). These data indicate that the development of a systemic fibrinolytic state contributes to success when using intracoronary thrombolytic agents in acute myocardial infarction. Rather than being considered an adverse effect of therapy, a systemic lytic state may serve as a reasonable clinical goal in attempting to produce thrombolysis.
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PMID:Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state. 403 24

A model was experimentally made with 2 hours serial infusion of thromboplastin (Tp) into rabbits to examine the drug's effect on a hemorrhagic tendency and to elucidate the coagulation and fibrinolytic system in acute DIC encountered in obstetrics, and the system was periodically observed. Groups given the drug, given it during pregnancy, those which bled massively, and those with accelerated fibrinolysis were prepared. The results are as follows. 1) Fibrinogen, PT, APTT, TEG, ELT, AT-III, antiplasmin activity, and platelet count varied markedly from the initiation of Tp injection, and returned to normal following termination. 2) Blood from the heparin dose group showed non-coagulation but decreases in the platelet count and fibrinogen were inhibited. 3) In the aprotinin dose group, serial 2 hour administration induced inhibition of fibrinolysis despite the relatively delayed appearance of anti-fibrinolytic activity. 4) No fibrinolytic effects were seen in anti-plasmin activity or ELT in the tranexamic acid dose group. 5) Lowering of parameters examined was marked in the Tp dose group during pregnancy. 6) The mortality rate up to 6 hours after Tp infusion was 54.5% with solely given, and 10% with group given drug. 7) Death within one hour of Tp infusion in the mass bleeding group, being rated for 50%, was improved to 16.7% by the pre-administration of urokinase.
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PMID:[Treatment of obstetrical disseminated intravascular coagulation--sequential changes of coagulation and fibrinolytic system in DIC rabbits]. 618 25

The function of fibrinolysis is to dissolve fibrin clots. The agent of fibrinolysis is plasmin, a glycoprotein with gram molecular weight (GMW) of 90,000. Under natural conditions, plasminogen is converted to plasmin by tissue plasminogen activator (TPA). Activation occurs on the fibrin surface, thus confining proteolytic activity to the appropriate site. Tissue plasminogen activator, produced by monoclonal methods, has recently been made available for limited therapeutic use. Currently streptokinase and urokinase are widely used therapeutically to activate plasminogen. These agents cause plasmin to be formed which is free in the circulation as well as bound to fibrin, resulting in proteolysis of circulating plasminogen and clotting factors. Fibrinolytic therapy has proven to be more beneficial than anticoagulation alone for deep vein thrombi and for pulmonary emboli. During therapy, laboratory studies demonstrate reduced concentrations of plasminogen, fibrinogen, and of alpha-2 plasmin inhibitor, and prolongation of activated partial thromboplastin time and thrombin time. Laboratory findings must be correlated with the clinical course. Demonstration of circulating plasmin-antiplasmin complex may be a useful indicator of active fibrinolysis.
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PMID:Fibrinolysis--a review. 623 87


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