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)

Eleven patients with systemic sclerosis (SSc) were studied for plasma and cutaneous fibrinolytic activity, residual (potential fibrinolysis) fibrinolytic activity (FA) fo the dermal vessels that is related to the endothelial storage of plasminogen activators that become available due to particular stimuli such as intradermic injection of histamine, and the serum levels of circulating von Willebrand antigen, antithrombin III, plasminogen, beta-thromboglobulin, and platelet aggregate ratio (PAR). Cutaneous FA (autohistographic fibrin film method) appeared normal or increased in non-affected skin, normal in lesional skin, and increased after intradermal (i.d.) injection of 0.1 ml of 0.01% histamine. Monoclonal antibodies directed against the catalytic site of tissue type plasminogen activator completely blocked the fibrinolytic activity, while anti-urokinase antibodies did not abolish the lysis areas. Plasmatic FA, euglobulin lysis time test, (ELT) and the levels of beta-thromboglobulin resulted similar to the controls. A significant increase in von Willebrand Factor VIII antigen (but not of Factor VIII coagulant) was observed in the patients (p less than 0.01). Platelet aggregate ratio, levels of plasma plasminogen and Antithrombin III showed a significant difference (p less than 0.01) when compared with the control subjects. Data suggest that primary injured microvessels in SSc are likely to be arteriolae while venulae could be affected by secondary hypoxia due to the arteriolar damage with consequent release of tissue type plasminogen activator. Therefore, the authors suggest that the fibrinolytic potential is maintained in SSc and that the fibrinolytic therapy should not be used in all patients with SSc but only in those cases with documented exhaustion of plasmatic and/or cutaneous FA.
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PMID:Cutaneous and plasma fibrinolytic activity in systemic sclerosis. Evidence of normal plasminogen activation. 212 82

To evaluate the availability of the fibrinolytic system in patients suffering from acute respiratory distress syndrome, ARDS, induced by septicemia or trauma, the following parameters were analysed: fibrinogen, FG, antithrombin III, AT III, plasma prekallikrein, PPK, plasminogen, PG, alpha 2-antiplasmin, alpha 2-AP, alpha 2-macroglobulin, alpha 2-MG, urokinase-inhibitor, UK-I, streptokinase-inhibitor, SK-I, C1-inhibitor, C1-I, alpha 1-antitrypsin, alpha 1-AT, and fibrinogen-fibrin degradation products, FDP. Survivors and non-survivors of septicemia induced ARDS showed a characteristic feature: marked increase of FG and pronounced decrease of AT III and PPK in the coagulation system; concerning the fibrinolytic system a decrease of PG, alpha 2-AP and alpha 2-MG as well as an increase of inhibitors of PG-activators (PG-antiactivators) UK-I, SK-I, C1-I and alpha 1-AT; the FDP-titer was elevated. This constellation of parameters is interpreted as indicative of a marked procoagulant stimulation rendering the organism a state of hypercoagulability coinciding with a diminished availability of the fibrinolytic system, due to exhaustion of the fibrinolytic potential and increase of PG-antiactivators. In the trauma group initially the rise of FG, SK-I, C1-I and alpha 1-AT is absent independent of the outcome, but develops with progression of the disease. As ARDS is more frequently associated with septicemia, diminished availability of the fibrinolytic system simultaneously with increased procoagulant stimulation may be a particular pathophysiologic mechanism in the pathogenesis of ARDS.
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PMID:Fibrinolysis inhibition in acute respiratory distress syndrome. 386 24

This report describes a plasmatic, fast-acting, specific inhibitor (antiactivator) of tissue-type plasminogen activator (t-PA) and urokinase (UK). After addition of t-PA to human plasma, biexponential decay of activity occurred. The initial rapid inhibition of t-PA activity (half-life of approximately one minute) was correlated with the formation of a complex of a molecular weight of 110,000, suggesting a molecular weight in the order of 40,000 for the antiactivator. Diisopropylfluorophosphate (DFP)-inactivated t-PA did not form complexes with antiactivator. The second-order rate constant for the interaction of t-PA with antiactivator is in the order of 10(7) mol/L-1 sec-1. In plasma, UK added at low concentrations rapidly formed complexes of a mol wt of 95,000. Preincubation of the plasma with t-PA prevented complex formation of UK, and vice versa, suggesting that the same inhibitor inactivates both t-PA and UK. After exhaustion of the antiactivator, t-PA and UK formed complexes with alpha 2-antiplasmin and C1'-inhibitor at a low rate.
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PMID:Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma. 643 6

Kinetics of lysis of human plasma clots immersed in plasma were studied in vitro at 37 degrees C under the influence of recombinant staphylokinase, single-chain urokinase-type plasminogen activator (scu-PA), and their simultaneous and consecutive combinations. Staphylokinase and scu-PA caused concentration- and time-dependent lysis of the clots; 32 nM staphylokinase and 75 nM scu-PA separately caused 50% lysis in 4 h. At these equally effective concentrations staphylokinase in 4 h induced a significantly lesser exhaustion of the plasma plasminogen, alpha(2)-antiplasmin, and fibrinogen than scu-PA. Combinations of staphylokinase (<30 nM) and scu-PA (<75 nM) rendered synergic thrombolytic action on the clots. The synergy of thrombolytic action was more pronounced on the simultaneous addition of the two agents than on their consecutive addition, scu-PA 30 min after staphylokinase. In 4 h after the addition, staphylokinase (25 nM) or scu-PA (15 nM) induced 24% and 2% lysis, respectively, whereas the simultaneous and consecutive combination of the same concentrations of these agents induced 58% and 50% lysis, respectively. The simultaneous combination of 15 nM staphylokinase and 15 nM scu-PA resulted in maximal 3.8-fold increase in the thrombolytic effect as compared to the expected total effect of the individual agents. Synergic combinations of the two agents caused lesser exhaustion of plasma plasminogen, alpha(2)-antiplasmin, and fibrinogen as compared with the expected total effect of these agents used separately. Thus, simultaneous and consecutive combinations of staphylokinase and scu-PA in a relatively narrow range of their concentrations possessed synergistic fibrin-selective thrombolytic action on the plasma clot in vitro.
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PMID:Synergy of in vitro thrombolytic action of combinations of recombinant staphylokinase and single-chain urokinase-type plasminogen activator. 1464 Sep 69