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 diagnosis of defibrination syndrome in shock, sepsis and neonatal hypoxia is based, in addition to the clinical picture, upon a few parameters of the hemostatic system, which, in part as global tests, provide information about the course of coagulation. The parameters measured are partial thromboplastin time, thromboplastin time, plasma thrombin time, fibrinogen, thrombin-coagulase and reptilase times as well as platelet count. Normal values of these laboratory parameters were established for healthy newborns 1--5 days of age, and for healthy adults. It is suggested that especially partial thromboplastin time, the thrombin-coagulase and reptilase times, the latter influenced by fibrinolysis cleavage products, are representative for the tentative diagnosis of disseminated intravascular coagulation with fibrinolysis syndrome (DICFS). The platelet fall often lags 1--2 days behind the event. Moreover normal values for newborns, are markedly higher than those for older children or adults. In the presence of DICFS, a low-dose heparin therapy is immediately initiated. If completed defibrination is manifest, therapy is supplemented with urokinase and streptokinase, For DICFS with congenital sepsis, an exchange transfusion with heparinized fresh blood is the treatment of choice.
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PMID:[Diagnostic therapeutic problems of defibrination syndrome in shock, sepsis, and neonatal hypoxia (author's transl)]. 32 24

Blood clotting and fibrinolytic systems were studied in the plasma of a sei whale (Balaenoptera borealis). The sei whale belongs to the suborder baleen whales of the order Cetacea. Whale plasma had a greatly prolonged kaolin-activated partial thromboplastin time and was deficient in Hageman factor (factor XII), Fletcher factor (a plasma prekallikrein), and PTA (factor XI). All other clotting factor activities were present in amounts comparable to that of normal human plasma. Whale plasminogen was activated by human urokinase, but not by streptokinase. Whale plasma contained inhibitory activities against thrombin, activated Stuart factor, activated PTA, activated Fletcher factor, and plasmin.
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PMID:Studies on the blood clotting and fibrinolytic system in the plasma from a sei (baleen) whale. 96 76

Optical density measurements of plasma clot formation and lysis were recorded using a platelet aggregometer and strip chart recorder. It was discovered that, by adding standard solutions of ellagic acid-activated partial thromboplastin, urokinase, and CaCl2, and monitoring the reaction via the recorder, characteristic curves would be generated by normal human plasma. The curve segments were labeled Tc (clotting time), which correlated with the activated partial thromboplastin time, Fc (maximum optical density change), which paralleled fibrinogen concentration, and Tl (lysis time), which corresponded generally to plasminogen levels. Deviations from normal curve segments, observed in disseminated intravascular coagulation, hypo- and hyperfibrinogenemia, factor VIII deficiency, severe hepatocellular disease, juvenile rheumatoid arthritis, and neonates (normally low in plasminogen), indicated abnormalities which were substantiated by standard procedures. This new test, given the acronym "CLUE" for clotting and lysis, urokinase enzyme activated, appears to be sensitive, inexpensive and easily performed on a sample of 0.2 ml. of plasma in only 15 minutes.
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PMID:The CLUE test. A multiparameter coagulation and fibrinolysis screening test using the platelet aggregometer. 111 Dec 77

Thirty-one patients (29 males and 2 females) with 34 thrombosed grafts were treated by direct intra-arterial infusion of urokinase; the lesions were acute in 27 cases and chronic (2-4 months) in 4. Urokinase was infused in doses of 50,000 UI/h. Angiographic follow-up exams were performed every 12 hours. The infusion was stopped when lumen patency was re-established and there was no significant mural thrombus or peripheral embolus. Treatment usually lasted 4-72 hours (average: 18 hours). The hematological status was controlled by measuring plasma fibrinogen, coagulation time, partial thromboplastin time, prothrombin and antiplasmin time. Initial success rate was 76% (23 patients). Overall 1-year patency was 56% in 23 cases: 85% in the patients with correctable lesions by means of surgery or PTA, and 46% in the patients with non-correctable lesions. After the first period, patency remained high in the patients followed up to 5 years. Our experience confirms that lysis of a thrombosed graft is possible by the local infusion of a low-dose fibrinolytic agent and exhibits high success rate and low complication rate in acute and chronic obstructions.
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PMID:[Loco-regional fibrinolysis in peripheral arterial bypasses. Our experience]. 163 28

All the thrombolytic agents currently in clinical use act as plasminogen activators. In this study evidence is presented that also oxidants of the phagocyte type are of fibrinolytic efficiency in vivo. Activated phagocytes participate in physiologic fibrinolysis. The cells generate plasminogen activators and reactive oxidants of the nitrogen-chlorine type. Experimental mimicry of this oxidative inflammatory response induces selective thrombolysis in a rabbit jugular vein model. Intravenous bolus administration of sub-millimolar blood concentrations of chloramine-T resulted in thrombolysis after about 30 min without notable systemic toxicity; the coagulation parameters activated partial thromboplastin time (aPTT), thrombin time, fibrinogen, and alpha-2-antiplasmin were not influenced. Control experiments with 2000 IU of urokinase/kg induced thrombolysis after about 90 min with systemic changes of the hemostatic system. The fibrinolysis promoting effect of the oxidants of the phagocyte type could be inhibited by quenchers of singlet molecular oxygen and was not affected at all by inhibitors of oxygen radicals. The data gives evidence that nonradical excited oxygen species (NEOS) act as powerful pro-fibrinolytic and anti-coagulant agents in vivo. It might be suggested that NEOS could represent a novel class of regulators of the fibrinolytic system. The long lived and hydrophilic chloramine derivatives can either accumulate or diffuse far from their site of generation. Therefore, on the one hand oxidants in high (local) concentrations might be considered as direct pro-fibrinolytic agents due to their powerful protein modulating efficacy. On the other hand, oxidants at low concentrations may act as indirect pro-fibrinolytic compounds, i.e. as chemoattractants to concentrate phagocytes to the site of a thrombus. In this case the oxidants would play the role of signal elements faraway from the thrombus, a self amplifying mechanism possibly mediated by oxidation of blood arachidonat/lipid metabolites.
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PMID:Nonradical excited oxygen species induce selective thrombolysis in vivo. 171 80

Umbilical artery catheterization is known to be associated with aortoiliac thrombosis in approximately 1% of newborns in whom catheters are placed. We describe a case of catheter-associated aortoiliac thrombosis in a newborn who was successfully treated by urokinase infusion. The infant was monitored by imaging studies followed by ultrasonography. The use of real-time ultrasonography enabled us to image this infant's aortoiliac thrombosis in an accurate, noninvasive manner and monitor the effectiveness of thrombolytic therapy. The fibrinolytic state was achieved with a combination of intravenous and intraarterial infusions of urokinase. Frequent measurement of prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time was used to guide fibrinolytic therapy. We reviewed the literature for similar cases of aortoiliac thrombosis in newborns; some were managed by medical means, others by operation. The success rate of the two approaches appeared to be approximately equal. Therefore we recommend the less invasive approach first--urokinase therapy--to be followed by surgical intervention if thrombolysis is unsuccessful.
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PMID:Urokinase treatment of neonatal aortoiliac thrombosis caused by umbilical artery catheterization: a case report. 194 79

Paeonia lactiflora with the action of promoting blood circulation and removing blood stasis had been shown to be able to inhibit thrombosis and platelet aggregation, increase fibrinolytic activity and promote thrombolysis. This paper described the influence of the extract of Paeonia lactiflora in vitro experiments on prothrombin time (PT), activated partial thromboplastin time (PTT), antithrombin effect, activity of plasminogen and urokinase. The experimental results showed that: (1) The extract of Paeonia lactiflora prolonged the time of PT and PTT. (2) The extract of drug was able significantly to inhibit the thrombin. (3) In study of fibrinolysis by fibrin standard plate experiments, the drug possessed activative effect on the plasminogen. (4) The activity of urokinase was reduced, while the extract of Paeonia lactiflora existed. The inhibitory effect on thrombin and effective effect on plasminogen of the drug might be an important mechanism of its action of promoting blood circulation and removing blood stasis.
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PMID:[Effect of an extract of Paeonia lactiflora on the blood coagulative and fibrinolytic enzymes]. 236 61

A highly selective inhibitor of plasma-kallikrein (PK), N-(trans-4-aminomethylcyclohexylcarbonyl)-L-phenylalanine 4-carboxymethyl-anilide hydrochloride, was designed and synthesized by the authors' group, called PKSI-527 in our laboratories. (I) PKSI-527 inhibited PK with a Ki value of 0.81 microM. By contrast, the Ki values for glandular kallikrein (GK), plasmin, thrombin, urokinase and factor Xa were greater than 500 microM, 390 microM, greater than 500 microM, 200 microM and greater than 500 microM, respectively. (II) Effects of PKSI-527 on bradykinin (BK) generation, coagulation and fibrinolysis by contact activation were examined using human plasma. (a) BK generation induced by kaolin appeared to be reduced by PKSI-527. Furthermore BK generation induced by lambda-carrageenan, a strong inflammatory agent, was also reduced by PKSI-527. (b) Partial thromboplastin time (PTT) was prolonged by PKSI-527, indicating the suppression of the intrinsic coagulation system. (c) Euglobulin clot lysis time (ECLT) of plasma which was shortened by activation with kaolin, was prolonged by the addition of PKSI-527, confirming the participation of PK in contact-fibrinolysis. These results indicate that PKSI-527 shows great potential in elucidating the significance of PK, and as such deserves further investigation.
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PMID:Effect of a highly selective plasma-kallikrein synthetic inhibitor on contact activation relating to kinin generation, coagulation and fibrinolysis. 238 57

Hetastarch, the currently marketed preparation of hydroxyethyl starch, affects coagulation by prolonging partial thromboplastin, prothrombin, and bleeding times; by lowering clotting proteins such as fibrinogen via hemodilution; by lowering clotting factor VIII (coagulant, von Willebrand antigen, and von Willebrand activity) to a greater degree than can be explained simply by hemodilution (i.e., presumably factor VIII affected by both hemodilutional plus additional, independent effects); and, finally, by shortening thrombin, reptilase, and urokinase-activated clot lysis times. Pentastarch, a new analog of hetastarch, was found to exert lesser effects on blood coagulation, despite its greater hemodiluting properties. When compared with hetastarch, pentastarch had little effect on factor VIII (except that due to hemodilution), shortened thrombin times to a significantly lesser degree, exerted no effect on the urokinase-activated clot lysis time, and did not prolong the bleeding time. Even when plasma hydroxyethyl starch levels were similar, pentastarch seemed to alter the results of coagulation assays to lesser degree than did hetastarch, which suggests the possibility of greater safety. Therefore, pentastarch may be a desirable drug, not only for leukapheresis, but also for plasma volume expansion in trauma and surgical patients who often have additional hemostatic abnormalities that place them at increased risk of hemorrhage.
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PMID:Pentastarch may cause fewer effects on coagulation than hetastarch. 245 88

We studied the effects of FR-860 on coagulative and fibrinolytic activities in human plasma compared to conventional unfractionated heparin (UF-heparin). Both FR-860 and UF-heparin dose-dependently prolonged the recalcification time, activated partial thromboplastin time, prothrombin time, factor Xa (F.Xa) clotting time and thrombin time. These effects of FR-860 were weaker than that of UF-heparin. FR-860 showed equipotent efficacy on the anti-F.Xa activity, and weak antithrombin activity compared to UF-heparin. FR-860 had no effects on the activity of ATIII and fibrinolytic activity. UF-heparin shortened the urokinase-activated euglobulin lysis time and showed antiplasmin activity, but did not influence the activities of ATIII, plasminogen and alpha 2-plasmin inhibitor. UF-heparin decreased the fibrinogen level at higher doses. These efficacies of FR-860 were weaker than that of UF-heparin. These results suggest that FR-860 is more efficient and lower in bleeding risk than UF-heparin in clinical use.
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PMID:[Effects of low molecular weight heparin (FR-860) on coagulative and fibrinolytic activities]. 261 5


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