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)

To identify patients at risk for immediate-type allergic reactions to streptokinase, we performed streptokinase skin tests on patients immediately before planned administration of intravenous streptokinase for treatment of acute myocardial infarction. Forty-five patients had negative skin tests and received streptokinase without allergic reaction. One patient had a positive skin test and was given urokinase instead, without incident. Positive skin tests were also present in a patient who had recently had an anaphylactic reaction to streptokinase, and in two physician volunteers who had been sensitized to streptokinase during initial determination of the optimal skin testing dose. Immunoassays for IgE to streptokinase were performed on serum samples from skin-tested patients and volunteers, and on 16 other patients who had not been skin tested but had previously received streptokinase without allergic reactions. The skin test was a sensitive and specific indicator of elevated levels of IgE to streptokinase. We propose that skin testing immediately before streptokinase administration is a practical approach for identifying patients at risk for immediate-type allergic reactions to streptokinase, and its use may possibly prevent anaphylaxis and death.
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PMID:Identification of patients at risk for anaphylaxis due to streptokinase. 394 91

Since serine protease in involved in histamine release from mast cells, we attempted to prepare new protease inhibitors, trans-4-(guanidinomethyl)cyclohexanecarboxylic acid (GmcHX-CO2H) esters, and examined their inhibitory effects on typical serine proteases and on histamine release induced by compound 48/80. We compared their effects with those of trans-4-(aminomethyl)cyclohexanecarboxylic acid (AmcHx-CO2H) esters. AmcHxCO2H and GmcHxCO2H esters inhibited the esterolytic activity of trypsin, but GmcHx-CO2H esters had little or no inhibitory effect on caseinolytic activity whereas AmcHxCO2H esters strongly inhibited the latter. AmcHCO2H esters strongly inhibited plasmin but had no effect on chymotrypsin. GmcHxCO2H esters strongly inhibited the esterolytic activity of chymotrypsin, but had no effect on chymotrypsin-induced caseinolysis. Both GmcHxCO2H an AmcHxCO2H esters inhibited urokinase. Of the esters of AmcHxCO2H and GmcHxCO2H tested, only GmcHxCO2H p-tert-butylphenyl ester (GmcHxCOOPhBut) at low concentration (27 microM) strongly inhibited histamine release from rat mast cells induced by compound 48/80. GmcHxCOOPhBut was effective in preventing active systemic anaphylaxis and passively sensitized guinea pigs. Its effectiveness in preventing anaphylactic phenomena might be due to its strong inhibitory effects on histamine release from mast cells.
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PMID:Inhibitory effects of aryl trans-4-(aminomethyl)cyclohexanecarboxylate and aryl trans-4-(guanidinomethyl)cyclohexanecarboxylate on serine proteases, and their antiallergic effects. 617 16

Central venous catheter (CVC) occlusion occurs frequently and remains a significant clinical problem in patients with cancer receiving infusional or intravenous chemotherapy. Thrombotic occlusions frequently limit the benefits of potentially curable cytotoxic agents by interrupting the delivery of infusion of chemotherapy, intravenous medication, nutritional support, and blood products, as well as the frequent acquisition of venous blood samples for laboratory testing. Urokinase has been used as a thrombolytic agent for dysfunctional occluded CVCs, but the alterations in manufacturing practice prompted the Food and Drug Administration to suspend further production of urokinase in 1999. Although streptokinase had a potential as a thrombolytic agent in place of urokinase, the risk of life-threatening anaphylaxis associated with this agent prompted researchers to look for newer agents to dissolve CVC occlusions. Several novel thrombolytic agents are currently being evaluated as a potential treatment for patients with CVC occlusions and acute or chronic peripheral arterial occlusions. Alfimeprase, a recombinant fibrinolytic zinc metalloprotease, has shown promising clinical utility in blood clot lysis in patients with CVC occlusions and peripheral arterial occlusions. Based on the encouraging data, alfimeprase has received orphan drug designation from the Food and Drug Administration and the Committee for Orphan Medicinal Products of the European Medicines Agency for the evaluation of acute peripheral arterial occlusions as a potential indication. Other novel thrombolytic agents such as alteplase and reteplase are undergoing clinical evaluation for their utility in restoring the function of occluded CVCs. The clinical potency of these novel agents and their ongoing clinical trials are discussed briefly herein.
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PMID:Clinical utility of novel agents in the treatment of central venous catheter occlusion. 1863 86