The preparation of a urokinase-AT-III-PGE1-methyldopa complex, and its effects on platelet adhesion, coagulation times, protein adsorption, and fibrinolysis.
Modifications of urokinase by substances possessing useful therapeutic activity permit combined action preparations to be obtained. Here an attempt was made to develop a complex having combined action for therapeutic activity. The possibility of repeatedly modified urokinase with antithrombin-III-methyldopa-prostaglandin E1 had been experimentally demonstrated. The complex was immobilized on albuminated substrate, which showed fibrinolytic, anticoagulant, and antiplatelet effects simultaneously, in addition to the normal antihypertensive action of methyldopa. The complex immobilized substrate also demonstrated an increase in albumin-surface attachment and a reduction in fibrinogen binding. This may be one of the parameters for a reduced platelet-surface attachment, which may also improve the blood compatibility of the substrate. The approaches suggested indicate the possible new ways of creating nonthrombogenic surfaces with wider applications. A better understanding of the mechanism of these complexes are needed in in vivo conditions to correlate these findings.
Biosurface Technology Division, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojapura, Trivandrum, India.
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D000818:Animals; D000990:Antithrombin III; D001704:Biopolymers; D001777:Blood Coagulation / Q000187:drug effects*; D001798:Blood Proteins / Q000187:drug effects*; D001807:Blood Vessel Prosthesis; D002417:Cattle; D004343:Drug Implants; D004591:Electrophoresis, Polyacrylamide Gel; D005342:Fibrinolysis / Q000187:drug effects; D008750:Methyldopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011076:Polycarboxylate Cement; D011458:Prostaglandins E; D011474:Prosthesis Design; D013499:Surface Properties; D014568:Urokinase-Type Plasminogen Activator
D001704:Biopolymers; D001798:Blood Proteins; D004343:Drug Implants; D011076:Polycarboxylate Cement; D011458:Prostaglandins E; C005506:polycarbonate; D008750:Methyldopa; C037908:methyldopa pivaloyloxyethyl ester; D000990:Antithrombin III; D014568:Urokinase-Type Plasminogen Activator