<Originals>Mechanism of platelet rich plasma clot lysis with anticoagulant and antiplatelet agents
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概要
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Resistance of a platelets-rich thrombus to lysis limits the thrombolytic therapy by plasminogen activators. To clarify the influence of dextran sulfate and (E)-3- [p-(1H-imidazol-1-ylmethyl) phenyl]-2-propenoic acid upon thrombolysis, effects of these substances on clot lysis of platelet rich plasma (PRP) by urokinase-type plasminogen activator (u-PA) were studied. The extent of clot lysis was assessed as the time (t1/2) when the turbidity of clot reached to the half of the maximum. The t1/2 value was significantly shortened by dextran sulfate or (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl]-2-propenoic acid in a dose-dependent. Also, coexistence of dextran sulfate and (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl] -2-propenoic acid enhanced PRP clot lysis. Electrophoretic enzymography was showed that dextran sulfate enhanced u-PA activity in the purified system (118-121% of control), the one in euglobulin fraction (124-127% of control), and the one in euglobulin fraction with exogenous u-PA (148-151% of control). However, (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl]-2-propenoic acid did not affect u-PA activity (97-103% of control). The kinetic analysis of u-PA activity with S-2444 revealed that (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl] -2-propenoic acid did not affect u-PA activity. The electrophoretic enzymography and kinetic analysis suggested that dextran sulfate enhanced u-PA activity without contributing factor XII-prekallikrein system. The solubility of PRP clot by urea was decreased by (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl]-2-propenoic acid in a dose dependent. To evaluate density of clot, the value of maximal O.D.(max O.D.) during clot formation. The value of max O.D. was decreased by (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl]-2- propenoic acid in a dose-dependent, but was not by dextran sulfate. These results suggest that both dextran sulfate and (E)-3-[p-(1H-imidazol-1-ylmethyl) phenyl]-2-propenoic acid enhance PRP clot lysis additivity.
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