Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reocclusion following thrombolysis is a major limitation of thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA). We investigated the effects of vapiprost ((1R-(1 alpha(Z),2 beta,3 beta,5 alpha))-7-(5-((1,1'-biphenyl)-4-yl-methoxy)- 3-hydroxy-2-(1-piperidinyl)cyclopentyl)-4-heptenoic acid, a thromboxane A2 receptor antagonist); argatroban ((2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfon yl] - L-arginyl)]-2-piperidine-carboxylic acid, a specific thrombin inhibitor) and MK-886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2- dimethylpropanoic acid, a specific leukotriene biosynthesis inhibitor) on the thrombolytic efficacy of rt-PA. The guinea pig femoral artery was thrombotically occluded by photochemical reaction between rose bengal and green light. Thirty min after the occlusion, rt-PA was administered and the time (T1) for reopening of the vessel and the frequency of reocclusion (Fro) 24 h after thrombolysis were monitored. With rt-PA alone, T1 was 28 +/- 7 min (n = 10) and Fro was 70%. T1 was reduced to 9 and 20 min by a combination of rt-PA with vapiprost and argatroban respectively. Fro was reduced by all three adjuvants. Histological observations revealed extensive adherence of polymorphonuclear leucocytes to the damaged endothelium at the site of thrombolysis. It is concluded that thromboxane A2, thrombin and leucocytes are involved in reocclusion after thrombolysis.
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PMID:Enhancement of thrombolytic efficacy of tissue-type plasminogen activator by adjuvants in the guinea pig thrombosis model. 785 82

Effects of (2R,4R)-4-methyl-1-[N(2)-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidine-carboxylic acid monohydrate (argatroban) and unfractionated heparin (UFH) were compared with respect to thrombus formation and tissue-type plasminogen activator (t-PA)-induced thrombolysis in a microvasculature thrombosis model. The antithrombotic activities of anticoagulants were evaluated with respect to the time required for the initiation of thrombus formation (T(i)) and the time required for the thrombus to stop blood flow (T(s)). The effects of anticoagulants administered with t-PA were evaluated by percent stenosis of the vessel and percent area of the thrombus. Argatroban (1-3 mg/kg/bolus) significantly prolonged T(i) and T(s) in a dose-dependent fashion compared to control. Argatroban (3 mg/kg/bolus) significantly prolonged both the T(i) and T(s) more effectively than UFH (100 anti-XaU (a-XaU)/kg/bolus), despite equivalent prolongation of the activated partial thromboplastin time (aPTT). Higher doses of UFH (300-500 a-XaU/kg) were required to significantly prolong T(i) and T(s), but at these doses, UFH caused over-prolongation of aPTT (>180 s), which might consequently cause bleeding complications. Argatroban (0.1-0.3 mg/kg/h) significantly accelerated thrombolysis by t-PA in both a dose- and time-dependent fashion. Although argatroban (0.1-0.2 mg/kg/h) did not significantly prolong the aPTT and bleeding time (BT) as compared with control, it significantly accelerated thrombolysis by t-PA at these doses of lower bleeding risk. Argatroban (0.3 mg/kg/h) significantly enhanced thrombolysis by t-PA, while UFH (12.5 anti-XaU/kg/h) attenuated it again, despite equivalent prolongation of the aPTT and BT. We conclude that argatroban seems to be a more efficient and safer anticoagulant than UFH for the prevention of thrombus formation and acceleration of t-PA-induced thrombolysis.
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PMID:Effects of argatroban and heparin on thrombus formation and tissue plasminogen activator-induced thrombolysis in a microvascular thrombosis model. 1267 32

Herein we report the synthesis and characterisation of a series of salalen and salan ligands derived from 2-(aminomethyl)piperidine. Depending on the choice of starting salicylaldehyde, a bicyclic salan type ligand (1-3H2) or imino salalen type ligand (4-6H, 7-9H2) were prepared. The ligands were successfully complexed to group 4 metals and aluminium; with hafnium and zirconium octahedral complexes, M(1-3)2, were realised; whilst with aluminium tetrahedral and trigonal bipyramidal complexes, Al(1-9)Mex (x = 1,2), were isolated. The complexes have been characterised in solution via(1)H and (13)C{(1)H} NMR spectroscopy and in the solid state by X-ray crystallography. The group 4 complexes were observed to have a fac-fac arrangement of ligands and there were two isomers present when 3H2 was ligated. The imino aluminium complexes Al(7-9)Me were isolated as a mixture of diastereoisomers. The resultant complexes were trialed in the ring opening polymerisation of rac-lactide with both heterotactic and isotactic PLA being demonstrated. Tacticity was found to be dependent on the nature of the ligand and metal used; the M(1-3)2 complexes were generally found to have a heterotactic preference (Pr = 0.67-0.76) and the aluminium polymerisation outcome was dictated more by the steric influence of the ligand, particularly for Al(4/6)Me2/Al(7/9)Me.
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PMID:Aminopiperidine based complexes for lactide polymerisation. 2690 43