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)

Vascular endothelial injuries induced by intravascular administration of radiographic contrast agents may be clinically relevant to the development of thrombosis and platelet activation. In this connection, we investigated the in vitro effects induced by iodamide, iopamidol, and ioxaglate on vascular endothelial ADPase activity and tissue plasminogen activator (t-PA) release in bovine aortic endothelium, in order to extend knowledge required to evaluate endothelial compatibility of radiographic contrast media. Undiluted and Tris-diluted contrast agent formulations were employed, and mannitol and sucrose hyperosmolar solutions were used as comparison. Results demonstrated that the high-osmolar ionic contrast agent iodamide, and to a lesser extent, the low-osmolar nonionic agent iopamidol, stimulated endothelial ADPase activity of the aortic endothelium; the low-osmolar ionic agent ioxaglate left endothelial ADPase activity unchanged. Furthermore, the diluted formulations of iodamide and iopamidol, as well as high-osmolar mannitol and sucrose solutions, were devoid of activity in ADPase. This suggests that the endothelial ADPase stimulation induced by both radiographic contrast media was a hyperosmolar-independent pharmacodynamic activity. Iopamidol and ioxaglate reduced endogenous t-PA release from bovine aortic endothelium only in undiluted formulation, while iodamide showed this inhibiting action in both diluted and undiluted formulations. No effect was observed when using mannitol solutions at different osmolarity values. Our in vitro findings agree with published data on the different thrombotic tendency attributed to the contrast agents used, suggesting endothelial enzymatic activities (ADPase and t-PA release) as suitable tools for evaluating endothelial vessel wall compatibility with radiographic contrast media.
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PMID:Modulation of ADPase and t-PA release by radiographic contrast media in bovine aortic endothelium. 929 6

To evaluate vascular and platelet compatibility of intravenous administration of beta-lactam antibiotics, we assessed the effects of therapeutic concentrations of ceftriaxone, aztreonam, and ceftazidime on platelet reactivity to different agonists (sodium arachidonate, collagen and adenosine diphosphate) and on selected vascular endothelial functions (adenosine diphosphatase activity, prostacyclin production and t-PA release). Ceftriaxone and, to a lesser degree, aztreonam, enhanced platelet reactivity, evaluated as onset of platelet aggregating response, and increased thromboxane production to subthreshold concentrations of arachidonate. There was no modification in platelet reactivity after ceftazidime treatment. Ceftriaxone and ceftazidime, but not aztreonam, inhibited endothelial adenosine diphosphatase activity. Prostacyclin production and t-PA release were inhibited only by ceftriaxone at high concentrations. While it is difficult to establish which marker (platelet or endothelial functions) has more clinical reference in human vascular compatibility, it seems feasible to consider aztreonam the most compatible of the beta-lactams studied.
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PMID:Beta-lactam antibiotic-mediated changes in platelet reactivity and vascular endothelial functions. 1139 90

In patients with acute myocardial infarction undergoing reperfusion therapy to restore blood flow through blocked arteries, simultaneous inhibition of platelet P2Y12 receptors with the current standard of care neither completely prevents recurrent thrombosis nor provides satisfactory protection against reperfusion injury. Additionally, these antiplatelet drugs increase the risk of bleeding. To devise a different strategy, we engineered and optimized the apyrase activity of human nucleoside triphosphate diphosphohydrolase-3 (CD39L3) to enhance scavenging of extracellular adenosine diphosphate, a predominant ligand of P2Y12 receptors. The resulting recombinant protein, APT102, exhibited greater than four times higher adenosine diphosphatase activity and a 50 times longer plasma half-life than did native apyrase. Treatment with APT102 before coronary fibrinolysis with intravenous recombinant human tissue-type plasminogen activator in conscious dogs completely prevented thrombotic reocclusion and significantly decreased infarction size by 81% without increasing bleeding time. In contrast, clopidogrel did not prevent coronary reocclusion and increased bleeding time. In a murine model of myocardial reperfusion injury caused by transient coronary artery occlusion, APT102 also decreased infarct size by 51%, whereas clopidogrel was not effective. These preclinical data suggest that APT102 should be tested for its ability to safely and effectively maximize the benefits of myocardial reperfusion therapy in patients with arterial thrombosis.
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PMID:Optimizing human apyrase to treat arterial thrombosis and limit reperfusion injury without increasing bleeding risk. 2523 97

The proteome composition of Russell's viper venom (RVV) from southern India (SI) was investigated by 1D-SDS-PAGE of venom followed by tandem mass spectrometry analysis of protein bands. A total of 66 proteins belonging to 14 snake venom protein families were identified by LC-MS/MS analysis against Viperidae (taxid 8689) protein entries from the non-redundant NCBI database. Phospholipase A2 (43.25%) and snaclec (14.57%) represented the most abundant enzymatic and non-enzymatic proteins, respectively. SI RVV was characterized as containing a higher quantity of PLA2 and a lower amount of Kunitz-type serine protease inhibitors, in comparison to RVV from other regions of the Indian subcontinent. The enzymatic activities, pharmacological properties, and clinical manifestations of RV envenomation in SI were well correlated with its proteome composition; however, ATPase, ADPase, and hyaluronidase enzymes were not identified by LC-MS/MS analysis, owing to paucity of the existing database. Neurological symptoms exhibited by RV-bite patients in SI were correlated to the presence of abundant neurotoxic phospholipase A2 enzymes (15.66%) in SI RVV. Neutralization studies, immunological cross-reactivity, and antivenomics studies unequivocally demonstrated the poor recognition and lowest neutralization of PLA2 enzymes by commercial polyvalent antivenom, which is a major concern for the treatment of RV-envenomed patients in SI.
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PMID:Quantitative proteomic analysis and antivenom study revealing that neurotoxic phospholipase A2 enzymes, the major toxin class of Russell's viper venom from southern India, shows the least immuno-recognition and neutralization by commercial polyvalent antivenom. 2992 81