Prior work at Rice University and elsewhere has demonstrated the extreme importance of the shear field present in flowing systems in promoting platelet reactions. The shear field can modify and activate the platelet directly, in addition to the role of increasing mixing, platelet motion, and collisions. The proposed project is a basic study of platelet reaction rates and mechanisms under controlled conditions. Platelets and platelet aggregates will be subjected to known, controlled levels of shear stress in-vitro by means of a rotational viscometer. By means of optical probes developed in this research program. indices of (1) aggregation, (2) dense granule release, and (3) intracellular calcium ion concentration will be monitored continuously. Studies will be carried out on reactions in the presence of various agents, including arachidonic acid metabolites, are of potential value in increasing our understanding of vascular disorders involving platelets. A population balance mathematical analysis, previously developed in this research program, will be improved and extended and used to analyze the experimental results. Parameters will be derived which are directly related to the state of activation of platelets and aggregates. Analysis of these results will help elucidate the time scales and mechanisms of events of significance in cerebrovascular disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
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Chen, Pei-Feng; Wu, Kenneth K (2009) Two synthetic peptides corresponding to the proximal heme-binding domain and CD1 domain of human endothelial nitric-oxide synthase inhibit the oxygenase activity by interacting with CaM. Arch Biochem Biophys 486:132-40
Wu, Jui-Sheng; Cheung, Wai-Mui; Tsai, Yau-Sheng et al. (2009) Ligand-activated peroxisome proliferator-activated receptor-gamma protects against ischemic cerebral infarction and neuronal apoptosis by 14-3-3 epsilon upregulation. Circulation 119:1124-34
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Deng, Wu-Guo; Tang, Shao-Tzu; Tseng, Hui-Ping et al. (2006) Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding. Blood 108:518-24
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Lin, Teng-Nan; Cheung, Wai-Mui; Wu, Jui-Sheng et al. (2006) 15d-prostaglandin J2 protects brain from ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 26:481-7
Wu, Kenneth K (2006) Transcription-based COX-2 inhibition: a therapeutic strategy. Thromb Haemost 96:417-22
Liou, Jun-Yang; Aleksic, Nena; Chen, Shu-Fen et al. (2005) Mitochondrial localization of cyclooxygenase-2 and calcium-independent phospholipase A2 in human cancer cells: implication in apoptosis resistance. Exp Cell Res 306:75-84

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