To cite this article: Wang J-S, Chow S-E, Chen J-K. Strenuous, acute exercise affects reciprocal modulation of platelet and polymorphonuclear leukocyte activities under shear¯ow in men. J Thromb Haemost 2003; 1: 2031±7.Summary. Vigorous exercise transiently increases the risk of primary cardiac arrest. The reciprocal modulation of platelet and polymorphonuclear leukocyte (PMN) activities is important in the pathogenesis of thrombosis. This study investigates how strenuous, acute exercise affects platelet±PMN reciprocal modulation by closely examining 18 sedentary men who exercised strenuously on a bicycle ergometer. Shear-induced platelet activation, PMN interaction with surface-adherent platelets under shear¯ow, and PMN-dependent inhibition of platelet activation were measured both before and immediately after exercise. Analytical results can be summarized as follows: (i) shear-induced platelet adhesion on ®bronectin-coated surface as well as ADP-induced release of platelet soluble Pselectin release and elevation of [Ca 2 ] i signi®cantly increases after strenuous exercise; (ii) strenuous exercise is associated with higher velocity and percentage of rolling PMNs and lower numbers of PMNs remaining bound to surface-adherent platelets under shear¯ow than at rest; (iii) PMN-dependent inhibition of platelet [Ca 2 ] i elevation and soluble P-selectin release after strenuous exercise is much greater than that at rest; and (iv) strenuous exercise increases PMN-derived nitric oxide metabolite level and reduces oxidized low-density lipoprotein-promoted interaction between platelets and PMNs. Therefore, we conclude that platelet activity may be sensitized by strenuous exercise. However, strenuous exercise can also simultaneously enhance the antiplatelet effect of PMNs. The ®nding provides a new insight into the negative feedback of PMNs against exercise-evoked platelet-related thrombotic risk.

DNp63, the N-terminal truncated isoform of p63, has been found to be overexpressed in several human epithelial cancers, including nasopharyngeal carcinomas (NPCs), suggesting a function in carcinogenesis. Trans-resveratrol (RSV) has been shown to exert proapoptotic activities through a p53-dependent or p53-independent pathway in various cancer cells. However, the effects of RSV on NPC are still unexplored. In this study, we investigated the apoptotic effects of RSV on DNp63-overexpressing NPC cell lines. We showed that RSV (12-100 mM) induced dose-dependent growth suppression, cell-cycle arrest in the S phase and caspasedependent apoptosis in NPC-TW076 and NPC-TW039 cells. The RSV effect was accompanied by the downregulation of DNp63 and the upregulation of p53 protein in a dose-dependent manner. By using small-interfering RNA (siRNA) technology, we found that the targeted silencing of DNp63 induced apoptosis and sensitized the NPC cells to RSV-induced apoptosis through caspase-3 activation, whereas suppression of p53 by siRNA did not inhibit RSV-induced apoptosis. Furthermore, transfection with p53 siRNA or pretreatment with caspase inhibitors (Z-VAD-fmk or Z-DEVD-fmk) had no influence on the RSV downregulation of DNp63. Interestingly, ecoptic expression of DNp63 did not significantly block RSV-induced cell death and was also downregulated after RSV treatment. Downregulation of DNp63 by RSV was shown to occur at the mRNA transcript and post-translational levels. Importantly, RSV enhanced chemotheraptic drug-induced apoptosis in NPC and two human carcinoma cell lines, HT1376 and Hep3B cells. These results suggested that DNp63, but not p53, is a molecular target of RSV-induced apoptosis and the regulation of DNp63 expression by RSV may provide a therapeutic effect of RSV in human NPC.