It has been suggested recently that cyclooxygenase-3, formed as a splice variant of cyclooxygenase-1, is the enzymatic target for acetaminophen. To investigate the relative roles of the putative three cyclooxygenase isoforms in different target tissues, we compared the inhibitory effects of acetaminophen, a cyclooxygenase-2-selective inhibitor; rofecoxib, a nonsteroid anti-inflammatory drug; na...

Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne proinflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates the central effects of circulating proinflammatory cytokines remain unclear. We hypothesized that proinflammatory cytokines act within the SFO to...

In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazolewith atypical structure-activity relationship was designed, synthesized, and biologicalevaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that althoughthe pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directlyattached to the central ring, it is in the sa...

In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazolewith atypical structure-activity relationship was designed, synthesized, and biologicalevaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that althoughthe pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directlyattached to the central ring, it is in the sa...

In this study, we use primary embryonic fibroblasts derived from cyclooxygenase-deficient transgenic embryos to further investigate the role of the two cyclooxygenases, cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), in the process of neoplastic transformation. Cells with either, neither, or both of the cyclooxygenases were transformed by Ha-ras and/or SV40. Our results show that when a ...