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http://ir.cmu.edu.tw/ir/handle/310903500/30225
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題名: | Serum IL-8 as a possible marker for determining the status of Helicobacter pylori infection in patients with untreated and treated peptic ulcer |
作者: | Cheng, KS;Tang, HL;Chou, FT |
貢獻者: | 醫學院醫學系;China Med Univ, China Med Univ Hosp, Coll Med, Dept Internal Med, Taichung 40421, Taiwan |
日期: | 2004 |
上傳時間: | 2010-09-24 14:51:27 (UTC+8) |
出版者: | HEALTH COMMUNICATIONS INC |
摘要: | Recent studies have suggested that dual inhibitors of cyclooxygenase (COX) and lipoxygenase (LO) may be more beneficial in the treatment of inflammatory diseases in which platelet-leukocyte interaction dominates the underlying inflammatory process, than inhibitors of COX or LO alone. In this study, we examined oxygenated xanthones, shown previously to inhibit platelet and neutrophil activation, with respect to the potency of COX inhibition. 1,3,6,7-Tetrahydroxyxanthone (norathyriol) was the most potent. Norathyriol suppressed thromboxane B-2 (TXB2) and leukotriene B-4 (LTB4) formation in calcium ionophore (A23187)- and formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated rat neutrophils. Norathyriol was 3-4 times more active against LTB4 formation than against TXB2 formation (IC50 about 2.8 vs. 10 muM, respectively). Norathyriol also inhibited prostaglandin D-2 (PGD(2)) formation in A23187-stimulated rat mast cells (IC50 3.0+/-1.2 muM) and in arachidonic acid (AA)-activated mast cell lysate. Norathyriol was a more effective inhibitor of 5-LO activity than of COX, as shown also by analyses of enzyme activities in a cell-free system, of COX and 5-LO metabolic capacity in neutrophils and of ex vivo TXB2 and LTB4 formation in A23187-stimulated neutrophils. Moreover, norathyriol inhibited COX-2 and 12-LO with IC50 values (19.6+/-1.5 and 1.2+/-0.1 muM, respectively) similar to those required for the inhibition of COX-1 and 5-LO (16.2+/-1.5 and 1.8+/-0.4 muM, respectively). Inhibition of 15-LO by norathyriol was slightly less active. Norathyriol had no effect on A23187-induced AA release from neutrophils and did not affect phospholipase A(2) (PLA(2)) activity in a cell-free system. These results indicate that norathyriol inhibits the formation of PGs and LTs in neutrophils probably through direct blockade of COX and 5-LO activities. Norathyriol, a single molecule with multiple targets, might provide a potential therapeutic benefit in the treatment of inflammatory diseases. |
關聯: | ADVANCES IN THERAPY 21(1):39-46 |
顯示於類別: | [醫學系] 期刊論文
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