Prostanoids in nociception and pain

Prostaglandins are lipid mediators produced by cyclooxygenases from arachidonic acid, which serve pivotal functions in inflammation and pain. Inhibition of their production is the major analgesic mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs)-but also the source of most of their unwanted effects. While the development of selective inhibitors of inducible cyclooxygenase (COX)-2 (so called coxibs) has greatly reduced gastrointestinal side effects, the recent disappointment about a potential cardiovascular toxicity of COX-2-selective inhibitors has boosted interest in alternative targets. The discovery of several prostaglandin synthases and of distinct prostaglandin receptors has unraveled an unforeseen diversity within the prostanoid synthetic pathway. Behavioral and electrophysiological work in particular with genetically engineered mice meanwhile provides new clues to the role of different prostaglandins, prostaglandin synthases and prostaglandin receptors in pain pathways.     

The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[alpha]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs

Wild Panax ginseng C.A. Meyer (WG) is a well-known medicinal herb. In this study, the protective effects of a water extract from the root of WG on benzo[alpha]pyrene (BP)-induced hepatotoxicity and the mechanism of these effects were investigated for the first time. The effects of WG on liver toxicities induced by BP were assessed by blood biochemical and histopathological analyses. BP caused severe liver injury in rats, as indicated by elevated plasma ALT, AST and LPO levels. Pretreatment with WG for 4 weeks completely abrogated increases in the ALT, AST and LPO levels when challenged with BP. Reductions in GSH content and GST activity by BP were reversed by WG. These protective effects of WG against BP-induced toxicity were consistent with the results of histopathological examinations. We next examined the effects of WG on the gene expression of the enzymes that metabolize BP in H4IIE cells. CYP1A1 mRNA and protein expression were increased by BP. WG moderately inhibited BP-induced CYP1A1 gene expression. Moreover, GSTA2, GSTA3 and GSTM2 gene expressions were significantly increased by WG through the Nrf2/antioxidant responsive element pathway for enzyme induction. In summary, WG is efficacious in protecting against BP-induced hepatotoxicity as results of metabolic regulations through both the inhibition of metabolic enzyme activation and the enhancement of electrophilic detoxification, implying that WG should be considered a potential chemopreventive agent.     

Genome-wide analysis of phenobarbital-inducible genes in Drosophila melanogaster

An oligoarray analysis was conducted to determine the differential expression of genes due to phenobarbital exposure in Drosophila melanogaster (w(1118) strain) third instar larvae. Seventeen genes were observed to be induced with increased expression by a statistical analysis of microarrays approach with a q < or = 0.05. At q < or = 0.12, four more genes (Cyp12d1, DmGstd4, and two genes with unknown function) were found to be up-regulated, and 11 genes with unknown function were found to be down-regulated. Fifteen of these genes, Cyp4d14, Cyp6a2, Cyp6a8, Cyp12d1, Cyp6d5, Cyp6w1, CG2065, DmGstd6, DmGstd7, Amy-p/Amy-d, Ugt86Dd, GC5724, Jheh1, Jheh2 and CG11893, were verified using quantitative real time polymerase chain reaction. Some of these genes have been shown to be over-transcribed in metabolically DDT-resistant Drosophila strains.     

复合芦笋对体内谷胱甘肽转移酶及超氧化物歧化酶活性的影响

复合芦笋能显著提高小鼠、健康人、肿瘤病人体内ＧＳＴ、ＳＯＤ活性。小鼠连续饮用含复合芦笋４０，２０，１０ｍｇ／ｍｌ的水溶液１５ｄ后，取眼球血测定ＧＳＴ和ＳＯＤ活性，发现实验组比对照组活性明显提高（Ｐ＜０．０１）。６４例接触化学毒物的健康工人口服复合芦笋１８ｄ后，取静脉血测定ＧＳＴ和ＳＯＤ活性，自身比较服用后比服用前明显提高（分别为Ｐ＜０．０１和Ｐ＜０．０５）。２２例手术后肿瘤病人口服复合芦笋１８ｄ后，取静脉血测得ＧＳＴ和ＳＯＤ活性亦明显提高（Ｐ＜０．０５）。     

颞颌关节紊乱综合征各期患者滑液中细胞因子的研究 第2报 IL－6水平及其意义

检测了３６例临床诊断为颞下颌关节紊乱综合征（ＴＭＪＤＳ）各期（功能紊乱期、结构紊乱期、器质性改变期）患者关节滑液中白介素－６（ＩＬ－６）的活性。结果表明：ＩＬ－６活性与ＴＭＪＤＳ病变程度有关，随病情加重，ＩＬ－６活性增高。ＩＬ－６水平在一定程度上反映了关节内自身免疫反应的强弱。ＴＭＪＤＳ患者关节内在在的骨关节病（ＯＡ）病变使软骨中的封闭抗原暴露，诱发自身免疫反应并刺激产生了ＩＬ－６，升高的ＩＬ－６活性反过来通过增强自身免疫反应来加重ＴＭＪＯＡ病变，如此形成恶性循环。对ＩＬ－６的研究，有助于解决ＴＭＪＯＡ病程迁延、久治不愈的问题，从而使临床治疗更为有效。