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131.
Donglu Zhang Marc Ogan Richard Gedamke Vikram Roongta Renke Dai Mingshe Zhu J Kent Rinehart Lewis Klunk James Mitroka 《Drug metabolism and disposition》2003,31(7):837-845
(3S)-(+)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one) (MaxiPost, BMS-204352) is a potent and specific opener for maxi-K channels and has potential to prevent and treat ischemic stroke. Following single intravenous doses of [14C]BMS-204352 to rats, only 10 to 12% of radioactivity was extractable from plasma with organic solvents. The unextractable radioactivity remained associated with the proteins (mostly albumin) after SDS-polyacrylamide gel electrophoresis or dialysis. Following acid hydrolysis in 6 M HCl for 24 h at 110 degrees C from plasma proteins collected from nine rats dosed with [14C]BMS-204352, one major radioactive product was isolated and identified as a lysine-adduct of des-fluoro des-O-methyl BMS-204352 by liquid chromatography/mass spectrometry and NMR analyses as well as by comparison with the synthetic analog, lysine-adduct of des-fluoro BMS-204352 (BMS-349821). The covalent binding of BMS-204352 results from the displacement of the ring-fluorine atom of des-O-methyl BMS-204352 with the epsilon-amino group of a lysine residue. Microsomal incubations of [14C]BMS-204352 resulted in low levels of covalent binding of radioactivity to proteins. This in vitro covalent binding required cytochrome P450-reductase cofactor NADPH and was attenuated by glutathione. P4503A inhibitors ketoconazole and troleadomycin selectively prevented the covalent binding in vitro. Based on these observations, a two-step bioactivation process for the protein covalent binding of BMS-204352 was postulated: 1) P4503A-mediated O-demethylation leading to spontaneous release of HF and the formation of an ortho-quinone methide reactive metabolite and 2) nucleophilic addition of the epsilon-amino group of protein lysine residue(s) in protein to form des-fluoro des-O-methyl BMS-204352 lysine adduct. 相似文献
132.
Population-based case-control study of CYP11A gene polymorphism and breast cancer risk. 总被引:9,自引:0,他引:9
Wei Zheng Yu-Tang Gao Xiao-Ou Shu Wanqing Wen Qiuyin Cai Qi Dai Jeffrey R Smith 《Cancer epidemiology, biomarkers & prevention》2004,13(5):709-714
The CYP11A gene encodes the cholesterol side-chain cleavage enzyme (P450scc) that catalyzes the first and rate-limiting step for the biosynthesis of sex hormones. A pentanucleotide repeat [(TAAAA)n] polymorphism in the 5' of the CYP11A gene has been reported to be related to the risk of polycystic ovary syndrome, an inherited endocrine disorder characterized by hyperandrogenemia. We investigated the association of this polymorphism with breast cancer risk in a population-based case-control study conducted among Chinese women in Shanghai. Genotype assays were completed for 1015 incident breast cancer cases and 1082 community controls. Three common alleles with 4, 6, or 8 TAAAA repeats were identified in the study population. The frequency of the 8 repeat allele was more common in cases (12.6%) than controls (8.5%) (odds ratio = 1.6, 95% confidence interval = 1.3-1.9; P < 0.0001). Compared to subjects who did not carry this allele, adjusted odds ratios were 1.5 (95% confidence interval = 1.2-1.9) and 2.9 (1.3-6.7) (P for trend, <0.001), respectively, for those who carried one and two copies of this allele. This positive association was observed in both pre- and postmenopausal women and all strata defined by major breast cancer risk factors, including years of menstruation, body mass index, and waist-to-hip ratio. The results from this study indicate that the TAAAA repeat polymorphism near the promoter region of the CYP11A gene may be an important susceptibility factor for breast cancer risk. 相似文献
133.
Purpose To observe therapeutic effect of electroacupuncture Neixiyan (Ex-LE 4) and Dubi (ST 35) in treating osteoarthritis of knee
joint.Method All the 120 cases were randomly divided into electroacupuncture and control groups, 60 cases in each group, and they were
given electroacupuncture and Ritalin slowreleased tablet respectively, and pain, mobility and swelling degree of knee joint
were observed before and after treatments.Results In treatment group, the average score increased by 18, while in control group, it increased by 12.33 (P<0.05) after treatment.Conclusion Therapeutic effect of electroacupuncture Neixiyan (Ex-LE 4) and Dubi (ST 35) in treating osteoarthritis of knee joint was
better than that of administration of Ritalin slow-released tablet.
Author: DAI Qi-ping (1966-), female, attending physician
Translator: Wu Xue-fei 相似文献
134.
Genetic polymorphisms in the estrogen receptor alpha gene and risk of breast cancer: results from the Shanghai Breast Cancer Study. 总被引:11,自引:0,他引:11
135.
216例恶性阻塞性黄疸患者手术疗效的因素分析 总被引:10,自引:0,他引:10
目的 探讨影响恶性阻塞性黄疸临床治疗的预后因素。方法 对1990年1月~1997年12月216例恶性阻塞性黄疸手术患者的17种临床指标进行分析。结果 173例(80.1%)手术后1个月存活,发生并发症81例,发生率37.5%。台术者胆管炎、胆瘘、出血、肾功能衰竭等并发症均高于姑息术者,差异均有显著性(P〈0.01);1月生存率和术后并发症发生率与ASA分级、黄疸持续的时间等有明显关系(P〈0.01 相似文献
136.
东莨菪碱预防吗啡、布比卡因持续硬膜外镇痛副作用的临床观察 总被引:3,自引:0,他引:3
目的:评价东莨菪碱预防上腹部手术后吗啡、布比卡因持续硬膜外镇痛副作用的优越性.方法:前瞻性设计,对上腹部手术ASA评分为Ⅰ~Ⅱ级者分二组,Ⅰ组(吗啡6 mg 布比卡因0.125 g 东莨菪碱2.4 mg),Ⅱ组(吗啡6 mg 布比卡因0.125 g),均在术后持续硬膜外镇痛泵给药.对吗啡、布比卡因镇痛效果及副作用发生率进行统计分析.结果:Ⅰ组VAS值为0.68,满意率为95.78%;Ⅱ组VAS值为1.62,满意率为86.27%,有显著性差异(P<0.01).恶心呕吐、多汗、尿潴留发生率Ⅰ组明显低于Ⅱ组,有显著性差异(P<0.05).嗜睡发生率两组相比无显著差别,且两组均未观察到呼吸抑制.结论:东莨菪碱不仅能增强镇痛效果、提高镇痛的满意率,而且能预防镇痛剂的副作用,为临床镇痛治疗提供新方法. 相似文献
137.
Horch RE Andree C Kopp J Tánczos E Voigt M Bannasch H Walgenbach KJ Dai FP Bittner K Galla TJ Stark GB 《Zentralblatt für Chirurgie》2000,125(Z1):74-78
A variety of reasons can afflict wound healing. Current research is focussed on the acceleration of wound healing by stimulating molecular processes. Gene therapy may offer completely new ways to treat chronic wounds. Possible advantages of gene therapeutic modulation of wound healing might be a long term efficiency, systemic or local regulation of gene expression and low side-effects. Current goals comprise the improvement of transfection efficiency and specificity. In vivo applications are therefore focussed on optimized inducible or even cell-type specific promotors, as well as on improved local application techniques. Studies from our laboratory demonstrate the possibility to combine modern cell culture techniques with different types of gene transfer. This enables the simultaneous grafting of manipulated cells to the wound with the continuous delivery of specific proteins of interest. Experimentally, this lead to accelerated closure of partial and full thickness animal wounds. Clinically, gene therapy for the treatment of chronic wounds seems to be a realistic goal within the next years and might be applicable for a variety of novel indications. 相似文献
138.
浅探溃疡病胃镜征象与中医辨证关系 总被引:3,自引:0,他引:3
通过观察116例溃疡病人内镜下病变部位的粘膜相,根据四诊资料进行辨证分型,试图从微观角度探讨中医病因、病机、诊断;分析了内镜诊断,胃粘膜相与中医舌象、传统辨证的关系,认为胃粘膜相与舌象改变基本一致。对有血瘀症状而无舌脉改变者,胃镜亦能提示瘀阻胃络的粘膜改变,故可作为中医望诊的延伸运用于临床。将宏观辨证与微观辨证有机结合,可补充传统辨证的不足,有利于对中医证型本质的探讨,为中医辨证论治开辟新的前景。 相似文献
139.
中西医结合治疗原发性肾病综合征78例疗效观察 总被引:4,自引:0,他引:4
以血瘀为纲进行辨证,分为湿热血瘀、气虚血瘀、气滞血瘀、阳虚血瘀及瘀水互阻6种证型,用中药配合激素和环磷酰胺治疗原发性肾病综合征78例。结果:完全缓解31例,部分缓解38例,无效9例,总缓解率为88.5%。 相似文献
140.
观察杏灵颗粒治疗冠心病心绞痛的临床疗效,共选择243例,其中治疗组153例,对照组90例。疗程为6周。治疗结果,对心绞痛疗效,两组分别为92.2%和77.8%;对心电图疗效,两组分别为62.6%和53.5%。治疗组明显优于对照组。本品对不同程度,不同类型的心绞痛患者均有较好疗效。 相似文献