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《Drug metabolism and pharmacokinetics》2019,34(5):308-316
LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel 18O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H218O in the presence of the enzyme, generating singly- and doubly-18O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery. 相似文献
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Kevin L. Greason M.D. Jose A. Acosta M.D. Thomas J. Magrino M.D. Moogil Choe M.D. 《Diseases of the colon and rectum》1996,39(6):702-704
PURPOSE: This study was undertaken to clarify the importance of bleeding vascular ectasia of the colon as the etiology of massive lower gastrointestinal hemorrhage in patients 40 years of age or younger. METHODS: An otherwise healthy 21-year-old male was admitted to a tertiary medical center with massive lower gastrointestinal hemorrhage. Technetium-labeled red blood cell scan, selective visceral angiography, and colonoscopy identified the source of bleeding as vascular abnormality of the descending colon. Segmental colonic resection was performed. RESULTS: Histologic review of the specimen demonstrated a vascular ectasia. The patient recovered uneventfully and has had no further stigmata of hemorrhage. A review of the literature was undertaken to make clear the significance of vascular ectasia as the source for massive colonic hemorrhage in the young adult. CONCLUSION: This is the first report that documents histologically a vascular ectasia as the source of massive lower gastrointestinal hemorrhage in an otherwise healthy patient less than 40 years of age. Vascular ectasia is an uncommon cause of lower gastrointestinal hemorrhage in the young adult.The Chief, Bureau of Medicine and Surgery, Navy Department, Washington, DC, Clinical Investigation Program sponsored this report #84-16-1968-532, as required by HSETCINST 6000.41A. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. 相似文献
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蛇床子水提取液抑瘤作用的实验研究 总被引:13,自引:0,他引:13
目的 :研究蛇床子水提取液的体内抗肿瘤作用。方法 :通过 S180 肉瘤移植建立荷瘤小鼠模型 ,给予不同剂量蛇床子水提取液后观察 S180 荷瘤小鼠肿瘤生长曲线、血清唾液酸 (SA)、瘤重及小鼠生存天数的变化。结果 :蛇床子水提取液能明显抑制肿瘤生长 ,降低荷瘤小鼠血清 SA水平 ,0 .0 6mg/(g· d) ,0 .1 1 mg/(g· d)、0 .2 1 mg/(g· d)剂量组平均瘤重低于肿瘤对照组 (P<0 .0 5 ) ,抑瘤率依次为 2 3 .2 %、2 9.1 %和 2 4 .8%,且能延长荷瘤小鼠生存天数 (P<0 .0 1 ) ,动物生命延长率依次为 :2 6 .9%、3 4 .8%和 2 6 .6 %。结论 :蛇床子水提取液具有较强的抗肿瘤效应 ,有很好的利用前景 ,值得对其进行深入研究。 相似文献
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我院治疗66例心间隔缺损的病例中,有4例合并哑性动脉导管未闭(简称PDA),发生率6%。全组病例术前均无PDA临床体征,1例术前再次复查心脏彩超时发现,其余3例均漏诊。1例先处理PDA,3例在纠正心内畸形同时处理PDA。心间隔缺损合并哑性PDA容易漏诊,但有其临床特点,手术可先处理PDA,或在体外循环下处理PDA。 相似文献
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颈椎后路螺钉-钛棒(板)内固定技术:初步临床报告 总被引:4,自引:1,他引:3
目的 报告利用螺钉-钛棒(板)固定技术治疗各种原因引起的颈椎不稳的初步临床结果。方法 作者1年来行颈椎后路螺钉-钛棒(板)技术内固定9例,其中齿突样骨引起的C1~C2不稳2例,手术后进行性颈椎后凸2例,颈椎管狭窄2例,C3-C4滑脱1例,C6~C7外伤滑脱2例。分别采用C1侧块、C2椎弓根螺钉、C3~C5侧块螺钉、C2-T2椎弓根螺钉植入技术,然后连接钛棒或钛板完成固定。9例病人共植入螺钉59枚。结果 所有病人在1周内带外支架进行活动,除1例因拒绝治疗死亡外,其余病人在1个月及1年后复查均未见内固定物移位。结论 颈椎后路螺钉-钛棒(板)固定为安全可靠的技术,可以术后即刻获得牢固内固定,为下一步治疗创造有利条件。 相似文献
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Akira Fukushima 《Psychiatry and clinical neurosciences》1994,48(Z1):1-4
Abstract: Historical changes in forensic psychiatric evaluation on criminal responsibility and proceedings in psychopathological findings of amphetamine psychosis are reviewed at first. The classification of amphetamine related mental disorders are proposed in 6 types. Among them, the clinical characteristics and psychopathological features of “Anxiety-situational reaction type” (Fukushima) are described. According to some reasonable grounds, offenders diagnosed as anxiety-situational reaction type should be evaluated as diminished responsibility in place of irresponsibility. Finally, two cases of murder committed under the influence of amphetamine, are reported in detail. 相似文献
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