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排序方式: 共有253条查询结果,搜索用时 15 毫秒
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Dario Siccardi Mark Gumbleton Yadollah Omidi Chistopher McGuigan 《European journal of pharmaceutical sciences》2004,22(1):25-31
The phosphoramidate triester prodrug approach is widely used to deliver nucleotide forms of nucleoside analogues into target cells. We investigated the stereoselective stability of a series of prodrugs of the anti-HIV agent 2',3'-didehydro-2',3'-dideoxythymidine (d4T). Chemical stability was evaluated in phosphate buffer at pH values of biological relevance (i.e. pH 2.0, 4.6, 7.4). Enzymatic stability was tested in human plasma, in Caco-2 cell homogenates and monolayers and in rat liver. The compounds were relatively stable to chemical hydrolysis. Between 50 and 70% of unchanged prodrug was recovered after 16h incubation in human plasma, with no stereoselective preference for phosphate diastereoisomers. The p-OMe phenyl derivative, however, was an exception and only 5% of one diastereoisomer was recovered. In Caco-2 cells the stability and stereoselectivity largely depended on the experimental conditions: high enzymatic activity and stereoselectivity was observed in cell homogenates, but not in monolayers. In rat liver S9 fractions the stability profile was similar to that in Caco-2 cells and carboxyl ester cleavage appeared to be the sole mechanism of degradation in both media. The large and unpredictable differences in stereoselective metabolic rate of the pronucleotide series here presented suggest that in vivo circulating levels of intact prodrug could exert profoundly different activity or toxicity due to preferential body distribution of one diastereoisomeric form. 相似文献
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Zahedpasha Y Ahmadpour-Kacho M Hajiahmadi M Naderi S Kamali AA 《The Southeast Asian journal of tropical medicine and public health》2008,39(3):557-561
Glucose-6-phosphate dehydrogenase (G6PD) deficiency may cause severe hyperbilirubinemia with bilirubin encephalopathy unless intervention is initiated. The aim of this study was to assess the efficacy of clofibrate in full term G6PD deficient neonates with jaundice. A randomized clinical trial study was performed in two groups of full-term G6PD deficient jaundiced neonates (clofibrate treated group, n = 21; control group, n = 19). Infants in the clofibrate group received a single oral dose of 100 mg/kg clofibrate, whereas control group received nothing. Both groups were treated with phototherapy. Serum total and direct bilirubin levels were measured at the onset of treatments, 16, 24 and 48 hours later. On enrollment, the mean total serum bilirubin (TSB) level in the clofibrate treated group was 18.40 +/- 2.41 and in the control group was 17.49 +/- 1.03 (p = 0.401). At 16, 24 and 48 hours of treatment, the mean TSB in the clofibrate group were 15.2 +/- 1.9, 12.6 +/- 2.4, and 10.1 +/- 2.4 and in the control group were 16.5 +/- 1.2, 13.3 +/- 2.2 and 11.4 +/- 2.4, respectively (p = 0.047). At 48 hours, 7 (33%) cases in the clofibrate group and one (5%) case in the control group were discharged with a TSB < 10 mg/dl (p = 0.031). No side effects were observed on serial examinations during hospitalization, or on the 1st and 7th days after discharge. The results show that clofibrate induces a faster decline in serum total bilirubin level, a shorter duration of phototherapy, and hospitalization with no side effects in full-term G6PD deficient neonates with jaundice. 相似文献
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Y. Harati MD C. Gooch MD M. Swenson MD D. Green MD P. Raskin MD P. Donofrio MD D. Cornblath MD R. Sachdeo MD C.O. Siu MD M. Kamin MD 《中国疼痛医学杂志》2005,11(4):252-255
目的:本研究旨在评价曲马多治疗糖尿病性神经病的有效性和安全性。背景:糖尿病性神经病疼痛是糖尿病患者的主要症状,其治疗和其它的末梢神经病变一样,不能令人满意。曲马多是作用于中枢的镇痛剂,用于治疗中到重度疼痛。方法:多中心、门诊病例、随机、双盲、安慰剂做对照、设置平行组的研究,包括药效消退期(在此期间停用所有镇痛剂)和一个为期42天的双盲治疗期。总共有131名患糖尿病性神经病疼痛的患者接受曲马多(n=65)或安慰剂胶囊治疗(n=66),每日4次。42天的治疗结束后或治疗中断后比较曲马多组和安慰剂组平均疼痛强度评分,进行初级药效分析。次级药效分析为疼痛缓解评分和根据日常活动和睡眠状况作出生活质量评估。结果:曲马多平均剂量为210mg/天,治疗糖尿病性神经病疼痛较安慰剂有显著疗效(P〈0.001)。曲马多组患者生理(P=0.02)和社会功能(P=0.04)的评分显著优于安慰剂组。未发现对睡眠有显著改善作用。曲马多最常见的不良事件是恶心、便秘、头疼和嗜睡。结论:安慰剂做对照的实验结果表明曲马多在治疗糖尿病性神经病疼痛上是安全和有效的。 相似文献
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Die Unfallchirurgie - Frakturen des 2. Halswirbels mit Beteiligung des Dens axis können in der Regel konservativ behandelt werden. Im Fall von hochgradig instabilen Frakturen sowie... 相似文献
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