上皮-间质转化在肿瘤多药耐药性发生中的作用

化学治疗是肿瘤综合治疗的重要方法之一,而多药耐药一直是导致肿瘤化学治疗失败的主要原因。上皮-间质转化(EMT)是正常发育、伤口愈合的基础,同时也在肿瘤发生、侵袭及转移过程中发挥着重要作用,近年来越来越多的研究证实EMT也参与了肿瘤多药耐药的发生。该文主要就EMT的概念、发生机制及其在肿瘤多药耐药过程中机制的研究进展进行综述。     

基于TBLT培养中医学专业学生中西融合临床思维方法

院校式中医医学教育取得了巨大成就,但依然存在一些不足,中医医学生临床基本功和临床实践能力不足,没有建立正确临床思维方法 ,中医疗效没有保障,成为中医医师更加晚熟的原因之一.本文基于任务型教学法(Task based language teaching,TBLT)的基本原理,从病例开始,逐步引导中医医学生完成疾病诊断与鉴...     

国内高压氧联合药物治疗突发性耳聋临床疗效的Meta分析

目的评价近几年来国内高压氧联合药物综合疗法治疗突发性耳聋的临床疗效。方法检索2008²012年近五年来中国学术期刊、中国数字图书馆、维普信息资源系统、超星数字图书馆、中国生物医学文献数据库、万方数据库中关于高压氧联合药物综合治疗突发性耳聋的随机对照研究,对符合纳入标准的文献进行方法学的评价,并用RevMan5.1软件对符合质量标准的随机对照研究进行Meta分析。结果纳入了20个随机对照研究,患者总数为2554例,其中有1347例接受高压氧联合药物治疗,即治疗组,另外1207例接受药物单纯疗法,即对照组。通过Meta分析表明治疗组比对照组的临床疗效显著(P<0.00001),而且早期使用高压氧治疗比晚期使用的临床疗效显著(P<0.00001)。结论在突发性耳聋的治疗过程中,应用高压氧联合药物综合疗法比药物单纯疗法的效果要显著,而且引入高压氧治疗的时间越早效果越好。     

绝经后骨质疏松症与牙周病的关系

绝经后妇女体内雌激素水平降低,从而易患骨质疏松症。绝经后骨质疏松症的形成机制,已为广大学者所证实,但它是否是牙周炎的易感因素,是否会促进牙周炎的发展,目前尚无定论。本文就绝经后骨质疏松症与牙周炎之间的关系做一简要综述。     

巴西SciELO平台国际化发展策略及启示

【目的】 分析母语非英语国家科技期刊出版策略,为国内期刊国际化发展提供借鉴。【方法】 以巴西SciELO平台为例,通过文献调研、平台调研、双语期刊案例调研等方法剖析巴西期刊出版策略。【结果】 作为国际上首个开放出版平台,SciELO平台更多是面向本国期刊质量提升与评估优化、数字化出版、出版语种平衡及国际影响力提升需要而提出的发展策略。【结论】 SciELO平台本身就是一种国际化策略,发挥了“造船出海“的功能,对整体提升巴西期刊国际影响力具有非常重要的作用,其数字出版平台的牵引作用和语种的平衡发展方式值得我国借鉴。     

Intestinal Absorption Studies on Peptide Mimetic α-Methyldopa Prodrugs

Two dipeptide mimetic prodrugs, 1 and 2 , and two tripeptide mimetic prodrugs, 3 and 4 , of l -α-methyldopa were evaluated for intestinal absorption by in-situ single-pass rat jejunal perfusion studies and by in-vitro uptake experiments in brush-border membrane vesicles (BBMVs) prepared from rat intestine. In the perfusion studies, compound 1 demonstrated a 3.5-fold increase in permeability (P_m* = 2.27) as compared with that of α-methyldopa (P_m* = 0.65), indicating that this prodrug was better absorbed in the intestine than its parent drug. Other prodrugs showed no significant improvement in intestinal permeability. The results correlated with the results of BBMV uptake studies. In the presence of an inward proton gradient, compound 1 showed Michaelis-Menton saturable kinetics of BBMV uptake with a low value of K_m (0.06 ± 0.13 mm ) and a high value of V_max/K_m (36.38 nmol (mg protein)^?1/30 s mm ^?1) at a low concentration range and a linear uptake at high concentrations with K_d = 0.14 ± 0.02 mm . Compounds 2 and 3 were mainly taken up in BBMVs via passive diffusion. Compound 4 was taken up in BBMVs basically via the carrier-mediated transport system, while the rate of uptake was much lower than that of compound 1 . The uptake of compounds 1 and 4 was significantly inhibited by dipeptides l -Gly-l -Pro and l -Gly-l -Phe, and cephradine, a β-lactam known to be transported via the dipeptide carrier system, indicating that both compounds were taken up in BBMVs via the H⁺-coupled dipeptide-mediated transport system. In contrast to the complicated uptake profile of α-methyldopa, the higher rate of BBMV uptake with less variation demonstrated on compound 1 suggested that the attached nonessential amino acid moiety, d -phenylglycine, is a feasible delivery tool in carrying the parent drug through the intestine.     

Systemic chemotherapy in patients with indwelling ureteral stenting

BACKGROUND: We investigated whether systemic chemotherapy increased episodes of acute pyelonephritis (APN) in patients with an indwelling double-J stent due to non-urological malignant ureteral obstruction. METHODS: A retrospective study was performed on a total of 74 patients (16 men and 58 women; median age, 53.0; range, 34-84 years) with non-urological malignant ureteral obstruction, who were managed by double-J stenting between October 1997 and December 2001. The patients were divided into those who received (33 patients, group I) and those who did not receive systemic chemotherapy (41 patients, group II) during the stent indwelling period (median, 7.0; range, 1-44 month). Routine antibiotic prophylaxis was not administered to any patient. Median follow-up was 10.5 (range, 1-45) months. Clinical features, including the incidence of febrility and APN, were compared between the two groups. RESULTS: Of the 74 patients, 18 patients (24.3%) experienced acute febrile episodes during ureteral stenting, but only five (6.8%) patients were diagnosed as having APN. No significant difference in the incidence of fever or APN was found between the two groups (P = 1.000 and P = 0.651, respectively). Univariate logistic analysis indicated that only the duration of follow-up was a risk factor for an episode of fever. Other parameters had no clinical significance. CONCLUSION: Our findings suggest that systemic chemotherapy may not predispose the risk of acute pyelonephritis in patients with an indwelling ureteral stent due to non-urological malignant ureteral obstruction.     

Chemical Approaches to Improve the Oral Bioavailability of Peptidergic Molecules

This review discusses both tools and strategies that may be employed as approaches towards the pursuit of orally active compounds from peptidergic molecules. Besides providing a review of these subjects, this paper provides an example of how these were utilized in a research programme at SmithKline Beecham involving the development of orally active GPIIb/IIIa antagonists. The tools for studying oral drug absorption in-vitro include variants of the Ussing chamber which utilize either intestinal tissues or cultured epithelial cells that permit the measurement of intestinal permeability. Example absorption studies that are described are mannitol, cephalexin, the growth hormone-releasing peptide SK&F 110679 and two GPIIb/ IIIa antagonist peptides SK&F 106760 and SK&F 107260. With the exception of cephalexin, these compounds cross the intestine by passive paracellular diffusion. Cephalexin, on the other hand, crosses the intestine via the oligopeptide transporter. Structure-transport studies are reviewed for this transporter. The tools for studying oral drug absorption in-vivo involve animals bearing in-dwelling intestinal or portal vein catheters. A study of the segmental absorption of SK&F 106760 is provided. The review concludes with two chemical strategies that may be taken towards the enhancement of oral bioavailability of peptidergic molecules. The first strategy involves the chemical modification of peptides which enhance intestinal permeability, specifically the modification of amide bonds. The second strategy involves the design of compounds bearing nonpeptide templates, which are more amenable to the discovery of compounds with oral activity, from peptide pharmacophore models. An example is given regarding the discovery of SB 208651, a potent orally active GPIIb/IIIa antagonist, designed from the peptides SK&F 106760 and SK&F 107260.