Do thiazolidinediones still have a role in treatment of type 2 diabetes mellitus?

Thiazolidinediones have been introduced in the treatment of type 2 diabetes mellitus (T2DM) since the late 1990s. Although troglitazone was withdrawn from the market a few years later due to liver toxicity, both rosiglitazone and pioglitazone gained widespread use for T2DM treatment. In 2010, however, due to increased risk of cardiovascular events associated with its use, the European Medicines Agency recommended suspension of rosiglitazone use and the Food and Drug Administration severely restricted its use. Thus pioglitazone is the only thiazolidinedione still significantly employed for treating T2DM and it is the only molecule of this class still listed in the American Diabetes Association‐European Association for the Study of Diabetes 2012 Position Statement. However, as for the other thiazolidinediones, use of pioglitazone is itself limited by several side effects, some of them potentially dangerous. This, together with the development of novel therapeutic strategies approved in the last couple of years, has made it questionable whether or not thiazolidinediones (namely pioglitazone) should still be used in the treatment of T2DM. This article will attempt to formulate an answer to this question by critically reviewing the available data on the numerous advantages and the potentially worrying shortcomings of pioglitazone treatment in T2DM.     

肝移植术后γδT细胞及其亚群的特征及临床意义

目的分析肝移植术后发生急性排斥反应的患者外周血中γδT细胞及其Vδ1、Vδ2亚群的特征及临床意义。方法应用流式细胞术（FCM）检测11例肝移植术后发生急排反应患者、16例不发生急排反应患者及12例健康对照者外周血中γδT细胞、Vδ1亚群、Vδ2亚群的频率,以及Vδ1/Vδ2的比值,并分析其与肝功能指标之间的关系。结果急排组外周血中Vδ1亚群频率、Vδ1/Vδ2比值低于稳定组差异有统计学意义（P〈0.05）;而Vδ2亚群频率高于稳定组,差异有统计学意义（P〈0.05）;两组间的γδT细胞频率差异无统计学意义,急排组与对照组的Vδ2亚群频率、γδT细胞频率、Vδ1/Vδ2比值差异均无统计学意义;Vδ1/Vδ2比值与ALT、AST、ALP、GGT水平呈明显的负相关。结论 Vδ1亚群可能在维持移植物免疫耐受中起重要作用,肝移植术后Vδ1/Vδ2比值可能作为急性排斥反应的预测指标。     

闭合复位Ⅲ型标准伽玛（γ）型髓内钉内固定治疗股骨转子问骨折

摘要目的：探讨Ⅲ型标准伽玛（γ）型髓内钉治疗股骨转子间骨折的临床效果。方法：回顾性分析2011年7月～2013年2月我院使用Ⅲ型标准伽玛（γ）型髓内钉装置闭合复位内固定治疗股骨转子间骨折患者25例的临床资料。结果：24例患者获得随访,1例失访,随访时间4—15个月,平均11个月。手术时间60—115分钟,平均86分钟。全部24例患者末次随访时的Harris评分为65～97分,平均85．6分,本组优12例,良10例,中2例,差1例,优良率为88％。92％的患者在术后疼痛短期内缓解,骨折愈合时间8～16周,平均11周。20例患者术后逐渐恢复到术前的行走水平。1例患者出现头颈部短缩。没有发生内置物失效断裂、没有发生股骨头缺血性坏死、没有切口不愈感染发生病例。结论：Ⅲ型标准伽玛（γ）型髓内钉是一种可依赖的治疗转子间骨折的内置物,闭合复位Ⅲ型标准伽玛（γ）型髓内钉内固定是目前治疗股骨转子间骨折较理想的手术方式,尤其适用于老年不稳定型股骨转子间骨折。     

A Comparison of In Vivo Cellular Responses to Cs-137 Gamma Rays And 320-kV X Rays

Research reported here relates to comparing the relative effectiveness of 320-kV X rays compared to Cs-137 gamma rays for two in vivo endpoints in C.B-17 mice after whole-body exposure: (1) cytotoxicity to bone marrow cells and splenocytes evaluated at 24-hours post exposure and (2) bone marrow and spleen reconstitution deficits (repopulation shortfalls) evaluated at 6 weeks post exposure. We show that cytotoxicity dose-response relationships for bone marrow cells and splenocytes are complex, involving negative curvature (decreasing slope as dose increases), presumably implicating a mixed cell population comprised of large numbers of hypersensitive, modestly radiosensitive, and resistant cells. The radiosensitive cells appear to respond with 50% being killed by a dose < 0.5 Gy. The X-ray relative biological effectiveness (RBE), relative to gamma rays, for destroying bone marrow cells in vivo is > 1, while for destroying splenocytes it is < 1. In contrast, dose-response relationships for reconstitution deficits in the bone marrow and spleen of C.B-17 mice at 6 weeks after radiation exposure were of the threshold type with gamma rays being more effective in causing reconstitution deficit.     

琥珀酸氢化可的松联合低剂量丙种球蛋白治疗儿童过敏性紫癜疗效观察

目的观察琥珀酸氢化可的松联合低剂量丙种球蛋白治疗儿童过敏性紫癜的疗效,为临床治疗提供依据。方法选取过敏性紫癜患3L70例,分为两组,对照组给予常规治疗;治疗组在此基础上给予琥珀酸氢化可的松、低剂量丙种球蛋白联合治疗,观察其药物疗效。结果治疗组总有效率明显高于对照组（P〈0.05）;治疗组尿常规检查恢复时间与对照组无显著性差异俨〉005）,皮疹消退、关节肿痛与消化道症状缓解时间明显缩短（P〈0.01）。结论琥珀酸氢化可的松联合低剂量丙种球蛋白治疗儿童过敏性紫癜疗效良好,能明显缓解过敏性紫癜的临床症状,减少其复发率。     

泌乳素腺瘤伽玛刀治疗后早期内分泌功能的改变及意义

目的 探讨泌乳素腺瘤患者伽玛刀治疗后早期内分泌功能的变化规律及意义.方法 对有完整近期随访资料的27例患者进行同顾分析,调查其临床症状和泌乳素(prolactin,PRL)水平在治疗后6个月的动态变化,并评估该变化可能的临床意义.结果 在随访的6个月中,临床症状短暂或持续好转者24例(89%),PRL水平短暂或持续降低21例(78%).临床症状好转和PRL下降主要发生于治疗后前2个月.l临床症状好转率及PRL水平在治疗后前2个月与其他月份间比较有显著差异(P<0.05).结论 泌乳素腺瘤伽玛刀治疗后内分泌功能紊乱的改善在2个月内更为显著,应被视为育龄女性着孕或避孕的重点时期之一.     

DRD4 and DAT1 polymorphisms modulate human gamma band responses

Gamma oscillations (30-80 Hz) have been demonstrated to be important for perceptual and cognitive processes. Animal and in vitro studies have revealed possible underlying generation mechanisms of the gamma rhythm. However, little is known about the neurochemical modulation of these oscillations during human cognition. Schizophrenia and Attention Deficit Hyperactivity Disorder, which lead to failure of attentional modulation and working memory, introduce significant changes in gamma responses and have significant associations with genetic polymorphisms of dopamine receptor D4 (DRD4), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT). Therefore, the presence of direct relations between these polymorphisms and gamma oscillations was investigated in human subjects using an auditory target detection paradigm. The 7-repeat isoform of the DRD4 polymorphism that produces a subsensitive variant of the D4 receptor enhanced the auditory evoked and induced gamma responses to both standard and target stimuli. The 10/10 genotype of the DAT1 polymorphism, which reduces DAT expression and hence yields an increase in extracellular dopamine, specifically enhanced evoked gamma responses to target stimuli. The COMT polymorphism did not significantly change gamma responses. It seems plausible to assume that the modulation pattern of the evoked gamma response by DRD4 polymorphism relates to reduced inhibition via the D4 receptor, whereas the DAT1 effect is related to the target detection mechanism probably mediated by the D1 receptor.     

Systemic administration of interleukin-4 expressing plasmid DNA delays the development of glomerulonephritis and prolongs survival in lupus-prone female NZB x NZW F1 mice.

BACKGROUND: T helper (Th)1/Th2 balance determines the direction of some kinds of autoimmune diseases. Th1 cytokines, especially interferon (IFN)-gamma has been proven important in the pathogenesis in lupus. The present study examined the effects of administration of interleukin (IL)-4 (Th2 cytokine) expressing plasmid DNA (IL-4pDNA) on the development of glomerulonephritis and survival in lupus-prone female NZB x NZW (B/W)F1 mice. METHODS: B/WF1 mice were administrated intraperitoneally either with IL-4pDNA (100 microg/mouse), plasmid (100 microg/mouse) or saline at 4 and 6 weeks of age and at 4 week intervals from 8 to 32 weeks of age. RESULTS: Compared to the saline and plasmid groups (controls), the IL-4pDNA-treatment drastically delayed the development of glomerulonephritis with deposits of IgG2a and C3 leading to excretion of urine protein, and prolonged survival. Clinical improvement was associated with the reduction in productions of IgG anti-dsDNA autoantibody. Also, compared to the other two controls the IL-4pDNA-treatment reduced production of IFN-gamma and increased IL-4 production from splenic cells. CONCLUSIONS: The present study suggests that systemic IL-4pDNA administration may delay lupus onset by suppressed IFN-gamma production due to shifting from Th1 to Th2 responses.     

Liver function tests in patients with bacteremia

The purpose of this study was to evaluate liver function tests as potential indicators of bacteremia. We examined 156 patients with laboratory-confirmed bacteremia (bacteremia group) and 211 bacteremia-negative patients with bacterial infections (control group). The patients of the two groups had no underlying liver diseases. For patients in the bacteremia group, we analyzed liver function tests results obtained the day when the first positive blood culture was ordered. For those in the control group, the same data were obtained on the day when the first of multiple negative blood cultures was ordered. At t-test analyses, serum levels of gamma-glutamyl transpeptidase (gamma-GT) and alkaline phosphatase (ALP) were significantly higher, and those of albumin, total cholesterol, and cholinesterase were significantly lower in the bacteremia group than in the control group. Multivariate analyses found serum cholinesterase as an independent factor with adjusted odds ratio of 0.319 (per 65 U/L, standard deviation [SD] size). Serum level of C-reactive protein (CRP), on the other hand, showed no significant difference between the two groups. Serum levels of gamma-GT, ALP, albumin, total cholesterol, and cholinesterase more rapidly altered when various bacterial infections accompanied bacteremia. Therefore, they may be useful in detecting sepsis in its early stages.     

伊曲康唑和γ-干扰素对裸小鼠、昆明种小鼠外周血IFN-γ、IL-10的影响

目的研究伊曲康唑和γ-干扰素治疗分别感染白念珠菌和新生隐球菌裸小鼠、昆明种小鼠外周血细胞因子IFN-γ、IL-10的改变及其临床意义。方法将白念珠菌和新生隐球菌分别注射入裸小鼠、昆明种小鼠体内,诱导成动物模型。用ELISA法检测IFN-γ和IL-10的水平。结果经过伊曲康唑和γ-干扰素治疗后,其外周血的IFN—γ上升而IL-10下降。结论伊曲康唑和γ-干扰素对真菌感染小鼠免疫功能的调节起着重要作用。