Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69?M?×?10^?5 at 24th hour and 3.93?M?×?10^?6 at 48th hour. IC50 dose for pioglitazone was 1.61?M?×?10^?3 at 24th hour and 2.85?M?×?10^?4 at 48th hour. Although cells were treated the dose of 40,225?mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.     

CHICAGO, PERISCOPE and PROactive: CV risk modification in diabetes with pioglitazone

Recent trials of intensive glycaemic control in patients with type 2 diabetes and its impact on cardiovascular disease have led to confusion and speculation amongst physicians. The Action to Control Cardiovascular Risk in Diabetes Study was terminated early because of a significant excess all‐cause mortality in the intensively‐treated group. Furthermore the ADVANCE and VADT trials did not demonstrate cardiovascular benefit with more intensive glycaemic control. Against this background, it is pertinent to re‐visit and critically appraise the results of the PROactive study which examined the effects of the thiazolidinedione, pioglitazone, on cardiovascular end‐points in a large, randomized, placebo‐controlled clinical trial in type 2 diabetic patients with symptomatic disease. PROactive has been rightly criticized in the choice of its composite primary end‐point which included a physician‐driven as opposed to a disease‐driven outcome, namely peripheral vascular re‐vascularization. This was primarily responsible for the primary composite end‐point not being achieved; whereas there was a significant beneficial impact on the major secondary end‐point of death, non‐fatal myocardial infarction and stroke. The results of PROactive have been supported by two subsequent studies examining the impact of pioglitazone on important surrogates of atherosclerosis, namely carotid intima/medial thickness (IMT) and coronary atheroma volume as delineated with intravascular ultrasound. The CHICAGO study demonstrated that IMT in type 2 diabetic patients treated with pioglitazone did not progress whereas those treated with glimepiride showed progression. In PERISCOPE atheroma volume progressed with glimepiride but did not with pioglitazone. This is exciting data pointing to the cardiovascular benefits of pioglitazone. In PROactive, CHICAGO and PERISCOPE there was a sustained effect of pioglitazone on glycaemic control and, in addition, beneficial effects in reducing triglycerides and increasing HDL‐cholesterol beyond that seen with concomitant statin therapy. These findings strongly suggest that pioglitazone has an important place in the management of type 2 diabetes.     

盐酸吡咯列酮治疗多囊卵巢综合征临床疗效分析

目的探讨盐酸吡咯列酮对多囊卵巢综合征（PCOS）患者血清睾酮、血脂、空腹胰岛素、血糖的影响，为其临床应用提供依据。方法应用自身对照研究，对30例PCOS患者给予盐酸毗咯列酮每日30mg口服，3个月。进行服药前后的血清睾酮、血脂、空腹胰岛素、血糖及服糖后2h胰岛素和血糖的测定，同时于服药后记录月经周期、体重变化，服药后不适感及B超监测排卵。结果服药前后体重无明显变化（P〉0．05）。服药后空腹胰岛素、服糖后2h胰岛素和血糖、HOMA指数均有下降（P〈0.05）。服药后血清睾酮明显下降，特别是肥胖组下降明显（P〈0.05），而非肥胖组无变化（P〉0.05）。服药后高密度脂蛋白（HDL）升高，甘油三脂（TG）降低（P〈0.05）。23例无排卵患者服药后观察69个周期，21个周期有排卵，排卵率为30．43％。26例月经异常者中20例得到改善，改善率为76．92％。不良反应中，乳房胀痛1例，胃痛1例，疲劳感1例，其余患者无不适主诉，未发现肝、肾功能异常。结论吡咯列酮可以改善PCOS患者胰岛素抵抗，降低血清睾酮水平，调节脂代谢、诱发排卵，短期应用未出现严重的不良反应。     

Peroxisome proliferator-activated receptor γ ligands regulate neural stem cell proliferation and differentiation in vitro and in vivo

Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated nuclear receptors and its ligands are known to control many physiological and pathological situations. Its role in the central nervous system has been under intense analysis during the last years. Here we show a novel function for PPARγ in controlling stem cell expansion in the adult mammalian brain. Adult rats treated with pioglitazone, a specific ligand of PPARγ, had elevated numbers of proliferating progenitor cells in the subventricular zone and the rostral migratory stream. Electron microscopy analysis also showed important changes in the subventricular zone ultrastructure of pioglitazone-treated animals including an increased number of migratory cell chains. These results were further confirmed in vitro. Neurosphere assays revealed significant increases in the number of neurosphere forming cells from pioglitazone- and rosiglitazone (two specific ligands of PPARγ receptor)-treated cultures that exhibited enhanced capacity for cell migration and differentiation. The effects of pioglitazone were blocked by the PPARγ receptor antagonists GW9662 and T0070907, suggesting that its effects are mediated by a mechanism dependent on PPARγ activation. These results indicate for the first time that activation of PPARγ receptor directly regulates proliferation, differentiation, and migration of neural stem cells in vivo.     

过氧化物酶体增殖物激活受体γ激动剂吡格列酮对大鼠创伤性脑损伤的影响

目的 观察PPARγ激动剂吡格列酮对大鼠创伤性脑损伤的神经保护作用.方法 将72只SD大鼠按随机数字表法分为假致伤组、对照组、吡格列酮治疗组,每组24只.采用改良的Feeney法制作脑创伤模型,治疗组采用吡格列酮(10 mg/kg)灌胃,假致伤组和对照组用等量生理盐水灌胃.致伤后在相应时相点行大鼠神经功能评分后,用干湿质量法进行脑组织含水量测定,进行HE、Nissl及TUNEL染色观察脑组织损伤、迟发性神经元死亡及神经细胞凋亡程度.结果 ①在伤后48 h、5 d,治疗组的神经功能评分[分别为(2.12±0.58)、(1.67±0.78)]好于对照组[(2.67±0.65)、(2.25±0.62),P<0.05];②伤后24 h治疗组与对照组脑组织含水量差异无统计学意义[分别为(78.84±1.92)%、(79.21±2.20)%,P>0.05];③伤后48 h,治疗组迟发性神经元死亡(38.59±1.97)%和神经细胞凋亡数(31.67±4.76)明显低于对照组[分别为(51.25±4.01)%、(45.33±4.68),P<0.05].结论 PPARγ激动剂吡格列酮能抑制创伤性脑损伤后的神经细胞凋亡,保护神经元,从而发挥神经保护作用.     

吡格列酮联合炔雌醇环丙孕酮治疗多囊卵巢综合征的疗效观察

目的 研究吡格列酮联合炔雌醇环丙孕酮治疗多囊卵巢综合征的疗效。方法 选择2014年1月—2017年12月东莞市人民医院治疗的63例多囊卵巢综合症患者作为研究对象,用抽签法随机将患者分为对照组（32例）和观察组（31例）。对照组在月经的第5天开始于睡前口服炔雌醇环丙孕酮片,1片/d,连服21 d。观察组在对照组治疗的基础上口服盐酸吡格列酮片,1片/d。两组共持续服用3个月经周期。观察患者的临床疗效,比较两组治疗前后的性激素和糖脂代谢指标水平,以及卵巢体积和体质量指数。结果 治疗后,观察组的总有效率为90.32%,明显高于对照组的71.87%,两组总有效率比较差异具有统计学意义（P<0.05）。两组治疗后的促卵泡刺激素（FSH）、睾酮（T）和促黄体生成素（LH）水平均明显降低（P<0.05）,观察组性激素水平明显低于对照组（P<0.05）。治疗后,观察组总胆固醇（TC）、空腹血糖（FBG）和三酰甘油（TG）水平明显降低,高密度脂蛋白（HDL）水平明显升高（P<0.05）;且观察组血糖和血脂水平显著优于对照组（P<0.05）。两组治疗后的卵巢体积和体质量指数明显降低（P<0.05）,且观察组明显低于对照组（P<0.05）。结论 吡格列酮联合炔雌醇环丙孕酮可以有效调节多囊卵巢综合症患者的性激素、血糖和血脂水平,具有一定的临床推广应用价值。     

吡格列酮治疗2型糖尿病的Ⅱ期临床试验

目的 :比较吡格列酮和二甲双胍降血糖、降血脂及改善胰岛素敏感作用。方法 :采用平行双盲随机对照研究。共 6 0例病人入选 ,分为 2组。A组予二甲双胍 5 0 0mg,po ,bid。B组予吡格列酮30mg ,po ,qd。疗程均为12wk ,观察 2组治疗前后血糖、血脂、胰岛素等指标的变化。结果 :共 5 3例病人完成试验 ,年龄 (5 6±s 6 )a ,男性 17例 ,女性 36例 ,A组为对照组 ,B组为试验组。 2组性别、年龄、体重指数等一般资料均无显著差异 (P >0 .0 5 )。治疗后 2组血糖、糖化血红蛋白均明显下降 (P <0 .0 1) ,组间无显著差异 (P >0 .0 5 )。试验组胰岛素、C肽均明显下降 (P <0 .0 1) ,对照组餐后 2h胰岛素下降 (6± 11)mU·L- 1,P <0 .0 5。试验组三酰甘油下降 (0 .5± 0 .8)mmol·L- 1,高密度脂蛋白 胆固醇较治疗前升高 (0 .5± 0 .3)mmol·L- 1,游离脂肪酸下降 (2 80± 396 ) μmol·L- 1(均P <0 .0 1)。对照组血脂各项较治疗前明显变化 (均P <0 .0 1) ,2组间比较 ,总胆固醇和低密度脂蛋白 胆固醇变化有差异 (P <0 .0 1或P <0 .0 5 )。试验组血尿酸下降 (2 7±4 4) μmol·L- 1。 2组治疗后均有红细胞和血红蛋白的降低 (P <0 .0 1) ,但 2组不良事件发生率比较无显著差异 (P >0 .0 5 )。结论 :吡格列酮和二甲双胍具有相?     

吡格列酮对自发性IGT-OLETF大鼠胰岛素抵抗的改善作用

目的研究胰岛素增敏剂吡格列酮（pioglitazone）对自发性IGT-OLETF大鼠胰岛素抵抗的改善作用。方法血糖测定采用葡糖氧化酶法，血胰岛素测定采用放射免疫法，游离脂肪酸（FFA）采用铜试剂显色法。结果 IGT-OLETF大鼠具有明显糖耐量、胰岛素耐量异常，脂代谢紊乱，胰岛素敏感指数显著降低等特征。吡格列酮可明显提高IGT-OLETF大鼠对外源性胰岛素的反应性，改善其高胰岛素血症，降低血甘油三酯（TG）、FFA水平，降低肝脂含量及骨骼肌TG含量，使胰岛素敏感指数基本恢复正常。结论吡格列酮可明显改善IGT-OLETF大鼠的胰岛素抵抗。     

吡格列酮或胰岛素治疗对2型糖尿病患者血尿酸的影响

目的:比较吡格列酮或胰岛素治疗对2型糖尿病患者（ type 2 diabetes mellitus T2DM）血糖及血尿酸的影响。方法：133名2型糖尿病合并高尿酸血症的患者随机分为3组,监测12周治疗前后空腹血糖、餐后2h血糖、糖化血红蛋白、血尿酸、肌酐、总胆固醇和甘油三酯。结果：吡格列酮组治疗后空腹血糖、餐后2h血糖、糖化血红蛋白、血尿酸、甘油三酯、总胆固醇等均较治疗前下降（P<0.05）。胰岛素治疗组空腹血糖、餐后2h血糖、HbA1c均较治疗前显著下降（P<0.05）。胰岛素组治疗前后空腹血糖、餐后2h血糖和HbA1c均低于吡咯列酮和常规治疗组（P<0.05）。吡格列酮组降低尿酸的作用显著高于胰岛素治疗组。常规治疗组降低血尿酸作用高于吡咯列酮组和胰岛素组。结论：胰岛素组的降糖作用最强。吡格列酮显著降低血尿酸。对于2型糖尿病合并高尿酸血症,无痛风的患者,宜选用吡格列酮。