Pioglitazone: A Review of Japanese Clinical Studies

Summary

Pioglitazone, a new thiazolidinedione agent, has been shown to increase insulin sensitivity in clinical trials. Pioglitazone HCl was rapidly absorbed within one hour, achieved peak concentrations at 2–3?h, and was eliminated from serum at 24–36?h. Pioglitazone demonstrated dose-dependent pharmacokinetics. Food did not significantly affect the pharmacokinetic profile of pioglitazone. The pharmacokinetic profile of sulfonylurea agents was not significantly altered by concurrent administration with pioglitazone. Pharmacokinetic studies in healthy volunteers and in patients with type 2 diabetes indicated that pioglitazone may be administered once daily. In patients with type 2 diabetes, pioglitazone as monotherapy and in combination with sulfonylureas or an α-glucosidase inhibitor significantly reduced fasting blood glucose, HbA1c, triglycerides, and free fatty acids, and significantly increased HDL-cholesterol. Pioglitazone demonstrated either minor increases or decreases in cholesterol with no adverse effect on LDL-cholesterol. No patients experienced jaundice or ALT elevations > three times the upper limit of normal. Adverse events were mild and transient; all subjects returned to their baseline health status or laboratory tests upon withdrawal from, or completion of, the studies. Based upon these preliminary studies, full-scale clinical investigations were conducted in Japan, the United States, and Europe. As a result, in many countries pioglitazone has gained approval for use in patients with type 2 diabetes.     

Central and Regional Hemodynamics During the Acute Onset of Renal Hypertension in Rats

The purpose of this study was to quantitate the regional changes in flow and resistance which occur during the acute onset of two-kidney, one clip renal hypertension. Anesthetized rats were implanted with a Doppler flow probe and balloon occluder on one renal artery. To produce acute hypertension, the occluder was inflated to reduce renal flow velocity by 50%. After 90 minutes, mean arterial pressure increased 25% above the prestenosis control period value as a result of a 22% increase in peripheral resistance. Regional flows and resistances were determined prior to and 90 minutes after renal artery stenosis by Injection of labelled microspheres into the left ventricle. Our major findings were that: 1) the regional hemodynamic changes in flow and resistance are unevenly distributed among individual organs; and 2) the major site of increased resistance resides in the splanchnic circulation with the largest increases occurring in the small intestine.     

核苷和核苷酸类药物治疗慢性乙型肝炎产生多重耐药的挽救治疗观察

目的探索核苷和核苷酸类药物治疗慢性乙型肝炎产生多重耐药（MDR）的挽救治疗方法。方法 2011年2月-2012年5月在本院住院及门诊产生MDR的慢性乙型肝炎患者27例,分成替诺福韦（TDF）加恩替卡韦（ETV）组、TDF单用组及阿德福韦（ADV）加ETV组。按4、12和24周时间段观察肝肾生化指标,病毒基因及HBV标志物检测值。率的比较采用卡方检验。结果TDF＋ETV联合组,4周时血清肝生化检测值正常、HBV DNA检测值低于检测下限9/9例。TDF单用组,4周时血清肝生化指标复常9/9例,HBV DNA检测值低于检测下限6/9例。12周时HBV DNA检测值低于检测下限9/9例。沿用耐药时的ADV＋ETV治疗组,24周未见应答。与前两组对照,χ2=5.35～6.40,P〈0.01。结论 TDF可有效用于慢性乙型肝炎核苷和核苷酸类药物MDR的挽救治疗,效果优于ADV＋ETV治疗。     

Racquetball Injuries

It doesn't take a lot of skill to play racquetball and benefit from the excellent exercise it provides. Most of the injuries can be prevented if safety precautions are observed.     

Impact of Insulin Resistance on Insulin-Like Growth Factor-1/Insulin Like Growth Factor-Binding Protein-3 Axis and on Early Weight Gain in Small for Gestational Age Infants

Objective: To assess insulin-like growth factor-1 (IGF-1)/IGF-binding protein-3 (IGFBP-3) axis and insulin resistance (IR) and the relationship of these parameters with growth in appropriate for gestational age (AGA) and small for gestational age (SGA) infants at birth and in early infancy.Methods: Postnatal blood samples for measurement of glucose, insulin, IGF-1, and IGFBP-3 were taken from 60 infants (30 AGA and 30 SGA) at birth and at one, three, and six months of age. Both SGA and AGA infants were divided into two groups: growing well and not growing well. Blood glucose, insulin, IGF-1, and IGFBP-3 values were assessed in all infants.Results: Homeostasis model assessment-IR (HOMA-IR) values in well-growing SGA infants in the third and sixth months were found to be higher than in not well-growing SGA infants (3.9±0.8 vs. 1.0±0.3 at 3 months and 3.3±0.9 vs. 2.4±0.9 at 6 months, p<0.05). IGF-1 levels in well-growing SGA infants at 3 and 6 months were found to be higher than those in not well-growing SGA infants (83.80±44.50 vs. 73.50±17.60 ng/mL at 3 months and 95.12±50.74 vs. 87.67±22.91 ng/mL at 6 months, p<0.05). The IGF-1 values were significantly lower in well-growing SGA infants than in well-growing AGA infants (83.80±44.50 vs. 103.31±30.81 ng/mL at 3 months and 95.12±50.74 vs. 110.87±26.44 ng/mL at 6 months, p<0.05).Conclusions: This study demonstrates the effects of accelerated early infant growth on IGF-1/IGFBP-3 axis in SGA-born infants.Conflict of interest:None declared.     

ICU嗜麦芽窄食单胞菌肺部感染的诱因及耐药性分析

目的分析重症监护病房（ICU）嗜麦芽窄食单胞菌（SMA）肺部感染的诱因及敏感情况。方法分析52例ICU嗜麦芽窄食单胞菌肺部感染患者的病例资料。结果 SMA肺部感染的主要诱因为人工气道建立、广谱抗生素≥14 d、侵入性操作、机械通气和皮质激素应用等;ICU内肺部感染的SMA呈多重耐药性,其中亚胺培南耐药性最高（96.2%）,替卡西林/克拉维酸敏感性最高（73.1%）。结论应严格根据药敏结果选择敏感抗生素,加强无菌操作规程,避免医源性传播,慎重使用免疫抑制剂,增强患者免疫力,从而降低SMA肺部感染的发病率。     

Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles

Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p < 0.05) in presence of 250 μg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole.