Detection of QTc interval prolongation using jacket telemetry in conscious non-human primates: comparison with implanted telemetry

Background and Purpose: During repeat-dose toxicity studies, ECGs are collected from chemically or physically-restrained animals over a short timeframe. This is problematic due to cardiovascular changes caused by manual restraint stress and anesthesia, and limited ECG sampling. These factors confound data interpretation, but may be overcome by using a non-invasive jacket-based ECG collection (JET). The current study investigated whether a jacketed external telemetry system could detect changes in cardiac intervals and heart rate in non-human primates (NHPs), previously implanted with a PCT transmitter.Experimental Approach: Twelve male cynomolgus monkeys were treated weekly with vehicle or sotalol (8, 16, 32 mg kg⁻¹) p.o. ECGs were collected continuously for 24 hours, following treatment, over 4 weeks. A satellite group of six NHPs was used for sotalol toxicokinetics.Key Results: Sotalol attained C_max values 1–3 hours after dosing, and exhibited dose-proportional exposure. In jacketed NHPs, sotalol dose-dependently increased QT/QTc intervals, prolonged PR interval, and reduced heart rate. Significant QTc prolongation of 27, 54 and 76 msec was detected by JET after 8, 16, and 32 mg kg⁻¹ sotalol, respectively, compared with time-matched vehicle-treated animals. Overall, JET-derived PR, QT, QTc intervals, QRS duration, and heart rate correlated well with those derived from PCT.Conclusions and Implications: The current findings clearly support the use of JET to quantify cardiac interval and rhythm changes, capable of detecting QTc prolongation caused by sotalol. JET may be a preferred method compared to restraint-based ECG because high-density ECG sampling can be collected in unstressed conscious monkeys, over several weeks.     

Genotoxic evaluation of titanium dioxide nanoparticles in vivo and in vitro

With the extensive application of titanium dioxide (TiO₂) nanoparticles (NPs) in food industry, there is a rising debate concerning the possible risk associated with exposure to TiO₂ NPs. The purpose of this study is to evaluate the genotoxicity of TiO₂ NPs using in vivo and in vitro test systems. In vivo study, the adult male Sprague-Dawley rats were exposed to anatase TiO₂ NPs (75 ± 15 nm) through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days. The γ-H₂AX assay showed TiO₂ NPs could induce DNA double strand breaks in bone marrow cells after oral administration. However, the micronucleus test revealed that the oral-exposed TiO₂ NPs did not cause damage to chromosomes or mitotic apparatus observably in rat bone marrow cells. In vitro study, Chinese hamster lung fibroblasts (V79 cells) were exposed to TiO₂ NPs at the dose of 0, 5, 10, 20, 50 and 100 μg/mL. Significant decreases in cell viability were detected in all the treated groups after 24 h and 48 h exposure. Significant DNA damage was only observed at the concentration of 100 μg/mL after 24 h treatment using the comet assay. The obvious gene mutation was observed at the concentration of 20 and 100 μg/mL after 2 h treatment using hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutation assay. This study presented a comprehensive genotoxic evaluation of TiO₂ NPs, and TiO₂ NPs were shown to be genotoxic both in vivo and in vitro tests. The gene mutation and DNA strand breaks seem to be more sensitive genetic endpoints for the detection of TiO₂ NPs induced genotoxic effects.     

HDAC inhibitors reverse acquired radio resistance of KYSE-150R esophageal carcinoma cells by modulating Bmi-1 expression

Tumors treated with fractionated doses of ionizing radiation (IR) often acquire radioresistance. Although histone deacetylase inhibitors (HDIs) have been demonstrated to sensitize intrinsic radioresistant cancer cell lines to IR, little is known on the impact of HDIs on the effects of IR in acquired radioresistant cancer cells. This study evaluates the mechanisms by which HDIs sensitize acquired radioresistant esophageal squamous cell carcinoma cells to IR. The HDIs trichostatin A and sodium butyrate were tested for their ability to sensitize acquired radioresistant KYSE-150R and radiosensitive KYSE-150 parental cells to IR. Although the HDIs induced similar levels of cytotoxicity in the KYSE-150 and the KYSE-150R cells, HDIs increased the: (i) radiosensitivity, (ii) IR-induced ROS generation, and (iii) IR-induced G2/M arrest and apoptosis of KYSE-150R cells compared with those of KYSE-150 cells. These changes were accompanied by increased p21expression and decreased mitochondrial membrane potential. When combined with IR, HDIs inhibited Bmi-1 expression in KYSE-150R cells and their ability to repair DNA damage. The results demonstrate the potential utility of HDIs in augmenting the efficacy of fractionated radiotherapy.     

低促性腺激素性腺功能减退症患者的促排卵

低促性腺激素性腺功能减退症(hypogonadotropic hypogonadism,HH)是一种罕见的、以低促性腺激素为特征的、引起第二性征及生殖系统发育障碍的疾病。本文将对该疾病定义、病因、临床表现、诊断及治疗进行全面的介绍。由于HH主要影响育龄女性的生育力,因此诱发排卵以及恢复生育力是该疾病治疗中的关键。治疗HH促排卵的方法较正常人特殊而且复杂,本文将着重介绍HH促排卵的各种原理和方法,同时结合最新的国内外进展以及临床实践经验对各种方法的有效性进行探讨。     

Major chemical compositions,possible sources,and mass closure analysis of PM2.5 in Jinan,China

The fine particulate matter samples for 24 h were carried out at the Environment Monitoring Station (EMS) and Shandong Jianzhu University (SJU) sites during 2010 in Jinan City, China. Eight water-soluble ion species were analyzed by ion chromatography, while organic carbon (OC) and elemental carbon (EC) were determined with the IMPROVE thermal optical reflectance method, and 20 inorganic elements were measured by inductively coupled plasma-atomic emission spectrometer and inductively coupled plasma-mass spectroscopy. The annual average mass concentration of PM_2.5 was 168.85 μg m^?3 at EMS and 148.67 μg m^?3 at SJU. The coefficient of divergence was 0.14, 0.19, 0.23, and 0.23 in spring, summer, fall, and winter, respectively, indicating that there was no obvious spatial difference at the two sampling sites. The highest PM_2.5, OC, and OC/EC ratio were in winter because of the enhanced emissions from coal combustion for heating and poor atmospheric dispersion. By the method of enrichment factors, the 20 inorganic elements were divided into three types owing to their sources. Al, Si, and Ti were mainly contributed by crustal sources. Na, Mg, P, K, Ca, V, Cr, Mn, Fe, Co, Ni, Ba, and Sr were from both natural emissions and anthropogenic sources. Cu, Zn, Pb, and Sn mainly originated from anthropogenic sources such as vehicular exhaust and industrial emission. Chemical mass closure calculation estimated that SO₄ ^2? was the largest contributor and explained 29.66 % of PM_2.5 mass at EMS, while 31.64 % was at SJU. The organic matter, crustal matter, and NO₃ ^–, respectively, accounted for 15.12, 12.87, and 13.77 % to PM_2.5 at EMS, while it accounted for 13.46, 13.96, and 14.93 % at SJU, respectively. By the positive matrix factorization analysis, the coal combustion and biomass burning, secondary sulfate, soil dust, secondary nitrate, and vehicle emissions were identified as the major emission sources.     

Effect of PGPR Serratia marcescens BC-3 and AMF Glomus intraradices on phytoremediation of petroleum contaminated soil

Soil contamination caused by petroleum hydrocarbons has become a worldwide environmental problem. Microorganism combined with phytoremediation appears to be more effective for removal and/or degradation of petroleum hydrocarbons from impacted soils. The current study investigated the effect of inoculated with PGPR Serratia marcescens BC-3 alone or in combination with AMF Glomus intraradices on the phytoremediation of petroleum-contaminated soil. Pot experiments were conducted to analyze the effect on plant and soil for 90 days in greenhouse. The inoculation treatments showed higher plant biomass and antioxidant enzyme activities than the non inoculation control. Inoculation treatments also improved rhizosphere microbial populations in petroleum contaminated soil. The degradation rate of total petroleum hydrocarbons with PGPR and AMP co-inoculation treatment was up to 72.24 %. The results indicated that plant combined with microorganisms for remediation of petroleum hydrocarbons would be a feasible method.     

零售药店药学服务功能弱化的调查分析

目的通过调查零售药店药学服务的状况,分析存在的问题,提出改进建议。方法采用文献查询、观察法、神秘顾客法和综合分析的方法进行调研。结果零售药店药学服务功能处于弱化状态;药店经营理念还没有转变,执业药师数量缺乏、素质不高。结论零售药店可以通过转变经营理念、探索建立可行的药学服务管理模式、提高药店从业人员的药学服务水平来改善药学服务功能弱化的状况。     

医院 2 149 张中草药处方分 析简

目的 分析医院中草药处方书写规范性和合理用药情况,为加强中草药处方管理和提高处方质量提供依据.方法 随机抽取每月第2周任意1d的处方,根据《处方管理办法》和《医院处方点评管理规范（试行）》等对处方进行评价.结果 2012年共抽查处方2 149张,不合理处方1 021张,处方不合格率为47.51％;其中不规范处方994张,占不合理处方的97.36％;用药不适宜处方29张,占不合理处方的2.84％.结论 医院中草药处方不合格率较高,应重视中草药处方的规范性,确保临床用药安全.     

慢性肾脏病患者蛋白质-能量消耗研究新进展

蛋白质-能量消耗在慢性肾脏病患者中发病率较高,临床上主要表现为饮食摄入、生化指标、体重指数、肌肉质量等方面的异常,其发病机制非常复杂,跟摄入不足、炎症、代谢性酸中毒、激素水平紊乱、透析相关因素等有关,严重影响透析患者的预后,因此早期发现、诊断和防治显得非常重要,将营养评估列入慢性肾脏病患者诊疗的日常工作当中,并对照诊断标准,及早诊断和采取各种措施防治蛋白质-能量消耗,最终提高慢性肾脏病患者的预后和生存率.本文对慢性肾脏病引起的蛋白质-能量消耗流行病学特点、发病机理、评估方式、治疗及干预措施等进行阐述.