Effects of lead nitrate and sodium selenite on DNA damage and oxidative stress in diabetic and non-diabetic rat erythrocytes and leucocytes

The adverse effects of lead nitrate (LN) and the preventive role of sodium selenite were investigated in diabetic and non-diabetic rat blood by measuring trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP), malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) also by evaluating DNA damage with comet assay. LN increased the levels of MDA, tail DNA%, mean tail length and tail moment, decreased the enzymes activities, FRAP and TEAC values. In sodium selenite + LN group, we observed the protective effect of sodium selenite on examining parameters. Diabetes caused alterations on these parameters, too. We found that sodium selenite did not protect against diabetes caused damages. As a result, LN caused toxic effects on blood cells and sodium selenite alleviated this toxicity but it did not show preventive effect against diabetes. Also, LN caused more harmfull effects in diabetic groups than non-diabetic groups.     

基于前瞻性人群队列的中国成年人排便频率与帕金森病的关联研究

目的检验成年人排便频率与随访期间确定的帕金森病的关联。方法研究对象来自于中国慢性病前瞻性研究,2004-2008年开展基线调查。在剔除基线自报患有恶性肿瘤者后,最终纳入510134人。随访截止到2016年12月31日,采用Cox比例风险回归模型计算排便频率和帕金森病的关联。结果研究对象随访(9.9±1.9)年,随访期间诊断帕金森病共808例。在全人群中,控制潜在混杂因素后,与排便频率1次/d者相比,排便频率<3次/周者、隔天1次者、>1次/d者随访期间出现帕金森病诊断的HR值(95%CI)分别为3.62(2.88~4.54)、2.13(1.74~2.60)和0.81(0.63~1.05),排便频率与帕金森病诊断之间的关联存在有统计学意义的线性趋势(P<0.001)。与排便频率≥1次/d者相比,排便频率<1次/d者的HR值(95%CI)在随访≤5年内为3.13(2.32~4.23),在随访>5年后为2.48(2.05~3.01)。分性别分析时的结果与全人群中相似。排便频率<1次/d与帕金森病诊断的关联在老年人中更强。结论基线排便频率越低的研究对象在未来平均10年的随访期内出现帕金森病诊断的风险越高。低排便频率作为一个容易识别的症状,可结合其他与帕金森病相关的早期症状,用于老年人群中帕金森病的早期发现。     

An aptasensor for selective,sensitive and fast detection of lead(II) based on polyethyleneimine and gold nanoparticles

Lead (Pb), as a major environmental contaminant, could be harmful to humans when inhaled or ingested. In this study, we developed a sensitive, selective and fast colorimetric aptasensor for Pb⁺² based on polyethylenimine (PEI) and gold nanoparticles (AuNPs). In the absence of Pb⁺², aptamer binds to PEI. So the well-dispersed AuNPs remain stable with a wine-red color. Upon the addition of Pb⁺², a conformational change happens and a G-quadruplex aptamer/Pb⁺² complex is formed, leading to the aggregation of AuNPs and a color change to blue. This sensor showed a high selectivity toward Pb⁺² with a limit of detection (LOD) as low as 702 pM. Moreover, our fabricated sensor was successfully applied for Pb⁺² detection in rat serum and tap water.     

In utero exposure to dexamethasone causes a persistent and age-dependent exacerbation of the neurotoxic effects and glia activation induced by MDMA in dopaminergic brain regions of C57BL/6J mice

Clinical and preclinical evidence indicates that prenatal exposure to glucocorticoids may induce detrimental effects in the offspring, including reduction in fetal growth and alterations in the CNS. On this basis, the present study investigated whether in utero exposure to high levels of glucocorticoids is a risk factor that may lead to an exacerbation of the central noxious effects induced by psychoactive drugs consumed later in life. To this end, pregnant C57BL6/J dams were treated with dexamethasone (DEX, 0.05 mg/kg per day) from gestational day 14 until delivery. Thereafter, the male offspring were evaluated to ascertain the magnitude of dopaminergic damage, astrogliosis and microgliosis elicited in the nigrostriatal tract by the amphetamine-related drug 3,4-­methylenedioxymethamphetamine (MDMA, 4 × 20 mg/kg, 2 h apart, sacrificed 48 h later) administered at either adolescence or adulthood. Immunohistochemistry was performed in the substantia nigra pars compacta (SNc) and striatum, to evaluate dopaminergic degeneration by measuring tyrosine hydroxylase (TH), as well as astrogliosis and microgliosis by measuring glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1), respectively. Moreover, immunohistochemistry was used to ascertain the co-localization of IBA-1 with either the pro-inflammatory interleukin (IL) IL-1β or the anti-inflammatory IL IL-10, in order to determine the microglial phenotype. In utero administration of DEX induced dopaminergic damage by decreasing the density of TH-positive fibers in the striatum, although only in adult mice. MDMA administration induced dopaminergic damage and glia activation in the nigrostriatal tract of adolescent and adult mice. Mice exposed to DEX in utero and treated with MDMA later in life showed a more pronounced loss of dopaminergic neurons (adolescent mice) and astrogliosis (adolescent and adult mice) in the SNc, compared with control mice. These results suggest that prenatal exposure to glucocorticoids may induce an age-dependent and persistent increase in the susceptibility to central toxicity of amphetamine-related drugs used later in life.     

我国30~79岁成年人中睡眠状况与衰弱的相关性研究

目的 描述我国30~79岁成年人的睡眠状况与衰弱的相关性,并探讨肥胖对二者关系的效应修饰作用。方法 基于中国慢性病前瞻性研究项目的基线调查数据,采用多分类logistic回归,分别分析全体研究对象、不同肥胖状态者睡眠时长较长（≥9 h/d）、较短（≤6 h/d）、失眠障碍、打鼾、不健康睡眠评分与衰弱前期、衰弱期的相关性,并根据分层分析判断肥胖的效应修饰作用。结果 在512 724名研究对象中,2.3%处于衰弱状态,40.1%处于衰弱前期状态。睡眠时长与衰弱评分之间呈U形关系。睡眠时长较短（OR=1.21,95%CI：1.19~1.23）、较长（OR=1.19,95%CI：1.17~1.21）、失眠障碍（OR=2.09,95%CI：2.02~2.17）、打鼾（OR=1.61,95%CI：1.59~1.63）、不健康睡眠评分为1分（OR=1.46, 95%CI：1.44~1.48）、2分（OR=1.97,95%CI：1.93~2.00）、3分（OR=3.43,95%CI：3.21~3.67）均与处于衰弱前期正相关。上述睡眠问题亦与处于衰弱期正相关。在正常体重组中,睡眠时长较短者处于衰弱或衰弱前期、失眠者处于衰弱前期的相关性高于超重肥胖组;而打鼾者处于衰弱或衰弱前期的相关性低于超重肥胖组,按中心性肥胖分层结果类似（交互P值均<0.007）。结论 睡眠时长较长或较短、失眠障碍、打鼾、不健康睡眠评分较高,均与处于衰弱前期或衰弱期正相关,超重肥胖对二者关系具有效应修饰作用。     

Genotypic Characterization of Methicillin-resistant Staphylococcus aureus Isolated from Pigs and Retail Foods in China

Objective To investigate the genotypic diversity of Methicillin-resistant Staphylococcus aureus (MRSA) isolated from pigs and retail foods from different geographical areas in China and further to study the routes and rates of transmission of this pathogen from animals to food. Methods Seventy-one MRSA isolates were obtained from pigs and retail foods and then characterized by multi-locus sequencing typing (MLST), spa typing, multiple-locus variable number of tandem repeat analysis (MLVA), pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. Results All isolated MRSA exhibited multi-drug resistance (MDR). Greater diversity was found in food-associated MRSA (7 STs, 8 spa types, and 10 MLVA patterns) compared to pig-associated MRSA (3 STs, 1 spa type, and 6 MLVA patterns). PFGE patterns were more diverse for pig-associated MRSA than those of food-associated isolates (40 vs. 11 pulse types). Among the pig-associated isolates, CC9-ST9-t899-MC2236 was the most prevalent clone (96.4%), and CC9-ST9-t437-MC621 (20.0%) was the predominant clone among the food-associated isolates. The CC9-ST9 isolates showed significantly higher antimicrobial resistance than other clones. Interestingly, CC398-ST398-t034 clone was identified from both pig- and food-associated isolates. Of note, some community- and hospital-associated MRSA strains (t030, t172, t1244, and t4549) were also identified as food-associated isolates. Conclusion CC9-ST9-t899-MC2236-MDR was the most predominant clone in pigs, but significant genetic diversity was observed in food-associated MRSA. Our results demonstrate the great need for improved surveillance of MRSA in livestock and food and effective prevention strategies to limit MDR-MRSA infections in China.     

Endocrine Disruptors: Data-based survey of in vivo tests,predictive models and the Adverse Outcome Pathway

The protection from endocrine disruptors is a high regulatory priority. Key issues are the characterization of in vivo assays, and the identification of reference chemicals to validate alternative methods. In this exploration, publicly available databases for in vivo assays for endocrine disruption were collected and compared: Rodent Uterotrophic, Rodent Repeated Dose 28-day Oral Toxicity, 21-Day Fish, and Daphnia magna reproduction assays. Only the Uterotrophic and 21-Day Fish assays results correlated with each other. The in vivo assays data were viewed in relation to the Adverse Outcome Pathway, using as a probe 18 ToxCast in vitro assays for the ER pathway. These are the same data at the basis of the EPA agonist ToxERscore model, whose good predictivity was confirmed. The multivariate comparison of the in vitro/in vivo assays suggests that the interaction with receptors is a major determinant of in vivo results, and is the critical basis for building predictive computational models. In agreement with the above, this work also shows that it is possible to build predictive models for the Uterotrophic and 21-Day Fish assays using a limited selection of Toxcast assays.     

Impairment in the mesohippocampal dopamine circuit following exposure to the brominated flame retardant,HBCDD

Many chemicals have been used to increase the safety of consumer products by reducing their flammability and risk for ignition. Recent focus on brominated flame retardants, such as polybrominated diphenyl ethers (PBDEs) has shown them to contribute to neurobehavioral deficits in children, including learning and memory. As the manufacture and use of PBDEs have been reduced, replacement chemicals, such as hexabromocyclododecane (HBCDD) have been substituted. Our current study evaluated the neurotoxicity of HBCDD, concentrating on dopaminergic innervation to the hippocampus. Using an in vivo model, we exposed male mice to HBCDD and then assessed alterations to the dopamine synapse 6 weeks later. These exposures elicited significant reductions in presynaptic dopaminergic proteins, including TH, COMT, MAO-B, DAT, VMAT2, and alpha-synuclein. In contrast, postsynaptic dopamine receptors were not impaired. These findings suggest that the mesohippocampal dopamine circuit is vulnerable to HBCDD and the dopamine terminal may be a selective target for alteration.     

Effects of pubertal exposure to thiazole-Zn on thyroid function and development in female rats

Thiazole-Zn is a newly chinese-created systemic fungicide, and belongs to the sort of thiadiazole compounds, some of which have been found to be thyroid disrupters. To determine the probable adverse effects of thiazole-Zn on thyroid gland and development function, the rodent 20-day Pubertal Female Assay in this study was used. Postnatal days (PND) 22-old Sprague–Dawley rats were administered with thiazole-Zn daily by oral gavage at doses 0, 40, 100, 200 mg/kg/day for 20 days. The thyroid endpoints and development endpoints were assessed. The results indicated that serum TT4 and TSH levels were significantly increased at all concentrations, serum TT3 levels were significantly reduced only at 40 mg/kg thiazole-Zn, but had no difference from controls at the other doses. Thyroid histology was significantly altered at all doses with a clear dose-dependent hypertrophy and hyperplasia of thyroid cell. No histological changes were observed in any of the other observed organs. In addition, this study also found that ovarian weights were significantly decreased, but age and weight at vaginal opening (VO), serum E2 levels were unaffected in all treatment groups. These results demonstrate that thiazole-Zn is likely a thyroid disrupter, but did not demonstrate that it has estrogenic/anti-estrogenic activity.     

Overview of REACH: Issues Involved in the Registration of Metals

New European legislation known as REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) was introduced in 2007 to increase the speed at which the health and/or environmental risks of industrial chemicals were being assessed and managed (REACH (EC) No 1907/2006). REACH consolidated earlier chemicals-control statutes and placed the burden of assessing, and identifying the means to manage risks on industry. This paper details the REACH process for controlling and managing hazardous chemicals and challenges encountered in applying the provisions of REACH and the guidance documents available from European Chemical Agency. Special attention is paid to challenges in evaluating potential health risks of metals such as aluminum and aluminum compounds. Lessons learned from over a decade of experience with REACH legislation are also noted.