Evaluation of endocrine disrupting activity of plasticizers in polyvinyl chloride tubes by estrogen receptor alpha binding assay

Polyvinyl chloride (PVC) tubing is an indispensable medical material for extracorporeal circulation therapy. However, di(2-ethylhexyl)phthalate (DEHP), a suspected endocrine disruptor, can be eluted from PVC, suggesting that an alternative material that does not contain DEHP is needed for clinical applications. First, we evaluated the endocrine disrupting risks of the plasticizers contained in PVC tubes by investigating their binding affinities for the human estrogen receptor alpha (ERα). Our results revealed that, while DEHP has some binding affinity for ERα, neither epoxidized soybean oil nor tris(2-ethylhexyl)trimellitate (an alternative to DEHP) has any affinity for ERα. Second, we evaluated the endocrine disrupting risks of a tube made of newly developed plasticizer-free (PF) materials. We confirmed the presence of DEHP and detected several unidentified substances in plasma stored within the PVC tube. This plasma's competitive binding affinity for ERα was significantly higher than that of control plasma (P < 0.01). In contrast, the profile of plasma stored in the PF tube was similar to that of the control, both in terms of high-performance liquid chromatography chromatograms and competitive binding capacity for ERα, suggesting that the PF tube is biocompatible and is useful for reducing the elution of substances capable of binding to ERα. Presented in part at the 42nd Congress of the Japanese Society for Artificial Organs, October 5–7, 2004, Tokyo, Japan     

鄂西山区1592例成人泌尿系统疾病(USD)调查分析

本文对鄂西自治州一市二县三所医院近八年来(1980年元月～1987年12月)成人USD住院患者1592例的构成比作了回顾性调查分析.结果表明:USD患者占同期住院总人数的3.90%,其常见病种依次为尿路结石,尿路感染,慢性肾炎.急性肾炎、肾结核,慢性肾衰和肾病综合征;上尿路结石病人数有逐年上升趋势,且右侧显著高于左侧(P<0.001);慢性肾衰的病人数每隔1～2年有突然增高现象,1987年比1980年增加了四倍;急性肾炎和肾结核占有较大比例,肾结核为慢性肾衰病因的第三位.这些均为本组USD的临床流行病学特点.作者对各常见病种的特点进行了讨论.     

硅油填充眼的超声检查

目的 观察硅油填充眼超声检查的声像特征及影响因素。 方法 对47例47只硅油填充眼硅油取出手术前后分别进行A型（测定眼轴长度）和B型超声检查。 按超声仪默认参数测定硅油取出手术前后眼轴长度及玻璃体腔容积并观察其声像图特征。 结果 A型超声检查，无晶状体眼硅油取出手术前眼轴长度是手术后的1.465倍，有晶状体眼硅油取出手术前眼轴长度是手术后的1.284倍。按硅油在超声波中的传输速度修改参数后，无晶状体眼硅油取出手术前眼轴长度比手术后长(0.78±0.34) mm，有晶状体眼硅油取出手术前眼轴长度比手术后长(0.56±0.32) mm。B型超声检查，硅油填充眼玻璃体腔容积明显扩大，根据硅油填充量的多少，可分为充满型和部分充满型硅油填充声像；合并视网膜脱离的硅油填充眼可见眼后节多个弧形回声带。 结论 硅油填充眼的眼轴增长，其B型超声影像特征主要受超声波在硅油中的传输速度、硅油填充量、硅油乳化等因素的影响。 （中华眼底病杂志，2004，20：349-351）     

地黄饮子对犬心肌缺血模型心血管血液动力学的影响

目的观察地黄饮子对犬心肌缺血模型作用。方法20只心肌缺血模型犬随机分为对照组、单硝酸异山梨酯组及地黄饮子组,治疗组用地黄饮子,对照组用单硝酸异山梨酯作为对照,服药前后观察心血管血液动力学各参数的影响。结果地黄饮子能显著增加犬心肌缺血模型的冠状动脉血流量和显著改善缺血性ECG,能显著增加心泵功能;对反映心肌收缩力的诸参数,与模型组比较整体上显示有改善的趋势;能防止因心肌缺血引起的血压下降。结论地黄饮子能改善心肌缺血模型心血管血液动力学,治疗心肌缺血。     

Entering markets and bodies: Increasing levels of the novel plasticizer Hexamoll® DINCH® in 24 h urine samples from the German Environmental Specimen Bank

DINCH (diisononylcyclohexane-1,2-dicarboxylate) was introduced into the world market in 2002 as a non-aromatic plasticizer and phthalate substitute. We analyzed 300 urine samples (24 h voids) of the German Environmental Specimen Bank (ESB for Human tissues, ESB Hum) for specific DINCH metabolites by on-line HPLC–MS/MS with isotope dilution quantification. Urine samples of the ESB Hum were from the years 1999, 2003, 2006, 2009 and 2012, chosen to investigate the appearance and a possible trend of DINCH exposure since its market introduction. No DINCH metabolites were detected in the 1999 and 2003 samples. From 2006 on, the percentage of samples with DINCH metabolites above the LOQ increased significantly over the years (7% in 2006, 43% in 2009 and 98% in 2012). The cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (OH-MINCH) was the predominant metabolite. Median (and 95th percentile) concentrations (in μg/l) increased from <LOQ (0.09) in 2006, to <LOQ (1.02) in 2009 to 0.39 (2.09) in 2012. All oxidized DINCH metabolites (OH-MINCH, cx-MINCH, oxo-MINCH) correlated strongly among each other (ρ > 0.75, p < 0.001). The median (95th percentile) DINCH intake in 2012 was calculated to be 0.14 (1.07) μg/kg body weight/day which is considerably below daily intakes currently deemed tolerable. DINCH is regarded to have a preferred toxicological profile over certain anti-androgenic phthalates. The continuation of DINCH measurements in the ESB Hum and other human biomonitoring studies like the German Environmental Survey (GerES) allows tracking the development of DINCH body burdens, the distribution of exposure levels and daily intakes, providing basic data for future toxicological assessment and further epidemiological studies.     

Urinary phthalate metabolites and metabolic syndrome in U.S. adolescents: Cross-sectional results from the National Health and Nutrition Examination Survey (2003–2014) data

Objective

There is limited research on the association between phthalates and metabolic syndrome (MetS). Among adolescents, phthalate exposure, which can occur from multiple sources, has been linked to several risk factors for MetS. The objective was to investigate the association between urinary phthalate metabolite concentrations (i.e., mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), mono-(3-carboxylpropyl) phthalate (MCPP), and di(2-ethylhexyl phthalate (DEHP)) and MetS in adolescents aged 12–19 years using the National Health and Nutrition Examination Survey (NHANES) data (2003–2014). A secondary aim was to assess if observed associations varied by a measure of socioeconomic status, economic adversity, which was defined using parental income and educational attainment as well as household food security.

DREADD: A Chemogenetic GPCR Signaling Platform

Recently, we created a family of engineered G protein-coupled receptors (GPCRs) called DREADD (designer receptors exclusively activated by designer drugs) which can precisely control three major GPCR signaling pathways (Gq, Gi, and Gs). DREADD technology has been successfully applied in a variety of in vivo studies to control GPCR signaling, and here we describe recent advances of DREADD technology and discuss its potential application in drug discovery, gene therapy, and tissue engineering.     

Promoting activity of di(2-ethylhexyl)phthalate in rat liver foci bioassay

Summary The plasticizer DEHP but not DEHS exerted a weak promoting effect in a 12-week rat liver foci bioassay, using weanling female Sprague-Dawley rats. The effect was similar after doses of 200 and 500 mg/kg body weight, given 3 times weekly by gavage for 11 consecutive weeks after initiation with a single oral dose of 8 mg DEN/kg body weight. Lower doses were ineffective. The incidence of foci with deficiency in ATPase was enhanced about twice compared to rats treated with DEN only. The incidence of foci with expression of GGTase was not affected by DEHP treatment. The results match the findings with lifetime exposure studies, when liver tumors were found in rats and mice. The actual risk for man from environmental DEHP contamination seems to be low; the intake from highly contaminated food is calculated to be about 400-fold lower than the lowest effective dose in this study.Abbreviations DEHP di(2-ethylhexyl)phthalate - DEHS di(2-ethylhexyl)sebacate - ATPase adenosine-5-triphosphatase (EC 3.6.1.3) - GGTase gamma-glutamyltranspeptidase (EC 2.3.2.2) - DEN diethylnitrosamine Supported by grants from Umweltbundesamt Berlin (UBA 10604017)