Exposure marker discovery of di-2(propylheptyl) phthalate using ultra-performance liquid chromatography-mass spectrometry and a rat model

Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer and has been suggested to be a subchronic toxicant in rats. DPHP has been approved to be used in food containers and handling by the U.S. Food and Drug Administration. The use of DPHP is still increasing, and the risk of human exposure to DPHP via food may be high. Exposure markers measured in human samples are commonly used to monitor human exposure levels. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a rat model were used to discover tentative DPHP exposure markers. DPHP and mono-(2-propylheptyl) phthalate (MPHP) were used as the precursors for calculating metabolite candidates using biotransformation mass changes of known enzymatic reactions. A rat model was designed to validate these metabolite candidates as tentative exposure markers. A total of 28 signals show dose–response relationships and these signals contain a few isomers. The chemical structures of 15 tentative exposure marker signals were speculated based on the product ion mass spectra from MS/MS analysis. These 15 signals included 7 chemical structures and some of them may be isomers. The different arrangement of the atoms in space of these isomers should be validated by standard compounds in the future studies. Among the 7 speculated chemical structures, 2 structures were novel tentative DPHP metabolites, and 5 structures have been previously reported in the literature. The results indicate that using UPLC-MS and a rat model can be used to identify tentative toxicant exposure markers.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

基于UPLC-LTQ-Orbitrap-MS分析刺果番荔枝叶的化学成分

目的利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶的化学成分进行定性分析。方法采用Waters Acquity UPLC HSS T 3色谱柱(2.1 mm×100 mm,1.8μm),流动相为0.1%甲酸水(A)和乙腈(B)梯度洗脱,流速为0.3 mL/min,进样量2μL,在电喷雾正负离子模式下采集数据。经Reaxys数据库检索番荔枝属类化合物信息,通过质谱信息比对各化合物的m/z值、保留时间、质谱特征碎片等,并结合文献数据对鉴定的化合物进行验证。结果根据各化合物的特征裂解规律,从刺果番荔枝叶中共鉴定出45个化合物,包括16个生物碱类,14个番荔枝内酯类,7个黄酮类和8个其他类化合物,其中以番荔枝内酯类和生物碱类成分居多,与文献报道番荔枝内酯与生物碱类化合物是发挥抗癌的主要活性成分一致。结论利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶中的化学成分进行了快速、准确的定性分析,为刺果番荔枝叶的提取分离与药效物质基础的研究提供依据。     

附件炎性包块的诊断

附件炎性包块是指盆腔炎性疾病引起的附件区包块，多由性传播疾病的病原体（如淋病奈瑟菌和沙眼衣原体）感染引起，性生活活跃的年轻女性是高危人群。附件炎性包块会严重影响女性的生殖健康，故预防重于治疗。盆腔炎性疾病的临床表现差异较大，尚无敏感且特异的实验室检查指标，阴道超声诊断附件炎性包块的准确性较高，是临床常用的检查手段。     

Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape affects the epidemiology of tuberculosis

This study was aimed at determining the cause for the high incidence of tuberculosis (TB) reactivation occurring in males with a low body mass index (BMI). Current thinking about pulmonary TB describes infection in the lung apex resulting in cavitation after reactivation. A different hypothesis is put forward for TB infection, suggesting that this occurs in subclinical apical cavities caused by increased pleural stress due to a low BMI body habitus. A finite element analysis (FEA) model of a lung was constructed including indentations for the first rib guided by paramedian sagittal CT reconstructions, and simulations were conducted with varying antero‐posterior (AP) diameters to mimic chests with a different thoracic index (ratio of AP to the transverse chest diameters). A Pubmed search was conducted about gender and thoracic index, and the effects of BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung apex in low BMI chests, and a four‐fold increase with a low thoracic index, r² = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean thoracic index was statistically significantly lower in males, P = 0.001, and increased with age in both genders. This article is the first to suggest a possible mechanism linking pulmonary TB reactivation to low BMI due to the flattened thoracic wall shape of young male adults. The low thoracic index in young males may promote TB reactivation due to tissue destruction in the lung apex from high pleural stress levels. Clin. Anat. 28:614–620, 2015. © 2015 Wiley Periodicals, Inc.