Spontaneously hypertensive rats develop pronounced hepatic steatosis induced by choline-deficient diet: Evidence for hypertension as a potential enhancer in non-alcoholic steatohepatitis

Aim: Patients with non‐alcoholic steatohepatitis (NASH) frequently have many co‐morbidities including essential hypertension, which is reported to increase vascular production of reactive oxygen species (ROS) and alter the hepatic anti‐oxidant defense system. Since ROS play a role in the pathogenesis of NASH, it is hypothesized that hypertension modulates the hepatic oxidative status and influences the development of NASH. The aim of this study was to investigate the potential effects of hypertension on the progression of NASH. Methods: Spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats as normotensive controls were fed choline‐deficient (CD) diet for 5 weeks. Histological changes, messenger RNA (mRNA) expression and thiobarbituric acid reactive substances (TBARS) levels in the liver were assessed in each group. Results: Choline‐deficient diet led to pronounced hepatic steatosis in SHR with an 8‐fold increase of the hepatic triglyceride content, while there was no significant increase in WKY. These changes in SHR were associated with significant reduction in the expression of mRNA for peroxisome proliferator activated receptor α, acyl‐CoA oxidase, microsomal triglyceride transfer protein, and apolipoprotein B100. Consistent with the significant reduction of hepatic superoxide dismutase activity and marked downregulation of the gene expression of hepatic antioxidant enzymes, the hepatic TBARS level and the plasma level of alanine aminotransferase were only increased in SHR on CD diet. Conclusions: Spontaneously hypertensive rats receiving CD diet showed severe hepatic steatosis associated with reduction of hepatic anti‐oxidant capacity, leading to increased hepatic oxidative stress and tissue damage. Accordingly, hypertension might have a potential effect on the progression of NASH.     

The role of metabolism in the developmental toxicity of polycyclic aromatic hydrocarbon-containing extracts of petroleum substances

In vitro assays presently used for prenatal developmental toxicity (PDT) testing only assess the embryotoxic potential of parent substances and not that of potentially embryotoxic metabolites. Here we combined a biotransformation system, using hamster liver microsomes, with the ES-D3 cell differentiation assay of the embryonic stem cell test (EST) to compare the in vitro PDT potency of two 5-ring polycyclic aromatic hydrocarbons (PAHs), benzo[a]pyrene (BaP) and dibenz[a,h]anthracene (DBA), and dimethyl sulfoxide extracts from five PAH-containing petroleum substances (PS) and a gas-to-liquid base oil (GTLb), with and without bioactivation. In the absence of bioactivation, DBA, but not BaP, inhibited the differentiation of ES-D3 cells into beating cardiomyocytes in a concentration-dependent manner. Upon bioactivation, BaP induced in vitro PDT, while its major metabolite 3-hydroxybenzo[a]pyrene was shown to be active in the EST as well. This means BaP needs biotransformation to exert its embryotoxic effects. GTLb extracts tested negative in the EST, with and without bioactivation. The PS-induced PDT in the EST was not substantially changed following bioactivation, implying that metabolism may not play a crucial role for the PS extracts under study to exert the in vitro PDT effects. Altogether, these results indicate that although some PAH require bioactivation to induce PDT, some do not and this latter appears to hold for the (majority of) the PS constituents responsible for the in vitro PDT of these complex substances.     

The rise of new psychoactive substances and psychiatric implications: A wide-ranging,multifaceted challenge that needs far-reaching common legislative strategies

The ever-growing number of novel psychoactive substances (NPS) that have been surfacing globally, as well as related changes in drug abuse trends, undoubtedly constitute a difficult and multifaceted challenge for psychiatry. The intake and abuse of such substances has been linked to a risk of psychopathological disturbances, which stem from imbalances of a range of neurotransmitter pathways and receptors. Through an analysis of relevant research articles and reviews (particularly those outlining NPS neurological and cerebral mechanisms of action and psychopathological consequences arising from NPS abuse; research papers more closely focused on chemical/pharmacological aspects have been ruled out), through a systematic analysis of Pubmed, Medline, PsycLIT and EMBASE literature, as well as data released by health care institutions and drug enforcement agencies (among which the World Health Organization, the United Nations Office on Drugs and Crime, the European Monitoring Centre for Drugs and Drug Addiction, Eurojust, the Novel Psychoactive Treatment UK Network, the Court of Justice of the European Union), the authors aimed to elaborate on the most relevant data relative to NPS-related psychiatric effects, focusing on the conceptual and definition-related complexities inherent to NPS, clinical management and motivations for NPS use; moreover, an effort has been made to highlight the possible measures in order to tackle the unremitting rise of such elusive and potentially harmful substances.     

中药制剂关键质量属性确认的思考

通过对中药制剂关键质量属性确认中应重点考虑的问题分析,提出药品关键质量属性的确定应全面考虑药物的有效性、安全性、药用物质本身的性质等方面的因素,同时还应关注中药制剂成型的要求,体现药物质量控制的整体性要求,以提取完整的能表征药品性质的质量控制指标,为企业生产过程控制和药品质量标准建立提供依据。     

地拉罗司有关物质的合成

为控制地拉罗司的药品质量,建立地拉罗司原料药的质量标准,从地拉罗司的合成路线入手,分析并合成其中可能存在的3个有关物质:2-(2-羟苯基)-4H-苯并［1,3-e］GFDA2嗪-4-酮(A)、2-羟基-N-(2-羟基苯甲酰基)-苯甲酰胺(B)、4-［3,5-二(2-羟基苯基)-1H-1,2,4-三氮唑-1-基］苯甲酸甲酯(C),并经¹H NMR和MS确证结构。     

New psychoactive substances: new service provider challenges

Abstract

This paper presents findings from a 6-month study of New Psychoactive Substance (NPS) use in Manchester, UK. Drawing on interviews with 53 NPS users and 31 stakeholders, the paper documents a notable shift in the drug using landscape. It highlights how the homeless community – traditionally associated with alcohol dependency and problematic intravenous heroin and/or crack cocaine use – are now switching to smoking synthetic cannabinoid receptor agonists, while men who have sex with men (MSM) and engage in chemsex – who have traditionally been strongly associated with the recreational use of ecstasy and other stimulants – are now developing problematic intravenous drug using habits. The paper goes on to discuss the implications of this shift for existing models of treatment service delivery. In particular, it outlines the necessity for treatment services to develop innovative engagement strategies, alongside clearer referral pathways and improved service integration.     

国产盐酸洛美沙星滴眼液的质量评价#br#

目的 评价国内不同厂家生产的盐酸洛美沙星滴眼液的质量现状及存在问题。方法 按照国家评价性抽验计划总体要求,采用法定检验方法结合探索性研究进行样品检验,统计分析检验结果。结果 共抽取样品153批次,按国家标准检验不合格率0.7%。探索性研究建立了有关物质检查方法,对光降解杂质的来源与结构进行了确证;考察了盐酸洛美沙星滴眼液处方合理性,发现多家企业处方不合理。结论 目前国内盐酸洛美沙星滴眼液总体质量一般;现行标准有待统一和提高;建议企业优化处方,加强内包装材料遮光性。     

超高效液相色谱-四级杆-静电场轨道阱高分辨液质联用解析泰地罗新注射液中的有关物质

目的 本方法建立了超高效液相色谱-四级杆-静电场轨道阱高分辨质谱联用(UHPLC-Q Exactive)分析注射用泰地罗新中的有关物质。方法 采用(Zorbax SB-C18, 100mm×3.0mm, 1.8μm) 色谱柱,以0.1%三氟乙酸溶液(A)-0.1%三氟乙酸乙腈溶液(B)为流动相,0.3mL/min线性梯度洗脱分离;采用全扫描及自动触发二级质谱扫描的功能测定。采集有关物质的质谱母离子及子离子谱,并进行解析,推测有关物质的结构。结果 在所建立的条件下,泰地罗新及其有关物质之间分离良好,检测出12个有关物质,并对其进行结构解析。结论 建立的Q Exactive四级杆-静电场轨道阱高分辨质谱法能有效地分离分析泰地罗新及其有关物质,为注射用泰地罗新的质量控制和工艺优化提供了参考。