In vitro metabolism of specific CYP2D and CYP3A opioid substrates using rat liver S9 fractions and mass spectrometry reveal a severe metabolic impairment with increasing age

Codeine and oxycodone are opioids used to alleviate pain. The outcome of the treatment is ultimately related to their metabolism by Cytochromes P450 (CYPs). Depending on the drugs used, alterations in the metabolism of drugs by CYPs can lead to severe consequences including alterations in their efficacy, safety and toxicity. The objectives of this study were to develop a novel HPLC–MS/MS method capable of quantifying codeine and oxycodone along with specific metabolites using an isotopic dilution strategy and study the rate of formation of morphine (CYP2D), norcodeine (CYP3A), oxymorphone (CYP2D) and noroxycodone (CYP3A). The chromatographic separation was achieved using a Biobasic C₁₈ 100 × 1 mm column combined with an isocratic mobile phase composed of methanol and 10 mm ammonium acetate (40:60) at a flow rate of 75 μL/min. The mass spectrometer was operating in scan mode MS/MS and the analytical range was set at 10–10 000 nm . The precision (RSD) and accuracy (RE) observed were 4.4–11.5 and −9.1–6.1% respectively. Liver S9 fractions from 3‐, 6‐, 12‐ and 18‐month‐old male Sprague–Dawley rats were prepared and Michaelis–Menten parameters were determined. The derived maximum enzyme velocity suggested a rapid saturation of the CYP2D and CYP3A active sites in the liver S9 fractions of 18‐month‐old rats. Moreover, metabolic stabilities of codeine and oxycodone in rat liver S9 fractions were significantly greater for the 18‐month‐old rats. This study suggests that there is an impairment of CYP2D and CYP3A metabolism in aging rats.     

基于用于推进的功率定量分析运输效率的发展趋势(英文)

基于Nakazawa教授提供的有关20世纪70年代到2008年相关船舶数据,对船舶特定输出功率(SOP)进行定量分析,探讨船舶运输效率的发展趋势和制约因素.     

试论未来我国财务管理的发展趋势

知识经济时代的到来，给我国财务管理的实践创造了广阔的前景。针对我国企业目前的财务管理状况，借鉴西方国家对财务管理活动的经验，对知识经济时代财务管理的发展趋势和特点进行了探讨。     

Microstructure evolution of T91 heat-resistant steels after long-time aging

To investigate the evolution of microstructure damage degree and the precipitated phases of heat-resistant metal in power plant under high temperature and stress environment, the high-temperature aging tests were conducted to investigate the aging behavior of T91 steel at different temperatures and stress. The optical microscopy, scanning electron microscopy, and transmission electron microscopy were used to investigate the structure and precipitated phases, the results showed that the orientation characteristics of tempered martensite was dispersed, and the grain size is obviously increased. The density of dislocation decreased with increasing temperature and stress. The important strengthening phase of M23C6 (M=Fe, Cr) was coarsened by the diffusion of main alloying elements Cr, while the smaller size MX (M=Nb,V; X=C, N) phase distributed in the grain is relatively stable in the aging.     

论辛亥革命时期女性报刊与女性解放思潮

就女性解放思潮而言,辛亥革命时期,在西方女权主义学说和资产阶级民族民主革命的冲击下,男女平等之说转换为＂男女平权＂,具有中国特色的女权思想终于形成,女性解放思潮的发展终于达到高峰期。而这时的女性报刊在女性解放思潮的冲击下,从戒缠足、倡导女学、要求女性自立、倡导婚姻自由等各个方面来进行鼓吹、宣传,可以说,作为女性解放思潮的体现者和宣传者,女性报刊向我们展示了极其丰富的内涵。而女性报刊的这些宣传鼓动反过来又推动着现实社会中女性解放思潮的发展。     

图书馆未来发展趋势探讨

介绍了现代图书馆的发展现状,分析了虚拟图书馆的局限性及传统图书馆的优越性,对图书馆未来发展的趋势进行了探讨.     

语文课堂教学中合理运用多媒体的探讨

由于Intemet技术性能的不断发展和完善，网络不仅可以提供最新信患，如今传统学校的教育活动也可以在网络上实施，于是多媒体教学成了教育方式的一股潮流。文章通过语文课堂教学中运用多媒体的现状进行分析，以期引发更深层次的思考。     

元数据发展趋势研究

以CNKI电子技术及信息技术数据库所收录的（2001-2009）1516篇文章为研究对象,以探讨量性与质性的内容分析,探究元数据（Metadata）在图书情报学科的研究发展。     

新世纪以来《日出》研究综述

对《日出》文本的深入解读,对《日出》人物形象的多方面剖析;对《日出》版本的研究等是近来年对《日出》研究的总体特征和趋势。     

词源学视阈下中西方教育差异探源

中西方教育的差异是一种事实性存在。造成中西方教育差异的一个重要原因就是中西方对教育概念的原初性定义的差异。事实上，中西方对教育概念的原初性定义的差异，己在思想上勾勒出了各自教育发展的“蓝图”，并在教育实践中生成了中国和西方国家教育不同的特点。