Determination of metabolic profile of anti-malarial trioxane CDRI 99/411 in rat liver microsomes using HPLC

CDRI 99/411 is a potent 1,2,4‐trioxane anti‐malarial candidate compound of the Central Drug Research Institute, India. This study aimed to conduct comprehensive in vitro metabolic investigations of CDRI 99/411 to corroborate its preclinical investigations. Preliminary in vitro metabolic investigations were performed to assess the metabolic stability [in vitro half‐life (t_1/2) and in vitro hepatic intrinsic clearance (Cl_int)] of CDRI 99/411 in male Sprague–Dawley rat and human liver microsomes using validated high‐performance liquid chromatography with photodiode array detector. The observed in vitro t_1/2 of the compound in rat and human liver microsomes was 13 min with in vitro Cl_int 130.7 ± 25.0 μL/min/mg and 19 min with in vitro Cl_int 89.3 ± 17.40 μL/min/mg. These observations suggested moderate metabolic degradation and in vitro Cl_int with insignificant difference (p > 0.05) in the metabolic stability profile in rat and human. Hence, in vitro metabolic investigations were performed with rat liver microsomes. It was observed that CDRI 99/411 exhibited sigmoidal kinetics. At nonlinear regression (r ≥ 0.99) EC₅₀ and Hill slope values were 17 µm and 1.50, respectively. The metabolism of CDRI 99/411 was primarily mediated by CYP3A2 and was inferred by CYP reaction phenotyping with known potent inhibitors. Two metabolites of CDRI 99/411 were detected which were undetectable on incubation with 1‐aminobenzotriazole and ketoconazole. Copyright © 2011 John Wiley & Sons, Ltd.     

基于唾液的拉曼光谱检测进行肝癌诊断的研究

表面增强拉曼光谱技术是近年来快速发展的一种痕量特征标记性物质检测技术, 达到了分子识别水平, 具有很高的灵敏度, 能够精确地分析和了解物质结构和成分。人体唾液中含有大量体征相关的特异性蛋白质和分泌物质。唾液检测具有无创、获取方便、适合开展大规模普查等优点。表面增强拉曼光谱检测技术可以快速地对唾液进行检测, 二者的结合, 有可能成为一种癌症诊断的新方法。本文利用表面增强光谱技术对肝癌患者进行实验研究, 通过对肝癌患者唾液的采集、样品的处理、光谱的采集及光谱分析, 肝癌特异性标记物AFP(alpha fetoprotein)的检测及分析等过程得到肝癌相关特征信息, 表明肝癌患者与正常人的唾液样本分类良好, 灵敏度及特异性较好; 进一步验证了AFP抗原的分子组成, 且AFP抗原的拉曼强度基本随浓度的递增呈递减趋势; 对肝癌患者的唾液样本及AFP抗原的拉曼光谱进行比对分析, 提示利用表面增强拉曼光谱检测唾液有可能诊断早期癌症。     

Active Site Titration of Horse Liver Alcohol Dehydro-Genase by Dual Wavelength Specthophotomethy

Abstract

A simple dual wavelength spectrophotometric method for determining the active site concentration of horse liver alcohol dehydrogenase is described. The method is rapid, sensitive, accurate and requires minute amounts of enzyme. A comparison between this new application of the dual wavelength technique and the conventional methods, ordinary photometry and spectrofluorometry is furthermore discussed.     

紫心甘薯多糖对四氯化碳肝损伤小鼠的保护作用

研究紫心甘薯多糖对四氯化碳(CCl4)诱导小鼠免疫性肝损伤的保护作用及可能作用机制.以不同剂量的紫心甘薯多糖200、400、800 mg.(kg.d)-1分别给予小鼠灌胃,设立对照组,连续10 d作预处理,腹腔注射0.1%的CCl410 ml.kg-1建立CCl4诱导小鼠肝损伤模型.测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)酶活力、总胆红素(TBIL)、总蛋白(TP)含量,测定肝组织中超氧化物岐化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)水平,并进一步观察肝组织病理组织学变化.紫心甘薯多糖各剂量组均能明显地抑制血清中ALT、AST、LDH、TBIL的升高和TP的下降,降低肝脏中MDA的含量,提高肝组织中SOD和GSH活性,减轻CCl4对肝脏细胞的病理损伤.紫心甘薯多糖对CCl4致小鼠急性肝损伤具有明显保护作用,其作用机理可能与抗氧化作用有关.     

补肾调肝法治疗对精液异常患者精液微量元素改变的观察

研究了２６例精液异常患者使用补肾调肝法治疗后其精液锌、铜、铅等元素的改变。２６例患者在治疗后精液质量有明显改善,其中精液中锌含量与治疗前相比有明显提高,治疗前后分别为（２．０６＋１．０９）ｍｍｏｌ．Ｌ和（２．４８±１．０５）ｍｍｏｌ·Ｌ（Ｐ＜０.０１）,差异具有显著性意义。精液中的铜含量也有所提高。铅含量比治疗前减少,但并不具显著性。     

Simultaneous supercritical-fluid extraction of nine individual aliphatic hydrocarbons, aroclor 1260, aroclor 5460 and four PCB congeners from chicken liver

Summary Supercritical carbon dioxide fluid extraction (SFE) has been used for selective extraction of nine aliphatic hydrocarbons, Aroclor 1260, Aroclor 5460, and four PCB congeners from chicken liver. Alumina was used as adsorbent and methanol as modifier. Recoveries were between 53 and 100% for aliphatic hydrocarbons, 83 and 95% for Aroclor 1260 and Aroclor 5460, and 81 and 98% for PCB congeners.     

利用PCC技术预测γ射线对肝癌细胞的辐射效应

利用早熟染色体凝集技术预测研究了γ射线对肝癌细胞SMMC-7721的辐射效应。结果表明,G1和G2期细胞内的染色单体和等点染色单体断裂数与照射剂量之间存在线性相关性,染色单体断裂总数与细胞存活率之间存在良好的线性相关性。说明辐射诱导的染色单体断裂可以作为预测SMMC-7721细胞内在辐射敏感性的指标,也可为临床诊断和治疗肝癌提供依据。     

Electrochemical Detection of Clenbuterol in Pig Liver at Pyrrole-DNA Modified Boron-doped Diamond Electrode

Introduction Clenbuterol { 4-amino-[( tert-butylamino) meth-yl]-3,5-dichlorobenzyl alcohol hydrochloride} is aβ-agonist drug[1]. It can improve the ratio of muscle tofat when it is administrated with high doses to ani-mals[2,3]. However, the residues of clenbuterol(CL)are toxic to humans, leading to sickness and possibleheart complication[4]. It has been reported that CL iseasy to accumulate in animal livers.Recently, some analytical methods for the detec-tion of CL, such as HPLC[5], GC…     

NaF饮水喂养的小白鼠肝脏线粒体代谢热化学研究

利用 L KB2 2 77生物活性检测系统 ,测定了用含不同浓度 Na F饮水喂养的小白鼠肝脏线粒体代谢热曲线 ,实验表明 ,饮水中 Na F浓度增加 ,最大热功率增大 ,代谢产热增加 ,停滞期和活性维持时间缩短 .热曲线测定完毕后的样品 ATP浓度分析表明 ,随着 Na F浓度增加 ,系统的 ATP浓度降低 .结合透射电镜对肝细胞超微结构研究结果 ,根据化学渗透假说对实验结果进行了比较完满的解释     

脂肪肝及其影响因素分析——中国科学技术大学体检专向调查

为探讨高级知识分子患脂肪肝的概率与肥胖、高血压、高胆固醇、高甘油三脂之间的关系 ,运用多因素数理统计分析方法对 4 91名副教授级以上教职工体检数据进行了分析。结果显示probit模型比 logistic模型能更好地拟合所分析的数据 ,而且脂肪肝与是否肥胖 ,是否高血压存在统计关联 ,既肥胖又患高血压的人患脂肪肝的概率是二者都正常的人的 2 .68倍。 χ2检验显示 ,患脂肪肝的男性显著高于女性。中国科大高级知识分子脂肪肝高检出率及其与肥胖、高血压关系的现象应引起足够重视