Genetic toxicity assessment using liver cell models: past,present, and future

ABSTRACT

Genotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment.     

缺血性卒中和短暂性脑缺血发作的二级预防指南的新认识

2006年2月,美国卒中协会主办的国际卒中大会和当月出版的Stroke颁布了新的卒中和短暂性脑缺血发作(transient ischemic attack,TIA)二级预防指南[1,2]。新指南撰写委员会主席、美国哥伦比亚大学Sacco教授强调,与以前的指南[3,4]相比,新指南有了新的改进,它是一个以充分和完整证     

养阴健脾法临床应用举隅

养阴健脾法系治疗脾阴不足证的一大法则，用于临床常获奇效。现仅援引验案几则介绍如下。     

在膀胱肿瘤并发前列腺增生症患者中采用同次施行膀胱肿瘤切除术和保留尿道粘膜前列腺切除术探讨

目的 探讨膀胱肿瘤并前列腺增生症患者同期施行膀胱肿瘤切除术和保留尿道粘膜前列腺切除术的可行性.方法 对同期施行经尿道膀胱肿瘤切除术及保留尿道粘膜前列腺切除术的16例膀胱癌合并前列腺增生症患者的临床资料进行了回顾性分析.结果 该组患者均顺利康复,无明显合并症,术后复诊,随访时间2～4年,3例出现肿瘤复发.结论 同期施行膀胱肿瘤切除术和保留尿道粘膜前列腺切除术,安全、效果肯定,值得基层医院推广应用.     

33例肺上沟癌的临床特点及放疗疗效

目的　探讨肺上沟癌的临床特点及放疗疗效和不良反应。方法　回顾性分析 3 3例肺上沟癌住院病人的临床特征和常规放疗的疗效。结果　肺上沟癌占原发性支气管肺癌的 2 9% ,常见症状为 :患侧肩、背和上肢疼痛 ( 78 8% ) ,后 1,2 ,3肋骨或椎骨破坏( 5 7 6% ) ,Horner’s综合征 ( 3 6 7% ) ;少见的症状为 :咳嗽 ( 2 7% ) ,咯血 ( 9% ) ;中位生存期为 8 4月 ;1,3 ,5年生存率分别为 3 5 6% ,12 3 % ,4 6% ;放疗反应可耐受。结论　肺上沟癌相当少见 ,其临床特征基本符合pancoast综合症 ,本病预后差 ,但放疗可缓解疼痛 ,提高生存质量。     

论我国医患冲突成因及和谐关系构建

目前我国医患之间的矛盾与冲突，实质上是新时期我国社会矛盾在卫生工作中的具体表现，反映了社会群体在经济状况、价值取向、角色意识、道德水平、法律法规等多方面的矛盾与冲突。和谐医患关系应是构建我国和谐社会的内容之一。和谐医患关系的构建需要完善的社会医疗保障体系建立、国家卫生行政管理加大、财政补偿合理投入、医疗服务质量提高、医学知识教育普及与提高、媒体理性传播、社会大众道德控制水平提升，法律法规完善等全方位的努力，有赖于医事主体双方及全社会的关注与通力改善。     

医改尚未成功,路在何方?

目前我国医疗制度改革尚未取得成功,这与计划经济向市场经济转轨这历史时期及卫生工作的特殊性有关,出现问题,甚至失误,在所难免。提出(1)医改的目的是确保全国人民健康,人人享有医疗保健。(2)把卫生系统推向市场,医疗机构商业化,不是医改的方向。(3)预防为主,健全预防医学制系。(4)国家增加投入。(5)制定公立及私立医院各项制度,保护医务人员的合法权益。(6)加强社区基层医疗机构的建设。     

Pulmonary Lophomonas blattarum infection in patients with kidney allograft transplantation

The aim of the study was to analyse the clinical manifestation and management of pulmonary Lophomonas blattarum infection in four allograft transplantation recipients retrospectively. Four patients with pulmonary L. blattarum infection were diagnosed by using Fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) examination. Their clinical manifestation and management are summarized. Four cases of pulmonary L. blattarum were found during the period from the second month to the third month after transplantation. Concurring infection by other pathogens was found in three of them. Common initial symptoms included fever (>38 degrees C) without cough and breathlessness. Lower lobe shadowing could be found on chest X-ray. Body temperature decreased to the normal range in three patients and to 37.5 degrees C in the other one, after intravenous injection of metronidazole and tapering immunosuppressant. Radiological examination confirmed improved health condition of the patients afterwards. Two patients received repeated FOB and only dead L. blattarum was found. Pulmonary L. blattarum infection in allograft transplant recipients carry relatively obscure initial symptoms. Possible L. blattarum infection needs to be screened in post-transplantation pulmonary infection patients with similar symptoms, especially in those who respond poorly to anti-infection treatment. Microscopic examination of BAL fluid can help to identify pulmonary L. blattarum infection and metronidazole is an ideal treatment choice.     

牙冠延长术在残根残冠修复中的临床疗效

目的评价牙冠延长术在牙体缺损达龈下的残根残冠修复中的临床疗效。方法自2004年5月至2005年6月,对32例患者的36颗牙体缺损达龈下的患牙,术前按断端位于龈下最深距离分为A组(20颗患牙,距离<3.0mm)和B组(16颗患牙,3.0mm≤距离≤4.0mm),均采用牙冠延长术暴露龈下牙体断面,术后6周行桩冠修复。分别记录和比较手术前、后牙周探诊深度(PD)、菌斑指数(PLI)、龈沟出血指数(SBI)和牙齿松动度,以观察临床疗效。结果术后随访患者6个月,两组病例术后6周牙体断端均暴露较好、龈缘颜色正常,术后修复效果有效率为100%,满意率为77.78%。A组术后无松动,修复效果满意;B组术后50.00%出现Ⅰ度松动,修复效果欠佳,两组修复效果比较差异有显著意义(P<0.05)。术后各阶段两组的PD、PLI、SBI均明显优于术前(P<0.05),但两组术后牙周指数比较差异无显著意义(P>0.05)。结论牙冠延长术有利于残根残冠的保存和修复,但要注意适应证的选择。