关键词： Solid organ transplantation   renal transplantation   immunosuppressive drugs  

摘要： In recent years solid organ transplantation has been rapidly developed as a therapeutic intervention that is life-saving and greatly contributes to a better quality of life in organ recipients. The rapid development has been made possible because of a drastic expansion in the immunosuppressive repertoire. Unfortunately, the side effects of these drugs can be severe, which is one of the reasons that life expectancy of transplant patients still significantly falls short of that of the general population. In this review manuscript we will discuss current and future immunosuppressive strategies that are employed in solid organ transplantation. Expanding our understanding of the human immune system will hopefully provide us with newer, smarter drugs that promote immunotolerance without the side effects observed today.

关键词： 药物基因组学   肝移植   免疫抑制药物   研究进展  

摘要： 移植排斥反应是肝移植术后最主要的危险因素,除非给予免疫抑制剂。不同个体之间免疫抑制剂的代谢是存在很大差异,而存在这种差异的原因很可能以药物代谢相关基因有很大关系,所以研究免疫抑制剂的药物基因组学对于提高肝移植术后药物疗效及减少不良反应的发生都有很重要的意义,同时这种方法也有助于免疫抑制剂的个体化用药。

关键词： 免疫抑制药物   器官移植   心脏病   骨髓干细胞移植   移植免疫耐受   髓腔内骨髓移植   心衰患者   心力衰竭  

摘要： 心力衰竭是冠心病、风心病、心肌病等各种心脏病的终末阶段，死亡率高达50％。据我国50家医院的调查，目前住院患者中约有2000万心衰患者。通过骨髓干细胞移植诱导心脏移植后免疫耐受，可以实现移植心脏被患者免疫系统“认可”，仅需少量甚至不需要服用免疫抑制药物，从而实现移植患者的长期生存，并大大减少患者家庭和社会医疗的负担。目前，该团队已成功完成5例骨髓腔内骨髓移植诱导心脏移植免疫耐受病例。

摘要： This article has no abstract.

关键词： 器官移植   免疫抑制剂   治疗性药物监测   药物基因组学  

摘要： 器官移植为保证移植器官在受者体内生存，需长期使用免疫抑制剂。免疫抑制药物在体内代谢的个体差异大，其血药浓度高低与肝、肾毒性损害和排斥反应密切相关。药物代谢转运蛋白（MDR）和药物代谢细胞色素P450同工酶（CYP450）的基因多态性可导致其编码的蛋白表达或活性呈现多态性，不同个体间对某种特定药物代谢的差异是不同个体编码基因的遗传多态性相互作用的结果，这种相互作用导致药物代谢分布以及药物靶标作用的较大差异。在常规临床血药浓度监测基础上，通过研究药物疗效中的遗传变异，分析个体遗传基因组成在决定药物疗效和代谢毒性的特征，检测个体药物反应遗传基因型和表型或基因多态性，预测个体对药物的治疗剂量已开始逐步应用于药物治疗的临床研究，这是临床检验工作者将面临的新任务与挑战。

关键词： 免疫抑制   肝移植   应用   不良反应   撤除   器官移植  

摘要： 背景:现今用于肝移植的抑制免疫排斥反应的药物种类繁多,新型药物也在不断开发中,免疫抑制治疗方案亦多种多样,尚无统一标准。目的:总结和评价肝移植后临床上常用的各型免疫抑制药物并介绍近年来关于免疫抑制治疗方案的热点问题。方法:由第一作者用计算机检索中国全文期刊数据库(CNKI:2000/2011)和PubMed(2000/2011)数据库,检索词分别为"肝移植、免疫抑制、应用、不良反应、撤除"和"Liver transplantation,Immunosuppression,Application,Side-effect,WithdrawaI"。从肝移植后免疫抑制药物的应用现状与进展、免疫抑制方案的选择、激素撤除与免疫抑制剂撤除等方面进行总结。共检索到158篇文献,按纳入和排除标准进行筛选,共纳入45篇。结果与结论:结果表明,目前临床用于肝移植的各种免疫抑制药物都存在着较多不良反应;各种新型、高效、低毒的免疫抑制药物仍在不断研发中,具有广阔前景。激素撤除与免疫抑制剂撤除等新治疗方案的尝试,在一定条件下取得了不错的临床效果,其长期的疗效和安全性有待证实。合理选择和使用免疫抑制药物、开发新型药物、探索新的免疫抑制治疗方案,使肝移植受者的生活质量和生存率得到不断改善。

关键词： Immunosuppressants   Adverse drug reactions   Renal allograft   Engraftment   Iran  

摘要： Objectives: To evaluate the pattern of immunosuppressive drug adverse reactions in adult kidney transplant recipients in Iran Materials and Methods: Adult kidney transplant outpatients under immunosuppressive therapy were recruited into the study. All adverse drug reactions to immunosuppressants and their relevant clinical and paraclinical characteristics were recorded. Causality assessment was performed by the Naranjo algorithm. The seriousness of adverse drug reactions was determined by the World Health Organization definition. The Schumock and Thornton questionnaire was used to assess the preventability of adverse drug reactions. Statistical analyses were performed. Results: A total of 1100 adverse drug reactions were detected from 120 kidney transplant recipients. Increased appetite (9.09%) was the adverse reaction reported most frequently. Causality assessment revealed that 1019 adverse drug reactions (92.64%) were possible. Forty adverse drug reactions (3.64%) were identified as serious. Six hundred seventy-one adverse drug reactions (61%) were preventable. Posttransplant duration was significantly correlated with the number of adverse drug reactions (R=0.19;P=.035). Conclusions: All renal allograft recipients experienced at least 1 immunosuppressant-related adverse reaction. Prolongation of immunosuppressive treatment resulted in an increase in adverse drug reactions.

关键词： Tacrolimus   mycophenolic acid   transplantation   maintenance dosage   swine  

摘要： Immunosuppressive (IS) medication is needed to avoid graft rejection in porcine transplantation models. An ideal IS therapy should have no side-effects, but increased susceptibility to infections, disturbed intestinal microflora and toxic effects on organs and tissues are commonly reported. The aim of the present study was to design an IS protocol with tacrolimus and mycophenolic acid to be used for maintenance therapy in the post-transplant period. An eligible whole blood trough value for tacrolimus was 5-15 mu g/L. Conventional specific pathogen-free pigs were fitted with an indwelling catheter under general anaesthesia, and after the acclimatization period three groups were formed: group A (n = 4) received 0.15 mg/kg body weight (BW) twice daily tacrolimus and 500 mg twice daily mycophenolic acid;group B (n = 4) received 0.3 mg/kg BW twice daily tacrolimus and 500 mg twice daily mycophenolic acid;group C (n = 2) did not receive any medication. Daily clinical examinations and analyses of blood concentrations of tacrolimus and glucose were performed. Total and differential white blood cell counts, enzyme activities, bilirubin and electrolyte concentrations were measured every fourth day. At the end of the experiment, the pigs were killed with an overdose of pentobarbital intravenously and a necropsy was performed immediately. All animals seemed to tolerate the IS treatment well. No alterations in their clinical state of health were observed throughout the study and daily weight gain was similar for the three groups. The necropsy did not reveal any pathological findings related to medication. The study showed that 0.25 mg/kg BW twice daily tacrolimus and 500 mg twice daily mycophenolic acid would be an appropriate maintenance dosage for conventional pigs.

关键词： Cyclosporine   Rapamycin   Sirolimus   Tubular epithelial cells  

摘要： The primary function of the kidney includes the elimination of waste products and the maintenance of fluid and electrolyte composition of the body. The functioning unit of the kidney is the nephron including the glomerulus with a filtration function and the tubule with a reabsorption and secretion function. The fluid and electrolyte homeostasis is achieved largely through selective, vectorial transport facilitated by the renal tubular epithelium. This involves both transcellular and paracellular transport. Paracellular transport across renal tubular epithelial tight junctions (TJs) varies in different parts of the nephron. The relative concentrations of different claudins that are located in the TJ at any time determine the ion and size selectivity of the paracellular diffusion pathway in the kidney as in other tissues. In this article, we review work from our own laboratory and others providing evidence that immunosuppressive drugs, especially cyclosporine A (CsA) and sirolimus (SRL) and can alter transport molecules in kidney tubules. We outline evidence that CsA and SRL can enhance renal epithelial barrier function as indicated by transepithelial electrical resistance (TEER). The possible signalling mechanisms involved in altering the TJs and claudins by CsA and SRL are outlined and involve both TGF-β1 and the ERK 1/2. These effects of CsA and SRL on kidney epithelia cell barrier function may help to explain some of the renal transport defects and nephrotoxicity seen with CsA and SRL. However if similar effects occur systemically in vivo, with these two immunosuppressive drugs, the enhancement of barrier function in areas of the body may decrease luminal antigen presentation, decreasing immune activation and support the immunosuppressive action of these drugs. © Slattery et al.

关键词： 血液滤过   紫癜性肾炎   免疫抑制剂   白细胞介素6   白细胞介素18   肿瘤坏死因子α  

摘要： 目的探讨血液滤过联合药物治疗重症紫癜性肾炎的有效性。方法将66例重症紫癜性肾炎患者按随机数字表法分为治疗组和对照组,每组33例。治疗组接受血液滤过联合常规泼尼松和环磷酰胺治疗,对照组接受常规泼尼松和环磷酰胺治疗,疗程均为1个月。观察两组患者治疗前、后的24 h尿蛋白定量、肾功能、超敏C反应蛋白、白细胞介素6、白细胞介素18、肿瘤坏死因子α水平的变化。结果基线时两组患者在年龄、性别、病程、24 h尿蛋白定量、血肌酐、尿素氮、白细胞介素6、白细胞介素18和肿瘤坏死因子α水平比较差异无统计学意义(P>0.05);经治疗后,治疗组患者的白细胞介素6、白细胞介素18、肿瘤坏死因子α、超敏C反应蛋白、肌酐、尿素氮水平与治疗前比较差异有统计学意义(P<0.05);对照组患者治疗后肌酐、尿素氮、24 h尿蛋白定量与治疗前比较差异也有统计学意义(P<0.05),而白细胞介素6、肿瘤坏死因子α、超敏C反应蛋白指标与治疗前比较差异无统计学意义(P>0.05)。结论血液滤过联合泼尼松、环磷酰胺治疗能有效降低重症紫癜性肾炎患者体内的炎症因子(白细胞介素6、白细胞介素18和肿瘤坏死因子α)水平,降低蛋白尿和改善肾功能。