Cyclosporin nephrotoxicity in heart and lung transplant patients

Twenty-two patients with heart, lung or heart and lung transplants maintained on cyclosporin for periods ranging from 3 months to 10 years developed renal insufficiency which was investigated by renal biopsy. The histopathological changes were: (i) severe vascular and glomerular damage due to thrombotic microangiopathy (TM); (ii) a form of focal segmental glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being separate entities, these changes appeared to represent a spectrum of pathology, some biopsies showing all three forms of glomerular injury. In all cases the glomerular changes were accompanied by arteriolar and arterial pathology, and we identified novel ultrastructural changes in the arteriolar endothelial basal lamina. Tubular atrophy was a consistent feature, the severity of which reflected the severity of the glomerular sclerosis, and which appeared to be a consequence of glomerular loss. Our findings are consistent with the nephrotoxic effects of cyclosporin being mediated chiefly via damage to preglomerular vessels and glomerular capillary endothelium. From an analysis of the clinical aspects of these cases, the effects of cyclosporin appear to be to some extent idiosyncratic, and therefore not entirely preventable, but strict monitoring of blood cyclosporin levels is essential to minimize the risk of permanent renal damage. Monitoring urinary protein in addition to plasma creatinine may detect the onset of FSGS, as proteinuria precedes creatinine elevation.      

中药癌痛克对人肝癌细胞HepG2增殖、凋亡及Rb基因表达的影响

目的:通过观察不同浓度癌痛克对肝癌细胞株HepG2增殖及凋亡的作用,以及在相应状态下细胞内Rb基因表达量的改变,探讨中药癌痛克抗肝癌的可能作用机制。方法:实验于2005-09/2006-03在广州医学院中心实验室完成。取对数生长期的HepG2细胞,使细胞静止于G0/G1期。随机分为癌痛克2,10,50mg/L组和对照组,癌痛克2,10,50mg/L组分别加入对应浓度癌痛克(购自河南省肿瘤研究所,由金蝎、土元、九香虫、大黄、人参、灵芝、黄芪等纯中药组成的粉状制剂,功能:消癌肿、消癌痛、消积水、升白排毒),对照组不加药物,每组设4个复孔。MTT法检测各组细胞24,48,72h增殖率,细胞增殖率=[(A570癌痛克组-A570对照组)/A570对照组]×100%;以流式细胞术检测各组细胞24,48,72h凋亡率;RT-PCR方法检测各组细胞24,48,72h细胞内Rb基因mRNA表达量。结果:①2～50mg/L癌痛克具有明显的增殖抑制作用,癌痛克2,10,50mg/L组在24,48,72h与对照组比较,差异有显著性意义(P<0.05);3组各时点两两之间比较差异有显著性意义(P<0.05);同组各时点之间比较差异有显著性意义(P<0.05)。②2～50mg/L癌痛克组可诱导HepG2细胞凋亡,相同作用时间癌痛克2,10,50mg/L组与对照组比较差异有显著性意义(P<0.001);同一时点各组比较差异有显著性意义(P<0.05);同组不同作用时间点比较差异有显著性意义(P<0.001)。③2～50mg/L癌痛克可上调Rb基因的表达,各浓度组在各时点与对照组比较,差异均有显著性意义(P<0.05);24,48,72h癌痛克2,10,50mg/L组之间比较差异无显著性意义(P>0.05);3组各时点比较差异有显著性意义(P<0.05)。结论:中药癌痛克可通过抑制HepG2细胞增殖或诱导其凋亡,而发挥抗肝癌作用;且其诱导细胞凋亡的机制之一可能为通过增加Rb基因的表达而实现。     

转染癌基因的骨髓基质干细胞体外分化特征

目的:观察转染癌基因的骨髓基质干细胞在体外分化情况,为肝细胞癌的细胞源研究提供实验依据。方法:实验于2003-05/2004-06在南方医科大学药理教研室实验室完成。①两步法获取大鼠肝细胞,梯度离心法分离大鼠骨髓基质干细胞。②单基因转染是单独将c-myc或K-ras癌基因瞬时转染大鼠骨髓基质干细胞,6孔培养板中培养,24h后荧光显微镜下观察骨髓基质干细胞转染结果。双基因转染步骤相同,只是将c-myc和K-ras癌基因同时转染大鼠骨髓基质干细胞。③c-myc癌基因转染组、K-ras癌基因转染组、双癌基因转染组常规培养,加入含体积分数为0.1胎牛血清的DMEM培养基,于37℃、体积分数为0.05的CO2孵箱培养,每24h半量更换培养液。④c-myc癌基因转染 肝细胞组、K-ras癌基因转染 肝细胞组、双癌基因转染 肝细胞组将已转染癌基因的骨髓基质干细胞,置于叠加的培养板半透膜的上方(细胞密度均为1×105个/cm2),再将肝细胞置于半透膜的下方(每孔细胞密度为3×105/cm2)进行共培养,其余步骤同常规培养。⑤通过反转录聚合酶式反应和细胞免疫组化检测骨髓基质干细胞分化情况。结果:①癌基因转染24h骨髓基质干细胞检测结果:单独转染c-myc或K-ras癌基因的细胞,其绿色荧光蛋白呈均匀一致分布;双基因转染的细胞,绿色荧光蛋白呈点片状分布。②各组骨髓基质干细胞向肿瘤细胞分化检测结果:c-myc癌基因转染组、K-ras癌基因转染组、双癌基因转染组的骨髓基质干细胞,均未向肿瘤细胞分化;c-myc癌基因转染 肝细胞组、K-ras癌基因转染 肝细胞组、双癌基因转染 肝细胞组的骨髓基质干细胞,均向肝细胞癌发展;空白对照组骨髓基质干细胞细胞均为阴性。此外,双癌基因转染 肝细胞组的骨髓基质干细胞分化增殖迅速,反转录聚合酶式反应和免疫组化检测发现,培养第7天出现甲胎蛋白表达,并迅速增加,而第7天出现的白蛋白和细胞角蛋白18表达迅速减弱,第14天消失。结论:转染癌基因的骨髓基质干细胞,在向肝细胞诱导的条件下,部分癌基因可以使干细胞分化为肝癌细胞;多癌基因转染时,更易于使干细胞分化为肝癌细胞。     

国内干细胞移植治疗心血管疾病的临床研究与应用进展

目的:一些研究证实,干细胞移植可以取代坏死心肌细胞、增加有功能的心肌细胞数量,并建立新血管来改善血供、改善心功能。本文旨在总结近年来国内干细胞移植治疗心血管系统疾病方面的情况。资料来源:应用计算机检索Medline、CBM、CNKI数据库2001-01/2006-11期间的相关文献。包括临床研究(不限研究对象年龄、性别)和基础研究,不限体内或体外研究。中文检索词包括“干细胞,移植,临床研究,心肌梗死,心衰”。英文检索词有“stem cell,bonemarrow,mesenchymal,transplantation”。资料选择:共收集到相关文献820篇,阅读全部文章的文题和大部分文章。纳入标准:①与干细胞移植相关。②与治疗心血管系统疾病相关。③与临床研究相关文献。排除标准:综述文献、重复性研究及Meta分析类文章。资料提炼:共得到符合纳入条件的文献225篇,排除595篇。选择其中30篇进行分析,其中英文13篇,中文19篇,其中中文有1篇为手工检索的增刊。资料综合:①国内于2002年陆续开展干细胞移植治疗心血管系统疾病的探索。②国内用于临床治疗的干细胞类型多为骨髓单个核细胞,其他有骨髓间充质干细胞、骨骼肌干细胞和外周血干细胞也见于临床实验的报道。③干细胞输注途径多以冠脉内注射为主,治疗的临床疾病主要为急性、陈旧性心肌梗死与慢性心功能不全等。结论:干细胞移植可以取代坏死心肌细胞、增加有功能的心肌细胞数量,并建立新血管来改善血供、改善心功能,已应用于临床,未出现安全性问题,故认为干细胞移植技术可以作为心血管系统疾病治疗的手段之一。     

Retention of the posterior cruciate ligament versus the posterior stabilized design in total knee arthroplasty: a prospective randomized controlled clinical trial

Background  

Prosthetic design for the use in primary total knee arthroplasty has evolved into designs that preserve the posterior cruciate ligament (PCL) and those in which the ligament is routinely sacrificed (posterior stabilized). In patients with a functional PCL the decision which design is chosen depends largely on the favour and training of the surgeon.     

创伤患者输血与供者白细胞微嵌合的相关性

输血是挽救创伤患者生命而普遍使用的治疗方法,但其又存在着明显和潜在的危险性。当今,经血液传播传染病和输血反应很少发生,但仍然存在。尽管在临床治疗中试图控制创伤患者休克的发展及损伤的严重度,但其输血后细菌感染、多脏器功能衰竭、死亡的发生率仍较高。     

Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors

Plasmodium falciparum malaria parasites with different capabilities of invading sialic acid-deficient erythrocytes were identified. Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase-treated and Tn erythrocytes twice as efficiently as Thai-2 parasites cultured in normal erythrocytes and seven to ten times more efficiently than a cloned line of Camp parasites cultured in normal erythrocytes. All three parasite lines required sialic acid for optimal invasion, but Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase- treated erythrocytes with 45% efficiency whereas Camp parasites invaded neuraminidase-treated erythrocytes with less than 10% efficiency. P falciparum malaria parasites probably possess two receptors: one that binds to a sialic acid-dependent ligand and another that binds to a sialic acid-independent ligand. Parasites may differ in the quantity or affinity of their receptors for the sialic acid-independent ligand.