Gliotoxin non-selectively induces apoptosis in fibrotic and normal livers.

BACKGROUND: Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis. Several lines of evidence indicate that inducing apoptosis of hepatic stellate cells (HSC) may lead to regression of liver fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC. However, the clinical use of GTX may be limited because of the lack of cell and tissue specificity, causing a high risk of potentially severe adverse effects. The aim of this study, therefore, was to study the effect of GTX on different cells of the liver. METHODS: We used normal and fibrotic precision-cut rat liver slices to study the effect of GTX on the various resident liver cell types. In these slices, the complex cell-cell interactions are preserved, which closely mimics the in vivo situation. RESULTS: GTX exhibited a potent apoptosis-inducing activity in these slices. Both immunohistochemical stainings and real-time mRNA techniques showed that this apoptosis-inducing effect was seen in HSC. However, Kupffer cells and liver endothelial cells were also affected by GTX, whereas hepatocytes were only mildly affected. CONCLUSIONS: This study indicates that the apoptosis-inducing strategy to treat liver fibrosis has high potential, but it will be necessary to develop an HSC-specific therapy to prevent adverse effects.     

乙肝Ⅲ号合近红外信息辐照治疗乙型肝炎肝纤维化的临床研究

目的：观察乙肝Ⅲ号合近红外信息辐照治疗乙型肝炎肝纤维化的疗效。方法：选择乙型肝炎肝纤维化住院病人234例，分为乙肝Ⅲ号治疗组(76例)、近红外信息辐照组(73例)和联合治疗组(85例)。在基础治疗(包括甘利欣，复方丹参液等)上采用单纯的中药外敷、肝病治疗仪近红外信息辐照以及两联合治疗等三种不同方法，观察各组患临床症状、体征、肝功能以及相关指标如PGA、肝纤三项(透明质酸(HA)、层黏蛋白(LN)、CⅣ型胶原(CⅣ))、肝血流的变化。结果：3组皆能改善临床症状，但以联合治疗组为；3组肝功能复常比较，差异有显性，但组间比较，差异无显性；在改善PGA、肝纤三项和肝血流量方面，联合治疗组优于乙肝Ⅲ号治疗组和近红外信息辐照组。结论：乙肝Ⅲ号合近红外信息辐照对乙型肝炎肝纤维化有一定的治疗作用，且较单一方法疗效明显。     

生三七对肝纤维化小鼠血液流变学的影响

目的:观察生三七对肝纤维化小鼠血液流变学的影响。方法:复制小鼠中毒性肝纤维化模型,生三七粉灌胃6周,检测全血粘度、血浆粘度、红细胞压积等血液流变学参数,并行肝脏病理组织切片检测。结果:与空白对照组比较,肝纤维化模型组小鼠全血粘度、血浆粘度、红细胞压积明显增高(P<0.05,P<0.01),生三七治疗后小鼠全血粘度、血浆粘度、红细胞压积明显降低(P<0.05,P<0.01);肝脏病理组织切片显示使用生三七后,肝纤维化程度有明显改善。结论:生三七可降低血液粘度,延缓肝纤维化的发展。     

Resolution of skin fibrosis and joint contractures in aggressive diffuse systemic sclerosis using autologous stem cell transplantation

The use of haematopoietic stem cell transplantation (HSCT) has now expanded beyond the domain of haematological diseases. Increasingly, the benefits of intense immunosuppression in the management of severe autoimmune diseases are being recognized. In diffuse systemic sclerosis (SSc), there has been increasing evidence of the efficacy of HSCT in improving morbidity and mortality. We present the first Australian patient to undergo autologous HSCT for SSc and review the current literature in the use of HSCT in SSc. Remarkably, the patient had complete resolution of skin disease (modified Rodnan skin score 27/51–0/51), tenosynovitis, synovitis and myositis.     

早期大剂量甲泼尼龙联合环孢素A冲击治疗对口服百草枯中毒患者预后的影响

目的 观察早期大剂量甲泼尼龙联合环孢素A冲击治疗对口服百草枯(PQ)中毒患者病死率、肺纤维化发生率的影响.方法 38例口服PQ中毒患者除常规给予洗胃、血液灌流等治疗外,早期给予大剂量糖皮质激素联合免疫抑制剂(环孢素A)冲击治疗.定期监测动脉血气分析、胸部CT、肝肾功能等指标.分析口服PQ中毒患者的病死率、肺纤维化的发生率.结果 38例PQ中毒患者中死亡13例,病死率为34.2%,其中12例患者在服毒后1周内死于多器官功能衰竭,另1例死于肺纤维化.25例存活者中,有18例在住院期间发生不同程度的氧合下降,其中17例胸部CT提示肺部间质性改变,13例出现两个以上脏器(肺、肝、肾)功能损伤.25例存活患者出院后随访1个月未诉特殊不适.结论 早期大剂量甲泼尼龙联合环孢素A冲击治疗可改善PQ中毒患者的预后,但进一步明确此方法 的疗效需开展大样本的随机、双盲对照研究.     

Haploinsufficiency of Pkd2 is associated with increased tubular cell proliferation and interstitial fibrosis in two murine Pkd2 models.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited human kidney disease and is caused by germline mutations in PKD1 (85%) or PKD2 (15%). It has been estimated that around 1% of tubular cells give rise to cysts, and cell hyperproliferation has been noted to be a cardinal feature of cystic epithelium. Nevertheless, it is uncertain whether the increase in proliferative index observed is an early or late feature of the cystic ADPKD kidney. METHODS: Two Pkd2 mouse mutants (WS25 and WS183) have been recently generated as orthologous models of PKD2. To determine the effect of Pkd2 dosage on cell proliferation, cyst formation and renal fibrosis, we studied renal tissue from Pkd2(WS25/WS25) and Pkd2(+/-) mice by histological analysis. We also examined the proliferative index in archival nephrectomy tissue obtained from patients with ADPKD and normal controls. RESULTS: The proliferative index of non-cystic tubules in Pkd2 mutant mice as assessed by proliferating cell nuclear antigen and Ki67-positive nuclei was between 1-2%, values 5-10 times higher than control tissue. Similarly, the proliferative index of non-cystic tubules in human ADPKD kidneys was 40 times higher than corresponding controls. In Pkd2 mutant mice, significant correlations were found between the fibrosis score and the mean cyst area as well as with the proliferative index. Of significance, proliferating tubular cells were uniformly positive for polycystin-2 expression in Pkd2(+/-) kidney. CONCLUSION: These results suggest that an increase in cell proliferation is an early event preceding cyst formation and can result from haploinsufficiency at Pkd2. The possible pathogenic link between tubular cell proliferation, interstitial fibrosis and cyst formation is discussed.     

腹腔镜改良性腹膜后淋巴清除术治疗临床Ⅰ期睾丸非精原细胞瘤

目的:探讨腹腔镜改良性腹膜后淋巴清除术初步经验,评估其手术可行性和近期临床疗效。方法:2004年10月~2006年7月,对7例临床诊断为Ⅰ期睾丸非精原细胞瘤患者,施行了经腹腔途径腹腔镜改良性腹膜后淋巴清除术,年龄26~36岁,平均年龄为30岁,睾丸肿瘤大小为3.0 cm×2.5 cm×2.0 cm~6.5 cm×4.5 cm×3.0 cm,左侧3例,右侧4例,均通过B超、腹膜后CT、胸片检查,并施行了根治性睾丸切除和病理证实。术后淋巴结阳性患者施行了3个疗程的化疗。结果:7例均获得成功,无1例改开放手术。手术时间为120~210 min,平均160 min,手术失血量50~200 ml,平均150 ml,均未输血。术后1~3 d肛门排气,于1~2 d拔除引流管;术后平均住院时间5.5 d。病理报告6例均无转移性淋巴结,其中1例为1/18淋巴结转移,术后无明显并发症。随访6~32个月,平均14个月,阴茎勃起功能良好,射精功能正常。定期复查血hCG、AFP均阴性,B超复查均未发现腹膜后淋巴结,胸片表现均正常。其中淋巴结阳性1例患者术后接受3个疗程的辅助化疗,随访6个月,无瘤存活。结论:腹腔镜改良性腹膜后淋巴清除术具有损伤小、并发症少、术后恢复快等特点,可以代替传统开放手术。     

参附注射液对单侧输尿管梗阻大鼠肾脏肝细胞生长因子表达的影响

目的：探讨单侧输尿管梗阻后大鼠肾间质纤维化发生过程中肝细胞生长因子（HGF）的表达及中药参附注射液对其的影响。方法：采用单侧输尿管结扎（UUO）制造梗阻性肾病模型，将56只大鼠随机分为对照组（假手术组）、手术组（UUO组）和治疗组（UUO＋参附），术后7d、14d观察肾组织病理改变，应用免疫组织化学方法检测肾组织中HGF的表达。结果：与对照组相比，手术组肾间质出现了明显的纤维化，HGF的表达在术后第7天明显增加，第14天较第7天减弱，与手术组相比，治疗组肾间质纤维化明显减轻，而且HGF的表达在术后第7天明显上调，第14天较第7天上调更明显，有统计学差异（P〈0．05）。结论：参附注射液可以上调肾组织HGF的表达，减轻肾小管一间质纤维化，发挥肾保护作用。     

Workshop on Late Renal Allograft Dysfunction

Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are quite varied in the overall recipient population, and that individual rates for many recipients may not change substantially over time. Moreover, analyses also reveal distinct predictive factors for both early and late functional decline. Long-term outcome studies for renal transplantation, however, might be significantly limited by incomplete data sets for assessing clinical endpoints. In view of the heterogeneous factors that may cause progressive allograft injury, more routine biopsy sampling would allow a more complete characterization of induced injuries. Elucidating mechanisms of renal fibrosis in response to injury, in experimental systems and humans, is also an important goal in better understanding chronic allograft damage. Regulation of cell senescence genes and epithelial to mesenchymal transition, studied in other models of renal fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent technical advances in analyzing biological samples may play a pivotal role in identifying and validating surrogate markers of allograft function for future interventional trials in transplantation.     

角蛋白人工腱膜预防全椎板切除术后硬脊膜黏连

[目的]探讨角蛋白（keratinsubstance，KS）人工腱膜材料用于预防全椎板切除术后硬脊膜黏连的效果。[方法]Wistar大白鼠60只，随机分3组，每组20只，咬除T。：全椎板，造成2rnrnX8rnlffl大小的椎板缺损，加入不同处理因素，A组：空白对照组；B组：人工腱膜组；C组：白体腱膜组。术后2、4、8，12周处死动物，各时间点大体观察采用Rydell瘢痕黏连程度评级标准评分。完整取出T。：节段，包括椎旁肌。经HE染色后，镜下组织学观察采用改良Nussbaum标准行评分。同时切取2，4、8、12周人工腱膜组硬膜外瘢痕组织进行透射电镜观察。所测数据行Kruskal—Wallis秩和检验，取a〈0．05作为统计显著差异的标准。[结果]KS人工腱膜材料无毒性和排异反应：A组的Rydell评分，改良Nussbaum评分高于B、C组（P〈0．05），B组C组比较无差别（P〉0．05）。B、C组与对照组比较，均能够明显减少椎板切除术后的硬膜外瘢痕形成。[结论]硬膜外瘢痕黏连主要来自硬膜后方的血肿和成纤维细胞（fibroblast，FB）的增殖。KS人工腱膜具有良好的组织相容性，无局部及全身的不良反应，具有良好物理屏障作用。将l（S人工腱膜放置在椎板缺损处，能够有效的防止纤维组织侵入椎管，预防硬膜外瘢痕黏连。在动物实验中，KS人工腱膜能够安全有效的预防椎板切除术后硬膜外瘢痕黏连。