Antimitochondrial antibodies (AMA) in primary biliary cirrhosis. I. Separation of the PBC antigen activity from mitochondrial ATPase activity

Antimitochondrial antibodies are found in a variety of autoimmune liver diseases, particularly primary biliary cirrhosis. The antigen against which these antibodies are directed is localized on the inner mitochondrial membrane. Earlier work suggested that this antigen was associated with the mitochondrial ATPase. However, we have succeeded in separating the enzyme activity from the antigenic activity using gel filtration and ion-exchange chromatography. Furthermore, the antigenic activity is not affected by modulators of ATPase enzymatic activity like aurovertin or oligomycin. The antigenic activity is, however, very susceptible to reagents which block thiol groups. The mitochondrial antigen, in contrast to the ATPase enzyme, is found in high amounts in brown fat mitochondria. Identification of this antigen may help to explain why specific antimitochondrial antibodies arise in the sera of patients with primary biliary cirrhosis.Abbreviations ATPase adenosine triphosphatase - PBC primary biliary cirrhosis - AMA antimitochondrial antibodies - SMPs submitochondrial particles - CFT complement fixation test - SDS sodium dodecyl sulfate - BSA bovine serum albumin - BAT brown adipose tissue     

穴位注射速尿治疗肝硬化腹水的疗效观察

目的:观察穴位注射速尿治疗肝硬化腹水的临床效果,寻求治疗肝硬化腹水的理想的治疗方式。方法:取穴足三里、三阴交、肾俞注射速尿20-40mg。结果:疗效显著经。统计学处理P<0.05据有显著差异。讨论:穴位注射速尿治疗肝硬化腹水,操作简单且用药剂量小,副作用小,安全性高疗效显著。     

Specific gene expression patterns in liver cirrhosis

Liver cirrhosis (LC) is a complex disease that can develop into hepatocellular carcinoma (HCC). In an effort to investigate genetic differences between LC and HCC, we used cDNA microarray analysis to characterize the gene expression profiles in LC and HCC tissues. Consistent differences were observed among the expression patterns in LC, HCC, and normal liver tissues. Interestingly, the expression patterns of LC without tumor association (LCT) were also readily distinguished from those of LC tissues near hepatic tumor tissues (near-tumor tissue, NTT). Moreover, 25 cirrhosis-specific genes could be used to divide the NTT samples into two groups: inflammatory active cirrhosis (NTTa) and inflammatory inactive cirrhosis (NTTi). We found that NTTa samples showed gene expression patterns similar to those of the LCT and HCC groups, whereas the expression patterns of the NTTi group were significantly different from those of the LCT, NTTa, and HCC groups. Finally, we selected two of the 25 LC-specific genes and showed that these markers could be used to successfully discriminate among the different LC subtypes. Collectively, these novel results allow the identification of new genetic subgroups of LC and provide new candidate genes for use as early markers for active cirrhosis and HCC.     

A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers

Thioacetamide (TAA) administration is an established technique for generating rat models of liver fibrosis and cirrhosis. Oxidative stress is believed to be involved as TAA-induced liver fibrosis is initiated by thioacetamide S-oxide, which is derived from the biotransformation of TAA by the microsomal flavine-adenine dinucleotide (FAD)-containing monooxygense (FMO) and cytochrome P450 systems. A two-dimensional gel electrophoresis-mass spectrometry approach was applied to analyze the protein profiles of livers of rats administered with sublethal doses of TAA for 3, 6 and 10 weeks respectively. With this approach, 59 protein spots whose expression levels changed significantly upon TAA administration were identified, including three novel proteins. These proteins were then sorted according to their common biochemical properties and functions, so that pathways involved in the pathogenesis of rat liver fibrosis due to TAA-induced toxicity could be elucidated. As a result, it was found that TAA-administration down-regulated the enzymes of the primary metabolic pathways such as fatty acid beta-oxidation, branched chain amino acids and methionine breakdown. This phenomenon is suggestive of the depletion of succinyl-CoA which affects heme and iron metabolism. Up-regulated proteins, on the other hand, are related to oxidative stress and lipid peroxidation. Finally, these proteomics data and the data obtained from the scientific literature were integrated into an "overview model" for TAA-induced liver cirrhosis. This model could now serve as a useful resource for researchers working in the same area.     

脐血干细胞治疗失代偿期肝硬化的疗效及对门静脉血流动力学的影响

目的:观察脐血干细胞治疗失代偿期肝硬化的疗效及对门静脉血流动力学的影响。方法:选取30例失代偿期肝硬化患者,用负收集法分离提取脐带血干细胞,经股动脉穿刺插管,从肝固有动脉缓慢注入。同时选择20例失代偿期肝硬化患者,分别于治疗前,治疗后1周、1个月、3个月、6个月观察肝功能、凝血指标、AFP、CT肝脏容积、门静脉血流动力学等指标。结果:干细胞治疗组与对照组同期比较:白蛋白治疗后4、12、24周明显改善,PT治疗后12、24周降低;AFP治疗后4、12、24周升高;两组患者治疗前后门静脉血流动力学参数变化差异无统计学意义;肝脏体积治疗组与对照组同期比较,肝脏体积有增大趋势但差异无统计学意义;治疗组1例第10周确诊为原发性肝细胞癌,与对照组比较差异无统计学意义。结论:脐血干细胞治疗失代偿期肝硬化可以改善肝脏的合成功能,促进肝组织再生,有新生血管重建情况发生,未发现门静脉血流动力参数的改变。     

肝硬化患者术后感染的危险因素及干预措施

目的:感染是肝硬化患者肝移植术后常见的并发症之一,影响患者的治疗效果和生存质量。本文针对肝硬化患者术后感染的危险因素进行分析,探讨有效的干预措施以提高临床疗效,为肝硬化术后并发症的预防提供可借鉴的方法。方法:对2008年10月-2013年9月在我院接受手术治疗的120例肝硬化患者的临床资料进行回顾性分析。根据术后并发症的发生情况选择其中60例发生感染的患者作为感染组,另外60例未发生感染的患者作为对照组。观察两组患者的年龄、肝硬化分期及用药情况等,对比不同的干预措施产生的临床效果。结果:感染组患者的平均年龄、肝功能障碍、抗生素使用量及术前合并感染的比率均显著高于正常对照组,差异具有统计学意义(P0.05)。两组患者进行针对性的护理干预均获得良好的治疗效果,未发生死亡病例。结论:患者的年龄、肝功能分级、用药及合并症等均为肝硬化术后感染的危险因素,临床中应实施针对性的干预措施以提高疗效。     

Th2-associated alternative Kupffer cell activation promotes liver fibrosis without inducing local inflammation

Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc) larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.     

Up-regulation of Metabotropic glutamate receptor 3 (mGluR3) in rat fibrosis and cirrhosis model of persistent hypoxic condition

Glutamate is the major excitatory neurotransmitter in the central nervous system, and evidence for peripheral glutamatergic fibers in mammals is still lacking. However, glutamate receptors have been identified in peripheral organs, including taste buds, myenteric plexus, and pancreatic islet cell. Protection against anoxic damage could also be explained by mechanisms mediated by postsynaptic mGluR2 or mGluR3, such as the inhibition of membrane excitability resulting from a reduction of cAMP formation by a G-protein-dependent modulation of ion channels. In addition, activation of mGluR3 present in glial cells may contribute to neuroprotection by enhancing the production of death. Thus, mGluR2/3 behaves potentially as a major defensive mechanism anoxia-tolerant species. There are a few reports for the regional pattern of hypoxic damage, which was inversely related to the expression of mGluR2/3. The aim of this study was to characterize the expression of mGluR3 in hypoxic liver in experimental model of rat liver. Proteomic analysis of protein extracts from CCl₄–induced cirrhotic liver revealed the presence␣of the mGluR3. The presence of mGluR3 in the cirrhotic liver was confirmed by immunohistochemical analysis. There were a number of macrophages expressing mGluR3 mainly in the fibrous septa. After 2 weeks recovery, however, most of mGluR3 positive macrophages disappeared with collagen fibers. These results demonstrate that mGluR3 involved in the liver in response to persistent hypoxic status such as fibrotic/cirrhotic condition, and suggest that the expression of mGluR3 may be a key role functional metabolism and viability in the liver by interacting with the glutamate receptors in vivo.     

肝硬化患者肠球菌感染及体外药敏监测

目的研究肝硬化患者肠球菌感染的现状及药敏特点,以加强对肝硬化肠球菌感染的认识,指导用药。方法留取标本进行细菌培养、鉴定及药敏试验。结果所有纳入研究范围的肝硬化患者共检出肠球菌112株,其中粪肠球菌89株,占79.5%,比例最高,屎肠球菌占14.3%,居第2位。腹水中检出肠球菌64株,占57.1%,其次为痰和尿液,分别为38.1%和14.4%。肠球菌对红霉素、奈替米星的耐药率超过80%,对青霉素G、氨苄西林、呋喃妥因的敏感率超过70%,对左氧氟沙星的敏感率为58.9%,对头孢唑啉、头孢派酮的敏感率分别只有25.0%和33.0%,检出高耐氨基糖苷类肠球菌(HLAR)58株,占51.8%,未检出耐万古霉素和替考拉宁肠球菌,但检出万古霉素中介肠球菌4株,占3.6%。结论肠球菌是肝硬化患者医院感染的重要致病菌,尤以粪肠球菌和屎肠球菌为主,屎肠球菌的耐药率高于粪肠球菌,万古霉素和替考拉宁是治疗肠球菌感染的首选药物。