原发性肝癌患者乙型及丙型肝炎病毒感染的检测

目的　调查原发性肝癌患者乙型及丙型肝炎病毒感染情况。　方法　采用免疫组织化学 SP法检测15 7例原发性肝癌患者乙型肝炎病毒 (HBV)及丙型肝炎病毒 (HCV)感染情况 ,每例患者均有血清学检测资料 ,另取 30例良性肝病组织作对照 ,所有数据用卡方检验。　结果　 15 7例原发性肝癌患者中 HBV感染阳性率为31.8% (5 0 / 15 7) ,HCV感染阳性率为 5 1.0 % (80 / 15 7) ,其中 10 7例原发性肝细胞癌 HBV、HCV感染阳性率分别为39.3% (42 / 10 7) ,4 5 .8% (49/ 10 7) ,5 0例胆管细胞癌 HBV、 HCV感染阳性率分别为 16 .0 % (8/ 5 0 ) ,6 2 .0 %(31/ 5 0 ) ,原发性肝细胞癌、胆管细胞癌 HBV、HCV重叠感染率分别为 2 7.1% (2 9/ 10 7) ,14 .0 % (7/ 5 0 ) ,良性肝病组HBV、HCV感染阳性率分别为 16 .7% (5 / 30 ) ,30 .0 % (9/ 30 )。原发性肝细胞癌 HBV感染、胆管细胞癌 HCV感染率高于良性肝病组 ,差异均有显著性 (P<0 .0 5 )。原发性肝细胞癌 HBV、HCV血清学检测阳性率分别为 87.8%(94 / 10 7) ,13.1% (14 / 10 7) ,胆管细胞癌 HBV、HCV血清学检测阳性率分别为 6 8.0 % (34/ 5 0 ) ,16 .0 % (8/ 5 0 )。　结论　原发性肝癌与 HBV、HCV的感染有密切关系     

B cells as a target of immune modulation

B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS) suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts). MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells) leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell–targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients

Peripheral immune responses can be sensitive indicators of disease pathology. We evaluated the autoimmune reactions to endocrine (insulin) and astrocytical (S100B) biomarkers in the blood sera of 26 Parkinson's disease (PD) patients compared with controls by using ELISA. We found a statistically significant increase of the autoimmune responses to both antigens in PD patients compared with controls with a mean increase of 70% and 50% in the autoimmune reactions towards insulin and S100B, respectively. Heterogeneity of the immune responses observed in patients may reflect the modulating effect of multiple variables associated with neurodegeneration and also changes in the basic mechanisms of individual autoimmune reactivity. We did not detect any pronounced immune reactions towards insulin amyloid fibrils and oligomers in PD patients, indicating that an amyloid-specific conformational epitope is not involved in immune recognition of this amyloid type, while sequential epitope of native insulin is hidden within the amyloid structures. Immune reactions towards S100B and insulin may reflect the neurodegenerative brain damaging processes and impaired insulin homeostasis occurring in PD.     

复方丹参注射液干扰素治疗乙肝后肝纤维化

目的探讨复方丹参注射液联合干扰素治疗慢性乙肝患者的疗效。方法110例慢性乙肝患者，按随机方法分成①对照组30例，应用普通保肝药物治疗，疗程6个月；②丹参组30例，应用复方丹参注射液（每ml含丹参、降香各1g）30ml加入10％葡萄糖溶液300ml中静脉注射1个月；③IFN组30例，应用IFN—α 3MU，隔日一次肌内注射，3个月；④联合组20例，应用复方丹参注射液30ml加10％葡萄糖溶液300ml静脉注射1个月，IFN-α 3MU，隔日一次肌内注射，3个月。丹参组，IFN组和联合组保肝药物治疗同对照组。四组病例在性别、年龄、病程，治疗前肝功能等方面均无统计学差异。治疗前检测肝功能，肝炎病毒标志，血清HA、IV—C、PCI—Ⅱ，部分病例进行肝穿病理检查。治疗开始后每月检测肝功能，3个月（治疗后）和6个月（随访时）时检测血清HA、IV—C、PCⅢ及乙肝病毒标志，治疗后1年行肝穿病理检查。结果治疗前四组患者血清HA、PCⅢ、IV—C水平无统计学差异；治疗后丹参组、IFN组、联合组血清HA、FCⅢ、IV—C水平较治疗前及对照组有不同程度的降低。结论复方丹参注射液联合IFN治疗可使血清HA、PCⅢ、IV—C有明显下降，肝组织病理改变明显改善，为目前有效的慢性乙肝治疗措施。     

Bile-pancreatic juice exclusion promotes Akt/NF-kB activation and chemokine production in ligation-induced acute pancreatitis

Using a unique surgical model (the donor rat model), we showed previously that duodenal replacement of bile-pancreatic juice, obtained fresh from a donor rat, ameliorates ligation-induced acute pancreatitis. We hypothesize that bile-pancreatic juice exclusion from gut exacerbates Akt/nuclear factor-kB (NF-kB) pathway activation and induces chemokine production in ligation-induced acute pancreatitis. We compared rats with bile-pancreatic duct ligation to those with duodenal bile-pancreatic juice replacement fresh from a donor rat beginning immediately before duct ligation. Sham control rats had ducts dissected but not ligated. Rats were killed 1 or 3 hours after operation (n=7/group). Akt activation (immunoblotting, immune-complex kinase assay, and ELISA), inhibitory protein I-kB (I-kB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates. NF-kB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases in pancreatic Akt, IkB, and NF-kB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-kB pathway and increased MCP-1 and RANTES production in response to duct ligation were significantly reduced by bile-pancreatic juice replacement (ANOVA, P<0.05). Bile-pancreatic juice exclusion stimulates Akt/NF-kB pathway activation and increases chemokine production in ligation-induced acute pancreatitis. Presented at the annual meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 16, 2005 (poster).     

Immunogenicity and safety of a novel yeast Hansenula polymorpha-derived recombinant Hepatitis B candidate vaccine in healthy adolescents and adults aged 10–45 years

The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B^®, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10–15 years, 10 μg HBsAg/dose) and one in Uruguay (344 participants aged 16–45 years, 20 μg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers ≥10 mIU/mL; delta non-inferiority limit of −10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10–15 year and 16–45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines.     

慢性乙型肝炎患者病毒e系统状态与肝纤维化关系的研究

目的:观察慢性乙型肝炎患者乙型肝炎病毒e系统状态和复制指标在肝纤维化发生过程中的变化及其与血清纤维化标志的关系,探讨它们在肝纤维化发生过程中的作用及其可能的临床意义.方法:188例慢性乙型肝炎患者根据肝纤维化程度分为S0～S4期等5组,分别用定量PCR及放免法检测患者血清中HBV-DNA及肝纤维化标志透明质酸、Ⅳ型胶原、Ⅲ型前胶原和层粘连蛋白的含量;HBeAg和抗-HBe采用酶联免疫吸附法(ELISA)检测,并观察其在不同肝病理纤维化分期时的变化.结果:随着肝纤维化程度加重,血清HBV-DNA含量逐渐升高,从S1期开始显著增加(P＜0.01);而HBeAg阳性率逐渐降低,S3、S4期较S0显著减少(P＜0.05和P＜0.01);抗-HBe阳性率呈相反的变化趋势,在S3和S4期的阳性率明显高于S0期(P＜0.05和P＜0.01).血清HBV-DNA( )HBeAg( )组血清纤维化标志最低,HBV-DNA(-)抗-HBe( )组最高,两者差异有显著性(P＜0.01).结论:HBV复制和e系统状态的改变与肝纤维化程度密切相关,肝内病毒复制标志与血清纤维化标志联合检测,对于判断肝纤维化程度和指导抗病毒治疗有重要的价值.