电镜下的乙型肝炎表面抗原

本文对81例乙型肝炎病人的肝活检组织进行了电镜观察,发现HBsAg的阳性率达93.8％。电镜下,HBsAg细丝不仅有一般的管状细丝型,还有分枝管型和管泡型,而且CAH病人肝组织不易找到HBsAg丝(易见者仅9％),CPH,CLH则多数(79.5％)为易见及可见,二者有高度显著性差异(P<0.01)。     

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.     

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。     

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.     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

早期大剂量维生素C对重症急性胰腺炎大鼠核因子-κB的影响

目的:观察早期大剂量应用抗坏血酸(维生素C)对重症急性胰腺炎(SAP)大鼠的核因子-!B(NF-!B)的影响,研究其作用机制。方法:将72只SAP模型SD大鼠随机分成3组,每组各24只。A组:由大鼠股静脉滴注生理盐水5 ml/kg。B组:大鼠股静脉滴注Vit C 15 mg/kg加生理盐水至5 ml/kg。C组:由大鼠股静脉滴注Vit C 150 mg/kg加生理盐水至5 ml/kg。另取8只SD大鼠作为正常对照组。各组分别于8 h和24 h处死8只大鼠,采血测淀粉酶、脂肪酶、维生素C(PV-C)、超氧化物歧化酶(SOD)、TNF-αI、L-6。大鼠处死时分别取胰头组织3份,一份组织HE染色,行光镜检查,按Kusske的方法,对水肿、炎症、出血和坏死分别评分;一份制成超薄切片,行电镜检查;另一份SP法进行免疫组化染色,检测NF-!B的表达。每组另外8只大鼠观察3 d内存活情况,计算3 d成活率。结果:各组大鼠3 d内的生存率为正常对照组100%(8/8),A组0%(0/8),B组12.5%(1/8),C组50%(4/8),C组的3 d生存率显著高于其他两组(P<0.05)。各组的4项病理学评分均高于正常对照组(P<0.01),C组的4项病理学评分均低于A、B组(P<0.05)。透射电镜检查示C组中分泌颗粒较少,其包膜完整、内质网轻度肿胀、线粒体清晰,未见大片坏死。SAP大鼠体内淀粉酶、脂肪酶、细胞因子TNF-α和IL-6的水平明显增高,血清SOD和P-VC降低,胰腺组织中NF-!B活化阳性胰腺细胞数明显增多。C组的血清淀粉酶和脂肪酶低于A、B组(P<0.05),SOD和P-VC水平高于A、B组(P<0.05),血清TNF-αI、L-6水平低于A、B组(P<0.05),胰腺组织NF-!B活化水平低于A、B组(P<0.05)。结论:早期大剂量应用Vit C有助于及时提高SAP大鼠的P-VC、E-SOD水平,降低体内淀粉酶、脂肪酶、TNF-αI、L-6水平,其作用机制可能与大剂量Vit C抑制SAP大鼠体内NF-!B活化、在整体水平上抑制细胞因子基因表达、有助于机体免受自由基和过量细胞因子的损伤及减轻胰腺组织的病理性改变等因素有关。     

The participation of adenosine receptors in the adenosine 5''-triphosphate-induced relaxation in the isolated rabbit corpus cavernosum penis

AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.