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.     

2型糖尿病患者卒中一级预防的现况调查

目的 了解2型糖尿病患者住院前及住院期间卒中各危险因素的干预状况，发现临床实践与证据之间的差距，提高临床医生对卒中一级预防的认识，指导今后的临床治疗。方法 本调查为横断面调查研究，回顾性调查167例2型糖尿病患者住院前及住院期间对卒中主要危险因素的干预情况。结果 被调查的患者中，入院前有46.7%的患者有高血压；36.0％的患者有吸烟史；19.8％的患者存在冠状动脉粥样硬化性心脏病，0.6％的患者有心房颤动；23.4％的患者有脂代谢异常。出院前有56.9％的患者被诊断高血压；81.4％的患者存在脂代谢异常。入院前与出院前对血压的药物干预率差异无统计学意义（分别为75.6%及80.0%，P >0.05）；入院前后的降脂治疗（分别为25.6%及69.1%，P <0.01）及降糖治疗（分别为82.0%及97.6%，P <0.01）的差异均有统计学意义。结论 2型糖尿病患者院前对危险因素干预的达标率较低，应加强2型糖尿病患者及临床医生对卒中一级预防的认识，提高卒中卒中相关危险因素的干预率。     

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.     

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.     

HBV转录激活蛋白HBx、MHBst78MHBst155真核重组载体构建

目的分别构建人乙型肝炎病毒(HBV)X蛋白、羧基端截断的中分子表面蛋白MHBst78、MHBst155编码基因的真核重组表达载体,以便进一步研究其转录激活功能及对宿主细胞信号传导通路的影响。方法设计合成3对寡核苷酸引物,以adr亚型HBV质粒pHBVDNA为模板,采用PCR法分别扩增HBVX基因、MHBst78与MHBst155编码基因片段;用HindⅢ,KpnⅠ双酶切HBVⅩ基因;用HindⅢ和BamHⅠ双酶切MHBst78与MHBst155编码基因片段后,分别定向插入到真核表达载体pcDNA3.1相应酶切位点,转化宿主菌JM109,提取质粒,分别用上述内切酶酶切及DNA测序鉴定重组质粒。结果酶切重组体显示所切下的片段大小均与预计相符,测序结果与文献报道序列及预计结果一致。结论成功构建了HBVX基因、羧基端截断的HBV中分子表面蛋白MHBst78、MHBst155编码基因的真核重组表达载体,为进一步研究HBV转录激活蛋白HBx、MHBst78MHBst155对宿主细胞信号转导通路的影响奠定基础。     

合并乙肝的涂阳肺结核病人DOTS中肝损害观察

目的 观察免费板式组合药在DOTS中对合并乙肝的涂阳肺结核病人肝损害情况。方法 比较HBsAg、HBeAg、HBcAb阳性的涂阳肺结核病人与无乙肝的涂阳肺结核病人DOTS前后肝功能损害情况。结果 合并乙肝病人肝损害发生率66．3％，无乙肝者肝损害发生率8．6％，两者相比差异有显著性（P〈0．01）。22．5％病人因肝损害需更改治疗方案。结论 DOTS中合并乙肝的病人采用板式组合药用2H3R3Z3E3／4H3R3方案易发生肝损害，对这类病人应慎用常规方案，并要密切全程观察肝功能，尽可能应用肝损害较小的抗结核药。     

Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba.

We report here the antiproteolytic and antihemorrhagic properties of triterpenoid saponin inhibitors, named macrolobin-A and B, from Pentaclethra macroloba, against Bothrops snake venoms. The inhibitors were able to neutralize the hemorrhagic, fibrin(ogen)olytic, and proteolytic activities of class P-I and P-III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. Clotting and fibrinogenolytic activities induced by snake venoms and isolated thrombin-like enzymes were partially inhibited. Furthermore, the potential use of these inhibitors to complement antivenom therapy as an alternative treatment and/or used as molecular models for development of new therapeutical agents in the treatment of snake bite envenomations needs to be evaluated in future studies.     

脂质体介导NF-κB decoy ODN对重症急性胰腺炎大鼠肺炎症因子mRNA表达和肺损伤的影响

目的 探讨脂质体（liposome）介导转录因子NF—κB诱捕物（decoy）寡聚脱氧核苷酸（oligodeoxynucleotide，ODN）对重症急性胰腺炎SD大鼠肺部NF-κB活性及受其调控炎症基因mRNA表达和肺损伤的影响。方法 以牛磺胆酸钠（STC）诱导SD大鼠建立重症急性胰腺炎模型，以假手术组为对照组，于建模后1h分别静脉注射裸ODN、脂质体／decoy ODN复合物、脂质体／scrambled ODN复合物和生理盐水，注射4h后应用电泳迁移率变动（EMSA）分析NF-κB的活性，利用逆转录-聚合酶链反应法（RT-PCR）检测肺组织ICAM-1、IL-1α、IL-2、TNF—α、VCAM-1mRNA表达，同时检测氧分压、肺组织湿／干重比率和肺组织髓过氧化物酶（MPO）。结果 EMSA显示脂质体／decoy ODN复合物组NF—κB活性明显低于生理盐水组、脂质体／scrambled ODN复合物组和裸ODN组（P〈0.05），RT—PCR显示脂质体／decoy ODN复合物组ICAM-1、IL-1α、IL-2、TNF—α、VCAM-1mRNA表达小于生理盐水组、脂质体/scrambled ODN复合物组和裸ODN组（P〈0．05）。与生理盐水组、脂质体／scrambled ODN复合物组和裸ODN组相比，脂质体／decoy ODN复合物组动脉血氧分压升高，肺组织湿／干重比率和肺组织髓过氧化物酶（MPO）活性降低（P〈0．05）、结论 NF—κB decoy ODN可特异性抑制肺NF-κB活性及其调控的炎症因子ICAM-1、IL—1α、IL-2、TNF-α、VCAM-1mRNA的表达，减轻肺损害。