A＋C群脑膜炎球菌多糖结合疫苗上市后安全性研究

目的对A＋C群脑膜炎球菌多糖结合疫苗（Group A and C Meningococcal Polysaccharide Conjugate Vaccine，MPCV．AC）进行上市后安全性评价，为在人群中应用提供参考。方法2011年10月～2012年9月，在广州市采用分层随机抽样方法抽取5月龄～5岁受种儿童，连续随访3天，主动监测不良反应发生情况。采用整群随机抽样方法，对受种儿童进行被动监测，观察接种后MPCV．AC不良反应发生情况。结果主动监测262名受种儿童，5N23月龄婴幼儿（60人）未观察到不良反应，2～5岁儿童7人（3．4653％，7/202）出现轻度局部不良反应。10356名被动监测儿童接种MPCV-AC后，19例（0．1835％）报告轻度局部反应（主要为硬结和红、肿），9人（0．0869％）出现全身反应。结论儿童接种MPCV-AC有良好的安全性。     

Study of a cross-linked hydrogel of Karaya gum and Starch as a controlled drug delivery system

Abstract

A cross-linked hydrogel was synthesized using a hybrid backbone of karaya gum starch and grafted with polyacrylic acid. It showed a maximum swelling ratio (SR) of 30.5?g/g at pH 10 and was explored as an oral drug delivery carrier using paracetamol and aspirin as model drugs. In vitro release experiments revealed that maximum drug release at pH 7.4 in comparison to pH 1.2 (simulated intestinal vs gastric fluid) and neutral medium. The release profiles of these drugs showed no initial burst. It also showed good hemocompatibilty and non-cytotoxicity for its employment as a site specific drug delivery agent.     

Vi capsular polysaccharide: Synthesis,virulence, and application

Vi capsular polysaccharide, a linear homopolymer of α-1,4-linked N-acetylgalactosaminuronate, is characteristically produced by Salmonella enterica serovar Typhi. The Vi capsule covers the surface of the producing bacteria and serves as an virulence factor via inhibition of complement-mediated killing and promoting resistance against phagocytosis. Furthermore, Vi also represents a predominant protective antigen and plays a key role in the development of vaccines against typhoid fever. Herein, we reviewed the latest advances associated with the Vi polysaccharide, from its synthesis and transport within bacterial cells, mechanisms involved in virulence, immunological characteristics, and applications in vaccine, as well as its purification and detection methods.     

A tethering mechanism for length control in a processive carbohydrate polymerization

Carbohydrate polymers are the most abundant organic substances on earth. Their degrees of polymerization range from tens to thousands of units, yet polymerases generate the relevant lengths without the aid of a template. To gain insight into template-independent length control, we investigated how the mycobacterial galactofuranosyltransferase GlfT2 mediates formation of the galactan, a polymer of galactofuranose residues that is an integral part of the cell wall. We show that isolated recombinant GlfT2 can catalyze the synthesis of polymers with degrees of polymerization that are commensurate with values observed in mycobacteria, indicating that length control by GlfT2 is intrinsic. Investigations using synthetic substrates reveal that GlfT2 is processive. The data indicate that GlfT2 controls length by using a substrate tether, which is distal from the site of elongation. The strength of interaction of that tether with the polymerase influences the length of the resultant polymer. Thus, our data identify a mechanism for length control by a template-independent polymerase.     

甘草对液体发酵中槐耳菌丝体生长及多糖影响初探

[目的] 以槐耳菌丝体生物量及多糖为主要指标,探究槐耳-甘草液体共发酵中最佳甘草的添加量和发酵时长。[方法] 采用液体发酵技术,在液体发酵培养基中加入甘草提取液,共发酵获得槐耳-甘草共发酵产物,苯酚-硫酸法及DNS法结合测定多糖含量。[结果] 槐耳-甘草液体共发酵实验中,添加甘草8 g/L、发酵终点设为192 h时,槐耳生物量和胞内多糖产量达到最大值。[结论] 运用槐耳-甘草液体共发酵可以提高槐耳生物量及多糖的含量,为深入研究槐耳-甘草液体共发酵机制提供了理论依据。     

卡介菌多糖核酸干预豚鼠急性过敏反应的研究

目的:研究卡介菌多糖核酸对豚鼠急性过敏反应的作用及可能的机制,探讨卡介菌多糖核酸的质量控制效力模型的提高方法。方法:建立牛血清白蛋白诱导豚鼠产生急性过敏反应模型。激发后30 min内观察豚鼠全身反应,并根据致敏性症状评分标准分级。取血用ELISA法测致敏前、攻击前及攻击后豚鼠血清总Ig E和组胺水平。结果:攻击后,模型组和卡介菌多糖核酸低剂量组豚鼠出现不同程度的急性过敏反应症状,而卡介菌中、高剂量组豚鼠急性过敏反应症状明显缓解。模型组在攻击前、后采集的血清总Ig E水平分别为1.637 0±0.158 6,1.683 1±0.228 1μg·ml-1,较正常对照组显著升高(P<0.01),而同时给予卡介菌多糖核酸后,卡介菌高剂量和中剂量处理组在攻击前、后采集的血清总Ig E水平与模型组比较均显著降低(P<0.01)。经牛血清蛋白致敏后,在攻击前后,模型组血清中组胺水平分别为1.499 7±0.133 1,1.512 1±0.050 6μg·ml-1,与阴性对照组相比均显著升高(P<0.01),而同时给予卡介菌多糖核酸后,卡介菌高、中、低各剂量处理组在攻击前、后采集的血清中组胺水平与模型组比较有明显降低(P<0.01)。结论:卡介菌多糖核酸可剂量依赖性抑制牛血清蛋白引起的急性过敏反应。其抗急性过敏反应的可能机制与降低血清总Ig E和组胺水平有关。     

因子设计-PCA法优化黄芪多糖干法制粒压片研究

摘 要 目的： 对黄芪多糖干法制粒压片后的物理指标进行表征,优化辅料选择。方法: 以微晶纤维素用量、乳糖用量、微粉硅胶用量为考察因素,以颗粒得率、片剂硬度、片剂脆碎度、崩解时间为考察指标,以因子设计法安排试验,以主成分分析法(Principal Component Analysis, PCA)综合评价试验指标。结果: 优选辅料为15%微晶纤维素、10%乳糖、10%微粉硅胶。结论: 因子设计 PCA法能优化干法制粒压片过程中辅料的选择。     

裙带菜多糖保护异丙肾上腺素诱导的心脏纤维化研究

目的：探讨裙带菜多糖在异丙肾上腺素（ISO）诱导的心脏纤维化中的作用。方法将40只C57BL／6J小鼠随机分为对照组、ISO组、ISO＋裙带菜多糖组、裙带菜多糖组。ISO组连续皮下注射ISO 14 d（前3 d 10 mg·kg－1·d－1,后11 d 5 mg· kg－1·d－1）,ISO＋裙带菜多糖组除做上述ISO处理外,ISO处理前7 d开始给予裙带菜多糖200 mg·kg－1·d－1灌胃,持续到ISO皮下注射第14天;裙带菜多糖组连续21 d裙带菜多糖200 mg·kg－1·d－1灌胃;对照组以生理盐水代替ISO皮下注射。心脏超声检测各组小鼠心功能的改变,病理染色检测心脏纤维化程度,实时定量PCR检测转化生长因子-β（TGF-β）、Ⅰ型胶原α（CollagenⅠα）和Ⅲ型胶原（CollagenⅢ）的mRNA表达量的变化,Western Blot检测各组小鼠心脏自噬的改变。结果裙带菜多糖明显改善心功能,减少ISO诱导的心脏纤维化程度,心脏胶原蛋白CollagenⅠα和CollagenⅢ的mRNA表达量比ISO组显著降低（P＜0．05）,且裙带菜多糖能减少ISO诱导的心脏自噬。结论裙带菜能减轻ISO诱导的心脏纤维化,其主要是通过降低ISO诱导的心脏自噬而发挥作用的。     

Astragalus polysaccharide attenuates isoproterenol-induced cardiac hypertrophy by regulating TNF-α/PGC-1α signaling mediated energy biosynthesis

We previously reported that Astragalus polysaccharide (APS) extracted from Chinese medicine Astragalus membranaceus (Fisch.) Bge, attenuates hypertrophy of neonatal rat ventricular myocytes (NRVMs) induced by isoproterenol (Iso). The present study was designed to investigate the effects and the possible mechanism of APS on Iso-induced hypertrophy in rats and NRVMs with focus on tumor necrosis factor α (TNF-α)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) signaling mediated energy biosynthesis. 36-Week old rats were randomly divided into 3 groups: (1) Control, rats received vehicle; (2) Iso, rats received isoproterenol injections; (3) Iso+APS, rats received isoproterenol injections and APS. NRVMs were divided into similar groups as rats. The results showed that combination of APS with Iso significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight (HW/BW) and left ventricular weight/BW (LVW/BW), improved the cardiac hemodynamics, down-regulated mRNA and protein expression of atrial natriuretic peptide (ANP), increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of free fatty acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with APS significantly decreased the surface area and protein content, down-regulated mRNA and protein expression of ANP, increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, APS increased the protein expressions of ATP5D, the σ subunit of ATP synthase, PGC-1α and pyruvate dehydrogenase kinase 4 (PDK4) in tissue and NRVMs respectively and inhibited the production of TNF-α in serum and culture medium compared with Iso alone. The results suggested that APS attenuates Iso-induced cardiac hypertrophy through regulating TNF-α/PGC-1α signaling mediated energy biosynthesis.     

PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants,Northern Territory,Australia

BackgroundWe assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants.MethodsIn an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17–39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30–36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months.ResultsThe consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI −12% to 31%) against infant ear disease and 30% (95% CI −34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI −2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth.ConclusionsIn a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs.