噬菌体抗菌治疗安全性评估体系的建立

人类已经进入后抗生素时代,噬菌体治疗近年来重新备受重视,噬菌体制剂不同于传统抗菌药物,已有对传统抗菌药物的安全性评估体系不适合用于对噬菌体治疗制剂的评估,需要建立对噬菌体治疗安全性评估的体系。本文就噬菌体治疗所涉及的安全性问题进行系统分析研究,通过噬菌体本身的选择、噬菌体制剂制备、制剂形式、制剂给予途径、剂量和频次等,以及噬菌体治疗细菌感染性疾病患者选择等所涉及的安全性和噬菌体治疗对周围微环境的影响等进行全面分析。建立噬菌体治疗安全性评估体系,为噬菌体治疗尽早进入临床奠定基础。     

载银纳米抗菌复合骨填充材料体外抗菌性能研究

目的探讨新型载银纳米抗菌复合骨填充材料(TiO2-Ag-nHA/PA66)的体外抗菌性能。方法采用抑菌环试验及菌落总数测定法检测不同纳米抗菌复合骨填充材料(A1、A2、A3)对金黄色葡萄球菌及大肠埃希菌的体外抗菌效果;扫描电镜观察其对细菌的抗粘附作用。结果抑菌环试验显示,不同载银纳米抗菌复合骨填充材料对金黄色葡萄球菌和大肠埃希菌均形成明显的抑菌环,以作用24 h抑菌环直径最大,并随作用时间延长,抑菌环直径逐渐缩小。其中银含量为0.64%(质量比)的材料A3的抗菌作用最明显,持续时间最长,其对金黄色葡萄球菌和大肠埃希菌的抑菌作用持续时间分别达到33 d和24 d;菌落总数测定法显示细菌与材料A3接触24 h后,对金黄色葡萄球菌和大肠埃希菌的抗菌率分别为94.18%和85.96%;扫描电镜发现载银材料能够明显减少细菌在材料表面的粘附。结论载银纳米抗菌复合骨填充材料体外对金黄色葡萄球菌及大肠埃希菌有明显抗菌作用,为其应用于慢性骨髓炎术后骨缺损修复提供理论依据。     

含铜抗菌不锈钢的抗菌性能研究

对铁素体和奥氏体2种含铜抗菌不锈钢的抗菌性能进行了考察.采用覆膜法检测抗菌率,用透射电镜观察与铁素体抗菌不锈钢作用后的大肠埃希菌细胞形态.2种抗菌不锈钢材料对供试的 17 株常见菌,除产气肠杆菌外均显示较强的抗菌性能,抗菌谱广;铁素体和奥氏体对1×107 cfu/mL及以下浓度的大肠埃希菌在 24 h内杀灭率达到99%;铁素体和奥氏体分别在作用 3 h和 9 h时可将1×107 cfu/mL的大肠埃希菌全部杀灭;打磨次数和环境温度的变化不影响2种抗菌不锈钢的杀菌率;透射电镜结果显示,与抗菌不锈钢作用后的大肠埃希菌菌体结构松散,细胞壁和细胞膜破裂,有内容物漏出.铁素体和奥氏体抗菌不锈钢均具优良的抗菌性能,抗菌谱广,与其作用后的细菌菌体破裂,有内容物溶出,最终致菌死亡.     

载铜蒙脱石的抗菌机理研究

研究载铜蒙脱石对副溶血弧菌的抗菌效果和机理。载铜蒙脱石对副溶血弧菌的最小抑菌浓度和最小杀菌浓度分别为75mg/L和300mg/L,而蒙脱石未显抗菌活性。细菌胞内酶活性结果显示,载铜蒙脱石可使细菌细胞膜发生损伤或通透性增大,导致细菌胞内酶的外漏。载铜蒙脱石对细菌呼吸代谢影响的结果表明,载铜蒙脱石可抑制三羧酸循环途径。原子力显微镜动态观察载铜蒙脱石作用下副溶血弧菌形态变化的结果发现,载铜蒙脱石能破坏细菌细胞膜。     

纳米生物效应及安全性研究

纳米生物效应是研究纳米尺度物质与生命过程相互作用及其结果的一个新兴科学领域。介绍了纳米生物效应研究的内容、科学意义、国际发展现状和我国的研究进展。     

Cu/PAA的制备及其抗菌性能研究

采用两步阳极氧化法制备出孔径为75nm的多孔阳极氧化铝(PAA75),并使用交流电沉积技术在PAA75孔道内装载纳米Cu。采用场发射扫描电镜(FESEM)观察样品微观形貌,进一步采用X射线衍射(XRD)、X射线光电子能谱分析(XPS)对材料化学组成及晶型进行了表征和分析。选用大肠杆菌(E.coli ATCC 8099)和金黄色葡萄球菌(S.aureus ATCC6538)测试Cu/PAA的抗菌性能。研究结果表明,本方法制备的Cu/PAA中Cu主要以Cu0存在,并且Al和Cu所占原子比为17.77∶0.71。体外抗菌测试表明,Cu(10s)/PAA对E.coli的1d、2d和3d抑菌率分别为82%±11%、78%±7%和45%±4%,对S.aureus的1d、2d和3d抑菌率分别为89%±4%、75%±8%和56%±11%。     

蕨类植物抗菌作用的初步研究

本文利用圆纸片法对十二种蕨类植物抗菌作用进行了研究,发现海金沙、凤尾蕨、抱石莲、兖州卷柏、乌韭、紫萁、翠云草等有较强的抗菌作用,在供试植物中,以海金沙抗菌活性最强.海金沙水提液和醇提液对金黄色葡萄球菌的最小抑制浓度(MIC)分别为10.、7.5%将海金沙、凤尾蕨、抱石莲三种植物等量组成复方,对该复方的水提液及醇提液与常用的化工合成防腐剂苯甲酸钠、山梨酸钾的防腐性能进行了比较.     

壳聚糖的结构及抗菌作用研究进展

综述了壳聚糖的结构特点、抗菌机理和抗菌特点,并简单介绍了应用方面的研究及存在的问题。     

新型载药高分子囊泡的制备与抗菌性能研究

相对于小分子抗菌剂,高分子抗菌材料会对细菌的胞膜产生物理破坏,从而降低病原体产生耐药性的可能;另外,高分子抗菌材料不但具有较高的抗菌性能,抗菌作用时效长,环境污染小,而且对人体伤害小,具有更好的选择性。因此,高分子抗菌材料的研究受到广泛关注。此外,还可以将小分子抗生素负载到高分子纳米载体中,实现小分子抗菌剂的传输与协同抗菌。本文构筑了两亲性高分子聚(N,N-二甲氨基乙酯-嵌段-聚苯氧异丙醇)(PDMAEMA-b-PPOPMA),自组装得到纳米囊泡,被用来物理包埋万古霉素(Vancomycin),对金黄色葡萄球菌(S.aureus)表现出良好的抗菌活性。     

锦灯笼宿萼提取物体外抗菌作用研究

采用纸片扩散法对锦灯笼宿萼提取物进行体外抗菌试验研究,以了解其抗菌谱。结果表明该提取物对金黄色葡萄球菌、甲型链球菌、乙型链球菌、蜡样芽胞杆菌、枯草芽胞杆菌均有抑制作用,而对绿脓杆菌、大肠杆菌、表皮葡萄球菌、腐生葡萄球菌以及白色念珠菌均无抑制作用,表明锦灯笼宿萼提取物中存在有效抗菌成分,其中以甲链、乙链、金葡菌高度敏感,锦灯笼宿萼精制提取物最低抑制浓度为25~50 g/L。     

Synthesis and characterization of chitosan/ZnO nanoparticle composite membranes

Novel chitosan/ZnO nanoparticle (CS/nano-ZnO) composite membranes were prepared via the method of sol-cast transformation and studied by UV-vis absorption spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray fluorescence spectrometry (EDX). The characterization revealed that ZnO nanoparticles dispersed homogeneously within the chitosan matrix. The mechanical and antibacterial properties of the product were investigated. The results showed that the ZnO content had an effect on the mechanical properties of CS/nano-ZnO composite membranes, and that the antibacterial activities of CS membranes for Bacillus subtilis, Escherichia coli, and Staphylococcus aureus were enhanced by the incorporation of ZnO. Further, CS/nano-ZnO composite membranes with 6-10 wt % ZnO exhibited high antibacterial activities.     

Biosynthesis and antibacterial activity of ZnO nanoparticles using Trifolium pratense flower extract

Zinc oxide (ZnO) has broad applications in various areas. Nanoparticle synthesis using plants is an alternative to conventional physical and chemical methods. It is known that the biological synthesis of nanoparticles is gaining importance due to its simplicity, eco-friendliness and extensive antimicrobial activity. Also, in this study we report the synthesis of ZnO nanoparticles using Trifolium pratense flower extract. The prepared ZnO nanoparticles have been characterized by UV–Vis absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) with Energy dispersive X-ray analysis (EDX). Besides, this study determines the antimicrobial efficacy of the synthesized ZnO nanoparticles against clinical and standard strains of S. aureus and P. aeruginosa and standard strain of E. coli.     

Antibacterial activity of ZnO nanoparticle suspensions on a broad spectrum of microorganisms

Nanoparticle metal oxides represent a new class of important materials that are increasingly being developed for use in research and health-related applications. Highly ionic metal oxides are interesting not only for their wide variety of physical and chemical properties but also for their antibacterial activity. Although the in vitro antibacterial activity and efficacy of regular zinc oxides have been investigated, little is known about the antibacterial activity of nanoparticles of ZnO. Preliminary growth analysis data suggest that nanoparticles of ZnO have significantly higher antibacterial effects on Staphylococcus aureus than do five other metal oxide nanoparticles. In addition, studies have clearly demonstrated that ZnO nanoparticles have a wide range of antibacterial effects on a number of other microorganisms. The antibacterial activity of ZnO may be dependent on the size and the presence of normal visible light. The data suggest that ZnO nanoparticles have a potential application as a bacteriostatic agent in visible light and may have future applications in the development of derivative agents to control the spread and infection of a variety of bacterial strains.     

粘菌素对耐碳青霉烯类抗生素鲍曼不动杆菌的抗菌作用

感染耐碳青霉烯的鲍曼不动杆菌(CR-Ab)常与高发病率和死亡率相关联,而可供选择的治疗方案有限,大多基于与粘菌素联用。长期用药导致CR-Ab对粘菌素也产生一定抗性。为了评估含有或不含有粘菌素的不同抗菌组合对从CR-Ab感染患者收集的CR-Ab临床分离株的体外抗菌活性,本研究从本院就诊的患者中收集CR-Ab菌株,通过常量肉汤稀释法(MBD)测定最低抑菌浓度(MICs),通过定性(棋盘法)和定量(即杀菌测试)方法评估各组药物协同活性。结果发现所有菌株均是碳青霉烯类抗性的,且其中两株菌对粘菌素有抗性。棋盘法结果表明含粘菌素的组合在不同处理时间下具有完全协同作用,粘菌素+万古霉素和粘菌素+利福平表现出最高的协同增效作用;不含粘菌素的组合则在35.7%的菌株中观察到完全协同作用。杀菌测试表明粘菌素+美罗培南、粘菌素+替加环素和美罗培南+替加环素组合对粘菌素敏感和低粘菌素抗性的菌株具有杀菌和协同作用,而只有粘菌素+万古霉素和粘菌素+利福平组合表现出持久的杀菌活性。     

中草药复方对拟态弧菌的体内外抗菌和拮抗外毒素的作用

目的探明拟态弧菌外毒素的致病性,筛选出对拟态弧菌具有良好抗菌和拮抗外毒素作用的中草药复方。方法培养拟态弧菌安徽分离株,采用蛋白分离技术提取其外毒素,测定其对实验草鱼的致病性。以黄连、大黄、金银花、夏枯草、丹皮、地锦草、连翘、茯苓、车前子、黄芪和甘草组成3个复方,采用改良微量稀释法测定不同中草药复方对拟态弧菌的体外抑菌作用。同时使用动物模型测定不同中草药复方拮抗外毒素作用和对拟态弧菌感染草鱼的保护作用。结果4株拟态弧菌产生的外毒素对实验鱼均具有较强的致死性。复方3的体外抑菌作用最强,对4株拟态弧菌的MIC值均为1.96g/L;其次为复方1,其MIC值介于3.92～7.84g/L;复方2的抑菌作用最差,其MIC值介于62.72～125g/L。复方3拮抗外毒素作用最强,其次为复方2,复方1不具有抗毒素作用。复方3对拟态弧菌感染草鱼具有最好的保护作用,保护率为100%;其次为复方2,保护率为23.81%;复方1的保护率最低,仅为19.05%。结论拟态弧菌外毒素在腹水病发生过程中起着重要致病作用。复方3具有良好的抗菌和拮抗外毒素作用,为筛选出的最佳复方,可进一步研制成为治疗腹水病的中草药复方制剂。     

枯草芽孢杆菌B115优化培养及其对气单胞菌的抗菌效果的研究

采用正交实验设计确定了枯草芽孢杆菌（Bacillus subtilis）B115的基础培养基成份为：胰蛋白胨1％,酵母膏0．25％,氯化钠0．5％;添加成份最优组合为（NH4）2SO4 0.1％,（K2HPO4＋KH2PO4）（1．4＋0．6）％和柠檬酸三钠0．1％;添加成分最优组合与基础培养基培养产量比较,表明添加K^＋、NH4^＋和柠檬酸三钠能极显著地促进B115的生长。研究了B115对致病性气单胞菌的抗菌效果,结果表明：B115对BSK-10和CL990920有明显抑、杀菌效果,对TL970424无抑菌效果。     

四种抗菌药物对BALB/c小鼠肠菌群的影响

本文给普通BALB/c小鼠口服红霉素、链霉素、新霉素和甲硝哒唑,以探讨同一实验条件下,该4种药代动力学特性各异的每种抗菌药物在不同给药剂量及不同用药时间对BALB/c小鼠肠菌群的影响。结果表明:除甲硝哒唑外,其他3种抗菌药当剂量达到或超过一定水平时对肠菌群均有明显影响。红霉素对肠菌群的影响表现在肠杆菌科细菌、拟杆菌显著减少,葡萄球菌、双歧杆菌减少,肠球菌增多。肠菌群的显著性变化在A组(10000mg/kg体重每日)出现在用药后第3天,B组(4000mg/kg体重每日)出现在第7天。链霉素与新霉素引起肠菌群相似的改变,只是新霉素引起的菌群改变较对应组的链霉素引起的菌群改变更显著一些。表现在肠杆菌科细菌增多,类杆菌、肠球菌减少。本文认为抗菌药物引起菌群改变与否及影响的程度主要取决于其用药剂量、用药时间及药物代谢动力学特性。     

Effects of combining biological treatment and activated carbon on hexavalent chromium reduction

The objectives of the present work were: (a) to analyze the Cr(VI) removal by combining activated sludge (AS) with powdered activated carbon (PAC), (b) to analyze the effect of PAC and Cr(VI) on the growth kinetics of activated sludge, and (c) to determine if the combined method (AS-PAC) for Cr(VI) removal can be considered additive or synergistic with respect to the individual processes. Chromate removal was improved by increasing PAC concentrations in both PAC and AS-PAC systems. Cr(VI) removal using the AS-PAC system was higher than using AS or PAC. The increase of Cr(VI) caused longer lag phase and lower observed specific growth rate (μ_obs), biomass yield (Y_X/S), and specific growth substrate consumption rate (q_S) of activated sludge; additionally, PAC did not enhance the growth kinetic parameters (μ_obs, Y_X/S, q_S). Cr(VI) reduction in AS-PAC system was the result of the additive effect of each individual Cr(VI) removal process.     

贯叶连翘总提取物对金黄色葡萄球菌的抗菌作用

以3株金黄色葡萄球菌为代表,分别探讨了经光照和未经光照处理后在培养24h的过程中贯叶连翘总提取物(TEHPL)对3株金黄色葡萄球菌的光密度(OD640mm)、活菌数(CFU)、总菌数(TCC)、最低杀菌浓度(MBC)的影响和对其中2株菌超氧化物歧化酶(SOD)的影响。结果表明TEHPL对金黄色葡萄球菌有抑菌和杀菌作用,其抑菌或杀菌作用与其浓度有关,不需光照。并且TEHPL诱导菌体细胞内SOD活力增高。     

Carbon-Mercaptooctadecane/Carboxylated Multi-walled Carbon Nanotubes Composite Based Genosensor for Detection of Bacterial Meningitis

Human brain bacterial meningitis is a life-threatening disease mainly caused by Neisseria meningitidis, lead to several complications including damage of brain or even death. The present available methods for diagnosis of meningitis have one or more limitations. A rmpM gene based genosensor was fabricated by immobilizing 5′-amino modified 19-mer single stranded DNA probe onto carbon-mercaptooctadecane/carboxylated multi-walled carbon nanotubes composite electrode and hybridized with 2.5–40 ng/6 μL of single stranded genomic DNA (ssG-DNA) of N. meningitidis from cerebrospinal fluid (CSF) of the suspected meningitis patients. The electrochemical response was measured by using cyclic voltammetry and differential pulse voltammetry (DPV) using 1 mM methylene blue as redox indicator in 30 min (including a response time of 1 min) at 25 °C. The sensitivity of the genosensor was 3.762 (μA/cm²)/ng and limit of detection was 2 ng of ssG-DNA of N. meningitidis with DPV. The genosensor has specificity only to N. meningitidis and does not hybridize with the genomic DNA of any other possible pathogen in human CSF. The immobilization of the probe and hybridization of the ssG-DNA were characterized by using electrochemical impedance in presence of 5 mM potassium ferricyanide and scanning electron microscopy. The genosensor loses only 12 % of its original DPV current on storage at 4 °C for 6 months. Carbon composite based electrochemical array can be constructed to detect multiple bacterial meningitis suspected patient CSF samples during an outbreak of the disease.