3种抗真菌药物对口腔白念珠菌最小抑菌浓度的体外对比研究

目的通过测定氟康唑、制霉菌素和洗必泰3种抗真菌药物对口腔白念珠菌临床分离株的最小抑菌浓度（MIC）,指导临床合理用药。方法采集疑诊为口腔念珠菌病患者的口腔拭子标本,分离、鉴定获得37株白念珠菌做为受试菌株。应用微量稀释法测定3种药物的MIC。质控菌株为白念珠菌ATCC22019（对氟康唑敏感）。结果 3种抗真菌药物对90%以上的受试菌株的MIC值分别为氟康唑≤2μg/ml,制霉菌素≤2μg/ml、洗必泰≤8μg/ml。经Kruskal-Wallis秩和检验,3种药物的MIC值差异有统计学意义（P〈0.01）;经Nemenyi法比较,氟康唑组与制霉菌素组差异无统计学意义（P〉0.05）,2组的MIC值均明显低于洗必泰组（P〈0.01）。结论 3种抗真菌药物对口腔白念珠菌在体外均有较强的抑菌能力,氟康唑和制霉菌素较高,洗必泰次之。     

黄芩苷对白色念珠菌生物膜形成的体外抑制作用

目的：研究黄芩苷体外对白色念珠菌生物膜形成的影响。方法扫描电镜下观察不同培养时间的生物膜形态,并用XTT减低法检测黄芩苷对白色念珠菌生物膜活性的影响,用结晶紫含量测定法检测黄芩苷对白色念珠菌生物膜生物量的影响。结果白色念珠菌在48h时形成成熟的生物膜。黄芩苷在浓度为8．0mg? mL －1时使白色念珠菌生物膜活性及生物量分别减少（90．6±5．2）％和（90．3±2．6）％,生物膜已基本无活性。结论黄芩苷对白色念珠菌生物膜的形成具有抑制作用。     

白色念珠菌生物膜中胞外DNA分布观察

目的：动态观察白色念珠菌生物膜形成过程中胞外DNA的分布情况。方法：在2．0cm^2载玻片上形成白色念珠菌生物膜。用核酸染料对膜中的胞外DNA进行染色．激光共聚焦显微镜下观察不同培养时间的生物膜中胞外DNA的分布。结果：白色念珠菌生物膜中舍有胞外DNA。结论：白色念珠菌生物膜中含有胞外DNA,随培养时间延长,生物膜内胞外DNA的增加,分布在活菌的周围。     

三种表面活性剂止孕作用的实验研究

本文对新洁尔灭、度米芬、洗必泰的止孕作用和安全性进行了比较研究，结果表明三种表面活性剂均有明显的抗早孕作用，可使受孕大鼠子宫蜕膜退变、坏死。对早孕及正常大鼠离体子宫有短暂的兴奋作用。小鼠腹腔注射三种药物后新洁尔灭毒性最大，洗必泰毒性最小，而静脉注射后则洗必泰毒性最大，度米芬毒性最小。对豚鼠三药皆有不同程度的致敏性。     

卡泊芬净对生物膜态白色念珠菌体外抑菌作用的试验研究

目的:检测卡泊芬净对生物膜态白色念珠菌分离株的抑菌作用,探讨临床治疗其相关感染的最适治疗剂量。方法:分别测定卡泊芬净对10株白色念珠菌临床株游离态及生物膜态的半数抑菌浓度(MIC50),并对比观察不同浓度卡泊芬净作用下白色念珠菌的增殖活性。结果:卡泊芬净对游离态白色念珠菌的MIC50为0.125～0.5mg.L-1,对生物膜态白色念珠菌的MIC50为0.25～256mg.L-1,当卡泊芬净浓度高于白色念珠菌MIC50时,全部游离态白色念珠菌的增殖活性几乎完全受到抑制,但有7株生物膜态白色念珠菌的增殖活性再次增强,且大于阳性对照的50%。结论:卡泊芬净对生物膜态白色念珠菌有抑菌作用,但并不呈浓度依赖性,当其用于治疗生物膜态白色念珠菌相关感染时的最适治疗剂量有待临床研究验证。     

白花丹素联合氟康唑对金黄色葡萄球菌与白色念珠菌混合生物膜的作用机制研究

摘要：目的:分析白花丹素单独或者联合氟康唑对金黄色葡萄球菌与白色念珠菌混合生物膜的作用及其机制。方法:收集2019年临床分离的2株耐甲氧西林金黄色葡萄球菌（MRSA）以及2株甲氧西林敏感金黄色葡萄球菌（MSSA）;利用分光光度计检测白花丹素或联合氟康唑后金黄色葡萄球菌与白色念珠菌混合菌群生长能力变化;菌落计数法测定白花丹素或联合氟康唑作用前后生物膜形成能力差异;实时荧光定量PCR（qRT-PCR）检测白花丹素存在与不存在条件下与白色念珠菌DAY185生物膜形成相关基因（ALS1、ALS3和RBT1）以及与金黄色葡萄球菌生物膜形成相关基因（icaA、sarA和cidA）的表达量。结果:白花丹素可以明显降低金黄色葡萄球菌与白色念珠菌混合菌群的生长能力,吸光度(A600)值可降至1.5,当与氟康唑联合使用时效果更佳,A600值可下降至1.0;生物膜形成能力试验显示白花丹素可以明显降低金黄色葡萄球菌与白色念珠菌混合生物膜的形成能力约2～2.5个数量级（P<0.01）;qRT-PCR结果表明：白花丹素主要可以降低白色念珠菌生物膜形成相关的黏附基因ALS3约3倍（P<0.05）以及与金黄色葡萄球菌生物膜形成相关基因sarA约4倍（P<0.05）的表达量。结论:白花丹素可以降低金黄色葡萄球菌与白色念珠菌混合生物膜的能力,其机制主要通过降低白色念珠菌菌丝形成的相关基因ALS3以及与金黄色葡萄球菌生物膜形成相关基因sarA的表达,当联合氟康唑时效果更强。     

氢氧化钙和洗必泰在年轻恒牙外伤后牙髓血运重建中的疗效

目的 评估氢氧化钙和洗必泰作为根管内药物,在治疗年轻恒牙因外伤致牙髓坏死后行牙髓血运重建治疗中的效果。方法 从2014年10月至2015年10月在安徽省立医院口腔医学中心门诊就诊患者中选取8例因外伤致年轻恒牙牙髓坏死的病例,术前记录患牙情况、X线片记录牙根发育情况,术中应用氢氧化钙和2%洗必泰凝胶作为消毒灭菌药物行牙髓血运重建术,术后2周及每6个月复查,并记录患牙发育状况。结果 术后2周复诊,所有患牙均无自觉症状和根尖炎的临床症状;18个月后7颗患牙临床检查无异常,X线片显示牙根继续发育,1颗患牙在术后6个月治疗失败改行根尖诱导成形术。结论 氢氧化钙和洗必泰作为根管内消毒灭菌药物在年轻恒牙的牙髓血运重建术中可以促使牙根继续发育,并且不会诱发牙冠变色。     

复方洗必泰含漱液与甲硝唑片剂治疗牙周病的比较

比较了复方洗必泰含漱液和甲硝唑片剂对治疗牙周病的疗效。结果显示：复方洗必泰含漱液的总有效率为98．6％,而片剂则为81．5％;复方洗必泰含漱液的用药剂量比片剂小,而龈沟液中药物浓度比片剂高。复方洗必泰含漱液对孕妇和肝、肾功能差等不宜内服药物的牙周病患者更为合宜,值得推广应用。     

抗菌药物对氟康唑动态抗真菌作用及透过生物膜的影响

目的：测定试验用抗菌药物与氟康唑联合的动态抗真菌作用,并评价试验用抗菌药物对氟康唑透过生物膜的影响。方法：采用活菌计数法描绘联合用药对白色念珠菌的动态杀菌曲线,以“三明治”透膜实验法评价试验用抗菌药物对氟康唑透过生物膜的影响。结果：试验抗菌药物对氟康唑有不同程度的增效作用,其中米诺环素和利福平对氟康唑透过耐药白色念珠菌生物膜的作用及其对氟康唑动态抗真菌的增效作用最强,氧氟沙星、阿奇霉素等次之。结论：试验用抗菌药物能促进氟康唑透过白色念珠菌生物膜,增强氟康唑的动态抗真菌作用。     

复方洗必泰栓的含量测定

复方洗必泰栓是在醋酸洗必泰栓的处方基础上加入适量的抑制厌氧菌药物甲硝基羟乙唑而制得,对治疗女性生殖道由细菌、原虫感染的疾病优于原醋酸洗必泰栓。     

亚抑菌浓度卡泊芬净对白念珠菌生物膜形成的影响及机制研究

目的 初步探讨亚抑菌浓度(sub-MIC)卡泊芬净对白念珠菌生物膜形成的影响,为清除生物膜策略的制定提供理论基础。方法 用微量肉汤稀释法测定卡泊芬净对白念珠菌的活性,并研究sub-MIC卡泊芬净对白念珠菌生长的影响;运用菌落计数、XTT染色和扫描电镜分析sub-MIC卡泊芬净作用下形成的白念珠菌生物膜特点;采用实时荧光定量RT-PCR测定Ece1,Can2,Hip1,GAP1,GCN4和Stp2等白念珠菌生物膜相关基因的mRNA表达水平。结果 12株白念珠菌对卡泊芬净的MIC值范围为0.625～0.875μg/mL,sub-MIC卡泊芬净对白念珠菌的生长有不同程度的抑制作用。针对白念珠菌生物膜的形成,1/4 MIC和1/8 MIC卡泊芬净皆对生物膜中的菌体数量、菌体代谢活性及生物膜结构有抑制作用,而1/16 MIC卡泊芬净则对生物膜无明显影响。1/4 MIC和1/8 MIC卡泊芬净对白念珠菌生物膜相关基因的表达水平也具有抑制作用,1/16 MIC卡泊芬净则对基因表达水平无影响。结论 sub-MIC卡泊芬净对白念珠菌生物膜的形成有一定抑制作用。但白念珠菌在sub-MIC卡泊芬净作用下仍能...     

奥硝唑联用醋酸氯己定对白色念珠菌的体外抗菌活性考察

目的:考察奥硝唑与醋酸氯己定联合用药对白色念珠菌的体外抗菌活性.方法:采用棋盘法设计,琼脂平板稀释法测定最低抑菌浓度 (MIC)值;计算分级抑菌浓度 (FIC)指数并判定联合效应, FIC≤ 0.5为协同作用, 0.5 2为拮抗作用.结果:奥硝唑与醋酸氯己定联合应用,其 MIC显著降低, FIC≤ 0.5.结论:奥硝唑与醋酸氯己定联合用药后,对白色念珠菌体外抗菌活性有协同作用.     

天葵化石汤提取液对尿结石矿物草酸钙形成的影响

目的：研究土家族药物天葵化石汤治疗尿石症的化学基础。方法：采用X射线衍射法（XRD）和傅立叶红外光谱（FT-IR）法研究了天葵化石汤提取液对尿石晶体草酸钙（CaOxa）结晶的影响。结果；当天葵化石汤提取液加入量小于5．0mL（相当于生药1．5g）时，与空白试验结果相近，主要形成一水草酸钙（COM）；随着提取液加入量分别增加至8．0，15．0mL，CaOxa晶相发生了明显的变化，分别形成了约73％，100％的二水草酸钙（COD）。结论：该结果在理论上支持临床使用天葵化石汤作为防治泌尿系结石的有效药物。     

Fungal biofilm inhibition by a component naturally produced by Candida albicans yeasts growing as a biofilm

The purpose of this work was to demonstrate production by the Candida yeasts growing as a biofilm of a compound that reduces candidal biofilm growth. An in vitro model of Candida albicans biofilm associated with silicone catheters was used. Supernatant medium recovered from 24-h-old C. albicans (ATCC 3153) biofilm (S24h) was added during the course of new biofilm formation by four C. albicans strains (182, 444, 2091 or ATCC 3153). Addition of S24h to adherent C. albicans cells induced an inhibition of biofilm growth (P<0.001) but displayed no activity on established biofilms. Ultrafiltration and purification assays demonstrated that the antagonistic molecule is hydrophilic and <3000Da in size.     

Effects of sub-minimum inhibitory concentrations of antimicrobial agents on Streptococcus mutans biofilm formation

Many studies have demonstrated that sub-minimum inhibitory concentrations (sub-MICs) of antimicrobial agents can inhibit bacterial biofilm formation. However, the mechanisms by which antimicrobial agents at sub-MICs inhibit biofilm formation remain unclear. At present, most studies are focused on Gram-negative bacteria; however, the effects of sub-MICs of antimicrobial agents on Gram-positive bacteria may be more complex. Streptococcus mutans is a major cariogenic bacterium. In this study, the S. mutans growth curve as well as the expression of genes related to S. mutans biofilm formation were evaluated following treatment with 0.5× MIC of chlorhexidine (CHX), tea polyphenols and sodium fluoride (NaF), which are common anticaries agents. The BioFlux system was employed to generate a biofilm under a controlled flow. Morphological changes of the S. mutans biofilm were observed and analysed using field emission scanning electron microscopy and confocal laser scanning microscopy. The results indicated that these three common anticaries agents could significantly upregulate expression of the genes related to S. mutans biofilm formation, and S. mutans exhibited a dense biofilm with an extensive extracellular matrix following treatment with sub-MICs of NaF and CHX. These findings suggest that sub-MICs of anticaries agents favour S. mutans biofilm formation, which might encourage dental caries progression.     

Studies on the instability of chlorhexidine, part I: kinetics and mechanisms

The objectives of the studies presented herein were to determine the pH-dependent chlorhexidine (CHD) degradation scheme, to determine the rate laws, and to propose reasonable mechanisms for CHD hydrolysis in aqueous solutions. A series of degradation kinetic studies was conducted at 90.0 °C using reaction mixtures containing 0.10 mM CHD prepared in the pH range of 0.5-9.0 using hydrochloric acid, sodium hydroxide, acetate, phosphate, or 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffers at a constant ionic strength of 0.500 M. Concentration-time profiles for all degradation products, intermediates, and substrates were determined by high-performance liquid chromatography (HPLC). Degradation products and intermediates were identified using a combination of liquid chromatography-mass spectrometry, kinetic analysis, and HPLC comparison with authentic compounds. pH-dependent degradation scheme and rate laws were parameterized using nonlinear regression. The direct formation of p-chloroaniline (PCA) from CHD is the major pathway in acidic conditions, whereas the indirect formation of PCA via the formation of p-chlorophenylurea is the main pathway in alkaline conditions.     

草决明与苯唑青霉素联用对临床MRSA菌株的杀菌作用研究

目的观察草决明醇提液对临床MRSA菌株生物膜形成的影响及其与苯唑青霉素联用对MRSA菌株的杀菌作用。方法构建生物膜形成阳性菌株,96孔板法测定草决明醇提液及苯唑青霉素对临床MRSA菌株生物膜形成的影响,棋盘法测定草决明与苯唑青霉素联用对临床MRSA菌株的杀菌作用。结果亚抑菌浓度的草决明醇提液可抑制临床MRSA菌株生物膜的形成,与苯唑青霉素联用对临床MRSA菌株杀菌作用有协同作用。结论草决明与苯唑青霉素联用时有协同杀菌作用,此作用可能与草决明醇提液抑制金葡菌生物膜形成有关。     

Efficacy of disinfectants and hot water against biofilm cells of Burkholderia cepacia

The effects of various disinfectants and hot water on planktonic cells and biofilm cells of Burkholderia cepacia were investigated. The survival rate of viable B. cepacia cells in suspension decreased to 0.001% or lower within 15 s of exposure to 0.5% benzalkonium chloride, within 30 s of exposure to 0.5% alkyldiaminoethyl glycine, or within 1 min of exposure to 0.1% alkyldiaminoethyl glycine, and decreased to about 0.1% with 60 min of exposure to 0.1% benzalkonium chloride or 0.5% chlorhexidine gluconate, but did not decrease to 1% or less with 60 min of exposure to 0.1% chlorhexidine gluconate. There were no effects of 0.1% and 0.2% chlorhexidine gluconate and 0.1% benzalkonium chloride against biofilm cells of B. cepacia, and 0.5% chlorhexidine gluconate, 0.5% benzalkonium chloride and 0.1% alkyldiaminoethyl glycine were barely effective against biofilm cells even after 60-min exposure. On the other hand, both planktonic cells and biofilm cells of B. cepacia were eradicated within 15 s by sodium hypochlorite, povidone-iodine, 80% v/v ethanol, and hot water at 65 degrees C or higher.