吡嗪酰胺介入凝胶体外抗结核活性及安全性评价

目的 :观察吡嗪酰胺凝胶体外抗结核作用和支气管介入的安全性。方法 :手工法、仪器法分别测定吡嗪酰胺单体、吡嗪酰胺凝胶的最小抑菌浓度 (MIC)和最小杀菌浓度 (MBC)及家兔经支气管介入的安全性试验。结果 :吡嗪酰胺凝胶对人型结核分枝杆菌标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为1mg/L、1mg/L、10mg/L ,MBC值分别为10mg/L、10mg/L、40mg/L ;吡嗪酰胺凝胶与吡嗪酰胺单体MIC、MBC值无显著性差异 ;动物安全性试验阴性。结论 :吡嗪酰胺凝胶具有与吡嗪酰胺单体相同的抗结核菌药效 ,卡波姆基质不影响吡嗪酰胺的抗菌活性 ;卡波姆基质吡嗪酰胺凝胶应用安全     

帕司烟肼介入凝胶体外抗结核活性及安全性研究

目的 观察帕司烟肼凝胶体外抗结核作用和支气管介入的安全性。方法 手工法、仪器法分别测定帕司烟肼及其凝胶的最小抑菌浓度和最小杀菌浓度及家兔经支气管介入的安全性试验。结果 帕司烟肼凝胶对H37Rv标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为0．1、0，1、0．4mg／L，MBC值分别为0，2、0．2和1．6mg／L；帕司烟肼凝胶与帕司烟肼单体MIC、MBC值无显著差异；动物实验表明该药应用安全。结论 帕司烟肼凝胶具有与帕司烟肼单体相同的抗结核菌药效，卡波姆基质不影响帕司烟肼的抗菌活性；以卡波姆为基质的帕司烟肼凝胶应用安全。     

异烟肼介入凝胶体外抗结核作用及安全性评价

目的：观察异烟肼凝胶体外抗结核活性和支气管介入的安全性。方法：手工法，仪器法分别测定异烟肼、异烟肼凝胶的最小抑菌浓度和最小杀菌浓度及家兔经支气管介入的安全性。结果：异烟肼凝胶对H37RV标准株，牛型结核分枝杆菌MIC值均为1mg.L^-1，对草分枝杆菌MIC值为8mg.L^-1，对H37RV标准株，牛型结核分枝杆菌MBC值均为4mg.L^-1，对草分枝杆菌MBC值为16mg.L^-1，异烟肼凝胶与异烟肼单体MIC、MBC值差异无显著性；动物安全性试验阴性，结论：异烟肼凝胶具有与异烟肼单体相同的抗结核菌药效，卡波姆基质不影响异烟肼的抗菌活性；卡波姆基质异烟肼凝胶应用安全。     

利复星凝胶对家兔体外抗结核的活性研究

目的研究利复星联合卡波姆凝胶对家兔体外抗结核的安全性。方法采用HPLC法测定血清中利复星浓度,在体外检测MIC、MBC、时间-杀菌及耐药梯度。测定利复星凝胶的最小抑菌、杀菌浓度及家兔经支气管介入的安全性。结果8例肺结核患者血药峰浓度于1.22h达4.52±0.72mg.L-1,分别1次给药24h后,最低血药浓度为0.52±0.26mg.L-1,表观分布容积V/FC为77.48±8.33mg.L-1。该药MIC、MBC值分别为0.5、1.0mg.L-1,耐药梯度范围0.5~48mg.L-1。利复星凝胶对H37RV标准株、牛型结核分枝杆菌、草分枝杆菌的MIC值分别为0.1、0.1、0.4mg.L-1,MBC值分别为0.2、0.21、.6mg.L-1;与利复星单体的MIC、MBC比较无显著差异。结论耐药肺结核患者服用利复星24h,其体内血药浓度维持在最低杀菌浓度MBC之上,介入治疗用药浓度应在48mg.L-1以上。     

苦参碱抑制结核菌的药效分析

为了解中药苦参碱对结核分枝杆菌的药效学情况,设计了苦参碱对结核杆菌的抑菌浓度(MIC)杀菌浓度(MBC)等试验。结果MIC为苦参碱为10mg/L,但杀菌效果欠佳。同时测得临床30例标本有70%在MIC范围,另证明苦参碱确实杀菌效果较弱。     

泌尿生殖道沙眼衣原体体外药物敏感性测定

目的　检测泌尿生殖道沙眼衣原体对 6种常用抗菌药米诺环素、阿奇霉素、克拉霉素、司帕沙星、氟罗沙星、左氧氟沙星的药物敏感性。方法　用 Mc Coy细胞培养法 ,以加入抗菌药后沙眼衣原体在细胞内不生长的最低浓度为最小抑菌浓度 (MIC) ,复板后在无抗菌药情况下仍不生长的最低浓度为最小杀菌浓度(MBC)。结果　米诺环素 MIC90 =0 .0 16 mg/ L,MBC90 =0 .0 32 mg/ L;阿奇霉素 MIC90 =0 .5 mg/ L,MBC90 =1.0 mg/ L ;克拉霉素 MIC90 =0 .0 32 mg/ L ,MBC90 =0 .12 8mg/ L ;司帕沙星 MIC90 =0 .0 32 mg/ L ,MBC90 =0 .0 6 3mg/ L ;氟罗沙星 MIC90 =2 .0 mg/ L ,MBC90 =8.0 mg/ L ;左氧氟沙星 MIC90 =0 .5 mg/ L ,MBC90 =2 .0 mg/L。结论　实验中未发现对这 6种抗菌药产生耐药的菌株 ,但氟罗沙星的 MIC90 与 MBC90 已在较高水平。此外 ,米诺环素的抑菌浓度已较以前报道升高。     

黄芩苷对结核分枝杆菌抑菌作用的初步研究

目的:通过体外抑菌试验探讨黄芩苷对结核分枝杆菌的体外抑菌活性.方法:采用改良罗氏培养基绝对浓度法检测黄芩苷对37株结核分枝杆菌的抑菌作用.结果:黄芩苷对37株结核分枝杆菌临床分离株的最低抑菌浓度(MIC)最低为1.5 g/L,最高＞48 g/L,MIC90为12g/L,MIC75和MIC50均为6g/L.全敏感菌株在MIC为6g/L时数量比例最大,随着MIC值向两侧递减;异烟肼(INH)低耐菌株的数量与MIC值无明显关联,乙胺丁醇(EMB)低耐菌株数量随着MIC由低到高的变化而显著增多;利福平(RFP)低耐菌株数量随着MIC由低到高的变化而逐步减少.结论:黄芩苷在体外对结核分枝杆菌具有一定的抑菌作用.     

结核分枝杆菌对吡嗪酰胺的药物敏感性试验分析

目的研究吡嗪酰胺对结核杆菌的药物敏感性,分析结核分枝杆菌对吡嗪酰胺的耐药现况,为结核病的临床用药和防治工作提供参考。方法对复活传代成功的结核分枝杆菌进行抗酸染色后,采用绝对浓度法的间接法,选用含缓冲对的蛋黄琼脂培养基,对结核杆菌菌株进行吡嗪酰胺的药物敏感性测定。结果测定的60株结核分枝杆菌中有15株敏感,44株耐药,一株未生长。结核分枝杆菌对吡嗪酰胺敏感率为25.42%(15/59),耐药率为74.58%(44/59)。结论随着吡嗪酰胺被广泛使用治疗,结核分枝杆菌对吡嗪酰胺的耐药性不断增高,目前耐药性比较高,临床用药时必须谨慎使用或联用其他药物有效治疗。     

葎草水提液的体外抑菌作用研究

目的:研究葎草水提液的体外抑菌效果。方法:采用倍比稀释法和96孔板微量肉汤稀释法对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌进行体外抑菌试验,测定其抑菌圈直径、最小抑菌浓度(MIC)和最低杀菌浓度(MBC)。结果:该药对试验菌株呈现不同程度的敏感,大肠埃希菌的MIC和MBC值浓度同为31.25 mg·ml-1;对金黄色葡萄球菌的MIC和MBC值浓度同为3.91 mg·ml-1;对铜绿假单胞菌的MIC和MBC值分别为125 mg·ml-1和250 mg·ml-1。结论:以水煎液为研究对象,考察葎草的体外抑菌效果更贴近临床应用形式,为葎草相关制剂的深入研究提供参考。     

纳米银凝胶抗菌活性的研究

目的:考察纳米银凝胶抗菌活性。方法:采用两倍稀释法进行体外抑菌试验,找出其最低抑菌浓度(MIC)和最小杀菌浓度(MBC),以比较纳米银凝胶、无色纳米银凝胶、市售中药妇科外用制剂的抗菌作用的强弱。结果:与中药妇科外用制剂作对照,纳米银凝胶组的MIC和MBC分别为0.156%-0.625%、0.312%-1.25%;中药妇科外用制剂的MIC和MBC分别为1.25%-2.50%、2.50%-5.00%。以含银量计,无色纳米银凝胶与纳米银凝胶的MIC为0.625μg/ml-1.25μg/ml,MBC值为0.25μg/ml-2.5μg/ml。结论:纳米银凝胶抗菌活性是中药妇科外用制剂的八倍;纳米银凝胶和改良后的无色纳米银凝胶抗菌活性基本一致。     

In vitro activity of linezolid against Mycobacterium tuberculosis complex, including multidrug-resistant Mycobacterium bovis isolates

The activity of linezolid was studied against 55 Mycobacterium tuberculosis (42 susceptible, 3 isoniazid resistant and 10 isoniazid and rifampicin resistant), one Mycobacterium bovis and two multidrug-resistant M. bovis isolates using the standard 7H10 agar proportion and the ESP Culture System II methods. Both methods displayed similar MIC(90) values (minimum inhibitory concentrations for 90% of the organisms) of 0.5mg/L; however, the former method yielded slightly lower MIC(50) values (MICs for 50% of the organisms) (0.25mg/L) compared with the latter method (0.5mg/L). No differences were observed between susceptible and resistant isolates, including multidrug-resistant M. bovis isolates, with a MIC range of 0.12-0.5mg/L. The potential role of linezolid in tuberculosis patients requires further in vivo evaluation.     

莫西沙星治疗耐多药肺结核患者的药效学研究

目的探讨莫西沙星片口服给药和局部介入治疗用药量的依据。方法莫西沙星血清中浓度采用高效液相色谱法测定,时间-杀菌、MIC、MBC及耐药梯度等试验在体外检测。结果 10例肺结核患者血峰浓度于1.81h到达（3.11±0.53）mg/L,1次单剂量给药24h后最低血药浓度为（0.26±0.06）mg/L,表观分布容积V/FC为（150.02±32.63）L,该药MIC.MBC值为0.20mg/L,1mg/L,耐药梯度范围在0.20～8mg/L。结论服用莫西沙星片治疗耐药肺结核患者,体内血药浓度24h应维持在最低杀菌浓度之上,介入治疗用药浓度应在8μg/ml以上。     

Growth inhibition of Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium in vitro: effect of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-2'-ribofuranosyl) pyrimidine nucleoside analogs

The resurgence of tuberculosis and the emergence of multiple-drug-resistant strains of Mycobacteria necessitate the search for new classes of antimycobacterial agents. We synthesized a series of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl) pyrimidine nucleosides possessing diverse sets of alkynyl, alkenyl, alkyl, and halo substituents at the C-5 position of the uracil and investigated their effect on activity against M. tuberculosis, M. bovis, and M. avium. Among these molecules, 5-alkynyl-substituted derivatives emerged as potent inhibitors of M. bovis, M. tuberculosis, and M. avium. Nucleosides 1-beta-D-2'-arabinofuranosyl-5-dodecynyluracil (5), 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-dodecynyluracil (24), and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-tetradecynyluracil (25) showed the highest antimycobacterial potency against M. bovis and M. tuberculosis. The MIC90 exhibited by compounds 5, 24, and 25 was similar or close to that of the reference drug rifampicin. The most active compounds 5, 24, and 25 were also found to retain sensitivity against a rifampicin-resistant strain of M. tuberculosis H37Rv at similar concentrations. Some of these analogs also revealed in vitro antimicrobial effect against several other gram-positive pathogens.     

An antibacterial from Hypericum acmosepalum inhibits ATP-dependent MurE ligase from Mycobacterium tuberculosis

In a project to characterise new antibacterial chemotypes from plants, hyperenone A and hypercalin B were isolated from the hexane and chloroform extracts of the aerial parts of Hypericum acmosepalum. The structures of both compounds were characterised by extensive one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and were confirmed by mass spectrometry. Hyperenone A and hypercalin B exhibited antibacterial activity against multidrug-resistant strains of Staphylococcus aureus, with minimum inhibition concentration ranges of 2-128 mg/L and 0.5-128 mg/L, respectively. Hyperenone A also showed growth-inhibitory activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG at 75 mg/L and 100mg/L. Neither hyperenone A nor hypercalin B inhibited the growth of Escherichia coli and both were non-toxic to cultured mammalian macrophage cells. Both compounds were tested for their ability to inhibit the ATP-dependent MurE ligase of M. tuberculosis, a crucial enzyme in the cytoplasmic steps of peptidoglycan biosynthesis. Hyperenone A inhibited MurE selectively, whereas hypercalin B did not have any effect on enzyme activity.     

In vitro evaluation of dinactin,a potent microbial metabolite against Mycobacterium tuberculosis

Current long duration treatment options and the emergence of drug resistance in tuberculosis (TB) have led to renewed interest in discovery of novel anti-tubercular agents or the scaffolds exhibiting enhanced efficacy with current anti-TB drugs. Herein, dinactin, a potent bioactive macrotetrolide isolated from Streptomyces puniceus AS13, was evaluated against Mycobacterium tuberculosis H37Rv and other susceptible and drug-resistant clinical isolates of M. tuberculosis. In vitro pharmacological assays showed that dinactin is bactericidal against laboratory standard strain M. tuberculosis H37Rv (minimum inhibitory concentration [MIC] 1 µg/mL and minimum bactericidal concentration [MBC] 4 µg/mL). Dinactin also retained its activity against various clinical isolates, including multidrug-resistant strains of M. tuberculosis. Whole cell interaction assays with standard first- and second-line anti-TB drugs showed the synergistic interaction of dinactin with rifampicin or amikacin, reflecting its suitability for use in combination regimens. The killing kinetics studies of dinactin against M. tuberculosis H37Rv revealed that it has strong concentration-dependent anti-TB activity that is also dependent on time. The kill curve also showed dynamic killing capacity of dinactin as it exhibited bactericidal potential at all concentrations tested. Kill curve data demonstrated that dinactin, like isoniazid, exerts its strong tuberculocidal activity within the first two days of exposure. This evidence strongly supports further evaluation of dinactin as a new option in the treatment of TB.     

Demethoxycurcumin and its semisynthetic analogues as antitubercular agents

Demethoxycurcumin, isolated from the rhizomes of Curcuma longa, was found to possess antitubercular activity against Mycobacterium tuberculosis H (37)Rv strain at 200 microg/mL. Derivatisation of this active principle yielded a potent agent 6, exhibiting considerable activity with a minimum inhibitory concentration (MIC) value of 7.8 microg/mL. H (37)Rv:Mycobacterium tuberculosis H (37)Rv strain MIC:minimum inhibitory concentration.     

Purified compounds and extracts from Euclea species with antimycobacterial activity against Mycobacterium bovis and fast-growing mycobacteria

Naphthoquinones and other compounds with antimycobacterial activity against Mycobacterium tuberculosis have previously been isolated from Euclea species. In this study, several constituents of Euclea natalensis and E. undulata, as well as organic extracts of the leaves, were assessed for efficacy against the zoonotic pathogen, Mycobacterium bovis. Also included in the battery of test organisms were M. bovis BCG and the fast-growing species M. smegmatis and M. fortuitum. The acetone extract of E. natalensis had potent activity against M. bovis (MIC=26 microg/ml). The naphthoquinone 7-methyljuglone was the most active compound, with an MIC as low as 1.55 microg/ml against pathogenic M. bovis. M. bovis BCG was not as susceptible to the test compounds as the pathogenic strain, but similar patterns of activity were observed between all the strains tested. M. smegmatis appeared to be a better predictor of antimycobacterial activity against pathogenic M. bovis (and M. tuberculosis), while MIC values obtained using M. fortuitum correlated well with those of M. bovis BCG.     

抗痨胶囊剂体内外抗肺结核作用研究

目的体内外评价抗痨胶囊防治肺结核作用。方法运用试管法观察两种制剂体外对结核菌生长的影响,运用结核豚鼠观察药物体内对结核病的防治作用。结果抗痨胶囊体外对人型H37RV结核杆菌、牛型分枝杆菌及耐异烟肼、耐利福平、耐链霉素和联合耐异烟肼、利福平及链霉素结核杆菌的MIC和MBC分别为0.5mg/ml和5mg/ml、10mg/ml和大于20mg/ml、5mg/ml和10mg/ml、5mg/ml和10mg/ml、10mg/ml和20mg/ml。体内抗结核实验结果显示：抗痨胶囊可显著减少结核豚鼠肺脏的结核结节及肺脏和脾脏的结核菌数量,同时还可减轻结核豚鼠肝脏、脾脏及肺脏的炎性反应。并可显著减少豚鼠脾脏的结核结节。结论上述结果显示,抗痨胶囊对肺结核有一定的防治作用,有一定的开发前景。