利福霉素类药物治疗结核病的临床应用研究进展

结核病是由结核分枝杆菌复合群引起的传染性疾病，是全球主要的流行病种之一。利福平是当前最主要的一线抗结核药物，因其长期应用和不规范治疗，利福平耐药逐渐增加，利福喷丁、利福布汀等利福霉素类衍生物在抗结核治疗方面起到了重要作用。基于利福霉素类药物的药理及药动学特性，对该类药物在结核病治疗中进行最优用药选择分析，并对该类药物与其他抗结核药物联用进行综述，旨在为利福霉素类抗结核药物的临床用药提供文献依据。     

HAART and anti-Koch’s impair sexual competence,sperm quality and offspring quality when used singly and in combination in male Wistar rats

This study investigated the impact of the administration of HAART and anti-Koch's, singly and in combination, on sexual competence and birth statistics. Adult male Wistar rats were randomised into distilled water-treated control, HAART-treated, anti-Koch's-treated and HAART + anti-Koch's-treated groups. The 56-day oral treatment led to impaired sexual competence evident by significantly reduced motivation to mate, prolonged latencies of mount, intromissions, ejaculations and post-ejaculatory interval, as well as reduced frequencies of mount, intromissions and ejaculations. This was accompanied by significant reductions in penile erection reflex and penile grooming. HAART and anti-Koch's, when administered singly or in combination, also led to significant reductions in the circulatory follicle-stimulating hormone, luteinizing hormone, testosterone and intratesticular testosterone, but a significant rise in prolactin. Also, HAART and/or anti-Koch's significantly reduced sperm count, sperm motility, sperm viability and spermatozoa with normal morphology. Furthermore, HAART and anti-Koch's, separately or in combination, significantly lowered fertility capacity, litter size and litter weight and offspring survival. The deleterious effects of these drugs were more pronounced when combined. Findings of the present study revealed that HAART and/or anti-Koch's impair sexual competence via a testosterone-dependent hyperprolactinemia-mediated mechanism. These events are associated with reduced fertility capacity, poor sperm quality and lowered offspring survival.     

中西医结合治疗肺痨咯血72例临床观察

目的观察中西医结合治疗肺痨咯血的疗效.方法将肺痨咯血患者属肺阴亏损证者138例随机分成两组.治疗组72例用抗痨 中药(月华化血丹) 山莨菪碱治疗;对照组66例用抗痨 止血药(对羧基苄胺、安特诺新)治疗,观察比较其疗效.结果止血疗效治疗组总有效率为95.83%,对照组为75.76%,治疗组优于对照组(P＜0.001).肺痨治愈率中初治涂阳治愈率治疗组为98.1%,对照组为83.3%,治疗组优于对照组(P＜0.01).结论中西医结合治疗肺痨咯血见效快、疗效确切.     

肝X-受体激动剂马尾藻甾醇的体外抗结核活性研究

目的 评价马尾藻甾醇及其24-差向异构体的抗结核活性。方法 运用半制备HPLC法分到马尾藻甾醇异构体,¹H-NMR鉴定异构体的化学结构;采用倍比稀释法测定化合物对结核分枝杆菌Mycobacterium tuberculosis的最小抑菌浓度(minimal inhibit concentration, MIC)、单独使用及联合用药的杀菌作用;采用PNPA法评价化合物对芳胺N-乙酰基转移酶(arylamine N-acetyltransferases, NAT)的抑制作用,并使用ledock go软件进行分子虚拟对接实验。结果 获得24S-和24R-马尾藻甾醇;马尾藻甾醇、24S异构体和24R异构体对M. tuberculosis的MIC值分别是25 μM、12.5 μM和 >100μM,对NAT蛋白的抑制率分别为45.27%、46.95%和29.20%。马尾藻甾醇和24S异构体还能增强氧氟沙星的杀菌作用。从数值上看,24S异构体活性强于24R异构体,分子对接实验提示24S异构体与NAT蛋白之间的结合比24R异构体更牢固。结论 马尾藻甾醇及其24S异构体在体外对结核分枝杆菌具有杀菌作用,可能与细菌胆固醇代谢有关,尚待深入研究。     

抗结核药物的研究进展

随着结核病耐药频率不断升高,结核病治疗面临严峻的挑战,因此,研发新型抗结核药物显得尤为重要。在过去十年中,抗结核药物的研发取得了重要进展。本文将对近年来被批准用于临床和正在进行临床试验的新化学实体按靶点进行分类,并综述其作用机制、体内外药理活性、药代动力学性质以及临床研究结果。对抗结核药物的研发进行了展望,以期对结核病药物研发提供参考。     

抗痨化瘀散结汤辅助抗结核化学药物治疗肺结核的疗效评价

目的评价抗痨化瘀散结汤对肺结核的作用。方法 117例患者分为:对照组(39例)常规抗结核化疗;治疗组(78例)在对照组上加抗痨化瘀散结汤2个月。总疗程6个月。结果治疗组症状完全改善率和所需时间明显优于对照组(P0.05或0.01)。在疗程第2和4个月时,治疗组痰菌阴转率以及肺部病灶吸收率均明显优于对照组(P0.05)。治疗组显效率(96.2%)也明显优于对照组(82.1%)(P0.05);其不良反应发生率较低。结论抗痨化瘀散结汤对改善肺结核症状、促使痰结核菌阴转和肺部病灶吸收以及减轻不良反应均有一定作用。     

Two new p-coumaroylated sesquiterpenoids from Pilea cavaleriei

A new p-coumaroylated santalane-type sesquiterpenoid, 8-p-coumaroyl-α-santalene (1), a new p-coumaroylated oplopanane-type sesquiterpenoid, 8-β-p-coumaroyl-oplopanone (2), and three known p-coumaroylated humulene-type sesquiterpenoids (3–5) were isolated from the ethanol extract of the whole herbs of Pilea cavaleriei. Their structures were elucidated based on the combination of 1D and 2D NMR and HRMS methods. Compound 2 was found to show anti-tuberculosis activity with MIC of 16 μg/ml.     

云南省抗结核二线药物使用现状调查报告

目的调查云南省各级医疗机构二线抗结核药物(second-line anti-tuberculosis drugs,SLD)的使用情况,为制定合理使用SLD的相关政策提供依据。方法省级、州(市)及县(市、区)级疾控中心结防门诊、结核病治疗定点医院、医疗机构及乡镇卫生院进行问卷调查,并将问卷调查进行汇总分析。结果调查的558个医疗机构中,76.95%的机构使用了SLD。各级SLD使用率分别为:省级100%、州(市)级61.7%、县级72.98%、乡镇级74.95%。不同类型的机构使用SLD的比例不相同,综合医院较高为88.46%,乡镇卫生院次之77.34%。结防机构相对较低53.42%。只有0.72%单位开展一线抗结核药物敏感试验。结论 SLD在各级医疗机构使用很普遍,而药物敏感性试验很少开展,应制定相关政策规范SLD的使用。     

左氧氟沙星治疗耐药肺结核的疗效分析

目的分析及评估左氧氟沙星联合其他抗痨方案在耐药肺结核（MDR-PTB）治疗中的疗效。方法将2004年01月～2008年12月例MDR-PTB病人随机分配至含左氧治疗组及不使用左氧对照组。治疗组方案为左氧为主联合力克肺疾、丙硫异烟胺、吡嗪酰胺、丁胺卡那,对照组用力克肺疾、丙硫异烟胺、吡嗪酰胺、丁胺卡那、乙胺丁醇,疗程为18个月。结果 86例病人完成疗程。治疗组46例,痰菌阴转42例（91%）;对照组40例,痰菌阴转21例﹙52%）;治疗组明显高于对照组,治疗组病灶吸收及空洞闭合均优于对照组。结论左氧氟沙星具有较强抗结核效果,含左氧氟沙星方案治疗MDR-TB,有助于痰菌转阴和病变吸收好转,有推广应用价值。