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Current Overview of Anti-Tuberculosis Drugs: Metabolism and Toxicities 抗结核药物的现状综述:代谢和毒性
Pub Date : 2016-05-26 DOI: 10.4172/2161-1068.1000209
Susmita Sarkar, Advaita Ganguly, H. Sunwoo
Tuberculosis, a global public health epidemic, is one of the leading causes of death by an infectious disease. According to the World Health Organization (WHO), one third of the world’s population is infected with Mycobacterium tuberculosis (MTb), 5-10% of whom will possibly go on to develop active disease. Tuberculosis (TB) is an epidemic especially in poor countries, and each year the disease kills approximately 1.7 million people worldwide. The Mycobacterium family has over 60 species but only a few of them can cause diseases in humans, such as Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium africanum and Mycobacterium avium. MTb can exist in the latent state, where it resides in the human body for an extended period of time without showing any clinical symptoms. Once the host’s immune system becomes weakened, whether by age or concomitant disease, the bacteria attains virulent or active form. With the increasing incidence of HIV infection, tuberculosis has reemerged as an important cause of morbidity and mortality worldwide.
结核病是一种全球性的公共卫生流行病,是一种传染病导致死亡的主要原因之一。根据世界卫生组织(WHO)的数据,世界上三分之一的人口感染了结核分枝杆菌(MTb),其中5-10%的人可能会发展成活动性疾病。结核病是一种流行病,特别是在贫穷国家,每年全世界约有170万人死于这种疾病。分枝杆菌科有60多种,但只有少数几种能引起人类疾病,如结核分枝杆菌、麻风分枝杆菌、非洲分枝杆菌和鸟分枝杆菌。结核分枝杆菌可处于潜伏状态,在人体内潜伏较长时间而不表现出任何临床症状。一旦宿主的免疫系统变弱,无论是由于年龄还是伴随疾病,细菌就会达到致命或活跃的形式。随着艾滋病毒感染发病率的增加,结核病已重新成为世界范围内发病率和死亡率的重要原因。
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引用次数: 38
Expression and Analysis of CXCL8 and CXCL10 Chemokines in Human SkinLesions Infected with M.leprae 麻疯病人皮肤病变中CXCL8和CXCL10趋化因子的表达及分析
Pub Date : 2016-05-24 DOI: 10.4172/2161-1068.1000208
K. Rawat, M. Chahar, P. Reddy, N. Srivastava, U. Gupta, M. Natrajan, V. Katoch, K. Katoch, D. Chauhan
This study is focused to analyze the expression profile of CXCL8 and CXCL10 chemokines genes and to address the contribution of these chemokines in late phase of M.leprae infection in human skin lesion samples. In this study skin biopsy samples from leprosy patients (n=35) were collected including BL-LL=12, BB=14, BT=8 and healthy volunteers (n=3). All the biopsy samples were collected in RNALater for mRNA expression study as well as 10% buffered formalin (BF) for histopathologic analysis. Total RNA was isolated from collected samples and cDNA was prepared. Level of mRNA expression of CXCL8 and CXCL10 chemokine genes was measured via q-PCR and insitu RT-PCR to locate the presence of CXCL8 and CXCL10 chemokines inside M. leprae infected tissue. The mRNA expression of CXCL8 was found relatively elevated in lepromatous (BL-LL) skin samples significantly as compared to BB category of leprosy; whereas in BT cases down-regulation was recorded. CXCL10 mRNA expression was found elevated in lepromatous (BL-LL) cases than other cases (BT, BB) of leprosy samples. In histopathological examination, 59.38% maximum infiltration was observed in BL-LL cases of leprosy and in-situ RT-PCR confirmed the presence of chemokines genes in tissue sections. Interestingly, chemokines CXCL-10 and CXCL-8 showed elevated expression in BL-LL category. The study advocated that CXCL10 and CXCL-8 possibly may have a role in lepromatous (BL-LL) form of leprosy.
本研究的重点是分析CXCL8和CXCL10趋化因子基因的表达谱,并探讨这些趋化因子在麻风晚期感染人皮肤病变样本中的作用。本研究收集麻风患者皮肤活检样本(n=35),其中BL-LL=12, BB=14, BT=8,健康志愿者(n=3)。所有活检标本在RNALater中进行mRNA表达研究,10%缓冲福尔马林(BF)进行组织病理学分析。从收集的样品中分离总RNA,制备cDNA。通过q-PCR和原位RT-PCR检测CXCL8和CXCL10趋化因子基因mRNA表达水平,定位麻风支原体感染组织中CXCL8和CXCL10趋化因子的存在。CXCL8 mRNA在麻风(BL-LL)皮肤样本中的表达明显高于BB类麻风;而在BT病例中则记录了下调。CXCL10 mRNA在麻风(BL-LL)病例中的表达高于其他麻风(BT、BB)病例。在组织病理学检查中,BL-LL型麻风患者的浸润率最高达59.38%,原位RT-PCR证实组织切片中存在趋化因子基因。有趣的是,趋化因子CXCL-10和CXCL-8在BL-LL组中表达升高。该研究主张CXCL10和cxcl8可能在麻风型(BL-LL)麻风中发挥作用。
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引用次数: 3
Extending a Step Further: Offering Tobacco Cessation Counselling to Contacts ofTuberculosis Patients 更进一步:向结核病患者接触者提供戒烟咨询
Pub Date : 2016-05-16 DOI: 10.4172/2161-1068.1000E131
P. Chavda, K. Mehta
The global adult tobacco survey conducted in India suggests that 35% of adults use some or the other form of tobacco out of which 9% use it in smoking form [1]. While the youth tobacco survey among adolescents in 13-15 years of age also showed tobacco usage at a high rate of around 15% with around 4% using it in smoking form [2]. This suggests that the habit of tobacco usage is picked up early in life right from the school age. The tuberculosis tobacco nexus suggests that we can expect higher rate of tobacco usage among tuberculosis patients. A study from southern India shows that 94% tuberculosis patients were ever smokers and 71% current smokers at the time of study [3].
在印度进行的全球成人烟草调查表明,35%的成年人使用某种或其他形式的烟草,其中9%以吸烟形式使用烟草。而对13-15岁青少年进行的青少年烟草调查也显示,烟草使用率高达15%左右,其中约4%以吸烟形式使用。这表明,吸烟的习惯是在生命早期从上学年龄开始养成的。结核病与烟草的关系表明,我们可以预期结核病患者的烟草使用率会更高。印度南部的一项研究表明,在研究开始时,94%的结核病患者曾经吸烟,71%目前吸烟。
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引用次数: 1
Minimally Invasive Ultrasound-guided Synovial Biopsy Using SuperCoreBiopsy Instrument 超声引导下使用SuperCoreBiopsy仪器进行滑膜微创活检
Pub Date : 2016-05-14 DOI: 10.4172/2161-1068.1000207
K. Lai, Hsin-Hua Chen, M. Wen, Yi-Ming Chen, J. Lan, Der-Yuan Chen
Background: To develop a new method for synovial biopsy with ultrasound (US) guidance and a semi-automatic SuperCore biopsy instrument. Materials and Methods: Twenty-two patients (8 men and 14 women, median age 57 years (range 22–79 years)) with active arthritis or tenosynovitis were enrolled from April 2012 through October 2012. Each patient had one joint or tendon biopsied. US examination was performed to determine the optimal synovial site for biopsy. After skin disinfection and local anaesthesia, a portal was established using a trephine needle as needed. An 18-gauge SuperCore biopsy needle was placed into the target synovial site via the portal or just percutaneously under US guidance with free hand technique. Repeated needle passes and cuts to obtain 3-10 pieces of synovial tissues in each joint. The success of biopsy was defined as identification of synovium on histological examination. Results: Synovium of 21 joints (10 knees, 6 wrists, 3 ankles, 1 elbow and 1 metacarpophalangeal joint) were biopsied. One patient had biopsy of flexor digitorum tendon sheath. All biopsies obtained adequate amounts of synovial tissues for histologic reading with a success rate of 100%. Synovial lining was identified in 18 (85.7%) of 21 joints. The patient with flexor digitorum tenosynovitis was proven to have mycobacterial infectionby histological examination. All patients tolerated the procedures well, and no complication was observed during 2-week follow up. Conclusions: US-guided synovial biopsy using SuperCore biopsy instrument is a promising method for synovial research. It has the advantages of simple, mini-invasiveness and high success rate. The complication is rare.
背景:研究一种超声引导下滑膜活检的新方法和半自动SuperCore活检仪。材料和方法:2012年4月至2012年10月,22例活动性关节炎或腱鞘炎患者(男8例,女14例,中位年龄57岁(22-79岁))入组。每位患者进行了一个关节或肌腱活检。进行US检查以确定最佳滑膜活检部位。皮肤消毒和局部麻醉后,根据需要使用环钻针建立门静脉。一根18号的SuperCore活检针经门静脉或在徒手技术指导下经皮穿刺入目标滑膜部位。在每个关节处反复穿刺和切割获得3-10块滑膜组织。活检的成功定义为在组织学检查中识别滑膜。结果:对21个关节(膝关节10个、手腕6个、踝关节3个、肘关节1个、掌指关节1个)进行了滑膜活检。1例患者行指屈肌腱鞘活检。所有活组织检查均获得足够数量的滑膜组织用于组织学读数,成功率为100%。21个关节中有18个(85.7%)发现滑膜内衬。本例患者为指屈肌腱滑膜炎,经组织学检查证实为分枝杆菌感染。所有患者耐受良好,随访2周无并发症发生。结论:超声引导下使用SuperCore活检仪进行滑膜活检是一种很有前途的滑膜研究方法。具有操作简单、微创、成功率高等优点。并发症是罕见的。
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引用次数: 2
Rv3802c in Tuberculosis Therapeutics Rv3802c在结核病治疗中的应用
Pub Date : 2016-04-25 DOI: 10.4172/2161-1068.1000204
P. Saravanan, S. Patra
The recent upsurge of life-threatening multidrug- and extreme drug- resistant tuberculosis along with HIV co-infection urge the need of new drug targets and drugs to cripple the survival and infection of Mycobacterium tuberculosis. The current scenario of tuberculosis might be dealt by targeting pathogen’s enzymes that participate in both cell wall and lipid metabolism.
最近危及生命的耐多药和极端耐药结核病以及艾滋病毒合并感染激增,迫切需要新的药物靶点和药物来削弱结核分枝杆菌的生存和感染。目前结核病的情况可能是通过靶向参与细胞壁和脂质代谢的病原体酶来处理的。
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引用次数: 3
Fulminant Pulmonary Tuberculosis by Infliximab in Patient withRheumatoid Arthritis 英夫利昔单抗治疗类风湿关节炎患者的暴发性肺结核
Pub Date : 2016-04-23 DOI: 10.4172/2161-1068.1000206
M. Hama, Y. Yamazaki, M. Kosaka, A. Ushiki, N. Goto, M. Sugawara, M. Hanaoka
A 72-year-old Japanese woman who had been suffering from rheumatoid arthritis for five years started treatment with infliximab. The screening of a chest X-ray before initiating infliximab treatment showed no abnormal shadows. After a month of infliximab, she was admitted to the emergency hospital with a half-month history of a fever, fatigue, dyspnea, and cough. She was diagnosed with tuberculosis from a culture smear and referred to our hospital. The chest images showed a bilateral massive cavity and infiltration. Despite the administration of an anti-tuberculous agent, the cavity and infiltration were enlarged on a chest X-ray and the patient died due to respiratory failure. Cases of tuberculosis resulting in death after a short duration of infliximab treatment have been rarely reported. We speculate that chest CT and the interferon-gamma release assay (IGRA) for tuberculosis screening should be evaluated before starting infliximab treatment, and preventive administration of isoniazid should be considered with consultation with a pulmonologist.
一名患有类风湿关节炎5年的72岁日本妇女开始用英夫利昔单抗治疗。开始英夫利昔单抗治疗前的胸部x线筛查未显示异常阴影。在英夫利昔单抗治疗一个月后,患者因发烧、疲劳、呼吸困难和咳嗽半个月的病史被送进了急诊医院。她通过培养涂片诊断为肺结核,并转介到我们医院。胸部图像显示双侧肿块腔及浸润。尽管使用了抗结核药物,但胸部x线片显示空洞和浸润扩大,患者死于呼吸衰竭。在短期英夫利昔单抗治疗后导致死亡的肺结核病例很少有报道。我们推测,在开始英夫利昔单抗治疗前,应评估胸部CT和用于结核病筛查的干扰素- γ释放试验(IGRA),并在咨询肺科医生的情况下考虑预防性使用异烟肼。
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引用次数: 3
The Yield of First Spot Double Slide Smears for the Diagnosis ofPulmonary Tuberculosis 首点双片涂片诊断肺结核的产率
Pub Date : 2016-04-22 DOI: 10.4172/2161-1068.1000205
B. Ayele
Background: Direct sputum smear microscopy is the cornerstone for the diagnosis of pulmonary tuberculosis (PTB) in resource-poor countries. However, the requirement for repeated visits to submit specimens and receive results is associated with considerable diagnostic delay, work load, patients drop-out and high expenses for patients. Although the World Health Organization (WHO) has recently changed its policy from spot morning spot (SMS) to spot morning (SM), the SM method still involves two days visits for a patient. The aim of this study was to evaluate the yield of first spot double slides smears for the diagnosis of PTB in high TB setting. Methods: A total of 362 patients who visited the out-patient department (OPD) of Dilla referral hospital and who were suspected of PTB were involved in the study. In addition SMS sputum samples were collected; double slides smears were prepared, stained by the Ziehl-Neelsen (ZN) method and 100 fields were examined under oil immersion objective for acid fast bacilli (AFB). Results: Of 362, 54 (14.92%) were smear-positives. Out of the 54 smear positive patients, 53 (98.15%) were positives by the first spot specimen. Additionally, 1 of 54 (1.85%) were positives by the morning specimen. Using the 2-day protocol (SMS) among 362 patients, 54 (14.92%) were smear positives by double slides and 53 (14.64%) by single slide smears. Whereas using the 1-day protocol (first spot); among 362 patients, 53 (14.64%) were smear positives both in double slides and single slide smears. Conclusion: The double slides smears from the first spot sputum samples appeared to be as effective as SMS strategy for the diagnosis of PTB though additional studies are required under various settings.
背景:在资源贫乏国家,直接痰涂片镜检是诊断肺结核(PTB)的基础。然而,需要反复访问以提交标本和接收结果,这与相当大的诊断延误、工作量、患者退出和患者的高费用有关。虽然世界卫生组织(WHO)最近将其政策从“现场上午检查(SMS)”改为“现场上午检查(SM)”,但SM方法仍然需要对患者进行两天的检查。本研究的目的是评估首次点双载玻片涂片在高结核环境中诊断PTB的产量。方法:选取在Dilla转诊医院门诊就诊的疑似肺结核患者362例进行研究。同时采集SMS痰液样本;制备双载片,Ziehl-Neelsen (ZN)法染色,油浸物镜下检测100个领域的抗酸杆菌(AFB)。结果:362例中涂片阳性54例(14.92%)。54例涂片阳性患者中,53例(98.15%)首次斑点标本阳性。54例中1例(1.85%)晨检阳性。采用2天方案(SMS)的362例患者中,54例(14.92%)双载片涂片呈阳性,53例(14.64%)单载片涂片呈阳性。鉴于使用1天协议(第一个点);362例患者中,53例(14.64%)双载片和单载片涂片均为阳性。结论:首次点痰样本的双载玻片涂片在诊断PTB方面似乎与SMS策略一样有效,尽管需要在各种情况下进行额外的研究。
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引用次数: 1
Thiopeptide Antibiotics act on both Host and Microbe to Deliver Double Punch on Mycobacterial Infection 硫肽类抗生素同时作用于宿主和微生物,对分枝杆菌感染产生双重作用
Pub Date : 2016-03-25 DOI: 10.4172/2161-1068.1000203
Qingfei Zheng, Wen Liu
Mycobacterial infection has long been one of the most serious infectious diseases throughout the world. Since the abuse of antibiotics, and for other reasons, the emergence of bacterial drug-resistance is now one of the most urgent clinical problems. Nowadays, the speed of antibiotic development is actually far more slowly than that of the bacterial drug-resistance generation. Thereby, searching for new efficient antibiotics is a top priority in pharmaceutical studies. In this commentary, we summarized the recent advances regarding the development of new thiopeptide antibiotics via biosynthetic strategy and the discovery of a novel dual mechanism of action against Mycobacterium marinum-represented intracellular pathogens.
分枝杆菌感染一直是世界范围内最严重的传染病之一。由于抗生素的滥用,以及其他原因,细菌耐药性的出现是目前最紧迫的临床问题之一。如今,抗生素的发展速度实际上远远慢于细菌耐药性的产生。因此,寻找新的高效抗生素是药物研究的首要任务。在这篇评论中,我们总结了通过生物合成策略开发新的硫肽抗生素的最新进展,以及对海洋分枝杆菌代表的细胞内病原体的新的双重作用机制的发现。
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引用次数: 4
Computational Approach in Understanding Mechanism of Action of Isoniazidand Drug Resistance 理解异烟肼和耐药作用机制的计算方法
Pub Date : 2016-03-22 DOI: 10.4172/2161-1068.1000202
Lingaraja Jena, G. Wankhade, Pranita J Waghmare, B. Harinath
Most Multi Drug Resistance and Extremely Drug Resistance clinical strains of Mycobacterium tuberculosis are found to be resistant to the anti-tuberculousis drugs such as Isoniazid and Rifampicin. The mechanism of action and drug resistance due to Isoniazid has been the subject of extensive study. According to Tuberculosis drug resistance mutation database, 22 genes/proteins are associated with Isoniazid resistance such as katG, nat, inhA, ahpc, ndh, kasA etc. Mutation in the gene seems to affect the formation of Isoniazid to its active form or enhancing the catabolism thus making it ineffective. Studies in different laboratories have shown usefulness of computational approach in elucidating the mechanism of action of Isoniazid and development of drug resistance. Computational studies in our laboratory showed that a mutation in KatG (S315T/S315N) prevents free radical formation, thus the development of resistance to the drug. Further, we observed through molecular dynamics simulation approach that mutation (G67R/G207E) in NAT enzyme increases the stability and catalytic ability of the mutant enzyme, thus making the drug ineffective.
大多数耐多药和极耐药结核分枝杆菌临床菌株对异烟肼和利福平等抗结核药物具有耐药性。异烟肼的作用机制和耐药性一直是人们广泛研究的课题。根据结核病耐药突变数据库,与异烟肼耐药相关的基因/蛋白有katG、nat、inhA、ahpc、ndh、kasA等22个。该基因的突变似乎影响异烟肼形成其活性形式或增强分解代谢,从而使其无效。不同实验室的研究表明,计算方法在阐明异烟肼的作用机制和耐药性的发展方面是有用的。我们实验室的计算研究表明,KatG (S315T/S315N)的突变可以阻止自由基的形成,从而产生对药物的耐药性。此外,我们通过分子动力学模拟方法观察到,NAT酶的突变(G67R/G207E)增加了突变酶的稳定性和催化能力,从而使药物失效。
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引用次数: 5
Detection of Mycobacterium Gilvum First Time from the Bathing Water of Leprosy Patient from Purulia, West Bengal 西孟加拉邦普鲁里亚麻风病人洗浴水中首次检出Gilvum分枝杆菌
Pub Date : 2016-03-21 DOI: 10.4172/2161-1068.1000201
M. Lavania, R. Turankar, I. Singh, A. Nigam, U. Sengupta
Introduction: Mycobacterium gilvum is a fast grower with smooth growth having pale yellow colour. This strain was first isolated from the sediment of the Grand Calumet River in North-western Indiana based on its ability to utilize pyrene, a toxic polycyclic hydrocarbon, as a growth substrate. Methods: The identification and characterization of this isolate was done by various conventional and molecular tests including 16S rDNA sequencing. Sequencing of the nearly complete 16S rRNA gene revealed a unique organism M.glivum, distantly related to M.vaccae group. Blast results showed similarity of these sequences with M.gilvum. Conclusion: Results might shed further light and its association with amoeba in the leprosy endemic area of this rare Mycobacterium species.
简介:gilvum分枝杆菌生长迅速,生长光滑,呈淡黄色。这种菌株最初是从印第安纳州西北部大卡卢梅特河的沉积物中分离出来的,基于它利用芘(一种有毒的多环烃)作为生长基质的能力。方法:采用16S rDNA测序等多种常规和分子检测方法对该分离物进行鉴定和鉴定。几乎完整的16S rRNA基因测序揭示了一种独特的生物M.glivum,与m .母牛群有远亲关系。Blast结果表明,这些序列与M.gilvum具有相似性。结论:该结果可进一步阐明该罕见分枝杆菌在麻风病流行区与变形虫的关系。
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引用次数: 4
期刊
Mycobacterial diseases : tuberculosis & leprosy
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