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https://www.readbyqxmd.com/read/29137108/tuberculosis-presenting-as-isolated-bronchonodal-fistula-in-a-patient-with-systemic-lupus-erythematosus-case-report
#1
Kyungsoo Bae, Kyung Nyeo Jeon, Ho Cheol Kim, Young Sun Suh, Gi Dong Lee, Ju-Young Kim, Dae Hyun Song
RATIONALE: Lymph node is a preferred site for extrapulmonary tuberculosis (TB). In the thorax, mediastinal tuberculous lymph nodes can erode adjacent structures such as heart, aorta, and esophagus, forming fistula, and causing fatal consequences. However, tuberculous bronchonodal fistula as a complication of lymph node TB in adults is rarely known in terms of imaging or clinical findings. Here, a case of isolated tuberculous bronchonodal fistula appearing as the first presentation of TB in a 74-year-old male with systemic lupus erythematosus (SLE) is reported...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29136155/a-model-informed-preclinical-approach-for-prediction-of-clinical-pharmacodynamic-interactions-of-anti-tb-drug-combinations
#2
Oskar Clewe, Sebastian G Wicha, Corné P de Vogel, Jurriaan E M de Steenwinkel, Ulrika S H Simonsson
Background: Identification of pharmacodynamic interactions is not reasonable to carry out in a clinical setting for many reasons. The aim of this work was to develop a model-informed preclinical approach for prediction of clinical pharmacodynamic drug interactions in order to inform early anti-TB drug development. Methods: In vitro time-kill experiments were performed with Mycobacterium tuberculosis using rifampicin, isoniazid or ethambutol alone as well as in different combinations at clinically relevant concentrations...
November 9, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29133558/pharmacokinetics-and-drug-drug-interactions-of-lopinavir-ritonavir-administered-with-first-and-second-line-antituberculosis-drugs-in-hiv-infected-children-treated-for-multidrug-resistant-tuberculosis
#3
Louvina E van der Laan, Anthony J Garcia-Prats, H Simon Schaaf, Tjokosela Tikiso, Lubbe Wiesner, Mine de Kock, Jana Winckler, Jennifer Norman, Helen McIlleron, Paolo Denti, Anneke C Hesseling
Background Lopinavir/ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir/ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir/ritonavir and routine drugs used for MDR-TB treatment in HIV-infected children.Methods A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 on MDR-TB treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin: and 16 without TB), who were established on a lopinavir/ritonavir-containing antiretroviral regimen...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29131662/isoniazid-monoresistance-and-rate-of-culture-conversion-among-confirmed-tuberculosis-patients-in-the-state-of-georgia-2009-2014
#4
Argita D Salindri, Rose-Marie F Sales, Lauren DiMiceli, Marcos C Schechter, Russell R Kempker, Matthew J Magee
RATIONALE: Isoniazid-monoresistant tuberculosis (INH-monoresistant TB) is the most common drug-resistant TB type in the US; however, its impact on TB treatment outcomes is not clear. OBJECTIVES: This study aims to understand: 1) factors associated with INH-monoresistant TB and 2) the association between INH-monoresistance and response to TB treatment. METHODS: We studied all patients with TB aged ≥15 years reported to the Georgia State Electronic Notifiable Disease Surveillance System (SENDSS) from 2009-2014...
November 13, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29130630/a-structure-based-strategy-toward-the-development-of-novel-candidates-for-antimycobacterial-activity-synthesis-biological-evaluation-and-docking-study
#5
Linhu Li, Yuanyuan Jin, Bin Wang, Zhaoyong Yang, Mingliang Liu, Huiyuan Guo, Jun Zhang, Yu Lu
Bacterial resistance to most of the available antibiotics has stimulated the discovery of novel efficacious antibacterial agents. Bedaquiline is first of its type that has been specifically introduced for the management of MDR-TB in combination with other drugs. In the current study, a series of isoniazid/ethambutol/pyrazinamide -quinoline conjugates based on the structures of Bedaquiline were designed and synthesized. Biological activity tests revealed that some of isoniazid/ethambutol-quinoline conjugates have useful antibiotic activity against MTB H37Rv (MIC: 2...
November 11, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29124333/assessment-of-hepatotoxicity-of-first-line-anti-tuberculosis-drugs-on-wistar-rats
#6
Radhika Sharma, Ramneek Kaur, Manishi Mukesh, Vijay L Sharma
Adverse drug reactions are inevitable risk factors associated with use of modern medicines. First-line anti-tuberculosis drugs contribute to diverse pathological complications, and hepatotoxicity is one of them. This study investigated the effects of anti-TB drugs in combination (rifampicin [RIF] + isoniazid [INH] + pyrazinamide [PZA]) on Wistar rats. Rats were grouped as control group (saline), toxicant group that was given (30.85 mg/kg b.wt., INH + 61.7 mg/kg b.wt., RIF + 132.65 mg/kg b.wt. PZA in dosage extrapolated from dose that is used in human)...
November 9, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29123480/impairment-of-mitochondrial-biogenesis-and-dynamics-involved-in-isoniazid-induced-apoptosis-of-hepg2-cells-was-alleviated-by-p38-mapk-pathway
#7
Tianguang Zhang, Takashi Ikejima, Lizhong Li, Ruiqin Wu, Xiaoyan Yuan, Jun Zhao, Yimei Wang, Shuangqing Peng
Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for INH-induced hepatotoxicity. In this study, we showed that INH impaired mitochondrial biogenesis and dynamics in human hepatocarcinoma HepG2 cells. INH reduced mitochondrial membrane potential (MMP) and induced mitochondria swelling...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29120971/a-systematic-review-of-salivary-versus-blood-concentrations-of-anti-tuberculosis-drugs-and-their-potential-for-salivary-therapeutic-drug-monitoring
#8
Simone H J van den Elsen, Lisette M Oostenbrink, Scott K Heysell, Daiki Hira, Daan J Touw, Onno W Akkerman, Mathieu S Bolhuis, Jan-Willem C Alffenaar
BACKGROUND: Therapeutic drug monitoring is useful in the treatment of tuberculosis to assure adequate exposure, minimize antibiotic resistance, and reduce toxicity. Salivary therapeutic drug monitoring could reduce the risks, burden, and costs of blood-based therapeutic drug monitoring. This systematic review compared human pharmacokinetics of anti-tuberculosis drugs in saliva and blood to determine if salivary therapeutic drug monitoring could be a promising alternative. METHODS: On December 2, 2016, PubMed and the Institute for Scientific Information Web of Knowledge were searched for pharmacokinetic studies reporting human salivary and blood concentrations of anti-tuberculosis drugs...
November 8, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29119205/secretome-profile-analysis-of-multidrug-resistant-monodrug-resistant-and-drug-susceptible-mycobacterium-tuberculosis
#9
Chanyanuch Putim, Narumon Phaonakrop, Janthima Jaresitthikunchai, Ratikorn Gamngoen, Khajornsak Tragoolpua, Sorasak Intorasoot, Usanee Anukool, Chayada Sitthidet Tharincharoen, Ponrut Phunpae, Chatchai Tayapiwatana, Watchara Kasinrerk, Sittiruk Roytrakul, Bordin Butr-Indr
The emergence of drug-resistant tuberculosis has generated great concern in the control of tuberculosis and HIV/TB patients have established severe complications that are difficult to treat. Although, the gold standard of drug-susceptibility testing is highly accurate and efficient, it is time-consuming. Diagnostic biomarkers are, therefore, necessary in discriminating between infection from drug-resistant and drug-susceptible strains. One strategy that aids to effectively control tuberculosis is understanding the function of secreting proteins that mycobacteria use to manipulate the host cellular defenses...
November 8, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/29118425/the-study-on-the-association-between-beijing-genotype-family-and-drug-susceptibility-phenotypes-of-mycobacterium-tuberculosis-in-beijing
#10
Yi Liu, Xiaoying Jiang, Wensheng Li, Xuxia Zhang, Wei Wang, Chuanyou Li
The predominant prevalent Mycobacterium tuberculosis (M. tb) lineage was the Beijing genotype family in Beijing. There has been no systematic study on the association between drug resistance and Beijing genotype. Here we collected 268 M. tb strains, analyzed the background information and the bacteriological characteristics. The mean age of the cases was 40.12 years; male patients were almost three times than female patients. After genotyping analyzation, 81.7% (219/268) strains were categorized as Beijing genotype; no significant difference was observed between Beijing and non-Beijing genotype in gender, age and treatment history...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29118176/highly-sensitive-detection-of-isoniazid-heteroresistance-in-mycobacterium-tuberculosis-by-deepmelt-assay
#11
Bin Liang, Yaoju Tan, Zi Li, Xueshan Tian, Chen Du, Hui Li, Guoli Li, Xiangyang Yao, Zhongan Wang, Ye Xu, Qingge Li
Detection of heteroresistance of Mycobacterium tuberculosis (MTB) remains challenging using current genotypic drug susceptibility testing methods. Here, we described a melting curve analysis-based approach, termed DeepMelt, that can detect less abundant mutants through selective clamping of the wild-type in mixed populations. Singleplex DeepMelt assay detected 0.01% katG S315T in 10(5) MTB genomes/μL. Multiplex DeepMelt TB/INH detected 1% of mutant species in the four loci associated with isoniazid resistance in 10(4) MTB genomes/μL...
November 8, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29116933/first-line-antituberculosis-drugs-disrupt-endocrine-balance-and-induce-ovarian-and-uterine-oxidative-stress-in-rats
#12
Olayinka A Adebayo, Omolola A Adesanoye, Olalekan A Abolaji, Aderemi O Kehinde, Oluwatosin A Adaramoye
BACKGROUND: The first-line antituberculosis (anti-TB) drugs, isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA), are effective in the treatment of pulmonary tuberculosis. However, the toxicity of these drugs in the clinical setting limits their use. Here, we evaluated the effects of anti-TB drugs on the reproductive system in female rats. METHODS: Thirty-five female Wistar rats were assigned into five groups of seven animals each. The control group received normal saline, whereas others received INH (5 mg/kg), RIF (10 mg/kg), EMB (15 mg/kg), and PZA (15 mg/kg) through gavage thrice a week for 8 consecutive weeks...
November 8, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29115507/cytochrome-p450-1a1-and-1b1-promoter-cpg-island-methylation-regulates-rat-liver-injury-induced-by-isoniazid
#13
Yanhui Li, Yuhong Li, Guoying Zheng, Lingyan Zhu, Jishun Wang, Shasha Mu, Qi Ren, Fumin Feng
DNA methylation is an important component of epigenetics that is involved in the occurrence and development of a variety of diseases. The present study aimed to clarify the relationship between cytochrome P450 (CYP)1A1 and CYP1B1 promoter CpG island methylation and isoniazid‑induced liver injury in rats, and to explore the possible mechanism, rats were given an intragastric dose of isoniazid (55 mg·kg‑1·d‑1). High performance liquid chromatography was used to analyze the DNA methylation level of the whole genome in liver tissue...
October 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29114781/self-administered-versus-directly-observed-once-weekly-isoniazid-and-rifapentine-treatment-of-latent-tuberculosis-infection-a-randomized-trial
#14
Robert Belknap, David Holland, Pei-Jean Feng, Joan-Pau Millet, Joan A Caylà, Neil A Martinson, Alicia Wright, Michael P Chen, Ruth N Moro, Nigel A Scott, Bert Arevalo, José M Miró, Margarita E Villarino, Marc Weiner, Andrey S Borisov
Background: Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective: To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design: An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin...
November 7, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/29110871/prevalence-of-rifampicin-resistant-mycobacterium-tuberculosis-among-human-immunodeficiency-virus-seropositive-patients-and-their-treatment-outcomes
#15
C K Vidyaraj, A Chitra, S Smita, M Muthuraj, S Govindarajan, B Usharani, S Anbazhagi
Multidrug resistant (MDR) and extensively drug resistant tuberculosis (TB) are a threat to the TB control programs in developing countries, and the situation is worsened by the human immunodeficiency virus (HIV) pandemic. This study was performed to correlate treatment outcome with the resistance patterns in HIV-seropositive patients coinfected with pulmonary TB. Sputum specimens were collected from 1643 HIV-seropositive patients and subjected to microscopy and liquid culture for TB. The smear- and culture-positive Mycobacterium tuberculosis isolates were subjected to Genotype MTBDRplus assay version 2...
December 2017: Journal of Epidemiology and Global Health
https://www.readbyqxmd.com/read/29108416/chlorflavonin-targets-acetohydroxyacid-synthase-catalytic-subunit-ilvb1-for-synergistic-killing-of-mycobacterium-tuberculosis
#16
Nidja Rehberg, Herve Sergi Akone, Thomas R Ioerger, German Erlenkamp, Georgios Daletos, Holger Gohlke, Peter Proksch, Rainer Kalscheuer
The flavonoid natural compound chlorflavonin was isolated from the endophytic fungus Mucor irregularis, which was obtained from the Cameroonian medicinal plant Moringa stenopetala. Chlorflavonin exhibited strong growth inhibitory activity in vitro against Mycobacterium tuberculosis (MIC90 1.56 μM) while exhibiting no cytotoxicity towards the human cell lines MRC-5 and THP-1 up to concentrations of 100 µM. Mapping of resistance-mediating mutations employing whole-genome sequencing, chemical supplementation assays, molecular docking studies as well as enzymatic characterization revealed that chlorflavonin specifically inhibits the acetohydroxyacid synthase catalytic subunit IlvB1, causing combined auxotrophies to branched chain amino acids and to pantothenic acid...
November 6, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29098993/effect-of-efflux-pump-inhibitors-on-the-susceptibility-of-mycobacterium-tuberculosis-to-isoniazid
#17
Indu Jaiswal, Amita Jain, Sanjeev Kumar Verma, Pooja Singh, Surya Kant, Mastan Singh
BACKGROUND: Mycobacterium can develop drug resistance (DR) by mutation of its existing gene. However, the existence of DR without mutation shows the need to look for an alternative mechanism such as the role of efflux pumps. In this study, we examined the effect of efflux pump inhibitors on isoniazid (INH) susceptibility in clinical isolates of Mycobacterium tuberculosis (Mtb). MATERIALS AND METHODS: Resazurin microtiter assay was used to examine the effect of efflux pump inhibitors on minimum inhibitory concentration (MIC) levels of INH in eighteen Mtb clinical isolates...
November 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/29097168/synthesis-and-biological-evolution-of-hydrazones-derived-from-4-trifluoromethyl-benzohydrazide
#18
Martin Krátký, Szilvia Bősze, Zsuzsa Baranyai, Jiřina Stolaříková, Jarmila Vinšová
Reflecting the known biological activity of isoniazid-based hydrazones, seventeen hydrazones of 4-(trifluoromethyl)benzohydrazide as their bioisosters were synthesized from various benzaldehydes and aliphatic ketones. The compounds were screened for their in vitro activity against Mycobacterium tuberculosis, nontuberculous mycobacteria (M. avium, M. kansasii), bacterial and fungal strains. The most antimicrobial potent derivatives were also investigated for their cytostatic and cytotoxic properties against three cell lines...
October 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29092043/emerging-resistant-clones-of-mycobacterium-tuberculosis-in-a-spatiotemporal-context
#19
Anna Vyazovaya, Klavdia Levina, Viacheslav Zhuravlev, Piret Viiklepp, Marge Kütt, Igor Mokrousov
Objectives: We assessed the genetic structure of the Mycobacterium tuberculosis population in Estonia with a special focus on major epidemic/endemic clones and drug resistance determinants. We investigated the hypothesis of the decisive impact of massive human influx on the locally circulating genotypes. Estonia received a mass immigration from Russia during 1945-90 followed by enhanced interaction with the EU since 1991. Methods: The study sample included M. tuberculosis isolates from patients newly diagnosed with TB in 2014 in North Estonia (including the capital Tallinn)...
October 30, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29091448/insights-on-the-mechanism-of-action-of-inh-c10-as-an-antitubercular-prodrug
#20
Diogo Vila-Viçosa, Bruno L Victor, Jorge Ramos, Diana Machado, Miguel Viveiros, Jacek Switala, Peter C Loewen, Ruben Leitão, Filomena Martins, Miguel Machuqueiro
Tuberculosis remains one of the top causes of death worldwide, and combating its spread has been severely complicated by the emergence of drug-resistance mutations, highlighting the need for more effective drugs. Despite the resistance to isoniazid (INH) arising from mutations in the katG gene encoding the catalase-peroxidase KatG, most notably the S315T mutation, this compound is still one of the most powerful first-line antitubercular drugs, suggesting further pursuit of the development of tailored INH derivatives...
November 13, 2017: Molecular Pharmaceutics
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