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https://www.readbyqxmd.com/read/28222243/studies-on-the-binding-of-modest-modulators-of-the-human-enzyme-sirtuin-6-using-std-nmr
#1
Beatriz E Bolívar, John T Welch
Pyrazinamide (PZA), an essential constituent of short course tuberculosis chemotherapy, binds weakly but selectively to Sirtuin 6 (SIRT6). Despite structural similarities between nicotinamide (NAM), PZA, and pyrazinoic acid (POA), these inhibitors modulate SIRT6 via different mechanisms and binding sites, as suggested by Saturation Transfer Difference (STD) Nuclear Magnetic Resonance (NMR). Available experimental evidence, such as that derived from crystal structures and kinetic experiments, is of only limited utility in the elucidation of the mechanistic details of sirtuin inhibition by NAM or other inhibitors...
February 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28221125/comparison-of-sputum-culture-conversion-for-mycobacterium-bovis-and-m-tuberculosis
#2
Colleen Scott, Joseph S Cavanaugh, Benjamin J Silk, Julia Ershova, Gerald H Mazurek, Philip A LoBue, Patrick K Moonan
Current US guidelines recommend longer treatment for tuberculosis (TB) caused by pyrazinamide-resistant organisms (e.g., Mycobacterium bovis) than for M. tuberculosis TB. We compared treatment response times for patients with M. bovis TB and M. tuberculosis TB reported in the United States during 2006-2013. We included culture-positive, pulmonary TB patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. Time to sputum-culture conversion was defined as time between treatment start date and date of first consistently culture-negative sputum...
March 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28221108/pnca-gene-mutations-associated-with-pyrazinamide-resistance-in-drug-resistant-tuberculosis-south-africa-and-georgia
#3
Salim Allana, Elena Shashkina, Barun Mathema, Nino Bablishvili, Nestani Tukvadze, N Sarita Shah, Russell R Kempker, Henry M Blumberg, Pravi Moodley, Koleka Mlisana, James C M Brust, Neel R Gandhi
Although pyrazinamide is commonly used for tuberculosis treatment, drug-susceptibility testing is not routinely available. We found polymorphisms in the pncA gene for 70% of multidrug-resistant and 96% of extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa and Georgia. Assessment of pyrazinamide susceptibility may be prudent before using it in regimens for drug-resistant tuberculosis.
March 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28214629/effects-of-metal-ion-replacement-on-pyrazinamidase-activity-a-quantum-mechanical-study
#4
Mahmoud Khadem-Maaref, Faramarz Mehrnejad, Arash Phirouznia
Pyrazinamidase (PZase), a metalloenzyme, is responsible for acidic modification of pyrazinamide (PZA), a drug used in tuberculosis treatment. The metal coordination site of the enzyme is able to coordinate various divalent metal cofactors. Previous experimental studies have demonstrated that metal ions, such as Co(2+), Mn(2+), and Zn(2+), are able to reactivate metal-depleted PZase, while others including Cu(2+), Fe(2+), and Mg(2+), cannot restore activity. In this study, we investigated binding of various metal ions to the metal coordination site (MCS) of the enzyme using quantum mechanical calculations...
February 2, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28207542/rifampicin-induced-disseminated-intravascular-coagulation-in-pulmonary-tuberculosis-treatment-a-case-report-and-literature-review
#5
Guo Chen, Jian-Qing He
RATIONALE: Disseminated intravascular coagulation (DIC) induced by daily rifampicin therapy is rare, especially the patient is absent of malignancy, severe infection, and prior exposure to rifampicin. PATIENT CONCERNS: We report a case of DIC induced by daily rifampicin treatment for pulmonary tuberculosis. A 22-year-old, previously healthy man received an anti-tuberculosis therapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide on the daily dose recommended by the World Health Organization tuberculosis guidelines after a diagnosis of pulmonary tuberculosis...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28196969/mutation-in-clpc1-encoding-an-atp-dependent-atpase-involved-in-protein-degradation-is-associated-with-pyrazinamide-resistance-in-mycobacterium-tuberculosis
#6
LETTER
Shuo Zhang, Jiazhen Chen, Wanliang Shi, Peng Cui, Jia Zhang, Sanghyun Cho, Wenhong Zhang, Ying Zhang
No abstract text is available yet for this article.
February 15, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28193504/strong-anti-epstein-barr-virus-ebv-or-cytomegalovirus-cmv-cellular-immune-responses-predict-survival-and-a-favourable-response-to-anti-tuberculosis-therapy
#7
REVIEW
Tumaini Nagu, Said Aboud, Martin Rao, Mecky Matee, Rebecca Axelsson, Davide Valentini, Ferdinand Mugusi, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Intact immune responses to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) represent a biologically and clinically relevant correlate of 'immunological fitness' in humans. However, there is a lack of knowledge concerning anti-EBV or anti-CMV responses in patients with pulmonary tuberculosis (TB), in whom aberrant immune responses may promote progression of clinical disease. METHODS: Venous blood samples were obtained at the time of (sputum smear positive) pulmonary TB diagnosis...
February 11, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28193240/substitution-of-ethambutol-with-linezolid-during-the-intensive-phase-of-treatment-of-pulmonary-tuberculosis-study-protocol-for-a-prospective-multicenter-randomized-open-label-phase-ii-trial
#8
Ji Yeon Lee, Deog Kyeom Kim, Jung-Kyu Lee, Ho Il Yoon, Ina Jeong, Eunyoung Heo, Young Sik Park, Jae Ho Lee, Sung Soo Park, Sang-Min Lee, Chang-Hoon Lee, Jinwoo Lee, Sun Mi Choi, Jong Sun Park, Joon-Sung Joh, Young-Jae Cho, Yeon Joo Lee, Se Joong Kim, Young Ran Hwang, Hyeonjeong Kim, Jongeun Ki, Hyungsook Choi, Jiyeon Han, Heejung Ahn, Seokyung Hahn, Jae-Joon Yim
BACKGROUND: Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis. METHODS/DESIGN: This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay...
February 13, 2017: Trials
https://www.readbyqxmd.com/read/28174307/a-bioengineered-three-dimensional-cell-culture-platform-integrated-with-microfluidics-to-address-antimicrobial-resistance-in-tuberculosis
#9
Magdalena K Bielecka, Liku B Tezera, Robert Zmijan, Francis Drobniewski, Xunli Zhang, Suwan Jayasinghe, Paul Elkington
: Antimicrobial resistance presents one of the most significant threats to human health, with the emergence of totally drug-resistant organisms. We have combined bioengineering, genetically modified bacteria, longitudinal readouts, and fluidics to develop a transformative platform to address the drug development bottleneck, utilizing Mycobacterium tuberculosis as the model organism. We generated microspheres incorporating virulent reporter bacilli, primary human cells, and an extracellular matrix by using bioelectrospray methodology...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28160272/suboptimal-exposure-to-anti-tb-drugs-in-a-tbm-hiv-population-is-not-related-to-anti-retroviral-therapy
#10
M E Török, G Aljayyoussi, D Waterhouse, Tth Chau, Nth Mai, N H Phu, T T Hien, W Hope, J J Farrar, S A Ward
A placebo-controlled trial that compares the outcomes of immediate versus deferred initiation of antiretroviral therapy in HIV+ve Tuberculous Meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of Rifampicin, Isoniazid, Pyrazinamide and Ethambutol were investigated in the presence and absence of anti-HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact upon the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low CSF and systemic exposures to rifampicin compared to previously reported HIV -ve cohorts...
February 4, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28157178/synthesis-of-novel-pyrazinamide-derivatives-based-on-3-chloropyrazine-2-carboxamide-and-their-antimicrobial-evaluation
#11
Ondrej Jandourek, Marek Tauchman, Pavla Paterova, Klara Konecna, Lucie Navratilova, Vladimir Kubicek, Ondrej Holas, Jan Zitko, Martin Dolezal
Aminodehalogenation of 3-chloropyrazine-2-carboxamide with variously substituted benzylamines yielded a series of fifteen 3-benzylaminopyrazine-2-carboxamides. Four compounds possessed in vitro whole cell activity against Mycobacterium tuberculosis H37Rv that was at least equivalent to that of the standard pyrazinamide. MIC values ranged from 6 to 42 μM. The best MIC (6 μM) was displayed by 3-[(4-methylbenzyl)amino]pyrazine-2-carboxamide (8) that also showed low cytotoxicity in the HepG2 cell line (IC50 ≥ 250 μM)...
February 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28152986/treatment-outcomes-of-fixed-dose-combination-versus-separate-tablet-regimens-in-pulmonary-tuberculosis-patients-with-or-without-diabetes-in-qatar
#12
Mohammad H Al-Shaer, Hanine Mansour, Hazem Elewa, Pascale Salameh, Fatima Iqbal
BACKGROUND: Tuberculosis is considered the second most common cause of death due to infectious agent. The currently preferred regimen for treatment of pulmonary tuberculosis (PTB) is isoniazid, rifampin, pyrazinamide, and ethambutol, which has been used either as separate tablets (ST) or as fixed-dose combination (FDC). To date, no studies have compared both regimens in Qatar. We aim to evaluate the safety and effectiveness of FDC and ST regimen for treating PTB, in addition to comparing safety and efficacy of FDC and ST regimens in patients with diabetes treated for TB...
February 2, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28151985/the-biodistribution-of-5-18f-fluoropyrazinamide-in-mycobacterium-tuberculosis-infected-mice-determined-by-positron-emission-tomography
#13
Zhuo Zhang, Alvaro A Ordonez, Peter Smith-Jones, Hui Wang, Kayla R Gogarty, Fereidoon Daryaee, Lauren E Bambarger, Yong S Chang, Sanjay K Jain, Peter J Tonge
5-[18F]F-pyrazinamide (5-[18F]F-PZA), a radiotracer analog of the first-line tuberculosis drug pyrazinamide (PZA), was employed to determine the biodistribution of PZA using PET imaging and ex vivo analysis. 5-[18F]F-PZA was synthesized in 60 min using a halide exchange reaction. The overall decay-corrected yield of the reaction was 25% and average specific activity was 2.6 × 106 kBq (70 mCi)/μmol. The biodistribution of 5-[18F]F-PZA was examined in a pulmonary Mycobacterium tuberculosis mouse model, where rapid distribution of the tracer to the lung, heart, liver, kidney, muscle, and brain was observed...
2017: PloS One
https://www.readbyqxmd.com/read/28111615/the-effects-of-first-line-anti-tuberculosis-drugs-on-the-actions-of-vitamin-d-in-human-macrophages
#14
Supavit Chesdachai, Susu M Zughaier, Li Hao, Russell R Kempker, Henry M Blumberg, Thomas R Ziegler, Vin Tangpricha
Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages...
December 2016: Journal of Clinical & Translational Endocrinology
https://www.readbyqxmd.com/read/28105975/simultaneous-determination-of-first-line-4-fdc-antituberculosis-drugs-by-uhplc-uv-and-hplc-uv-a-comparative-study
#15
Pedro H C Franco, Paula R Chellini, Marcone A L Oliveira, Gerson A Pianetti
Tuberculosis is the second most deadly infectiousdisease, surpassed only by HIV/AIDS, and hasresulted in over 1 billion deaths in the last200 years. The World Health Organization estimatesthat in 2014, 9.6 million people were infected bythis disease and 1.5 million had died. First-choicetreatment consists of fixed-dose combinationtablets containing rifampicin, isoniazid,pyrazinamide, and ethambutol hydrochloride(4-FDC). There are pharmacopeial protocolsavailable to test 4-FDC, but they are prolonged,two-step methods...
January 19, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28100438/high-dose-rifampicin-moxifloxacin-and-sq109-for-treating-tuberculosis-a-multi-arm-multi-stage-randomised-controlled-trial
#16
Martin J Boeree, Norbert Heinrich, Rob Aarnoutse, Andreas H Diacon, Rodney Dawson, Sunita Rehal, Gibson S Kibiki, Gavin Churchyard, Ian Sanne, Nyanda E Ntinginya, Lilian T Minja, Robert D Hunt, Salome Charalambous, Madeleine Hanekom, Hadija H Semvua, Stellah G Mpagama, Christina Manyama, Bariki Mtafya, Klaus Reither, Robert S Wallis, Amour Venter, Kim Narunsky, Anka Mekota, Sonja Henne, Angela Colbers, Georgette Plemper van Balen, Stephen H Gillespie, Patrick P J Phillips, Michael Hoelscher
BACKGROUND: Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. METHODS: We did a randomised controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15-20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15-20 mg/kg ethambutol)...
January 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28081036/one-year-mortality-of-hiv-positive-patients-treated-for-rifampicin-and-isoniazid-susceptible-tuberculosis-in-eastern-europe-western-europe-and-latin-america
#17
(no author information available yet)
OBJECTIVES: The high mortality among HIV/tuberculosis (TB) coinfected patients in Eastern Europe is partly explained by the high prevalence of drug-resistant TB. It remains unclear whether outcomes of HIV/TB patients with rifampicin/isoniazid-susceptible TB in Eastern Europe differ from those in Western Europe or Latin America. METHODS: One-year mortality of HIV-positive patients with rifampicin/isoniazid-susceptible TB in Eastern Europe, Western Europe, and Latin America was analysed and compared in a prospective observational cohort study...
January 28, 2017: AIDS
https://www.readbyqxmd.com/read/28063906/pyrazinamide-induced-hepatotoxicity-is-alleviated-by-4-pba-via-inhibition-of-the-perk-eif2%C3%AE-atf4-chop-pathway
#18
Hong-Li Guo, Hozeifa M Hassan, Ping-Ping Ding, Shao-Jie Wang, Xi Chen, Tao Wang, Li-Xin Sun, Lu-Yong Zhang, Zhen-Zhou Jiang
Pyrazinamide (PZA)-induced serious liver injury, but the exact mechanism of PZA-induces hepatotoxicity remains controversial. Endoplasmic reticulum (ER) stress-caused cell apoptosis plays a critical role in the development of drug-induced liver injury (DILI). However, the direct connection between PZA toxicity and ER stress is unknown. In this study, we describe the role of ER stress in PZA induced hepatotoxicity in vivo and in vitro. We found that PZA induces apoptosis in HepG2 cells, and causes liver damage in rats, characterized by increased serum ALT, AST and TBA levels...
January 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28060046/serious-adverse-reactions-from-anti-tuberculosis-drugs-among-599-children-hospitalized-for-tuberculosis
#19
Yiyuan Li, Yu Zhu, Qin Zhong, Xiaojun Zhang, Min Shu, Chaomin Wan
BACKGROUNDS: The purpose of the study was to summarize the clinical characteristics of serious adverse reactions (ARs) related to anti-tuberculosis (TB) drugs in children hospitalized for TB. A comprehensive understanding of these drug-related ARs may serve to improve patient prognosis. METHOD: Inpatients diagnosed with TB from 2008 to 2013 were enrolled retrospectively. The patients' demographics, diagnosis and ARs were recorded and analyzed for comprehensive evaluation...
January 3, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28043638/activity-of-drugs-against-dormant-mycobacterium-tuberculosis
#20
A Iacobino, G Piccaro, F Giannoni, A Mustazzolu, L Fattorini
OBJECTIVE/BACKGROUND: Heterogeneous mixtures of cellular and caseous granulomas coexist in the lungs of tuberculosis (TB) patients, with Mycobacterium tuberculosis (Mtb) existing from actively replicating (AR) to dormant, nonreplicating (NR) stages. Within cellular granulomas, the pH is estimated to be less than 6, whereas in the necrotic centres of hypoxic, cholesterol/triacylglycerol-rich, caseous granulomas, the pH varies between 7.2 and 7.4. To combat TB, we should kill both AR and NR stages of Mtb...
December 2016: International Journal of Mycobacteriology
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