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https://www.readbyqxmd.com/read/28646656/azide-alkyne-cycloaddition-towards-1h-1-2-3-triazole-tethered-gatifloxacin-and-isatin-conjugates-design-synthesis-and-in%C3%A2-vitro-anti-mycobacterial-evaluation
#1
Zhi Xu, Xu-Feng Song, Yuan-Qiang Hu, Min Qiang, Zao-Sheng Lv
Twelve novel 1H-1,2,3-triazole-tethered gatifloxacin (GTFX) isatin conjugates 5a-l with greater lipophilicity compared with GTFX were designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37Rv and MDR-TB as well as cytotoxicity. The preliminary results showed that all the targets (MIC: 0.10-8 μg/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but eight of them (CC50: 7.8-62.5 μg/mL) were much more toxic than the parent GTFX (CC50: 125 μg/mL)...
June 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28646367/ifn%C3%AE-producing-cd4-t-lymphocytes-the-double-edged-swords-in-tuberculosis
#2
Pawan Kumar
IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28642632/mcl-plays-an-anti-inflammatory-role-in-mycobacterium-tuberculosis-induced-immune-response-by-inhibiting-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#3
Qingwen Zhang, Xinru Jiang, Weigang He, Kailin Wei, Jinxia Sun, Xiangyang Qin, Yuejuan Zheng, Xin Jiang
Mycobacterium tuberculosis (Mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB). Micheliolide (MCL), a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28642013/identifying-mechanisms-driving-formation-of-granuloma-associated-fibrosis-during-mycobacterium-tuberculosis-infection
#4
Hayley C Warsinske, Robert M DiFazio, Jennifer J Linderman, JoAnne L Flynn, Denise E Kirschner
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a pulmonary pathogen of major global concern. A key feature of Mtb infection in primates is the formation of granulomas, dense cellular structures surrounding infected lung tissue. These structures serve as the main site of host-pathogen interaction in TB, and thus to effectively treat TB we must clarify mechanisms of granuloma formation and their function in disease. Fibrotic granulomas are associated with both good and bad disease outcomes...
June 19, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28636540/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#5
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633698/feasibility-of-a-streamlined-tuberculosis-diagnosis-and-treatment-initiation-strategy
#6
P B Shete, T Nalugwa, K Farr, C Ojok, M Nantale, P Howlett, P Haguma, E Ochom, F Mugabe, M Joloba, L H Chaisson, D W Dowdy, D Moore, J L Davis, A Katamba, A Cattamanchi
OBJECTIVE: To assess the feasibility of a streamlined strategy for improving tuberculosis (TB) diagnostic evaluation and treatment initiation among patients with presumed TB. DESIGN: Single-arm interventional pilot study at five primary care health centers of a streamlined, SIngle-saMPLE (SIMPLE) TB diagnostic evaluation strategy: 1) examination of two smear results from a single spot sputum specimen using light-emitting diode fluorescence microscopy, and 2) daily transportation of smear-negative sputum samples to Xpert® MTB/RIF testing sites...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633546/identification-of-specific-antibodies-against-the-ag85c-mpt51-hspx-fusion-protein-cmx-for-serological-screening-of-tuberculosis-in-endemic-area
#7
Adrielle Zagmignan, Adeliane Castro da Costa, José Lima Viana, Lídio Gonçalves Lima Neto, Cristina de Andrade Monteiro, Ariosvaldo Guimarães Gaioso Neto, Ana Paula Junqueira Kipnis, Eduardo M de Sousa
OBJECTIVES: Development of new tools for rapid and accurate diagnosis of tuberculosis (TB) is considered a strategy for controlling the disease. The recombinant CMX fusion protein is composed of immunodominant epitopes of the Ag85C (Rv0129c), MPT51 (Rv3803c) and the entire HspX (Rv2031c) proteins from Mycobacterium tuberculosis H37Rv (Mtb). The aim of this study was to evaluate the applicability of a test using the CMX protein in individuals suspected of TB. METHODS: Indirect ELISA was used to measure serum anti-CMX IgM and IgG in individuals with pulmonary TB...
June 21, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28630193/pyrazinamide-susceptibility-and-pnca-mutation-profile-of-mycobacterium-tuberculosis-among-multi-drug-resistant-tuberculosis-patients-in-bangladesh
#8
Arfatur Rahman, Sara Sabrina Ferdous, Shahriar Ahmed, S M Mazidur Rahman, Mohammad Khaja Mafij Uddin, Suporn Pholwat, Jean Gratz, Eric Houpt, Sayera Banu
Pyrazinamide (PZA) is a front line anti-tuberculosis (anti-TB) drug used in both first and second line treatment regimen. However, due to complex laboratory requirements, the PZA susceptibility test is rarely performed leading to the scarcity of data. Bangladesh is both a high TB and multi-drug resistant (MDR-TB) burden country but to our knowledge the published data on PZA susceptibility is limited, especially among MDR-TB patients. We aimed to analyze the PZA susceptibility pattern of Mycobacterium tuberculosis (MTB) isolates from MDR-TB patients and to correlate pncA mutation with PZA resistance in Bangladesh...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630063/listeria-vectored-vaccine-expressing-the-mycobacterium-tuberculosis-30-kda-major-secretory-protein-via-the-constitutively-active-prfa-regulon-boosts-bcg-efficacy-against-tuberculosis
#9
Qingmei Jia, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30)...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28629306/%C3%AE-ca-specific-inhibitor-dithiocarbamate-fc14-584b-a-novel-antimycobacterial-agent-with-potential-to-treat-drug-resistant-tuberculosis
#10
Ashok Aspatwar, Milka Hammarén, Sanni Koskinen, Bruno Luukinen, Harlan Barker, Fabrizio Carta, Claudiu T Supuran, Mataleena Parikka, Seppo Parkkila
Inhibition of novel biological pathways in Mycobacterium tuberculosis (Mtb) creates the potential for alternative approaches for treating drug-resistant tuberculosis. In vitro studies have shown that dithiocarbamate-derived β-carbonic anhydrase (β-CA) inhibitors Fc14-594 A and Fc14-584B effectively inhibit the activity of Mtb β-CA enzymes. We screened the dithiocarbamates for toxicity, and studied the in vivo inhibitory effect of the least toxic inhibitor on M. marinum in a zebrafish model. In our toxicity screening, Fc14-584B emerged as the least toxic and showed minimal toxicity in 5-day-old larvae at 300 µM concentration...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28628665/a-chromosome-5q31-1-locus-associates-with-tuberculin-skin-test-reactivity-in-hiv-positive-individuals-from-tuberculosis-hyper-endemic-regions-in-east-africa
#11
Rafal S Sobota, Catherine M Stein, Nuri Kodaman, Isaac Maro, Wendy Wieland-Alter, Robert P Igo, Albert Magohe, LaShaunda L Malone, Keith Chervenak, Noemi B Hall, Mecky Matee, Harriet Mayanja-Kizza, Moses Joloba, Jason H Moore, William K Scott, Timothy Lahey, W Henry Boom, C Fordham von Reyn, Scott M Williams, Giorgio Sirugo
One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28628437/nontuberculous-mycobacteria-infections-at-a-provincial-reference-hospital-cambodia
#12
Maryline Bonnet, Kim Chamroeun San, Yati Pho, Chandara Sok, Jean-Philippe Dousset, William Brant, Northan Hurtado, Khun Kim Eam, Elisa Ardizzoni, Seiha Heng, Sylvain Godreuil, Wing-Wai Yew, Cathy Hewison
Prevalence of nontuberculous mycobacteria (NTM) disease is poorly documented in countries with high prevalence of tuberculosis (TB). We describe prevalence, risk factors, and TB program implications for NTM isolates and disease in Cambodia. A prospective cohort of 1,183 patients with presumptive TB underwent epidemiologic, clinical, radiologic, and microbiologic evaluation, including >12-months of follow-up for patients with NTM isolates. Prevalence of NTM isolates was 10.8% and of disease was 0.9%; 217 (18...
July 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28627432/high-diversity-of-multidrug-resistant-mycobacterium-tuberculosis-central-asian-strain-isolates-in-nepal
#13
Yogendra Shah, Bhagwan Maharjan, Jeewan Thapa, Ajay Poudel, Hassan Mahmoud Diab, Basu Dev Pandey, Eddie Solo, Norikazu Isoda, Yasuhiko Suzuki, Chie Nakajima
OBJECTIVES: Tuberculosis caused by Mycobacterium tuberculosis (MTB) poses a major public health problem in Nepal. Although it has been reported as one of the dominant genotypes of MTB in Nepal, little information on the Central Asian Strain (CAS) family is available, especially isolates related to multidrug resistance (MDR) cases. Here, we aimed to elucidate the genetic and epidemiological characteristics of MDR CAS isolates in Nepal. METHODS: A total of 145 MDR CAS isolates collected in Nepal from 2008 to 2013 were characterized by spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis and drug resistance-associating gene sequencing...
June 13, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28627431/evaluation-of-the-quantamatrix-multiplexed-assay-platform-system-for-simultaneous-detection-of-mycobacteirum-tuberculosis-and-rifampicin-resistance-gene-using-culture-positive-mycobacteria
#14
Hye-Young Wang, Young Uh, Seoyong Kim, Tae-Sun Shim, Hyeyoung Lee
BACKGROUND: The differentiation of Mycobacterium tuberculosis complex (MTBC) from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of anti-tuberculosis drugs. Prevailing data on rifampicin (RIF)-resistant TB is essential for early management of multidrug resistant-TB. The aim of this study was to evaluate the usefulness of a newly developed multiplexed, bead-based bioassay (Quantamatrix Multiplexed Assay Platform; QMAP) for the rapid differentiation of 23 Mycobacterium species including MTBC and RIF-resistant strains...
June 13, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28625141/bedaquiline-a-new-hope-for-shorter-and-better-anti-tuberculosis-regimens
#15
Niccolò Riccardi, Filippo Del Puente, Federica Magnè, Lucia Taramasso, Antonio Di Biagio
In 2014, an estimated 1.8 million people died from Mycobacterium tuberculosis (MTB); moreover, 680,000 people developed multidrug-resistant TB (MDR-TB). Currently available anti-MDR and XDR regimens are long-lasting and expensive, need high adherence and are undermined by a high frequency of adverse drug events, thus leading to a low success rate; moreover, in the last 50 years only two new molecules, bedaquiline (BDQ) and delamanid, have been approved and released for treatment of MDR-TB. BDQ is a diarylquinoline anti-mycobacterial drug, active regardless the state of MTB; in fact, its efficacy is conserved against replicating and non-replicating bacilli, despite extracellular or intracellular location...
June 19, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/28623303/xtractb-assay-a-mycobacterium-tuberculosis-molecular-screening-test-with-sensitivity-approaching-culture
#16
Jennifer L Reed, Debby Basu, Matthew A Butzler, Sally M McFall
Nucleic acid amplification tests are increasingly used to diagnose tuberculosis (TB) due to their speed and sensitivity compared to sputum smear microscopy. However, these tests fail to equal culture's sensitivity with sputum smear microscopy negative specimens and therefore cannot be used to rule out TB disease. For molecular tests to match culture's sensitivity, they must detect ≤10 genomic copies of Mycobacterium tuberculosis (MTB) DNA, the limit of detection of culture, process ≥1 ml of sputum ensuring sufficient number of MTB are in the reaction, and efficiently remove sputum associated inhibitors from this large sample...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622763/treatment-decisions-and-mortality-in-hiv-positive-presumptive-smear-negative-tb-in-the-xpert%C3%A2-mtb-rif-era-a-cohort-study
#17
Sabine M Hermans, Juliet A Babirye, Olive Mbabazi, Francis Kakooza, Robert Colebunders, Barbara Castelnuovo, Christine Sekaggya-Wiltshire, Rosalind Parkes-Ratanshi, Yukari C Manabe
BACKGROUND: The Xpert™ MTB/RIF (XP) has a higher sensitivity than sputum smear microscopy (70% versus 35%) for TB diagnosis and has been endorsed by the WHO for TB high burden countries to increase case finding among HIV co-infected presumptive TB patients. Its impact on the diagnosis of smear-negative TB in a routine care setting is unclear. We determined the change in diagnosis, treatment and mortality of smear-negative presumptive TB with routine use of Xpert MTB/RIF (XP). METHODS: Prospective cohort study of HIV-positive smear-negative presumptive TB patients during a 12-month period after XP implementation in a well-staffed and trained integrated TB/HIV clinic in Kampala, Uganda...
June 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28620844/comparison-of-the-characteristics-of-mycobacterium-tuberculosis-isolates-from-sputum-and-lung-lesions-in-chronic-tuberculosis-patients
#18
M-S Hong, Y Kim, E-J Cho, J-S Lee, H-K Kwak, J-H Kim, C-T Kim, J-S Cho, S-K Park, D Jeon, Y-I Choi, H Lee, S-Y Eum
Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB...
June 15, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28619539/systemic-immunological-changes-in-patients-with-distinct-clinical-outcomes-during-mycobacterium-tuberculosis-infection
#19
Tatiane Figueiredo Morais-Papini, Jordana Grazziela Alves Coelho-Dos-Reis, Ana Paula Barbosa Wendling, Lis Ribeiro do Vale Antonelli, Pryscilla Fanini Wowk, Vânia Luiza Deperon Bonato, Valéria Maria Augusto, Silvana Elói-Santos, Olindo Assis Martins-Filho, Cláudia Martins Carneiro, Andréa Teixeira-Carvalho
BACKGROUND: The lung lesions in an individual infected with tuberculosis (TB) are surprisingly variable and independent of each other. However, there is no circulating biomarker yet able to segregate patients according to the extent of lung lesions. MATERIALS AND METHODS: In this study, the phenotypic and functional profile of leukocytes of patients with active pulmonary tuberculosis (TB) and controls (CO) were fully scrutinized by immunophenotyping assays and in vitro short-term whole blood culture...
May 26, 2017: Immunobiology
https://www.readbyqxmd.com/read/28619229/cost-effectiveness-of-xpert-mtb-rif-for-tuberculosis-diagnosis-in-south-africa-a-real-world-cost-analysis-and-economic-evaluation
#20
Anna Vassall, Mariana Siapka, Nicola Foster, Lucy Cunnama, Lebogang Ramma, Katherine Fielding, Kerrigan McCarthy, Gavin Churchyard, Alison Grant, Edina Sinanovic
BACKGROUND: In 2010 a new diagnostic test for tuberculosis, Xpert MTB/RIF, received a conditional programmatic recommendation from WHO. Several model-based economic evaluations predicted that Xpert would be cost-effective across sub-Saharan Africa. We investigated the cost-effectiveness of Xpert in the real world during national roll-out in South Africa. METHODS: For this real-world cost analysis and economic evaluation, we applied extensive primary cost and patient event data from the XTEND study, a pragmatic trial examining Xpert introduction for people investigated for tuberculosis in 40 primary health facilities (20 clusters) in South Africa enrolled between June 8, and Nov 16, 2012, to estimate the costs and cost per disability-adjusted life-year averted of introducing Xpert as the initial diagnostic test for tuberculosis, compared with sputum smear microscopy (the standard of care)...
July 2017: Lancet Global Health
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