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https://www.readbyqxmd.com/read/29148755/novel-anti-tubercular-6-dialkylaminopyrimidine-carboxamides-from-phenotypic-whole-cell-high-throughput-screening-of-a-softfocus-library-structure-activity-relationship-and-target-identification-studies
#1
Colin R Wilson, Richard K Gessner, Atica Moosa, Ronnett Seldon, Digby F Warner, Valerie Mizrahi, Candice Soares de Melo, Sandile B Simelane, Aloysius T Nchinda, Efrem Abay, Dale Taylor, Mathew Njoroge, Christel Brunschwig, Nina Lawrence, Helena I M Boshoff, Clifton E Barry, Frederick A Sirgel, Paul van Helden, C John Harris, Richard Gordon, Sonja Ghidelli-Disse, Hannah Pflaumer, Markus Boesche, Gerard Drewes, Olalla Sanz, Gracia Santos, Maria José Rebollo-Lopez, Beatriz Urones, Carolyn Selenski, Maria Jose Lafuente-Monasterio, Matthew Axtman, Joël Lelièvre, Lluis Ballell, Rudolf Mueller, Leslie J Street, Sandeep R Ghorpade, Kelly Chibale
A BioFocus DPI SoftFocus library of ~35,000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with anti-tubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc1 complex, disruption of cell-wall homeostasis, and DNA damage. Among the hits which passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization...
November 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29147748/graphene-quantum-dots-terbium-ions-as-novel-sensitive-and-selective-time-resolved-luminescent-probes
#2
Eulogio J Llorent-Martínez, Gema M Durán, Ángel Ríos, Antonio Ruiz-Medina
We propose an alternative approach for the development of analytical methods based on terbium-sensitized luminescence (TSL). TSL is based on the complexation between Tb(III) ions and fluorescent organic compounds that have appropriate functional groups to complex with Tb(III). We report the use of graphene quantum dot (GQDs) nanoparticles to improve the sensitivity and selectivity of TSL detection. GQDs can react with terbium ions through the carboxylic groups present in their structure. These Tb(III)-GQD complexes, formed in situ in aqueous solution, can be used as time-resolved luminescent probes...
November 16, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29146858/whole-genome-shotgun-sequences-of-three-multidrug-resistant-mycobacterium-tuberculosis-strains-isolated-from-morocco
#3
Lamiaa Lahlou, Nadia El Mrimar, Meriem Laamarti, Tarek Alouane, Mohammed A Bendahou, Fatna Bssaibis, Yassine Ben Lahlou, Adil Zegmout, N El Hafidi, Rachid ElJaoudi, Mohammed Frikh, Abdelhay Lemnouar, Mostafa Elouennass, Azeddine Ibrahimi
Tuberculosis is a contagious disease that usually attacks the lungs but sometimes attacks other parts of the body, such as the kidneys, glands, and bones. It is an endemic and major public health problem in Morocco. Tuberculosis is transmitted through the airways via the inhalation of microdroplets containing Mycobacterium tuberculosis We present here the whole-genome shotgun sequences of three multidrug-resistant M. tuberculosis strains isolated from Morocco.
November 16, 2017: Genome Announcements
https://www.readbyqxmd.com/read/29145924/pharmacokinetic-interaction-between-bedaquiline-and-clofazimine-in-patients-with-drug-resistant-tuberculosis
#4
G Maartens, M J E Brill, M Pandie, E M Svensson
<h2>BACKGROUND:</h2>Bedaquiline (BDQ) and clofazimine (CFZ) are both recommended for treating drug-resistant tuberculosis (DR-TB). As CFZ is an inhibitor of the cytochrome P450 isoenzyme 3A4 (CYP3A4) in vitro, and BDQ a substrate of CYP3A4, there is a potential for pharmacokinetic (PK) drug-drug interaction that may result in increased BDQ exposure when co-administered with CFZ, which could increase the toxicity of BDQ.<h2>METHODS:</h2>We assessed the effect of co-administered CFZ on BDQ bioavailability, or on clearance of BDQ and its N-monodesmethyl metabolite (M2), in patients with DR-TB using a population PK model developed from data of patients with DR-TB...
November 16, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29145844/development-and-evaluation-of-an-interferon-gamma-assay-for-the-diagnosis-of-tuberculosis-in-red-deer-experimentally-infected-with-mycobacterium-bovis
#5
María Ángeles Risalde, Jobin Thomas, Iker Sevilla, Miriam Serrano, Jose Antonio Ortíz, Joseba Garrido, Mercedes Domínguez, Lucas Domínguez, Christian Gortázar, Jose Francisco Ruíz-Fons
BACKGROUND: Red deer (Cervus elaphus) is regarded as an epidemiologically relevant host for Mycobacterium bovis (M. bovis) and closely related members of the Mycobacterium tuberculosis complex that cause animal tuberculosis (TB). The standard antemortem screening test for the detection of TB in deer is the intradermal tuberculin skin test, but the detection of interferon-gamma (IFNγ) produced by white blood cells exposed to M. bovis antigens can be used as an alternative or supplemental assay in most TB eradication/control programs...
November 16, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29145776/role-of-computed-tomography-of-abdomen-in-difficult-to-diagnose-typhoid-fever-a-case-series
#6
Wajid Hafeez, S Rajalakshmi, S Sripriya, M Madhu Bashini
Background and Aim Diagnosis of typhoid is challenging when blood cultures fail to isolate Salmonella species. We report our experience with interpreting computed tomography (CT) abdomen findings in a case series of typhoid fever. Methods The case series consisted of patients who had a CT abdomen done as part of their investigations and a final diagnosis of typhoid fever. The CT films were reviewed and findings evaluated for distinctive features. Results During 2011-2017, 11 patients met the inclusion criteria...
January 1, 2017: Tropical Doctor
https://www.readbyqxmd.com/read/29145483/sequential-inflammatory-processes-define-human-progression-from-m-tuberculosis-infection-to-tuberculosis-disease
#7
Thomas J Scriba, Adam Penn-Nicholson, Smitha Shankar, Tom Hraha, Ethan G Thompson, David Sterling, Elisa Nemes, Fatoumatta Darboe, Sara Suliman, Lynn M Amon, Hassan Mahomed, Mzwandile Erasmus, Wendy Whatney, John L Johnson, W Henry Boom, Mark Hatherill, Joe Valvo, Mary Ann De Groote, Urs A Ochsner, Alan Aderem, Willem A Hanekom, Daniel E Zak
Clincialtrials.gov, NCT01119521.
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29145454/reduction-of-hiv-associated-excess-mortality-by-antiretroviral-treatment-among-tuberculosis-patients-in-kenya
#8
Dickens O Onyango, Courtney M Yuen, Kevin P Cain, Faith Ngari, Enos O Masini, Martien W Borgdorff
BACKGROUND: Mortality from TB continues to be a global public health challenge. TB ranks alongside Human Immunodeficiency Virus (HIV) as the leading infectious causes of death globally. HIV is a major driver of TB related morbidity and mortality while TB is the leading cause of mortality among people living with HIV/AIDS. We sought to determine excess mortality associated with HIV and the effect of antiretroviral therapy on reducing mortality among tuberculosis patients in Kenya. METHODS: We conducted a retrospective analysis of Kenya national tuberculosis program data of patients enrolled from 2013 through 2014...
2017: PloS One
https://www.readbyqxmd.com/read/29145154/a-pipeline-for-proteome-scale-identification-and-studies-on-hormone-sensitive-lipases-in-mycobacterium-tuberculosis
#9
Durairaj Sherlin, Sharmila Anishetty
Hormone sensitive lipases (HSLs) play an important role in the survival of M. tuberculosis during dormancy. They help in the utilization of fatty acids from stored lipids. The objective of the current study was to identify all HSLs from the proteome of M. tuberculosis H37Rv. We have developed a novel HSL identification pipeline, based on amino acid sequence homology, presence of conserved motifs and other sequence features deciphered from known HSL dataset. Through this pipeline, we identified 10 proteins as putative HSLs in M...
November 7, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29144174/secondary-metabolites-from-triclisia-gilletii-de-wild-staner-menispermaceae-with-antimycobacterial-activity-against-mycobacterium-tuberculosis
#10
Eric Robert Tiam, Dominique Serge Ngono Bikobo, Auguste Abouem A Zintchem, Norbert Mbabi Nyemeck, Esther Del Florence Moni Ndedi, Patrick Hervé Betote Diboué, Maximilienne Ascension Nyegue, Alex de Théodore Atchadé, Dieudonné Emmanuel Pegnyemb, Christian G Bochet, Ulrich Koert
Triclisinone (2), a new ochnaflavone derivative, was isolated from the aerial parts of Triclisia gilletii, along with known drypemolundein B (1) and eight other known compounds. The chemical shifts of drypemolundein B (1) have been partially revised based on reinterpretation of NMR spectroscopic data. The eight other secondary metabolites are composed of: (+)-nonacosan-10-ol (3); stigmasterol (4), 3-O-β-D-glucopyranosylsitosterol (5), 3-O-β-D-glucopyranosylstigmasterol (6); oleanic acid (7); myricetin (8), quercetin (9) and 3-methoxyquercetin (10)...
November 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/29143466/tuberculosis-serosurveillance-and-management-practices-of-captive-african-elephants-loxodonta-africana-in-the-kavango-zambezi-transfrontier-conservation-area
#11
L E Rosen, T G Hanyire, J Dawson, C M Foggin, A L Michel, K P Huyvaert, M A Miller, F J Olea-Popelka
Transfrontier conservation areas represent an international effort to encourage conservation and sustainable development. Their success faces a number of challenges, including disease management in wildlife, livestock and humans. Tuberculosis (TB) affects humans and a multitude of non-human animal species and is of particular concern in sub-Saharan Africa. The Kavango-Zambezi Transfrontier Conservation Area encompasses five countries, including Zimbabwe, and is home to the largest contiguous population of free-ranging elephants in Africa...
November 16, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29143375/an-immunoinformatics-approach-to-define-t-cell-epitopes-from-polyketide-and-non-ribosomal-peptide-synthesis-proteins-of-mycobacterium-tuberculosis-as-potential-vaccine-candidates
#12
S Dhivya, V Baskar, S R Kumar, R Sathishkumar
The role of polyketide and non-ribosomal proteins from the class of small molecule metabolism of Mycobacterium tuberculosis is well documented in envelope organization, virulence, and pathogenesis. Consequently, the identification of T cell epitopes from these proteins could serve to define potential antigens for the development of vaccines. Fourty-one proteins from polyketide and non-ribosomal peptide synthesis of small molecule metabolism proteins of M tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nanomeric peptides...
November 16, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29142889/rapid-detection-of-streptomycin-resistant-mycobacterium-tuberculosis-by-rpsl-restriction-fragment-length-polymorphism
#13
Sediqe Karimi, Hossein Mirhendi, Fatemh Riyahi Zaniani, Soroor Erfani Manesh, Mahshd Salehi, Bahram Nasr Esfahani
Background: Molecular methods for the detection of drug-resistant tuberculosis (DR-TB) are potentially more rapid than conventional culture-based drug susceptibility testing, facilitating the commencement of appropriate treatment for patients with DR-TB. The aim of this study was to evaluate and develop polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays for the detection of mutations within rpsL, and for the determination of streptomycin (STR) resistance in Mycobacterium tuberculosis...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/29142798/verification-of-diagnosis-in-tuberculosis-a-case-report-and-discussion
#14
Amanda M Dave, Abed Adelrahman, Vishist Mehta, Stephen Cavalieri, Renuga Vivekanadan
Tuberculosis (TB), caused by strains of Mycobacterium tuberculosis complex (M. tuberculosis), is a pulmonary infection that is spread by airborne droplet transmission. The development and spread of drug-resistant strains of M. tuberculosisgreatly jeopardize TB control efforts. We report the case of a previously healthy 43-year-old male, visiting from China, who presented to the emergency department complaining of hemoptysis of 10 days' duration. Cultures were positive for acid fast bacteria and negative for fungi...
September 3, 2017: Curēus
https://www.readbyqxmd.com/read/29142508/proteomic-characterisation-of-bovine-and-avian-purified-protein-derivatives-and-identification-of-specific-antigens-for-serodiagnosis-of-bovine-tuberculosis
#15
José Antonio Infantes-Lorenzo, Inmaculada Moreno, María de Los Ángeles Risalde, Álvaro Roy, Margarita Villar, Beatriz Romero, Nieves Ibarrola, José de la Fuente, Eugenia Puentes, Lucía de Juan, Christian Gortázar, Javier Bezos, Lucas Domínguez, Mercedes Domínguez
Background: Bovine purified protein derivative (bPPD) and avian purified protein derivative (aPPD) are widely used for bovine tuberculosis diagnosis. However, little is known about their qualitative and quantitative characteristics, which makes their standardisation difficult. In addition, bPPD can give false-positive tuberculosis results because of sequence homology between Mycobacterium bovis (M. bovis) and M. avium proteins. Thus, the objective of this study was to carry out a proteomic characterisation of bPPD, aPPD and an immunopurified subcomplex from bPPD called P22 in order to identify proteins contributing to cross-reactivity among these three products in tuberculosis diagnosis...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/29141374/-association-of-pd-1-tim-3-and-trem-1-single-nucleotide-polymorphisms-with-pulmonary-tuberculosis-susceptibility
#16
F M Wang, X Zhang, L Lan, J M Ji, H B Tang, X J Yao, Y Jiang, J Qian, X G Xu, Q Li, P Yao, J H Li, Y P Shen
Objective: To investigate the association of programmed cell death 1(PD-1), T cell immunoglobulin mucin 3 (TIM-3) and triggering receptor expressed on myeloid cells-1 (TREM-1) genes polymorphisms with pulmonary tuberculosis susceptibility. Methods: In this case-control study, peripheral venous blood of 100 pulmonary tuberculosis patients (pulmonary tuberculosis group) in the Jintan People's Hospital of Changzhou and of community physical examination volunteers (health control group) was collected from Mar 2015 to Sep 2016...
November 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29140996/childhood-tuberculosis-is-associated-with-decreased-abundance-of-t-cell-gene-transcripts-and-impaired-t-cell-function
#17
Cheryl Hemingway, Maurice Berk, Suzanne T Anderson, Victoria J Wright, Shea Hamilton, Hariklia Eleftherohorinou, Myrsini Kaforou, Greg M Goldgof, Katy Hickman, Beate Kampmann, Johan Schoeman, Brian Eley, David Beatty, Sandra Pienaar, Mark P Nicol, Michael J Griffiths, Simon J Waddell, Sandra M Newton, Lachlan J Coin, David A Relman, Giovanni Montana, Michael Levin
The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB...
2017: PloS One
https://www.readbyqxmd.com/read/29140946/comparison-of-the-quantiferon-tb-gold-in-tube-assay-with-tuberculin-skin-test-for-the-diagnosis-of-latent-tuberculosis-infection-among-hiv-infected-and-uninfected-children
#18
Walter Dehority, Rolando M Viani, Maria Rosario G Araneta, Graciano Lopez, Stephen A Spector
BACKGROUND: Diagnosis of latent tuberculosis infection (LTBI) is facilitated by tuberculin skin testing (TST) or interferon-gamma release assays such as the QuantiFERON TB Gold In-Tube (QTF-GIT) assays. Limited data exist on the utility of interferon-gamma release assays in HIV-infected children, which may be falsely negative due to immunosuppression. METHODS: A cross-sectional study comparing TST to QTF-GIT for the diagnosis of suspected LTBI was performed in children in Tijuana, Mexico, and in San Diego, California...
December 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29140933/t-spot-tb%C3%A2-performance-in-routine-pediatric-practice-in-a-low-tb-burden-setting
#19
Anna M Mandalakas, Heather Y Highsmith, Nadine M Harris, Anna Pawlicka, H Lester Kirchner
BACKGROUND: The T-SPOT.TB, an interferon-γ release assay (IGRA), is an indirect test of Mycobacterium tuberculosis infection. Due to sparse and conflicting evidence, IGRA use is limited in young and HIV-infected children. We determined the prevalence of invalid, borderline, positive, and negative results and associations with key demographic variables during routine pediatric use in a TB low-burden setting. METHODS: For pediatric samples received at Oxford Diagnostic Laboratories from 2010-2015, the associations between initial test outcome and demographics were estimated by bivariate analysis and logistic regression...
November 14, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29140686/the-regulatory-mechanism-of-mycobacterium-tuberculosis-phosphoserine-phosphatase-serb2
#20
Gregory A Grant
Almost all organisms contain the same biosynthetic pathway for the synthesis of l-serine from the glycolytic intermediate, D-3-phosphoglycerate. However, regulation of this pathway varies from organism to organism. Many organisms control the activity of the first enzyme in the pathway, D-3-phosphoglyerate dehydrogenase (PGDH), by feedback inhibition through the interaction of l-serine with the ACT domains within the enzyme. The last enzyme in the pathway, phosphoserine phosphatase (PSP) has also been reported to be inhibited by l-serine...
November 15, 2017: Biochemistry
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