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Modeling tuberculosis

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https://www.readbyqxmd.com/read/28226776/an-in-silico-model-of-the-effects-of-vitamin-d3-on-mycobacterium-infected-macrophage
#1
Maya Gough, Elebeoba May, Maya Gough, Elebeoba May, Maya Gough, Elebeoba May
Mycobacterium tuberculosis is a global health concern, causing over one million deaths a year. Alveolar macrophages, as the primary host cell of this intracellular bacterium, play an important role in the course of disease. Vitamin D3 is known to have a potent effect on macrophage behavior during infection, modulating the production of pro- and anti-inflammatory cytokines and immune effector molecules. In a vitamin D3 deficient host, the immune systems response to infection is greatly impaired. We used a quantitative systems biology approach to model the intracellular effects of vitamin D3 and compared our simulation output to our in vitro model of mycobacterium infection of macrophages in the presence and absence of Vitamin D3...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225909/tuberculosis-as-a-marker-of-inequities-in-the-context-of-socio-spatial-transformation
#2
Alexandre San Pedro, Gerusa Gibson, Jefferson Pereira Caldas Dos Santos, Luciano Medeiros de Toledo, Paulo Chagastelles Sabroza, Rosely Magalhães de Oliveira
OBJECTIVE: This study aims to analyze the association between the incidence of tuberculosis and different socioeconomic indicators in a territory of intense transformation of the urban space. METHODS: This is an ecological study, whose analysis units were the neighborhoods of the city of Itaboraí, state of Rio de Janeiro, Brazil. The data have been analyzed by generalized linear models. The response variable was incidence of tuberculosis from 2006 to 2011. The independent variables were the socio-demographic indicators...
February 16, 2017: Revista de Saúde Pública
https://www.readbyqxmd.com/read/28225907/characterisation-of-iunh-gene-knockout-strain-from-mycobacterium-tuberculosis
#3
Anne Drumond Villela, Valnês da Silva Rodrigues, Antônio Frederico Michel Pinto, Priscila Lamb Wink, Zilpa Adriana Sánchez-Quitian, Guilherme Oliveira Petersen, Maria Martha Campos, Luiz Augusto Basso, Diógenes Santiago Santos
BACKGROUND: Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis. The better understanding of important metabolic pathways from M. tuberculosis can contribute to the development of novel therapeutic and prophylactic strategies to combat TB. Nucleoside hydrolase (MtIAGU-NH), encoded by iunH gene (Rv3393), is an enzyme from purine salvage pathway in M. tuberculosis. MtIAGU-NH accepts inosine, adenosine, guanosine, and uridine as substrates, which may point to a pivotal metabolic role...
March 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28225889/roles-of-monocyte-chemotactic-protein-1-and-nuclear-factor-%C3%AE%C2%BAb-in-immune-response-to-spinal-tuberculosis-in-a-new-zealand-white-rabbit-model
#4
X H Guo, Z Bai, B Qiang, F H Bu, N Zhao
This study aimed to explore the roles of monocyte chemotactic protein 1 (MCP-1) and nuclear factor kappa B (NF-κB) in immune response to spinal tuberculosis in a New Zealand white rabbit model. Forty-eight New Zealand white rabbits were collected and divided into four groups: experimental group (n=30, spinal tuberculosis model was established), the sham group (n=15, sham operation was performed) and the blank group (n=3). The qRT-PCR assay and western blotting were applied to detect the mRNA and protein expressions of MCP-1 and NF-κB in peripheral blood...
February 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28225343/infection-control-and-tuberculosis-in-health-care-workers-an-assessment-of-28-hospitals-in-south-africa
#5
L M O'Hara, A Yassi, E A Bryce, A Janse van Rensburg, M C Engelbrecht, M Zungu, L E Nophale, J M FitzGerald
SETTING: Twenty-eight public hospitals in the Free State Province, South Africa. OBJECTIVE: To examine the association between tuberculosis (TB) infection control (IC) scores in Free State hospitals and the incidence of TB disease among health care workers (HCWs) in 2012. DESIGN: A cross-sectional survey and mixed-methods analysis of TB IC policies, practices and infrastructure using a comprehensive, 83-item IC audit and observation tool. RESULTS: As the total IC score increased, the probability of TB in an HCW at that hospital decreased...
March 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28225342/outcomes-from-the-first-multidrug-resistant-tuberculosis-programme-in-kenya
#6
H Huerga, M Bastard, M Kamene, S Wanjala, A Arnold, N Oucho, I Chikwanha, F Varaine
SETTING: In March 2006, the first multidrug-resistant tuberculosis (MDR-TB) treatment programme was implemented in Kenya. OBJECTIVE: To describe patients' treatment outcomes and adverse events. DESIGN: A retrospective case note review of patients started on MDR-TB treatment at two Médecins Sans Frontières-supported sites and the national referral hospital of Kenya was undertaken. Sites operated an ambulatory model of care. Patients were treated for a minimum of 24 months with at least 4-5 drugs for the intensive phase of treatment, including an injectable agent...
March 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28223967/secretome-prediction-of-two-m-tuberculosis-clinical-isolates-reveals-their-high-antigenic-density-and-potential-drug-targets
#7
Fernanda Cornejo-Granados, Zyanya L Zatarain-Barrón, Vito A Cantu-Robles, Alfredo Mendoza-Vargas, Camilo Molina-Romero, Filiberto Sánchez, Luis Del Pozo-Yauner, Rogelio Hernández-Pando, Adrián Ochoa-Leyva
The Excreted/Secreted (ES) proteins play important roles during Mycobacterium tuberculosis invasion, virulence, and survival inside the host and they are a major source of immunogenic proteins. However, the molecular complexity of the bacillus cell wall has made difficult the experimental isolation of the total bacterial ES proteins. Here, we reported the genomes of two Beijing genotype M. tuberculosis clinical isolates obtained from patients from Vietnam (isolate 46) and South Africa (isolate 48). We developed a bioinformatics pipeline to predict their secretomes and observed that ~12% of the genome-encoded proteins are ES, being PE, PE-PGRS, and PPE the most abundant protein domains...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28223515/rational-design-of-adjuvants-targeting-the-c-type-lectin-mincle
#8
Alexiane Decout, Sandro Silva-Gomes, Daniel Drocourt, Sophie Barbe, Isabelle André, Francisco J Cueto, Thierry Lioux, David Sancho, Eric Pérouzel, Alain Vercellone, Jacques Prandi, Martine Gilleron, Gérard Tiraby, Jérôme Nigou
The advances in subunit vaccines development have intensified the search for potent adjuvants, particularly adjuvants inducing cell-mediated immune responses. Identification of the C-type lectin Mincle as one of the receptors underlying the remarkable immunogenicity of the mycobacterial cell wall, via recognition of trehalose-6,6'-dimycolate (TDM), has opened avenues for the rational design of such molecules. Using a combination of chemical synthesis, biological evaluation, molecular dynamics simulations, and protein mutagenesis, we gained insight into the molecular bases of glycolipid recognition by Mincle...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28219528/mycobacterium-tuberculosis-rv1987-induces-th2-immune-responses-and-enhances-mycobacterium-smegmatis-survival-in-mice
#9
Shanshan Sha, Xiaoxia Shi, Guoying Deng, Lina Chen, Yi Xin, Yufang Ma
Mycobacterium tuberculosis can interfere with host immune response and escape clearance through its specific antigens. M. tuberculosis Rv1987 encoded by region of difference (RD)-2 gene is a secretory protein with immunogenic potency. Here, we investigated the impact of Rv1987 on host cytokine responses and T cell polarization in mouse aerosol model. A recombinant M. smegmatis mc(2)155 strain that overexpressed Rv1987 protein (named MS1987) was constructed and used to infect C57BL/6 mice. The mc(2)155 harbored the empty vector (named MSVec) was as a control...
April 2017: Microbiological Research
https://www.readbyqxmd.com/read/28215501/serial-quantiferon-testing-and-tuberculosis-disease-risk-among-young-children-an-observational-cohort-study
#10
Jason R Andrews, Elisa Nemes, Michele Tameris, Bernard S Landry, Hassan Mahomed, J Bruce McClain, Helen A Fletcher, Willem A Hanekom, Robin Wood, Helen McShane, Thomas J Scriba, Mark Hatherill
BACKGROUND: The value of quantitative interferon-γ release assay results for predicting progression from Mycobacterium tuberculosis infection to active disease is unknown. We aimed to investigate the relation between QuantiFERON-TB Gold In-Tube (QFT) conversion interferon-γ values and risk of subsequent active tuberculosis disease and of QFT reversion. METHODS: We analysed data from a reported vaccine efficacy trial of the tuberculosis vaccine MVA85A in South Africa...
February 16, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28208151/bacillus-calmette-gu%C3%A3-rin-confers-neuroprotection-in-a-murine-model-of-japanese-encephalitis
#11
Sahil Kulkarni, Sandeepan Mukherjee, Anupama Pandey, Ritwik Dahake, Usha Padmanabhan, Abhay S Chowdhary
OBJECTIVE: Japanese encephalitis (JE) is a debilitating disease caused by infection with the JE virus (JEV; family: Flaviviridae), which leaves neurological sequelae in survivors but more often leads to mortality. Neurodegeneration caused by inflammation is the primary pathology behind the clinical manifestation of encephalitis caused by JEV. Bacillus Calmette-Guérin (BCG) has been used in immunoprophylaxis for tuberculosis and in the adjuvant therapy of many malignancies, and has exhibited neuroprotective activities in experimental models of Parkinson and Alzheimer disease...
February 17, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28205025/the-multistate-tuberculosis-pharmacometric-model-a-semi-mechanistic-pharmacokinetic-pharmacodynamic-model-for-studying-drug-effects-in-an-acute-tuberculosis-mouse-model
#12
Chunli Chen, Fatima Ortega, Joaquin Rullas, Laura Alameda, Iñigo Angulo-Barturen, Santiago Ferrer, Ulrika Sh Simonsson
The Multistate Tuberculosis Pharmacometric (MTP) model, a pharmacokinetic-pharmacodynamic disease model, has been used to describe the effects of rifampicin on Mycobacterium tuberculosis (M. tuberculosis) in vitro. The aim of this work was to investigate if the MTP model could be used to describe the rifampicin treatment response in an acute tuberculosis mouse model. Sixty C57BL/6 mice were intratracheally infected with M. tuberculosis H37Rv strain on Day 0. Fifteen mice received no treatment and were sacrificed on Days 1, 9 and 18 (5 each day)...
February 15, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28202093/tuberculosis-and-risk-of-acute-myocardial-infarction-a-propensity-score-matched-analysis
#13
M A Huaman, R J Kryscio, C J Fichtenbaum, D Henson, E Salt, T R Sterling, B A Garvy
Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs with Mycobacterium tuberculosis infection is unclear. We assessed if tuberculosis disease increased the risk of acute myocardial infarction (AMI). We identified patients with tuberculosis index claims from a large de-identified database of ~15 million adults enrolled in a U.S. commercial insurance policy between 2008 and 2010. Tuberculosis patients were 1:1 matched to patients without tuberculosis claims using propensity scores...
February 16, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28202091/isolation-unit-for-multidrug-resistant-tuberculosis-patients-in-a-low-endemic-country-a-step-towards-the-world-health-organization-end-tb-strategy
#14
M C Payen, J P VAN Vooren, O Vandenberg, N Clumeck, S DE Wit
Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates...
February 16, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28199375/has-universal-screening-with-xpert%C3%A2-mtb-rif-increased-the-proportion-of-multidrug-resistant-tuberculosis-cases-diagnosed-in-a-routine-operational-setting
#15
Pren Naidoo, Rory Dunbar, Judy Caldwell, Carl Lombard, Nulda Beyers
SETTING: Primary health services in Cape Town, South Africa where the introduction of Xpert® MTB/RIF (Xpert) enabled simultaneous screening for tuberculosis (TB) and drug susceptibility in all presumptive cases. STUDY AIM: To compare the proportion of TB cases with drug susceptibility tests undertaken and multidrug-resistant tuberculosis (MDR-TB) diagnosed pre-treatment and during the course of 1st line treatment in the previous smear/culture and the newly introduced Xpert-based algorithms...
2017: PloS One
https://www.readbyqxmd.com/read/28198919/natural-compounds-from-mexican-medicinal-plants-as-potential-drug-leads-for-anti-tuberculosis-drugs
#16
Rocio Gómez-Cansino, Silvia Laura Guzmán-Gutiérrez, María Guadalupe Campos-Lara, Clara Ines Espitia-Pinzón, Ricardo Reyes-Chilpa
In Mexican Traditional Medicine 187 plant species are used in the treatment of respiratory conditions that may be associated with tuberculosis. In this contribution, we review the ethnobotany, chemistry and pharmacology of 63 species whose extracts have been assayed for antimycobacterial activity in vitro. Among these, the most potent is Aristolochia brevipes (MIC= 12.5 µg/mL), followed by Aristolochia taliscana, Citrus sinensis, Chrysactinia mexicana, Persea americana, and Olea europaea (MIC<64 µg/mL)...
February 9, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28198210/a-minority-of-patients-newly-diagnosed-with-aids-are-started-on-antiretroviral-therapy-at-the-time-of-diagnosis-in-a-large-public-hospital-in-the-southeastern-united-states
#17
Neela D Goswami, Jonathan Colasanti, Jonathan J Khoubian, Yijian Huang, Wendy S Armstrong, Carlos Del Rio
Prompt antiretroviral therapy (ART) initiation after AIDS diagnosis, in the absence of certain opportunistic infections such as tuberculosis and cryptococcal meningitis, delays disease progression and death, but system barriers to inpatient ART initiation at large hospitals in the era of modern ART have been less studied. We reviewed hospitalizations for persons newly diagnosed with AIDS at Grady Memorial Hospital in Atlanta, Georgia in 2011 and 2012. Individual- and system-level variables were collected. Logistic regression models were used to estimate the odds ratios (ORs) for ART initiation prior to discharge...
January 1, 2017: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/28196957/a-novel-small-molecule-inhibitor-of-the-mycobacterium-tuberculosis-demethylmenaquinone-methyltransferase-meng-is-bactericidal-to-both-growing-and-nutritionally-deprived-persister-cells
#18
Paridhi Sukheja, Pradeep Kumar, Nisha Mittal, Shao-Gang Li, Eric Singleton, Riccardo Russo, Alexander L Perryman, Riju Shrestha, Divya Awasthi, Seema Husain, Patricia Soteropoulos, Roman Brukh, Nancy Connell, Joel S Freundlich, David Alland
Active tuberculosis (TB) and latent Mycobacterium tuberculosis infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable to the existence of nonreplicating M. tuberculosis "persisters" that are difficult to kill using conventional anti-TB treatments. Compounds that target the respiratory pathway have the potential to kill both replicating and persistent M. tuberculosis and shorten TB treatment, as this pathway is essential in both metabolic states. We developed a novel respiratory pathway-specific whole-cell screen to identify new respiration inhibitors...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28196762/enteric-helminth-induced-type-i-interferon-signalling-protects-against-pulmonary-virus-infection-through-interaction-with-the-microbiota
#19
Amanda J McFarlane, Henry J McSorley, Donald J Davidson, Paul M Fitch, Claire Errington, Karen J Mackenzie, Eva S Gollwitzer, Chris J C Johnston, Andrew S MacDonald, Michael R Edwards, Nicola L Harris, Benjamin J Marsland, Rick M Maizels, Jürgen Schwarze
BACKGROUND: Helminth parasites have been reported to have beneficial immune modulatory effects in allergic and autoimmune conditions and detrimental consequences in tuberculosis and some viral infections. Their role in co-infection with respiratory viruses is not clear. OBJECTIVE: Here, we investigated the effects of strictly enteric helminth infection with Heligmosomoides polygyrus on respiratory syncytial virus (RSV) infection in a mouse model. METHODS: A murine helminth/ RSV co-infection model was developed...
February 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28193650/interaction-of-rifampicin-and-darunavir-ritonavir-or-darunavir-cobicistat-in-vitro
#20
Owain Roberts, Saye Khoo, Andrew Owen, Marco Siccardi
Treatment of HIV patients co-infected with tuberculosis (TB) is challenging due to drug-drug interactions (DDIs) between antiretrovirals (ARVs) and anti-TB drugs. The aim of this study was to quantify the effects of cobicistat (COBI), or ritonavir (RTV), in modulating DDIs between darunavir (DRV) and rifampicin (RIF) in a human hepatocyte-based in vitro model. Human primary hepatocyte cultures were incubated with RIF alone, or in combination with either COBI or RTV for three days, followed by co-incubation with DRV for one hour...
February 13, 2017: Antimicrobial Agents and Chemotherapy
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