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Modeling AND tuberculosis

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https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#1
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#2
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28525582/challenges-in-the-estimation-of-the-annual-risk-of-mycobacterium-tuberculosis-infection-in-children-aged-under-5-years
#3
P Y Khan, J R Glynn, T Mzembe, D Mulawa, R Chiumya, A C Crampin, K Kranzer, K L Fielding
Accurate estimates of Mycobacterium tuberculosis (M.tb) infection in young children provide a critical indicator of on-going community M.tb transmission. Cross reactions due to infection with environmental mycobacteria and/or Bacille Calmette-Guérin (BCG) vaccination compromise the estimates derived from population-level tuberculin skin test surveys using traditional cut-off methods. Newer statistical approaches are prone to failure of model convergence, especially in settings where the prevalence of M.tb infection is low and environmental sensitisation is high...
May 19, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28523507/tof-sims-parallel-imaging-ms-ms-of-lipid-species-in-thin-tissue-sections
#4
Anne Lisa Bruinen, Gregory L Fisher, Ron M A Heeren
Unambiguous identification of detected species is essential in complex biomedical samples. To date, there are not many mass spectrometry imaging techniques that can provide both high spatial resolution and identification capabilities. A new and patented imaging tandem mass spectrometer, exploiting the unique characteristics of the nanoTOF II (Physical Electronics, USA) TOF-SIMS TRIFT instrument, was developed to address this.Tandem mass spectrometry is based on the selection of precursor ions from the full secondary ion spectrum (MS(1)), followed by energetic activation and fragmentation, and collection of the fragment ions to obtain a tandem MS spectrum (MS(2))...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28522990/animal-models-for-tuberculosis-in-translational-and-precision-medicine
#5
REVIEW
Lingjun Zhan, Jun Tang, Mengmeng Sun, Chuan Qin
Tuberculosis (TB) is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28520909/large-scale-data-driven-integrative-framework-for-extracting-essential-targets-and-processes-from-disease-associated-gene-data-sets
#6
Gaston K Mazandu, Emile R Chimusa, Kayleigh Rutherford, Elsa-Gayle Zekeng, Zoe Z Gebremariam, Maryam Y Onifade, Nicola J Mulder
Populations worldwide currently face several public health challenges, including growing prevalence of infections and the emergence of new pathogenic organisms. The cost and risk associated with drug development make the development of new drugs for several diseases, especially orphan or rare diseases, unappealing to the pharmaceutical industry. Proof of drug safety and efficacy is required before market approval, and rigorous testing makes the drug development process slow, expensive and frequently result in failure...
May 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28520768/mobile-phone-reminders-and-peer-counseling-improve-adherence-and-treatment-outcomes-of-patients-on-art-in-malaysia-a-randomized-clinical-trial
#7
Surajudeen Abiola Abdulrahman, Lekhraj Rampal, Faisal Ibrahim, Anuradha P Radhakrishnan, Hayati Kadir Shahar, Norlijah Othman
BACKGROUND: Adherence to treatment remains the cornerstone of long term viral suppression and successful treatment outcomes among patients receiving Antiretroviral Therapy (ART). OBJECTIVE(S): Evaluate the effectiveness of mobile phone reminders and peer counseling in improving adherence and treatment outcomes among HIV positive patients on ART in Malaysia. METHODS: A single-blind, parallel group RCT conducted in Hospital Sungai Buloh, Malaysia in which 242 adult Malaysian patients were randomized to intervention or control groups...
2017: PloS One
https://www.readbyqxmd.com/read/28520704/adverse-events-associated-with-treatment-of-multidrug-resistant-tuberculosis-in-china-an-ambispective-cohort-study
#8
Yang Zhang, Shanshan Wu, Yinyin Xia, Ni Wang, Lin Zhou, Jing Wang, Renfei Fang, Feng Sun, Mingting Chen, Siyan Zhan
BACKGROUND Adverse events are under-appreciated negative consequences that are significant clinical problems for patients undergoing anti-MDR-TB treatment due to longer duration of treatment and more need for concurrent use of multiple second-line drugs. The aim of this study was to determine the incidence of adverse events and their impact on MDR-TB therapy and treatment outcome, and to identify possible drug-event pairs in China. MATERIAL AND METHODS An ambispective cohort study was conducted based on hospital medical records, which included a retrospective study that enrolled 751 MDR-TB patients receiving standardized regimen between May 2009 and July 2013, and a follow-up investigation of treatment outcome conducted in December 2016 in China...
May 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28517109/the-studies-of-para-and-parb-dynamics-reveal-asymmetry-of-chromosome-segregation-in-mycobacteria
#9
Katarzyna Ginda, Isabella Santi, Djenet Bousbaine, Jolanta Zakrzewska-Czerwińska, Dagmara Jakimowicz, John McKinney
Active segregation of bacterial chromosomes usually involves the action of ParB proteins, which bind in proximity of chromosomal origin (oriC) regions forming nucleoprotein complexes - segrosomes. Newly duplicated segrosomes are moved either uni- or bidirectionally by the action of ATPases - ParA proteins. In Mycobacterium smegmatis the oriC region is located in an off-centred position and newly replicated segrosomes are segregated toward cell poles. The elimination of M. smegmatis ParA and/or ParB leads to chromosome segregation defects...
May 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28515317/characterization-of-a-secretory-hydrolase-from-mycobacterium-tuberculosis-sheds-critical-insight-into-host-lipid-utilization-by-m-tuberculosis
#10
Khundrakpam Herojit Singh, Bhavya Jha, Abhisek Dwivedy, Eira Choudhary, Arpitha G N, Anam Ashraf, Nisheeth Agarwal, Bichitra Kumar Biswal
Mycobacterium tuberculosis causes tuberculosis in humans and predominantly infects alveolar macrophages. To survive inside host lesions and to evade immune surveillance, this pathogen has developed many strategies. For example, M. tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged persistence within hypoxic host microenvironments. M. tuberculosis imports these metabolites through its respective transporters, and in the case of host fatty acids, a pertinent question arises: does M. tuberculosis have the enzyme(s) for cleavage of fatty acids from host lipids? We show herein that a previously uncharacterized membrane-associated M...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28514962/revisiting-annual-screening-for-latent-tuberculosis-infection-in-healthcare-workers-a-cost-effectiveness-analysis
#11
Guillaume A Mullie, Kevin Schwartzman, Alice Zwerling, Dieynaba S N'Diaye
BACKGROUND: In North America, tuberculosis incidence is now very low and risk to healthcare workers has fallen. Indeed, recent cohort data question routine annual tuberculosis screening in this context. We compared the cost-effectiveness of three potential strategies for ongoing screening of North American healthcare workers at risk of exposure. The analysis did not evaluate the cost-effectiveness of screening at hiring, and considered only workers with negative baseline tests. METHODS: A decision analysis model simulated a hypothetical cohort of 1000 workers following negative baseline tests, considering duties, tuberculosis exposure, testing and treatment...
May 17, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28513983/book-review-the-foundations-of-immunology-and-their-pertinence-to-medicine
#12
REVIEW
A Corthay
We are in the era cursed with overspecialization. Charles Darwin's foundational Origin of Species, published in 1859 was accessible to the broadly educated individual. Starting with this statement, Peter Bretscher in his new book aims at explaining foundational concepts of immunology to a broad public. His standpoint is that foundational ideas usually can be simply expressed. This book describes first how foundational concepts of immunology have evolved over the last two and a half centuries. The importance of self-nonself discrimination by the immune system is acknowledged and models for immunological tolerance are compared...
May 17, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28512022/synthesis-antimycobacterial-activity-and-docking-study-of-2-aroyl-1-benzopyrano-4-3-c-pyrazol-4-1h-one-derivatives-and-related-hydrazide-hydrazones
#13
Violina T Angelova, Violeta Valcheva, Tania Pencheva, Yulian Voynikov, Nikolay Vassilev, Rositsa Mihaylova, Georgi Momekov, Boris Shivachev
A new convenient method for preparation of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives 5b-g and coumarin containing hydrazide-hydrazone analogues 4a-e was presented. The antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and cytotoxicity against the human embryonic kidney cell line HEK-293 were tested in vitro. All compounds demonstrated significant minimum inhibitory concentrations (MIC) ranging 0.28-1.69μM, which were comparable to those of isoniazid. The cytotoxicity (IC50>200µM) to the "normal cell" model HEK-293T exhibited by 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives 5b-e, was noticeably milder compared to that of their hydrazone analogues 4a-e (IC50 33-403µM)...
May 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28507951/the-phytochemical-bergenin-enhances-t-helper-1-responses-and-anti-mycobacterial-immunity-by-activating-the-map-kinase-pathway-in-macrophages
#14
Ved P Dwivedi, Debapriya Bhattacharya, Vinod Yadav, Dhiraj K Singh, Santosh Kumar, Mona Singh, Durbadal Ojha, Anand Ranganathan, Luc Van Kaer, Debprasad Chattopadhyay, Gobardhan Das
Tuberculosis (TB) remains one of the greatest health concerns worldwide, which has hindered socioeconomic development in certain parts of the world for many centuries. Although current TB therapy, "Directly Observed Treatment Short-course," is effective, it is associated with unwanted side effects and the risk for the generation of drug-resistant organisms. The majority of infected individuals successfully confine the mycobacterial organisms and remain asymptotic unless immune responses are perturbed. Thus, host immunity can protect against TB and immunomodulation is therefore an attractive therapeutic option...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28507475/macrophage-migration-inhibitory-factor-173-g-c-polymorphism-and-risk-of-tuberculosis-a-meta-analysis
#15
Mohammad Naderi, Mohammad Hashemi, Hossein Ansari
The aim of the present meta-analysis was to find out the impact of MIF -173 G > C polymorphism on risk of tuberculosis (TB). We conducted a search of case-control studies on the associations of -173 G > C variant of MIF with susceptibility to tuberculosis in PubMed, ISI Web of Science, and Scopus. We extracted the data from eligible studies and achieved a meta-analysis to examine the relationship between MIF -173 G > C polymorphism and the risk of TB. Odds ratios (ORs) with the corresponding 95 % confidence intervals (CIs) were pooled to find out the impact of MIF -173G > C promoter polymorphism on TB risk...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28507063/the-mycobacterium-tuberculosis-mmpl11-cell-wall-lipid-transporter-is-important-for-biofilm-formation-intracellular-growth-and-non-replicating-persistence
#16
Catherine C Wright, Fong Fu Hsu, Eusondia Arnett, Jennifer L Dunaj, Patrick M Davidson, Sophia A Pacheco, Melanie J Harriff, David M Lewinsohn, Larry S Schlesinger, Georgiana E Purdy
The mycobacterial cell wall is crucial to the host-pathogen interface since it provides a barrier against antibiotics and the host immune response. In addition, cell wall lipids are mycobacterial virulence factors. The mycobacterial membrane protein large (MmpL) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and M. tuberculosis pathogenesis. MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria, consistent with an important role in the basic physiology of the bacterium...
May 15, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28502122/humanized-nog-mice-as-a-model-for-tuberculosis-vaccine-induced-immunity-a-comparative-analysis-with-the-mouse-and-guinea-pig-models-of-tuberculosis
#17
Ajay Grover, Amber Troy, Jenny Rowe, JoLynn M Troudt, Elizabeth Creissen, Jennifer McLean, Prabal Banerjee, Gerold Feuer, Angelo A Izzo
The humanized mouse model has been developed as a model to identify and characterize human immune responses to human pathogens and has been used to better identify vaccine candidates. In the current studies, the humanized mouse was used to determine the ability of a vaccine to affect the immune response to infection with Mycobacterium tuberculosis. Both human CD4(+) and CD8(+) T cells responded to infection in humanized mice as a result of infection. In humanized mice vaccinated with either BCG or with CpG-C, a liposome-based formulation containing the M...
May 14, 2017: Immunology
https://www.readbyqxmd.com/read/28499828/estimating-the-future-burden-of-multidrug-resistant-and-extensively-drug-resistant-tuberculosis-in-india-the-philippines-russia-and-south-africa-a-mathematical-modelling-study
#18
Aditya Sharma, Andrew Hill, Ekaterina Kurbatova, Martie van der Walt, Charlotte Kvasnovsky, Thelma E Tupasi, Janice C Caoili, Maria Tarcela Gler, Grigory V Volchenkov, Boris Y Kazennyy, Olga V Demikhova, Jaime Bayona, Carmen Contreras, Martin Yagui, Vaira Leimane, Sang Nae Cho, Hee Jin Kim, Kai Kliiman, Somsak Akksilp, Ruwen Jou, Julia Ershova, Tracy Dalton, Peter Cegielski
BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa...
May 9, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28499541/sequence-analysis-of-haemagglutinin-and-neuraminidase-of-h1n1-strain-from-a-patient-coinfected-with-mycobacterium-tuberculosis
#19
Ahmed N Alghamdi, Mohammad E Mahfouz, Fahd A Hamdi, Daifullah Al Aboud, Tawfiq Z Al-Laylah, Mohammed I Alotaibi, Khalid W A Al-Thomali, Ahmed S Abdel-Moneim
The 2009 H1N1 pandemic (H1N1pdm09) was associated with a considerable influenza-related morbidity and mortality. Among the complications, Mycobacterial tuberculosis was recorded as a coinfection with influenza in rare cases. The full-length sequences of the viral haemagglutinin and neuraminidase of H1N1pdm09 influenza A virus were analyzed from a recently infected patient. The patient was chronically infected with Mycobacterium tuberculosis. Molecular modelling and in-silico docking of the virus, and other selected strains with the drug oseltamivir were conducted and compared...
May 9, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/28499279/a-single-nucleotide-polymorphism-in-the-interferon-%C3%AE-gene-ifng-874-t-a-is-associated-with-susceptibility-to-tuberculosis
#20
Zhang Wei, Shen Wenhao, Mi Yuanyuan, Li Yang, Daming Zhou, Xian Jiangchun, Jiang Jijun
Interferon-γ (Interferon gamma, IFNG) is an important cytokine involved in providing resistance to mycobacterial diseases. Common variants of IFNG, such as IFNG +874 T/A(rs2430561), may be related to tuberculosis susceptibility, but this association has not been consistently observed. We performed an updated meta-analysis to evaluate the association between the IFNG +874 T/A (rs2430561) polymorphism and tuberculosis susceptibility. PubMed and SinoMed databases were searched up to October 2016, and odds ratios (OR) and 95% confidence intervals (CI) were used to assess the association strength...
April 20, 2017: Oncotarget
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