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https://www.readbyqxmd.com/read/28228760/perturbed-microrna-expression-by-mycobacterium-tuberculosis-promotes-macrophage-polarization-leading-to-pro-survival-foam-cell
#1
Pankaj Kumar Ahluwalia, Rajan Kumar Pandey, Prabodh Kumar Sehajpal, Vijay Kumar Prajapati
Tuberculosis (TB) is one of the prevalent causes of death worldwide, with 95% of these deaths occurring in developing countries, like India. The causative agent, Mycobacterium tuberculosis (MTb) has the tenacious ability to circumvent the host's immune system for its own advantage. Macrophages are one of the phagocytic cells that are central to immunity against MTb. These are highly plastic cells dependent on the milieu and can showcase M1/M2 polarization. M1 macrophages are bactericidal in action, but M2 macrophages are anti-inflammatory in their immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28225346/cd4-count-and-risk-of-anti-tuberculosis-drug-associated-cutaneous-reactions-in-hiv-infected-thai-patients
#2
L Boonyagars, P Hirunwiwatkul, C P Hurst
OBJECTIVES: Tuberculosis (TB) is a major cause of morbidity and mortality in human immunodeficiency virus (HIV) infected patients. However, anti-tuberculosis drugs can cause cutaneous adverse drug reactions (CADRs). This study was conducted to evaluate differences in CADR incidence between low and high CD4 cell count in patients with low and high CD4 cell count and to identify other risk factors for CADR in HIV-TB co-infected patients. DESIGN: In a retrospective cohort of adult HIV-TB co-infected patients receiving standard anti-tuberculosis treatment between January 2008 and December 2015 at Vajira Hospital, Bangkok, Thailand, baseline demographic, clinical characteristics and factors associated with CADRs, including CD4 cell count status, were collected...
March 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28222400/antiprotozoal-antimycobacterial-and-anti-inflammatory-evaluation-of-cnidoscolus-chayamansa-mc-vaugh-extract-and-the-isolated-compounds
#3
Mariana Z Pérez-González, Gabriel A Gutiérrez-Rebolledo, Lilián Yépez-Mulia, Irma S Rojas-Tomé, Julieta Luna-Herrera, María A Jiménez-Arellanes
Cnidoscolus chayamansa is a medicinal and edible plant known as Chaya, is commonly used as an anti-inflammatory, antiprotozoal, antibacterial agent and as a remedy for respiratory illness, gastrointestinal disorders, and vaginal infections related with the inflammation process. In this paper, we describe the plant's phytochemical analysis and biological activities (antimycobacterial, antibacterial, antiprotozoal, and anti-inflammatory properties) of the CHCl3:MeOH (1:1) leaves extract and isolated compounds, as well as the acute and sub-acute toxic effects...
February 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28208905/n-acetylcysteine-combined-with-home-based-physical-activity-effect-on-health-related-quality-of-life-in-stable-copd-patients-a-randomised-controlled-trial
#4
Vijay Tukaram Salve, Jitesh S Atram
INTRODUCTION: Quality of life is adversely affected in Chronic Obstructive Pulmonary Disease (COPD), due to irreversible, progressive nature of the disease and limitations of current treatment options available. One of the important aim of treatment of COPD is to improve Quality of Life (QoL). Cigarette smoke contains numerous free radicals and other oxidants. Oxidative stress has been implicated in pathogenesis, progression of disease and exacerbation in COPD. Pulmonary tuberculosis, outdoor and indoor air pollution and many others are aetiologies of COPD in non-smokers...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28202315/mycobacterium-tuberculosis-chorismate-mutase-a-potential-target-for-tb
#5
REVIEW
Manjulatha Khanapur, Mallika Alvala, Maddela Prabhakar, K Shiva Kumar, R K Edwin, P S V K Sri Saranya, Raj Kumar Patel, Gopalakrishnan Bulusu, P Misra, Manojit Pal
Mycobacterium tuberculosis chorismate mutase (MtbCM) catalyzes the rearrangement of chorismate to prephenate in the shikimate biosynthetic pathway to form the essential amino acids, phenylalanine and tyrosine. Two genes encoding chorismate mutase have been identified in Mtb. The secretory form,∗MtbCM (encoded by Rv1885c) is assumed to play a key role in pathogenesis of tuberculosis. Also, the inhibition of MtbCM may hinder the supply of nutrients to the organism. Indeed, the existence of chorismate mutase (CM) in bacteria, fungi and higher plants but not in human and low sequence homology among known CM makes it an interesting target for the discovery of anti-tubercular agents...
February 4, 2017: Bioorganic & Medicinal Chemistry
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
#6
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/28195652/identification-of-the-anti-mycobacterial-functional-properties-of-piperidinol-derivatives
#7
Collette S Guy, Esther Tichauer, Gemma L Kay, Daniel J Phillips, Trisha L Bailey, James Harrison, Christopher M Furze, Andrew D Millard, Matthew I Gibson, Mark J Pallen, Elizabeth Fullam
BACKGROUND AND PURPOSE: Tuberculosis (TB) remains a major global health threat and is now the leading cause of death from a single infectious agent worldwide. The current TB drug regimen is inadequate and new anti-tubercular agents are urgently required to be able to successfully combat the increasing prevalence of drug-resistant TB. The purpose of this study was to investigate a piperidinol compound derivative that is highly active against the Mycobacterium tuberculosis bacillus. EXPERIMENTAL APPROACH: The antibacterial properties of the piperidinol compound and its corresponding bis-Mannich base analogue were evaluated against Mycobacterium smegmatis and Gram-negative organisms...
February 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28193668/towards-selective-mycobacterial-clpp1p2-inhibitors-with-reduced-activity-against-the-human-proteasome
#8
Wilfried Moreira, Sridhar Santhanakrishnan, Grace J Y Ngan, Choon Bing Low, Kanda Sangthongpitag, Anders Poulsen, Brian W Dymock, Thomas Dick
Mycobacterium tuberculosis (TB) is responsible for the greatest number of deaths worldwide due to a bacterial agent. We recently identified bortezomib (1) as a promising anti-TB compound. We showed that 1 inhibits the mycobacterial caseinolytic protease ClpP1P2 and exhibits bactericidal activity and established 1 and ClpP1P2 as an attractive lead/target couple. However, 1 is a human proteasome inhibitor currently approved for cancer therapy, and as such exhibits significant toxicity. Selective inhibition of the bacterial protease over the human proteasome is desirable in order to maintain antibacterial activity while reducing toxicity...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28160418/comparison-of-the-risk-of-infections-in-different-anti-tnf-agents-a-meta-analysis
#9
Hongxing Liao, Zhixiong Zhong, Zhanliang Liu, Xuenong Zou
BACKGROUND: Anti-tumor necrosis factor α (anti-TNF-α) treatments are widely used in patients with rheumatoid arthritis (RA); however, the increased risk of infections is one of the most important side effects of anti-TNF-α agents. This study evaluated the differences between monoclonal antibodies and the soluble receptor for infections in patients with RA by direct comparison of observation studies. METHODS: A systemic literature search was conducted in March 2014 and an up-to-date search was conducted in August 2014...
February 3, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28157465/missed-opportunities-for-screening-child-contacts-of-smear-positive-tuberculosis-in-zambia-a-high-prevalence-setting
#10
C Chabala, G Chongwe, E Jumbe-Marsden, S W Somwe
OBJECTIVE: To evaluate whether contact screening recommendations for child household contacts of adult smear-positive tuberculosis (TB) cases were implemented in Lusaka, Zambia. METHODS: A cross-sectional survey of smear-positive adults receiving anti-tuberculosis treatment was conducted. The main outcomes were proportions of TB patients with under-five children who were aware, informed and/or had a child screened and/or commenced on isoniazid (INH). RESULTS: Of 371 TB patients (median age 33 years, 70% males), 259 (70%) lived with a child aged <15 years, of whom 48% (177) were aged <5 years...
January 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28157125/planarity-of-benzoylthiocarbazate-tuberculostatics-iii-diesters-of-3-2-hydroxybenzoyl-dithiocarbazic-acid
#11
Małgorzata Szczesio, Andrzej Olczak, Ida Mazerant, Katarzyna Gobis, Henryk Foks, Marek L Główka
Searches for new tuberculostatic agents are important considering the occurrence of drug-resistant strains of Mycobacterium tuberculosis. The structures of three new potentially tuberculostatic compounds, namely isopropyl methyl (2-hydroxybenzoyl)carbonohydrazonodithioate, C12H16N2O2S2, (Z)-benzyl methyl (2-hydroxybenzoyl)carbonohydrazonodithioate, C16H16N2O2S2, and dibenzyl (2-hydroxybenzoyl)carbonohydrazonodithioate propan-2-ol monosolvate, C22H20N2O2S2·C3H8O, were determined by X-ray diffraction. The mutual orientation of the three main fragments of the compounds, namely an aromatic ring, a dithioester group and a hydrazide group, can influence the biological activity of the compounds...
February 1, 2017: Acta Crystallographica. Section C, Structural 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/28149517/primary-ethambutol-resistance-among-iranian-pulmonary-tuberculosis-patients-a-systematic-review
#13
REVIEW
Mohammad Javad Nasiri, Abbas Ali Imani Fooladi, Hossein Dabiri, Ali Pormohammad, Alireza Salimi Chirani, Masoud Dadashi, Hamidreza Houri, Mohsen Heidary, Mohammad Mehdi Feizabadi
INTRODUCTION: Ethambutol (EMB) is an anti-mycobacterial agent that is most commonly used in combination with other anti-tuberculosis (TB) drugs in the treatment of TB. Studies have shown that primary resistance rates of Mycobacterium tuberculosis to EMB vary widely, that is, from 1% to as high as 14%. In this study, we aimed to determine the exact prevalence of primary EMB resistance among pulmonary TB cases. METHODS: Several databases, including Medline, Embase, and Iranian databases, were searched from March 2000 to January 2016 to identify studies addressing EMB-resistant TB in Iran...
October 2016: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28122281/anti-cancer-effect-of-clofazimine-as-a-single-agent-and-in-combination-with-cisplatin-on-u266-multiple-myeloma-cell-line
#14
İpek Z Durusu, Hazal H Hüsnügil, Heval Ataş, Ayşenur Biber, Selin Gerekçi, Ezgi A Güleç, Can Özen
Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. CLF (10μM, 24h) treatment resulted up to 72% growth suppression on a panel of hematological cell lines...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28122162/targeting-proteasomes-in-infectious-organisms-to-combat-disease
#15
REVIEW
Betsaida Bibo-Verdugo, Zhenze Jiang, Conor R Caffrey, Anthony J O'Donoghue
Proteasomes are multisubunit, energy-dependent, proteolytic complexes that play an essential role in intracellular protein turnover. They are present in eukaryotes, archaea, and in some actinobacteria species. Inhibition of proteasome activity has emerged as a powerful strategy for anticancer therapy and three drugs have been approved for treatment of multiple myeloma. These compounds react covalently with a threonine residue located in the active site of a proteasome subunit to block protein degradation. Proteasomes in pathogenic organisms such as Mycobacterium tuberculosis and Plasmodium falciparum also have a nucleophilic threonine residue in the proteasome active site and are therefore sensitive to these anticancer drugs...
January 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28120710/the-role-of-universal-stress-proteins-in-bacterial-infections
#16
Andrew O Connor, Siobhán McClean
Universal stress proteins are ubiquitously expressed in bacteria, archaea and plants and other eukaryotes. A general property of USPs is their role in adaptation of bacteria to oxidative stress, high temperature, low pH and/or hypoxia. There is increasing evidence that these proteins facilitate the adaption of bacterial pathogens to the human host environment, thereby facilitating colonisation and pathogenicity. USPs in Mycobacterium tuberculosis are well studied and may play a role in latency of tuberculosis...
January 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28117224/drug-resistance-mechanisms-and-novel-drug-targets-for-tuberculosis-therapy
#17
REVIEW
Md Mahmudul Islam, H M Adnan Hameed, Julius Mugweru, Chiranjibi Chhotaray, Changwei Wang, Yaoju Tan, Jianxiong Liu, Xinjie Li, Shouyong Tan, Iwao Ojima, Wing Wai Yew, Eric Nuermberger, Gyanu Lamichhane, Tianyu Zhang
Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis...
January 20, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28103537/hybrids-of-thienopyrimidinones-and-thiouracils-as-anti-tubercular-agents-sar-and-docking-studies
#18
Mahesh M Pisal, Laxman U Nawale, Manoj D Patil, Sujit G Bhansali, Jayant M Gajbhiye, Dhiman Sarkar, Subhash P Chavan, Hanumant B Borate
A number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against Mycobacterium tuberculosis H37Ra wherein it was observed that the compounds 11-14 exhibited antitubercular activity in vitro (MIC 7.6-19.1 μg/mL, 12-35 μM) against dormant stage while the compound 15 exhibited antitubercular activity in vitro against dormant (MIC 23.4 μg/mL, 41 μM) as well as active (MIC 25.4 μg/mL, 45 μM) stage. Structural modifications of the compound 15 were carried out to study the structure-activity relationship and it was observed that the compound 18 exhibited antitubercular activity comparable to the compound 15...
January 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28074051/anti-folates-potentiate-bactericidal-effects-of-other-antimicrobial-agents
#19
Kun Li, Xu-de Wang, Shan-Shan Yang, Jing Gu, Jiao-Yu Deng, Xian-En Zhang
Synergies between sulfonamides and other antimicrobial agents have long been reported, but the reason still remains unclear. Previously, Vilchèze et al. found that, sulfamethoxazole (SMX) could potentiate the bacterialcidal activity of isoniazid (INH) and rifampin (RIF) in Mycobacterium tuberculosis. To test if this was also the case in other bacteria, the ability to potentiate bactericidal effect of RIF by SMX was evaluated in Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Mycobacterium smegmatis...
January 11, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28060290/visualization-of-the-charcoal-agar-resazurin-assay-for-semi-quantitative-medium-throughput-enumeration-of-mycobacteria
#20
Ben Gold, Julia Roberts, Yan Ling, Landys Lopez Quezada, Jou Glasheen, Elaine Ballinger, Selin Somersan-Karakaya, Thulasi Warrier, Carl Nathan
There is an urgent need to discover and progress anti-infectives that shorten the duration of tuberculosis (TB) treatment. Mycobacterium tuberculosis, the etiological agent of TB, is refractory to rapid and lasting chemotherapy due to the presence of bacilli exhibiting phenotypic drug resistance. The charcoal agar resazurin assay (CARA) was developed as a tool to characterize active molecules discovered by high-throughput screening campaigns against replicating and non-replicating M. tuberculosis. Inclusion of activated charcoal in bacteriologic agar medium helps mitigate the impact of compound carry-over, and eliminates the requirement to pre-dilute cells prior to spotting on CARA microplates...
December 14, 2016: Journal of Visualized Experiments: JoVE
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