23,736 results match your criteria Isoniazid Hepatotoxicity


Ascorbate peroxidase overexpression protects Leishmania braziliensis against trivalent antimony effects.

Mem Inst Oswaldo Cruz 2018 Nov 14;113(12):e180377. Epub 2018 Nov 14.

Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Belo Horizonte, MG, Brasil.

Ascorbate peroxidase (APX) is a redox enzyme of the trypanothione pathway that converts hydrogen peroxide (H2O2) into water molecules. In the present study, the APX gene was overexpressed in Leishmania braziliensis to investigate its contribution to the trivalent antimony (SbIII)-resistance phenotype. Western blot results demonstrated that APX-overexpressing parasites had higher APX protein levels in comparison with the wild-type line (LbWTS). Read More

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November 2018

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

J Clin Transl Res 2018 28;4(1). Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, US.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

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Does adjunctive corticosteroid and aspirin therapy improve the outcome of tuberculous meningitis?

Neurol India 2018 Nov-Dec;66(6):1672-1677

Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Background: Stroke is common in tuberculous meningitis (TBM), and aspirin has been shown to reduce mortality. A combination of aspirin and corticosteroid may be more useful in this condition.

Aim: To evaluate the effect of aspirin and corticosteroid adjunctive therapy alone or in combination in determining the outcome of TBM. Read More

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December 2018

Structural Basis for Inhibition of Enoyl-[Acyl Carrier Protein] Reductase (InhA) from Mycobacterium tuberculosis.

Curr Med Chem 2018 Dec 3. Epub 2018 Dec 3.

Laboratory of Computational Systems Biology, School of Sciences - Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, Porto Alegre-RS 90619-900. Brazil.

Background: The enzyme trans-enoyl-[acyl carrier protein] reductase (InhA) is a central protein for the development of antitubercular drugs. This enzyme is the target for the pro-drug isoniazid, which is catalyzed by the enzyme catalase-peroxidase (KatG) to become active.

Objective: Our goal here is to review the studies on InhA, starting with general aspects and focusing on the recent structural studies, with emphasis on the crystallographic structures of complexes involving InhA and inhibitors. Read More

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December 2018
3 Reads

Current research towards optimizing dosing of first-line antituberculosis treatment.

Expert Rev Anti Infect Ther 2018 Dec 1. Epub 2018 Dec 1.

a Division of Clinical Pharmacology, Department of Medicine , University of Cape Town , South Africa .

Introduction: Drug concentrations in tuberculosis patients on standard regimens vary widely with clinically important consequences. Areas covered: We review the available literature identifying factors correlated with pharmacokinetic variability of antituberculosis drugs. Based on population pharmacokinetic models and the weight, height and sex distributions in a large data base of African tuberculosis patients, we propose simplified weight-based doses of the available fixed dose combination(FDC) for adults with drug susceptible tuberculosis. Read More

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December 2018

The isoniazid metabolites hydrazine and pyridoxal isonicotinoyl hydrazone modulate heme biosynthesis.

Toxicol Sci 2018 Dec 4. Epub 2018 Dec 4.

Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN.

In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase in protoporphyrin IX (PPIX), the penultimate heme precursor. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to upregulate Alas1 but downregulate Fech protein levels in mice; however, the mechanism by which isoniazid mediates disruption of heme synthesis has been unclear. Read More

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December 2018
1 Read

[Molecular diagnosis of multidrug-resistant tuberculosis in sputum samples by melting curve analysis].

Rev Peru Med Exp Salud Publica 2018 Jul-Sep;35(3):433-440

. Laboratorio de Referencia de Tuberculosis y Microbiología, Dirección Regional de Salud Callao. Lima, Perú.

Objectives.: To analyze melting curves for the diagnosis of multidrug-resistant tuberculosis from sputum samples.

Materials And Methods. Read More

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January 2018
3 Reads

Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children.

Indian J Pediatr 2018 Dec 4. Epub 2018 Dec 4.

Department of Pediatrics, St John's Medical College Hospital, Bengaluru, Karnataka, India.

Objectives: To compare the incidence of anti tuberculosis drug-induced hepatotoxicity (ATDH) with those on old vs. revised WHO doses in human immunodeficiency virus (HIV) negative children. The secondary objective was to determine the overall incidence of hepatitis in children on Anti tubercular treatment (ATT) and isoniazid prophylactic therapy (IPT). Read More

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December 2018
2 Reads

Clofazimine, but Not Isoniazid or Rifampicin, Augments Platelet Activation .

Front Pharmacol 2018 20;9:1335. Epub 2018 Nov 20.

Department of Internal Medicine, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa.

Although the inclusion of the cationic amphiphilic, anti-mycobacterial agent, clofazimine, in the chemotherapeutic regimens of patients with multidrug-resistant tuberculosis (TB) has contributed to improved outcomes, concerns remain about the cardiotoxic potential of this agent. Accordingly, the current study was undertaken with the primary objective of investigating the effects of clofazimine, on the reactivity of human platelets , a seemingly unexplored, mechanism of cardiotoxicity. Platelet-rich plasma (PRP) prepared from the blood of healthy, adult humans was treated with clofazimine (0. Read More

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November 2018
1 Read

Drug susceptibility testing of mature Mycobacterium tuberculosis H37Ra and Mycobacterium smegmatis biofilms with calorimetry and laser spectroscopy.

Tuberculosis (Edinb) 2018 Dec 3;113:91-98. Epub 2018 Oct 3.

Center of Biomechanics & Calorimetry Basel (COB), University Basel, C/o Department of Biomedical Engineering (DBE), Gewerbestr. 14, CH-4123, Allschwil, Switzerland. Electronic address:

Biofilms are more resistant to antibiotics and antimicrobial stressors than planktonic bacteria; however, only a limited number of standardized assays enable investigation of this phenomenon. Here, we utilized non-invasive and independent techniques, including isothermal microcalorimetry (IMC) and tunable diode laser absorption spectroscopy (TDLAS), to measure the effect of isoniazid on metabolic activity and respiratory capability of mature Mycobacterium tuberculosis H37Ra (an avirulent strain) and Mycobacterium smegmatis biofilms. We detected only minor changes in metabolic heat production and respiratory rates (O and CO) for mature M. Read More

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December 2018

Validation of the FluoroType MTBDR assay using respiratory and lymph node samples.

Tuberculosis (Edinb) 2018 Dec 19;113:76-80. Epub 2018 Sep 19.

Research Center Borstel, National Reference Center for Mycobacteria, Borstel, Germany; London School of Hygiene and Tropical Medicine, London, United Kingdom. Electronic address:

Background: Tuberculosis (TB), especially drug-resistant TB, is a global public health problem. This study aimed to validate a new molecular diagnostic test, the FluoroType MTBDR.

Method: Samples underwent routine diagnostic procedures (fluorescence microscopy, culture, species differentiation and phenotypic drug susceptibility testing). Read More

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December 2018

Uncloaking an ancient adversary: Can pathogen biomarker elicitors play a role in confirming extrapulmonary TB and latent TB infection?

Tuberculosis (Edinb) 2018 Dec 31;113:30-37. Epub 2018 Aug 31.

Independent Researcher; P.O. Box 56224, Atlanta, GA 30343, USA. Electronic address:

Latent tuberculosis infection (LTBI) is diagnosed immunologically using the Mantoux tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). While widely used, immunodiagnostics can produce false negative or false positive results. Pathogen biomarkers provide an alternative, but direct detection in LTBI and extrapulmonary TB cases is challenging. Read More

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December 2018

Multicentre laboratory validation of the nitrate reductase assay using liquid medium for the rapid detection of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis.

Tuberculosis (Edinb) 2018 Dec 3;113:242-248. Epub 2018 Nov 3.

Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Electronic address:

To perform a multicentre study evaluating the performance of the nitrate reductase assay (NRA) using liquid medium for the detection of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis and to establish the MICs and critical concentrations of rifampicin, isoniazid, ofloxacin, amikacin, kanamycin and capreomycin. The study was carried out in three phases. Phase I determined the MIC of each drug. Read More

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December 2018

Treatment outcomes for isoniazid-monoresistant tuberculosis in Peru, 2012-2014.

PLoS One 2018 4;13(12):e0206658. Epub 2018 Dec 4.

TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Resistance to isoniazid is the most common form of drug-resistance in tuberculosis. However only a tiny proportion of TB patients in the world have access to isoniazid drug susceptibility testing-the widely implemented Xpert MTB/RIF technology only tests for resistance to rifampicin. Patients with isoniazid mono resistance that is not identified at baseline are treated with a standard regimen that effectively results in rifampicin mono-therapy during the latter four months of the six month treatment course, exposing remaining viable organisms to a single agent and greatly increasing the risk of development of multi drug-resistant TB. Read More

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December 2018

A First Insight into the katG and rpoB Gene Mutations of Multidrug-Resistant Mycobacterium tuberculosis Strains from Ecuador.

Microb Drug Resist 2018 Dec 4. Epub 2018 Dec 4.

3 One Health Research Group, Facultad de Ciencias de la Salud, Universidad de Las Américas , Quito, Ecuador .

The aim of this study was to characterize the most frequent mutations associated with rifampicin (RIF) and isoniazid (INH) resistance of Mycobacterium tuberculosis isolates from Ecuador. Sequence analysis of 40 strains, resistant for the tuberculosis drugs INH, RIF, or for both showed that of the 31 strains with resistance to INH, 20 strains (64.5%) carried a mutation in the katG gene (codon 315). Read More

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December 2018

Impact of tetracationic calix[4]arene conformation - from conic structure to expanded bolaform- on their antibacterial and antimycobacterial activities.

Chembiochem 2018 Dec 4. Epub 2018 Dec 4.

FRANCE.

The four possible conformers of a new tetra-guanidino calix[4]arene thought to interact deleteriously with bacterial membrane were synthesized, characterized and evaluated for their in vitro antibacterial activity against various reference Gram negative and Gram positive bacteria: E. coli, P. aeruginosa, S. Read More

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December 2018
1 Read
3.090 Impact Factor

Spontaneous mutations conferring antibiotic resistance to antitubercular drugs at a range of concentrations in Mycobacterium smegmatis.

Drug Dev Res 2018 Dec 3. Epub 2018 Dec 3.

Department of Biological Sciences, Benue State University, Makurdi, Benue State, Nigeria.

Hit, Lead & Candidate Discovery Mycobacteria populations can undergo mutations in their DNA sequence during replication, which if not repaired would be transferred to future generations. Earlier studies have tackled the estimation of mutation rate in mycobacteria at fixed concentrations. However, in this study, in vitro spontaneous mutations in Mycobacterium smegmatis (Msm) mc 155 (Msm) that confers resistance to some of the most important antitubercular drugs; isoniazid (INH ), rifampicin (RIF ), kanamycin (KAN ) and streptomycin (STR ) were first determined at several highly lethal concentrations, a few of which have not been previously investigated, in a fluctuation assay. Read More

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December 2018

Pharmacogenetic Association between Gene Polymorphisms and Isoniazid Induced Hepatotoxicity: Trial Sequence Meta-analysis as Evidence.

Biosci Rep 2018 Dec 3. Epub 2018 Dec 3.

Research and Scientific Studies Unit, College of Nursing & Allied Health Sciences, Jazan University, Jazan, Saudi Arabia

Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 ( ) gene polymorphisms with isoniazid induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. Read More

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December 2018

Isoniazid-loaded chitosan/carbon nanotubes microspheres promote secondary wound healing of bone tuberculosis.

J Biomater Appl 2018 Dec 3:885328218814988. Epub 2018 Dec 3.

Department of orthopedics, Gansu Provincial People's Hospital, Lanzhou, Gansu Province, China.

Poor blood circulation makes it difficult for antitubercular drugs to achieve effective bactericidal concentration at tuberculose focus. The residual Mycobacterium tuberculosis around surgical wound would multiply, resulting in nonunion or sinus formation. Carbon nanotubes have strong tissue penetration and can cross many kinds of physiological barriers. Read More

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December 2018

[The chemical toxicological determination of isoniazid and metoclopramide in the objects used for animals poisoning and in biological fluids].

Sud Med Ekspert 2018 ;61(6):33-38

Department of Pharmaceutical Chemistry, Saint-Petersburg State Chemical Pharmaceutical Academy, Ministry of Health of the Russia, Saint-Petersburg, Russia, 197376.

The number of mass casualty incidents among the dogs has significantly increased during a few recent years in the cities of this country; they are most frequently attributed to the activities of the so-called dog hunters. The dog hunters make use of a variety of chemical compounds for poisoning the dogs. Most of them are the multi-component substances, with their chemical composition being highly variable and continuously modified. Read More

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January 2018

Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet!

Clin Infect Dis 2018 Nov;67(suppl_3):S359-S364

Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.

Background: One approach that could increase the efficacy and reduce the duration of antituberculosis therapy is pharmacokinetics/pharmacodynamics-based optimization of doses. However, this could increase toxicity.

Methods: We mimicked the concentration-time profiles achieved by human equivalent doses of moxifloxacin 800 mg/day, rifampin 1800 mg/day, and pyrazinamide 4000 mg/day (high-dose regimen) vs isoniazid 300 mg/day, rifampin 600 mg/day, and pyrazinamide 2000 mg/day (standard therapy) in bactericidal and sterilizing effect studies in the hollow fiber system model of tuberculosis (HFS-TB). Read More

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November 2018
5 Reads

Transformation Morphisms and Time-to-Extinction Analysis That Map Therapy Duration From Preclinical Models to Patients With Tuberculosis: Translating From Apples to Oranges.

Clin Infect Dis 2018 Nov;67(suppl_3):S349-S358

Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Dallas, Texas.

Background: A major challenge in medicine is translation of preclinical model findings to humans, especially therapy duration. One major example is recent shorter-duration therapy regimen failures in tuberculosis.

Methods: We used set theory mapping to develop a computational/modeling framework to map the time it takes to extinguish the Mycobacterium tuberculosis population on chemotherapy from multiple hollow fiber system model of tuberculosis (HFS-TB) experiments to that observed in patients. Read More

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November 2018
1 Read

Ethionamide Pharmacokinetics/Pharmacodynamics-derived Dose, the Role of MICs in Clinical Outcome, and the Resistance Arrow of Time in Multidrug-resistant Tuberculosis.

Clin Infect Dis 2018 Nov;67(suppl_3):S317-S326

Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.

Background: Ethionamide is used to treat multidrug-resistant tuberculosis (MDR-TB). The antimicrobial pharmacokinetics/pharmacodynamics, the contribution of ethionamide to the multidrug regimen, and events that lead to acquired drug resistance (ADR) are unclear.

Methods: We performed a multidose hollow fiber system model of tuberculosis (HFS-TB) study to identify the 0-24 hour area under the concentration-time curve (AUC0-24) to minimum inhibitory concentration (MIC) ratios that achieved maximal kill and ADR suppression, defined as target exposures. Read More

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November 2018
1 Read

Metabolomic Study to Determine the Mechanism Underlying the Effects of Polysaccharide on Isoniazid- and Rifampicin-Induced Hepatotoxicity in Mice.

Molecules 2018 Nov 27;23(12). Epub 2018 Nov 27.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100102, China.

In this study, a non-targeted metabolic profiling method based on ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was used to characterize the plasma metabolic profile associated with the protective effects of the polysaccharide (SSP) on isoniazid (INH)-and rifampicin (RFP)-induced hepatotoxicity in mice. Fourteen potential biomarkers were identified from the plasma of SSP-treated mice. The protective effects of SSP on hepatotoxicity caused by the combination of INH and RFP (INH/RFP) were further elucidated by investigating the related metabolic pathways. Read More

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November 2018
4 Reads

[Culture proven extra pulmonary tuberculosis: drug susceptibility and genetic profile analysis].

Tuberk Toraks 2018 Sep;66(3):234-238

Department of Medical Microbiology, Faculty of Medicine, Ege University, Izmir, Turkey.

Introduction: Tuberculosis is seen generally in the lungs. Besides, all organs in the body can be affected by tuberculosis. Diagnosis of extra pulmonary tuberculosis (EPTB) is more difficult than pulmonary tuberculosis (PTB). Read More

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September 2018
2 Reads

Prevalence and Clinical Features of Drug Reactions With Eosinophilia and Systemic Symptoms Syndrome Caused by Antituberculosis Drugs: A Retrospective Cohort Study.

Allergy Asthma Immunol Res 2019 Jan;11(1):90-103

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Purpose: Although there have been reported cases of drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome caused by antituberculosis drugs, there has been no research to examine its prevalence. This study assessed the prevalence and clinical characteristics of DRESS syndrome caused by antituberculosis drugs.

Methods: The electronic medical records of a cohort consisting of adult patients diagnosed with tuberculosis between July 2006 and June 2010 were reviewed and retrospectively inspected. Read More

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January 2019

Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: a prospective, multicentre, randomised, open-label, phase 2 trial.

Lancet Infect Dis 2018 Nov 23. Epub 2018 Nov 23.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. Electronic address:

Background: Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis.

Methods: We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul-Seongnam, South Korea). Read More

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November 2018
2 Reads

Challenges and Progress with Diagnosing Pulmonary Tuberculosis in Low- and Middle-Income Countries.

Diagnostics (Basel) 2018 Nov 23;8(4). Epub 2018 Nov 23.

International Union Against Tuberculosis and Lung Disease, 68 Boulevard Saint Michel, 75006 Paris, France.

Case finding and the diagnosis of tuberculosis (TB) are key activities to reach the World Health Organization's End TB targets by 2030. This paper focuses on the diagnosis of pulmonary TB (PTB) in low- and middle-income countries. Sputum smear microscopy, despite its many limitations, remains the primary diagnostic tool in peripheral health facilities; however, this is being replaced by molecular diagnostic techniques, particularly Xpert MTB/RIF, which allows a bacteriologically confirmed diagnosis of TB along with information about whether or not the organism is resistant to rifampicin within two hours. Read More

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November 2018
1 Read

Molecular modelling and simulation studies of the Mycobacterium tuberculosis multidrug efflux pump protein Rv1258c.

PLoS One 2018 26;13(11):e0207605. Epub 2018 Nov 26.

School of Pharmacy, University of the Western Cape, Bellville, South Africa.

Mycobacterial efflux pumps play a major role in the emergence of antimycobacterial drug resistance. Of particular interest is the proteinaceous multi-drug efflux pump protein Rv1258c that encodes a tetracycline/aminoglycoside resistance (TAP-2)-like efflux pump which is active in susceptible and drug resistant Mycobacterium tuberculosis. Rv1258c is implicated in drug resistance to numerous antimycobacterials including first line drugs rifampicin and isoniazid as well as fluoroquinolone and aminoglycoside antibiotic classes. Read More

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November 2018
6 Reads

Intensified antibiotic treatment of tuberculous meningitis.

Expert Rev Clin Pharmacol 2018 Nov 24. Epub 2018 Nov 24.

f Department of Internal Medicine and Radboud Center for Infectious Diseases , Radboud university medical center , Nijmegen , the Netherlands.

Introduction: Meningitis is the most severe manifestation of tuberculosis, resulting in death or disability in over 30% of those affected, with even higher morbidity and mortality among patients with HIV or drug resistance. Antimicrobial treatment of Tuberculous meningitis (TBM) is similar to treatment of pulmonary tuberculosis, although some drugs show poor central nervous system penetration. Therefore, intensification of antibiotic treatment may improve TBM treatment outcome. Read More

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November 2018

In vivo phenotyping of cytochrome 450 isoforms involved in the metabolism of anti-HIV and anti-tubercular drugs in human using cocktail approach: An LC-MS/MS analysis.

J Pharm Biomed Anal 2018 Nov 16;164:698-705. Epub 2018 Nov 16.

Department of Biochemistry, School of Chemical and Life Science, Jamia Hamdard (Deemed University), Hamdard Nagar, New Delhi, 110062, India. Electronic address:

Purpose: In vivo phenotyping of CYP isoforms involved in the metabolism of anti-HIV and antitubercular drugs is important to determine therapeutic dose levels in HIV/AIDS-TB coinfections. In this study, we used a cocktail of bupropion, losartan and dapsone for in vivo phenotyping of CYP2B6, CYP2C9 and N-acetyltransferase-2 (NAT2) in plasma. CYP2B6 is the main catalyst of anti-HIV efavirenz, while NAT2 is involved in antitubercular drug isoniazid metabolism. Read More

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November 2018
1 Read

Bioassay-guided isolation of a Mycobacterium tuberculosis bioflim inhibitor from Arisaema sinii Krause.

Microb Pathog 2018 Nov 22;126:351-356. Epub 2018 Nov 22.

Pharmacy College of Guizhou University, Guiyang, 550025, China. Electronic address:

Mycobacterium tuberculosis biofilms harbour drug-tolerant bacteria. Identification of drugs that inhibit biofilm formation could enable the dramatic shortening of tuberculosis treatments using standard antibiotics. Arisaema sinii Krause is used to treat pulmonary and lymphatic tuberculosis by Dong People of China. Read More

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November 2018
8 Reads

Repurposing antitubercular agent isoniazid for treatment of prostate cancer.

Biomater Sci 2018 Nov 23. Epub 2018 Nov 23.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

The development of versatile antitumor agents with tumor-imaging, targeting and therapeutic activity is promising for clinical cancer therapy. Prostate cancer is still the one of the leading threats to males. Current therapies have restricted clinical efficiency for patients with advanced and metastatic prostate cancer. Read More

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November 2018
4 Reads

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury.

Curr Pharmacol Rep 2018 Jun 15;4(3):171-181. Epub 2018 Mar 15.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Storrs, CT 06269, USA.

Purpose Of This Review: In order to combat the development of drug resistance, the clinical treatment of tuberculosis requires the combined use of several anti-tuberculosis (anti-TB) drugs, including isoniazid and rifampicin. Combinational treatment approaches are suggested by the World Health Organization (WHO) and are widely accepted throughout the world. Unfortunately, a major side effect of the treatment is the development of anti-tuberculosis drug-induced liver injury (AT-DILI). Read More

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June 2018
1 Read

[Diagnostic accuracy of line probe assays for drug-resistant tuberculosis: a Meta-analysis].

Authors:
L Xu Y X Sun S Y Zhan

Zhonghua Liu Xing Bing Xue Za Zhi 2018 Nov;39(11):1491-1495

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

To evaluate the diagnostic accuracy of line probe assays for drug- resistant tuberculosis (TB) in China. Chinese databases (CNKI, Wanfang, SinoMed, VIP Information) and English databases (PubMed, Embase, Cochrane Library) were used to retrieve the literatures regarding the accuracy of line probe assays in the diagnosis of drug-resistant tuberculosis in China between January 1, 2000 and September 1, 2017. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the included studies. Read More

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November 2018
1 Read

High Prevalence of Active and Latent Tuberculosis in Children and Adolescents in Tibetan Schools in India: The Zero TB Kids Initiative in Tibetan Refugee Children.

Clin Infect Dis 2018 Nov 20. Epub 2018 Nov 20.

Center for TB Research, School of Medicine Division of Infectious Diseases, Johns Hopkins University, Baltimore, USA.

Background: Tuberculosis prevalence is high among Tibetan refugees in India, with almost half of cases occurring in congregate facilities, including schools. A comprehensive program of tuberculosis case-finding, and diagnosis and treatment of TB infection (TBI) was undertaken in schools for Tibetan refugee children.

Methods: Under the Zero TB Kids program, schoolchildren and staff in Tibetan schools in Himachal Pradesh, India, were screened for tuberculosis with an algorithm using symptom criteria, chest radiography, molecular diagnostics, and tuberculin skin tests. Read More

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November 2018
4 Reads

Differentially Detectable Mycobacterium tuberculosis Cells in Sputum from Treatment-Naive Subjects in Haiti and Their Proportionate Increase after Initiation of Treatment.

MBio 2018 Nov 20;9(6). Epub 2018 Nov 20.

Department of Microbiology & Immunology, Weill Cornell Medicine, New York, New York, USA

Recent reports indicate that the sputum of 80% or more of treatment-naive subjects with tuberculosis recruited in England or South Africa contained more viable cells detected by limiting dilution (LD) in liquid culture than detected as CFU. Efforts to generate such differentially detectable (DD) populations have been difficult to reproduce, and the LD assay is prone to artifact. Here, we applied a stringent version of the LD assay to sputum from 33 treatment-naive, HIV-negative Haitian subjects with drug-sensitive tuberculosis (TB) and to a second sputum sample after two weeks of standard treatment with isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) for 13 of these subjects. Read More

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November 2018
4 Reads

Using Video Technology to Increase Treatment Completion for Patients With Latent Tuberculosis Infection on 3-Month Isoniazid and Rifapentine: An Implementation Study.

J Med Internet Res 2018 Nov 20;20(11):e287. Epub 2018 Nov 20.

Bureau of Tuberculosis Control, New York City Department of Health and Mental Hygiene, Long Island City, NY, United States.

Background: Since January 2013, the New York City (NYC) Health Department Tuberculosis (TB) Program has offered persons diagnosed with latent TB infection (LTBI) the 3-month, once-weekly isoniazid and rifapentine (3HP) treatment regimen. Patients on this treatment are monitored in-person under directly observed therapy (DOT). To address patient and provider barriers to in-person DOT, we piloted the use of a videoconferencing software app to remotely conduct synchronous DOT (video directly observed therapy; VDOT) for patients on 3HP. Read More

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November 2018
1 Read

Discovery of a cofactor-independent inhibitor of InhA.

Life Sci Alliance 2018 Jun 1;1(3):e201800025. Epub 2018 Jun 1.

Anacor Pharmaceuticals, Palo Alto, CA, USA.

New antitubercular agents are needed to combat the spread of multidrug- and extensively drug-resistant strains of . The frontline antitubercular drug isoniazid (INH) targets the mycobacterial enoyl-ACP reductase, InhA. Resistance to INH is predominantly through mutations affecting the prodrug-activating enzyme KatG. Read More

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June 2018
1 Read

Lessons learned from two interventions designed to increase adherence to LTBI treatment in Latino youth.

Contemp Clin Trials Commun 2018 Dec 16;12:129-136. Epub 2018 Aug 16.

School of Medicine, University of California, San Diego, CA, United States.

Effort is required to meet the Healthy People 2020 goal of tuberculosis (TB) disease reduction to 1 new case per 100,000 in the United States (US) and reduce burden among those disparately affected. Preventing new cases by reducing conversion from latent TB infection (LTBI) to infectious disease is one approach to reducing disease burden. This paper describes the outcome of a trial designed to determine if LTBI-positive youth prescribed daily Isoniazid with peer counseling would achieve higher adherence than attention control participants. Read More

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December 2018
1 Read

Current Medical Management of Pulmonary Tuberculosis.

Authors:
Robert W Belknap

Thorac Surg Clin 2019 Feb;29(1):27-35

Denver Metro Tuberculosis Program, Denver Health and Hospital Authority, 605 Bannock, Denver, CO 80204, USA; Division of Infectious Diseases, Department of Medicine, University of Colorado Denver Anschutz Medical Campus, 12700 East 18th Avenue, RC2, Aurora, CO 80045, USA. Electronic address:

Tuberculosis (TB) remains a common cause of infection and disease in much of the world. The majority of disease occurs from reactivation months or years after initial infection and most often involves the lungs. Sputum smears for acid-fast bacilli remain the initial diagnostic test but have limited sensitivity and specificity. Read More

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February 2019
3 Reads

Treatment completion for latent tuberculosis infection in Norway: a prospective cohort study.

BMC Infect Dis 2018 Nov 19;18(1):587. Epub 2018 Nov 19.

Department of Vaccine Preventable Diseases, Norwegian Institute of Public Health, Oslo, Norway.

Background: Successful treatment of latent tuberculosis infection (LTBI) is essential to reduce tuberculosis (TB) incidence rates in low-burden countries. This study measures treatment completion and determinants of non-completion of LTBI treatment in Norway in 2016.

Methods: This prospective cohort study included all individuals notified with LTBI treatment to the Norwegian Surveillance System for Infectious Diseases (MSIS) in 2016. Read More

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November 2018
6 Reads

The impact of combined gene mutations in inhA and ahpC genes on high levels of isoniazid resistance amongst katG non-315 in multidrug-resistant tuberculosis isolates from China.

Emerg Microbes Infect 2018 Nov 16;7(1):183. Epub 2018 Nov 16.

MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, 100176, Beijing, China.

Whole-genome sequencing was used to analyze the profiles of isoniazid (INH) resistance-related mutations among 188 multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB) and mono-INH-resistant isolates collected in a recent Chinese national survey. Mutations were detected in 18 structural genes and two promoter regions in 96.8% of 188 resistant isolates. Read More

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November 2018
8 Reads

Clue to the diagnosis on chest X-ray in a child with neck swelling.

Arch Dis Child Educ Pract Ed 2018 Nov 15. Epub 2018 Nov 15.

Department of Paediatric Neurology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.

Differentiated thyroid cancer is a rare disease in children and adolescents and manifests exclusively in the form of papillary thyroid cancer (PTC). We present a rare case of PTC who presented initially with lung symptoms and miliary nodules on chest X-ray. This case emphasises the important differential of miliary mottling of the lungs. Read More

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November 2018
4 Reads

Mycobacterium fortuitum infection associated with achalasia.

Tunis Med 2018 May;96(5):311-313

The association achalasia and non tuberculous Mycobacteria lung infection is described in the literature. Most of the time Mycobacterium Fortuitum is responsible of aspiration pneumonia that didn't respond to usual antibiotic therapy. We report a new case about a 15 year-old woman with Allgrove's syndrome history. Read More

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May 2018
1 Read

Modifying aroylhydrazone prochelators for hydrolytic stability and improved cytoprotection against oxidative stress.

Bioorg Med Chem 2018 Dec 5;26(22):5962-5972. Epub 2018 Nov 5.

Duke University, Department of Chemistry, 124 Science Dr., Durham, NC 27708, USA. Electronic address:

BSIH ((E)-N'-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylidene)isonicotinohydrazide) is a prodrug version of the metal chelator SIH ((E)-N'-(2-hydroxybenzylidene)isonicotinohydrazide) in which a boronate group prevents metal chelation until reaction with hydrogen peroxide releases SIH, which is then available for sequestering iron(III) and inhibiting iron-catalyzed oxidative damage. While BSIH has shown promise for conditionally targeting iron sequestration in cells under oxidative stress, the yield of SIH is limited by the fact that BSIH exists in cell culture media as an equilibrium mixture with its hydrolysis products isoniazid and 2-formylphenyl boronic acid. In the current study, several BSIH analogs were evaluated for their hydrolytic stability, reaction outcomes with HO, and prochelator-to-chelator conversion efficiency. Read More

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December 2018
3 Reads

A Challenging Diagnosis of Ascites: A Case Report of Peritoneal Tuberculosis.

Case Rep Infect Dis 2018 23;2018:8136476. Epub 2018 Oct 23.

University of Florida-COM, Division of Internal Medicine, Jacksonville, FL, USA.

Approximately 2 billion people, which is about one third of the world's population, are infected with tuberculosis (TB). Around 10% of infected people will develop active TB at one point in their lifetime. We present a rare case of a 68-year-old male who presented to the emergency department with a 2-week progressive dyspnea. Read More

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October 2018
3 Reads

Molecular detection of rifampin, isoniazid, and ofloxacin resistance in Iranian isolates of by high-resolution melting analysis.

Infect Drug Resist 2018 18;11:1819-1829. Epub 2018 Oct 18.

Tehran Tuberculosis Regional Reference Laboratory, Tehran University of Medical Sciences, Tehran, Iran.

Background: The emergence of drug resistance among (MTB) strains is a serious health concern worldwide. The development of rapid molecular diagnostic methods in recent years has a significant impact on the early detection of resistance to major anti-TB drugs in MTB isolates, which helps in employing appropriate treatment regimen and prevents the spread of drug-resistant strains. This study was designed to evaluate the efficacy of real-time PCR and high-resolution melting (HRM) curve analysis for the determination of resistance to rifampin (RIF), isoniazid (INH), and ofloxacin (OFX) in MTB isolates and to investigate their resistance-related mutations. Read More

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October 2018
3 Reads

[Measurement of rifampicin concentrations in tuberculous pleural effusion before and after combination treatment with oral and local rifampicin].

Zhonghua Jie He He Hu Xi Za Zhi 2018 Nov;41(11):853-856

The Second Department of the Respiratory Medicine, Affiliated Hospital of Zunyi Medical College, Zunyi 563003, China.

To investigate the changes of rifampin concentrations in pleural effusion before and after combination treatment with oral and pleural administration of rifampicin by electro-phonophoresis(EP). A self-control study was performed in 32 cases of tuberculous pleurisy treated in the Second Department of Respiratory Medicine of Affiliated Hospital of Zunyi Medical College between September 2016 and January 2018. Based on the weight of each patient, an oral administration of isoniazid (0. Read More

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November 2018
1 Read

Maternal Motivation to Take Preventive Therapy in Antepartum and Postpartum Among HIV-Positive Pregnant Women in South Africa: A Choice Experiment.

AIDS Behav 2018 Nov 10. Epub 2018 Nov 10.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD, 21205, USA.

HIV-positive pregnant women who are initiated on lifelong antiretroviral therapy (ART) and isoniazid preventive therapy (IPT) have lower adherence rates after delivery. We quantified maternal motivation to take preventive therapy before and after delivery among pregnant women newly diagnosed with HIV. We enrolled pregnant women (≥ 18 years) with a recent HIV diagnosis (< 6 months) at 14 public primary health clinics in Matlosana, South Africa and followed them in the postpartum period. Read More

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November 2018
1 Read