Displaying publications 1 - 20 of 31 in total

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  1. Khattak M, Rehman AU, Muqaddas T, Hussain R, Rasool MF, Saleem Z, et al.
    Ann Med, 2024 Dec;56(1):2313683.
    PMID: 38346381 DOI: 10.1080/07853890.2024.2313683
    BACKGROUND: The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid, pyrazinamide, ethambutol and rifampicin) for a period of six months to eradicate the TB infection completely. Diabetes mellitus (DM) is recognized as one of a strong contributor of TB according to World Health Organization (WHO). The presence of diabetes mellitus type 2 (DM type 2) makes TB treatment complicated. Thus, the objective of the current meta-analysis was to identify and quantify the impact of type 2 DM on treatment outcomes of TB patients treated under the DOTS Programme.

    METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Through a systematic review of relevant literature, we focused on studies investigating treatment outcomes including extended treatment duration and recurrence for individuals with both TB and DM undergoing DOTS therapy. The extracted information included study designs, sample sizes, patient characteristics and reported treatment results.

    RESULTS: In 44 studies from different parts of the world, the pooled HR for the impact of DM on extended treatment duration and reoccurrence were HR 0.72, 95% CI 0.56-0.83, p 

    Matched MeSH terms: Isoniazid/therapeutic use
  2. Barathan M, Zulpa AK, Vellasamy KM, Mariappan V, Shivashekaregowda NKH, Ibrahim ZA, et al.
    In Vivo, 2021 8 20;35(5):2675-2685.
    PMID: 34410956 DOI: 10.21873/invivo.12551
    BACKGROUND/AIM: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells.

    MATERIALS AND METHODS: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays.

    RESULTS: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G2/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death.

    CONCLUSION: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.

    Matched MeSH terms: Isoniazid/therapeutic use; Isoniazid/toxicity
  3. Mohamad S, Ibrahim P, Wahab HA
    Chemotherapy, 2007;53(4):263-6.
    PMID: 17595540
    Our previous study demonstrated that the effects of isoniazid (INH) on Mycobacterium tuberculosis at the cellular level varied according to the growth phases. In this study, the variations in the INH action on M. avium strain NCTC 8559 are reported. M. avium cells grown on Middlebrook 7H10 agar were harvested at different stages of their growth cycle, exposed to the minimum inhibitory concentration of INH, stained with acid-fast staining for morphological changes and acid fastness properties, and the number of colonies were evaluated for viability studies. The study demonstrated that M. avium NCTC 8559 cells at the initial and fragmentation stages of the growth cycle were most susceptible to INH.
    Matched MeSH terms: Isoniazid/pharmacology*
  4. Barathan M, Shivashekaregowda NKH, Hoong SM, Vellasamy KM, Vadivelu J
    Toxicol Appl Pharmacol, 2023 Dec 15;481:116767.
    PMID: 38007073 DOI: 10.1016/j.taap.2023.116767
    Current treatments for stomach cancer are often effective in curing cancer. However, these treatments can also have significant side effects, and they may not be effective in all cases. Hence synthetic compounds exhibit promise as potential agents for cancer treatment. In a previous study, we identified (E)-N'- (2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) as a novel antimycobacterial derivative of isoniazid with cytotoxic effects on the MCF-7 breast cancer cell line. This led us to investigate the potential anti-cancer properties of ITHB4 against adenocarcinoma gastric (AGS) cell line. The cytotoxic effect of ITHB4 has been determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and further confirmed for anticancer properties by means of apoptosis, reactive oxygen species (ROS), nuclear fragmentation, lactate dehydrogenase (LDH), caspases, cytokines and morphological including phenotypic changes of cells assay. The ITHB4 demonstrated a lower IC50 in inhibiting growth of AGS cells at 24 h compared to 48 and 72 h. ITHB4 has also shown no toxicity human immune cells. Treatment of ITHB4 against AGS for 24 h eventually lead to formation of early apoptotic AGS cells, reduced mitochondrial membrane potential, nuclear condensation, and nuclear fragmentation lastly increased in ROS levels together with the release of LDH, and secretion of caspases. The altered cytokine profile in ITHB4 treated AGS hints at the possibility that ITHB4 may possess anti-tumor and anti-inflammatory properties. Our results in this study demonstrate that ITHB4 has almost similar chemotherapeutic properties against gastric adenocarcinoma cells compared to breast cancer cell. This is suggesting that the anticancer capabilities of this compound should be in vivo and clinically assessed.
    Matched MeSH terms: Isoniazid/pharmacology
  5. Ismail NA, Ismail MF, Noor SS, Camalxaman SN
    Malays J Med Sci, 2016 Jan;23(1):22-6.
    PMID: 27540322 MyJurnal
    Drug resistant tuberculosis (DR-TB) remains a public health issue that is of major concern on a global scale. The characterisation of clinical isolates may provide key information regarding the underlying mechanisms of drug resistance, and helps to augment therapeutic options. This study aims to evaluate the frequency of gene mutations associated with Rifampicin (RIF) and Isoniazid (INH) resistance among nine clinical isolates.
    Matched MeSH terms: Isoniazid
  6. Mohamad S, Ibrahim P, Sadikun A
    Tuberculosis (Edinb), 2004;84(1-2):56-62.
    PMID: 14670346
    In this study, the susceptibility of Mycobacterium tuberculosis to isoniazid (INH) was compared with its derivative, 1-isonicotinyl-2-nonanoyl hydrazine (INH-C9), prepared synthetically. The minimum inhibitory concentration (MIC) of the drugs was determined using the 1% proportion method. INH-C9 was found to lower the MIC of INH from 0.05 to 0.025 microg/ml. Further studies on the effects of INH and INH-C9 on M. tuberculosis were assessed by exposing the cells to the above at the MIC level. M. tuberculosis cells grown on Middlebrook 7H10 agar were harvested at different stages of their growth cycle (initial stage, 24 and 72 h), exposed to the MICs of INH and INH-C9, and stained with acid-fast staining. The observations were made for a week. The cellular morphologies and staining characteristics were examined using a Brightfield microscope. The result indicated cells only at the initial stage of growth were most susceptible to the drugs resulting in the loss of acid-fastness and intact cellular morphology in the majority of cells.
    Matched MeSH terms: Isoniazid/analogs & derivatives; Isoniazid/pharmacology*
  7. Saifullah B, Arulselvan P, El Zowalaty ME, Fakurazi S, Webster TJ, Geilich BM, et al.
    Int J Nanomedicine, 2014;9:4749-62.
    PMID: 25336952 DOI: 10.2147/IJN.S63608
    The primary challenge in finding a treatment for tuberculosis (TB) is patient non-compliance to treatment due to long treatment duration, high dosing frequency, and adverse effects of anti-TB drugs. This study reports on the development of a nanodelivery system that intercalates the anti-TB drug isoniazid into Mg/Al layered double hydroxides (LDHs). Isoniazid was found to be released in a sustained manner from the novel nanodelivery system in humans in simulated phosphate buffer solutions at pH 4.8 and pH 7.4. The nanodelivery formulation was highly biocompatible compared to free isoniazid against human normal lung and 3T3 mouse fibroblast cells. The formulation was active against Mycobacterium tuberculosis and gram-positive bacteria and gram-negative bacteria. Thus results show significant promise for the further study of these nanocomposites for the treatment of TB.
    Matched MeSH terms: Isoniazid/pharmacokinetics*; Isoniazid/pharmacology; Isoniazid/toxicity; Isoniazid/chemistry*
  8. Wahab HA, Choong YS, Ibrahim P, Sadikun A, Scior T
    J Chem Inf Model, 2009 Jan;49(1):97-107.
    PMID: 19067649 DOI: 10.1021/ci8001342
    The continuing rise in tuberculosis incidence and the problem of drug resistance strains have prompted the research on new drug candidates and the mechanism of drug resistance. Molecular docking and molecular dynamics simulation (MD) were performed to study the binding of isoniazid onto the active site of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA) in an attempt to address the mycobacterial resistance against isoniazid. Results show that isonicotinic acyl-NADH (INADH) has an extremely high binding affinity toward the wild type InhA by forming stronger interactions compared to the parent drug (isoniazid) (INH). Due to the increase of hydrophobicity and reduction in the side chain's volume of A94 of mutant type InhA, both INADH and the mutated protein become more mobile. Due to this reason, the molecular interactions of INADH with mutant type are weaker than that observed with the wild type. However, the reduced interaction caused by the fluctuation of INADH and the mutant protein only inflected minor resistance in the mutant strain as inferred from free energy calculation. MD results also showed there exists a water-mediated hydrogen bond between INADH and InhA. However, the bridged water molecule is only present in the INADH-wild type complex, reflecting the putative role of the water molecule in the binding of INADH to the wild type protein. The results support the assumption that the conversion of prodrug isoniazid into its active form INADH is mediated by KatG as a necessary step prior to target binding on InhA. Our findings also contribute to a better understanding of INH resistance in mutant type.
    Matched MeSH terms: Isoniazid/analogs & derivatives; Isoniazid/metabolism; Isoniazid/pharmacology*; Isoniazid/chemistry*
  9. Puri MM, Arora VK
    Med J Malaysia, 2000 Sep;55(3):382-4.
    PMID: 11200723
    A 25 year old woman developed a right pleural effusion 6 weeks after commencement of short course chemotherapy for left sided tuberculous pleural effusion. Since the patient improved following continuation of the same treatment, it is presumed to be a case of paradoxical response to anti-tuberculosis treatment.
    Matched MeSH terms: Isoniazid/adverse effects; Isoniazid/therapeutic use
  10. Low JM, Wong KW
    Med J Malaysia, 2019 12;74(6):553-554.
    PMID: 31929489
    Patients with end stage renal disease have higher risk of tuberculosis due to lower cell-mediated immunity. Standard regime of anti-tuberculosis contains isoniazid where neurological side effects such as seizure and encephalopathy have been documented. We present a case of isoniazid-induced encephalopathy in a haemodialysis patient. A literature review on isoniazid-induced encephalopathy was done. Recognition of this condition is important as it is reversible with cessation of isoniazid and institution of high dose pyridoxine.
    Matched MeSH terms: Isoniazid/adverse effects*; Isoniazid/therapeutic use
  11. Nur Hidayah Masod, Noraziah Mohamad Zin, Alfizah Hanafiah
    Sains Malaysiana, 2018;47:543-549.
    Tuberculosis (TB) is a major health problem in many developing countries including Malaysia. In Malaysia, the number of death due to tuberculosis has decreased, but there is rising concern on the increase of drug resistance (multi drug resistance tuberculosis) cases. In this study, patients’ demographic data were analyzed and the susceptibility of Mycobacterium tuberculosis against anti-tuberculosis agents (isoniazid, streptomycin, rifampicin and ethambutol) was determined using susceptibility MYCOTB plates. A total of 40 clinical M. tuberculosis isolates, isolated from patients in PPUKM were randomly selected. Among these, 62.5% were male (mean age: 36.9±17.9 years) and 37.5% were female (mean age: 42.6±16.6 years). Malay patients accounted for the highest percentage of TB cases which was 60%, followed by Indians 15%, 5% Chinese and 20% other ethnics. The isolation of M. tuberculosis from clinical samples were 60%, 17.5%, 7.5%, 7.5%, 5% and 2.5% from sputum, tracheal aspirate, pus, blood, BAL and tissue, respectively. This is correlated with the majority of the patients (67.5%) infected with M. tuberculosis having persistent cough symptoms. The results from MYCOTB and BACTEC MGIT 960 susceptibility testing were compared. The average time taken to do the anti-TB susceptibility test by using MYCOTB plate and BACTEC MGIT 960 was 2 and 40.5 min, respectively. Cost per sample for MYCOTB and BACTEC MGIT 960 was RM16.65 and RM42.80, respectively. To conclude, based on our demographic data, TB infection was the highest amongst male Malay patients and the main specimens that been received was sputum sample. MYCOTB plate was more preferable than BACTEC MGIT 960 for the susceptibility testing and all clinical samples were 100% susceptible to all tested anti-TB agents. Data gathered from this study can be used as guideline for the management of TB diagnosis and treatment in the future.
    Keywords: BACTEC MGIT 960; Mycobacterium tuberculosis; MYCOTB plate; tuberculosis
    Matched MeSH terms: Isoniazid
  12. Myo, Thura Zaw, Ahmad Faris Abdullah, Naing, Oo Tha, Zainal Arifin Mustapha, Nor Amalina Emran, Zaw, Lin
    MyJurnal
    Emergence of multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) is one of the reasons why tuberculosis (TB) continues to cause great mortality and morbidity in less-developed countries. The development of rapid diagnostic methods targeting genetic mutations associated with resistance to the anti-tuberculous drugs is essential to fight this deadly pathogen. Isoniazid (INH) has been included in the multidrug regimens for the treatment of drug-susceptible TB for the decades. In the worldwide setting, isoniazid resistance was highly prevalent and was observed in one of every seven TB cases. Since katG315 mutation is highly prevalent, the common mutation in the enzyme essential for the activation of the INH concerned with the mechanism of drug resistance and associated with high level resistance to INH, katG315 mutation was necessary to be identified by molecular method as a molecular determinant of INH resistant Mycobacterium tuberculosis. The prevalence of katG315 mutation in various countries was discussed in this report and a new molecular method for the detection of the mutation was proposed.
    Matched MeSH terms: Isoniazid
  13. Jalalonmuhali M, Lee YY, Lee CK, Ismail R, Chandran PA
    Int J Dermatol, 2014 Feb;53(2):234-7.
    PMID: 22913324 DOI: 10.1111/j.1365-4632.2012.05463.x
    Matched MeSH terms: Isoniazid/therapeutic use
  14. Jalleh RD, Kuppusamy I, Soshila R, Aziah AM, Faridza MY
    Med J Malaysia, 1993 Jun;48(2):113-6.
    PMID: 8350784
    Eight hundred and fifty-six strains of Mycobacterium tuberculosis from previously untreated patients with pulmonary tuberculosis from various states in West Malaysia were studied during the period 1984 to 1987. All the strains were tested for in vitro susceptibility to the anti-tuberculosis drugs isoniazid (INH), streptomycin (SM), rifampicin (RMP) and ethambutol (ETB). One hundred and twenty-one of the isolates (14.18%) were resistant to 1 drug while 17 (1.97%) were resistant to 2 drugs. No strain was found to be resistant to more than 2 drugs. The prevalence of primary resistance to INH was 4.20%, SM was 7.59%, RMP was 0.95% and ETB was 1.44%. In 1.86% of isolates, resistance was noted to both INH and SM, while 0.11% were resistant to both RMP and ETB. There was no significant difference in distribution of resistant bacilli between the sexes (p > 0.01).
    Matched MeSH terms: Isoniazid/pharmacology*
  15. AlMatar M, Makky EA, Var I, Kayar B, Köksal F
    Pharmacol Rep, 2018 Apr;70(2):217-226.
    PMID: 29475004 DOI: 10.1016/j.pharep.2017.09.001
    Tuberculosis (TB) is described as lethal disease in the world. Resistant to TB drugs is the main reason to have unfavourable outcomes in the treatment of TB. Therefore, new agents to replace existing drugs are urgently needed. Previous reports suggested that InhA inhibitors, an enoyl-ACP-reductase, might provide auspicious candidates which can be developed into novel antitubercular agents. In this review, we explain the role of InhA in the resistance of isoniazid. Furthermore, five classes of InhA inhibitors, which display novel binding modes and deliver evidence of their prosperous target engagement, have been debated.
    Matched MeSH terms: Isoniazid/therapeutic use
  16. Webb AH
    N Z Med J, 1973 Nov 14;78(502):490-12.
    PMID: 4129254
    Matched MeSH terms: Isoniazid/therapeutic use
  17. Ferguson GC, Nunn AJ, Fox W, Miller AB, Robinson DK, Tall R
    Tubercle, 1971 Sep;52(3):166-81.
    PMID: 4106401
    Matched MeSH terms: Isoniazid/administration & dosage; Isoniazid/adverse effects
  18. Kar SS, Bhat VG, Shenoy VP, Bairy I, Shenoy GG
    Chem Biol Drug Des, 2019 01;93(1):60-66.
    PMID: 30118192 DOI: 10.1111/cbdd.13379
    In our efforts to develop druggable diphenyl ethers as potential antitubercular agents, a series of novel diphenyl ether derivatives (5a-f, 6a-f) were designed and synthesized. The representative compounds showed promising in vitro activity against drug-susceptible, isoniazid-resistant, and multidrug-resistant strains of Mycobacterium tuberculosis with MIC values of 1.56 μg/ml (6b), 6.25 μg/ml (6a-d), and 3.125 μg/ml (6b-c), respectively. All the synthesized compounds exhibited satisfactory safety profile (CC50  > 300 μg/ml) against Vero and HepG2 cells. Reverse phase HPLC method was used to probe the physicochemical properties of the synthesized compounds. This series of compounds demonstrated comparatively low logP values. pKa values of representative compounds indicated that they were weak acids. Additionally, in vitro human liver microsomal stability assay confirmed that the synthesized compounds possessed acceptable stability under study conditions. The present study thus establishes compound 6b as the most promising antitubercular agent with acceptable drug-likeness.
    Matched MeSH terms: Isoniazid
  19. Al-Darraji HA, Kamarulzaman A, Altice FL
    Int J Tuberc Lung Dis, 2012 Jul;16(7):871-9.
    PMID: 22410101 DOI: 10.5588/ijtld.11.0447
    Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide and the main cause of death in correctional facilities in middle- and low-income countries. Due to the closed environment and the concentration of individuals with TB-related risk factors, effective measures are required to control TB in such settings. Isoniazid preventive therapy (IPT) represents an effective and cost-effective measure. Despite international recommendations that IPT be integral to TB control, it is seldom deployed. A systematic review of interventions used to assess IPT initiation and completion in correctional facilities was conducted using published studies from two biomedical databases and relevant keywords. Additional references were reviewed, resulting in 18 eligible studies. Most (72%) studies were conducted in the United States and in jail settings (60%), with the main objective of improving completion rates inside the facility or after release. Studies that provided data about initiation and completion rates showed poor success in correctional facilities. Adverse consequences and treatment interruption ranged from 1% to 55% (median 5%) in reported studies; hepatotoxicity was the most prevalent adverse reaction. Despite its accelerating effect on the development of active TB, information on human immunodeficiency virus (HIV) status was provided in only half of the studies. Among the four studies where IPT effectiveness was assessed, the results mirror those described in community settings. Future studies require thorough assessments of IPT initiation and completion rates and adverse effects, particularly in low- and middle-income countries and where comorbid viral hepatitis may contribute significantly to outcomes, and in settings where TB and HIV are more endemic.
    Matched MeSH terms: Isoniazid/therapeutic use*
  20. Khajotia R, Manthari K
    Can Fam Physician, 2011 Mar;57(3):311-3.
    PMID: 21402968
    Matched MeSH terms: Isoniazid/therapeutic use
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