Displaying publications 281 - 300 of 322 in total

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  1. Othman FN, Muthuraju S, Noor SSM, Abdullah S, Mohd Yusoff AA, Tharakan J, et al.
    Tuberculosis (Edinb), 2018 09;112:45-51.
    PMID: 30205968 DOI: 10.1016/j.tube.2018.07.007
    The present study aimed to investigate the involvement of the angiogenic marker vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax in the neurons and astrocytes in the brain infected by Mycobacterium tuberculosis. The immunohistochemistry staining was performed to analyze the expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The expression of VEGF was high in neurons and astrocytes in both the infected brain and control tissues with no difference of angiogenic activity (p = 0.40). Higher Bcl-2 expression was seen in astrocytes of infected brain tissues compared to the control tissues (p = 0.004) promoted a higher anti-apoptotic activity in astrocytes. The neurons expressed strong Bax expression in the infected brain tissues compared to the control tissues (p 
    Matched MeSH terms: Mycobacterium tuberculosis/pathogenicity*
  2. Subramaniam M, Arshad NM, Mun KS, Malagobadan S, Awang K, Nagoor NH
    Biomolecules, 2019 10 18;9(10).
    PMID: 31635311 DOI: 10.3390/biom9100626
    Cancer development and progression are extremely complex due to the alteration of various genes and pathways. In most cases, multiple agents are required to control cancer progression. The purpose of this study is to investigate, using a mouse model, the synergistic interactions of anti-cancer agents, 1'-S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP), and cisplatin (CDDP) in double and triple combinations to treat chemo-sensitize and immune-sensitize breast cancer. Changes in tumor volume and body weight were monitored. Organs were harvested and stained using hematoxylin-eosin for histopathological assessment. Milliplex enzyme-linked immunosorbent assay (ELISA) was performed to determine cytokine levels, while immunohistochemistry (IHC) was conducted on tumor biopsies to verify systemic drug effects. In vivo mouse models showed tumor regression with maintenance of regular body weight for all the different treatment regimens. IHC results provided conclusive evidence indicating that combination regimens were able to down-regulate nuclear factor kappa-B activation and reduce the expression of its regulated pro-inflammatory proteins. Reduction of pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IFN-ɣ) levels were observed when using the triple combination, which indicated that the synergistic drug combination was able to significantly control cancer progression. In conclusion, ACA, MIP, and CDDP together serve as promising candidates for further development and for subsequent clinical trials against estrogen-sensitive breast cancer.
    Matched MeSH terms: Mycobacterium/isolation & purification*
  3. Saifullah B, Maitra A, Chrzastek A, Naeemullah B, Fakurazi S, Bhakta S, et al.
    Molecules, 2017 Oct 12;22(10).
    PMID: 29023384 DOI: 10.3390/molecules22101697
    Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human and cattle every year worldwide. More than 50 years after its discovery, ethambutol continues to be an effective part of the World Health Organization's recommended frontline chemotherapy against TB. However, the lengthy treatment regimens consisting of a cocktail of antibiotics affect patient compliance. There is an urgent need to improve the current therapy so as to reduce treatment duration and dosing frequency. In this study, we have designed a novel anti-TB multifunctional formulation by fabricating graphene oxide with iron oxide magnetite nanoparticles serving as a nano-carrier on to which ethambutol was successfully loaded. The designed nanoformulation was characterised using various analytical techniques. The release of ethambutol from anti-TB multifunctional nanoparticles formulation was found to be sustained over a significantly longer period of time in phosphate buffer saline solution at two physiological pH (7.4 and 4.8). Furthermore, the nano-formulation showed potent anti-tubercular activity while remaining non-toxic to the eukaryotic cells tested. The results of this in vitro evaluation of the newly designed nano-formulation endorse its further development in vivo.
    Matched MeSH terms: Mycobacterium/drug effects
  4. Kar SS, Bhat G V, Rao PP, Shenoy VP, Bairy I, Shenoy GG
    Drug Des Devel Ther, 2016;10:2299-310.
    PMID: 27486307 DOI: 10.2147/DDDT.S104037
    A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 µg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs.
    Matched MeSH terms: Mycobacterium tuberculosis/drug effects*
  5. Bose RJC, Tharmalingam N, Choi Y, Madheswaran T, Paulmurugan R, McCarthy JR, et al.
    Int J Nanomedicine, 2020;15:8437-8449.
    PMID: 33162754 DOI: 10.2147/IJN.S271850
    BACKGROUND: Lipid polymer hybrid nanoparticles (LPHNPs) have been widely investigated in drug and gene delivery as well as in medical imaging. A knowledge of lipid-based surface engineering and its effects on how the physicochemical properties of LPHNPs affect the cell-nanoparticle interactions, and consequently how it influences the cytological response, is in high demand.

    METHODS: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages.

    RESULTS: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls.

    CONCLUSION: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.

    Matched MeSH terms: Mycobacterium smegmatis/drug effects
  6. Verma R, Boshoff HIM, Arora K, Bairy I, Tiwari M, Varadaraj BG, et al.
    Drug Dev Res, 2020 May;81(3):315-328.
    PMID: 31782209 DOI: 10.1002/ddr.21623
    A new series of novel triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20-40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20-40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion) properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the protein-ligand complex and the protein-ligand interaction in detail.
    Matched MeSH terms: Mycobacterium tuberculosis/drug effects*
  7. Mahyudin M, Choo MM, Ramli NM, Omar SS
    Case Rep Ophthalmol, 2010 Aug 02;1(1):30-35.
    PMID: 21116342
    A 23-year-old man presented with central retinal vein occlusion. The retinal haemorrhages worsened and signs of retinal vasculitis appeared later as vision dropped from 6/60 to Counting Fingers. No signs of systemic disease were observed. Routine Mantoux test and chest radiograph were negative for tuberculosis. Fundus flourescein angiogram confirmed presence of retinal vasculitis. Both systemic and topical corticosteroid therapy were ineffective. Polymerase chain reaction analysis of vitreous fluid showed presence of Mycobacterium tuberculosis. A full 6-month course of antituberculosis therapy was given and inflammation subsided. Vision improved to 3/60. This is a rare case of ocular tuberculosis without evidence of systemic infection, presenting first as a central retinal vein occlusion.
    Matched MeSH terms: Mycobacterium tuberculosis
  8. Subramaniam M, In LL, Kumar A, Ahmed N, Nagoor NH
    Sci Rep, 2016;6:19833.
    PMID: 26817684 DOI: 10.1038/srep19833
    Mycobacterium indicus pranii (MIP) is a non-pathogenic mycobacterium, which has been tested on several cancer types like lung and bladder where tumour regression and complete recovery was observed. In discovering the potential cytotoxic elements, a preliminary test was carried out using four different fractions consisting of live bacteria, culture supernatant, heat killed bacteria and heat killed culture supernatant of MIP against two human cancer cells A549 and CaSki by 3-(4,5-dimethyl thiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis was investigated in MCF-7 and ORL-115 cancer cells by poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation assays. Among four MIP fractions, only heat killed MIP fraction (HKB) showed significant cytotoxicity in various cancer cells with inhibitory concentration, IC50 in the range 5.6-35.0 μl/(1.0 × 10(6) MIP cells/ml), while cytotoxicity effects were not observed in the remaining fractions. HKB did not show cytotoxic effects on non-cancerous cells contrary to cancerous cells, suggesting its safe usage and ability to differentially recognize between these cells. Evaluation on PARP assay further suggested that cytotoxicity in cancer cells were potentially induced via caspase-mediated apoptosis. The cytotoxic and apoptotic effects of MIP HKB have indicated that this fraction can be a good candidate to further identify effective anti-cancer agents.
    Matched MeSH terms: Mycobacterium
  9. Yakubu Y, Ong BL, Zakaria Z, Hassan L, Mutalib AR, Ngeow YF, et al.
    Prev Vet Med, 2016 Mar 1;125:147-53.
    PMID: 26775804 DOI: 10.1016/j.prevetmed.2016.01.008
    Elephant tuberculosis (TB) caused by Mycobacterium tuberculosis is an important re-emerging zoonosis with considerable conservation and public health risk. We conducted prospective cohort and cross-sectional studies in elephants and wildlife staff respectively in order to identify potential risk factors associated with TB in captive Asian elephants and their handlers in Peninsular Malaysia. Sixty elephants in six different facilities were screened for TB longitudinally using the ElephantTB STAT-PAK and DPP VetTB assays from February 2012 to May 2014, and 149 wildlife staff were examined for tuberculosis infection using the QuantiFERON-TB Gold In-tube (QFT) assay from January to April, 2012. Information on potential risk factors associated with infection in both elephants and staff were collected using questionnaires and facility records. The overall seroprevalence of TB amongst the elephants was 23.3% (95% CI: 13.8-36.3) and the risk of seroconversion was significantly higher among elephants with assigned mahouts [p=0.022, OR=4.9 (95% CI: 1.3-18.2)]. The percentage of QFT responders among wildlife staff was 24.8% (95% CI: 18.3-32.7) and the risk of infection was observed to be significantly associated with being a zoo employee [p=0.018, OR=2.7 (95% CI: 1.2-6.3)] or elephant handler [p=0.035, OR=4.1 (95% CI: 1.1-15.5)]. These findings revealed a potential risk of TB infection in captive elephants and handlers in Malaysia, and emphasize the need for TB screening of newly acquired elephants, isolating sero-positive elephants and performing further diagnostic tests to determine their infection status, and screening elephant handlers for TB, pre- and post-employment.
    Matched MeSH terms: Mycobacterium tuberculosis
  10. Sharma JN, Srivastava KC, Gan EK
    Pharmacology, 1994 Nov;49(5):314-8.
    PMID: 7862743
    This study examined the effect of eugenol and ginger oil on severe chronic adjuvant arthritis in rats. Severe arthritis was induced in the right knee and right paw of male Sprague-Dawley rats by injecting 0.05 ml of a fine suspension of dead Mycobacterium tuberculosis bacilli in liquid paraffin (5 mg/ml). Eugenol (33 mg/kg) and ginger oil (33 mg/kg), given orally for 26 days, caused a significant suppression of both paw and joint swelling. These findings suggest that eugenol and ginger oil have potent antiinflammatory and/or antirheumatic properties.
    Matched MeSH terms: Mycobacterium tuberculosis
  11. Meryl Grace Lansing, Malehah Mohd Noh, Mohd Hakimi Nordin
    MyJurnal
    Introduction: Tuberculosis (TB) of the elbow joint is uncommon. Prompt diagnosis and treatment are important to prevent joint destruction and preserve function. We present a case of TB synovitis of the elbow joint in a patient with active rheumatoid arthritis (RA). Case description: A 56-year-old woman with a known seropositive RA on metho-trexate and Leflunomide was seen in the outpatient rheumatology clinic as part of her monthly follow-up. She com-plained of persistent bilateral elbow pain and swelling, despite optimisation of her disease-modifying antirheumatic drugs (DMARD) and steroid therapy. The suspicion for another diagnosis for her elbow symptoms stems from the persistent pain and swelling amidst increased titration of methotrexate and prednisolone dosages. Ultrasound scan of her elbows revealed bilateral complex olecranon bursitis with active synovitis. The left elbow aspiration yielded cloudy yellowish synovial fluid and the sample was sent for fluid culture, acid-fast bacilli (AFB) stain, and GeneXpert. No AFB was seen but the GeneXpert test confirmed the presence of Mycobacterium Tuberculosis. Thus, a diagnosis of TB synovitis of the left elbow was made, and she was promptly started on anti-tubercular therapy (ATT) consisting of Rifampicin, Isoniazid, Ethambutol and Pyrazinamide with the aim to complete 9 months of ATT. Conclusion: The diagnosis of tuberculous synovitis is challenging. In the absence of constitutional or respiratory symptoms, joint TB is usually low on the initial differential diagnosis in patients presenting with joint pain and swelling. The diagnosis is made even more difficult in patients with concomitant rheumatoid arthritis. This case demonstrates the importance of a high index of suspicion for TB, particularly when evaluating patients in high TB prevalence area with an underlying immunosuppressive state.
    Matched MeSH terms: Mycobacterium tuberculosis
  12. Hikmawati D, Maulida HN, Putra AP, Budiatin AS, Syahrom A
    Int J Biomater, 2019;2019:7179243.
    PMID: 31341479 DOI: 10.1155/2019/7179243
    The most effective treatment for spinal tuberculosis was by eliminating the tuberculosis bacteria and replacing the infected bone with the bone graft to induce the healing process. This study aims to synthesize and characterize nanohydroxyapatite-gelatin-based injectable bone substitute (IBS) with addition of streptomycin. The IBS was synthesized by mixing nanohydroxyapatite and 20 w/v% gelatin with ratio of 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, and 75:25 ratio and streptomycin addition as antibiotic agent. The mixture was added by hydroxypropyl methylcellulose as suspending agent. FTIR test showed that there was a chemical reaction occurring in the mixture, between the gelatin and streptomycin. The result of injectability test showed that the highest injectability of the IBS sample was 98.64% with the setting time between 30 minutes and four hours after injection on the HA scaffold that represents the bone cavity and coat the pore scaffold. The cytotoxicity test result showed that the IBS samples were nontoxic towards BHK-21 fibroblast cells and human hepatocyte cells since the viability cell was more than 50% with significant difference (p-value<0.05). The acidity of the IBS was stable and it was sensitive towards Staphylococcus aureus with significantly difference (p-value<0.05). The streptomycin release test showed that the streptomycin could be released from the IBS-injected bone scaffold with release of 2.5% after 4 hours. All the results mentioned showed that IBS was suitable as a candidate to be used in spinal tuberculosis case.
    Matched MeSH terms: Mycobacterium tuberculosis
  13. Yeap KC, Sivagurunathan PD, Raman P, Khalid KHM
    GMS Ophthalmol Cases, 2019;9:Doc25.
    PMID: 31355123 DOI: 10.3205/oc000114
    Purpose: To report a rare case of non-tuberculous mycobacterial (NTM) choroiditis masquerading as choroidal tumour, where the initial diagnosis was masked by keratitis. Casedescription: A 57-year-old heroin chaser with a pre-existing left eye blindness due to past blunt trauma presented with diffuse bacterial keratitis on the same side. Systemic examination revealed multiple non-tender cervical lymphadenopathies. B-scan ultrasonography showed a hyperechoic choroidal mass with surrounding exudative retinal detachment, resembling a choroidal tumour. However, computed tomography (CT) and magnetic resonance imaging (MRI) scan findings were suggestive of inflammatory choroidal changes. Inflammatory markers were significantly raised and infective screening was positive for HIV and Hepatitis C. Tuberculosis workup was normal. In view of intractable pain, evisceration was done and his vitreous humour was sent for polymerase chain reaction (PCR). It was reported to be positive for Mycobacterium Fortuitum. Conclusion: NTM ocular infections are rare, challenging to diagnose, and potentially sight threatening. Early recognition and prompt treatment is life and vision saving.
    Matched MeSH terms: Mycobacterium fortuitum
  14. Teo SP, Bhakta S, Stapleton P, Gibbons S
    Antibiotics (Basel), 2020 Dec 16;9(12).
    PMID: 33339285 DOI: 10.3390/antibiotics9120913
    The present study aimed to screen plants for bioactive compounds with potential antibacterial activities. In our efforts to evaluate plants from Borneo, we isolated and elucidated the structures of four natural products from the bioactive fraction of a chloroform extract of Goniothalamus longistipetes using various chromatographic and spectroscopic techniques. The bioactive compounds were identified as a known styryllactone, (+)-altholactone ((2S,3R,3aS,7aS)-3-hydroxy-2-phenyl-2,3,3a,7a-tetrahydrobenzo-5(4H)-5-one) (1), a new styryllactone, (2S,3R,3aS,7aS)-3-hydroxy-2-phenyl-2,3,3a,7a-tetrahydrobenzo-5(4H)-5-one) (2) as well as a new alkaloid, 2,6-dimethoxyisonicotinaldehyde (3) and a new alkenyl-5-hydroxyl-phenyl benzoic acid (4). 1 and 4 showed broad-spectrum anti-bacterial activities against Gram-positive and Gram-negative bacteria as well as acid-fast model selected for this study. Compound 2 only demonstrated activities against Gram-positive bacteria whilst 3 displayed selective inhibitory activities against Gram-positive bacterial strains. Additionally, their mechanisms of anti-bacterial action were also investigated. Using Mycobacterium smegmatis as a fast-growing model of tubercle bacilli, compounds 1, 2 and 4 demonstrated inhibitory activities against whole-cell drug efflux and biofilm formation; two key intrinsic mechanisms of antibiotic resistance. Interestingly, the amphiphilic compound 4 exhibited inhibitory activity against the conjugation of plasmid pKM101 in Escherichia coli using a plate conjugation assay. Plasmid conjugation is a mechanism by which Gram-positive and Gram-negative-bacteria acquire drug resistance and virulence. These results indicated that bioactive compounds isolated from Goniothalamus longistipetes can be potential candidates as 'hits' for further optimisation.
    Matched MeSH terms: Mycobacterium smegmatis
  15. Burud I, Ikram MA, Tata MD, Jaafar J
    Pan Afr Med J, 2020;36:16.
    PMID: 32774593 DOI: 10.11604/pamj.2020.36.16.20697
    Bone and joint tuberculosis is a serious medical problem; tuberculosis of sternoclavicular joint is rare. We present a case of a healthy 37-year old man with sternoclavicular joint tuberculosis. The subject presented with a three weeks history of left sternoclavicular joint painless swelling without fever or weight loss. He had no previous history of pulmonary tuberculosis. Laboratory testing revealed erythrocyte sedimentation rate of 70 mm/hour, C-reactive protein of 30 mg/liter and a normal leucocyte count. Biopsy of the lesion showed caseous necrosis and pus culture revealed Mycobacterium tuberculosis. He was treated with joint debridement and anti-tuberculous medications. Tuberculosis resolved completely but post-infection patients had residual joint arthritis. Tuberculosis may infect unusual joints such as the sternoclavicular joint.
    Matched MeSH terms: Mycobacterium tuberculosis
  16. Kabir S, Parash MTH, Emran NA, Hossain ABMT, Shimmi SC
    PLoS One, 2021;16(5):e0251858.
    PMID: 34015016 DOI: 10.1371/journal.pone.0251858
    The incidence of pulmonary tuberculosis (PTB) can be reduced by preventing transmission with rapid and precise case detection and early treatment. The Gene-Xpert MTB/RIF assay is a useful tool for detecting Mycobacterium tuberculosis (MTB) with rifampicin resistance within approximately two hours by using a nucleic acid amplification technique. This study was designed to reduce the underdiagnosis of smear-negative pulmonary TB and to assess the clinical and radiological characteristics of PTB patients. This cross-sectional study included 235 participants who went to the Luyang primary health care clinic from September 2016 to June 2017. The demographic data were analyzed to investigate the association of patient gender, age group, and ethnicity by chi-square test. To assess the efficacy of the diagnostic test, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. The area under the curve for sputum for both AFB and gene-Xpert was analyzed to compare their accuracy in diagnosing TB. In this study, TB was more common in males than in females. The majority (50.71%) of the cases belonged to the 25-44-year-old age group and the Bajau ethnicity (57.74%). Out of 50 pulmonary TB cases (smear-positive with AFB staining), 49 samples were positive according to the Gene-Xpert MTB/RIF assay and was confirmed by MTB culture. However, out of 185 smear-negative presumptive cases, 21 cases were positive by Gene-Xpert MTB/RIF assay in that a sample showed drug resistance, and these results were confirmed by MTB culture, showing resistance to isoniazid. In comparison to sputum for AFB, Gene-Xpert showed more sensitivity and specificity with almost complete accuracy. The additional 21 PTB cases detection from the presumptive cases by GeneXpert had significant impact compared to initial observation by the routine tests which overcame the diagnostic challenges and ambiguities.
    Matched MeSH terms: Mycobacterium tuberculosis
  17. Nik Zuraina NMN, Goni MD, Amalina KN, Hasan H, Mohamad S, Suraiya S
    Diagnostics (Basel), 2021 Apr 22;11(5).
    PMID: 33922299 DOI: 10.3390/diagnostics11050753
    A thermostabilized, multiplex polymerase chain reaction (mPCR) assay was developed in this study for the detection of six respiratory bacterial pathogens. Specific primers were designed for an internal amplification control (IAC) and six target sequences from Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Haemophilus influenzae. The resultant seven-band positive amplification control (PAC) of this heptaplex PCR assay corresponded to 105 base pairs (bp) of IAC, 202 bp of K. pneumoniae, 293 bp of S. aureus, 349 bp of S. pneumoniae, 444 bp of P. aeruginosa, 505 bp of M. tuberculosis, and 582 bp of H. influenzae. Results found that 6% (w/v) of the stabilizer was optimum to preserve the functional conformation of Taq DNA polymerase enzyme. This assay was stable at ambient temperature for at least 6 months. The sensitivity and specificity of this assay were both 100% when testing on the intended target organisms (n = 119) and non-intended species (n = 57). The mPCR assay developed in this study enabled accurate, rapid, and simple detection of six respiratory bacteria.
    Matched MeSH terms: Mycobacterium tuberculosis
  18. Ravichandran R, Ridzwan NFW, Mohamad SB
    J Biomol Struct Dyn, 2020 Dec 31.
    PMID: 33382017 DOI: 10.1080/07391102.2020.1867641
    The disease Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis (Mtb). The bacterial cell-wall consists of peptidoglycan layer maintains the cellular integrity and cell viability. The main problem resides in the cell cycle of Mycobacterium tuberculosis in its quiescent form which is not targeted by any drugs hence there is an immediate need for new antibiotics to target the cell wall. The current study deals with the dTDP-4-dehydrorahmnose reductase (RmlD) which is the final enzyme in the series of cell-wall proteins of Mtb. The RmlD is a part of Carbohydrate biosynthesis has been considered as a good drug target for the novel class of antibiotics. Our study begins with the protein structure prediction, Homology studies were conducted using the Phyre2 web server. The structure is then refined and subjected to molecular dynamics simulations for 50 ns using GROMACS. The clustering analysis has been carried out and generated 41 clusters with 2 Å as the cut-off. Blind docking virtual screening was performed against RmlD protein using the Super Natural-II database with AutoDock4.0. its results helped to screen top ligands based on best binding energies. In both dockings, there are some common residues in which the ligands are interacting and forming the Hydrogen bonds such as Asp-105, Val-158, Thr-160, Gly-161, Arg-224, Arg-256. The ligand-567 giving the best results by being in the top-3 of all the clusters in both blind docking as well as the active-site docking. Hence ligand-567 can be a potential inhibitor of RmlD which can further inhibit the cell-wall synthesis of Mycobacterium tuberculosis.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Mycobacterium tuberculosis
  19. Suppian R, Nor NM
    Trop Life Sci Res, 2013 Aug;24(1):9-18.
    PMID: 24575238 MyJurnal
    Heterologous prime-boost immunisation strategies can evoke powerful antibody responses and may be of value in developing an improved malaria vaccine. Herein, we show that an immunisation protocol that primes Balb/c mice with a recombinant Bacille Calmette-Guérin (rBCG) vaccine consisting of a plasmid encoding a synthetic fragment of the ESAT-6 epitope of Mycobacterium tuberculosis, the fragment 2 region II of erythrocyte-binding antigen (F2RIIEBA) and the three repeat sequences of the circumsporozoite protein (NANP)3 of Plasmodium falciparum before subsequently boosting the mice with either two doses of the rBCG clone or with a DNA vaccine expressing the native form of F2RIIEBA generating higher serum anti-F2RIIEBA antibody levels than an immunisation protocol that calls for a homologous prime-boost with two doses of rBCG. These results demonstrate the potential of DNA vaccination in boosting the antibody response to a recombinant vaccine expressing multiple epitopes.
    Matched MeSH terms: Mycobacterium tuberculosis
  20. Mariana, D., Quah, B.S., Mazidah, A.R.
    MyJurnal
    Even though vaccines are effective for prevention of diseases, compliance with recommended schedules of immunisation in early childhood is not always complete. Identification of potential risk factors associated with under-immunisation may help increase vaccination uptake. The objectives of this study were to determine the prevalence and risk factors of under-immunisation in hospitalised preschool children in Universiti Sains Malaysia Hospital (HUSM). Children aged 1 month to 2 years admitted between December 1998 and December 2000 in medical paediatric wards at HUSM were studied. Parents/guardians were interviewed during admission regarding immunisation status and potential risk factors. Children who did not have home-based cards during admission were excluded. Among 401 children, 37.9% had complete immunisation, 43.4% had delayed immunisation and 34.9% had incomplete immunisation. The uptake of BCG, DPT/OPV 1, DPT/OPV2, Hepatitis B3, DPT/OPV3, and measles were 98.5%, 90.7%, 83.2%, 81.4%,79.2% and 72.9% respectively. Vaccines scheduled to be given at later ages were significantly less likely to be taken (p=0.002) compared with vaccines scheduled to be given at an earlier age. Significant independent risk factors for under-immunisation were elderly mothers (3 40 years old) (OR 3.0, 95% CI: 1.2-8.0), low birth weight £2.0 kg (OR 6.2; 95% CI: 1.8-21.4) and presence of chronic illness in the child (OR 4.5; 95% CI: 2.5-7.9). In children whose father's education was low (primary school or no education), low maternal education was significantly associated with lower rate of under-immunisation (p = 0.005, OR 0.11 95%CI 0.02-0.51).
    In conclusion this study showed that a large proportion of hospitalised preschool children were under-immunised, and vaccines scheduled to be given at a later age had lower uptakes. The situation can be rectified if every opportunity is taken to immunise all children, who have lapsed in their immunisation schedule.
    Matched MeSH terms: Mycobacterium bovis
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