National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR

Āgra, India

National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR

Āgra, India
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Lone M.Y.,Central University of Gujarat | Athar M.,Central University of Gujarat | Gupta V.K.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Jha P.C.,Central University of Gujarat
Biochemical and Biophysical Research Communications | Year: 2017

Enormous efforts have been endeavored to develop inhibitors against the potential therapeutic target, mycobacterium tuberculosis 3-dehydroquinate dehydratase (MtbDHQase) to combat resistance. Over a dozen of small molecules have been crystallized to characterize the structural basis of the inhibition. However, the studies accomplished so far, have not incorporated all the essential interactions of these complexes simultaneously, to identify the novel inhibitors. Therefore, an attempt was made to construct the pharmacophore models and identify the essential features that can be employed to prioritize the molecules against this target. Based on validation and expertise, we have identified such complimentary features from the natural compounds that can be used as initial hits. Subsequently, these hits were tested for their inhibitory roles in reducing the mycobacterium tuberculosis (Mtb) culture growth. Moreover, the docking simulations were performed to seek the possible interactions accountable for the activity of these candidates against MtbDHQase. © 2017 Elsevier Inc.


Saraogi G.K.,Dr Hari Singh Gour University | Sharma B.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Joshi B.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Gupta P.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | And 3 more authors.
Journal of Drug Targeting | Year: 2011

The mannosylated gelatin nanoparticles (Mn-GNPs) were prepared for the selective delivery of an antitubercular drug, isoniazid (INH), to the alveolar macrophages. The gelatin nanoparticles (GNPs) were prepared by using a two-step desolvation method and efficiently conjugated with mannose. Various parameters such as particle size, polydispersity index, zeta potential, % entrapment efficiency, in vitro drug release, macrophage uptake, in vivo biodistribution, antitubercular activity and hepatotoxicity of plain and Mn-GNPs were determined. The size of nanoparticles (both plain and Mn-GNPs) was found to be in range of 260-380nm, and maximum drug payload was found to be 40-55%. Average particle size of Mn-GNPs was more, whereas drug entrapment was lesser compared to plain GNPs. The organ distribution studies demonstrated the efficiency of Mn-GNPs for spatial delivery of INH to alveolar tissues. Intravenous administration of INH loaded Mn-GNPs (I-Mn-GNPs) resulted in significant reduction in bacterial counts in the lungs and spleen of tuberculosis-infected (TB-infected) mice and also reduction in the hepatotoxicity of the drug. This study revealed that mannose conjugated GNPs may be explored as potential carrier for safer and efficient management of TB through targeted delivery of INH when compared to plain GNPs and free drug. © 2011 Informa UK, Ltd.


Saraogi G.K.,Dr Hari Singh Gour University | Gupta P.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Gupta U.D.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Jain N.K.,Dr Hari Singh Gour University | Agrawal G.P.,Dr Hari Singh Gour University
International Journal of Pharmaceutics | Year: 2010

The aim of the research work was to develop and characterize rifampicin (RIF) loaded gelatin nanoparticulate delivery system for the effective management of tuberculosis. Gelatin nanoparticles (GPs) containing RIF were prepared using two-step desolvation method. Formulations were characterized through transmission electron microscopy (TEM), atomic force microscopy (AFM), size and size distribution analysis, polydispersity index (PDI), zeta potential, percent drug entrapment, percent nanoparticulate yield and in vitro drug release. Formulations were further characterized for in vitro cytotoxicity, in vivo biodistribution, and antitubercular activity. The nanoparticles were found to be spherical in shape. The size of nanoparticles was found to be 264 ± 11.2 nm with low PDI suggesting the narrow particle size distribution. The drug release showed the biphasic pattern of release i.e. initial burst followed by a sustained release pattern. The cytotoxicity studies revealed that nanoparticles are safe, non toxic as compared to free drug. In vivo biodistribution study showed higher localization of RIF loaded GPs in various organs, as compared to plain RIF solution in PBS (pH 7.4). In contrast to free drug, the nanoparticles not only sustained the plasma level but also enhanced the AUC and mean residence time (MRT) of the drug, suggesting improved pharmacokinetics of drug. RIF GPs additionally resulted in significant reduction in bacterial counts in the lungs and spleen of TB-infected mice. Hence, GPs hold promising potential for increasing drug targetability vis a vis reducing dosing frequency with the interception of minimal side effects, for efficient management of tuberculosis. © 2009 Elsevier B.V. All rights reserved.


Verma J.S.,Safdarjung Hospital | Gupta Y.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Nair D.,Safdarjung Hospital | Manzoor N.,Jamia Millia Islamia University | And 2 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014

Objectives: To evaluate gidB alterations for possible impact on the cumulative mechanism underlying the acquisition of high-level streptomycin resistance in Mycobacterium tuberculosis. Methods: Fifty-two isolates with high streptomycin resistance and 23 isolates with low streptomycin resistance were sequenced for mutational analysis in the rpsL, rrs and gidB region. As the gidB protein has a complex substrate and no activity assay has yet been formulated, mutants of interest were subjected to in silico modelling and were structurally mapped together with active-site amino acid residues for assessment of the relevance to activity of the mutations found. Results: Eight novel sense mutations and four novel mis-sense mutations in gidB were identified. Findings showed that active-site morphology is not only greatly affected by mutants lying in close proximity to the active-site pocket, but also by other mutations altering secondary-structure motifs and having an overall effect on protein structure. Conclusions:We conclude that gidB mutations address many unanswered questions and explain the whole story behind phenotypic streptomycin-resistant strains exhibiting no mutation in rpsL or rrs. They also validate the hypothesis of sequential progression of resistance from low to high due to the existence of gidB alterations in the genetic background. © The Author 2014.


Yadav R.,Chhatrapati Shahu Ji Maharaj University | Jee B.,Chhatrapati Shahu Ji Maharaj University | Jee B.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Awasthi S.K.,Chhatrapati Shahu Ji Maharaj University
Indian Journal of Clinical Biochemistry | Year: 2015

Curcumin is a major bioactive compound of turmeric that exerts its anti-inflammatory effects by suppressing the many pro-inflammatory cytokines and chemokines in a number of cell types and pathologic conditions. Interleukin-18 (IL-18) is a novel pro-inflammatory cytokine which plays an important role not only in generating Th1 responses but also in inducing severe inflammatory reactions. As curcumin induced inhibition of IL-18 production in keratinocytes and mice is well known, effect of curcumin on IL-18 release in macrophages remains unknown. Hence, this present study has been designed to evaluate the effect of curcumin on IL-18 production and necrotic cell death in murine macrophages-like cells treated with or without lipopolysaccharide (LPS). The IL-18 secretion in cell culture supernatants was assayed by enzyme-linked immunosorbent assay and cytotoxicity was determined by lactate dehydrogenase release assay. Our results demonstrate that curcumin significantly inhibited the production of pro-inflammatory cytokine IL-18 in E.coli LPS stimulated murine macrophage-like cells RAW264.7 in a concentration-dependent manner. Interestingly, curcumin had no cytotoxic effect on murine macrophage-like cells. Our findings suggest that curcumin may be used as a potential therapeutic agent for the treatment of inflammatory diseases. © 2014, Association of Clinical Biochemists of India.


Girdhar A.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Kumar A.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Girdhar B.K.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR
Leprosy Review | Year: 2011

Aim: To assess if there is any additional short and long term effect of adding larithromycin to rifampicin, ofloxacin and minocycline (ROM), the combination here after called C-ROM, in treating single lesion PB leprosy detected in the field. Methods: 300 patients, detected on active search in Agra district, who had single lesion leprosy but no nerve thickening, were randomly allocated (using random number table) to two treatment groups, 151 to ROM and 149 to C-ROM. All the patients were given single dose of ROM or C-ROM and followed up every 6 months for disease status, cure rate, reaction and relapse. Survival analysis was used to compare relapse rate. Results: The cure rate at 2 years was 93·1% in ROM and 91·4% in C-ROM group. By this time three relapses had occurred in the ROM group while two patients were found to have relapsed in the C-ROM group. Thus, there was no statistical difference in relapse rates (2·1% vs. 1·41%, P=0·287) in the two groups. Long term observations over 3-5 years revealed nine relapses (five in ROM, four in C-ROM) giving relapse rate of 1·05/100 Person years in ROM and 0·90/100 person years in C-ROM group - again no significant difference was observed (P=0·87). Conclusion: The study shows that addition of clarithromycin to ROM does not significantly improve the efficacy as measured in terms of cure rates and relapse rates in single skin lesion leprosy patients. © Lepra.


Hussain T.,National JALMA Institute For Leprosy and Other Mycobacterial Diseases ICMR
Journal of Clinical and Diagnostic Research | Year: 2014

This is a case report of spinal tuberculosis which could not be diagnosed in the early stages. Individuals who work in hospital settings and suffer from psychological stress need to be aware of the various hospital acquired infections and consequences of late diagnoses. A CT scan is indicated to rule out the spinal involvement, at the beginning of a severe backache, which does not respond to painkillers, rest, and if X-ray is normal. It is of immense help and much of the problems like paraplegia and morbidity which are associated with this kind of extra - pulmonary tuberculosis, could be avoided. Once paraplegia sets in, the response to treatment as well as the recovery are slow. The cost of CT Scan or MRI (Magnetic Resonance Imaging), no doubt, is very high, which ranges from Rs.4,500/- to Rs.5,000/- for an average Indian, but which goes a long way in reducing the debilitating conditions, excruciating pain and confinement to bed which occur during the spinal tuberculosis. Prolonged follow-up is essential in cases of Pott's disease, as it was in the presented case. A strict treatment schedule of 18 months, combined with good nutritional support and bed rest, with spinal braces, is adequate for recovery from immobility and paraplegia caused by an advanced stage of spinal infection. This case therefore, supports an approach of nonoperative treatment over surgery, where the patient had progressive paralysis.


Kumar A.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Girdhar A.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Kumar Girdhar B.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR
BMJ Open | Year: 2012

Objectives: If leprosy is a public health problem, it is due to the disabilities it causes. Surprisingly little is known about the risk of disabilities. Even now, mainly cross-sectional studies report disability prevalence. The present study aims to report the risk of disability in pre and post-WHO multidrug therapy (MDT) in multibacillary leprosy patients and to assess the extent of the incidence of disability. Methods: The study design is prospective and the setting is an institutional field area. Patients were detected during 2001-6 field surveys. Of the 289 multibacillary patients, 146 completed the study. Both sexes were involved. The primary outcome planned was to study cure of disease, relapses and disability in patients receiving MDT. The secondary outcome was to measure reaction and default. Assessment was done clinically. Data have been analysed using SPSS software, logistic, survival analysis was performed and the χ 2 test of significance was used. Results: An important risk factor was found to be three or more nerves involved with odds of 3.73 (1.24-11.2), and delay in treatment; 2.27 (1.04-4.96) at the pre-MDT stage and three or more nerves involved with odds of 2.81 (1.0-7.9) at the post-MDT stage. The incidence of disability was found to be 2.74/ 100 person-years; 2.69 in the MDT arm and 2.84 in defaulters, with slightly higher disability among early defaulters (3.08) than among late defaulters (2.30). The study suggests that the incidence of disability could be slightly higher if treatment is not completed. Conclusion: Early treatment for leprosy is a must for reducing the risk of disability, and treatment delay would increase the risk of disability. It is important to note that the incidence of disability between defaulters and those completing treatment was not found to be significantly different.


Kumar A.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Girdhar A.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR | Girdhar B.K.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR
Indian Journal of Medical Research | Year: 2013

Background & objectives: The reported low relapse rates after 24 months multidrug therapy (MDT) for multibacillary leprosy (MB) led to the recommendation of reducing duration of therapy to 12 months. However, only a few reports exist on long term follow up data after 12 months fxed duration therapy (FDT). The present study was done to assess the incidence of relapse in MB leprosy patients after 12 months treatment. Methods: The leprosy patients detected in feld surveys during 2001-2006 in Agra district, Uttar Pradesh, India, were put on WHO-MDT and followed up for treatment completion, relapse, reactions and development of disability. The assessment was done clinically by following up the patients until January 2011. Data collected were analyzed for risk and survival analysis. Results: The incidence of relapse was found to be 1.97/100 person years of follow up. The incidence of relapse by age (34 yr vs >34 yr), sex (male vs female), delay in detection (<36 months vs >36 months) and smear status (smear +ve vs -ve) was not found to be signifcantly different but patients with no nerve involvement were observed to have signifcantly higher relapses than those with three or more nerve involvement (P<0.05). Similarly, borderline-borderline and BB with reaction (BB/BBR) patients were observed to have signifcantly high relapses than among those with borderline tuberculoid or BT with reaction (BT/BTR) or borderline lipromatous/lepromatous/neuritic (BL/LL/N) type of leprosy (P<0.01). Interpretation & conclusion: From the observations in the study, it can be suggested that relapses occur in 12 months FDT and almost as much as reported in 24 months FDT for MB leprosy. Although, early relapses may be due to insuffcient treatment, late relapses may be due to persistent dormant mycobacteria. However, a study relating to immunological response of treatment and change in immunological profile relating to the occurrence of relapses and its clinical correlates may suggest better information on causes of relapses.


Husain S.,National JALMA Institute for Leprosy and Other Mycobacterial Diseases ICMR
Indian Journal of Leprosy | Year: 2011

History of prevention of deformities is practically as old as the appearance of the deformities themselves, unfortunately without much understanding to start with. In medieval era and even earlier, leprosy and deformities were treated synonymously and the disease's infectivity too was closely associated with appearance of deformities. Menee, to reduce chances of deformities caused by leprosy in healthy population, the patients having deformities were driven away from the society presuming that only deformed patients spread the disease. Unfortunately, it never worked. However, in later period, factors behind the deformities and disabilities were recognized and understood. These are basically limited to involvement of peripheral nerves and their proper management (medical treatment, surgical interventions, physiotherapy, ergonomics and counseling) by one rule of thumb i.e. early, timely and adequately. © Hind Kusht Nivaran Sangh, New Delhi.

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