Defense Research and Development Establishment

Gwalior, India

Defense Research and Development Establishment

Gwalior, India
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Chaudhary H.S.,Madhav Institute of Technology and Science | Yadav J.,Madhav Institute of Technology and Science | Shrivastava A.R.,Madhav Institute of Technology and Science | Singh S.,Madhav Institute of Technology and Science | And 2 more authors.
Journal of Advanced Pharmaceutical Technology and Research | Year: 2013

The main objective of the present study was isolation, purification, and characterization of actinomycetes from soil samples, having antimicrobial activity against 12 selected pathogenic strains. Soils samples were taken from different niche habitats of Sheopur district, Madhya Pradesh, India. These samples were serially diluted and plated on actinomycete isolation agar media. Potential colonies were screened, purified, and stored in glycerol stock. Isolates were morphologically and biochemically characterized. These isolates were subjected to extraction for production of the antibacterial compound. Antibacterial activity and Minimum Inhibitory Concentration (MIC) of the purified extract of isolates were evaluated. Totally 31 actinomycete isolates were tested for antagonistic activity against 12 pathogenic microorganisms. Isolates AS14, AS27, and AS28 were highly active, while AS1 showed less activity against the pathogenic microorganisms. Isolate AS7 exhibited the highest antagonistic activity against Bacillus cereus (24 mm) and AS16 showed the highest activity against Enterococcus faecalis (21 mm). MIC was also determined for actinomycete isolates against all the tested microorganisms. MIC of actinomycete isolates was found to be 2.5 mg/ml against Shigella dysenteriae, Vancomycin-resistant enterococci, and Klebsiella pneumoniae, and was 1.25 mg/ml for Staphylococcus saprophyticus, Streptococcus pyogenes, Staphylococcus epidermidis, Methicillin-resistant Staphylococcus, Bacillus cereus, Staphylococcus xylosus, Methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, and Staphylococcus aureus. All actinomycetes isolates showed antibacterial activity against S. aureus, while they showed less activity against S. dysenteriae. These isolates had antibacterial activity and could be used in the development of new antibiotics for pharmaceutical or agricultural purposes.

Yadav A.,Defense Research and Development Establishment | Lomash V.,Defense Research and Development Establishment | Samim M.,Jamia Hamdard University | Flora S.J.S.,Defense Research and Development Establishment
Chemico-Biological Interactions | Year: 2012

Water-soluble nanoparticles of curcumin were synthesized, characterized and applied as a stable detoxifying agent for arsenic poisoning. Chitosan nanoparticles of less than 50 nm in diameter containing curcumin were prepared. The particles were characterized by TEM, DLS and FT-IR. The therapeutic efficacy of the encapsulated curcumin nanoparticles (ECNPs) against arsenic-induced toxicity in rats was investigated. Sodium arsenite (2 mg/kg) and ECNPs (1.5 or 15 mg/kg) were orally administered to male Wistar rats for 4 weeks to evaluate the therapeutic potential of ECNPs in blood and soft tissues. Arsenic significantly decreased blood δ-aminolevulinic acid dehydratase (δ-ALAD) activity, reduced glutathione (GSH) and increased blood reactive oxygen species (ROS). These changes were accompanied by increases in hepatic total ROS, oxidized glutathione, and thiobarbituric acid-reactive substance levels. By contrast, hepatic GSH, superoxide dismutase and catalase activities significantly decreased on arsenic exposure, indicative of oxidative stress. Brain biogenic amines (dopamine, norepinephrine and 5-hydroxytryptamine) levels also showed significant changes on arsenic exposure. Co-administration of ECNPs provided pronounced beneficial effects on the adverse changes in oxidative stress parameters induced by arsenic. The results indicate that ECNPs have better antioxidant and chelating potential (even at the lower dose of 1.5 mg/kg) compared to free curcumin at 15 mg/kg. The significant neurochemical and immunohistochemical protection afforded by ECNPs indicates their neuroprotective efficacy. The formulation provides a novel therapeutic regime for preventing arsenic toxicity. © 2012 Elsevier Ireland Ltd. All rights reserved.

Lal J.,Jiwaji University | Gupta S.K.,Jiwaji University | Thavaselvam D.,Defense Research and Development Establishment | Agarwal D.D.,Jiwaji University
European Journal of Medicinal Chemistry | Year: 2013

Five series of curcumin derivatives with sulfonamides 3a-3e, 4a-4e, 5a-5e, 6a-6e and 7a-7e have been synthesized and evaluated for in vitro antibacterial activity against selected medically important gram-(+) and gram-(-) bacterial species viz. Staphylococcus aureus, Bacillus cereus, Salmonella typhi, Pseudomonas aeruginosa and Escherichia coli, and antifungal activity against few pathogenic fungal species viz. Aspergillus niger, Aspergillus flavus, Trichoderma viride and Curvularia lunata. The cytotoxicity has been determined by measuring IC50 values against human cell lines HeLa, Hep G-2, QG-56 and HCT-116. Among the compounds screened, 3a-3e showed the most potent biological activity against tested bacteria and fungi. Compounds 3a-3e displayed higher cytotoxicity than curcumin. The curcumin derivatives were also evaluated for in vivo anti-inflammatory activity. In contrast, the compounds 6a-6e and 7a-7e showed dramatically decrease in biological activity. © 2013 Elsevier Inc. All rights reserved.

Lal J.,Jiwaji University | Gupta S.K.,Jiwaji University | Thavaselvam D.,Defense Research and Development Establishment | Agarwal D.D.,Jiwaji University
Bioorganic and Medicinal Chemistry Letters | Year: 2012

3,4-Dihydropyrimidinones of curcumin were synthesized in excellent yield by multi-component one-pot condensation of curcumin, substituted aromatic aldehydes and urea/thiourea under solvent free conditions using SnCl 2·2H 2O catalyst. All the synthesized compounds have been characterized by IR, 1H NMR, 13C NMR, Mass spectra as well as elemental analyses. The synthesized compounds 4a-n were evaluated for their synergistic antimicrobial (antibacterial and antifungal) activity against bacteria and fungi. Zone of inhibition was measured by adopting disc diffusion method. In vitro minimum inhibitory concentrations were measured using broth microdilution and food poisoning method. In addition to this in vitro cytotoxicity of synthesized compounds against three human cancer lines Hep-G2, HCT-116 and QG-56 were also evaluated. Most of the compounds showed interesting antimicrobial and cytotoxic activity as compared to curcumin, that is, the compounds derived from 2-hydroxy benzaldehyde, 4-hydroxy benzaldehyde and 4-hydroxy-3-methoxy benzaldehyde showed the highest biological activity as compared to other compounds. © 2012 Elsevier Ltd. All rights reserved.

Kumar P.,Jawaharlal Nehru University | Mishra D.K.,Jawaharlal Nehru University | Deshmukh D.G.,SVRN Government Medical College | Jain M.,Defense Research and Development Establishment | And 3 more authors.
Clinical Microbiology and Infection | Year: 2014

Vibrio cholerae O1 biotype El Tor producing Haitian variant Cholera Toxin (HCT) and showing reduced susceptibility to ciprofloxacin caused a cholera outbreak associated with a high case fatality rate (4.5) in India. HCT-secreting strains responsible for severe cholera epidemics in Orissa (India), Western Africa and Haiti were associated with increased mortality. There is a pressing need for an integrated multidisciplinary approach to combat further spread of newly emerging variant strains. The therapeutic effect of ciprofloxacin was diminished whereas use of doxycycline in moderate to severe cholera patients was found to be effective in outbreak management. © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Sivakumar R.R.,Aravind Eye Hospital | Prajna L.,Aravind Medical Research Foundation | Arya L.K.,Aravind Medical Research Foundation | Muraly P.,Aravind Eye Hospital | And 3 more authors.
Ophthalmology | Year: 2013

Purpose: To describe the ocular features of West Nile virus (WNV) infection proven by serology and molecular diagnostic techniques. Design: Prospective case series. Participants: Fifty-two patients who presented to the uveitis clinic with ocular inflammatory signs and history of fever preceding ocular symptoms between January 2010 and January 2012 were enrolled for laboratory diagnosis. Serum samples were collected from 30 healthy controls from the same geographic area. Methods: Patients were tested for all endemic infectious diseases that can cause ocular inflammation by serology or molecular diagnostics. When patients had positive antibodies for WNV, serum/plasma samples were tested by real-time reverse transcription (RT) polymerase chain reaction (PCR) and RT loop-mediated isothermal gene amplification assays. The PCR product was subjected to nucleotide sequencing. Fundus fluorescence angiography (FFA), optical coherence tomography (OCT), and indocyanine green angiography were performed. Visual prognosis was analyzed. Main Outcome Measures: Clinical signs (retinitis, neuroretinitis, and choroiditis) and ocular complications (decrease in vision). Results: A total of 37 of 52 patients (71%) showed positive results for at least 2 laboratory tests for WNV. Fundus examination revealed discrete, superficial, white retinitis; arteritis; phlebitis; and retinal hemorrhages with or without macular star. The FFA revealed areas of retinal inflammation with indistinct borders, vascular and optic disc leakage, vessel wall staining, or capillary nonperfusion. Indocyanine green angiography confirmed choroidal inflammation in 1 of the patients who was diabetic. The OCT scan of the macula revealed inner retinal layer edema in active inflammation and retinal atrophy in late stage. At the final visit, 43% of patients had visual acuity better than 6/12. Conclusions: In addition to previously reported clinical signs, retinitis, neuroretinitis, and retinal vasculitis were seen in this population. Atrophy of the inner retinal layer was seen on OCT after resolution of inflammation. Visual prognosis was good in patients with focal retinitis and poor in patients with occlusive vasculitis. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2013 American Academy of Ophthalmology.

Ram Kumar M.,Sri Venkateswara University | Flora S.J.S.,Defense Research and Development Establishment | Reddy G.R.,Sri Venkateswara University
Environmental Toxicology and Pharmacology | Year: 2013

Chronic exposure to arsenic in drinking water is associated with skin lesions, neurological effects, hypertension and high risk of cancer. The treatment in use at present employs administration of thiol chelators, such as meso-2,3-dimercaptosuccinic acid (DMSA) which are compromised with number of limitations due to their lipophobic nature. To address this problem, therapeutic efficacy of monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), an analog of DMSA having lipophilic character, was examined against chronic arsenic poisoning in rats. Adult male Wistar rats were orally exposed to arsenic (2. mg sodium arsenite/kg body weight) for 10 weeks followed by treatment with MiADMSA (50. mg/kg, orally, once daily for 5 consecutive days). As-exposed rats showed significant differences in behavioral functions (open field behavior, total locomotor activity, grip strength and exploratory behavior) and water maze learning. Further, the biochemical studies performed on three brain regions (cerebellum, cortex and hippocampus) also showed significant elevation in malondialdehyde (MDA) levels with a concomitant decrease in the oxidative stress marker enzymes Mn-superoxide dismutase (Mn-SOD), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST). The alterations were more pronounced in cortex compared to cerebellum and hippocampus. The results showed that MiADMSA significantly reversed the As-induced alterations in behavior and biochemical variables suggestive of oxidative injury. © 2013 Elsevier B.V.

Khan M.,Defense Research and Development Establishment | Dhanwani R.,Defense Research and Development Establishment | Rao P.V.L.,Defense Research and Development Establishment | Parida M.,Defense Research and Development Establishment
Virus Research | Year: 2012

The recent resurgence of Chikungunya virus in India and Indian Ocean Islands with unusual clinical severity is a matter of great public health concern. Despite the fact that CHIKV resurgence is associated with epidemic of unprecedented magnitude, none of the vaccine candidate has been approved so far. The envelope protein E1 and E2 being the major immunodominant structural proteins with crucial role in virus attachment and entry, can prove to be potential vaccine candidates. In the present study, the immunogenic potential of bacterially expressed CHIKE1 and CHIKE2 recombinant proteins along with various adjuvants is reported. Assessment of the protective efficacy of both the vaccine formulations was further confirmed by both in vitro and in vivo neutralisation tests. Splenocytes from immunized mice, cultured in vitro when stimulated with the vaccine antigens revealed induction of very high levels of both pro- and anti- inflammatory cytokines indicating a balance of Th1 and Th2 response. © 2012 Elsevier B.V.

Verma S.K.,Defense Research and Development Establishment | Jain S.,Defense Research and Development Establishment | Kumar S.,Defense Research and Development Establishment
World Journal of Microbiology and Biotechnology | Year: 2012

Brucellosis is one of the world's major zoonoses. No vaccine is available for the prevention of brucellosis in human. Efforts are needed to develop an effective, safe, stable, vaccine with long lasting immunity against human brucellosis. Here, we cloned and expressed recombinant dihydrolipoamide succinyltransferase (rE2o) of Brucella abortus in Escherichia coli and purified up to homogeneity by metal affinity chromatography. The purified rE2o is immunoreactive with brucellosis positive cattle sera. The immunogenicity and the protective potential of recombinant dihydrolipoamide succinyltransferase (rE2o) were evaluated in BALB/c mice with two different adjuvants i. e., Freund's and aluminium hydroxide gel. Mice were tested for humoral immune response by ELISA. Cell mediated immune response was tested by lymphocyte proliferation assay and cytokine profiling. The recombinant E2o (rE2o) generated high IgG antibody and its isotypes IgG1, and induced significant production of INF-γ, IL-10 and IL-4 cytokines. The rE2o protein induced significant lymphoproliferation of splenocytes. Altogether, these results suggest that rE2o induces a mixed but a predominant Th2 type of immune response in BALB/c mice and provides partial protection against challenge with pathogenic Brucella abortus. © 2012 Springer Science+Business Media B.V.

Vijayan V.,Defense Research and Development Establishment | Meshram G.P.,Defense Research and Development Establishment
Drug and Chemical Toxicology | Year: 2013

The possible genotoxic potential of NIM-76, a volatile fraction obtained from neem oil, having promising contraceptive activity, as well as its formulation product, called pessary (7.5% NIM-76 in polyethylene glycol), were evaluated in the Ames assay and mouse bone marrow micronucleus (MN) assay. Genotoxicity of NIM-76 (0.1-1000g/plate) and pessary (0.1-10000g/plate) were studied using the liquid preincubation protocol of the Ames assay both in the presence and absence of S9. Likewise, the ability of NIM-76 [1-1000mg/kg body weight (b.w.)] and its formulation product (18.75-300mg/kg b.w.) to induce clastogenic effects were studied in the female mouse bone marrow MN test by using a two-dose intraperitoneal treatment protocol. There was no increase in the number of revertant colonies resulting from NIM-76 or pessary at any of their doses over the respective negative control plates, either in the presence or absence of S9. Similarly, in the MN assay, neither of them showed any clastogenic activity because there was no significant increase in the frequency of micronucleated polychromatic erythrocytes, over the negative control group of animals. The use of this compound in humans is therefore not likely to have mutagenic effects and may be considered as safe with regard to genotoxic potential. © 2013 Informa Healthcare USA, Inc. All rights reserved.

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