Abstracts of the Accepted Research Papers
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The National Academy of Sciences, India 5, Lajpatrai Road, Allahabad – 211002 ABSTRACTS OF THE ACCEPTED RESEARCH PAPERS FOR PRESENTATION In 84th Annual Session to be held At Jai Narayan Vyas University, Jodhpur December 5-6, 2014 1 Oral Presentation SECTION OF BIOLOGICAL SCIENCES 1. Differential proteomics approach to identify putative protective antigens of Mycobacterium tuberculosis presented during early stages of macrophage infection and their evaluation as DNA vaccines Shingar Sharmaa,b , RS Rajmanib , Arun Kumarb, Pawan Sharmab , Ashima Bhaskarb, Amit Singhb , Venkatasamy Manivelb, Anil K Tyagia and Kanury VS Raob aDepartment of Biochemistry, University of Delhi South Campus, New Delhi bImmunology group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi There is an urgent need for an effective vaccine against tuberculosis (TB), as the currently available BCG vaccine has not performed satisfactorily, especially against the adult pulmonary disease. In this study we have employed differential proteomics to obtain a list of antigens as potential vaccine candidates. Bacterial epitopes being presented at early stages on MHC class I and class II molecules of macrophages infected with Mycobacterium tuberculosis (M.tb) were identified using iTRAQ labelling and reverse phase LC-MS/MS. The putative vaccine candidates thus identified were tested as plasmid DNA vaccines in mice to ascertain their protective efficacy against a challenge of aerosolized M.tb, based on the ability of the vaccine candidates to reduce the bacterial load in the lungs of infected mice. We report here that four of the seventeen selected antigens imparted significant protection against the challenge of M.tb. The four shortlisted antigens were further assessed in the more stringent guinea pig model, where too, they demonstrated significant protection. This proof of concept study shows that combining a proteomics approach with the in vivo assessment of vaccine candidates in animal models can be very valuable in identifying new potential candidates to expand the antigenic repertoire for novel vaccines against TB. 2. Lipid profile under vanadium stress in albino rats and its remediation by Eucalyptus tereticornis and Liv.52 Aparna Shukla and Prabhu N. Saxena Toxicology Laboratory, Department of Zoology, School of Life Sciences, Dr. B.R. Ambedkar University, Agra-282002 Metal concentration in environment has serious repercussions which have been recognized globally and are being tackled strategically. One such strategy includes exploration of biomedical activities of different parts of plants. With this aim, the present study was undertaken to see the effects of vanadium (V2O5) on lipid profile in albino rats and the possible role of Eucalyptus tereticornis and Liv.52 as protective agents for ill effects under vanadium stress. Administration of vanadium in acute (1d) and subacute studies (7, 14, 21 & 28 ds) was followed after LD50 determination which was registered as 69.6 mg/kg b.wt. Lipid profile was estimated in terms of serum total lipids, cholesterol, 2 triglycerides and phospholipids in all treatment schedules (vanadium alone, vanadium followed by Eucalyptus tereticornis and vanadium followed by Liv.52). Liver being an important metabolic organ performing vital functions of biotransformation and metabolism get affected which is well observed by alteration in the level of lipid profile. Pretreatment of Eucalyptus tereticornis and Liv.52 separate exhibited better performance for restoration of changed value of lipid profile. This could be possible of various chemical ingredients present in Liv.52 and Eucalyptus tereticornis. 3. Review on spleen and splenomegaly due to long term feeding of Pan Masala (PM) and its Blend-Tobacco (PMT) in mice S.K. Nigam1 and H. Venkatakrishna-Bhatt2 1Indian Council of Medical Research, NIOH, Meghani Nagar, Ahmedabad-380016 2ENVIS-NIOH and Head, Department of Neurobehavioural Toxicology, NIOH, Meghani Nagar, Ahmedabad-380016 Spleen is the largest human lymphatic organ found recently vital because of housing stem cells. Spleen filters the blood and maintains healthy red and white blood cells and platelets. Swiss albino mice in 3 groups (control and experimental I and II) of 60 each were fed staple diet (control) composed with 2$ pan masala plain (PMP) and its blend (PM-tobacco) were examined by post- mortem at intervals of 16, 56 and 70 weeks observing spleen volume, whether palpable, contour, texture and bleeding points. The PMP and PMT on chronic exposure damages spleen within three weeks shows enlargement of spleen, thus starts dysfunction even its association with other organs exhibiting lung, gastric and hepatic problems resulting in injury due to itching and nasal, corneal, oral bleeding, aphagia non-responsiveness due to defective immune system and in 3 months even abscess and in certain rupture and bleeding. Further PMP and PMT induced proliferation of splenic cells commensurate with cumulative dose/duration exposure parallel with hyperkeratosis, enlargement due to congregation of white blood cells. Thus the splenic trauma (splenomegaly) leads to severe immunological effects sensory and muscle problems, completely damaging all organs and functional systems including defense mechanisms by 70 weeks. 4. Search for antimalarial drugs and Schizontocides: A review Sukesh Narayana Sinha and H. Venkatakrishna Bhatt Departments of Air-Pollution and Neurobehavioural Toxicology, National Institute of Occupational Health, Meghani Nagar, Ahmedabad-380016 The resistance of mosquitoes to pesticides and successive more cases of malaria warrants for potential anti-malarial drugs both in temperate and tropical countries. Malaria is a WHO notified disease and prevention is by pesticide spray at the vector breeding sites and also by therapeutically effective anti-malarial and schizontocidal drugs. Primaquine is an antimalarial drug of gametocidal activity with side effects in subjects with glucose-6-phophodehyrogenase (G-6-PD) and forbidden 3 during pregnancy. Development of the 8-aminoquinolines was from 1981 when methylene blue was tested against malaria.The first synthetic anti-malarial and schizontocidal drug, pamaquine, a 6- methoxy 3-amino quinoline was announced in 1926. Subsequently, 4 drugs i.e. pentaquine, isopentaquine, 6- methozy aminobutylamino quinoline and primaquine were found better than pamaquine. 5-phenozy derivates of primaquine were more active and less toxic than primaquine. In the blood schizontocidal mouse screen, 5-(4-chloro)-phenoxy primaquine and 5-(4-fluoro)-phenoxy primaquine enabled radical cure in a Plasmodium cynomolgi/Macaca mulata model but in mice 5 folds less effective and 20 times less toxic than primaquine. The later was better than primaquine in primates and its activity was abolished by a replacement of lipophilic halogen group by an acetamido group. In continuation, Chinese team synthesized many 5-phenoxy, 6-methoxy-8-(4-phthalimido-l- methyl-butyl-amino) quinolines and 5-phenoxy, 6-methoxy-8-(4-phthalimido amyl amino) quinolines being antimalarial and less potent than primaquine. The 5-anilinoderivatives were found to be less active than 5-phenylthio primaquines. Aromatic substitution in 5th position reduces primaquine toxicity. The microsomal degradation of primaquine and its derivatives was found by deamination in rats and mouse. The yeast Candida tropicalis was found to convert Primaquine into N-acetylated derivative and finally a minor dimeric form. Streptomyces reseochromogenus yielded an acetylated metabolite and methyline-linked dimeric product. Currently WR 238605 was found significantly active as gametocytocidal drug than primaquine in P.berghei and highly active P.yoelii. Originally the drug was designed as a casual prophylactic and radical curative drug to replace primaquine for the prevention of relapsing malaria, it is now in phase I trial in USA. In an in vitro study, WR 238605 was extensively metabolized to aminophenolic compounds by air oxidation during the isolation process to a mixture of quinones and quiononeimines. Another primaquine CDRI, India compound is 80/53 is in phase II clinical trial against P.viavx infections. Two other compounds, 6-methoxy-5,8 di (4-‘amino- l’-methylbutylamino)Quinoline and 5,5 di-[6-methoxy, 8(4-amino-l’-methylbutylamino)Quinoline] were found to be 3 to 4 times potential gametocidal activity than primaquine. 5. Production, statistical optimization and characterization of multicomponent holocellulase produced by Streptomyces sp. ssr-198 isolated from desert soil Surender Singh1, Kumar Pranaw1, Balkar Singh2, Rameshwar Tiwari1 and Lata Nain1 1Division of Microbiology, Indian Agricultural Research Institute, New Delhi- 110012 2Head, Department of Botany and Biotechnology, Arya P G College, Panipat-132103 A novel thermotolerant actinomycete Streptomyces sp. ssr-198 with capacity to produce multicomponent holocellulolytic enzymes was isolated from the desert soil of Bikaner and identified using 16S rDNA sequencing. Important chemical components of medium were optimized by rotatable central composite design (RCCD) using response surface methodology (RSM) to achieve maximal yield of holocellulolytic (endoglucanase, exoglucanase and xylanase) enzymes. Optimization resulted in 246, 83, and 96% higher yield of endoglucanase, exoglucanase and xylanase respectively as compared to unoptimized conditions. The concentrated crude enzymes were partially characterized in terms of optimum pH (6.0) and temperature (60 °C).