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1.
Parasite Immunol ; 39(9)2017 Sep.
Article in English | MEDLINE | ID: mdl-28665520

ABSTRACT

Although the precise host-defence mechanisms are not completely understood, T-cell-mediated immune responses are believed to play a pivotal role in controlling parasite infection. In this study, the potential HLA*A2 restricted peptides were predicted and the ability of peptides to bind HLA-A*02 was confirmed by a MHC stabilization assay. Two of the peptides tested stabilized HLA-A*02: (a) LLATTVSGL (P1) and (b) LMTNGPLEV (P3). The potential of the peptides to generate protective immune response was evaluated in patients with treated visceral leishmaniasis as well as in healthy control subjects. Our data suggest that CD8+ T-cell proliferation against the selected peptide was significantly higher compared to unstimulated culture conditions. The stimulation of peripheral blood mononuclear cells with epitopes individually or as a cocktail upregulated IFN-γ production, which indicates its pivotal role in protective immune response. The IFN-γ production was mainly in a CD8+ T-cells-dependent manner, which suggested that these epitopes had an immunoprophylactic potential in a MHC class I-dependent manner. Moreover, no role of the CD3+ T cell was observed in the IL-10 production against the selected peptides, and no role was found in disease pathogenesis. Further studies on the role of these synthetic peptides may contribute significantly to developing a polytope vaccine idea towards leishmaniasis.


Subject(s)
Cysteine Proteases/immunology , Epitopes, T-Lymphocyte/immunology , HLA-A2 Antigen/immunology , Leishmania/immunology , Leishmaniasis Vaccines/immunology , Leishmaniasis, Visceral/immunology , Adolescent , Adult , CD8-Positive T-Lymphocytes/immunology , Cell Proliferation , Cysteine Proteases/chemistry , Epitopes, T-Lymphocyte/chemistry , Female , HLA-A2 Antigen/chemistry , Humans , Immunogenicity, Vaccine , Interleukin-10/metabolism , Leishmania/enzymology , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/parasitology , Leukocytes, Mononuclear/immunology , Male , Models, Molecular , Peptides/chemical synthesis , Peptides/chemistry , Peptides/immunology , Young Adult
2.
SAR QSAR Environ Res ; 24(3): 215-34, 2013.
Article in English | MEDLINE | ID: mdl-23437769

ABSTRACT

Kinase-insert domain-containing receptor (KDR) is one of the important mediators of Vascular endothelial growth factor (VEGF) function in endothelial cells. Inhibition of KDR can be therapeutically advantageous for treatment of a number of diseases. The present study focuses on exploring novel KDR inhibitors by means of pharmaco-informatics methodologies. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis by atom-based pharmacophore mapping over a set of 85 molecules provides a proposition regarding the molecular fingerprint that can be optimized for designing more active inhibitors. The model was statistically validated with Q(2) = 0.865 for training and r(2) = 0.789, Pearson-r = 0.903 for test set molecules; r(2)(0.925) by external validation suggests model robustness and indicates it as a strong query for screening any compound library. Virtual screening shows the importance of active site and hinge region residue for interaction with KDR inhibitors. Remarkably the retrieved hits contain a urea backbone, implicating urea derivatives as promising candidate for designing KDR inhibitors. The hydrophobicity of active site, which has until now been overlooked, has been raised into the picture by this study. This can impact on KDR drug development. The study thus quantifies crucial structural requirements necessary for a favourable interaction with the receptor binding site while the cooperative pattern provides important structural clues to chemists for framing potent medicinal agents in future.


Subject(s)
Drug Discovery/methods , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Molecular Structure , Quantitative Structure-Activity Relationship , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/chemistry , Binding Sites , Hydrophobic and Hydrophilic Interactions
5.
Adv Biochem Eng Biotechnol ; 75: 209-42, 2002.
Article in English | MEDLINE | ID: mdl-11783841

ABSTRACT

In this paper an overview of the developments in liquid membrane extraction of cephalosporin antibiotics has been presented. The principle of reactive extraction via the so-called liquid-liquid ion exchange extraction mechanism can be exploited to develop liquid membrane processes for extraction of cephalosporin antibiotics. The mathematical models that have been used to simulate experimental data have been discussed. Emulsion liquid membrane and supported liquid membrane could provide high extraction flux for cephalosporins, but stability problems need to be fully resolved for process application. Non-dispersive extraction in hollow fiber membrane is likely to offer an attractive alternative in this respect. The applicability of the liquid membrane process has been discussed from process engineering and design considerations.


Subject(s)
Acremonium/metabolism , Cephalosporins/isolation & purification , Drug Industry/methods , Membranes, Artificial , Acremonium/growth & development , Drug Industry/economics , Drug Industry/instrumentation , Drug Stability , Emulsions , Equipment Design , Fermentation , Ion Exchange Resins , Models, Chemical , Solutions
6.
Indian J Otolaryngol Head Neck Surg ; 53(4): 267-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-23119819

ABSTRACT

Age and ageing is a biological property of all living beings. It has been estimated that there would be more than 120 crore people by 2020 over 65 years in the world out of which 90 crores alone n.ill be in the developed countries. At present there are than 30% people in Europe who are more than 60 Years the highest being in Sweden. Lin India the percentage of old people is around 10 which is comparatively low. But the total number of such people is very significant due to the vast population, increasing life expectancy and better health care. Hence there is an increasing awareness of the multitude problems in the field of geriatic Otolaryngology due to various degenerative changes in the Head and Neck region. Not only the affection of the special sense organs of hearing & olfaction reduces the quality of life but also the life span is reduced as head & neck malignancy is very common in old age. The cosmetic problems of an ageing face poses a formidable challenge due to the ever increasing appetite for a youthful appearance in the modern soicety.

7.
8.
Indian J Otolaryngol Head Neck Surg ; 52(3): 281-2, 2000 Jul.
Article in English | MEDLINE | ID: mdl-23119697

ABSTRACT

Rhinosporidiosis is a chronic disease that classically presents with the involvement of nose and nasopharynx. However, it can be present in various other sites including conjunctiva, vulva, vagina, larynx and scalp. We report a case with a Rhinosporidial mass in the nose extending to oropharynx and multiple cutaneous lesions of Rhinosporidiosis in a patient with HIV, This case is the first of its kind where HIV has been associated with Rhinosporidiosis.

9.
Indian J Otolaryngol Head Neck Surg ; 51(3): 50-4, 1999 Jul.
Article in English | MEDLINE | ID: mdl-23119545

ABSTRACT

Laryngeal manifestation of allergy though less common than, Rhinosinusitis, tubotympanitis and bronchopulmanary allergy but it is not that uncommon which is usually misdiagnosed and mistreated in children. Hence the importance of larynx as the allergic shock organ in children with spasmodic croup and laryngotracheo bronchits. In the present study in children bellow five years, presenting with stridor and/or hoarsness were evaluated regarding the history of allergy, direct laryngoscopic finding, mesurement of serum 1 g E. Presence of eosinophilia and histopathological examination of laryngeal biopsy. Out of the 80 cases studied 9 cases (11.2%) presented with associated allergic manifestation, 8 cases (10%) having family history of allergy, 4 cases (5%) having raised serum 1 g E, 12 cases (15%) with eosinophilia 3 cases (3.75%) with eosinophilic infiltration on histopathological examination of the biopsy material taken during the direct laryngoscopy.

10.
Indian J Otolaryngol Head Neck Surg ; 52(1): 54-7, 1999 Dec.
Article in English | MEDLINE | ID: mdl-23119622

ABSTRACT

Laryngeal manifestation of allergy though less common than rhinosinusitis, tubotympanitis and bronchopulmonary allergy is not that uncommon and is usually misdiagnosed and mistreated in children. Hence, the importance of larynx as the allergic shock organ in children with spasmodic croup and laryngotracheo hronchits. In the present study, children below five years, presenting with Stridor and/or hoarseness were evaluated regarding the history of allergy, direct laryngoscopic finding, measurement of serum IgE,. presence of eosinophilia and histopathological examination of laryngeal biopsy. Out of the 80 cases studied, 9 cases (11.2%) presented with associated allergic manifestation, 8 cases (10%) having family history of allergy. 4 cases (5%) having raised serum lgE, 12 cases (15%) with eosinophilia and 3 cases (3.75%) with eosinophilic infiltration on histopathological examination of the biopsy material taken during the direct laryngoscopy.

12.
Indian J Otolaryngol Head Neck Surg ; 50(4): 320-5, 1998 Oct.
Article in English | MEDLINE | ID: mdl-23119452

ABSTRACT

With the exploration of new horizons in the frontiers of genetic linkage with head and neck cancer by advanced molecular biological technique it may be possible to know the various steps involved in the cancer development and new prognostic markers for not only predicting prognosis but also progression and predisposition including routine diagnostic tests for mutantgenes for a better diagnosis and treatment of squamous cell cancers of head and neck. Various oncogens and their products so far identified are ras, myc, c-erb, Bl, PRAD-.l, int-2, hst-1 and p 53 etc with lirikage to head and neck malignancy. The HLA gene association is the most convincing evidence for the role of genetics in the aetiology of nasopharyngeal cancer. EGFR looks to be a promising prognostic indicator as its interaction with the polypeptide epidermal growth factor stimulates proliferation of target cells.

14.
Indian J Otolaryngol Head Neck Surg ; 49(2): 91-3, 1997 Apr.
Article in English | MEDLINE | ID: mdl-23119267
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