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Biomedical subjects

S S Mohapatra

Publications and source records attributed to S S Mohapatra.

At least 19 recordsLinked to original sources
PubMed2004

Cationic silica nanoparticles as gene carriers: synthesis, characterization and transfection efficiency in vitro and in vivo.

The potential of cationic SiO2 nanoparticles was investigated for in vivo gene transfer in this study. Cationic SiO2 nanoparticles with surface modification were generated using amino-hexyl-amino-propyltri-methoxysilane (AHAPS). The zeta potential of the nanoparticles at pH = 7.4 varied from -31.4 mV (unmodified particles; 10 nm) to +9.6 mV (modified by AHAPS). Complete immobilization of DNA at the nanoparticle surface was achieved at a particle ratio of 80 (w/w nanoparticle/DNA ratio). The surface modified nanoparticle had a size of 42 nm with a distribution from 10-100 nm. The ability of these particles to transfect pCMVbeta reporter gene was tested in Cos-1 cells, and optimum results were obtained in the presence of FCS and chloroquine at a particle ratio of 80. These nanoparticles were tested for their ability to transfer genes in vivo in the mouse lung, and a two-times increase in the expression levels was found with silica particles in comparison to EGFP alone. Very low or no cell toxicity was observed, suggesting silica nanoparticles as potential alternatives for gene transfection.

Animals↗
PubMed2004

Cationic poly(lactide-co-glycolide) nanoparticles as efficient in vivo gene transfection agents.

Poly(lactide-co-glycolide) (PLGA), a biocompatible and biodegradable polyester co-polymer of PLA and PGA, has been recognized for its ability to deliver genes. However, gene delivery by PLGA nanoparticles is limited by their negative charge and their poor transport through mucosal barriers. In this study, PLGA nanoparticles were surface modified with cationic chitosan in an effort to improve their gene delivery capability. PLGA nanoparticles were synthesized by emulsion-diffusion-evaporation technique using PVA-chitosan (PLGA1) or PVA-chitosan-PEG (PLGA2) blend as stabilizers. This method is reproducible and produces nanoparticles with hydrodynamic diameter <200 nm. The nanoparticles were characterized by zetasizer, photon correlation spectroscopy and atomic force microscopy. A549 epithelial cells were transfected in vitro with PLGA particles complexed with a reporter plasmid encoding green fluorescent protein. PLGA particles transferred EGFP gene, but were less efficient than the lipofectamine control. The nanoparticles were also tested for their ability to transport across the nasal mucosa in vivo in mice. The results show that both PLGA1 and PLGA2 facilitate gene delivery and expression in vivo with increased efficiency and without causing inflammation, as measured by IL-6. Together, these results indicate that chitosan-modified PLGA nanoparticles have greater potential as gene carriers.

Animals↗
PubMed2001

Blocking intercellular adhesion molecule-1 on human epithelial cells decreases respiratory syncytial virus infection.

The respiratory syncytial virus (RSV) causes potentially fatal lower respiratory tract infection in infants. The molecular mechanism of RSV infection is unknown. Our data show that RSV colocalizes with intercellular adhesion molecule-1 (ICAM-1) on the HEp-2 epithelial cell surface. Furthermore, a neutralizing anti-ICAM-1 mAb significantly inhibits RSV infection and infection-induced secretion of proinflammatory chemokine RANTES and mediator ET-1 in HEp-2 cells. Similar decrease in RSV infection is also observed in A549, a type-2 alveolar epithelial cell line, and NHBE, the normal human bronchial epithelial cell line when pretreated with anti-ICAM-1 mAb prior to RSV infection. Incubation of virus with soluble ICAM-1 also significantly decreases RSV infection of epithelial cells. Binding studies using ELISA indicate that RSV binds to ICAM-1, which can be inhibited by an antibody to the fusion F protein and also the recombinant F protein can bind to soluble ICAM-1, suggesting that RSV interaction with ICAM-1 involves the F protein. It is thus concluded that ICAM-1 facilitates RSV entry and infection of human epithelial cells by binding to its F protein, which is important to viral replication and infection and may lend itself as a therapeutic target.

Antibodies, Monoclonal↗
PubMed2001

Elimination of iodine deficiency disorders by 2000 and its bearing on the people in a district of Orissa, India: a knowledge-attitude-practices study.

A knowledge-attitude-practices (KAP) study was conducted along with a prevalence study of iodine deficiency disorders (IDD) between 1998-99 in the district of Bargarh, Orissa state, India. A total of 635 people were interviewed by a pretested structured questionnaire, adopting the probability proportional to size cluster sampling method. The aim was to assess the baseline information on the KAP of the people regarding IDD. Only 37% of the males and 29.3% of the females perceived goitre as a disease. Less than 5% of both sexes knew how goitre is caused. Only 16.4% used iodised salt regularly. The awareness and perception of IDD does not correspond with the time and effort we have spent in education of this disease. The implications of this poor knowledge about IDD and consequent poor use of iodised salt is contrasted to the optimistic target of elimination of IDD. This aspect is discussed in this paper, at a time when we are at the beginning of the new millennium.

Adult↗
PubMed2001

IFN-gamma and IL-12 plasmid DNAs as vaccine adjuvant in a murine model of grass allergy.

BACKGROUND: Plasmids encoding cytokines such as IFN-gamma and IL-12 are potential genetic adjuvants that might increase the effectiveness of allergen vaccines. OBJECTIVE: The role of plasmids expressing the cytokines IFN-gamma (pIFN-gamma) and/or IL-12 (pIL-12) as adjuvants in modulating allergic immune responses, inflammation, and asthma was investigated in a murine model of Kentucky blue grass (KBG) allergy. METHODS: Groups of naive B6D2F1 mice were vaccinated subcutaneously with KBG allergens and administered intramuscularly with pIFN-gamma, pIL-12, pIFN-gamma plus pIL-12, or a vector control. Mice were then sensitized with KBG allergens in alum (intraperitoneally) and later challenged intranasally. Mice were examined for modulation of specific immunity, prevention of the development of airway hyperresponsiveness, and inflammation. RESULTS: Mice vaccinated with cytokine plasmid adjuvants had relatively lower levels of total serum IgE and higher levels of grass allergen-specific IgG2a in comparison with control mice. The lowest IgE and highest IgG2a levels were found in mice vaccinated with the combination of pIFN-gamma and pIL-12 as an adjuvant. The vaccination of mice with both pIFN-gamma and pIL-12 as an adjuvant induced the highest level of T(H)1 cytokines, IFN-gamma, and IL-2 in comparison with mice given either of the plasmids alone. The most profound decrease in airway hyperresponsiveness and pulmonary inflammation was observed in mice receiving both pIFN-gamma and pIL-12 as an adjuvant. CONCLUSION: These results demonstrate that pIFN-gamma and pIL-12 together provide an effective adjuvant to parenteral grass allergen vaccines and show that this adjuvant can significantly enhance the effectiveness of allergen immunotherapy in human beings.

Adjuvants, Immunologic↗
PubMed2001

Allergology and clinical immunology--XVII International Congress.

A quarter of the world's population has a genetic predisposition to atopy and suffers from one kind of allergy or another. Allergic diseases, including allergic rhinitis, atopic dermatitis, asthma, and anaphylaxis, were first identified as being important at the beginning of the 20th century. Since the discovery of allergens as agents that induce 'reaginic' (now known as IgE) antibodies, there have been spectacular advances in our knowledge of the various effector cells and molecules involved in allergic diseases. This international meeting, held every three years, provides a forum for the discussion of major advances in the field. There was no unifying theme, and the topics covered range from epidemiology and genetics, effector cells and molecules, to immunomodulatory and pharmacotherapeutic treatment.

Journal Article↗
PubMed2000

Recurrent respiratory syncytial virus infections in allergen-sensitized mice lead to persistent airway inflammation and hyperresponsiveness.

Respiratory syncytial virus (RSV) infection is considered a risk factor for bronchial asthma; however, the synergy between allergen sensitization and RSV infection in the development of pulmonary inflammation and asthma has been controversial. In this study the effects of primary and recurrent RSV infection on allergic asthma were examined in a group of control, RSV-infected, Dermatophagoides farinae (Df) allergen-sensitized, and Df allergen-sensitized plus RSV-infected BALB/c mice. Primary RSV infection in Df-sensitized mice transiently increases airway responsiveness, which is accompanied by increases in eosinophilic infiltration, the expression of ICAM-1, and macrophage inflammatory protein-1alpha (MIP-1alpha) in the lung tissue. A secondary RSV infection persistently enhances airway responsiveness in Df-sensitized mice, with a concomitant increase in MIP-1alpha and RSV Ag load in lung tissues. Bulk cultures of thoracic lymph node mononuclear cells demonstrate that acute RSV infection augments both Th1- and Th2-like cytokines, whereas secondary and tertiary infections shift the cytokine profile in favor of the Th2-like cytokine response in Df-sensitized mice. The elevated total serum IgE level in the Df-sensitized mice persists following only RSV reinfection. Thus, recurrent RSV infections in Df-sensitized mice augment the synthesis of Th2-like cytokines, total serum IgE Abs, and MIP-1alpha, which are responsible for persistent airway inflammation and hyperresponsiveness, both of which are characteristics of asthma.

Allergens↗
PubMed2000

Differential cytokine mRNA expression in Dermatophagoides farinae allergen-sensitized and respiratory syncytial virus-infected mice.

The interaction between mite allergen sensitization and respiratory syncytial virus (RSV) infection at the level of cytokine mRNA expression was examined in a murine model in the present study. Primary RSV infection enhances expression of inflammatory cytokines such as IL-6, IFN-gamma, and eotaxin in the lung and upregulates the expression of Th2-like cytokines IL-10 and IL-13 in the spleen in BALB/c mice. Mite antigen-sensitized and RSV-infected (ASRSV) mice show enhanced (P < 0.05) total serum IgE compared to antigen-sensitized mice. However, the levels of viral mRNA in the lung tissues are comparable between RSV-infected and ASRSV mice. It is concluded that compartmentalization of cytokine expression following RSV infection plays a role in the augmentation of Th2-like and IgE antibody response to RSV.

Allergens↗
PubMed1999

Intranasal IFN-gamma gene transfer protects BALB/c mice against respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a major respiratory pathogen in infants, young children and the elderly and causes severe bronchiolitis and asthma. In an effort to develop a preventive IFN-gamma therapy against RSV infection, an intranasal gene transfer strategy was utilized. Intranasal administration of a plasmid expressing the IFN-gamma cDNA (pIFN-gamma) resulted in the expression of IFN-gamma in murine lungs and decreased RSV replication. The mice administered with pIFN-gamma and then infected with RSV exhibited a significant decrease in broncho-alveolar lavage lymphocyte and neutrophil counts. A significant reduction in epithelial cell damage, infiltration of mononuclear cells in the peribronchiolar and perivascular regions, and thickening of the septa was observed in the lungs of mice treated with pIFN-gamma when compared to controls. These results suggest that intranasal IFN-gamma gene transfer results in decreased RSV replication and pulmonary inflammation and may be useful against RSV infection.

Administration, Intranasal↗
PubMed1999

A recombinant BCG vaccine generates a Th1-like response and inhibits IgE synthesis in BALB/c mice.

The tubercle vaccine, bacille Calmette-Guérin (BCG), is a strong inducer of T-helper type 1 (Th1) responsiveness, and it has been suggested that recombinant BCG (rBCG), which produces and secretes antigens, may be used to prevent allergic diseases. The effects of rBCG vaccination on allergic responses in a murine model were examined in this study. A BCG-Escherichia coli shuttle vector was developed with the promoter and signal sequence of the alpha-antigen of Mycobacterium bovis, and the vector was tested using E. coli beta-galactosidase as the model antigen and allergen. This vector enabled the expression of the E. coli beta-galactosidase gene in BCG, which was detected in its protein extract by immunoblotting analysis. Vaccination of mice with a single dose of 106 recombinant BCG generated a beta-galactosidase-specific antibody response. The splenocytes of vaccinated mice compared with controls produced significantly higher amounts of interferon-gamma (IFN-gamma) (P<0. 01) and interleukin-2 (IL-2) (P<0.05) and lower amounts of IL-5 (P<0. 01). Mice vaccinated with rBCG had significantly less (P<0.01) serum IgE compared with controls. These results together demonstrate that rBCG secreting antigens or allergens may be utilized for the induction of a Th1-like response and the down-regulation of IgE antibody response.

Animals↗
PubMed1998

Respiratory syncytial virus induces the expression of 5-lipoxygenase and endothelin-1 in bronchial epithelial cells.

Respiratory syncytial virus (RSV) infection causes and exacerbates asthma, yet the mechanism by which RSV triggers asthma is poorly understood. Herein, an in vitro model of RSV infection was established using HEp-2 and BEAS-2B bronchial epithelial cell lines, and the expression of 5-lipoxygenase (5-LO), and endothelin-1 (ET-1) was examined. RSV infection increased the expression of 5-LO mRNA and protein in both cell lines, as detected by RT-PCR and western blot analysis, respectively. The levels of leukotrienes also increased in the supernatants of RSV infected cells. Furthermore, RSV infection increased the expression of ET-1 mRNA and protein following RSV infection in a time-dependent manner. It is concluded that RSV infection upregulates the expression of ET-1 and 5-LO in the epithelial cells leading to the production of leukotrienes, which may mediate the consequent exacerbation of asthma.

Arachidonate 5-Lipoxygenase↗
PubMed1998

CD8+ T cells inhibit immunoglobulin E synthesis in low responder SJL/J mice.

In an effort to examine the basis for low IgE responsiveness of SJL/J strain mice, we analysed the profiles of cytokines, such as interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma), in SJL/J and A.SW/SnJ mice following immunization. Splenocytes of ovalbumin (OVA)-immunized SJL/J mice, secreted significantly higher levels of IL-4 and lower levels of IFN-gamma than those of A.SW/SnJ mice. A time-course analysis of cytokine expression in in vitro cultures of spleen cells indicated that the levels of IL-4 and IL-2 remained persistently high throughout in the cultures of SJL/J splenocytes as opposed to those of A.SW/SnJ. Depletion of CD4+ T cells in vivo suppressed the production of IL-2, IL-4 and IFN-gamma suggesting that CD4 T cells are the producers of most cytokines in both SJL/J and A.SW/SnJ mice. Depletion of CD8+ T cells in vivo not only induced productive epsilon transcript but also enhanced IgE production in SJL/J mice. Moreover, CD8 depletion in SJL/J mice led to decreased production of IFN-gamma, resulting in a net decrease in the ratio of IFN-gamma to IL-4. A similar shift in the IFN-gamma/IL-4 ratio was found in splenocytes of SJL/J mice following irradiation, which is known to enhance IgE synthesis in these mice. Taken together, it is concluded that low IgE responsiveness in SJL/J mice is not due to a defect in IL-4 production per se. Increased IFN-gamma production by the CD8+ T cells inhibits class switch and suppresses IgE antibody production in SJL/J mice.

Animals↗
PubMed1997

Vaccination with a multi-epitopic recombinant allergen induces specific immune deviation via T-cell anergy.

Prophylactic vaccination has recently emerged as a major paradigm toward the prevention and therapy of allergies and asthma; however, the immunological basis of this approach remains to be elucidated. We examined the potential and mechanism of prophylaxis of allergic response in B6D2F1 mice with a multi-epitopic recombinant allergen, rKBG8.3 (MERA-8.3), which represents a major group of allergens of grass pollens, used herein as a model of MERA vaccine. Vaccination (subcutaneous) with soluble MERA-8.3, prior to immunization with the MERA-8.3 in alum, led to suppression of the IgE antibody response and a concomitant increase in IgG2a antibody response specific to the MERA-8.3 in a dose-dependent manner. Analysis of cytokine patterns in spleen and lymph node cells revealed a marked decrease of interleukin-2 (IL-2) and IL-4 production and to a lesser extent a decrease of interferon-gamma (IFN-gamma) synthesis, resulting in an increased ratio of IFN-gamma: IL-4 in vaccinated-immunized mice compared with untreated-immunized control mice. Furthermore, splenocytes of mice treated with the MERA-8.3 alone proliferated to MERA-8.3 in vitro with reduced capacity compared with the splenocytes of MERA-8.3-alum immunized mice, owing to a markedly reduced level of IL-2 production in the former. Collectively, these results suggest that vaccination with the MERA-8.3 induces T-cell anergy, which is pivotal to deviation of specific immunity from Th2- to Th1-like, and may serve as an important approach to prevention and therapy of allergic disorders.

Allergens↗
PubMed1997

Airway responsiveness in two inbred strains of mouse disparate in IgE and IL-4 production.

The mouse provides an excellent model for genetic studies of asthma, which is characterized by airway hyperexcitability and hyperreactivity. The former is a function of the properties of the membrane of the airway smooth muscle (ASM), whereas the latter is a function, albeit indirectly, of the mechanical properties of the muscle contractile apparatus. The very small size of the muscle has in the past hampered its study. We report herein that contractile properties of tracheal smooth muscle (TSM) can be measured in mice. We examined TSM strips from two inbred strains of mouse, ASW and SJL, which are high and low IgE responders, respectively. Force-velocity relationships were measured in four groups of mice, two ASW (control and sensitized)/and two SJL (control and sensitized). Muscle strips from sensitized SJL mice exhibited shortening velocities (V0) and maximum shortening capacities (deltaLmax), that were significantly greater than those of the other groups. However, no difference was found between the two strains in maximal isometric force (P0). The two strains also showed differences in their potential to express cytokines such as interleukin-4 (IL-4) and IL-5 in ex vivo splenocyte cultures, as measured by the cytokines' messenger RNA (mRNA) and protein expression. The SJL strain, which exhibited TSM hyperreactivity, was found to produce significantly greater amounts of IL-4 than the ASW strain. We conclude that the altered contractile properties of TSM in sensitized SJL mice are independent of IgE response, but linked to increased amounts of IL-4.

Animals↗