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Results for “Administration, Intranasal”

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PubMed1985

[Sensitizing and protective activity of a staphylococcal vaccine made of water-soluble antigens, depending on the method and schedule of administration].

An experiment on guinea pigs immunized with staphylococcal vaccine prepared from water-soluble antigens revealed that the degree of developing sensitization and specific resistance was essentially determined by the method and schedule of the administration of the preparation. The intranasal administration of the vaccine induced a lesser degree of sensitization in comparison with its subcutaneous injection. The optimum response to the administration of the vaccine (a low sensitization level and a high degree of protection from infection) was observed in the animals immunized first intranasally and then by subcutaneous injection. The subcutaneous injection of the preparation in combination with its subsequent intranasal application induced a more pronounced degree of sensitization and a lesser degree of protection from infection.

Administration, Intranasal↗

PubMed1981

Mitogenicity and pathogenicity of Mycoplasma pulmonis in rats. I. Atypical interstitial pneumonia induced by mitogenic myeoplasmal membranes.

Mitogenic preparations of nonviable lysed cells and purified membranes of Mycoplasma pulmonis induced interstitial pneumonia and tracheitis after intranasal administration to pathogen-free rats. The pneumonia, characterized by peribronchial, perivascular, and alveolar wall infiltration by lymphocytes, was indistinguishable from that produced by viable M. pulmonis. Both pathologic and mitogenic effects were significanlty reduced by prior treatment of membranes with heat or proteolytic enzyme. Intranasal administration of the thymus-derived-cell mitogen, concanavalin A, produced interstitial pneumonia but not tracheitis. These results indicate a correlation of mitogenicity and pathogenicity and suggest that activation of thymus-derived lymphocytes is the major cause of the pneumonia resulting from infections with M. pulmonis.

Animals↗

PubMed2001

Depletion of alveolar macrophages exerts protective effects in pulmonary tuberculosis in mice.

Mycobacterium tuberculosis bacilli are intracellular organisms that reside in phagosomes of alveolar macrophages (AMs). To determine the in vivo role of AM depletion in host defense against M. tuberculosis infection, mice with pulmonary tuberculosis induced by intranasal administration of virulent M. tuberculosis were treated intranasally with either liposome-encapsulated dichloromethylene diphosphonate (AM(-) mice), liposomes, or saline (AM(+) mice). AM(-) mice were completely protected against lethality, which was associated with a reduced outgrowth of mycobacteria in lungs and liver, and a polarized production of type 1 cytokines in lung tissue, and by splenocytes stimulated ex vivo. AM(-) mice displayed deficient granuloma formation, but were more capable of attraction and activation of T cells into the lung and had increased numbers of pulmonary polymorphonuclear cells. These data demonstrate that depletion of AMs is protective during pulmonary tuberculosis.

Administration, Intranasal↗

PubMed1998

Inhibition of tumor necrosis factor alpha decreases inflammation and prolongs adenovirus gene expression in lung and liver.

The clinical application of adenoviral gene therapy currently is impeded by the potent host immune response to the virus, which limits the duration of its effects. In these studies, we investigated the role of TNF-alpha and of a soluble TNF receptor (TNF-bp) in the inflammatory response and expression of a lacZ-expressing adenovirus (AdCMVlacZ) in the liver and lung of mice. The expression of the recombinant adenovirus was studied in mouse liver and lung by determining the activity of the lacZ gene product of the adenovirus. The mononuclear cell inflammatory response was determined histologically at different times after intravenous or intranasal administration of AdCMVlacZ. The cytotoxic T cell and antibody response to the adenovirus was determined. Treatment with TNF-bp reduced circulating levels of TNF-alpha, greatly reduced the inflammatory response, and resulted in prolonged expression of lacZ for up to 30 days in the liver and lung after either intravenous or intranasal administration of adenovirus. Treatment with TNF-bp had no effect on anti-adenovirus antibodies and induction of cytotoxic T cells 30 days after administration of AdCMVlacZ. These results indicate that TNF-alpha is the primary factor driving the early inflammatory response leading to elimination of adenovirus-infected cells in the liver and lung and that TNF-bp is capable of inhibiting these effects.

Adenoviridae↗

PubMed1985

Effects of dose, pH, and osmolarity on nasal absorption of secretin in rats.

The effects of dose, pH, and osmolarity on the nasal absorption of a secretin solution were studied in rats. The nasal absorption of secretin was determined by measuring the increased secretion of pancreatic juice, and this was compared with the same response on intravenous administration. The relative bioavailability of secretin on intranasal administration compared with intravenous administration, as estimated from the pharmacological response, was approximately one-tenth. It was enhanced in acid solution and reached a maximum in a 0.462 M sodium chloride solution.

Absorption↗

PubMed1983

Effects of aspirin on nasal responses in atopic subjects.

Preliminary experiments indicated that solutions of aspirin (ASA) in buffered saline, pH 7.35, did not significantly change nasal airways resistance (NAR) when 0.1 ml of solution containing 22.5 mg (or less) per deciliter was sprayed into each nostril. Subsequently it was shown that this quantity of ASA administered intranasally did not significantly change NAR responses 15 min later to intranasal administration of increasing concentrations of histamine, methacholine, or an irritant (NH3 gas). However, the same atopic subjects demonstrated significantly decreased responses to intranasal challenge with short ragweed extract (SRW) after intranasal ASA. In addition, prior oral administration of ASA, Na salicylate, and indomethacin significantly inhibited nasal challenge responses to SRW in sensitive subjects under controlled conditions.

Administration, Intranasal↗

PubMed2006

Interstitial nephritis in cats inoculated with Crandell Rees feline kidney cell lysates.

Parenteral administration of Crandell Rees feline kidney (CRFK) cell lysates or feline herpesvirus 1, calicivirus, and panleukopenia virus-containing vaccines (FVRCP) grown on CRFK cells induces antibodies against CRFK cells. These antibodies also react with feline renal cell extracts. The purpose of this study was to determine whether interstitial nephritis would be detected in cats that were immunologically sensitized with CRFK lysates, boosted with CRFK lysates, and then biopsied 2 weeks after the booster. Cats (2 per group) were immunologically sensitized against CRFK lysates by administering 10 microg, 50 microg, or 50 microg plus alum 13 times (12 times in the first 50 weeks) over 2 years. Two cats were inoculated three times, 4 weeks apart with an FVRCP vaccine for intranasal administration as kittens, boosted 50 and 102 weeks later, and then renal biopsies taken 2 weeks after the last booster. Neither of the cats vaccinated with the FVRCP for intranasal administration had detectable renal inflammation. One cat in each of the three CRFK lysate sensitization groups had lymphocytic-plasmacytic interstitial nephritis.

Animals↗

PubMed2000

Impaired control of Brucella melitensis infection in Rag1-deficient mice.

After intranasal inoculation, Brucella melitensis chronically infects the mononuclear phagocyte system in BALB/c mice, but it causes no apparent illness. Adaptive immunity, which can be transferred by either T cells or antibody from immune to naive animals, confers resistance to challenge infection. The role of innate, non-B-, non-T-cell-mediated immunity in control of murine brucellosis, however, is unknown. In the present study, we documented that BALB/c and C57BL/6 mice had a similar course of infection after intranasal administration of 16M, validating the usefulness of the model in the latter mouse strain. We then compared the course of infection in Rag1 knockout mice (C57BL/6 background) (referred to here as RAG-1 mice) which have no B or T cells as a consequence of deletion of Rag1 (recombination-activating gene 1), with infection in normal C57BL/6 animals after intranasal administration of B. melitensis 16M. C57BL/6 mice cleared brucellae from their lungs by 8 to 12 weeks and controlled infection in the liver and spleen at a low level. In contrast, RAG-1 mice failed to reduce the number of bacteria in any of these organs. From 1 to 4 weeks after inoculation, the number of splenic bacteria increased from 2 to 4.5 logs and remained at that level. In contrast to the consistently high numbers of brucellae observed in the spleens, the number of bacteria rose in the livers sampled for up to 20 weeks. Immunohistologic examination at 8 weeks after infection disclosed foci of persistent pneumonia and large amounts of Brucella antigen in macrophages in lung, liver, and spleen in RAG-1, but not C57BL/6, mice. These studies indicate that T- and B-cell-independent immunity can control Brucella infection at a high level in the murine spleen, but not in the liver. Immunity mediated by T and/or B cells is required for clearance of bacteria from spleen and lung and for control of bacterial replication in the liver.

Animals↗

PubMed1996

Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23).

The observation that overt type I diabetes is often preceded by the appearance of insulin autoantibodies and the reports that prophylactic administration of insulin to biobreeding diabetes-prone (BB-DP) rats, nonobese diabetic (NOD) mice, and human subjects results in protection from diabetes suggest that an immune response to insulin is involved in the process of beta cell destruction. We have recently reported that islet-infiltrating cells isolated from NOD mice are enriched for insulin-specific T cells, that insulin-specific T cell clones are capable of adoptive transfer of diabetes, and that epitopes present on residues 9-23 of the B chain appear to be dominant in this spontaneous response. In the experiments described in this report, the epitope specificity of 312 independently isolated insulin-specific T cell clones was determined and B-(9-23) was found to be dominant, with 93% of the clones exhibiting specificity toward this peptide and the remainder to an epitope on residues 7-21 of the A chain. On the basis of these observations, the effect of either subcutaneous or intranasal administration of B-(9-23) on the incidence of diabetes in NOD mice was determined. The results presented here indicate that both subcutaneous and intranasal administration of B-(9-23) resulted in a marked delay in the onset and a decrease in the incidence of diabetes relative to mice given the control peptide, tetanus toxin-(830-843). This protective effect is associated with reduced T-cell proliferative response to B-(9-23) in B-(9-23)-treated mice.

Administration, Intranasal↗

PubMed1989

[Immunologic assessment of preparations of the RS virus at the stages of its purification and concentration].

The work demonstrates the immunogenic potency of some preparations of RS virus, differing in the degree of their purification and introduced by multiple intranasal administration. The immunogenic potency of these preparations was manifested by the synthesis of antibodies determined in the coagglutination test (the specificity of these antibodies was confirmed in the reaction of the neutralization of RS virus), as well as by sensitization determined in the leukocyte migration inhibition test. Immunization with concentrated virus was more effective than immunization with the preparation of virion fraction. The intranasal administration of live RS virus to mice induced the appearance of a morphologically determined disease which was not prevented by the development of immune response accompanying the disease. The conclusion was made that further improvement in the system of testing the preparations of RS virus was necessary.

Animals↗

PubMed1999

Transient gene transfer of non-ELR chemokines to rodent lung induces mononuclear cell accumulation and activation.

The in vivo function of the CXC chemokines interferon-inducible protein-10 (IP-10) and monokine induced by gamma (MIG) was examined using replication-deficient adenoviral vectors expressing human IP-10 (AdIP-10) or murine MIG (AdMIG). Intratracheal and intranasal administration of AdIP-10 or AdMIG into rats and mice produced transient chemokine overexpression from the bronchial epithelium. IP-10 concentrations in the bronchoalveolar lavage fluid (BAL) of AdIP-10-treated animals showed peak expression (>2 ng/ml) 24-48 h after AdIP-10 administration. Dramatic transient increases in BAL cellularity (macrophages, monocytes, lymphocytes, and neutrophils) were observed in AdIP-10-treated and AdMIG-treated animals, and histologic examination of AdIP-10-treated lungs revealed transient infiltrations of mononuclear cells primarily localized around the bronchus and extending throughout the lung parenchyma. However, in immunocomprised SCID mice, only increases in natural killer cell populations were detected in BAL following AdIP-10 intranasal administration, indicating that monocyte/macrophage and neutrophil accumulation was likely the result of factors released from activated lymphocytes.

Adenoviridae↗

PubMed2002

Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice.

Protease-activated receptor-2 (PAR2) acts as a receptor for trypsin and trypsin-like enzymes. The role of this receptor in airway inflammation is uncertain. In this study we assessed the effect of activation of PAR2 following intranasal administration of the peptide activator of PAR2, SLIGRL, over 72 h in mice. The extent of immune cell infiltration into the airways and activities of matrix metalloprotease-2 (MMP-2) and MMP-9 were assessed in bronchoalveolar lavage (BAL) by differential cell counts and gelatin zymography, respectively. SLIGRL did not cause a change in the number or types of cells retrieved in BAL at any time point and did not alter the levels of MMP-2 and MMP-9 present in BAL. In contrast, similar intranasal administration of bacterial lipopolysaccharide (LPS) caused a large influx of neutrophilic polymorphonuclear leukocytes, which was associated with increased MMP-2 at 3 h only and MMP-9 activity from 3-72 h. Simultaneous administration of SLIGRL and LPS transiently potentiated increased MMP-9 activity at 3 h but markedly inhibited neutrophil influx and elevated MMP-2 activity at 3 h. These findings suggest that PAR2 agonists may be useful therapeutic molecules in pulmonary inflammatory diseases.

Animals↗

PubMed2002

Design of biodegradable particles for protein delivery.

Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate protein carriers in order to overcome mucosal barriers. We have attempted to combine both issues through the conception of new biodegradable polymer nanoparticles: (i) poly(ethylene glycol) (PEG)-coated poly(lactic acid) (PLA) nanoparticles, chitosan (CS)-coated poly(lactic acid-glycolic acid (PLGA) nanoparticles and chitosan (CS) nanoparticles. These nanoparticles have been tested for their ability to load proteins, to deliver them in an active form, and to transport them across the nasal and intestinal mucosae. Additionally, the stability of some of these nanoparticles in simulated physiological fluids has been studied. Results showed that the PEG coating improves the stability of PLA nanoparticles in the gastrointestinal fluids and helps the transport of the encapsulated protein, tetanus toxoid, across the intestinal and nasal mucosae. Furthermore, intranasal administration of these nanoparticles provided high and long-lasting immune responses. On the other hand, the coating of PLGA nanoparticles with the mucoadhesive polymer CS improved the stability of the particles in the presence of lysozyme and enhanced the nasal transport of the encapsulated tetanus toxoid. Finally, nanoparticles made solely of CS were also stable upon incubation with lysozyme. Moreover, these particles were very efficient in improving the nasal absorption of insulin as well as the local and systemic immune responses to tetanus toxoid, following intranasal administration. In summary, these results show that a rational modification in the composition and structure of the nanoparticles, using safe materials, increases the prospects of their usefulness for mucosal protein delivery and transport.

Animals↗

PubMed1999

Formulation of HIV-envelope protein with lipid vesicles expressing ganglioside GM1 associated to cholera toxin B enhances mucosal immune responses.

Taking advantage of the ability of pentameric cholera toxin B subunit (CTB) to bind selectively to GM1, we developed recently a CTB-mediated GM1 lipid vesicle delivery system to target drugs and proteins to mucosal tissues [1]. In this report, we present the use of such a strategy to deliver an HIV envelope protein (HIV-env) to mucosal tissues via intranasal route. Intranasal administration of a recombinant HIV envelope protein formulated in CTB-associated GM1 lipid vesicles enhanced mucosal IgA antibody responses detected in the nasal and gut tissues, compared to that of control animals immunized with antigen formulated in GM1-free vesicles with CTB or formulated in alum-associated vesicles with CTB. We found a nearly 2- to 3-fold enhancement in IgA antibody titers detected both in nasal and gut tissues using the CTB-GM1 lipid vesicle delivery system, compared to using the GM1-free lipid vesicle system. Intranasal administration of HIV-env formulated in the CTB-associated GM1 vesicles also induced a significant level of serum IgG and cellular immune responses against HIV-env. IgG isotype analysis indicates that CTB in GM1 vesicle delivery system enhanced both IgG1 and IgG2a while CTB in alum formulation enhanced only IgG1. However, IgA and IgG antibody responses against CTB were similar for GM1 vesicles regardless of whether HIV-env was present in the vaccine formulation. Collectively, these data indicate that delivery of HIV-env to mucosal epithelial cells with CTB-associated GM1 lipid vesicles enhanced mucosal and systemic immune responses against the HIV-envelope protein. It is possible that both the CTB-mediated targeted delivery of antigen-loaded GM1 lipid vesicles and mucosal adjuvanticity of CTB may be involved in enhancing the immune responses.

Adjuvants, Immunologic↗

PubMed2003

Adjuvant activity of free Bordetella pertussis filamentous haemagglutinin delivered by mucosal routes.

The development of safe and potent mucosal adjuvants remains a major objective in vaccinology. The potential usefulness of filamentous haemagglutinin (FHA) of Bordetella pertussis as an adjuvant was assessed in a mouse model. The glutathione-S-transferase of Schistosoma mansoni (Sm28GST) was used for intranasal administration, while the gut-resistant keyhole limpet haemocyanin (KLH) was administrated by the oral route. For both antigens, coadministration with FHA increased antigen-specific immunoglobulin titres. This adjuvant effect did not require chemical cross-linking or direct interaction between FHA and the antigen tested. FHA also behaved as an adjuvant by the subcutaneous route, indicating that its adjuvanticity is not restricted to binding to mucosal surfaces. The FHA-induced adjuvanticity was also observed in mice with high anti-FHA antibody titres as a result of antipertussis vaccination, indicating that pre-existing anti-FHA antibodies do not impair FHA adjuvanticity. No mRNA coding for proinflammatory cytokines was induced in the lungs after intranasal FHA administration. However, an increase in the levels of mRNAs coding for B7-1, transforming growth factor (TGF)-beta and major histocompatibility complex (MHC)-II was detected in the lungs after FHA administration. Although the molecular mechanisms of the FHA-induced adjuvanticity remain to be elucidated, the data presented here indicate that this adhesin, already assessed for human use as a pertussis vaccine constituent, represents a promising adjuvant to improve the humoral immune response when given by mucosal routes.

Adhesins, Bacterial↗

PubMed2006

Motives, diversion and routes of administration associated with nonmedical use of prescription opioids.

OBJECTIVES: The main objectives of this study were to assess the motives, diversion sources and routes of administration associated with the nonmedical use of prescription opioids as well as to examine substance use related problems associated with the nonmedical use of prescription opioids. METHOD: A self-administered, cross-sectional Web survey was conducted in 2005 at a large public Midwestern 4-year university in the U.S. using a probability-based sampling approach. The final sample included 4580 full-time undergraduate students. RESULTS: The three most common motives associated with the nonmedical use of prescription opioids were to relieve pain, get high, and experiment. The leading sources of prescription opioids were friends and parents although there were gender differences in reports of primary sources. More than 1 in every 10 nonmedical users reported intranasal administration. Multivariate analyses indicated nonmedical users of prescription opioids who used for motives other than to relieve pain, obtained these drugs from non-parental sources, or used these drugs via non-oral routes of administration were significantly more likely to experience substance use related problems. CONCLUSIONS: These results indicate that nonmedical use of prescription opioids represents a considerable problem for particular subgroups of college students. While additional research is needed, the present study offers important new directions for policy and research regarding prescription opioid misuse.

Administration, Intranasal↗

PubMedDate not supplied

[Current state of the world's experiences with vaccination against rubella].

In order to avoid the severe consequences that may result from intrauterine infection, the prevention of maternal rubella is of most importance. It should be remarked that the damage induced in the infant by the rubella virus is not confined to the first trimester of pregnancy, but may occur also in the following months, and some lesions, especially the auditive ones, may become worse during the childhood. From an immunological point of view in the present paper it is emphasized the prominent importance of neutralizing antibodies; these should be more broadly assayed in epidemiological investigations and in studies concerning the effects of the different vaccines that are available nowadays. In this connection, the RA 27/3 vaccine (prepared with human diploid cells) appears to be more effective than other vaccines (e.g.: Cendehill and HPV-77) in stimulating the formation of circulating antibodies. Furthermore this vaccine, which may be administrated intranasally, can produce a local resistence due to the presence of specific IgA in the secretions. The following programs have been proposed for the prevention of rubella: a mass-vaccination (as in the United States) and a selective vaccination of female prepubere subjects who appear to be non protected against the infection. The Authors consider the second program as the more advantageous and suggest that the age range should be 10-11 years. It may be interesting to note that a new anti-rubella vaccine has been recently employed in Soviet Union with satisfactory results, while an alive attenuate non-teratogenic vaccine has been prepared in Japan. However, the opinion of the Authors is that further studies are needed in order to obtain a really non-teratogenic vaccine and administrable intranasally; this should be the most effective means against all problems correlated to rubella infection.

Age Factors↗

PubMed1998

Adjuvant action of Chenopodium quinoa saponins on the induction of antibody responses to intragastric and intranasal administered antigens in mice.

Saponins extracted from the seed of Chenopodium quinoa (quinoa) were studied for their ability to act as mucosal adjuvants upon their intragastric or intranasal administration together with model antigens in mice. Quinoa saponins, co-administered intragastrically or intranasally with cholera toxin or ovalbumin, potentiated specific IgG and IgA antibody responses to the antigens in serum, intestinal and lung secretions. The potentiating effect of the saponins appeared, to some extent, mediated by increased permeability of the mucosa, allowing increased uptake of the antigen. The intragastric administration of 99mTc-radio-labeled human serum albumin together with quinoa saponins revealed an increased presence of the radiolabeled protein in blood, liver, spleen and lungs of mice. This study indicates the potential of quinoa saponins as adjuvants for mucosally administered vaccines.

Adjuvants, Immunologic↗