(1/2093) Complement fixation titers in cattle following intranasal inoculation of Hemophilus somnus.
Five bulls were inoculated intranasally with a live culture of Hemophilus somnus originally isolated from a clinical case of Hemophilus septicemia. Preinoculation and postinoculation blood samples were taken at weekly intervals for nine weeks for measuring complement fixation titers and daily postinoculation temperatures were taken for one week. Three animals had transient fever and slight lethargy was observed in two animals had a transitory rise in complement fixation titers in the second to fifth weeks postexposure while one animal which had been seronegative on preinoculation testing produced little serological response to the organism. The experiment demonstrated that the nasal instillation of young cattle using an originally pathogenic H. somnus isolate is capable of stimulating only transitory complement fixation antibody titer. (+info)
(2/2093) Zonula occludens toxin is a powerful mucosal adjuvant for intranasally delivered antigens.
Zonula occludens toxin (Zot) is produced by toxigenic strains of Vibrio cholerae and has the ability to reversibly alter intestinal epithelial tight junctions, allowing the passage of macromolecules through the mucosal barrier. In the present study, we investigated whether Zot could be exploited to deliver soluble antigens through the nasal mucosa for the induction of antigen-specific systemic and mucosal immune responses. Intranasal immunization of mice with ovalbumin (Ova) and recombinant Zot, either fused to the maltose-binding protein (MBP-Zot) or with a hexahistidine tag (His-Zot), induced anti-Ova serum immunoglobulin G (IgG) titers that were approximately 40-fold higher than those induced by immunization with antigen alone. Interestingly, Zot also stimulated high anti-Ova IgA titers in serum, as well as in vaginal and intestinal secretions. A comparison with Escherichia coli heat-labile enterotoxin (LT) revealed that the adjuvant activity of Zot was only sevenfold lower than that of LT. Moreover, Zot and LT induced similar patterns of Ova-specific IgG subclasses. The subtypes IgG1, IgG2a, and IgG2b were all stimulated, with a predominance of IgG1 and IgG2b. In conclusion, our results highlight Zot as a novel potent mucosal adjuvant of microbial origin. (+info)
(3/2093) The posterior nasal nerve plays an important role on cardiopulmonary reflexes to nasal application of capsaicin, distilled water and l-menthol in anesthetized dogs.
The sensory innervation of the cardiopulmonary reflexes to nasal application of capsaicin (CAPS), distilled water (DW) and l-menthol (LM) was studied in anesthetized dogs breathing through tracheostomy. A marked cardiopulmonary reflex was observed by CAPS and DW into the nasal cavity, while a prolongation of expiration was induced by LM. All these reflexes were significantly decreased by bilateral section of the posterior nasal nerve (PNN) and completely abolished by topical nasal anesthesia with lidocaine. Responses of the whole nerve activity of the PNN to these substances corresponded to the magnitude of the reflexes. These results indicate that PNN afferents play an important role on the reflex elicitation of the noxious, water and cold stimuli from the nasal cavity. (+info)
(4/2093) Protective immune response against Streptococcus pyogenes in mice after intranasal vaccination with the fibronectin-binding protein SfbI.
Despite the significant impact on human health of Streptococcus pyogenes, an efficacious vaccine has not yet been developed. Here, the potential as a vaccine candidate of a major streptococcal adhesin, the fibronectin-binding protein SfbI, was evaluated. Intranasal immunization of mice with either SfbI alone or coupled to cholera toxin B subunit (CTB) triggered efficient SfbI-specific humoral (mainly IgG) and lung mucosal (14% of total IgA) responses. CTB-immunized control mice were not protected against challenge with S. pyogenes (90%-100% lethality), whereas SfbI-vaccinated animals showed 80% and 90% protection against homologous and heterologous challenge, respectively. Multiple areas of consolidation with diffused cellular infiltrates (macrophages and neutrophils) were observed in lungs from control mice; the histologic structure was preserved in SfbI-vaccinated animals, which occasionally presented focal infiltrates confined to the perivascular, peribronchial, and subpleural areas. These results suggest that SfbI is a promising candidate for inclusion in acellular vaccines against S. pyogenes. (+info)
(5/2093) Central nervous system effects of intranasally administered insulin during euglycemia in men.
Insulin receptors have been detected in several structures of the brain, yet the biological significance of insulin acting on the brain remains rather unclear. In humans, direct central nervous effects of insulin are difficult to distinguish from alterations in neuronal functions because of insulin-induced decrease in blood glucose levels. Since several intranasally administered viruses, peptides, and hormones have been shown to penetrate directly from the nose to the brain, we tested whether insulin after intranasal administration likewise has access to the brain. After a 60-min baseline period, insulin (20 IU H-Insulin 100 Hoechst) or vehicle (2.7 mg/ml m-Cresol) was intranasally administered every 15 min to 18 healthy subjects according to a double-blind within-subject crossover design. Auditory-evoked potentials (AEP) indexing cortical sensory processing were recorded while the subjects performed a vigilance task (oddball paradigm) during the baseline phase and after 60 min of intranasal treatment with insulin or placebo. Blood glucose and serum insulin levels were not affected by intranasal insulin. Compared with placebo, intranasal administration of insulin reduced amplitudes of the N1 (P < 0.005) and P3 (P < 0.02) components of the AEP and increased P3 latency (P < 0.05). The reduction in P3 amplitude was most pronounced over the frontal recording site (2.42 +/- 1.00 vs. 4.92 +/- 0.79 microV, P < 0.0005). At this site, after insulin administration, a broad negative shift developed in the AEP between 280 and 500 ms poststimulus (area under the curve -166.0 +/- 183.8 vs. 270.8 +/- 138.7 microV x ms after placebo, P < 0.01). The results suggest that after intranasal administration, insulin directly enters the brain and exerts distinct influences on central nervous functions in humans. (+info)
(6/2093) Lesions and transmission of experimental adenovirus hemorrhagic disease in black-tailed deer fawns.
Adenovirus infection was the cause of an epizootic of hemorrhagic disease that is believed to have killed thousands of mule deer (Odocoileus hemionus) in California during the latter half of 1993. A systemic vasculitis with pulmonary edema and hemorrhagic enteropathy or a localized vasculitis associated with necrotizing stomatitis/pharyngitis/glossitis or osteomyelitis of the jaw were common necropsy findings in animals that died during this epizootic. To study transmission of adenovirus infection in deer and susceptibility of black-tailed deer (Odocoileus hemionus columbianus) fawns to adenovirus infection, six 3-6-month-old black-tailed fawns were divided into two treatment groups. One group was inoculated intravenously and the other group was inoculated through the mucous membranes of the eyes, nose and mouth with purified adenovirus. Each treatment group also included two additional fawns (four total) that were not inoculated but were exposed to inoculated animals (contact animals). One fawn served as a negative control. Between 4 and 16 days postinoculation, 8/10 fawns developed systemic or localized infection with lesions identical to lesions seen in animals with natural disease that died during the epizootic. Transmission was by direct contact, and the route of inoculation did not affect the incubation period or the distribution of the virus (systemic or the localized infection). Immunohistochemical analysis using polyclonal antiserum against bovine adenovirus type 5 demonstrated staining in endothelial cells of vessels in numerous tissues in animals with systemic infection and endothelial staining only in vessels subtending necrotic foci in the upper alimentary tract in animals with the localized form of the disease. All inoculated or exposed animals had staining in the tonsillar epithelium. Transmission electron microscopic examination of lung and ileum from two fawns with pulmonary edema and hemorrhagic enteropathy demonstrated endothelial necrosis and adenovirus virions in endothelial cell nuclei. Adenovirus was reisolated in black-tailed deer pulmonary artery endothelial cells using lung homogenate of the first fawn that developed systemic adenovirus infection. Serum virus neutralization test results suggest that this deer adenovirus is a new serotype. (+info)
(7/2093) Intranasally inoculated Mycoplasma hyorhinis causes eustachitis in pigs.
Specific-pathogen-free pigs were experimentally inoculated with Mycoplasma hyorhinis, Pasteurella multocida, or both bacterial isolates to evaluate the role of these bacteria in the pathogenesis of otitis media. Six pigs were inoculated intranasally with 4.4 X 10(8) colony-forming units (CFU) of M. hyorhinis. Twenty-one days later, three of these six pigs were inoculated intranasally with 5.0 X 10(8) CFU of P. multocida. Three additional pigs were also inoculated intranasally at the time with P. multocida alone. Two pigs served as uninoculated controls. Seven days later, all pigs were euthanatized. Histologically, subacute inflammation was found in 10 auditory tubes of six pigs and two tympanic cavities of two pigs inoculated with M. hyorhinis. Immunohistochemically, M. hyorhinis antigens were detected on the luminal surface of eight of 10 inflamed auditory tubes, and ultrastructural examination confirmed mycoplasmal organisms in two pigs. M. hyorhinis was isolated from the inflamed tympanic cavities of two pigs. None of the pigs inoculated only with P. multocida had otitis, and P. multocida was not isolated from the tympanic cavity. These findings indicate that M. hyorhinis can cause eustachitis but rarely otitis media in specific-pathogen-free pigs. (+info)
(8/2093) Comparison of intranasal triamcinolone acetonide with oral loratadine in the treatment of seasonal ragweed-induced allergic rhinitis.
A double-blind, randomized, multicenter, parallel-group controlled study compared the efficacy and safety of intranasal triamcinolone acetonide (220 micrograms/day) and oral loratadine (10 mg/day) in patients with at least two seasons of ragweed-induced seasonal allergic rhinitis. A 28-day screening period, including a 5-day baseline period, preceded a 4-week treatment period. Reduction in rhinitis symptom scores was evident in both groups as early as day 1, with no significant between-group differences during week 1. At weeks 2, 3, and 4, patients treated with triamcinolone acetonide were significantly (P < 0.05) more improved in total nasal score, nasal itch, nasal stuffiness, and sneezing than were patients treated with loratadine. At weeks 3 and 4, rhinorrhea and ocular symptoms were significantly (P < 0.05) more improved from baseline among triamcinolone acetonide patients compared with loratadine patients. There was no significant between-group difference in relief from postnasal drip at any time point. Physicians' global evaluations significantly (P = 0.002) favored triamcinolone acetonide at the final visit, with moderate to complete relief of symptoms attained by 68% of triamcinolone acetonide patients and 59% of loratadine patients. Over the 4-week treatment period, triamcinolone acetonide patients had significantly greater improvement in total nasal score, nasal itch, nasal stuffiness, sneezing, and ocular symptoms. Both treatments were well tolerated, with headache being the most frequently reported drug-related adverse effect in both the triamcinolone acetonide (15%) and loratadine (11%) groups. These results indicate that triamcinolone acetonide is more effective than oral loratadine in relieving the symptoms of ragweed-induced seasonal allergic rhinitis. (+info)