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  • Key words: Guinea pig — NK1 receptor antagonist — Substance P — Plasma exudation — Nasal allergy  (1)
  • Key words: Leukotriene — Allergic rhinitis — Guinea pig models — Total airway resistance — Nasal symptoms  (1)
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  • 1
    ISSN: 1420-908X
    Keywords: Key words: Leukotriene — Allergic rhinitis — Guinea pig models — Total airway resistance — Nasal symptoms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: To define the role of leukotriene (LT) in allergic rhinitis, we examined the effects of a cysteinyl (Cys) LT antagonist (ONO-1078, pranlukast).¶Material: Actively sensitized Dunkin-Hartley guinea pigs.¶Treatment: ONO-1078 (pranlukast), 3–100 mg/kg p.o. l h before antigen challenge.¶Methods: Nasal symptoms (sneezing, nasal scratches), changes of total airway resistance (TAR by plethysmography) and eosinophil infiltration into the nasal mucosa were determined following topical antigen (OA) challenge. Dunnet's test (TAR and symptoms) and the Mann-Whitney U-test (eosinophils) were applied.¶Results: Control animals showed bi-phasic nasal responses, peaking 10 min and 240 min after the topical antigen challenge, respectively. While the early-phase response was characterized by nasal symptoms of sneezing and scratching accompanied by the increase in TAR, the late-phase was characterized by an increase in TAR accompanied by eosinophil infiltration into nasal mucosa. The nasal symptoms (sneezing and scratching) were not inhibited by pretreatment with ONO-1078 at doses up to 100 mg/kg (p.o., n = 15). Although early peak responses of TAR were not affected with even the highest dose (30 mg/kg, p.o., n = 6), late-phase TAR peak response (control: 174.8 ± 8.2%, n = 6) were significantly inhibited by 10 mg/kg (142.7 ± 15.8%; p 〈 0.05, n = 6) and 30 mg/kg (118.0 ± 6.6%; p 〈 0.01, n = 6) of ONO-1078 (p.o.). In addition, the eosinophil infiltration induced by the antigen was not inhibited by ONO-1078 (30 and 100 mg/kg, p.o., n = 6).¶Conclusions: Our results suggest that Cys LT may play an important role in the late-phase increase in TAR in the guinea pig model of allergic rhinitis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1420-908X
    Keywords: Key words: Guinea pig — NK1 receptor antagonist — Substance P — Plasma exudation — Nasal allergy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract.   Objective: To study the inhibitory effects of two NK1 receptor antagonists on substance P (SP) and antigen-induced increase of nasal vascular permeability in ovalbumen (OA)-sensitized guinea pigs. ¶Material: Male Dunkin-Hartley guinea pigs. ¶Treatment: SP (100 〈mu〉;mol/l), FK224 (1–10 〈mu〉 mol/kg) and FK888 (0.2– 2 〈mu〉mol/kg). ¶Methods: The in vivo model of nasal microvascular leakage was used for nasal allergic challenge in ovalbumin (OA)-sensitized guinea pigs, or nasal stimulation with substance P (SP) in non-sensitized animals. Nasal microvascular leakage was measured by the accumulation of Evans Blue dye after intravenous injection. ¶Results: Following nasal stimulation with SP 100 〈mu〉M, the concentration of dye in the nasal lavage fluid rapidly increased. NK1 receptor antagonists FK224 (10 〈mu〉mol/kg i.v.) and FK888 (2 〈mu〉mol/kg i.v.) inhibited SP-induced microvascular leakage. In OA-sensitized guinea pigs, exudation of dye into nasal lavage fluid was observed soon after topical antigenic stimulation and continued for over 60 min. Both NK1 receptor antagonists inhibited the immediate phase of the antigen-induced microvascular leakage. ¶Conclusions: We conclude that the immediate change of vascular permeability during the nasal allergic response is mediated by activation of the NK1 receptor in the guinea-pig.
    Type of Medium: Electronic Resource
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