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  • Coproporphyrinogen oxidase  (1)
  • Key words: Hypersensitivity — Allergic rhinitis — Guinea pig — Cyclosporin A — Glucocorticosteroid  (1)
  • Key words: Leukotriene — Allergic rhinitis — Guinea pig models — Total airway resistance — Nasal symptoms  (1)
  • 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: Hypersensitivity — Allergic rhinitis — Guinea pig — Cyclosporin A — Glucocorticosteroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: In an attempt to study the pathogenesis of mucosal hypersensitivity in allergic rhinitis, we investigated the suppressive effects of cyclosporin A (CyA) and glucocorticosteroids on ovalbumin (OA)-induced hypersensitivity to topical histamine challenge.¶Materials: Actively sensitized Dunkin-Hartley guinea pigs.¶Treatment: OA and alum were applied to guinea pigs intraperitoneally 3 times at two-week intervals. After general sensitization, OA inhalation was performed every day for 6 days as topical sensitization. Before inhalation, treatment with CyA (50 mg/kg, p.o.), glucocorticosteroids (beclomethasone propionate (1.0 mg/kg, i.p.), fluticasone propionate (FP, 0.5 mg/kg, i.p.)) or vehicle were performed, and the sensitivity to histamine was measured before and after the inhalation. Moreover, in actively (general and topical) sensitized guinea pigs, FP (0.5 mg/kg, i.p.) was applied every day for 5 days and histamine sensitivity was evaluated before and after the application.¶Results: We found that histamine sensitivity was significantly increased by nasal antigen challenge in this guinea pig model, and that the occurrence of histamine hypersensitivity was inhibited by the pretreatment with CyA and glucocorticosteroids. Although multiple administration of FP gradually reduced the histamine hypersensitivity according to the period of administration, it did not significantly alter the histamine hypersensitivity after the occurrence of hypersensitivity.¶Conclusion: It is concluded that CyA and glucocorticosteroids suppress antigen-induced histamine hypersensitivity in a guinea pig model of allergic rhinitis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 261 (1999), S. 1012-1020 
    ISSN: 1617-4623
    Keywords: Key words Porphyrin biosynthesis ; Protoporphyrinogen oxidase ; Coproporphyrinogen oxidase ; Overexpression ; Enzymatic conversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Protoporphyrinogen oxidase, the penultimate enzyme involved in the biosynthetic pathway for heme, catalyzes the removal of six electrons from protoporphyrinogen IX to generate protoporphyrin IX. In Escherichia coli, this enzyme is encoded by the hemG gene. In this study we examined possible alternate pathways for the oxidation of protoporphyrinogen IX to protoporphyrin IX, by isolating and investigating E. coli mutants that can still grow normally when the hemG gene is disrupted. One of these mutants was characterized in detail and had a mutation in the promoter region of the hemF gene, which encodes aerobic coproporphyrinogen oxidase, the enzyme involved in the step immediately before protoporphyrinogen oxidase. Measurement of the promoter activity of the hemF gene showed that the level of transcription was elevated by the mutation. Overexpression of a wild-type hemF gene cloned in a multicopy plasmid also restored the growth of ΔhemG strain. Extracts from cells that overexpress hemF exhibited an increased ability to oxidize protoporphyrinogen IX to protoporphyrin IX. These findings suggest that the E. coli aerobic coproporphyrinogen oxidase has an intrinsic capacity to oxidize not only coproporphyrinogen III but also protoporphyrinogen IX.
    Type of Medium: Electronic Resource
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