A novel murine model of pharyngeal candidiasis with local symptoms characteristic of pharyngeal thrush produced by using an inhaled corticosteroid

Hu, Weimin; Ninomiya, Kentaro; Ishibashi, Hidetoshi; Maruyama, Naho; Oshima, Hiroki; Yamaguchi, Hideyo; Abe, Shigeru

doi:10.1080/13693780601103098

Cited by 6 publications

(4 citation statements)

References 18 publications

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“…We can assume that BDP exuded from the BDP-film facilitated colonization, perhaps through suppression of host defense mechanisms, based on our previous report 7) indicating that oral inhalation of BDP allows elongated deterioration of experimental pharyngeal candidiasis in mice. However, a glucocorticoid may suppress various types of host defense mechanisms against microbial infections; in this study we examined the effects on neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…7) Here, we compared the effects of the attachment of BDP-containing film, topical application of BDPsuspension and subcutaneous administration of prednisolone. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Before conducting clinical research on this film, the effects of application of this film on oral infection were examined in an animal model, since it is well known that glucocorticoids predispose to oral or pharyngeal Candida infection. [1][2][3][4][5][6] In our previous papers, a murine oral candidiasis model 6) or an esopharynxial model 7) were used, allowing the examination of the effects of topical application of mucoadhesive films.…”

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confidence: 99%

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Oral Candidiasis Deteriorated by Local Application of a Glucocorticoid-Containing Film in a Mouse Model

Yanagi

Hisajima

Ishibashi

et al. 2008

Biological & Pharmaceutical Bulletin

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The anti-inflammatory agent glucocorticoid is one of the most effective and widely-used drugs for various kinds of inflammatory diseases. However, it has serious side effects, including suppression of host defense mechanisms against microbial infections. Therefore, more efficient delivery methods of glucocorticoids are required for various types of inflammatory diseases. For clinical use films containing glucocorticoids have been developed for oral inflammatory diseases, including mucosal lesions in the oral cavity. Very recently we succeeded in preparing mucoadhesive hydroxypropyl cellulose (HPC)-film containing more than 100 mg/cm 2 of beclomethasone dipropionate (BDP). Before conducting clinical research on this film, the effects of application of this film on oral infection were examined in an animal model, since it is well known that glucocorticoids predispose to oral or pharyngeal Candida infection. [1][2][3][4][5][6] In our previous papers, a murine oral candidiasis model 6) or an esopharynxial model 7) were used, allowing the examination of the effects of topical application of mucoadhesive films.In the present study, we examined the effects of BDP-and neutrophil-Candida interactions in vitro, as well as the level to which oral application of BDP-containing HPC-film predisposes towards oral candidiasis in this murine model. MATERIALS AND METHODS Film PreparationThe film was composed of one layer of HPC (150-400 cP; Wako Pure Chemical Industries, Ltd., Osaka, Japan) as the base component. To prepare BDP-containing film, BDP (Wako) was first dissolved in ethanol, HPC added, and then ethanol added to give a final volume of 30 ml per 0.9 g HPC. A 10-ml aliquot of this solution was cast using a graduated pipette at a rate of 10 ml/4 min into a flat round Teflon dish of diameter 75 mm and then dried on a clean bench overnight. These dried films were then cut into circles of diameter 30 mm for the release study or into rectangles of 0.6 cmϫ0.5 cm for the oral candidiasis study in mice.Release of BDP from the Film Measurement of BDPrelease from the BDP-containing films was performed as follows. A dissolution apparatus was modified from the original construction of Okamoto et al.8) Briefly, a 10-ml beaker was used as the receptor compartment and a piece of sample film (3-cm diameter) attached to the inner wall of the beaker using double-sided tape, to produce the donor side. An 0.1 M phosphate buffer (PB) (pH 7.0) was then added to the beaker, which was maintained at 37°C and stirred at a constant speed using a magnetic bead. Aliquots (100 ml each) were withdrawn at preset times (1, 2, 3, 4, 5, and 30 min), and then the amount of BDP released estimated using an HPLC system (Shimadzu Co., Ltd., Kyoto, Japan) equipped with a UV detector (wavelengthϭ254 nm). To maintain a constant volume and sink conditions in the experiment, the removed solution was replaced each time with 100 ml of 0.1 M PB prewarmed to 37°C. The cumulative amount of drug release per 1 cm 2 of BDP film was then calculated. Each experiment was perf...

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Section: Discussionmentioning

confidence: 99%

“…7) Here, we compared the effects of the attachment of BDP-containing film, topical application of BDPsuspension and subcutaneous administration of prednisolone. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Oral Candidiasis Deteriorated by Local Application of a Glucocorticoid-Containing Film in a Mouse Model

Yanagi

Hisajima

Ishibashi

et al. 2008

Biological & Pharmaceutical Bulletin

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“…Therefore, we believe it is possible that the beneficial effects of farnesol on oral candidiasis may be limited locally. In this regard, we can note that oral or pharyngeal infection by Candida is easily influenced by local treatments with immunosuppressive agents, as our previous report indicated that oral inhalation of beclomethasone dipropionate degenerated the lesions of experimental pharyngeal candidiasis in mice (13).…”

Section: Discussionmentioning

confidence: 90%

Protective effects of farnesol against oral candidiasis in mice

Hisajima

Maruyama

Tanabe

et al. 2008

Microbiology and Immunology

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Farnesol is known as a quorum-sensing molecule for Candida albicans and is recognized to play pathogenic roles in Candida infection. To assess the possible role of farnesol in mucosal C. albicans infection, the effects of farnesol treatment against experimental oral candidiasis in mice were examined. Prednisolone-pretreated ICR mice were orally infected with C. albicans and 3, 24 and 30 hr later the animals were orally given farnesol. Forty-eight hr later they were killed for observation. Farnesol treatment in a dose ranging between 1.125 and 9 μmol/mouse showed a protective effect against oral candidiasis in a dose-dependent manner, at least as estimated by symptom scores of tongues. At 9 μmol/mouse it decreased bodyweight loss. Histological studies of 2.25 μmol/mouse farnesol-treated animals indicated that farnesol suppressed mycelial growth of C. albicans on the surface of tongues, but microbiological study did not prevent the change of CFU of C. albicans cells not only on tongues but also in feces, kidneys and livers. These results suggest that farnesol has very characteristic roles in protection against mucosal candidiasis.

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Candida Infections and Modelling Disease

MacCallum

2009

Pathogenic Yeasts

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A novel murine model of pharyngeal candidiasis with local symptoms characteristic of pharyngeal thrush produced by using an inhaled corticosteroid

Cited by 6 publications

References 18 publications

Oral Candidiasis Deteriorated by Local Application of a Glucocorticoid-Containing Film in a Mouse Model

Oral Candidiasis Deteriorated by Local Application of a Glucocorticoid-Containing Film in a Mouse Model

Protective effects of farnesol against oral candidiasis in mice

Candida Infections and Modelling Disease

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