| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Research Abstract |
To develop agents for severe pruritus related to atopic dermatitis, we established an assay for evaluating pruritus using the frequency of scratching in mice as an index. In addition, we clarified the mechanism of pruritus using the model, and investigated new inhibitors from natural.
1.We established seven transient pruritus models, in which administration of a pruritus-inducing substance to normal mice induced scratching activities, and three chronic pruritus models, in which induced scratching in the disease skin of atopic dermatitis NC mice or type I + IV allergy model mice by sensitization with hen-egg white lysozyme (HEL). We investigated the mechanism of pruritus using those models. Histamine, serotonin and PAF all induced scratching behavior in both model of normal and disease skin. However, threshold concentration of some pruritus-induced substances in disease skin was lower than that in normal skin (pruritus sensitivity phenomenon). Also, central nerve system plays some role in chronic and severe puritus.
2.We discovered a phenomenon in which the blood flow (BF) in vein microcirculation markedly decrease in the type I + IV allergy model mice with pruritus sensitivity skin. Therefore, we investigated the mechanism of the BF decrease in order to clarify the relation between decrease BF and pruritus sensitivity phenomenon. The mechanism of the BF decrease by HEL-sensitization is very complicated, which is involving various factors such as of nitric oxide, cyclooxygenase -1 and -2, thromboxane A_2, prostaglandin I_2 and endothelin-1.
3.Using several established assays, we demonstrated the anti-pruritus activity of the flower of Impatiens Textori, the callus of Hypericum patulum and the bud of Hibiscus syriacus, isolated active compounds from each natural sources, analyzed the structures of them, and investigated the action mechanism to develop new agents for pruritus.
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