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Pharmacological profiles of high-concentration (20 microg/g) tacalcitol ointment: effects on cutaneous inflammation, epidermal proliferation, and differentiation in mice.

Abstract
This study focused on the effects of tacalcitol (1,24 (R) (OH)2D3, TV-02) ointment (20 micro g/g) on cutaneous inflammation, epidermal proliferation, and differentiation and compared them with tacalcitol ointment (2 micro g/g) and other anti-psoriatic ointments using hairless mice. Tacalcitol ointment (0, 2 and 20 micro g/g) significantly inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cutaneous inflammation, histopathologically. The effect of tacalcitol ointment (20 micro g/g) on cutaneous inflammation was much stronger than that of tacalcitol ointment (0, 2 micro g/g), and as effective as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). Tacalcitol ointment (20 micro g/g) also significantly inhibited TPA-induced myeloperoxidase (MPO) activity, as effectively as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). The effect of tacalcitol ointment on epidermal proliferation [ornithine decarboxylase (ODC) activity] and differentiation [transglutaminase (TGase) activity] was dose-dependent from 0 micro g/g to 20 micro g/g. The effect of tacalcitol ointments on epidermal proliferation was significant at the doses of 2 micro g/g and 20 micro g/g, and that on epidermal differentiation was significant at the doses of 0.2 micro g/g or more. The effect of tacalcitol ointment (20 micro g/g) on epidermal differentiation was significantly stronger than tacalcitol ointment (2 micro g/g). In this study, tacalcitol ointment (20 micro g/g) was found to have a marked effect on cutaneous inflammation and improved effect on epidermal differentiation, although tacalcitol ointment (2 micro g/g) also had significant effects on epidermal proliferation and differentiation. These findings support the clinical effectiveness of tacalcitol ointment (20 micro g/g) against psoriasis.
AuthorsHiroaki Sato, Yasuhiro Ogino, Hideko Takagi, Junko Hata, Satoshi Asano, Tomohiro Ohta, Keiji Komoriya
JournalThe Journal of dermatology (J Dermatol) Vol. 30 Issue 7 Pg. 510-24 (Jul 2003) ISSN: 0385-2407 [Print] England
PMID12928540 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Dihydroxycholecalciferols
  • Ointments
  • 1 alpha,24-dihydroxyvitamin D3
Topics
  • Administration, Topical
  • Animals
  • Biopsy, Needle
  • Dermatitis (drug therapy, pathology)
  • Dihydroxycholecalciferols (pharmacology)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epidermis (drug effects, pathology)
  • Female
  • Immunohistochemistry
  • Mice
  • Mice, Hairless
  • Ointments
  • Psoriasis (drug therapy, pathology)
  • Reference Values
  • Treatment Outcome

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