H Koga

Nihon Nohyaku Co., Ltd., Edo, Tōkyō, Japan

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Publications (8)19.75 Total impact

  • Medical Mycology 10/2008; 37(5):351-355. DOI:10.1111/j.1365-280X.1999.00243.x · 2.34 Impact Factor
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    ABSTRACT: To investigate the mode of action of the newly synthesized optically active imidazole compound, NND-502, (-)-(E)-[4-(2, 4-dichlorophenyl)-1,3-dithiolan-2-ylidene]-1-imidazolylacetonit rile, its effect on ergosterol biosynthesis in cell-free extracts of Candida albicans was examined and compared with that of the (S)-enantiomer of NND-502 in addition to lanoconazole and bifonazole, both of which are clinically used for the treatment of dermatomycoses. NND-502 was found to interfere with ergosterol biosynthesis by inhibition of sterol 14alpha-demethylase, while no interference due to the (S)-enantiomer of NND-502 was found, indicating that the stereochemical orientation of the 2, 4-dichlorophenyl group plays an important role in the interaction with the enzyme. In terms of drug concentration exerting 50% inhibition of ergosterol biosynthesis, NND-502 was 2.5 and 28 times more effective than that of lanoconazole and bifonazole, respectively.
    Medical Mycology 11/1999; 37(5):351-5. DOI:10.1046/j.1365-280X.1999.00243.x · 2.34 Impact Factor
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    ABSTRACT: To assess the migratory response of fibroblasts in vitro, normal human dermal fibroblasts (NHDF) were cultured in the presence of L-ascorbic acid 2-phosphate to induce a multilayered structure. Round wounds were made by punching, and the migratory response was evaluated by counting the number of migrating cells in the wounded areas. Collagenase activity in the culture-medium was then measured. When the wound model was treated with bFGF, IL-1 alpha or PDGF, the migratory response was facilitated with increased collagenase secretion. In contrast, treatment with TGF-beta reduced the migratory response and collagenase secretion. Since the multilayered structure is rich in collagenous matrix, degradation of the matrix by secreted collagenase is probably necessary for the cells to migrate into the wounded areas. Furthermore, malotilate, which is now under development as an agent for wound therapy, facilitated the migratory response of NHDF with increased collagenase secretion in this wound model, suggesting that the wound healing effect of malotilate is in part attributable to stimulated migration of fibroblasts to wounded areas subsequent to extracellular matrix-degradation.
    Journal of Dermatological Science 07/1998; 17(2):123-31. DOI:10.1016/S0923-1811(98)00003-6 · 3.42 Impact Factor
  • Journal of Dermatological Science 06/1996; 12(2):215-215. DOI:10.1016/0923-1811(96)89601-0 · 3.42 Impact Factor
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    ABSTRACT: The wound healing effect of malotilate (CAS 59937-28-9, NKK-105) was investigated by using an excisional skin-wound model produced on the back of normal and healing-impaired (induced by prednisolone pretreatment) rats. The rapid decrease in the square measure of wound areas and the improvement in the histological evaluation clarified that 0.3% and 1% cream preparations of malotilate were obviously effective in accelerating spontaneous healing in the normal rats. The accelerative effect of malotilate cream preparations was likely superior to that of an ointment containing 5% deproteinized calf blood extract used as a reference agent. The same effect was also observed in the healing-impaired rats. The histological findings revealed that a thicker and more cellular granulation tissue, which in turn created an adequate bed for rapid re-epithelization, was formed in the malotilate-treated animals. Acceleration of granulation tissue formation by malotilate was also supported by the cotton pellet implantation method. It is concluded from these results that malotilate seems to be a promising agent for topical wound therapy.
    Arzneimittel-Forschung 05/1996; 46(4):450-5. · 0.70 Impact Factor
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    ABSTRACT: The wound healing effect of cream preparations of lanoconazole (CAS 101530-10-3, NND-318), an antimycotic imidazole compound, was examined using an excisional open skin-wound model produced on the back of rats. The rapid decrease in the size of wounded areas showed that 0.5% and 1% lanoconazole creams accelerated spontaneous healing. The effectiveness was almost similar to that of an ointment containing 5% deproteinized calf blood extract (DCBE), a wound healing agent on the market. In contrast, neither 1% clotrimazole cream nor 1% bifonazole cream, both of which are imidazole antimycotics, showed an accelerative effect. The wound healing effect of lanoconazole was further confirmed by histological evaluation; a thicker and more cellular granulation tissue was formed, and epidermal regeneration was more stimulated by lanoconazole than by non-treatment or vehicle alone. The effect of lanoconazole on the formation of granulation tissue in rats was also studied using a cotton pellet implantation method. Lanoconazole accelerated the formation of this tissue in terms of dry weight in a dose dependent manner (0.5-4 mg/pellet), and collagen content and angiogenesis also increased in the stimulated tissue, indicating that these accompany the compound-induced acceleration of tissue formation. These results suggest that lanoconazole has a distinctive wound healing effect which is a feature no other imidazole antimycotic is known to possess to date.
    Arzneimittel-Forschung 03/1996; 46(2):218-23. · 0.70 Impact Factor
    Journal of Dermatological Science 08/1994; 8(1). DOI:10.1016/0923-1811(94)90498-7 · 3.42 Impact Factor
    Journal of Dermatological Science 09/1992; 4(2). DOI:10.1016/0923-1811(92)90219-2 · 3.42 Impact Factor