Talas, Gyorgyi; (2000) The role of phenytoin (5, 5-diphenylhydantoin) and structurally related compounds in wound healing. Doctoral thesis (Ph.D.), University College London.

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Abstract

Low concentrations of PHT (5-10<IMG WIDTH=8 HEIGHT=14 ALIGN=MIDDLE SRC="/maths/mu.gif">g/ml) were found to upregulate the proliferation of some fibroblast and keratinocyte cell lines, but not others. Micro Chemotaxis Chamber assays revealed PHG (5-50<IMG WIDTH=8 HEIGHT=14 ALIGN=MIDDLE SRC="/maths/mu.gif">g/ml) to be a chemoattractant for both normal and RDEB fibroblasts and keratinocytes, indicating that it may facilitate the recruitment of cells into the wound space. Prolonged treatment with PHG (20<IMG WIDTH=8 HEIGHT=14 ALIGN=MIDDLE SRC="/maths/mu.gif">g/ml) reduced the contraction of both the normal and the hypercontractile RDEB fibroblasts in vitro as measured by the reduction in surface area of untethered fibroblast-populated collagen lattices or directly by the Culture Force Monitor. Good correlations were observed with this finding in vivo in reducing wound contraction of pigs without impairment of healing after two or three weeks post-operatively (with either PHT powder or incorporated into Fibrin Sealant). The effects of compounds structurally related to PHT were also investigated to see if a structure-activity relationship could be determined which would provide clues for the design of new drugs for wound healing. Both Micro Chemotaxis Chamber assays and Culture Force Monitor measurements indicated that metabolites of PHT were more active than the parent compound.

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