title: Topical diphenylhydantoin sodium can improve healing in a diabetic incisional animal wound model.
abstract: OBJECTIVE
  Anecdotally, topical application of diphenylhydantoin sodium (DpH) (phenytoin) has been shown to aid wound healing. We previously reported improved healing following topical infiltration of DpH in a healthy animal wound model. This study evaluates its effect on an incisional wound model in diabetic animals.
  
  
  METHODS
  Twenty-five male Sprague-Dawley rats were rendered diabetic by a single intraperitoneal injection of streptozotocin. Two caudal and two cephalad wounds were made on the dorsal surface. A polyvinyl alcohol sponge was placed in a subcutaneous pocket created proximal to both cephalad wounds. Each wound was either treated topically with 10mg DpH in a 200microl carrier or an equal volume of the saline vehicle (control) on the day of wounding and days 3 and 6 post-incision. The animals were sacrificed on day 10. The breaking strength of fresh and fixed wounds was determined by tensiometry, and the hydroxyproline content was determined spectrophotometrically.
  
  
  RESULTS
  There was a significant overall increase in both fresh (24%) and fixed (18%) wound-breaking strength of the DpH-treated wounds when compared with the controls (p<0.05). This was associated with an increase in collagen synthesis as indicated by the increased hydroxyproline content in the DpH-infiltrated sponges when compared with the controls.
  
  
  CONCLUSIONS
  Our data suggest that topical DpH improves healing in a diabetic wound model. Topical administration of DpH has the potential to accelerate diabetic wound healing and should be evaluated in human diabetic wounds.
authors.affiliation: Department of Surgical Research, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. fchan@rcsi.ie
authors.forename: F C
authors.initials: FC
authors.lastname: Chan
authors.forename: C
authors.initials: C
authors.lastname: Kennedy
authors.forename: R P
authors.initials: RP
authors.lastname: Hanson
authors.forename: B
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: J
authors.initials: J
authors.lastname: Kelly
authors.forename: D
authors.initials: D
authors.lastname: Bouchier-Hayes
mesh_terms: D000818:Animals; D003094:Collagen / Q000032:analysis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006909:Hydroxyproline / Q000032:analysis / Q000187:drug effects; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D008297:Male; D010672:Phenytoin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000627:therapeutic use; D013053:Spectrophotometry; D013311:Streptozocin; D013718:Tensile Strength; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D014950:Wounds, Penetrating / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D012965:Sodium Chloride; D013311:Streptozocin; D010672:Phenytoin; D003094:Collagen; D006909:Hydroxyproline