title: The topical use of insulin accelerates the healing of traumatic tympanic membrane perforations.
abstract: OBJECTIVE
  In recent years, there has been a tendency to search for regulatory substances that can optimize the healing process of perforated tympanic membranes (TMs). The purpose of this study was to determine the effects of using topical insulin on the healing process of traumatic TMs perforations.
  
  
  METHODS
  Experimental.
  
  
  METHODS
  Tympanic membranes of 20 Wistar rats were perforated in two sections, anterior and posterior to the malleus. The rats were divided into two groups: control and insulin. The insulin group was treated with topical regular insulin. The TMs were histologically examined 3, 5, and 7 days after the perforation through a morphometric analysis of the epithelial layer thickness, perforation size, TM cross-sectional area, semiquantitative and qualitative evaluation of the collagen production by polarization microscopy, and immunohistochemical evaluation of epithelial cells and myofibroblasts markers.
  
  
  RESULTS
  Insulin accelerated the healing process of the perforated TMs (P < 0.01); stimulated early thickening of the outer epithelial layer (P < 0.01); contributed to a larger identification of the antipankeratin antibody as epithelial marker (P < 0.05); and increased labeling of smooth muscle anti-alpha-actin antibody (P < 0.05), indicating greater proliferation of myofibroblasts. When the topical insulin was used, it resulted in a greater formation of collagen tissue (P < 0.05), with thicker and better-organized collagen fibers (P < 0.05).
  
  
  CONCLUSIONS
  Insulin accelerated the healing process of TMs traumatic perforations.
authors.affiliation: Department of Ophthalmology, Otolaryngology and Head and Neck Surgery.
authors.forename: Marcos Miranda
authors.initials: MM
authors.lastname: Araujo
authors.affiliation: Department of Ophthalmology, Otolaryngology and Head and Neck Surgery.
authors.forename: Adriana Andrade Batista
authors.initials: AA
authors.lastname: Murashima
authors.affiliation: Department of Cell and Molecular Biology and Pathogenic Bioagents, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Vani Maria
authors.initials: VM
authors.lastname: Alves
authors.affiliation: Department of Cell and Molecular Biology and Pathogenic Bioagents, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maria Célia
authors.initials: MC
authors.lastname: Jamur
authors.affiliation: Department of Ophthalmology, Otolaryngology and Head and Neck Surgery.
authors.forename: Miguel Angelo
authors.initials: MA
authors.lastname: Hyppolito
mesh_terms: D000287:Administration, Topical; D000818:Animals; D004195:Disease Models, Animal; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D014432:Tympanic Membrane / Q000187:drug effects*; D018058:Tympanic Membrane Perforation / Q000188:drug therapy* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D007328:Insulin
keywords: Tympanic membrane; collagen; immunohistochemistry; insulin; wound healing