title: Extending Myringotomy Patency with Topical Everolimus in Rats.
abstract: BACKGROUND
  Everolimus is an immunosuppressant agent that has antiproliferative properties and negative effects on wound healing. The effect of everolimus use to delay the closure time of myringotomy is not known.
  
  
  OBJECTIVE
  The aim of the study was to evaluate the impact of topical everolimus on myringotomy patency and to investigate its histopathologic effects on the tympanic membrane.
  
  
  METHODS
  Twenty Sprague-Dawley rats were bilaterally myringotomized with a myringotomy knife. Gelfoam soaked in 0.05% everolimus in a microemulsion formulation was applied to the right myringotomy site of the rats for 10 min (the everolimus group). The myringotomy sites of the left ears were treated with sterile saline topically (the control group). The tympanic membranes were routinely examined otomicroscopically every other day for 31 days. The membranes were then harvested and evaluated histologically after 31 days.
  
  
  RESULTS
  All tympanic membranes were closed by the 15(th) day in the control group, while in the everolimus group the myringotomy remained open in five rats (25%) on day 31. The mean durations of myringotomy patency in the everolimus group and control group were 20.90 ± 7.85 and 10.10 ± 3.14 days, respectively. The difference was found to be statistically significant (p < 0.01). In the histopathological examination of the tympanic membranes, there was less fibrosis and less inflammation in the everolimus group than in the control group (p < 0.01).
  
  
  CONCLUSIONS
  Topical everolimus application is effective in extending myringotomy patency in rat tympanic membranes. Inflammatory reactions and fibrosis in the lamina propria were observed to be significantly less when topical everolimus was used.
authors.affiliation: Department of Otolaryngology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey.
authors.forename: Sevtap
authors.initials: S
authors.lastname: Akbulut
authors.affiliation: Department of Otolaryngology, Acibadem Hospital, Istanbul, Turkey.
authors.forename: Hande
authors.initials: H
authors.lastname: Altintas
authors.affiliation: Department of Otolaryngology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Berk
authors.affiliation: Department of Pathology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey.
authors.forename: Nagehan
authors.initials: N
authors.lastname: Ozdemir
mesh_terms: D000287:Administration, Topical; D000818:Animals; D004337:Drug Carriers; D004655:Emulsions; D000068338:Everolimus / Q000008:administration & dosage*; D005355:Fibrosis; D005781:Gelatin Sponge, Absorbable; D008297:Male; D008876:Middle Ear Ventilation / Q000295:instrumentation; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014432:Tympanic Membrane / Q000187:drug effects* / Q000473:pathology / Q000601:surgery*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D000068338:Everolimus