title: Prophylactic efficacy of enteral miconazole administration for neonatal intestinal perforation and its potential mechanism.
abstract: OBJECTIVE
  Intestinal perforation (IP) is a fatal complication in extremely low birth weight infants (ELBWI). We started administrating enteral miconazole (MCZ) to ELBWI in 2002. Since then, the incidence of IP has significantly decreased. The aim of this study was to elucidate the prophylactic effect of MCZ for the treatment of neonatal IP, and to establish a new prophylactic concept for this disease.
  
  
  METHODS
  In in vivo experiments, the effects of MCZ were examined histopathologically using a mouse model of intestinal ischemia. In in vitro experiments, the cytoprotective effect of MCZ against hypoxia was evaluated using Caco-2 intestinal cells, and its anti-inflammatory potential using a co-culture model of Caco-2 and HL60 cells.
  
  
  RESULTS
  MCZ showed a tissue protective effect against intestinal ischemia. MCZ reduced high mobility group-box 1 (HMGB1) release in Caco-2 cells under hypoxic stress and attenuated the potential to activate co-cultured HL60 leukocytes with Caco-2 cells by suppressing interleukin-8 (IL-8).
  
  
  CONCLUSIONS
  MCZ may have preventive roles in the clinical management of IP in ELBWI by the suppression of IL-8 and HMGB-1.
authors.affiliation: Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan. motori@m.kufm.kagoshima-u.ac.jp.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Torikai
authors.affiliation: Department of Neonatology, Perinatal Medical Center, Kagoshima City Hospital, Kagoshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ibara
authors.affiliation: Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ieiri
authors.affiliation: Department of Preventive Medicine supported by Shin Nippon Biomedical Laboratories, Ltd. (SNBL), Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Division of Pediatric Surgery, Kagoshima City Hospital, Kagoshima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Division of Clinical Pathology, Kagoshima City Hospital, Kagoshima, Japan.
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Sueyoshi
authors.affiliation: Department of Preventive Medicine supported by Shin Nippon Biomedical Laboratories, Ltd. (SNBL), Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Department of Preventive Medicine supported by Shin Nippon Biomedical Laboratories, Ltd. (SNBL), Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Abeyama
mesh_terms: D000818:Animals; D018938:Caco-2 Cells / Q000187:drug effects; D065688:Cytochrome P-450 CYP2C9 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D007416:Intestinal Perforation / Q000517:prevention & control*; D007422:Intestines / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008825:Miconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D065688:Cytochrome P-450 CYP2C9 Inhibitors; D008825:Miconazole
keywords: HMGB1; IL-8; Intestinal perforations; Miconazole; Necrotizing enterocolitis; Newborn