Motofumi Torikai1, Satoshi Ibara2, Satoshi Ieiri3, Takashi Hamada4, Hiroyuki Noguchi5, Kazunobu Sueyoshi6, Takeo Fukuda4, Kazuhiro Abeyama4. 1. 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. 2. Department of Neonatology, Perinatal Medical Center, Kagoshima City Hospital, Kagoshima, Japan. 3. 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. 4. 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. 5. Division of Pediatric Surgery, Kagoshima City Hospital, Kagoshima, Japan. 6. Division of Clinical Pathology, Kagoshima City Hospital, Kagoshima, Japan.
Abstract
PURPOSE: 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). CONCLUSION: MCZ may have preventive roles in the clinical management of IP in ELBWI by the suppression of IL-8 and HMGB-1.
PURPOSE: 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). CONCLUSION:MCZ may have preventive roles in the clinical management of IP in ELBWI by the suppression of IL-8 and HMGB-1.
Authors: M Thyoka; P de Coppi; S Eaton; K Khoo; N J Hall; J Curry; E Kiely; D Drake; K Cross; A Pierro Journal: Eur J Pediatr Surg Date: 2012-03-20 Impact factor: 2.191
Authors: Ruben Zamora; Anatoli Grishin; Catarina Wong; Patricia Boyle; Jin Wang; David Hackam; Jeffrey S Upperman; Kevin J Tracey; Henri R Ford Journal: Am J Physiol Gastrointest Liver Physiol Date: 2005-06-09 Impact factor: 4.052