doi:10.1111/j.1440-1746.2006.04353.x Journal of Gastroenterology and Hepatology 22 (2007) 749–756 © 2006 The Authors 749 Journal compilation © 2007 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd Blackwell Publishing AsiaMelbourne, AustraliaJGHJournal of Gastroenterology and Hepatology0815 93192006 Blackwell Publishing Asia Pty Ltd200622749756Original Article Candida aggravates duodenal perforationT Nakamura et al. GASTROENTEROLOGY Candida albicans aggravates duodenal ulcer perforation induced by administration of cysteamine in rats Tetsuya Nakamura,* Masashi Yoshida,* Hideki Ishikawa, † Kaori Kameyama, ‡ Go Wakabayashi,* Yoshihide Otani,* Motohide Shimazu,* Minoru Tanabe,* Shigeyuki Kawachi,* Koichiro Kumai, § Tetsuro Kubota,* Yoshiro Saikawa,* Katsuko Sano* and Masaki Kitajima* Departments of *Surgery and † Emergency and Critical Care Medicine, ‡ Division of Diagnostic Pathology, and § Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan Abstract Background: Candida sp are frequently isolated from the ascitic fluid of patients with perforated ulcers. The present study was performed to examine whether Candida infection may be involved in the process of ulcer perforation. Methods: Male Wistar rats were divided into a saline group ( n = 15) and a Candida group ( n = 17). Cysteamine-HCl (Sigma; 31 mg/100 g) was administered thrice on day 1 to both groups of animals. Candida albicans at a density of 10 8 in 0.5 mL of saline was adminis- tered 1 h before, and 12 h and 24 h after the first administration of cysteamine in the Candida group. Results: Perforated duodenal ulcers were observed in 94.1% of the rats in the Candida group, but only 26.7% of the rats in the saline group (P < 0.01). The area of the duodenal ulcers in the Candida group was 40.89 ± 33.07 mm 2 , whereas that in the saline group was 16.53 ± 20.4 mm 2 (P < 0.05). The mortality rate was significantly higher in the Candida group than in the saline group. In the Candida group, colonization by C. albicans was recognized at the ulcer base, surrounded by marked granulocytic infiltration. The number of eosinophils infiltrating the ulcer base was also significantly greater in the Candida group than in the saline group. Immunohistochemical analysis revealed the expression of secre- tory aspartyl protease (SAP) in the region of the ulcer showing colonization by C. albicans in the Candida group. Conclusion: Candida albicans aggravates duodenal ulcer perforation in the experimental model of cysteamine-induced duodenal ulcer perforation. The present findings suggest that SAP and host–parasite relationships, including granulocyte-dependent mechanisms, may be involved in the aggravation of ulcer perforation by C. albicans. Introduction Although the mechanisms of ulcer formation have been well- studied, the process of ulcer perforation has not yet been clearly elucidated. While the incidence of surgical intervention in gas- troduodenal ulcer diseases has reduced dramatically with the development of effective antisecretory drugs and effective regi- mens for the eradication of Helicobacter pylori , the incidence of ulcer perforation remains unchanged. 1 A strong association has been reported between gastroduodenal ulcers and H. pylori infec- tion, and the mean reported prevalence of H. pylori infection in uncomplicated ulcer disease is 90–100%. 2 In contrast, the mean prevalence of H. pylori infection in patients with perforated peptic ulcers is only approximately 42.1–73.3%. 2–4 Therefore, it was surmised that some other factors may be involved in the process of ulcer perforation. In a previous study, Candida species were isolated from the peritoneal fluid in 23 out of 62 patients with perforated peptic ulcer, and bacteria were isolated in 10 out of the remaining 39 cases. 5 In another study, fungal colonization was reported in 54.2% of cases of gastric ulcer, 10.3% of cases of chronic gastritis, and 4.3% of negative controls. 6 Pathological examination of resected specimens from patients with perforated ulcers in one study revealed the abundant presence of Candida albicans in the effusion layer, granulation layer, and the necrotic tissue layer at the ulcer base. 7 Thus, we speculated that C. albicans may play a role Key words eosinophil, helicobacter pylori, infection, secretory aspartyl protease, stomach. Accepted for publication 16 September 2005. Correspondence Dr Masashi Yoshida, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan. Email: masashi@sc.itc.keio.ac.jp