title: Influence of gastric colonization with Candida albicans on ulcer healing in rats: effect of ranitidine, aspirin and probiotic therapy.
abstract: OBJECTIVE
  Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. MATERIAL AND METHODS. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg(-1) day(-1) s.c.) and 2) aspirin (ASA) (60 mg kg(-1) day(-1) i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1beta and TNF-alpha and growth factors EGF and TGFalpha were assessed in the gastric mucosa.
  
  
  RESULTS
  Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1beta, TNF-alpha, EGF and TGFalpha and a significant increment in plasma IL-1beta and TNF-alpha levels.
  
  
  CONCLUSIONS
  1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1beta and TNFalpha and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.
authors.affiliation: Department of Physiology and Pathomorphology, Jagiellonian University School of Medicine, Cracow, Poland
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zwolinska-Wcislo
authors.forename: Peter C
authors.initials: PC
authors.lastname: Konturek
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kwiecien
authors.forename: Danuta
authors.initials: D
authors.lastname: Drozdowicz
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: Jerzy
authors.initials: J
authors.lastname: Stachura
authors.forename: Alicja
authors.initials: A
authors.lastname: Budak
authors.forename: Józef
authors.initials: J
authors.lastname: Bogdal
authors.forename: Wieslaw W
authors.initials: WW
authors.lastname: Pawlik
authors.forename: Eckhart G
authors.initials: EG
authors.lastname: Hahn
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001706:Biopsy; D001783:Blood Flow Velocity / Q000502:physiology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development*; D002908:Chronic Disease; D015169:Colony Count, Microbial; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism / Q000382:microbiology; D005755:Gastrins / Q000097:blood; D005786:Gene Expression Regulation; D007779:Lactobacillus acidophilus; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D019936:Probiotics / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011899:Ranitidine / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D016207:Cytokines; D005755:Gastrins; D012333:RNA, Messenger; D011899:Ranitidine; D001241:Aspirin