title: Detection of epithelial apoptosis in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis.
abstract: BACKGROUND
  Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP.
  
  
  OBJECTIVE
  Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP.
  
  
  METHODS
  Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot.
  
  
  RESULTS
  Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups.
  
  
  CONCLUSIONS
  Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.
authors.affiliation: Coloproctology Unit of the Surgery Department, University of Campinas (UNICAMP), Medical School, São Paulo, Brazil. raquelleal@mpc.com.br
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Leal
authors.forename: Maria de Lourdes S
authors.initials: Mde L
authors.lastname: Ayrizono
authors.forename: Marciane
authors.initials: M
authors.lastname: Milanski
authors.forename: João J
authors.initials: JJ
authors.lastname: Fagundes
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Moraes
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Meirelles
authors.forename: Lício A
authors.initials: LA
authors.lastname: Velloso
authors.forename: Cláudio S R
authors.initials: CS
authors.lastname: Coy
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000473:pathology / Q000601:surgery*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000473:pathology / Q000601:surgery*; D039021:Colonic Pouches / Q000009:adverse effects / Q000473:pathology*; D006801:Humans; D007082:Ileum / Q000033:anatomy & histology / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C506592:APAF1 protein, human; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053181:Caspase 8; D053453:Caspase 9