Ulcerative Colitis: Duclos B

Calon A, Gross I, Lhermitte B, Martin E, Beck F, Duclos B, Kedinger M, Duluc I, Domon-Dell C, Freund JN. · INSERM U682, 3 Avenue Molière, 67200 Strasbourg, France. · Gut. · Pubmed #17595234 No free full text.

Abstract: AIMS: The CDX1 and CDX2 homeoproteins are intestine-specific transcription factors regulating homeostasis. We investigated their relevance in experimentally-induced intestinal inflammation. METHODS: The response to intestinal inflammation induced by dextran sodium sulfate (DSS) was compared in wild type, Cdx1(-/-) and Cdx2(+/-) mice. Intestinal permeability was determined in wild type and Cdx2(+/-) mice. Protein-protein interactions were investigated by co-immunoprecipitation and GST-pulldown, and their functional consequences were assessed using Luciferase reporter systems. RESULTS: Heterozygous Cdx2(+/-) mice, but not Cdx1(-/-) mice, were hypersensitive to DSS-induced acute inflammation as all these mice showed blood in the stools at day 1 of DSS treatment. Hypersensitivity was associated to a 50% higher intestinal permeability. In Cdx2(+/-) mice, the colonic epithelium was repaired during the week after the end of DSS treatment, whereas two weeks were required for wild type animals. Subsequently, no colonic tumour was observed in Cdx2(+/-) mice subjected to 5 repeated cycles of DSS, in contrast to the 2.7 tumours found per wild type mouse. Based on the fact that Smad3(+/-) mice, like Cdx2(+/-) mice, better repair the damaged intestinal epithelium, we found that the CDX2 protein interacts with SMAD3, independently of SMAD4, resulting in a 5-fold stimulation of SMAD3 transcriptional activity. CDX1 also interacted with SMAD3 but it inhibited by 10-fold the SMAD3/SMAD4-dependent transcription. CONCLUSION: The Cdx1 and Cdx2 homeobox genes have distinct effects on the outcome of a pro-inflammatory challenge. This is mirrored by different functional interactions of the CDX1 and CDX2 proteins with SMAD3, a major element of the TGFbeta signalling pathway.

Reumaux D, Colombel JF, Masy E, Duclos B, Heresbach D, Belaïche J, Cortot A, Duthilleul P, Anonymous00047. · Département d'Hématologie-Immunologie-Cytogénétique, Centre Hospitalier de Valenciennes, France. · Inflamm Bowel Dis. · Pubmed #11149558 No free full text.

Abstract: The relationship between anti-neutrophil cytoplasmic auto-antibodies (ANCA) and disease activity in inflammatory bowel diseases remains controversial. The aim of this study was to highlight the relationship between ANCA presence or titers and disease activity in ulcerative colitis (UC). Three groups of patients with UC were studied: 1) group A included 39 patients who had not undergone colectomy, 2) group B, 43 patients with subtotal colectomy and ileo-rectal anastomosis, 3) group C, 98 patients with proctocolectomy and ileo-anal anastomosis, including 88% with pouchitis and 12% without pouchitis at the time of the study. Determination of ANCA was performed using the standardized indirect immunofluorescence assay. ANCA were positive in 59%, 65%, and 54% of patients from groups A, B, and C, respectively (NS). No relationship between ANCA presence or titers and UC activity could be detected within groups A and B. In group C, 45 of 86 patients (52%) without pouchitis and 8 of 12 patients (67%) with pouchitis, were ANCA positive (NS). These results do not support a relationship between ANCA and UC activity in this cohort of 180 patients.

Reimund JM, Duclos B, Koehl C, Lehr L, Ezenfis J, Baumann R. · Service d'Hépato-Gastroentérologie et d'Assistance Nutritive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, France. · Eur J Gastroenterol Hepatol. · Pubmed #10503839 No free full text.

Abstract: OBJECTIVE: Increased nitric oxide (NO) has been demonstrated in inflammatory bowel diseases (IBD). Plasma and urinary nitrite and nitrate are usually considered to reflect global NO generation. Recently it has been suggested that plasma nitrate may be a discriminant indicator between infectious enterocolitis (IC) and IBD. To investigate this hypothesis we compared plasma and 24 h urinary nitrite and nitrate in 13 healthy controls, 44 patients with IBD [Crohn's disease (CD) n = 30; ulcerative colitis (UC) n = 14], 16 patients presenting with IC and seven chronic radiation enterocolitis (RE) patients. RESULTS: Despite a trend towards higher plasma nitrate in IC (54.6+/-11.4 micromol/l) than in the other groups (CD: 38.4+/-4.8, UC: 34.8+/-8.4, RE: 34.7+/-7.5, controls: 31.1+/-5.2), this difference was not statistically significant. Urinary nitrate was higher in IBD, IC and RE than in controls, with no difference between these groups. Nitrite concentrations were not different. Nitrate levels were positively correlated with blood and 24 h urinary neopterin (e.g. plasma nitrate and blood neopterin: r = 0.54, P<0.0001), and in some cases, to C-reactive protein. CONCLUSIONS: High nitrate (in our case only urinary nitrate) appears to be secondary to the magnitude of the inflammation rather than the aetiology of the diarrhoea. It should therefore more likely be considered as a marker of the severity of the inflammatory response rather than used as a discriminant indicator between IC and IBD patients.

Reimund JM, Jung-Chaigneau E, Chamouard P, Wittersheim C, Duclos B, Baumann R. · Service d'Hépato-Gastroentérologie et d'Assistance Nutritive, Hôpitaux Universitaires de Strasbourg, France. · Gastroenterol Clin Biol. · Pubmed #10470529 No free full text.

Abstract: OBJECTIVE: To evaluate the diagnostic accuracy of high resolution sonography in patients with inflammatory bowel disease (MICI). PATIENTS AND METHODS: In patients with Crohn's disease (n = 48), ulcerative colitis (n = 23), indeterminate colitis (n = 3), inflammatory (n = 21) and non-inflammatory (n = 23) controls, high resolution sonography was performed and compared to colonoscopy (+/- retrograde ileoscopy) and/or baryum studies of the small bowel and the colon. RESULTS: Diagnosis of intestinal inflammation or not was correct in 69/74 MICI patients (sensitivity: 94.4%, specificity: 66.7%, global accuracy: 93.2%). Segment location was accurate in 58/74 (sensitivity: 80.3%, specificity: 66.7%, global accuracy: 79.7), more frequently in Crohn's disease, than in ulcerative colitis. Five out of six complications of Crohn's disease were diagnosed. In Crohn's disease, the method was more accurate in case of colonic or ileocolonic involvement. CONCLUSION: High resolution sonography is a reliable diagnostic tool for the detection of intestinal inflammation and related complications in MICI. In can be of value in the follow-up and seems particularly interesting in the case of temporary contraindication of invasive methods.