Ulcerative Colitis: Bonaz B

Reimund JM, Bonaz B, Gompel M, Michot F, Moreau J, Veyrac M, Wagner Ballon J. · Service de gastroentérologie, Hôpital de Hautepierre, 67098 Strasbourg. · Gastroenterol Clin Biol. · Pubmed #15672571 No free full text.

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Stanke-Labesque F, Pofelski J, Moreau-Gaudry A, Bessard G, Bonaz B. · Laboratory of Pharmacology, Grenoble University Hospital, Grenoble, France. · Inflamm Bowel Dis. · Pubmed #18286646 links to  free full text

Abstract: BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders collectively referred to as inflammatory bowel diseases (IBD). Cysteinyl leukotrienes are proinflammatory 5-lipoxygenase-derived products that play a major role in the immune and inflammatory response. Consequently, they may be involved in the pathogenesis of IBD. The aim of this study was therefore to evaluate 1) the urinary excretion of leukotriene E(4) (LTE(4)) in IBD patients and healthy volunteers, and 2) the association between LTE(4) production and the activity (relapse/remission) of the disease. METHODS: IBD patients and healthy volunteers were prospectively recruited. CD and UC activity was determined on inclusion with the Crohn's Disease Activity Index and Clinical Activity Index, respectively. Urine was collected and the urinary excretion of LTE(4) was measured by liquid chromatography tandem mass spectrometry. RESULTS: 32 CD patients, 28 UC patients, and 30 controls were enrolled in the study. LTE(4) urinary excretion was significantly increased (P < 0.01) in CD [52.0 pg/mg creatinine (10th-90th percentiles: 26.2-148.0)] and UC [64.1 pg/mg creatinine (10th-90th percentiles: 26.7-178.0)] patients compared to controls [32.3 pg/mg creatinine (10th-90th percentiles: 21.8-58.8)]. LTE(4) levels were higher (P < 0.001) in patients with active disease than in patients in remission, for whom the levels of LTE(4) were similar to the levels of controls. CONCLUSIONS: Cysteinyl leukotriene pathway activation could contribute to the inflammation associated with IBD. The quantification of urinary LTE(4) could be an interesting noninvasive biomarker for the assessment of IBD activity.

Roblin X, Germain E, Phelip JM, Ducros V, Pofelski J, Heluwaert F, Oltean P, Faucheron JL, Bonaz B. · Département d'hépatogastroentérologie, département de biologie appliquée, CHU de Grenoble, France. · Rev Med Interne. · Pubmed #16376461 No free full text.

Abstract: BACKGROUND: A high prevalence (52%) of hyperhomocysteinemia is observed in Crohn disease (CD), however it is not well documented in ulcerative colitis (UC). Furthermore, in the different works studying hyperhomocysteinemia the associated factors are different. AIM: Prospective evaluation of hyperhomocysteinemia in inflammatory bowel disease (IBD) patients, of the risk factors and the determination of a potential risk of colorectal carcinoma in case of hyperhomocysteinemia. PATIENTS AND METHODS: IBD patients followed in our department were prospectively recruited between November 2003-September 2004. To be included patients should have passed a coloscopy in the two years. Patients with kidney failure or drugs supposed, to interfere with homocystéine metabolism (folates, vitamin B12, methotrexate) were excluded from the study. The following parameters were analysed: age, sex, clinical activity indexes (CDAI for Crohn disease and CAI for ulcerative colitis), length-extent and type of the disease (CD or UC), smoking, plasma homocystein concentration, folates and vitamin B12. RESULTS: Eighty-one patients (60 CD, 21 UC, mean age 43.8 +/- 17.3) were included, 30 had an active disease at inclusion and 16 were smokers. The prevalence of high homocystein concentration was 55.6%. In univariate analysis a low rate of folates was the only risk factor for a high homocystein concentration (74 vs. 52.8%; P = 0.018). Smoking was almost an associated factor. In multivariate analysis, a low rate of folate was the only risk factor of hyperhomocysteinemia, OR = 3.59 [1.27-10.17]. Five endoscopic lesions considered as precancerous were described; these patients had all a hyperhomocysteinemia. CONCLUSION: The prevalence of hyperhomocysteinemia is high in UC and in CD. A low folate rate is the only risk factor observed in our study. There is a possible link between colorectal cancer and hyperhomocysteinemia. A high Plasma homocystein concentration must be search in inflammatory bowel disease patients and a substitutive treatment of folates and vitamin B12 is necessary in case of hyperhomocysteinemia.

Roblin X, Serre-Debeauvais F, Phelip JM, Faucheron JL, Hardy G, Chartier A, Helluwaert F, Bessard G, Bonaz B. · Département d'Hépato-Gastroentérologie, CHU de Grenoble, 38043 Grenoble Cedex, France. · Aliment Pharmacol Ther. · Pubmed #15801918 links to  free full text

Abstract: BACKGROUND: 6-Thioguanine (6-tioguanine) nucleotides are the active metabolites of azathioprine. AIM: The aim of the study was to evaluate the rate of clinical remission without steroids in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine, the medium- and long-term efficacy and the predictive factors of clinical response when monitoring 6-tioguanine. METHODS: Steroid-dependent Crohn's disease and ulcerative colitis patients receiving either azathioprine or not (treated later with a daily dose of 2.5 mg/kg) were prospectively included. 6-tioguanine was monitored at 1 and 2 months and every 3 months thereafter for 1 year. The azathioprine dose was adapted to reach a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells. Thiopurine methyltransferase genotype/phenotype was evaluated in some patients. RESULTS: A total of 106 patients were prospectively included (70 Crohn's disease, 36 ulcerative colitis). The clinical remission rate without steroids in patients receiving azathioprine, in intention-to-treat analysis, was 72% and 59% at 6 and 12 months, respectively. The remission rate was significantly higher in patients with 6-tioguanine >250 pmol/8 x 10(8) RBC (86% and 69% at 6 and 12 months, respectively; P < 0.01). No significant difference was observed between Crohn's disease and ulcerative colitis patients whether treated by azathioprine or not on inclusion. In the univariate analysis, the absence of Crohn's disease stenosis, a 6-tioguanine level >250 pmol/8 x 10(8) RBC, and an increase of erythrocyte mean corpuscular volume were the factors predictive of a favourable clinical response. In the multivariate analysis, only a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells was a predictive factor of favourable clinical remission. CONCLUSIONS: Clinical remission without steroids is significantly more likely when monitoring 6-tioguanine so as to reach a level of >250 pmol/8 x 10(8) red blood cells in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine (86% and 69% at 6 and 12 months, respectively).

Roblin X, Bonaz B. · No affiliation provided · Dis Colon Rectum. · Pubmed #15690679 No free full text.

This publication has no abstract.