Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis

Background: Rectal budesonide is an effective treatment of active ulcerative proctitis or proctosigmoiditis. Aim: To compare the therapeutic efficacy, tolerability and safety, and patient's preference of budesonide foam vs. budesonide enema. Methods: Patients with active ulcerative proctitis or proctosigmoiditis (clinical activity index >4 and endoscopic index ≥4) were eligible for this double-blind, double-dummy, randomized, multicentre study. They received 2 mg/25 mL budesonide foam and placebo enema (n = 265), or 2 mg/100 mL budesonide enema and placebo foam (n = 268) for 4 weeks. Primary endpoint was clinical remission (clinical activity index ≤4) at the final/withdrawal visit (per protocol). Results: A total of 541 patients were randomized - 533 were evaluable for intention-to-treat analysis and 449 for per protocol analysis. Clinical remission rates (per protocol) were 60% for budesonide foam and 66% for budesonide enema (P = 0.02362 for non-inferiority of foam vs. enema within a predefined non-inferiority margin of 15%). Both formulations were safe and no drug-related serious adverse events were observed. Because of better tolerability and easier application most patients preferred foam (84%). Conclusion: Budesonide foam is as effective as budesonide enema in the treatment of active ulcerative proctitis or proctosigmoiditis. Both budesonide formulations are safe, and most patients prefer foam.publishersversionPeer reviewe

Studies on the genetic and non-genetic (physiological) variation of human erythrocyte glutamic oxaloacetic transaminase

The thermostability profile of seven different electrophoretic variants of human erythrocyte GOT found in 13 different, unrelated families from a racially heterogeneous population was examined. The five different slow-variant and the two different fast-variant classes could be grouped into four different thermostability classes which were termed unstable, less stable, normal and more stable than normal. The thermostability differences among and within the electrophoretic variant classes permitted differentiation of the 13 individusals possessing an electrophoretic variant phenotype into a total of ten different variants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66025/1/j.1469-1809.1982.tb00711.x.pd

Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease

Contains fulltext : 96924.pdf (publisher's version ) (Open Access)BACKGROUND: We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD. METHODS: mRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls. RESULTS: mRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD. CONCLUSIONS: FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients