Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation.

Objective: Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a beneficial effect on bone density of the bisphosphonate risedronate in osteopenic Crohn's disease patients.

Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European Project.

Objective: Through genome-wide association scans and meta-analyses thereof, over 70 genetic loci (Crohn's disease (CD) single nucleotide polymorphisms (SNPs)) are significantly associated with CD. We aimed to investigate the influence of CD-SNPs and basic patient characteristics on CD clinical course, and develop statistical models to predict CD clinical course.

Design: This retrospective study included 1528 patients with CD with more than 10 years of follow-up from eight European referral hospitals.

Matrix metalloproteinases and their tissue inhibitors as prognostic indicators for diagnostic and surgical recurrence in Crohn's disease.

Background: Recurrence of disease after surgically induced remission constitutes a major and largely unpredictable problem in Crohn's disease (CD). Matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMP) are involved in the (etio)pathogenesis of CD and may thereby also affect postsurgical outcome. We studied the predictive value of 1) allelic composition at MMP, TIMP, and TNF-alpha single nucleotide polymorphism loci, and 2) MMP and TIMP intestinal protein levels relative to important clinical variables for recurrence of CD after resection of diseased bowel.

Role of matrix metalloproteinase, tissue inhibitor of metalloproteinase and tumor necrosis factor-alpha single nucleotide gene polymorphisms in inflammatory bowel disease.

Aim: To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1, -2, -3, -9, tissue inhibitors of metalloproteinases (TIMP)-1, -2 and tumor necrosis factor (TNF)-alpha in the etiopathogenesis of inflammatory bowel diseases (IBD), that may enhance susceptibility and/or disease severity.

Methods: Genomic DNA from 134 Crohn' s disease (CD), 111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR.

Infliximab treatment influences the serological expression of matrix metalloproteinase (MMP)-2 and -9 in Crohn's disease.

Background: Matrix metalloproteinases (MMPs) are actively involved in the pathogenesis of Crohn's disease (CD). We assessed the effect of the anti-tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody infliximab on the in vitro and in vivo expression of MMP-2 and MMP-9 in CD.

Methods: Infliximab-treated fistulizing (n = 10) or active disease (n = 7) CD patients, from an in-house study, and fistulizing CD patients (n = 42) and active CD patients (n = 24) from 2 placebo controlled studies were evaluated for serum MMP levels and clinical response.

Effect of the anti-tumor necrosis factor-alpha antibody infliximab on the ex vivo mucosal matrix metalloproteinase-proteolytic phenotype in inflammatory bowel disease.

Background: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-a antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9, and their inhibitors TIMP-1, -2 by IBD versus control intestinal mucosa ex vivo and to assess the regulatory capacity by infliximab of the proteolytic phenotype.

Methods: Intestinal mucosal explants from 20 IBD and 15 control patients were cultured with or without infliximab and/or the T-cell activator pokeweed mitogen (PWM).

Is perianal Crohn's disease associated with intestinal fistulization?

Background: When cases of Crohn's disease (CD) are described as "fistulizing," distinctions are often not drawn between perianal and intestinal fistulization. The question, therefore, remains open as to whether or not there is truly an association between perianal fistulization and intraabdominal intestinal fistulization in CD.

Aims: We have sought to determine the association between perianal and intestinal fistulization by analyzing the cases of CD recorded in databases from six international centers.

Absorption of the oral bisphosphonate alendronate in osteoporotic patients with Crohn's disease.

The absorption of bisphosphonates from the gut is poor. The question arises whether the absorption of alendronate, and thus its bioavailability, is further altered by the local inflammatory process in patients with Crohn's disease, thereby potentially affecting clinical outcome when used in the treatment of osteoporosis. To address this question, urinary excretion of alendronate was evaluated 3 months and 6 months after start of treatment with oral alendronate at a dose of 10 mg/day in 19 osteoporotic patients with stable Crohn's disease, 12 of whom had an intestinal resection.

Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease.

Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO).

Differential mucosal expression of three superoxide dismutase isoforms in inflammatory bowel disease.

Mucosal tissue damage and dysfunction in chronic inflammatory bowel disease (IBD) are partly caused by an enduring exposure to excessive amounts of reactive oxygen metabolites (ROMs). Although the three human isoforms of superoxide dismutase (SOD), copper/zinc (Cu/Zn)-SOD, manganese (Mn)-SOD, and extracellular (EC)-SOD, form the primary endogenous defence against ROMs, their expression levels and cellular localization in IBD mucosa are largely unknown. The present study used enzyme-linked immunosorbent assays (ELISAs), spectrophotometric activity assays, and immunohistochemistry to evaluate the protein concentration, enzymatic activity, and distribution of Cu/Zn-, Mn-, and EC-SOD in paired inflamed and non-inflamed mucosal resection specimens of patients with Crohn's disease (CD) or ulcerative colitis (UC) and compared these with the levels obtained in normal control mucosa.