Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease.

Aim: To investigate a possible genetic influence of claudin (CLDN)1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.

Methods: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease -families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.

Short-fiber protein of ad40 confers enteric tropism and protection against acidic gastrointestinal conditions.

The lack of vectors for selective gene delivery to the intestine has hampered the development of gene therapy strategies for intestinal diseases. We hypothesized that chimeric adenoviruses of Ad5 (species C) displaying proteins of the naturally enteric Ad40 (species F) might hold the intestinal tropism of the species F and thus be useful for gene delivery to the intestine. As oral-fecal dissemination of enteric adenovirus must withstand the conditions encountered in the gastrointestinal tract, we studied the resistance of chimeric Ad5 carrying the short-fiber protein of Ad40 to acid milieu and proteases and found that the Ad40 short fiber confers resistance to inactivation in acidic conditions and that AdF/40S was further activated upon exposure to low pH.

Addition of metronidazole to azathioprine for the prevention of postoperative recurrence of Crohn's disease: a randomized, double-blind, placebo-controlled trial.

Background: Endoscopic recurrence occurs in up to 80% of patients with Crohn's disease 1 year after intestinal resection. Imidazole antibiotics, thiopurines, and particularly their combination have proven efficacy in preventing endoscopic recurrence. The aim of the study was to compare the efficacy of the addition of metronidazole (for 3 months after the surgical treatment) to azathioprine for the prevention of postsurgical endoscopic recurrence.

Omega-3 fatty acids and inflammatory bowel diseases - a systematic review.

Background & Aim: Despite their well known anti-inflammatory actions, the clinical usefulness of omega-3 PUFA in inflammatory bowel disease is controversial. We aimed to systematically review the available data on the performance of omega-3 PUFA as therapeutic agents in these patients.

Methods: Electronic databases were systematically searched for RCT of fish oil or omega-3 PUFA therapy in both active and inactive ulcerative colitis or Crohn's disease, without limitation on either the length of therapy or the form it was given, including nutritional supplements and enteral formula diets.

Functionally enhanced siRNA targeting TNFα attenuates DSS-induced colitis and TLR-mediated immunostimulation in mice.

Tumor necrosis factor (TNFα) is a proinflammatory cytokine involved in the pathogenesis of inflammatory bowel disease (IBD). Although TNFα has been extensively targeted using systemic drugs, the use of antisense and small interfering RNA (siRNA) to drive down its expression at the site of inflammation should provide important advantages. In this study, native and chemically modified siRNA against TNFα was developed and characterized using a murine model of IBD.

Bacteria and spontaneous experimental colitis: immunological changes.

Background: Intestinal commensal flora seems to be a requisite for both human and experimental intestinal inflammation. Our aim was to assess the immunological changes in the colon of IL-10(-/-) mice depending on the environmental conditions.

Materials And Methods: Twelve wild-type (WT) and 24 IL-10(-/-) 4-week-old mice were kept under specific pathogen-free (SPF) conditions for 4 weeks.

Therapeutic effect of antisecretory factor-rich egg yolk on the late phases of 2,4,6-trinitrobenzenesulphonic acid colitis in mice.

Antisecretory factor (AF) is expressed in all tissues of mammals, inhibits intestinal hypersecretion and has anti-inflammatory properties as well. Endogenous AF synthesis may be stimulated by feeding hydrothermally processed cereals. Alternatively, freeze-dried egg yolk can be used as a source of exogenous AF.

Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease.

Background: Apoptosis resistance of T-cells is considered an abnormality of immune pathways in Crohn's disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy.

A mixture of Lactobacillus plantarum CECT 7315 and CECT 7316 enhances systemic immunity in elderly subjects. A dose-response, double-blind, placebo-controlled, randomized pilot trial.

Background & Aim: Immunosenescence can increase morbi-mortality. Lactic acid producing bacteria may improve immunity and reduce morbidity and mortality in the elderly. We aimed to investigate the effects of a mixture of two new probiotic strains of Lactobacillus plantarum--CECT 7315 and 7316--on systemic immunity in elderly.

Decision tree for early introduction of rescue therapy in active ulcerative colitis treated with steroids.

Background: Corticosteroids are the treatment of choice for moderate-to-severe active ulcerative colitis (UC) but up to 30%-40% of patients fail to respond. It has been reported that early clinical-biological parameters may identify those patients at high risk of colectomy. The aim was to identify predictors of rapid response to systemic steroids in moderate-to-severe attacks of UC.

Appropriateness of therapy for active Crohn's disease: Results of a multidisciplinary international expert panel-EPACT II.

Unlabelled: The increasing number of trials testing management strategies for luminal Crohn's disease (CD) has not filled all the gaps in our knowledge and thus, in clinical practice, many decisions for CD patients have to be taken without the benefit of high-quality evidence.

Methods: A multidisciplinary European expert panel used the RAND Appropriateness Method to develop and rate explicit criteria for the management of individual patients with active, steroid-dependent (ST-D) and steroid-refractory (ST-R) CD.

Results: Overall, 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD were rated.

Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease.

Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS.

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions.

Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice.

Background: Most available data on infliximab therapy come from large, short-term, pivotal RCTs and concerns about long-term safety profile still remain.

Aim: To evaluate the long-term safety profile of infliximab in inflammatory bowel disease (IBD) in a clinical practice setting.

Methods: Since 1999, all IBD patients treated with infliximab were registered and clinical outcomes prospectively recorded up to March 2008, loss of follow-up or patient's death.

Clinical outcome of newly diagnosed Crohn's disease: a comparative, retrospective study before and after infliximab availability.

Background: Infliximab (IFX) could change the course of Crohn's disease (CD) by reducing steroid use, surgery or prompting earlier introduction of immunomodulators (IMM).

Aim: To evaluate the impact of IFX availability on the course of early CD.

Methods: Two cohorts of newly diagnosed CD patients were identified: The first cohort included patients diagnosed from January 1994 to December 1997 and the second from January 2000 to December 2003.

Regulation of colorectal cancer cell apoptosis by the n-3 polyunsaturated fatty acids Docosahexaenoic and Eicosapentaenoic.

Several studies have suggested that the n-3 fatty acids Docosahexaenoic (DHA) and Eicosapentaenoic (EPA) have an important protective effect on colorectal cancer, and this could be at least partly due to their proapoptotic activity. It is unclear, however, how this phenomenon is triggered and what mechanisms are implicated. Here, we show that both DHA and EPA have an important proapoptotic effect on colorectal cancer cells with different molecular phenotypes but not in noncancerous cells.

Prospective, observational, cross-sectional study of intestinal infections among acutely active inflammatory bowel disease patients.

Background: Intestinal infections have been claimed to precipitate or aggravate flares of inflammatory bowel disease (IBD). The reported incidence of such infections among IBD patients varies between 9 and 13%, but only a few prospective studies have been conducted.

Aims: To evaluate the incidence of intestinal infections by enteropathogens in patients with active IBD, their impact on clinical outcome, and to identify associated risk factors.

Infliximab reintroduction is not associated to a higher rate of immune-related adverse effects in patients with inflammatory bowel disease initially treated with a three-infusion induction regimen.

Background: Episodic infliximab (IFX) treatment is associated with a higher risk for acute infusion reactions (AIR) and secondary loss of response (SLR), but this has not been evaluated in patients initially treated with an induction regimen with 3 IFX infusions.

Aims: To evaluate whether IFX reintroduction after > or = 4 months in patients treated with a 3-infusion induction regimen is associated with a higher incidence of AIR or SLR.

Methods: Incidence of immunogenic adverse effects was assessed in patients with inflammatory bowel disease who received > or = 4 consecutive IFX infusions (3 infusions at weeks 0, 2, and 6, plus > or = 1 maintenance infusion) (Continuous, n=47) and patients who were treated with a successful initial 3-infusion induction scheme and in whom IFX was then discontinued because of a complete response but reintroduced > or = 4 months later (Reintro, n=29).