Relapse rates at 1year following elective withdrawal of anti-TNF are 36%, with high retreatment response rate. Predictors of relapse include ileocolonic involvement, previous anti-TNF therapy and raised FC. Endoscopic/radiologic assessment prior to cessation of therapy does not appear to predict those at lower risk of relapse.
BackgroundKeratins are intermediate filament (IF) proteins, which form part of the epithelial cytoskeleton and which have been implicated pathology of inflammatory bowel diseases (IBD).MethodsIn this study biopsies were obtained from IBD patients grouped by disease duration and subtype into eight categories based on cancer risk and inflammatory status: quiescent recent onset (<5 years) UC (ROUC); UC with primary sclerosing cholangitis; quiescent long-standing pancolitis (20–40 years) (LSPC); active colitis and non-inflamed proximal colonic mucosa; pancolitis with dysplasia-both dysplastic lesions (DT) and distal rectal mucosa (DR); control group without pathology. Alterations in IF protein composition across the groups were determined by quantitative proteomics. Key protein changes were validated by western immunoblotting and immunohistochemical analysis.ResultAcute inflammation resulted in reduced K8, K18, K19 and VIM (all p<0.05) compared to controls and non inflamed mucosa; reduced levels of if– associated proteins were also seen in DT and DR. Increased levels of keratins in LSPC was noted relative to controls or ROUC (K8, K18, K19 and VIM, p<0.05). Multiple K8 forms were noted on immunoblotting, with K8 phosphorylation reduced in progressive disease along with an increase in VIM:K8 ratio. K8 levels and phosphorylation are reduced in acute inflammation but appear restored or elevated in subjects with clinical and endoscopic remission (LSPC) but not apparent in subjects with elevated risk of cancer.ConclusionsThese data suggest that keratin regulation in remission may influence subsequent cancer risk.
4Cultech Limited, Christchurch Rd Port Talbot, Neath Port TalbotThere is a growing body of evidence indicating that the gut microbiota communicates with the CNS influencing mood and behaviour (1)(2)(3)(4)(5)(6)(7) and a role for the microbiota in the development of brain plasticity and the subsequent physiological response has been suggested (2) . Furthermore treatment with probiotics has been shown to alter functional task-related brain activity and changes in midbrain connectivity 9 . To date no study has demonstrated cognitive modification in response to probiotic treatment. The aims of the study were i) To examine the mood effects of probiotic supplementation at rest and in response to psychological stressors ii) To examine the effects of probiotic administration on cognitive functioning.In this pilot study, healthy participants (n = 50) were recruited to take part in a double blind, randomised, controlled trial. Participants were randomized to receive either a probiotic preparation comprising two strains of Lactobacillus acidophilus CUL60 (NCIMB 30157) and CUL21 (NCIMB 30156), Bifidobacterium lactis CUL34 (NCIMB 30172) and Bifidobacterium bifidum CUL20 (NCIMB 30153) at a total of 2.5 × 10 10 cfu/capsule or a placebo for 6 weeks. The sample population comprised 18 males and 32 females, mean age 23.22 years (range 19-38, SD 3.846), with a BMI <30. Participants underwent morphometric measurements (height, weight, % total body fat, hip and waist measurement) and completed mood, stress and depression questionnaires (Bond Lader Mood Scales, Stait Trait Anxiety Inventory and NASA Task Load Index). Participants also were required to perform a battery of computerised cognitive test (COMPASS) measuring attention, executive function, working memory and episodic memory.In terms of mood measures, a significant interaction showed that 'trait' anxiety levels decreased in the active probiotic condition whilst increasing in the placebo condition over the course of the 6 week intervention (p = 0.042). A significant interaction was also observed for tasks of attention; 'continuity of attention increased in response to the probiotic treatment and decreased with the placebo group (p = 0.035). No morphometric changes between the two treatment conditions were recorded during the intervention period. The findings of this pilot trial provide a justification for further studies to characterise the potential cognitive and mood enhancing benefits of probiotics in healthy populations.
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