This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions.

SUMMARY Background

Background: The absorption of water and ions (especially Na+ and Cl−) is an important function of colonic epithelial cells in both physiological and pathophysiological conditions. Despite the comprehensive animal studies, there are only scarce available data on the ion transporter activities of the normal and inflamed human colon. Methods: In this study, 128 healthy controls and 69 patients suffering from ulcerative colitis (UC) were involved. We investigated the expressional and functional characteristics of the Na+/H+ exchangers (NHE) 1–3, the epithelial sodium channel (ENaC), and the SLC26A3 Cl−/HCO 3− exchanger downregulated in adenoma (DRA) in primary colonic crypts isolated from human biopsy and surgical samples using microfluorometry, patch clamp, and real‐time reverse‐transcription polymerase chain reaction (RT‐PCR) techniques. Results: Data collected from colonic crypts showed that the activities of electroneutral (via NHE3) and the electrogenic Na+ absorption (via ENaC) are in inverse ratio to each other in the proximal and distal colon. We found no significant differences in the activity of NHE2 in different segments of the colon. Surface cell Cl−/HCO 3− exchange is more active in the distal part of the colon. Importantly, both sodium and chloride absorptions are damaged in UC, whereas NHE1, which has been shown to promote immune response, is upregulated by 6‐fold. Conclusions: These results open up new therapeutic targets in UC. (Inflamm Bowel Dis 2011;)

SUMMARY BackgroundSome of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy.

This is, to our knowledge, the first study examining the efficacy of CT-P13 induction therapy on mucosal healing in UC. The results indicate that mucosal healing is achieved in two-thirds of UC patients by the end of the induction treatment with CT-P13.

BackgroundCytoplasmic lipid-droplets are common inclusions of eukaryotic cells. Lipid-droplet binding thalidomide analogs (2,6-dialkylphenyl-4/5-amino-substituted-5,6,7-trifluorophthalimides) with potent anticancer activities were synthesized.ResultsCytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER), induction of reactive oxygen species (ROS), ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis.ConclusionsBecause of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.

In the colonic mucosa of patients with active UC, NHE3 transport capacity was found significantly decreased despite correct NHE3 location and abundance in the brush border, independent of current treatment. These findings suggest functional NHE3 transport as a novel factor for inflammatory diarrhea in UC patients.

Serum LBP and sCD14 are markers of disease activity in CD with a similar accuracy as hs-CRP. In addition, LBP, sCD14, and a high frequency of previous relapses were independent predictors for 1-year clinical flare-up. (Inflamm Bowel Dis 2011).