Cyclosporine is a potent immunomodulator and has a beneficial effect in the treatment of ulcerative colitis (UC). We analyzed the mechanism of the effects of cyclosporine on the regulation of epithelial apoptosis via TGF-β-related signaling, because the balance between the apoptosis and regeneration of epithelial cells seems to be a key factor to maintain the intestinal homeostasis. For this purpose, colitis was induced by treatment of 4% dextran sulfate sodium (DSS), and the effect of treatment with cyclosporine and anti-TGF-β antibody was assessed. Treatment with cyclosporine ameliorated body weight loss, mucosal destruction, and epithelial apoptosis in DSS-induced colitis. Cyclosporine was shown to upregulate the expression of TGF-β in the colonic tissue, enhance the expression of p-Smad2 and cFLIP in epithelial cells, and inhibit caspase-8 activity but not caspase-1 or -9. Upregulation of cFLIP in the colonic epithelial cells, amelioration of body weight loss, and mucosal destruction by cyclosporine were attenuated by anti-TGF-β antibody treatment. These results indicated that cyclosporine could have a protective role against epithelial apoptosis associated with upregulation of TGF-β-related signaling.
Background: Maintenance of mucosal healing may lead to a better outcome in patients with Crohn's disease (CD). Magnetic resonance diffusion-weighted imaging (MR-DWI) scans 1 year after infliximab (IFX) induction therapy were assessed as predictors of maintained response, or remission, through 3 years of treatment in patients with CD. Summary: MR-DWI and endoscopy data were prospectively collected throughout IFX treatment. Altogether, 86 lesions from 13 patients given IFX as induction (weeks 0, 2 and 6) and maintenance (5 mg/kg every 8 weeks beginning at week 14) therapy were analyzed with MR-DWI for 0.5-1.5 years from the starting point. Mucosal findings were confirmed by endoscopy at 1 and 3 years (gold standard). Of the 86 lesions, 65 were graded ‘0' and 21 were graded ‘1' based on their hyperintensity (HI; or lack thereof) on MR-DWI. Two years after the first evaluation, 7 of 15 false-negative lesions had turned positive based on colonoscopy findings, and 60 of 62 true-negative lesions had not. Thus, 0.03% of those predicted to remain in remission had relapsed (negative predictive value 0.9677, p < 0.0001). MR-DWI-HI at 1 year coincided with the presence of endoscopic inflammation, with sensitivity of 66.67%, specificity of 80.52%, and an area under the curve (AUC) value of 0.7359 (0.5479-0.9240, p = 0.0211). The AUC value of MR-DWI-HI at 3 years was 0.8402 (0.7460-0.9343, p = 0.001) with sensitivity of 94.12% and specificity of 73.91%. Key Message: A definition of the response on the basis of MR-DWI-HI might be helpful for optimizing treatment for patients with CD under treatment with IFX.
The aim of this study was to assess the perioperative invasiveness of endoscopic submucosal dissection for colorectal cancer quantitatively by using energy metabolism. In fifty-three patients who underwent endoscopic submucosal dissection for colorectal cancer, resting energy expenditure using an indirect calorimeter, body weight and basal energy expenditure using the Harris–Benedict equation before and after endoscopic submucosal dissection. Resting energy expenditure/body weight and resting energy expenditure/basal energy expenditure were 19.7 ± 2.5 kcal/kg/day and 0.96 ± 0.12 on the day of endoscopic submucosal dissection, whereas one day after the endoscopic submucosal dissection they increased to 21.0 ± 2.9 kcal/kg/day and 1.00 ± 0.13 (p<0.001 and p<0.05, respectively). The stress factor on the postoperative day 1 was computed as 1.06. The increase was lower comparing with that experienced for surgery, suggesting that the perioperative invasiveness of colorectal endoscopic submucosal dissection is lower in comparison to that during surgery. Furthermore, in spite of technical difficulty, stress factor of colorectal endoscopic submucosal dissection was approximately equal to that of gastric endoscopic submucosal dissection. (The study of the resting energy metabolism and stress factor using an indirect calorimeter in the perioperative period of endoscopic operation: UMIN000027135)
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