No abstract

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4 + T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro , using lamina propria (LP) CD4 + T cells in T cell transfer IBD models in which SCID mice had been injected with CD4 + CD45RB high T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4 + T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo . BBR-fed mice showed AMPK activation in the LPCD4 + T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4 + T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

A 44-year-old woman was admitted to our hospital for investigation and treatment of sudden abdominal pain and distention. Plain abdominal radiography and abdominal computed tomography (CT) findings were suggestive of sigmoid volvulus. She underwent an emergency colonoscopy, and the scope passed easily through the sigmoid colon and reached the ascending colon quickly. However, stenosis with concentricity of the fold was observed in the cecum, which was shifted upward and to the left. Based on these findings, we diagnosed cecal volvulus caused by mobile cecum syndrome. The patient's symptoms resolved quickly after colonoscopic reduction and elective laparoscopic surgery was performed 18 days after admission. Perioperative examination revealed a mobile cecum caused by an elongated ascending colon. We sutured the cecum and ascending colon to the lateral peritoneum laparoscopically with interrupted sutures. The patient recovered well and was discharged on postoperative day 7. An unfixed intestine can be detected easily during laparoscopic surgery, which is minimally invasive and cosmetically, physically, and economically beneficial. Thus, we recommend laparoscopic cecopexy for mobile cecum syndrome.

Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohn's disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted.

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn’s disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.