The Flavonoid Luteolin Worsens Chemical-Induced Colitis in NF-κBEGFP Transgenic Mice through Blockade of NF-κB-Dependent Protective Molecules

BackgroundThe flavonoid luteolin has anti-inflammatory properties both in vivo and in vitro. However, the impact of luteolin on experimental models of colitis is unknown.Methodology/Principal FindingsTo address the therapeutic impact of luteolin, NF-κBEGFP transgenic mice were fed a chow diet containing 2% luteolin- or isoflavone-free control chow (AIN-76), and acute colitis was induced using 3% dextran sodium sulfate (DSS). Additionally, development of spontaneous colitis was evaluated in IL-10−/−;NF-κBEGFP transgenic mice fed 2% luteolin chow diet or control chow diet. Interestingly, NF-κBEGFP transgenic mice exposed to luteolin showed worse DSS-induced colitis (weight loss, histological scores) compared to control-fed mice, whereas spontaneous colitis in IL-10−/−;NF-κBEGFP mice was significantly attenuated. Macroscopic imaging of live resected colon showed enhanced EGFP expression (NF-κB activity) in luteolin-fed mice as compared to control-fed animals after DSS exposure, while cecal EGFP expression was attenuated in luteolin-fed IL-10−/− mice. Interestingly, confocal microscopy showed that EGFP positive cells were mostly located in the lamina propria and not in the epithelium. Caspase 3 activation was significantly enhanced whereas COX-2 gene expression was reduced in luteolin-fed, DSS-exposed NF-κBEGFP transgenic mice as assessed by Western blot and immunohistochemical analysis. In vitro, luteolin sensitized colonic epithelial HT29 cells to TNFα-induced apoptosis, caspase 3 activation, DNA fragmentation and reduced TNFα-induced C-IAP1, C-IAP2 and COX-2 gene expression.Conclusions/SignificanceWe conclude that while luteolin shows beneficial effects on spontaneous colitis, it aggravates DSS-induced experimental colitis by blocking NF-κB-dependent protective molecules in enterocytes

Histologic discrepancy between endoscopic forceps biopsy and endoscopic mucosal resection specimens of colorectal polyp in actual clinical practice

Background/AimsWe aimed to assess the rate of histologic discrepancy (HD) between endoscopic forceps biopsy (EFB) and totally resected specimens in colorectal polyp and analyze the risk factors of discordant group, especially under-diagnosis (UD) cases before complete removal of colorectal polyp.MethodsFrom 2010 to 2015, a total of 290 polyps in 210 patients which had baseline pathology report before endoscopic resection (ER) were analyzed. UD cases were defined as those in which the diagnosis changed to a more advanced histologic feature after ER.ResultsA change in the final histology after ER was noted in 137 cases (47.2%), and after excluding 9 insignificant cases, 128 cases were further categorized into over-diagnosed and under-diagnosed group. UD occurred in 86 cases (29.7%) and change from benign to malignancy was noted in 26 cases (8.9%). On univariate analysis, a larger polyp size (>10 mm) was significantly associated with both HD (P10 mm was the single most significant predictor of both HD (P10 mm was the most important predictor of both HD and UD. We should be careful in making treatment strategy of colorectal polyp based on histologic report of EFB especially when the size of polyp is >10 mm

A Common Bile Duct Stone formed by Suture Material after Open Cholecystectomy

The use of non-absorbable suture materials for cystic duct ligation after cholecystectomy can expose patients to the risk of recurrent stone formation in the common bile duct (CBD). However, in Korea suture materials have rarely been found to act as a nidus for common bile duct calculus formation. Recently, we experienced a case in which suture material, that had migrated from a previous cholecystectomy site into the CBD, probably served as a nidus for common bile duct stone formation. The stone was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) and removed successfully using a basket. The authors report a case of surgical suture migration and discuss its subsequent role as a stone forming nucleus within the CBD in a patient who underwent open cholecystectomy; and include a review of the literature

Cordycepin induces human lung cancer cell apoptosis by inhibiting nitric oxide mediated ERK/Slug signaling pathway

Nitric oxide (NO) is an important signaling molecule and a component of the inflammatory cascade. Besides, it is also involved in tumorigenesis. Aberrant upregulation and activation of the ERK cascade by NO often leads to tumor cell development. However, the role of ERK inactivation induced by the negative regulation of NO during apoptosis is not completely understood. In this study, treatment of A549 and PC9 human lung adenocarcinoma cell lines with cordycepin led to a reduction in their viability. Analysis of the effect of cordycepin treatment on ERK/Slug signaling activity in the A549 cell line revealed that LPS-induced inflammatory microenvironments could stimulate the expression of TNF-α, CCL5, IL-1β, IL-6, IL-8 and upregulate NO, phospho-ERK (p-ERK), and Slug expression. In addition, constitutive expression of NO was observed. Cordycepin inhibited LPS-induced stimulation of iNOS, NO, p-ERK, and Slug expression. L-NAME, an inhibitor of NOS, inhibited p-ERK and Slug expression. It was also found that cordycepin-mediated inhibition of ERK downregulated Slug, whereas overexpression of ERK led to an upregulation of Slug levels in the cordycepin-treated A549 cells. Inhibition of Slug by siRNA induced Bax and caspase-3, leading to cordycepin-induced apoptosis. Cordycepin-mediated inhibition of ERK led to a reduction in phospho-GSK3β (p-GSK3β) and Slug levels, whereas LiCl, an inhibitor of GSK3β, upregulated p-GSK3β and Slug. Overall, the results obtained indicate that cordycepin inhibits the ERK/Slug signaling pathway through the activation of GSK3β which, in turn, upregulates Bax, leading to apoptosis of the lung cancer cells

Remission of intestinal Behçet's disease treated with anti-tumor necrosis factor α monoclonal antibody (Infliximab)

Behçet's disease (BD) is a chronic relapsing multisystem disease characterized by oral ulceration, genital ulceration and ocular lesions. Gastrointestinal involvement is rare, often difficult to treat and associated with a high mortality rate. We treated a 47-year-old Korean man with BD who had a recurrent intestinal ulcer with tumor necrosis factor α antibody (infliximab); he initially underwent right hemicolectomy due to uncontrolled intestinal bleeding. For patients with intestinal BD who fail to respond to conventional treatment, infliximab may be a safe and effective new therapeutic option

Bowel Preparation for Capsule Endoscopy: A Prospective Randomized Multicenter Study

Background/Aims: The ability to visualize the small bowel mucosa by capsule endoscopy is limited. Moreover, studies involving small-bowel preparation with purgative drugs have failed to establish which preparations produce better images and higher diagnostic yields. The aim of this study was to evaluate the efficacies and diagnostic yields of different bowel preparations. Methods: A cohort of 134 patients with suspected small bowel disease was randomly assigned to 3 groups. Patients in group A (n=44) fasted for 12 h before being administered an M2A capsule (Given Imaging, Yoqneam, Israel). Patients in group B (n=45) were asked to drink two doses of 45 mL of sodium phosphate (NaP) with water during the afternoon and evening on the day before the procedure and to drink at least 2 L of water thereafter. Patients in group C (n=45) drank 2 L of a polyethylene glycol (PEG) lavage solution the evening before the procedure. Results: Overall cleansing of the small bowel was adequate in 43% of patients in group A, 77% of those in group B, and 56% of those in group C (group A vs; group B, p=0.001). Diagnoses for obscure gastrointestinal bleeding were established in 9 patients (39%) in group A, 16 patients (69%) in group B, and 14 patients (50%) in group C. No significant difference in diagnostic yield was observed between groups. Conclusions: Bowel preparation with NaP for capsule endoscopy improved small-bowel mucosal visualization when compared to 12-h overnight fasting. (Gut and Liver 2009;3:180-185)Wei W, 2008, AM J GASTROENTEROL, V103, P77, DOI 10.1111/j.1572-0241.2007.01633.xCheon JH, 2007, GUT LIVER, V1, P118van Tuyl SAC, 2007, ENDOSCOPY, V39, P1037, DOI 10.1055/s-2007-966988Ben-Soussan E, 2005, J CLIN GASTROENTEROL, V39, P381FIREMAN Z, 2005, WORLD J GASTROENTERO, V11, P5863DAI N, 2005, GASTROINTEST ENDOSC, V61, P28Viazis N, 2004, GASTROINTEST ENDOSC, V60, P534Niv Y, 2004, SCAND J GASTROENTERO, V39, P1005, DOI 10.1080/00365520410003209Fireman Z, 2004, ISRAEL MED ASSOC J, V6, P521Albert J, 2004, GASTROINTEST ENDOSC, V59, P487Pennazio M, 2004, GASTROENTEROLOGY, V126, P643, DOI 10.1053/j.gastro.2003.11.057Mylonaki M, 2003, GUT, V52, P1122Costamagna G, 2002, GASTROENTEROLOGY, V123, P999, DOI 10.1053/gast.2002.35988Lewis BS, 2002, GASTROINTEST ENDOSC, V56, P349, DOI 10.1067/mge.2002.126906Kastenberg D, 2001, GASTROINTEST ENDOSC, V54, P705Aronchick CA, 2000, GASTROINTEST ENDOSC, V52, P346

Nonimmunity against hepatitis B virus infection in patients newly diagnosed with inflammatory bowel disease

Background/AimsThis study aimed to elucidate the prevalence of hepatitis B virus (HBV) serologic markers in Korean patients newly diagnosed with, but not yet treated for inflammatory bowel disease (IBD).MethodsWe prospectively enrolled 210 patients newly diagnosed with IBD (109 with ulcerative colitis and 101 with Crohn's disease). Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were measured and compared with those of 1,100 sex- and age-matched controls.ResultsThe prevalence of chronic HBV infection (positive HBsAg, positive anti-HBc, and negative anti-HBs results) and past infection (negative HBsAg, positive anti-HBc, and positive or negative anti-HBs results) were not significantly different between the patients and controls (chronic HBV infection: IBD, 3.8% vs. control, 4.9%, P=0.596; past infection: IBD, 26.2% vs. control, 28.8%, P=0.625). The patients with IBD aged <20 years were at a higher susceptibility risk (nonimmune) for HBV infection than the controls (IBD, 41.5% vs. control, 22.4%; P=0.018). In the multivariate analysis, an age of <20 years (P=0.024) and symptom duration of ≥12 months before diagnosis (P=0.027) were identified as independent risk factors for nonimmunity against HBV infection.ConclusionsThe patients newly diagnosed with IBD were susceptible to HBV infection. The frequency of nonimmunity was high, especially in the patients aged <20 years and those with a longer duration of symptoms before diagnosis. Therefore, it is necessary to screen for HBV serologic markers and generate a detailed vaccination plan for patients newly diagnosed with IBD

Clinical Characteristics of Microscopic Colitis in Korea: Prospective Multicenter Study by KASID

Background/Aims: Microscopic colitis (MC) encompasses collagenous and lymphocytic colitis and is characterized by chronic diarrhea. In cases of MC, colonic mucosae are macroscopically normal, and diagnostic histopathological features are observed only upon microscopic examination. We designed a prospective multicenter study to determine the clinical features, pathological distribution in the colon and prevalence of MC in Korea. Methods: We prospectively enrolled patients having watery diarrhea no more than 3 times a day between March 2008 and February 2009. We obtained patient histories and performed colonoscopies with random biopsies at each colon segment. Results: A total of 100 patients with chronic diarrhea were enrolled for a normal colonoscopy and stool exam. MC was observed in 22 patients (22%) (M:F 1.2:1; mean age, 47.5 years). Of those 22 patients, 18 had lymphocytic colitis and 4 had collagenous colitis. The entire colon was affected in only 3 cases (13.6%), the ascending colon in 6 cases (27.2%), the transverse colon in 3 cases (13.6%), and the left colon in 3 cases (13.6%). More than 2 segments were affected in 7 cases (31.8%). Nonsteroidal anti-inflammatory drug-associated MCs were observed in 4 cases (18.2%), 3 of which showed improved diarrhea symptoms following discontinuation of the medication. Frequently associated symptoms were abdominal pain and weight loss. Autoimmune diseases were observed in 4 cases (18.2%). Half of the 22 patients with MC improved with conservative care by loperamide or probiotics. Conclusions: In a prospective multicenter study of Korean patients with chronic diarrhea, the frequency of MC was found to be approximately 20%, similar to the percentage observed in Western countries. Therefore, the identification of MC is important for the adequate management of Korean patients with chronic diarrhea. (Gut Liver 20115:181-186

A wide variation of the quality of colonoscopy reporting system in the real clinical practice in southeastern area of Korea

Background/AimsEstablishment of a colonoscopy reporting system is a prerequisite to determining and improving quality. This study aimed to investigate colonoscopists' opinions and the actual situation of a colonoscopy reporting system in a clinical practice in southeastern area of Korea and to assess the factors predictive of an inadequate reporting system.MethodsPhysicians who performed colonoscopies in the Daegu-Gyeongbuk province of Korea and were registered with the Korean Society of Gastrointestinal Endoscopy (KSGE) were interviewed via mail about colonoscopy reporting systems using a standardized questionnaire.ResultsOf 181 endoscopists invited to participate, 125 responded to the questionnaires (response rate, 69%). Most responders were internists (105/125, 84%) and worked in primary clinics (88/125, 70.4%). Seventy-one specialists (56.8%) held board certifications for endoscopy from the KSGE. A median of 20 colonoscopies (interquartile range, 10–47) was performed per month. Although 88.8% of responders agreed that a colonoscopy reporting system is necessary, only 18.4% (23/125) had achieved the optimal reporting system level recommended by the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. One-third of endoscopists replied that they did not use a reporting document for the main reasons of "too busy" and "inconvenience." Non-endoscopy specialists and primary care centers were independent predictive factors for failure to use a colonoscopy reporting system.ConclusionsThe quality of colonoscopy reporting systems varies widely and is considerably suboptimal in actual clinical practice settings in southeastern Korea, indicating considerable room for quality improvements in this field