Quercetin negatively regulates TLR4 signaling induced by lipopolysaccharide through Tollip expression.

Polyphenolic compounds have been regarded as one of the most promising dietary agents for the prevention and treatment of inflammation-related chronic diseases; however, the anti-inflammatory activities of flavonoids, such as quercetin, are not completely characterized, and many features remain to be elucidated. In this study, we showed the molecular basis for the downregulation of TLR4 signal transduction by quercetin. Quercetin markedly elevated the expression of the Toll-interacting protein, a negative regulator of TLR signaling. Lipopolysaccharide-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1ß, IL-6, and IL-12p70) were inhibited by quercetin, and this action was prevented by Toll-interacting protein silencing. In addition, quercetin-treated macrophages inhibited lipopolysaccharide-induced activation of mitogen-activated protein kinases, such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase, and the translocation of nuclear factor-κB and p65 through Toll-interacting protein. Treatment with quercetin resulted in a significant decrease in prostaglandin E2 and cyclooxygenase-2 levels as well as inducible nitric oxide synthase-mediated nitric oxide production induced by lipopolysaccharide. Taken together, these findings represent new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and effective therapeutic intervention for the treatment of inflammatory disease.

Argon plasma coagulation with submucosal saline injection for gastric adenoma on outpatient basis.

Gastric adenoma with low-grade dysplasia (LGD) is a less progressive disease than with high-grade dysplasia; nevertheless, a certain portion of lesions can progress. The purpose of this study was to evaluate the effectiveness of argon plasma coagulation (APC) with submucosa saline injections (APC-SSI) for gastric adenoma with LGD on an outpatient department (OPD) basis. We included 57 patients with 64 lesions of gastric adenoma with LGD. Endoscopic type was flat elevated in 58 lesions and central depressed in 6 lesions. Normal saline was injected into the submucosa under the lesion before APC. APC was performed to the lesion and its surrounding mucosa. After treatment, patients underwent regular endoscopy follow-ups. One case each of pneumoperitoneum and Mallory-Weiss tearing occurred and could be managed with conservative care. One case of overt bleeding occurred after 2 weeks and was treated with APC. After 19.5 months of follow-up, four residual adenomas (6.3%) were found and treated with additional APC-SSI. Fourteen metachronous lesions were noted in eight patients (14.0%). Twelve lesions were adenoma with LGD and two lesions were intramucosal adenocarcinoma. APC-SSI is an effective and safe treatment modality for gastric adenoma with LGD on an OPD basis and it is recommended for patients with risk factors of endoscopic mucosal resection (EMR). After treatment of gastric adenoma, meticulous follow-up endoscopy is recommended for detection of metachronous lesions.

Diagnostic value of terminal ileum intubation during colonoscopy.

BACKGROUND AND AIM: Since the diagnostic value of ileoscopy is not well documented, it is uncertain if terminal ileum intubation should be performed routinely in patients undergoing colonoscopy. We aimed to assess the diagnostic yield of terminal ileum intubation during colonoscopy according to indications for colonoscopy. METHODS: We routinely performed terminal ileum intubation in subjects who underwent colonoscopy at Ajou University Hospital between 1 January 2005 and 31 December 2005. Demographic data, indications for colonoscopy, endoscopic, and histopathologic findings of the terminal ileum were assessed. RESULTS: A total of 3921 subjects underwent colonoscopy. The terminal ileum was successfully intubated in 3417 cases (87.1%). Macroscopic abnormality on terminal ileum was present in 125 cases (3.7%), and biopsies were taken for all of them. Clinically significant histopathology was observed in 11 cases, giving a 0.3% diagnostic yield in all ileoscopies. Seven out of 11 cases were diagnosed as Crohn's disease. The rate of diagnostic yield was 1.8% in patients with right lower quadrant (RLQ) abdominal pain and 0.4% in patients with diarrhea. This rate in cases with RLQ pain was significantly greater compared with the indications for medical check-ups. CONCLUSIONS: Terminal ileum intubation during colonoscopy identifies significant pathology in 1.8% of cases who have RLQ abdominal pain, suggesting diagnostic value in this setting. However, its diagnostic yield is very low in other indications for colonoscopy. Thus the decision to perform ileoscopy or not during colonoscopy needs to be made on a case-by-case basis.

[Relapse rates of ulcerative colitis in remission and factors related to relapse].

BACKGROUND/AIMS: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with heterogeneous clinical features. Data on the disease course and prognosis of UC patients who have been regularly treated are lacking. We aimed to investigate relapse rates of UC in remission and factors related to relapse. METHODS: We retrospectively analyzed clinical courses of 84 patients (43 males, median age 43 years, ranged 20-73 years) diagnosed as UC at Ajou University Hospital between January 1997 and December 2005 based on clinical, endoscopic and pathologic findings, and who were regularly followed for at least one year after the remission. RESULTS: Study subjects consisted of 32 proctitis (38%), 21 left-sided colitis (25%), and 31 subtotal or total colitis (37%). Of 84 patients, relapse was observed in 52 patients (62%) during the follow-up period (ranged 1-9 years). The relapse rate was 24%, 41%, 51%, 65%, 71%, and 79% at 1 year, 2 years, 3 years, 4 years, 5 years and 6 years, respectively. Among sex, age, hemoglobin, ESR, and the extent of disease on admission, decrease of hemoglobin level was the only independent factor related to relapse (odds ratio=2.67, 95% CI (1.32-5.42), p<0.01). CONCLUSIONS: In Korea, relapse of UC in remission is not rare. Decrease of hemoglobin level is an independent risk factor related to its relapse, while the extent of disease is not.