[Show abstract][Hide abstract] ABSTRACT: Despite improvements in endoscopic hemostasis and pharmacological therapies, upper gastrointestinal (UGI) ulcers repeatedly bleed in 10% to 20% of patients, and those without early endoscopic reintervention or definitive surgery might be at a high risk for mortality. This study aimed to identify the risk factors for intractability to initial endoscopic hemostasis.
We analyzed intractability among 428 patients who underwent emergency endoscopy for bleeding UGI ulcers within 24 hours of arrival at the hospital.
Durable hemostasis was achieved in 354 patients by using initial endoscopic procedures. Sixty-nine patients with Forrest types Ia, Ib, IIa, and IIb at the second-look endoscopy were considered intractable to the initial endoscopic hemostasis. Multivariate analysis indicated that age ≥70 years (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.07 to 4.03), shock on admission (OR, 5.26; 95% CI, 2.43 to 11.6), hemoglobin <8.0 mg/dL (OR, 2.80; 95% CI, 1.39 to 5.91), serum albumin <3.3 g/dL (OR, 2.23; 95% CI, 1.07 to 4.89), exposed vessels with a diameter of ≥2 mm on the bottom of ulcers (OR, 4.38; 95% CI, 1.25 to 7.01), and Forrest type Ia and Ib (OR, 2.21; 95% CI, 1.33 to 3.00) predicted intractable endoscopic hemostasis.
Various factors contribute to intractable endoscopic hemostasis. Careful observation after endoscopic hemostasis is important for patients at a high risk for incomplete hemostasis.
[Show abstract][Hide abstract] ABSTRACT: Long-term administration of low-dose aspirin (LDA) is associated with a greater risk of adverse events, including gastroduodenal ulcers. The purpose of this study was to identify the risk factors for and assess the role of medication use in the development of peptic ulcer disease in Japanese patients with no history of peptic ulcers.
Consecutive outpatients receiving LDA (75 mg/day) who underwent esophagogastroduodenoscopy between January and December 2010 were enrolled. Clinical parameters, peptic ulcer history, concomitant drugs, the presence of Helicobacter pylori infection, reason for endoscopy, and endoscopic findings were analysed.
Of 226 total patients, 14 (6.2%) were endoscopically diagnosed with peptic ulcer. Age, sex, current smoking status, current alcohol consumption, endoscopic gastric mucosal atrophy, and abdominal symptoms were not significantly associated with peptic ulcers. Diabetes mellitus was more frequent (42.9% vs. 16.5%; P = 0.024) in patients with peptic ulcers than in those without peptic ulcers. Using multiple logistic regression analysis, co-treatment with anticoagulants or proton pump inhibitors (PPIs) was significantly associated with increased and decreased risk for peptic ulcer, respectively (odds ratio [OR], 5.88; 95% confidence interval [CI], 1.19 - 28.99; P = 0.03 and OR, 0.13; 95% CI, 0.02 - 0.73; P = 0.02, respectively). Co-treatment with additional antiplatelet agents, H2-receptor antagonists, angiotensin II Type 1 receptor blockers, angiotensin-converting enzyme inhibitor, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, or nonsteroidal anti-inflammatory drugs was not associated with peptic ulcer development.
The use of PPIs reduces the risk of developing gastric or duodenal ulcers in Japanese patients taking LDA without pre-existing gastroduodenal ulcers. However, this risk is significantly increased in both patients ingesting anticoagulants and patients with diabetes. These results may help identify patients who require intensive prophylaxis against aspirin-induced peptic ulcers.
[Show abstract][Hide abstract] ABSTRACT: Short-chain fatty acids (SCFAs), which are produced by the fermentation of dietary fiber by intestinal microbiota, may positively influence immune responses and protect against gut inflammation. SCFAs bind to G protein-coupled receptor 43 (GPR43). Here, we show that SCFA-GPR43 interactions profoundly affect the gut inflammatory response.
Colitis was induced by adding dextran sulfate sodium to the drinking water of GPR43 knockout (-/-) and wild-type mice.
Dextran sulfate sodium-treated GPR43 mice exhibited weight loss, increased disease activity index (a combined measure of weight loss, rectal bleeding, and stool consistency), decreased hematocrit, and colon shortening, resulting in significantly worse colonic inflammation than in wild-type mice. Tumor necrosis factor alpha and interleukin 17 protein levels in the colonic mucosa of GPR43 mice were significantly higher than in wild-type mice. Treatment of wild-type mice with 150 mM acetate in their drinking water markedly improved these disease indices, with an increase in colon length and decrease in the disease activity index; however, it had no effect on GPR43 mice. Mononuclear cell production of tumor necrosis factor alpha after lipopolysaccharide stimulation was suppressed by acetate. This effect was inhibited by anti-GPR43 antibody.
SCFA-GPR43 interactions modulate colitis by regulating inflammatory cytokine production in mononuclear cells.
[Show abstract][Hide abstract] ABSTRACT: Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.
Journal of Clinical Biochemistry and Nutrition 07/2013; 53(1):55-9. · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Recently, the relationship between gut microbiota and obesity has been highlighted. The present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing the gut microbiota of T2DM patients. METHODS: This study included 60 patients who received placebo or TGD orally (300 or 900 mg/day) for 12 weeks, and blood and fecal samples were collected before and after 12 weeks. Comparisons of fecal bacterial communities were performed before and after the TGD treatment and were performed between T2DM patients and 10 healthy individuals, using the terminal-restriction fragment length polymorphism analysis. RESULTS: The Clostridium cluster IV and subcluster XIVa components were significantly decreased, whereas the Lactobacillales and Bifidobacterium populations significantly increased in the T2DM patients compared with the healthy individuals. By dendrogram analysis, most of the healthy individuals (6/10) and T2DM patients (45/60) were classified into cluster I, indicating no significant difference in fecal bacterial communities between the healthy individuals and the T2DM patients. In the placebo and TGD groups, the bacterial communities were generally similar before and after the treatment. However, after 12 weeks of TGD therapy, the Bacteroidetes-to-Firmicutes ratio in the TGD groups significantly increased and was significantly higher compared with that in the placebo group, indicating that TGD improved the growth of the fecal bacterial communities in the T2DM patients. CONCLUSIONS: Therefore, TGD treatment decreased blood glucose levels and prevented body weight gain in the T2DM patients by inducing the production of oligosaccharides in the alimentary tract and modulating gut microbiota composition.Trial registration: UMIN-CTR UMIN000010318: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000012067&language=E.
[Show abstract][Hide abstract] ABSTRACT: It is known that the pharmacokinetic profile of proton pump inhibitors (PPIs) after postprandial administration may differ among PPIs. The purpose of this study was to compare the inhibitory effects of gastric acid secretion by PPIs administered after a meal, based on a 24-hour intragastric pH monitoring.
Ten healthy men who provided written informed consent participated in the study. They were given a 20-mg omeprazole tablet and a 30-mg lansoprazole orally dispersing tablet in a two-way crossover manner. At baseline, the anti-HP-IgG antibody levels in blood and the pepsinogen (PG) I/II ratio were measured. Participants were given a standardized meal and 200 mL of water at 9:30 am, 13:30 pm, and 18.30 pm. Participants took the PPI after breakfast.
Two of the ten participants tested positive for Helicobacter pylori infection. The PG I/II ratio indicated negative gastric atrophy in all the participants. The percentage 24-hour intragastric pH > 4 holding times (median, range) with omeprazole and lansoprazole were 29.3, 19.3-50.0% and 27.8, 13.0-42.3%, respectively, which shows that with the administration of omeprazole, the pH was maintained at >4 for a longer period (p < 0.05). Each median intragastric pH value per hour at 3, 17, and 18 hours after a dose of omeprazole was significantly higher than that of lansoprazole (p < 0.05).
Compared with lansoprazole, a single postprandial dose of omeprazole showed a more rapid and sustained acid-inhibitory effect.
Journal of the Chinese Medical Association 03/2013; 76(3):131-4. · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Laryngopharyngeal reflux (LPR) is defined as the retrograde flow of gastric contents up through the esophagus to the larynx and hypopharynx; this is an extra-esophageal manifestation of gastroesophageal reflux disease (GERD). Although both LPR and GERD are caused by reflux of stomach contents, their clinical presentations and treatments differ. PATIENTS AND METHODS: In the present study, we assessed esophago-gastroendoscopic findings related to GERD, specifically endoscopic-positive esophagitis (EE), laryngopharyngeal findings, and GERD symptoms on the 12-question frequency scale for the symptoms of gastroesophageal reflux disease (FSSG). Then, independent predictors of EE were analyzed, and relationships among EE, laryngopharyngeal findings, and patients' symptoms and characteristics were investigated. RESULTS: Hiatal hernia (odds ratio [OR]: 2.70; 95% confidence interval [CI]: 1.17-6.23, P-value 0.019) and edema of theinterarytenoid mucosa (OR, 3.77; 95% CI, 1.26-16.3; P-value 0.035) were significantly related with EE and independent predictors of EE. However, patients' characteristics and the FSSG score had no significant relationship with EE; there was no relationship between patients' characteristics and EE, regardless of its severity. CONCLUSIONS: Although LPR symptoms had no significant relationship with the findings of EE, hiatal hernia and edema of the interarytenoid mucosa were significantly related with EE and were considered to be independent predictors of EE.
[Show abstract][Hide abstract] ABSTRACT: A previously a healthy 64-year-old woman complained of a two-week history of hemorrhaging upon defecation. The laboratory and urinalysis findings were normal, and no serum or urine M components were detectable on protein electrophoresis. An air contrast barium enema revealed an elevated lesion measuring -20 mm in diameter with a smooth surface and a depression in the sigmoid colon. Colonoscopy revealed a red colored and congested tumor. The exposed surface of the submucosal tumor (SMT) center was somewhat yellow in color and covered with fuzz. All other portions of the colon were normal. The endoscopy and double-contrast barium revealed a normal upper gastrointestinal tract and a normal small intestine, respectively. A histopathological evaluation of a biopsy specimen obtained from the SMT suggested amyloid deposition. However, the other biopsy specimens of the esophagus, stomach, duodenal bulb, second portion of the duodenum, terminal ileum and other portions of the colon demonstrated no amyloid deposition. Colonoscopic ultrasonography (US) revealed the hypoechoic, homogeneous SMT to be mainly localized within the submucosa. An endoscopic submucosal resection (EMR) of the solitary amyloidosis was performed and the immunohistopathology revealed the entire SMT to consist of amyloid light chain kappa amyloid deposition. We considered that the US followed by EMR contributed to the precise diagnosis of solitary amyloidosis and the treatment of hematochezia caused by a solitary area of amyloidosis within the sigmoid colon.
Internal Medicine 01/2013; 52(22):2523-7. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 63-year-old woman was admitted with symptoms of watery diarrhea and generalized edema lasting for five months. She had been administered 15 mg/day of lansoprazole. Laboratory findings revealed severe hypoproteinemia with normal liver, renal, thyroid and adrenal functions and no proteinuria. Colonoscopy revealed edematous mucosa, minor diminished vascular transparency and apparent longitudinal linear lacerations. The histopathological findings were compatible with a diagnosis of collagenous colitis (CC). Protein leakage from the colon was identified on (99m)Tc-human serum albumin scintigraphy. The results indicated CC associated with protein-losing enteropathy. Discontinuing lansoprazole ameliorated the watery diarrhea and generalized edema, increased the serum albumin level and improved the hypoproteinemia.
Internal Medicine 01/2013; 52(11):1183-1187. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy, safety, and long-term outcomes of endoluminal gastroplication (ELGP) in patients with proton pump inhibitor (PPI)-resistant, non-erosive reflux disease (NERD).
The subjects were NERD patients, diagnosed by upper endoscopy before PPI use, who had symptoms such as heartburn or reflux sensations two or more times a week even after 8 wk of full-dose PPI treatment. Prior to ELGP, while continuing full-dose PPI medication, patients' symptoms and quality of life (QOL) were assessed using the questionnaire for the diagnosis of reflux disease, the frequency scale for symptoms of gastro-esophageal reflux disease (FSSG), gastrointestinal symptoms rating scale, a 36-item short-form. In addition, 24-h esophageal pH monitoring or 24-h intraesophageal pH/impedance (MII-pH) monitoring was performed. The Bard EndoCinch(TM) was used for ELGP, and 2 or 3 plications were made. After ELGP, all acid reducers were temporarily discontinued, and medication was resumed depending on the development and severity of symptoms. Three mo after ELGP, symptoms, QOL, pH or MII-pH monitoring, number of plications, and PPI medication were evaluated. Further, symptoms, number of plications, and PPI medication were evaluated 12 mo after ELGP to investigate long-term effects.
The mean FSSG score decreased significantly from before ELGP to 3 and 12 mo after ELGP (19.1 ± 10.5 to 10.3 ± 7.4 and 9.3 ± 9.9, P < 0.05, respectively). The total number of plications decreased gradually at 3 and 12 mo after ELGP (2.4 ± 0.8 to 1.2 ± 0.8 and 0.8 ± 1.0, P < 0.05, respectively). The FSSG scores in cases with no remaining plications and in cases with one or more remaining plications were 4.4 and 2.7, respectively, after 3 mo, and 2.0 and 2.8, respectively, after 12 mo, showing no correlation to plication loss. On pH monitoring, there was no difference in the percent time pH < 4 from before ELGP to 3 mo after. Impedance monitoring revealed no changes in the number of reflux episodes or the symptom index for reflux events from before ELGP to 3 mo after, but the symptom sensitivity index decreased significantly 3 mo after ELGP (16.1 ± 12.9 to 3.9 ± 8.3, P < 0.01). At 3 mo after ELGP, 6 patients (31.6%) had reduced their PPI medication by 50% or more, and 11 patients (57.9%) were able to discontinue PPI medication altogether. After 12 mo, 3 patients (16.7%) were able to reduce the amount of PPI medication by 50% or more, and 12 patients (66.7%) were able to discontinue PPI medication altogether. A high percentage of cases with remaining plications had discontinued PPIs medication after 3 mo, but there was no difference after 12 mo. No serious complications were observed in this study.
ELGP was safe, resulted in significant improvement in subjective symptoms, and allowed less medication to be used over the long term in patients with PPI-refractory NERD.
World Journal of Gastroenterology 11/2012; 18(41):5940-7. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effects of omeprazole on gastric mechanosensitivity in humans.
A double lumen polyvinyl tube with a plastic bag was introduced into the stomach of healthy volunteers under fluorography and connected to a barostat device. Subjects were then positioned so they were sitting comfortably, and the minimal distending pressure (MDP) was determined after a 30-min adaptation period. Isobaric distensions were performed in stepwise increments of 2 mmHg (2 min each) starting from the MDP. Subjects were instructed to score feelings at the end of every step using a graphic rating scale: 0, no perception; 1, weak/vague; 2, weak but significant; 3, moderate/vague; 4, moderate but significant; 5, severe discomfort; and 6, unbearable pain. After this first test, subjects received omeprazole (20 mg, after dinner) once daily for 1 wk. A second test was performed on the last day of treatment.
No adverse effects were observed. Mean MDP before and after treatment was 6.3 ± 0.3 mmHg and 6.2 ± 0.5 mmHg, respectively. One subject before and 2 after treatment did not reach a score of 6 at the maximum bag volume of 750 mL. After omeprazole, there was a significant increase in the distension pressure required to reach scores of 1 (P = 0.019) and 2 (P = 0.017) as compared to baseline. There were no changes in pressure required to reach the other scores after treatment. Two subjects before and one after omeprazole rated their abdominal feeling < 1 at MDP, and mean (± SE) abdominal discomfort scores at MDP were 0.13 ± 0.09 and 0.04 ± 0.04, respectively. Mean scores induced by each MDP + 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 (mmHg) were 1.1 ± 0.3, 2.0 ± 0.4, 2.9 ± 0.5, 3.3 ± 0.4, 4.6 ± 0.3, 5.2 ± 0.3, 5.5 ± 0.2, 5.5 ± 0.3, 5.7 ± 0.3, and 5.4, respectively. After omeprazole, abdominal feeling scores for the same incremental pressures over MDP were 0.3 ± 0.1, 0.8 ± 0.1, 2.0 ± 0.4, 2.8 ± 0.4, 3.8 ± 0.4, 4.6 ± 0.4, 4.9 ± 0.3, 5.4 ± 0.4, 5.2 ± 0.6, and 5.0 ± 1.0, respectively. A significant decrease in feeling score was observed at intrabag pressures of MDP + 2 mmHg (P = 0.028) and + 4 mmHg (P = 0.013), respectively, after omeprazole. No significant score changes were observed at pressures ≥ MDP + 6 mmHg.
Although the precise mechanisms are undetermined, the present study demonstrated that omeprazole decreases mechanosensitivity to mild gastric distension.
World Journal of Gastroenterology 10/2012; 18(39):5576-80. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 41-year-old woman was admitted to our hospital with abdominal pain that developed about 1 year after a Cesarean section. Pelvic computed tomography (CT) revealed diffuse dilation of the small intestine with fluid shadows and a pelvic tumor 55 mm in diameter. The density of the tumor, which was not enhanced by intravenous contrast medium, was diffuse and similar to that of muscular tissue, whereas the density of a capsule surrounding the mass was relatively high. T1- and T2-weighted pelvic magnetic resonance imaging (MRI) of the tumor revealed the same diffuse low-intensity signals as muscular tissue, and diffuse high-intensity signals, respectively. The CT and MRI findings were consistent with those of a gastrointestinal stromal tumor (GIST) causing ileus of the small intestine. As inserting an ileus tube did not improve her symptoms, the patient was scheduled for tumor resection. The operative findings revealed a hard, solid tumor adhering to the surrounding small intestine. The macroscopic findings revealed that the tumor consisted of layers of stratified gauze surrounded by a thick granulomatous wall. The gossypiboma was considered to have originated from gauze that had been left behind after the Cesarean section. If a patient has a history of surgery, the possibility of gossypiboma should be considered when CT or MRI findings indicate features of GIST.
Case Reports in Gastroenterology 05/2012; 6(2):232-7.
[Show abstract][Hide abstract] ABSTRACT: In this 12-week, randomized, double-blind, placebo-controlled trial, the efficacy and safety of transglucosidase (TGD) were compared with placebo in patients with type 2 diabetes mellitus (T2DM). At 12 weeks, TGD 300 mg/day and TGD 900 mg/day significantly reduced HbA1c (0.18 and 0.21%) and insulin concentration (19.4 and 25.0 pmol/l), respectively, vs. placebo. TGD 300 mg/day and TGD 900 mg/day also significantly reduced low-density lipoprotein cholesterol (0.22 and 0.17 mmol/l, respectively). TGD 900 mg/day significantly reduced triglyceride by 0.24 mmol/l and diastolic blood pressure by 8 mmHg. Placebo was associated with a significant increase from baseline in body mass index, alanine aminotransferase and aspartate aminotransferase (0.17 kg/m(2) , 3 and 2 U/l, respectively), whereas TGD was not. TGD 300 mg/day significantly increased high-molecular-weight adiponectin by 0.6 µg/ml. Adverse events did not differ significantly between the groups. TGD resulted in lowering of HbA1c and blood insulin level and improvements in metabolic and cardiovascular risk factors in T2DM.
Diabetes Obesity and Metabolism 11/2011; 14(4):379-82. · 5.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In case 1, endoscopy revealed a submucosal tumor with central ulceration in the esophagus of a 54- year-old man. A biopsy specimen revealed small cell carcinoma without metastasis and the stage of the cancer was stage I (T2N0M0). Two cycles of concurrent cisplatin, etoposide and radiotherapy resulted in an incomplete response/stable disease. The tumor recurred and had metastasized to the brain, lung, liver, lymph nodes of the mediastinum, abdomen and bones after six cycles. Two cycles of irinotecan and cisplatin then elicited a complete response in the primary esophageal lesion. However, progressive disease was identified in the metastatic bone tumors. Despite two further cycles of therapy, he died 447 days after the initial course. In case 2, a biopsy specimen of a tumor with central ulceration in the esophagus of a 77-year old man with swallowing difficulty indicated small cell carcinoma. The stage of the cancer was diagnosed as stage II (T3N0M0). Two cycles of irinotecan, cisplatin and concurrent radiotherapy elicited a complete response. However, the tumor metastasized to the brain and the liver 644 days after starting treatment. Two cycles of carboplastin plus irinotecan elicited a partial response in the metastatic tumors, but he died 988 days after starting chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: An implication of the drinking test for gastric function is controversial. We evaluated the usefulness of a nutrient drinking test for examining gastric function by comparing it with a gastric barostat study.
We investigated perceived pressure of an intragastric bag with stepwise distension and postprandial peak gastric volume (accommodation volume) with a consistent pressure after drinking a liquid meal (200 ml, 300 kcal) in 18 volunteers. Drinking a similar liquid meal on a different day at a continual rate of 15 ml/min was performed to score satiety and bloated sensations at 5-min intervals. An additional 10 volunteers performed the drinking test before and after administration of mosapride citrate or a placebo in a double-blind crossover study.
Pressure to induce severe discomfort correlated positively with maximum satiety volume in the drinking test (r = 0.60, p = 0.02). Accommodation volume in the barostat study showed a significant correlation (r = 0.59, p = 0.03) with threshold volume to induce bloating in the drinking test. Mosapride tended to increase the volume inducing the first bloated sensation as compared to the placebo.
The present drinking test may be useful for evaluating the threshold to induce severe discomfort and accommodation volume.
[Show abstract][Hide abstract] ABSTRACT: Background/Aims: Endoscopic submucosal dissection (ESD) is technically demanding and requires considerable skill. We previously described sheath-assisted counter traction ESD that uses simple materials and methods to improve cutting line visualization. We recently improved counter-traction of the submucosal layer using a novel chemically treated sheath that reduces slippage and maintains traction, and investigated the utility of the novel sheath for ESD. Methodology: Forty-three and 25 consecutive patients with early gastric carcinomas were treated by standard ESD and traction ESD assisted with novel sheaths, respectively. The mean duration of procedures relative to tumor size and location, as well as complications after ESD between the two groups were compared. Results: The mean duration of ESD procedures for lesions =20mm in diameter was significantly reduced using the novel sheath. The mean duration of procedures for all locations of resected tumors in the stomach was significantly reduced using the novel sheath. However, no perforation and delayed bleeding developed after treatment with the novel sheath. Conclusions: Sheath-assisted counter traction ESD by the novel sheath was technically simpler and thus less time-consuming regardless of the location of lesions, especially when =20mm in diameter. The traction ESD with the novel sheath is safe and not invasive, and it can be universally applied to standard ESD.
[Show abstract][Hide abstract] ABSTRACT: TANK-binding kinase 1 (TBK1) regulates the interferon regulatory factor (IRF) 3 and IRF7 activation pathways by double strand RNA (dsRNA) via Toll-like receptor (TLR) 3 and by lipopolysaccharide (LPS) via TLR4. Rebamipide is useful for treating inflammatory bowel disease (IBD). Although IBD is associated with nuclear factor-κB (NF-κB), any association with the TBK1-IRF pathway remains unknown. How rebamipide affects the TBK1-IRF pathway is also unclear. We analyzed the relationship between IBD (particularly ulcerative colitis; UC) and the TLR-TBK1-IRF3/7 pathway using human colon tissue, a murine model of colitis and human colonic epithelial cells. Inflamed colonic mucosa over-expressed TKB1, NAP1, IRF3, and IRF7 mRNA compared with normal mucosa. TBK1 was mainly expressed in inflammatory epithelial cells of UC patients. The expression of TBK1, IRF3, IRF7, IFN-α and IFN-β mRNA was suppressed in mice given oral dextran sulfate-sodium (DSS) and daily rectal rebamipide compared with mice given only DSS. Rebamipide reduced the expression of TBK1, IRF3 and IRF7 mRNA induced by LPS/dsRNA, but not of NF-κB mRNA in colonic epithelial cells. Rebamipide might suppress the TLR-TBK1 pathway, resulting in IRF3/7-induction of IFN-α/β and inflammatory factors. TBK1 is important in the induction of inflammation in patients with UC. If rebamipide represses the TLR-TBK1 pathway, then rectal administration should suppress inflammation of the colonic mucosa in patients with UC.
Journal of Clinical Biochemistry and Nutrition 03/2011; 48(2):154-60. · 2.25 Impact Factor