Yasushi Funaki

Transglucosidase improves the gut microbiota profile of type 2 diabetes mellitus patients: a randomized double-blind, placebo-controlled study

BackgroundRecently, 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.MethodsThis 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.ResultsThe 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.ConclusionsTherefore, 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 registrationUMIN-CTR UMIN000010318

ENDOSCOPIC SUBMUCOSAL DISSECTION WITH SHEATH-ASSISTED COUNTER TRACTION FOR EARLY GASTRIC CANCERS

Aim:u2002 Endoscopic submucosal dissection (ESD) is associated with frequent complications, such as bleeding and perforation. The procedure is technically difficult, requires considerable skill and is longer than conventional endoscopic mucosal resection (EMR). Thus, non‐invasive tools and methods are needed to facilitate direct visualization of the submucosal layer during ESD.

Low-dose aspirin-associated upper gastric and duodenal ulcers in Japanese patients with no previous history of peptic ulcers

BackgroundLong-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.MethodsConsecutive outpatients receiving LDA (75xa0mg/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.ResultsOf 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%; Pu2009=u20090.024) 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], 1.19u2009−u200928.99; Pu2009=u20090.03 and OR, 0.13; 95% CI, 0.02u2009−u20090.73; Pu2009=u20090.02, 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.ConclusionThe 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.

Enhanced somatostatin secretion into the gastric juice with recovery of basal acid output after Helicobacter pylori eradication in gastric ulcers.

Background and Aim: Antral somatostatin interacts with gastric acid secretion. We aimed to investigate the effect of eradication on gastric acid, somatostatin secretion and mucosal histology in gastric ulcer patients with Helicobacter pylori (H. pylori) infection.

Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury

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.

eNOS plays an important role in the regulation of colonic inflammation: A novel therapeutic target and a predictive marker for the prognosis of ulcerative colitis

Abstract Background. We reported that deficiency of the eNOS protein exacerbates colitis induced by dextran sodium sulfate (DSS-induced colitis). However, the role of eNOS in colitis remains controversial. Therefore, we studied how over-expression of eNOS affected this inflammatory condition, using vascular endothelial cells and mice as in vitro and in vivo models, respectively. Furthermore, we investigated the influence of a polymorphism in the eNOS gene on the clinical features of ulcerative colitis (UC). Methods. We examined the effect of eNOS overexpression on the expression of adhesion molecules in the endothelium and assessed the degree of DSS-induced colitis in eNOS transgenic (eNOS-Tg) mice. We also investigated the relationship between a polymorphism in the eNOS gene and clinical features of patients with UC. Results. The expression of adhesion molecules, under inflammatory conditions, was attenuated in eNOS gene-transfected vascular endothelial cells, as measured by western blot analysis. Symptoms of DSS-induced colitis were likewise attenuated in eNOS-Tg mice, which exhibited lower weight loss, mortality, histological damage (by inflammation score and crypt damage score), and colonic myeloperoxidase activity, tumor necrosis factor-α expression, and MAdCAM-1 expression than in wild-type mice. Furthermore, there was a significant relationship between intractable cases of UC and a polymorphism in the eNOS gene promoter (c.-786 T > C) that decreases eNOS expression. Conclusion. The eNOS gene plays an important role in the regulation of colonic inflammation. The level of eNOS expression may be a predictive marker for prognosis of UC, and eNOS expression may be a novel therapeutic target.

Effects of transglucosidase on diabetes, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes: a 12‐week, randomized, double‐blind, placebo‐controlled trial

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/m2, 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.

The Influence of Snare Size on the Utility and Safety of Cold Snare Polypectomy for the Removal of Colonic Polyps in Japanese Patients

Background Cold snare polypectomy (CSP) has been recently reported to be useful for the removal of small colonic polyps. However, the relationship between the histologically complete resection rate and snare size used during CSP has not been reported. Our aim was to assess the utility of CSP. Methods We analyzed the histologically complete resection rates and the frequency of complications for 175 colon polyps removed by CSP. Moreover, we examined the histologically complete resection rate associated with different snare sizes used during CSP. Results There was no significant difference in the histologically complete resection rate between endoscopic mucosal resection (EMR) (60.9%) and CSP (53.1%). There were also no significant differences in the frequency of complications including perforation and postoperative bleeding between EMR (perforation: none; postoperative bleeding: two patients) and CSP (perforation: none; postoperative bleeding: none). Histological examination revealed that the complete resection rate of CSP using a short snare (61.6%) was significantly higher than that of CSP using a long snare (44.9%; P < 0.05). There were no significant differences in the frequency of complications between CSP using the short snare and that using the long snare. Conclusions CSP is a safe, useful method for the removal of colonic polyps. CSP using the short snare improved the histologically complete resection rates compared to the long snare. Future studies to further assess the utility of CSP are required.

A Patient with Vigorous Achalasia and Rapid Enlargement of an Epiphrenic Esophageal Diverticulum.

A 47-year-old man was found to have a 3-cm epiphrenic esophageal diverticulum on an upper gastrointestinal (UGI) barium study. He developed the symptoms of heartburn approximately 12 months later. UGI endoscopy indicated non-erosive gastroesophageal reflux disease (NERD) and an epiphrenic esophageal diverticulum. A proton pump inhibitor (PPI) did not relieve the symptoms. An UGI barium study at that time showed that the epiphrenic esophageal diverticulum had enlarged to 7 cm, and esophageal manometry showed findings of achalasia and diffuse esophageal spasm (DES), thus vigorous achalasia was diagnosed. Resection of the epiphrenic esophageal diverticulum, myotomy, and fundoplication (the Heller-Dor procedure) were successfully performed and no postoperative symptoms were encountered.

Effect of aspirin cessation before endoscopy in Japanese patients with low-dose-aspirin-associated gastroduodenal mucosal injury

Background The incidence of upper gastrointestinal injury by low-dose aspirin (LDA) has increased. Objective We aimed to clarify the risk factors and prevention strategies associated with LDA-induced gastroduodenal ulcer in Japanese patients. Methods A retrospective study involving 284 LDA users who underwent oesophagogastroduodenoscopy between January and December 2010 were included. We investigated the patients’ clinical characteristics and endoscopic findings. Results Of 284 patients, 29 (10.2%) had gastro and/or duodenal ulcers. Male gender, peptic ulcer history, abdominal symptoms, half-dose proton pump inhibitors (PPIs), complete-dose PPIs, and nonsteroidal anti-inflammatory drugs were significantly associated with LDA-induced gastro and/or duodenal ulcers: odds ratio (95% confidence interval) 3.62 (1.06–12.27), 6.60 (1.84–23.62), 3.06 (1.12–8.40), 0.16 (0.03–0.94), 0.07 (0.01–0.61), and 9.68 (1.64–57.18), respectively. PPI significantly reduced gastric ulcers and/or duodenal ulcers (pu2009=u20090.03). The modified Lanza score for gastric mucosal lesion in the LDA cessation group was significantly lower than in the LDA noncessation group (0.53 vs. 1.02; pu2009=u20090.008). Conclusions Half-dose PPIs as well as complete-dose PPIs were effective for preventing LDA-induced gastric and/or duodenal ulcers. The cessation of LDA before endoscopy may lead to an underestimation of LDA-induced gastric injury.