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Background/Aims The gastric acid pocket has an important role in gastroesophageal reflux disease development. In this study, we utilized a novel 8-channel pH monitoring system with sensor intervals of 1 cm on the vertical axis for evaluation of postprandial gastric acid pocket in healthy Japanese adults, as well as the effects of vonoprazan and rabeprazole. Methods Twelve healthy volunteers without Helicobacter pylori infection were enrolled. A catheter was inserted transnasally and positioned under X-ray guidance, then postprandial acid pocket formation was monitored over time in a sitting position. Thereafter, acid pocket changes were assessed following administration of vonoprazan (20 mg) or rabeprazole (20 mg). Results The gastric acid pocket was successfully measured by use of the present system in 10 cases, while failure occurred in 2 because of inappropriate catheter positioning. Observed acid pockets were visualized with a mean length of 2.2 ± 0.4 channels on the top layer of food contents approximately 20 minutes after finishing a meal. There were some variations for lasting time of the acid pocket. Complete elimination within 3 hours after administration of vonoprazan was noted in all cases. Likewise, following administration of rabeprazole, the acid pocket was eliminated in 7 cases, while acidity was reduced though the pocket remained observable in 3. Conclusions Gastric acid pocket observations were possible using our novel vertical 8-channel sensor catheter. The present findings showed that vonoprazan strongly suppressed acid secretion within a short period, suggesting its effectiveness for gastroesophageal reflux disease treatment. (J Neurogastroenterol Motil 2021;27:370-376)

Heterotopic gastric mucosa (HGM) of esophagus, primarily occurring in cervical esophagus, is usually asymptomatic. A healthy woman (mid-40s) with postprandial heartburn was diagnosed with middle esophageal HGM and esophageal ulcers by esophagogastroduodenoscopy. Using 8-channel pH monitoring, a sensor near the HGM area detected postprandial acid phase (pH 3-4), while areas adjacent to the proximal and distal sensors were neutral, suggesting acid secretion from the HGM. A biopsy showed fundic gland tissue expressing H

We report a case of sigmoid endometriosis diagnosed preoperatively based on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) findings. A 42-year-old female came to us with left lower abdominal pain and bloating that had started 3 months prior. CT and MRI results showed wall thickening of the sigmoid colon. A colonoscopy procedure could not be completed because passage through the sigmoid colon was blocked due to severe stenosis, while mucosal biopsy samples obtained during that procedure could not confirm a diagnosis. EUS-FNA was then performed and specimens were obtained from the muscular layer with stenosis, which revealed a thickened hypoechoic lesion. Histological findings obtained by use of EUS-FNA demonstrated a large amount of fibrosis in endometrial glands and a diagnosis of sigmoid endometriosis was confirmed by additional immunostaining. Thus, a laparoscopic sigmoidectomy was performed, with sigmoid endometriosis finally diagnosed. Confirmation of a diagnosis of intestinal endometriosis based on histological findings of mucosal biopsy specimens obtained by colonoscopy is difficult, because endometrial implants are primarily located in the serosal and/or muscular layer. When safe aspiration is possible, we consider that EUS-FNA can be an effective method for preoperative diagnosis of intestinal endometriosis, which may contribute to avoidance of unnecessary or excessive surgery.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder that is characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation.1,2 Its prevalence has been increasing rapidly in both Western and Asian countries. In Japan, most of the cases of esophageal eosinophilia (EE) are found in an upper endoscopy examination for gastric cancer screening performed during a comprehensive health check-up.3,4 Indeed, we frequently encounter patients with asymptomatic EE showing typical endoscopic findings, such as linear furrows, as well as histologic findings compatible with EoE. However, the current clinical guidelines for EoE diagnosis include symptoms related to esophageal dysfunction, thus patients without symptoms do not fulfill the diagnostic criteria.1,2 The clinical characteristics remain to be fully elucidated,5 thus we aimed to clarify clinical features of asymptomatic EE as compared with those of EoE.

The correct name of the corresponding author should be ''Nobuhiko Fukuba'', and not ''Nobuhiko Fukuban'' as given in the original publication of the article.

A 50-year-old male underwent abdominal computed tomography at a city hospital in Japan, which revealed a tumor 38 mm in diameter in the tail of the pancreas. Based on findings from endoscopic ultrasonography-guided fine needle aspiration using a 22-gauge needle with a side hole, the tumor was diagnosed as an invasive ductal carcinoma. The patient was referred to our hospital and underwent a distal pancreatectomy. Esophagogastroduodenoscopy performed as part of a medical checkup at another hospital 2 years later revealed a 20-mm-sized submucosal tumor in the posterior wall of the upper body of the stomach. Examination of a biopsy specimen obtained from the top of the lesion revealed adenocarcinoma. Partial resection of the stomach was performed and pathological findings showed an adenocarcinoma in all layers of the stomach wall, consistent with recurrence derived from needle tract seeding of the previously excised cancerous tumor from the pancreatic tail. Additional experimentation performed for confirmation with an agar model showed that agar on the deep side leaked to the shallow side following puncture with a needle with a side hole used with a slow-pull technique.

We investigated the effect of cardiac-targeting erythropoietin (EPO)-encapsulated liposomes with sialyl LewisX (SLX) on myocardial infarct (MI) size, left ventricular (LV) remodeling and function, and its molecular mechanism for repairing infarcted myocardium. In rabbits, MI was induced by 30 min of coronary occlusion followed by reperfusion. EPO-encapsulated liposomes with SLX (L-EPO group), EPO-encapsulated liposomes without SLX (L-EPO without SLX group), liposomes with SLX without EPO (L group), or saline (saline group) were intravenously administered immediately after MI. MI sizes and numbers of microvessels were assessed 14 days after MI. Prosurvival proteins and signals were assessed by Western blot analysis 2 and 14 days after MI. Confocal microscopy and electron microscopy showed the specific accumulation of liposomes with SLX in the infarcted myocardium. MI and cardiac fibrosis areas were significantly smaller in the L-EPO group than in the other groups. LV function and remodeling were improved in the L-EPO group. The number of CD31-positive microvessels was significantly greater in the L-EPO group than in the other groups. Higher expressions of EPO receptors, phosphorylated (p)Akt, pERK, pStat3, VEGF, Bcl-2, and promatrix metalloproteinase-1 were observed in the infarct area in the L-EPO group than in the other groups. EPO-encapsulated liposomes with SLX selectively accumulated in the infarct area, reduced MI size, and improved LV remodeling and function through activation of prosurvival signals and by exerting antifibrotic and angiogenic effects. EPO-encapsulated liposomes with SLX may be a promising strategy for active targeting treatment of acute MI.

Summary 1. The present study examined whether or not cilostazol reduces the myocardial infarct size, and investigated its mechanism in a rabbit model of myocardial infarction. 2. Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 h of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was given intravenously 5 min before ischaemia. 8-p-sulfophenyl theophylline (8SPT; an adenosine receptor blocker, 7.5 mg/kg), Nω-nitro-l-arginine methylester (l-NAME; an NOS inhibitor, 10 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD; a mitochondrial ATP-sensitive potassium (KATP) channel blocker, 5 mg/kg) was given intravenously 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area. 3. The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) during ischaemia and reperfusion, and the intensity of myocardial dihydroethidium staining were determined. 4. Infarct size was significantly reduced in the cilostazol 1 mg/kg (38.4% (2.9%)) and cilostazol 5 mg/kg (30.7% (4.7%)) groups compared with that in the control group (46.5% (4.2%)). The infarct size-reducing effect of cilostazol was completely abolished by 8SPT (46.6% (3.5%)), l-NAME (49.0% (5.5%)), or 5HD (48.5% (5.1%)). 8SPT, l-NAME or 5HD alone did not affect the infarct size. Cilostazol treatment significantly increased myocardial levels of adenosine and NOx during ischaemia, and attenuated the intensity of dihydroethidium staining during reperfusion. 5. These findings show that cilostazol reduces the myocardial infarct size by increasing adenosine and NOx levels, attenuating superoxide production and opening the mitochondrial KATP channels. Cilostazol might provide a new strategy for the treatment of coronary heart disease.

BACKGROUND AND PURPOSE We previously reported that pre-ischaemic i.v. miglitol reduces myocardial infarct size through the inhibition of glycogenolysis during ischaemia. Oral administration of miglitol has been reported to produce glucagon-like peptide 1 (GLP-1). We hypothesized that p.o. administration of miglitol, an absorbable antidiabetic drug, reduces myocardial infarct size by stimulating GLP-1 receptors and inhibiting glycogenolysis in the myocardium. EXPERIMENTAL APPROACH The effects of p.o. and i.v. administration of miglitol on myocardial infarct size were compared in a rabbit model of ischaemia induced by 30 min of coronary occlusion and 48 h of reperfusion. The levels of phospho(p)-PI3kinase and p-Akt were measured in cardiac tissue by use of Western blot analysis. RESULTS Both p.o. and i.v. administration of miglitol reduced the infarct size, and this effect was greater after p.o. than after i.v. administration under similar plasma miglitol concentrations. The reduction in infarct size induced by p.o. miglitol but not that induced by i.v. miglitol was partially inhibited by treatment with exendin(9-39), a GLP-1 receptor blocker. Both p.o. and i.v. miglitol improved ejection fraction and ±dP/dt after myocardial infarction. Miglitol administered p.o. but not i.v. up-regulated the myocardial expression of phospho(p)-PI3kinase and p-Akt following myocardial infarction; an effect that was inhibited by exendin(9-39). CONCLUSIONS AND IMPLICATIONS Administration of miglitol p.o. reduces myocardial infarct size through stimulation of GLP-1 receptors and activation of PI3kinase-Akt pathway in addition to the inhibition of glycogenolysis. These findings may have clinical implications for the p.o. administration of miglitol for the treatment of patients with diabetes mellitus combined with coronary artery disease.

Granulocyte colony-stimulating factor (G-CSF) has been reported to improve cardiac function after myocardial infarction. However, whether postinfarct acute effect of G-CSF is mediated through the same signaling pathways as those of ischemic postconditioning is still unclear. We examined the postinfarct acute effect of G-CSF on myocardial infarct size and its precise molecular mechanism. Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Rabbits were intravenously injected 10 μg/kg of G-CSF (G-CSF group) or saline (control group) immediately after reperfusion. The wortmannin + G-CSF, PD-98059 + G-CSF, Nω-nitro-l-arginine methyl ester (l-NAME) + G-CSF, and 5-hydroxydecanoic acid sodium salt (5-HD) + G-CSF groups were respectively injected with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), l-NAME (10 mg/kg), and 5-HD (5 mg/kg) 5 min before G-CSF administration. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the signals such as protein kinase B (Akt), extracellular signal-regulated protein kinase (ERK), eNOS, p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK3β) in the ischemic myocardium after 48 h of reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7 ± 2.7%) than in the control group (42.3 ± 4.6%). The infarct size-reducing effect of G-CSF was completely blocked by wortmannin (44.7 ± 4.8%), PD-98059 (38.3 ± 3.9%), l-NAME (42.1 ± 4.2%), and 5-HD (42.5 ± 1.7%). Wortmannin, PD-98059, l-NAME, or 5-HD alone did not affect the infarct size. Western blotting showed higher myocardial expression of phospho-Akt, phospho-ERK, phosho-eNOS, phosho-p70S6K, and phosho-GSK3β at 10 min and 48 h after reperfusion in the G-CSF group than in the control group. In conclusion, postreperfusion G-CSF administration reduces myocardial infarct size via activation of phosphatidylinositol 3-kinase-Akt and ERK prosurvival signaling pathways and their downstream targets eNOS, p70S6 kinase, GSK3β, and mitochondrial ATP-dependent K+ channel.

1. The present study examined whether or not cilostazol reduces the myocardial infarct size, and investigated its mechanism in a rabbit model of myocardial infarction. 2. Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 h of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was given intravenously 5 min before ischaemia. 8-p-sulfophenyl theophylline (8SPT; an adenosine receptor blocker, 7.5 mg/kg), Nω-nitro-L-arginine methylester (l-NAME; an NOS inhibitor, 10 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD; a mitochondrial ATP-sensitive potassium (KATP) channel blocker, 5 mg/kg) was given intravenously 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area. 3. The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) during ischaemia and reperfusion, and the intensity of myocardial dihydroethidium staining were determined. 4. Infarct size was significantly reduced in the cilostazol 1 mg/kg (38.4% (2.9%)) and cilostazol 5 mg/kg (30.7% (4.7%)) groups compared with that in the control group (46.5% (4.2%)). The infarct size-reducing effect of cilostazol was completely abolished by 8SPT (46.6% (3.5%)), L-NAME (49.0% (5.5%)), or 5HD (48.5% (5.1%)). 8SPT, L-NAME or 5HD alone did not affect the infarct size. Cilostazol treatment significantly increased myocardial levels of adenosine and NOx during ischaemia, and attenuated the intensity of dihydroethidium staining during reperfusion. 5. These findings show that cilostazol reduces the myocardial infarct size by increasing adenosine and NOx levels, attenuating superoxide production and opening the mitochondrial KATP channels. Cilostazol might provide a new strategy for the treatment of coronary heart disease.

Glucagon-like peptide 1 (GLP-1) reportedly exerts a protective effect against cardiac ischemia. We hypothesized that the alpha-glucosidase inhibitor voglibose, an unabsorbable antidiabetic drug with cardioprotective effects, may act through stimulation of GLP-1 receptors. The results of the present study suggest oral administration of voglibose reduces myocardial infarct size and mitigates cardiac dysfunction in rabbits after 30 minutes of coronary occlusion and 48 hours of reperfusion. Voglibose increased basal and postprandial plasma GLP-1 levels and reduced postprandial plasma glucose levels. The infarct size-reducing effect of voglibose was abolished by treatment with exendin(9-39), wortmannin, Nomega-nitro-L-arginine methylester, or 5-hydroxydecanoate), which inhibit GLP-1 receptors, phosphoinositide 3-kinase, nitric oxide synthase, and K(ATP) channels, respectively. Western blot analysis showed that treatment with voglibose upregulated myocardial levels of phospho-Akt, phosphoendothelial nitric oxide synthase after myocardial infarction. The upregulation of phospho-Akt was inhibited by exendin(9-39) and wortmannin. These findings suggest that voglibose reduces myocardial infarct size through stimulation of GLP-1 receptors, activation of the phosphoinositide 3-kinase-Akt-endothelial nitric oxide synthase pathways, and the opening of mitochondrial K(ATP) channels. These findings may provide new insight into therapeutic strategies for the treatment of patients with coronary artery disease.

It has been reported that granulocyte-colony-stimulating factor(G-CSF) improves cardiac function after myocardial infarction (MI). However, its direct effect on the myocardium and its signaling pathway remain unclear. We examined the acute beneficial effect of G-CSF on myocardial infarct size and its precise mechanisms in a rabbit model of myocardial infarction. In 80 Japanese white rabbits, MI was induced by 30 min of ischemia and 48 hours of reperfusion. Rabbits were intravenously injected with 10 μg/kg of G-CSF (G-CSF group, n=10) or saline (control group, n=10) immediately after reperfusion. The G-CSF+5HD group (n=10) was injected with 5-HD(5-hydroxydecanoate, a mitochondrial KATP channel blocker) 5 min before G-CSF injection. The G-CSF +wortmaninn group (n=10) was injected wortmaninn (0.6mg/kg) 5 min before G-CSF injection. G-CSF+L-NAME group (n=10) was injected with L-NAME (10mg/kg) 5 min before G-CSF injection. The 5HD alone (n=10), wortmannin alone (n=10), L-NAME alone (n=10) groups were respectively injected 5HD, wortmannin and L-NAME immediately after reperfusion. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the Akt and phospho-Akt and phospho-eNOS in the ischemic myocardium at 48 hours of reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7±2.7%) than in the control group (42.3±4.6%). The infarct size-reducing effect of G-CSF was completely blocked by 5-HD (42.5±1.66%), wortmaninn(44.7±4.81) and L-NAME (42.1±4.2%). Wortmannin, L-NAME or 5HD alone did not affect the infarct size. Western blotting showed higher expression of phospho-Akt and phosho-eNOS in the infarct area in the G-CSF group than in the control group. G-CSF administered immediately after reperfusion reduces myocardial infarct size via activation of PI3K, Akt, eNOS and opening the mitochondrial KATP channels.

Statins have been reported to be protective against myocardial infarction (MI). Moreover, statin drugs upregulate nitric oxide (NO) in coronary artery independent of lipid-lowering effects. However their precise mechanism for MI-protection is unclear. We investigated the effect of lipophilic statin administration in a normocholesterolemic rabbit MI model.Nω-nitro-L-arginine methylester (L-NAME, 10 mg/kg) or vehicle alone was intravenously administered 20 min before inducing ischemia, followed by intravenous administration of simvastatin (5 mg/kg) or saline 10 min before ischemia. Rabbits then underwent 30 min of coronary occlusion followed by 48 h of reperfusion. The at-risk and infarct areas were calculated as a percentage of the total left ventricular slice area.Determination of infarct size revealed that pre-ischemic treatment with simvastatin reduced infarct size (30.5 ± 4%) in comparison to controls (45.0 ± 3%) (P0.05). This infarct size-reducing effect of simvastatin could be completely abrogated by pretreatment with L-NAME (42.0 ± 4%).Pre-ischemic treatment with simvastatin reduces MI size via NO production. Simvastatin could be a useful drug for coronary artery disease patients without dyslipidemia as it has direct protective effects.