SUMMARYBackground: Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. Aim: To investigate oesophageal hypersensitivity in Japanese NERD patients. Patients and methods: We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups.

The localization and the expression patterns of tight-junction proteins were different in the controls and the rat esophagitis model. The expression of claudin-3 in the esophageal mucosa was decreased, while that of claudin-1 was increased. It is postulated that these alterations in tight-junction proteins most likely increase the permeability of the esophageal the epithelium, thereby impairing the defense mechanism of this epithelium.

SUMMARYBackground: It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. Aim: To clarify the histological changes after the cure of H. pylori infection through a literature survey. Methods: Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. Results: Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-

Summary Background:  An antimicrobial susceptibility test for Helicobacter pylori before second‐line treatment is often performed, although whether the test is truly necessary remains unknown. Patients and methods:  Eighty‐two patients with H. pylori infection for whom first‐line treatment with a 1‐week proton pump inhibitor/amoxicillin–clarithromycin (AC) regimen had failed were randomly assigned to two groups: those having or not having the susceptibility test before re‐treatment. The cure rates for these two groups were compared. Results:  Five of the 82 patients were excluded from the analysis. For 38 patients in the susceptibility‐test group, we used what we considered the best regimen based on susceptibility testing: 10 patients [no resistance to clarithromycin (CAM)] received the lansoprazole–amoxicillin–clarithromycin regimen, 22 patients [19 CAM resistant, metronidazole (MNZ) susceptible; three failure of culture] were given the lansoprazole‐amoxicillin‐metronidazole (LAM) regimen, and six patients (both MNZ and CAM resistant) received dual therapy with omeprazole (OPZ) and amoxicillin (AMOX) in which the OPZ dose was determined by the CYP2C19 gene polymorphism. For 39 patients in the group with no susceptibility testing, LAM regimens were prescribed. The intention‐to‐treat (ITT)‐based cure rates in the groups with and without susceptibility testing were 81.6% (95% confidence interval; 66–92%) and 92.4% (79–98%), respectively, and there was no significant difference between these two groups. Conclusion:  Susceptibility testing is not necessarily required before second‐line therapy if the first‐line treatment has been performed using proton pump inhibitor/AC regimens.

Both eGERD and NERD, but especially NERD, exhibited esophageal hypersensitivity not only to acid but also saline perfusion, suggesting that hyperalgesia to acid and other factors (eg, psychologic and/or autonomic nerve disturbance) may play some roles in symptom generation in NERD.

The simple twice-daily and short-term quadruple regimen for only 5 days provided an excellent eradication rate. Compliance with the regimen was high, and serious adverse effects were few. Therefore, the RACM regimen can be considered as safe and effective.

SUMMARYBackground: A decrease in pepsinogen and gastrin levels 1-3 months after Helicobacter pylori eradication is well known. However, few data are available on the longterm progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori-negative patients with dyspepsia. Aim: We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori-negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I ⁄ II ratio. Methods: We enrolled 172 H. pylori-positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non-treated H. pylori-negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed

Microcirculation plays a crucial role in mucosal physiological function as well as repair of gastric mucosal damage. Endothelial cell damage is known to disturb microcirculation and suppress angiogenesis. Therefore, the direct effect of Helicobacter pylori on endothelial cells in vitro was investigated with H. pylori water extract. The effect of H. pylori water extract on cell proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) was evaluated. The ratio of BrdU-positive HUVECs in both cagA/vacA-positive and -negative H. pylori water extract-treated groups was significantly lower at 24 h than that in the control group, but Escherichia coli water extract did not affect the proliferation of these endothelial cells. Apoptosis was induced by H. pylori water extracts after incubation for 24 h in a cagA/vacA-independent manner. In the mitochondrial permeability transition assay, tetramethylrhodamine methyl ester was accumulated in mitochondria of HUVECs. Western blot analysis showed no difference in the level of total p53 protein in H. pylori water extract-treated and non-treated cells, but the level of phosphorylated p53 protein was increased in the treated cells at 15 and 60 min after addition of the extract. Reverse transcription (RT)-PCR products for p21 and Bax were elevated in the H. pylori water extract-treated cells. p21 levels began to increase 0.5-1 h after addition of the extract, whereas Bax increased in the period 0.5-2 h. H. pylori induced a disturbance of cell proliferation and apoptosis in the vascular endothelial cells which may contribute to gastric mucosal injury and to delayed healing of gastric lesions.