Kunimitsu Inoue

Aspirin-induced small bowel injuries and the preventive effect of rebamipide

AIM To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide. METHODS This study was conducted as a single-center, randomized, double-blind, cross-over, placebo-controlled study. Eleven healthy male subjects were enrolled. Each subject underwent video capsule endoscopy after 1 and 4 wk of taking aspirin and omeprazole, along with either rebamipide or placebo therapy. The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk. RESULTS The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) were 1 at 1 wk and 1 at 4 wk on the jejunum, and 6 at 1 wk (P = 0.0061) and 7 at 4 wk on the ileum (P = 0.0019). Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group (P = 0.0173 at 1 wk and P = 0.0266 at 4 wk). CONCLUSION Longer-term, low-dose aspirin administration induced damage in the small bowel. Rebamipide prevented this damage, and may be a candidate drug for treating aspirin-induced small bowel complications.

Helicobacter pylori Eradication Improves Gastric Atrophy and Intestinal Metaplasia in Long-Term Observation

Background and Aim:Helicobacter pylori has been shown to cause atrophic gastritis and intestinal metaplasia (IM), both of which are precancerous lesions. To clarify the mechanism by which H. pylori eradication prevents gastric cancer, we monitored atrophy and IM improvement in gastric mucosa over a long period after H. pylori eradication. Methods: We monitored 118 patients (72 males, 46 females; mean age 61.3 ± 5.1 years) for a mean of 8.6 years (range 5–13) after successful H. pylori eradication. Biopsy specimens were taken from the greater curvatures of the antrum (A2) and the corpus (B2). Results: Atrophy was significantly decreased in patients with successful H. pylori eradication, both at A2 (from 1.60 ± 0.09 to 1.02 ± 0.08; p < 0.001) and B2 (from 0.71 ± 0.10 to 0.02 ± 0.02; p < 0.001), and IM score was significantly decreased at B2 (from 0.17 ± 0.12 to 0.00 ± 0.00; p < 0.05), but not at A2 (from 0.60 ± 0.11 to 0.43 ± 0.09; p = NS). In patients without successful eradication, however, there were no differences in scores over time. Before eradication, IM score was significantly higher in males than in females, both at A2 (0.81 ± 0.12 vs. 0.25 ± 0.10; p < 0.05) and B2 (0.32 ± 0.08 vs. 0.07 ± 0.04; p < 0.05). Conclusion: We were able to monitor the gastric mucosa for a mean of 8.6 years after H. pylori eradication, the longest period reported to date. Significant improvements in gastric atrophy and IM after H. pylori eradication may decrease the risk of gastric cancer.

Comparison of amoxicillin-metronidazole plus famotidine or lansoprazole for amoxicillin-clarithromycin-proton pump inhibitor treatment failures for Helicobacter pylori infection

Background:  Proton pump inhibitor–amoxicillin–metronidazole is recommended as second‐line Helicobacter pylori therapy in Japan. The authors assessed the efficacy and safety of second‐line eradication using the H2‐receptor antagonist famotidine as a substitute for proton pump inhibitor.

Impact of Helicobacter pylori CagA diversity on gastric mucosal damage: An immunohistochemical study of East-Asian-type CagA

Background and Aims:  Recently, we successfully produced an anti‐East‐Asian‐type CagA‐specific antibody called α‐EAS Ab, which is specifically immunoreactive only with East‐Asian‐type CagA but not Western‐type CagA. In this study, the correlations between Helicobacter pylori CagA protein diversity and gastric mucosal condition was investigated using immunohistochemical staining with α‐EAS Ab in Japan.

Evaluation of a New Tumor Necrosis Factor‐α‐Inducing Membrane Protein of Helicobacter pylori as a Prophylactic Vaccine Antigen

Background:  Tumor necrosis factor (TNF)‐α‐inducing protein (Tipα) is a newly identified carcinogenic factor present in Helicobacter pylori. Tipα has the unique function of inducing TNF‐α production by gastric cells in vitro and is assumed to be related with the development of gastritis and gastric cancer. We investigated the effects of vaccination with Tipα against H. pylori infection and analyzed the immune responses.

Commensal Microbiota Contributes to Chronic Endocarditis in TAX1BP1 Deficient Mice

Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced ‘germ free’ status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mices inflammatory lesions. These pathological conditions, as we named ‘pseudo-infective endocarditis’ were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.

Helicobacter pylori and NSAID-induced gastric ulcer in a Japanese population

A recent meta-analysis by Huang et al. clarified that Helicobacter pylori infection and nonsteroidal antiinflammatory drugs (NSAIDs) are important factors for peptic ulcer. The results showed that the risk for ulcer in NSAID(+)/H. pylori(+) patients was 61.1 fold higher when compared with NSAID(−)/H. pylori(−) patients. Some gastric ulcers detected in patients on NSAID therapy may actually be caused by H. pylori, but it is difficult to differentiate NSAID-induced gastric ulcer from H. pylori-induced gastric ulcer. Several studies have investigated the effects of H. pylori eradication on ulcer healing. One study reported that H. pylori eradication actually lowered the healing rate of gastric ulcers. Because there have been no studies finding that H. pylori eradication facilitates healing, H. pylori eradication is not recommended for NSAID users. Concerning the efficacy of H. pylori eradication in the prevention of NSAID-induced gastric ulcer, a meta-analysis concluded that among all patients on NSAID therapy, H. pylori eradication lowered the prevalence of ulcer, which was particularly marked in NSAID-naïve patients. When compared with those of proton pump inhibitors (PPIs), the preventative effects of H. pylori eradication were inferior. In Japan, national health insurance does not cover procedures that prevent or lower the risk for NSAID-induced ulcer. When administering NSAID to patients with risk factors, it is desirable to administer antiulcer agents.

Risk Factors for Dysmotility, Acid Reflux Symptoms, and Overlap Using FSSG in Japan

Aims. FSSG {frequency scale for the symptoms of gastroesophageal reflux disease (GERD)} was developed as a diagnostic tool for dysmotility and acid reflux symptoms. We first used FSSG to investigate the prevalence and risk factors for dysmotility and acid reflux symptoms and overlap of the two symptoms in a Japanese population. Methods. A cross-sectional survey was performed in Japanese underwent the routine medical examination. Dysmotility and acid reflux symptom were diagnosed by using FSSG. Subjects met both criteria were considered as overlap group. Results. Among 778 subjects, 395 persons were included in the final analyses. Dysmotility symptoms were found in 32.6% and acid reflux symptoms in 20.5%. Their overlap was found in 13.9% of all 395 subjects, which in 42.6% of dysmotility symptoms and 67.9% of acid reflux symptoms. Multiple logistic analysis showed that female gender was significantly associated with dysmotility symptoms compared with controls. Female gender, smoking, and hiatus hernia were significantly associated with overlap. Smoking was significantly associated with overlap compared with dysmotility symptoms alone and acid reflux symptoms alone. Conclusions. Overlap between dysmotility and acid reflux symptoms was common in Japan. Smoking was an independent risk factor for overlap among two symptoms.