[Acid-suppressive strategy against gastroesophageal reflux diseases and non-erosive reflux diseases: the alternative of proton- pump inhibitors or H2 receptor antagonists].

Gastroesophageal reflux disease (GERD) is categorized into three distinct entities: erosive reflux diseases(ERD), non -erosive reflux diseases(NERD) and Barrett's esophagus. In ERD, early symptomatic relief as well as healing of the esophageal mucosal injury to prevent complications is the goal of the treatment, whereas in NERD, alleviation of the symptoms leading to better quality of life is the main goal. According to the results of randomized controlled trials comparing proton-pump inhibitors (PPIs) with H2-receptor antagonists (H2RAs) head-to-head, PPIs are superior to H2RAs in the treatment for ERD. However, H2RA was equally effective with PPI to the Japanese ERD patients with low-grade esophageal mucosal breaks and positive Helicobacter pylori (H. pylori) infection. PPIs are also more beneficial than H2RAs in NERD in Western literatures but overall therapeutic gains of PPIs in NERD are lower than those reported in ERD, indicating heterogeneity of NERD pathophysiology. Again, H2RA was reported to show equal effectiveness with PPI in NERD patients with positive H. pylori status in Japan. Thus, on -demand treatment with H2RA in NERD patients with positive H. pylori status could be an alternative option. In conclusion, optimal management of the Japanese GERD patients with acid suppressive therapies should be tailored to individual conditions.

Changes in plasma ghrelin levels, gastric ghrelin production, and body weight after Helicobacter pylori cure.

BACKGROUND: Ghrelin is a body weight-regulating peptide produced and secreted primarily by the gastric mucosa. Helicobacter pylori infection impairs gastric ghrelin production, leading to a lower plasma ghrelin concentration. However, the effect of H. pylori eradication on plasma ghrelin levels and its relation to body weight change after H. pylori cure are still uncertain. We examined the association of plasma ghrelin levels with gastric ghrelin production and body weight change before and after H. pylori eradication. METHODS: Plasma ghrelin concentrations, gastric ghrelin expression, and body weight were determined in a total of 134 consecutive individuals before and 12 weeks after successful H. pylori eradication. Gastric ghrelin expression was evaluated by determining mRNA expression levels and the number of ghrelin-producing cells in gastric mucosa biopsy specimens by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Plasma ghrelin concentration increased in 50 patients and decreased in 84 patients after H. pylori eradication. After H. pylori cure, however, gastric preproghrelin mRNA expression was increased nearly fourfold (P < 0.0001), and the number of ghrelin-positive cells was increased or unchanged. In contrast, plasma ghrelin changes after H. pylori cure were inversely correlated with both body weight change (P < 0.0001) and initial plasma ghrelin levels (P < 0.0001). CONCLUSIONS: Changes in plasma ghrelin concentrations before and after H. pylori cure were inversely correlated with body weight change and initial plasma ghrelin levels but not with gastric ghrelin production in Japanese patients.

Impaired production of gastric ghrelin in chronic gastritis associated with Helicobacter pylori.

Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. The effects of Helicobacter pylori infection on plasma ghrelin concentration and gastric ghrelin production still have not been well known. We determined plasma ghrelin concentration in a total of 160 consecutive individuals with normal body mass index including 110 H. pylori-infected and 50 H. pylori-negative subjects. The expression levels of ghrelin mRNA and ghrelin-producing cells in the gastric mucosa were quantified with real-time quantitative RT-PCR and immunohistochemistry, respectively. The severity of gastric atrophy was evaluated by serum pepsinogen concentrations. Plasma ghrelin concentration, gastric ghrelin mRNA, and ghrelin-positive cell numbers in gastric mucosa were significantly lower in H. pylori-infected subjects. The decrease in plasma ghrelin concentration in H. pylori-positive subjects was accompanied by an attenuation of ghrelin mRNA expression and a reduction of ghrelin-positive cell numbers in the gastric mucosa. Moreover, lower serum pepsinogen I concentrations and I/II ratio were significantly associated with lower plasma ghrelin concentrations in H. pylori-positive subjects. These findings suggest that impaired gastric ghrelin production in association with atrophic gastritis induced by H. pylori infection accounts for the decrease in plasma ghrelin concentration.

Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa.

BACKGROUND: There have been no detailed reports directly comparing the expression of CDX1 with that of CDX2 in the inflammatory esophageal mucosa and Barrett's epithelium. The present study was designed to examine the expression of CDX 1/2 in inflammatory esophageal mucosa with or without Barrett's epithelium. METHODS: The expression of CDX1/2 genes was analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) in 34 human esophageal biopsy specimens, and CDX2 expression was also evaluated immunohistochemically, using anti-human CDX2 monoclonal antibody. The biopsy specimens for RNA extraction were taken endoscopically from esophageal mucosa with mucosal break due to gastroesophageal reflux disease (GERD), Barrett's epithelium, and normal epithelium. The expressions of mucin markers (MUC2) and intestine-specific genes (sucrase-isomal-tase, human defensin-5, alkaline phosphatase) were also comparatively analyzed. RESULTS: CDX1/2 expression was not found in the normal esophageal mucosa. The prevalence of CDX1/2 mRNA expression was significantly higher in the mucosa with Barrett's epithelium than in the mucosa without Barrett's epithelium. It is noteworthy, however, that the CDX2 mRNA expression was initiated at the stage of esophagitis, when neither CDX1 nor intestine-specific genes had emerged yet. In contrast to CDX2, CDX1 was expressed only in Barrett's epithelium. Immunohistochemical study demonstrated strong and extensive nuclear immunoreactivity for CDX2 in Barrett's epithelium. Furthermore, fine granular cytoplasmic staining was also observed in the cytoplasm in Barrett's epithelium, as well as in inflammatory esophageal mucosa. CONCLUSIONS: We report here, for the first time, that CDX2 is expressed in patients with Barrett's epithelium and inflammatory esophageal mucosa. These findings imply that the expression of CDX2 may be an early event leading to the development of Barrett's esophagus.