Shoichi Nagahashi

Attenuated Apoptosis in H. pylori-Colonized Gastric Mucosa of Mongolian Gerbils in Comparison with Mice

Although gastric cancer formation with H. pylori in Mongolian gerbils was recently reported, the same inoculation procedure did not result in cancer formation in other animals such as mice. Disturbed regulation of apoptosis and cell proliferation are known to link the multistep process of carcinogenesis. The present study is designed to examine the level of gastric epithelial cell apoptosis in Mongolian gerbils colonized with the H. pylori (Sydney strain: SS1) in comparison with that in mice. Mice (C57BL/6) and Mongolian gerbils were orally inoculated with SS1 and the stomachs were examined 9 and 18 months later. MPO activity increased persistently in gerbils, but increased transiently in mice. While the levels of DNA fragmentation, caspase-3 activity, and the number of TUNEL-positive cells increased significantly in mice, such parameters were attenuated in gerbils. On the other hand, the number of PCNA-positive cells increased after SS1 inoculation only in Mongolian gerbils, suggesting the enhancement of cell turnover in H. pylori-colonized gerbils. In conclusion, the SS1-induced increase in gastric mucosal apoptosis observed in mice was attenuated significantly in Mongolian gerbils, suggesting the causative role for the higher incidence of gastric carcinogenesis in this animal.

Rat CXC chemokine GRO/CINC-1 paradoxically stimulates the growth of gastric epithelial cells

Background: CXC chemokines such as interleukin (IL)‐8 are neutrophil chemoattractants, the levels of which increase in Helicobacter pylori‐infected gastric mucosa. Many investigators have focused on the chemotactic aspects of IL‐8; however, CXC chemokines are also reported to have angiogenic activity and to serve as remodelling factors. Rat GRO/CINC‐1 is a rodent counterpart of human GROα, a member of the family of CXC chemokines. Gastric mucosa infected with H. pylori is in a state of hyperproliferation, with increases in the amounts of growth factors such as hepatocyte growth factor (HGF).

Treatment with a proton pump inhibitor promotes corpus gastritis in patients with Helicobacter pylori-infected antrum-predominant gastritis

Proton pump inhibitors have been reported to modify the level of Helicobacter pylori gastritis.

Proton pump inhibitor modifies inflammatory reaction in human gastric mucosa infected by Helicobacter pylori

To examine whether proton pump inhibitors modify the production of oxygen‐derived free radicals and related cytokines in the human gastric mucosa infected with H. pylori.

Ammonia aggravates stress-induced gastric mucosal oxidative injury through the cancellation of cytoprotective heat shock protein 70.

The relationship between Helicobacter pylori colonization and the formation of stress-induced gastric mucosal injury remains unknown. Since ammonia (NH(3)) is known as one of the injurious factors in H. pylori-colonized gastric mucosa, the present study is designed to investigate the level of stress-induced gastric mucosal oxidative injury with or without intragastric NH(3) overloading. To apply emotional stress, the communication box paradigm was used in the mouse model. Mice (C57BL/6, male) were pretreated with distilled water (responder-H(2)O) or 0.01% NH(3) (responder-NH(3)) through a gastric tube once a day for a week. Emotional stress was then applied to the responder mice for 3 h per day for 3 d by watching and hearing the behavior of the sender mice subjected to electric shocks to the feet (2 mA, 10 s, 50 s interval). After the communication box protocol, the tissue MPO activity, the contents of TBA-reactive substances (TBARS), and the level of gastric mucosal HSP70 were examined. Responder-NH(3) mice developed more severe gastric lesions than the responder-H(2)O subjects. MPO activity and TBARS contents were enhanced significantly in the responder-NH(3) group compared with the responder-H(2)O subjects. Although the contents of HSP70 in the gastric mucosa increased in the responder-H(2)O group compared with the control-H(2)O animals, they were significantly attenuated in the responder-NH(3) mice. Excess intragastric NH(3) was able to enhance the formation of emotional stress-induced gastric mucosal lesions. This injury may be associated with the enhanced production of oxygen free radicals from accumulated neutrophils under the NH(3)-mediated cancellation of gastric mucosal cytoprotective HSP70.

Rabeprazole treatment attenuated Helicobacter pylori-associated gastric mucosal lesion formation in Mongolian gerbils

Background and Aim: Although rabeprazole (RPZ), a proton pump inhibitor, has been reported to have a bactericidal effect on Helicobacter pylori (H. pylori), no studies have been conducted regarding the effect of RPZ on gastric mucosal lesion formation caused by this bacterium. In the present study, we investigated the effect of RPZ on H. pylori‐associated gastric mucosal lesion formation.

Protective role of adrenal glucocorticoids for gastric mucosa in spontaneously hypertensive rats.

Background: Spontaneously hypertensive rats (SHR) are a representative animal model for disturbance of the pituitary–adrenal axis, as well as disturbance of the autonomic nervous system.

Ethanol intake preceding Helicobacter pylori inoculation promotes gastric mucosal inflammation in Mongolian gerbils

Background : Mongolian gerbils have been reported to be a suitable model for Helicobacter pylori‐associated gastric mucosal injury, including gastric cancer. Although ethanol is known to be one of the harmful substances in the gastric mucosa, the relationship between ethanol and H. pylori infection remains unknown. The aim of the present study is to investigate the effect of ethanol treatment prior to H. pylori inoculation on associated gastric mucosal injury.

Helicobacter pylori‐eradication therapy decreases the level of neutrophil‐derived oxidants in the ulcerous mucosa of the human stomach: Relationship between ulcer stage and mucosal oxidant level

Background:  The purpose of the present study was to determine the effect of Helicobacter pylori eradication on the intensity of inflammation in the ulcerous mucosa by measuring the level of neutrophil‐associated oxidants and to understand the role of mucosal inflammation in ulcer relapse from the viewpoints of the scarring stage and the H. pylori‐infection status. The level of inflammation in the gastric mucosa after the eradication of H. pylori was examined using biopsy samples obtained from patients with gastric ulcers.

Ammonia enhances emotional stress-induced mouse gastric mucosal damage in communication box paradigm

Background. The relationship between Hipylori (Hpj-colonization and the formation of stress-induced gastric mucosal injury has remained unknown. In the Hp-infected gastric mucosa, urease-dependent ammonia (NH3) production is reportedly important to induce gastric lesions. The present study was designed to investigate whether NHrpretreatment enhances the formation of gastric lesion in response to emotional stress. Method. Twelve CS7BL/6 mice were treated with 0.01%-NH3 through the gastric tube once a day for a week before applying emotional stress, and other II mice were treated with distilled water. To provide emotional stress, the communication box paradigm, in which each mouse (responder) was placed in transparent plastic compartment adjacent to mice receiving electrical stimulation (3 hours (19:30-22:30) per day for 3 days; sender), was used. After the overnight fasting, the stomach of each animal was examined. Macroscopic and microscopic evaluation were performed in each stomach. Mucosal activity of myeloperoxidase (MPO), an index of neutrophil accumulation, as well as the contents of thiobarbitulate reactive substances (TBARS), an index of mucosal lipid peroxidation were measured (Free Radie. Bioi. Med. 26:679, 1999). Results. The responder mice pretreated with 0.01%-NH3 (NH3-responder) developed more severe gastric lesions than those pretreated with distilled water (control-responder). MPO activity was enhanced in NH3-responder (0.72±0.3S mU/mg protein) more than that in the control-responder (0.3S±0.09 mU/mg protein) (p<O.OS). TBARS contents further increased in NH3-responder (4.84± 1.36 nmol/mg protein) compared with those in the control-responder (2.2S±0.6S nmol/mg protein) (p<O.OS). Luminol-dependent chemiluminescence (compatible to neutrophil-derived OCn was higher in NHrresponder (S.22±0.S4 countsl mg) than that in the control-responder (2.76± 1.S0 counts/mg). Conclusion. Intragastric ammonia overloading such as Hp-colonization could enhance gastric mucosal lesion in response to emotional stress. This injury may be associated with an enhanced production of oxygen free radicals from accumulated neutrophils.