Takeshi Miwa

Helicobacter pylori induces apoptosis in gastric epithelial cells through inducible nitric oxide

Background : Gastric mucosal injury by Helicobacter pylori has been suggested to be mediated by various cytokines induced by this organism. Nitric oxide (NO) is an important effector molecule involved in immune regulation and defence. To clarify the mechanisms by which H. pylori induces gastric mucosal cell injury, we examined whether H. pylori induces gastric epithelial death via NO production.

Ammonia as an Accelerator of Tumor Necrosis Factor Alpha-Induced Apoptosis of Gastric Epithelial Cells in Helicobacter pylori Infection

ABSTRACT The mechanism by which Helicobacter pylori induces apoptosis remains unclear. In a previous study using biopsy samples, we found a significant correlation between the urease activity of anH. pylori strain and the apoptosis level induced by this strain. Therefore, in this study, we investigated whether urease and/or the ammonia generated by urease can induce apoptosis. Human gastric epithelial cell lines were cocultured with H. pylori, and the levels of apoptosis and ammonia production were measured. The medium was supplemented (or not supplemented) with urea and cytokines. While a large amount of ammonia (>30 mM) accumulated in the coculture containing urease-positive H. pylori and urea, no significant degree of apoptosis occurred. In the presence of tumor necrosis factor alpha (TNF-α), however, a marked acceleration of apoptosis was found in this coculture. Such enhancement of apoptosis was also induced by the addition of 4 to 8 mM ammonia to the cell culture without either H. pylori or urea but containing TNF-α. These results suggested that ammonia accelerates cytokine-induced apoptosis in gastric epithelial cells, while ammonia or urease molecules alone are unable to induce a significant degree of apoptosis.

Effects of Inflammatory Cytokines Induced by Helicobacter pylori Infection on Aminopyrine Accumulation in Parietal Cells Isolated from Guinea Pigs

The effects of inflammatory cytokines induced byHelicobacter pylori infection on acid secretion have notbeen well defined. The purpose of this study was toinvestigate the direct effects of these cytokines on parietal cells isolated from guinea pigs. Weexamined the effects of human recombinant IL-1β(0.05-100 ng/ml), IL-8 (2-256 ng/ml), and TNF-α(0.625- 80 ng/ml) on acid secretion stimulated by three secretagogues (10-4 M histamine,10-4 M carbachol, and 10-5 Mtetragastrin) and on basal acid secretion from isolatedparietal cells, which was measured by the aminopyrineaccumulation method. None of three cytokines showed any significant effects onstimulated or basal acid secretion from isolated guineapig parietal cells. We concluded that inflammatorycytokines induced by Helicobacter pylori infection may affect acid secretion through mechanismsother than direct actions on parietal cells.

Protein Kinase C Gene Expression in Dispersed Guinea-Pig Gastric Parietal Cells

Background Aims: It has been implicated that protein kinase C (PKC) is involved in gastric acid secretion. The purpose of this study is to examine whether mRNA expression of PKC isoforms is observed in guinea-pig gastric parietal cells, and whether such PKC expression is regulated by agonists that stimulate gastric acid secretion. Methods: Expression of PKC mRNA was assessed using isolated guinea-pig gastric parietal cells treated with or without three kinds of agonists by Nothern blot analysis. Results: (1) α, γ and ζPKC mRNAs were expressed in guinea-pig gastric parietal cells; (2) both carbachol and gastrin increased the level of α and γPKC mRNAs, but synthesis of ζPKC mRNA was not affected by these agonists, and (3) histamine did not affect the expression level of α, γ and ζPKC mRNAs. Conclusion: α and γPKC isoforms may be involved in the regulation of gastric acid secretion.

Eradication of Helicobacter pylori with lansoprazole, amoxicillin, and plaunotol in duodenal ulcer patients

Helicobacter pylori eradication therapy combining amoxicillin (AMPC), plaunotol (PL), and a proton pump inhibitor (PPI) was examined as an alternative to triple therapy, which has a high rate of side effects and low patient compliance. Thirty-two H. pylori-positive patients (24 men, 8 women) with duodenal ulcers were examined. The diagnosis of H. pylori infection was made by the urease test on specimens biopsied from two sites in the stomach. Simultaneously, the IgG antibody against H. pylori was measured by the EIA method. The therapeutic regimen was lansoprazole (LPZ) 30 mg q.d. (6 weeks) and AMPC 1,500 mg t.i.d. (2 weeks) plus PL320 mg b.i.d. (6 weeks). The rate of ulcer healing was judged endoscopically after 6 weeks. Cases that become urease-negative after the cessation of the therapy were defined as having achieved clearance, and those negative after 1 month as eradication. Within 6 weeks, 31 of 32 patients had healed ulcers. All patients were H. pylori antibody-positive before therapy. The clearance rate was 71.9% (23/32) and the eradication rate was 45.8% (11/24). Adverse effects were observed only in one case. We conclude that combination therapy with LPZ, AMPC, and PL has a high therapeutic effect on ulcer healing and moderate effectiveness for eradication of H. pylori.

Plaunotol suppresses interleukin-8 secretion induced by Helicobacter pylori: therapeutic effect of plaunotol on H. pylori infection.

Background : It has been suggested that gastric mucosal injury induced by Helicobacter pylori infection is mediated by interleukin‐8 (IL‐8).

New Modalities of Contact Nd:YAG Laser Endoscopy for General Application in the Gastrointestinal Tract

It is generally recognized that fiberoptic endoscopy has both diagnostic and therapeutic uses and is one of the most common procedures in clinical gastroenterology. In the last decade, several endoscopic modalities for the treatment of gastrointestinal hemorrhage and neoplasms have been applied clinically. They include laser irradiation,1–5 electrocoagulation,6 topical injection, sclerotherapy, thermoprobes,7 and intubation of prosthesis.8 All of these procedures naturally have both advantages and disadvantages. Laser endoscopy is an unique procedure. Since the middle 1970s, Nd:YAG lasers have been applied using the noncontact method with the optical quartz fiber.1–5,8,9 There are distinct disadvantages of noncontact irradiation, such as the difficulty in keeping a constant distance from the tip of the quartz fiber to the lesion, allowing reliable tissue changes to occur related to the applied power. Furthermore, the quartz tip will be damaged when it comes into contact with tissue or blood. To overcome these disadvantages, the SLT contact method® with SLT endoprobes® directly connected to the quartz fiber was developed following reports of experimental research with the surgical probe, which was made of new ceramic materials.10–12 We initiated experimental and clinical studies of endoscopic Nd:YAG laser therapy, comparing the new SLT contact ceramic endoprobes with the single noncontact quartz fiber endoprobes, in order to evaluate the histologic effects and safety of each method. In this chapter, we discuss the possibilities of the clinical application of SLT contact endoprobes as a new endoscopic modality in the gastrointestinal tract.13–16

Phase I study of cisapride. 3. Single intravenous dosing study.

A Phase l study on cisapride (R 51 619), a new gastrointestinal prokineti cagent, was conducted in 7 healthy Japanese male volunteers.The safety and phafmacokinetics of the drug were studied in single intravenous doses of 2 and 4 mg.The 2 men of group 1 received 2 mg, and the remaining 5 men (group2) were given 4 mg.There were no complaints about subjective symptoms.No abnormalities were seen in ECGs or laboratory tests.Among vital signs, a rise of pulse rate was observed after the 4 mg dosing.The time-concentration curves of cisapride could be fitted into a three compartment open model.The half-life of the unchanged drug in the π-phase, the α-phase, and the β-phase rate was 0.032, 0.90 and 6.4 hours respectively.The above results confirmed the safety of cisapride in single intravenous dosing in healthy male vorunteers.