Kensuke Asagoe

Products of neutrophil metabolism increase ammonia-induced gastric mucosal damage

Recent studies have indicated that ammonia is involved in the pathophysiology ofHelicobacter pylori-associated gastric mucosal damage.Helicobacter pylori-associated chronic active gastritis is characterized by an invasion of neutrophils. We investigated the interrelationship among hypochlorous acid (oxidant produced by neutrophil), ammonia (product ofHelicobacter pylori urease), and monochloramine (product of ammonia and hypochlorous acid) in the development of gastric mucosal damage in rats. Gastric mucosal lesions were produced by exposure of the gastric mucosa to ammonia, urea with urease, or urea withHelicobacter pylori in rats subjected to ischemia. Pretreatment with taurine (scavenger of hypochlorous acid) or antineutrophil serum significantly attenuated gastric mucosal lesions induced by the above test agents. Ammonia-induced gastric mucosal lesions were exacerbated in the presence of hypochlorous acid with concomitant generation of monochloramine. These results suggest that the ammonia, hypochlorous acid, and monochloramine triad may be important inHelicobacter pylori-mediated gastric mucosal damage.

Gastric ammonia has a potent ulcerogenic action on the rat stomach

BACKGROUND The pathophysiological mechanism by which Helicobacter pylori induces mucosal injury has not been clarified. The aim of this study was to investigate the role of urea, urease, and ammonia in rat gastric mucosal lesions using an ex vivo chamber model. METHODS Two groups of rats, normotensive rats and those subjected to ischemia, were studied. The gastric mucosa was examined histologically and macroscopically, and the transmucosal potential difference was measured. RESULTS Instillation of urea into the stomach generated ammonia in the presence of urease. The amount of ammonia was increased depending on the concentration of urea and was closely associated with the severity of the histological lesions. The exposure of the stomach to 15-60 mmol/L ammonium hydroxide induced both a reduction in transmucosal potential difference and microscopic damage to the gastric mucosa in normotensive rats. Moreover, 15-60 mmol/L ammonium hydroxide produced severe macroscopic gastric lesions in the rats subjected to ischemia. CONCLUSIONS These results show that ammonia is deleterious to the gastric mucosa and suggest the importance of urea, urease, and ammonia in the pathophysiology of gastric diseases in H. pylori-infected patients.

CASE REPORT: Autoimmune Pancreatitis Detected as a Mass in the Head of the Pancreas with Contiguous Fibrosis Around the Superior Mesenteric Artery

Several cases of chronic pancreatitis associated with autoimmunity have been reported (1–3), and the concept of autoimmune pancreatitis was recently proposed (4, 5). This clinical entity is characterized by diffuse or focal swelling of the pancreas, irregular narrowing of the main pancreatic duct on endoscopic retrograde pancreatography (ERP), hypergammaglobulinemia, and the presence of autoantibodies, together with remarkable responsiveness to corticosteroid therapy. Some cases showing focal swelling or multiple focal masses that simulate pancreatic cancer or lymphoma have been reported by us and others (3, 6–10). Here, we report a case of autoimmune pancreatitis, detected as a mass in the head of the pancreas with a contiguous mass around the superior mesenteric artery, that was treated successfully with corticosteroid.

Therapeutic effects of lansoprazole on peptic ulcers in elderly patients

We studied the effects of lansoprazole on ulcer healing and Helicobacter pylori infection in elderly patients with peptic ulcers. In a group of 24 patients with gastric ulcers, the H. pylori infection rate was 100%. In the course of gastric ulcer healing with famotidine or lansoprazole alone, the H. pylori infection showed no signs of decline. The ulcer healing rates after 8 weeks were similar between the H2-receptor antagonist famotidine (73%), and the proton pump inhibitor lansoprazole (82%). When eradication of H. pylori infection was attempted by concomitant administration of lansoprazole and amoxicillin 500 mg b.i.d. for 2 weeks, the eradication rate was 33% in the group given lansoprazole 30 mg q.d. plus ampicillin 500 mg b.i.d., whereas it was 77% in the group given lansoprazole 30 mg b.i.d. plus ampicillin 500 mg b.i.d. Lansoprazole is considered to be a useful agent for the treatment of patients with peptic ulcers and H. pylori infection and its effectiveness in H. pylori eradication is improved by b.i.d. administration along with ampicillin.

Helicobacter pylori has an ulcerogenic action in the ischemic stomach of rats.

Helicobacter pylori (H. pylori) is now accepted as an important cause of chronic active gastritis. There also seems to be an association between the colonization of H. pylori in the gastric mucosa and peptic ulceration. However, it has not demonstrated that the instillation of H. pylori into the stomach produces the ulcerative gastric lesions in animals or humans. We carried out an experiment to study whether or not H. pylori has an ulcerogenic action in the ischemic stomach of rats, using an ex vivo gastric chamber. The rat stomachs were exposed to 1 ml of H. pylori solution (200 IU of urease/ml) and 1 ml of urea (400 mg/dl) for 60 min after the creation of ischemia in the stomach (by withdrawal of 3 ml of blood). The exposure of the stomach to both H. pylori and urea resulted in severe hemorrhagic gastric mucosal lesions with a marked decrease in potential difference (PD) with a concomitant increase in ammonia concentration in rats with ischemia, whereas gastric lesions and a fall in PD were hardly observed in rats without ischemia. These results have demonstrated that H. pylori has an ulcerogenic action on the stomach subjected to mucosal ischemia.

Histamine chloramines have a persistent stimulating effect on histamine H2 receptors and gastric acid secretion

Histamine plays an important role in the control of gastric acid secretion. Recently, chlorinated derivatives of histamine have been identified as having multiple effects on the intestinal tract. The aim of this study was to investigate the role of histamine chloramines on gastric acid secretion. We compared the effects of histamine and histamine chloramines on the histamine H2 receptors in vitro using guinea pigs and on gastric acid secretion in rats. With respect to the effects on histamine H2 receptors, histamine monochloramine showed agonist effects similar to those seen with histamine, but the agonist effects of histamine dichloramine were about half those of histamine. Unlike histamine effects, the histamine H2 receptor agonist effects of histamine monochloramine and histamine dichloramine did not disappear after repeated washout. With respect to the stimulation of gastric acid secretion in vivo, histamine monochloramine was similar to histamine, while the effect of histamine dichloramine was 42.2-52.7% of that of histamine. The recovery time to the basal secretory level after completion of stimulation by histamine chloramines was significantly prolonged compared with histamine. These results suggest that histamine chloramines, which bind strongly with histamine H2 receptors, may delay the termination of gastric acid secretion and increase the burden on the gastric and duodenal mucosa.