Deficiency of endogenous prostanoids in gastric and duodenal ulcer diseases

The levels of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (PGF₁α) and thromboxane B₂ (TXB₂) in endoscopic biopsy specimens from the gastric and duodenal mucosa of healthy volunteers and ulcer patients were measured by radio-immunoassay. The PGE₂ and PGF₁α levels in the mucosa of the corpus of the stomach were lower and the TXB₂ level was higher in 10 patients with gastric ulcer in the corpus than in the 16 healthy subjects. The PGE₂ level in the antral mucosa of 14 patients with gastric ulcer in the antrum was lower than in the controls. In 18 patients with duodenal ulcer, PGE₂ deficiency was more widespread in the entire gastric and duodenal mucosa while the reduced PGF₁α level was limited in the gastric corpus. Lower levels of PGE₂ in patients with antral or duodenal ulcer and of PGE₂ and PGF₁α in patients with corpus ulcer in the anatomical mucosal area including the ulcer site may predispose the mucosa to ulceration.     

Role of prostanoids in experimental duodenal ulcer in rat

The purposes of this study were to determine whether inhibition of cyclooxygenase is a mechanism by which cysteamine and mepirizole produce duodenal ulcers, identify qualitative or quantitative differences in prostanoid production between gastric mucosa and duodenum, and determine whether differences in cyclooxygenase sensitivity to inhibition by aspirin exist between these two tissues. In fed female rats, gastric mucosal prostaglandin E₂ (PGE₂) and prostacyclin (PGI₂) generation was 235±25 and 832±40 ng/g/min, respectively, whereas full-thickness duodenal PGE₂ and PGI₂ generation was 665±46 and 662±49 ng/g/min, respectively. Over an intraperitoneal dose range of 0– 25 mg/kg, aspirin-induced cyclooxygenase inhibition was dose-dependent and similar for the two tissues. Duodenal ulceration (16.7 mm²) produced by cysteamine, 425 mg/kg, was associated with a 46% reduction in duodenal PGE₂ generation, while having no effect on PGI₂ generation; however, cysteamine, 213 mg/kg, produced no visible duodenal mucosa injury yet reduced duodenal PGE₂ generation 39% compared to control values. In fed male rats, gastric mucosal PGE₂ and PGI₂ generation was 179± 18 and 813± 61 ng/g/min, respectivley, whereas duodenal PGE₂ and PGI₂ generation was 321± 27 and 454± 38 ng/g/min, respectively. Duodenal ulceration (7.7 ± 2.3 mm²) produced by oral mepirizole was associated with a 63% reduction in duodenal PGE₂ generation compared to control values, while having no effect on PGI₂ generation. Subcutaneous aspirin, 100 mg/kg, which reduced duodenal PGE₂ generation to a greater degree than either ulcerogen, given in conjunction with pentagastrin, did not produce visible duodenal ulceration. It therefore seems unlikely that reduced PGE₂ generation within the duodenum is the primary mechanism of gross injury associated with these two ulcerogens.Supported by grant AM 17328 from NIADDK.     

Effect of duodenal juice on pathogenesis of gastric ulcer

The purpose of the present study was to elucidate the effect of duodenal juice on development of gastric ulcer, in relation to changes of lipid composition and energy metabolism of the gastric mucosa in dogs. For regurgitation of duodenal juice and stagnation of gastric contents in the stomach, the duodenum was constricted below the papilla of Vater, accompanying with pyloroplasty and upper gastro-jejunostomy. Furthermore, to induce ischemia in the gastric mucosa, 0.5 ml of 1% formalin solution was injected into a descending branch of the left gastric artery. Three weeks later, U1 II-III gastric ulcer developed at the formalin injected area with severe gastritis but not with hyperacidity, and the histologic findings were similar to the one of a human gastric ulcer with hypoacidity. On assay of lipid composition in the gastric mucosa, lecithin decreased and both lysolecithin and NEFA increased, showing that lecithin of the gastric mucosa was decomposed by phospholipase A2 of the duodenal juice. In the gastric mucosa, ATP and energy charge decreased, and AMP and lactate increased, indicating that the energy metabolism was led to anaerobic glycolysis. These results revealed that the gastric mucosa becomes very fragile when duodenal juice regurgitates into the stomach and that gastric ulcer may develop even without hyperacidity when the microcirculation is disturbed in this condition.     

Relationship between Helicobacter pylori infection and gastric metaplasia in the duodenal bulb in the pathogenesis of duodenal ulcer

BACKGROUND: The aim of this study was to determine whether the amount of Helicobacter pylori and the extent of gastric metaplasia in the duodenal mucosa play critical roles in the pathogenesis of duodenal ulcer. METHODS: Duodenal and gastric biopsy specimens were obtained from H. pylori-positive patients with duodenal ulcer, gastric ulcer or chronic gastritis. The extent of gastric metaplasia was evaluated histologically and endoscopically using the methylene blue test. In this study, we performed competitive polymerase chain reaction, a highly sensitive and quantitative method for determining the amount of H. pylori gastric and duodenal mucosa. The prevalence and extent of gastric metaplasia and the amount of H. pylori in the duodenal bulb in the three patient groups were compared. The correlation between the amount of H. pylori in the duodenum and gastric antrum and extent of gastric metaplasia were also determined. RESULTS: The prevalence and extent of gastric metaplasia and the amount of H. pylori in the duodenal bulb in patients with duodenal ulcer were much higher than in patients with gastric ulcer or chronic gastritis. A positive correlation was found between the amount of H. pylori in the duodenum and the extent of gastric bulb and that in the antrum. CONCLUSIONS: The findings of this study indicate that H. pylori colonization in the duodenal bulb may play a critically important role in the pathogenesis of duodenal ulcer and that the amount of H. pylori in the duodenal bulb may be related to the amount of H. pylori in the gastric antrum and the extent of gastric metaplasia in the duodenal bulb.     

Prostanoid synthesis by cultured gastric and duodenal mucosa: Possible role in the pathogenesis of duodenal ulcer

Cultured duodenal mucosa obtained from normal subjects synthesized and secreted significantly less prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and thromboxane B2 (TXB2) than cultured gastric mucosa obtained from the same subjects. Accumulation of PGE2, 6-keto-PGF1 alpha, and TXB2--the stable metabolites of prostacyclin I2 and thromboxane A2, respectively--by cultured gastric mucosa obtained from 21 untreated patients with active duodenal ulcer was significantly lower than their respective accumulation by cultured gastric mucosa obtained from 14 normal subjects. Accumulation of all three prostanoids by cultured duodenal mucosa obtained from patients with active duodenal ulcer and from normal subjects was not significantly different. PGE2, 6-keto-PGF1 alpha, and TXB2 accumulation was five to six times higher than their respective content in fresh tissue before culture and was inhibited by flufenamic acid. These results suggest that a decrease in endogenous gastric prostanoid synthesis may have a role in the pathogenesis of peptic ulcer disease.     

Cost-effectiveness of cimetidine maintenance therapy in chronic gastric and duodenal ulcer

The effects of cimetidine maintenance therapy on the socioeconomic life of patients with peptic ulcers in the 3 years after healing and the extent to which treatment was cost-effective were studied. Three hundred eleven patients with healed ulcers (184 gastric, 127 duodenal) were studied for periods of up to 3 years; 261 patients (152 gastric ulcer, 109 duodenal ulcer) completed the 3-year follow-up. Cimetidine (400 mg at night) was compared with placebo in a double-blind, randomized prospective study. Intention-to-treat analysis was used. In the placebo group, the major costs of ulcer disease in gastric ulcer patients were attributable to endoscopic procedures and absenteeism; in duodenal ulcer patients, the major costs were endoscopic procedures, absenteeism, and surgery. Cimetidine was cost-effective in both gastric ulcer and duodenal ulcer patients in the first 2 years after healing. Over the 3-year period it was also cost-effective, but no benefit was seen in the third year.     

Role of homocytotropic antibodies in pathogenesis of gastric ulcer.

Praomys (Mastomys) natalensis were sensitised by peritoneal injection of ovalbumin mixed with aluminium hydroxide. The animals developed homocytotoropic IgE and IgG 1 antibodies. When presensitised animals were challenged with ovalbumin in the gastric wall, a gastric ulcer appeared. This ulceration, induced by an immunological release of histamine, could be inhibited by the administration of disodium cromoglycate. The present model is useful for producing a gastric ulcer in a determined site. It supports the theory of a possible allergic component in the pathogenesis of the human disease.     

Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: A model

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Some notes on the pathogenesis of duodenal ulcer

Conclusions If peptic ulcer may be regarded as a failure of the tissues to resist the action of gastric digestive secretions, then in most patients with gastric ulcer the mucosal resistance appears to be subnormal, while in most patients with duodenal ulcer the digestive power of the secretion seems to be supranormal. The majority of the data on the hypersecretion of acid in patients with duodenal ulcer can be satisfactorily accounted for by supposing that they have more than the usual number of acid-secreting and pepsin-secreting cells. In some patients there is also a failure of the mechanism which inhibits gastric secretion. It has not been possible to show that gastric emptying is unduly rapid in patients with duodenal ulcer.     

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

Helicobacter pylori(H.pylori)infection underlies gastric ulcer disease,gastric cancer and duodenal ulcer disease.The disease expression reflects the pattern and extent of gastritis/gastric atrophy(i.e.,duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis).Gastric and duodenal ulcers and gastric cancer have been known for thousands of years.Ulcers are generally non-fatal and until the 20th century were difficult to diagnose.However,the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present.It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century.Here,we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern,as it proved to be when it could be examined directly in the late 19th century.The environment before the 20th century favored acquisition of H.pylori infection and atrophic gastritis(e.g.,poor sanitation and standards of living,seasonal diets poor in fresh fruits and vegetables,especially in winter,vitamin deficiencies,and frequent febrile infections in childhood).The latter part of the 19th century saw improvements in standards of living,sanitation,and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent.In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for"surgical disease"or for"Sippy"diets.We show that while H.pylori remained common and virulent in Europe and the United States,environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H.pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H.pylori-related diseases.