The role of prostaglandin E2 in duodenal mucosa of healthy subjects and duodenal ulcer patients

The distribution of the mucosal PGE2-generating capacity was bioassayed in the duodenum of 17 patients with duodenal ulcer (age range 20-58 years), and in 17 subjects (age range 21-57 years) who did not suffer from this disease. The age of the subjects within both groups was precisely matched in pairs. In contrast to the "young" controls or the "young" patients (under 37) or the "old" patients (over 37) the "old" control group of subjects showed an age-dependent increase in the mucosal PGE2 generation. It is concluded that with increasing age the mucosal PGE2 plays an increasingly important role in the protection against duodenal ulcers.     

Gastric functional exploration. Comparison between secretory results in 72 non-ulcer dyspeptic patients and 289 non-operated duodenal ulcer patients. Predictive criteria for the efficacy of fundus vagotomy in duodenal ulcer]

Basal and pentagastrin- or insulin- stimulated secretion was studied in 72 non ulcer dyspectic patients (NUD), in 289 non operated duodenal ulcer patients (DU), and in 30 DU, before and after highly selective vagotomy (HSV). Acidity, proteolytic activity, choline indicating the presence of duodenogastric refluxed material and sialic acid bound to mucus glycoprotein, marker of mucus erosion, were measured. Basal and pentagastrin-stimulated acid and pepsin secretions in NUD were significantly reduced with regard to those in DU. Sialic acid content was weak in basal secretion and markedly increased in response to pentagastrin reaching the values observed in DU. DU basal secretions of acid and of pepsin were modulated according to the stimulating secretory mechanism. Mucus glycoprotein erosion was related to pepsin mucolytic activity and/or to the presence in gastric juice of refluxed material. In DU the increase of peptic mucolysis corresponded to a biological signal of the ulcer attack when no duodenogastric reflux was identified. High values pepsin output in basal secretion and in response to insulin and of basal sialic acid content combined with a pepsin/acid basal output ratio higher than 80 were biological arguments anticipating the efficacy of HSV in DU. Multiparametric analysis of gastric secretion allows to evaluate the ratio between aggressive factors and mucosal defense corresponding to an equilibrium in NUD and to greater aggressivity in DU whose intensity is related to the course of disease.     

Enzyme activities in the duodenal mucosa in duodenal ulcer patients

The mucosal enzyme activities of 11 marker enzymes from the brush border, basolateral membrane, and lysosomes of 45 patients with an active duodenal ulcer (DU) were determined by analysis of homogenized biopsy specimens obtained from the duodenal bulb and descending duodenum at endoscopy. They were compared with activities measured in 22 controls. In the duodenal bulb lactase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.0005), and monoamine oxidase (p less than 0.0005) were significantly decreased in DU patients. In the descending duodenum all the brush border enzymes except sucrase were significantly decreased when compared with controls. DU patients with inflammation in the biopsy specimens from the duodenal bulb had decreased levels of lactase (p less than 0.05), sucrase (p less than 0.05), neutral-alpha-glucosidase (p less than 0.05), leucyl-beta-naphthylamidase (p less than 0.05), and acid phosphatases (p less than 0.05) when compared with DU patients with normal histology in this region. In the descending duodenum the activities of leucyl-beta-naphthylamidase (p less than 0.05) were decreased in patients with inflammation compared with those without such histologic changes. DU patients who had taken antacids before the investigation had decreased activities of lactase (p less than 0.05) in the descending duodenum when compared with those who had not taken antacids. Activities of lactase (p less than 0.005), sucrase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.05), and acid beta-glucuronidase (p less than 0.0005) in the descending duodenum were significantly lower in smokers than in non-smokers with active DU.     

Prostaglandin E and F2 alpha receptors in human uterine leiomyomas

9uman uterine leiomyomas specifically bound less (P less than 0.01) [3H]prostaglandin E1 ([3H]PGE1) and [3H] PGF2 alpha than adjacent normal myometria [leiomyomas: mean [3H]PGE1, 16.4 (range, 11.1-25.2) fmol/mg protein; mean [3H]PGF2 alpha, 4.7 (range, 0.8-12.1) fmol/mg protein; adjacent normal myometria: mean [3H]PGE1, 41.7 (range 27.1-60.7) fmol/mg protein; mean [3H]PGF2 alpha, 7.8 (range, 4.3-16.3) fmol/mg protein]. The lower binding of both [3H]PGs by leiomyomas was due to lower numbers of available high and low affinity sites. Leiomyomas and normal adjacent myometria bound 4-7 times more [3H]PGE1 than [3H]PGF2 alpha, and this appears to be due to high affinity and high numbers of low affinity PGE sites. The smooth muscle content was lower (P less than 0.01) in leiomyomas (mean, 28.0%; range, 9.7-45.5%) than that of adjacent normal myometria (mean, 58.9; range, 51.4-71.2%). In summary, this is the first demonstration of PGE and PGF2 alpha receptors in human uterine leiomyomas. Lower receptor numbers in leiomyomas appear to be due to the lower smooth muscle content of the tissue.     

Prostaglandin E2 and prostaglandin F2 alpha biosynthesis in human gastric mucosa: effect of chronic alcohol misuse.

BACKGROUND AND AIMS: The results of experimental studies support the hypothesis that decreased prostaglandin production might play a part in the gastric mucosal injury induced by alcohol. In this study, it was investigated whether alcohol misuse impairs the synthesis of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) in gastric mucosa. PATIENTS: Fifty six alcoholic patients and 66 subjects without alcohol misuse were included in the study. METHODS: Mucosal biopsy specimens were obtained from the antrum and body of the stomach. Maximal synthesis rates of PGE2 and PGF2 alpha were determined in the microsomal fraction of the biopsy specimens. RESULTS: The rates of synthesis of both prostaglandins in biopsy specimens from the antrum were not significantly different from those obtained in the body. Synthesis of both prostaglandins was significantly reduced in alcoholic patients who abstained less than five days compared with the non-alcoholic group with normal mucosa (PGE2-40%, PGF2 alpha-42% respectively). In non-alcoholic patients with severe gastritis PGE2 synthesis was increased (+30%, p < 0.05) and PGF2 alpha synthesis was decreased (-42.5%, p < 0.025). In alcoholic patients with severe gastritis PGE2 synthesis was depressed by almost 60% (p < 0.001) compared with the non-alcoholic group with severe gastritis. Neither colonisation of Helicobacter pylori nor smoking had a significant influence on the prostaglandin synthesis. CONCLUSIONS: Chronic alcohol misuse is associated with significantly reduced capacity for prostaglandin synthesis in gastric mucosa and this alcohol induced decrease in prostaglandin synthesis is modulated by the presence and degree of gastritis.     

Cholecystokinin-like activity in the duodenal mucosa of duodenal ulcer patients.

Cholecystokinin-like activity in the duodenal mucosa was measured by the bioassay method described by Ljungberg to elucidate its significance in 14 duodenal ulcer patients as well as in 13 normal subjects with no evidence of gastrointestinal diseases. The stage of duodenal ulceration was determined endoscopically according to the criterion of the Japanese Gastroenterological Endoscopic Society. The cholecystokinin-like activity in the duodenal mucosa of duodenal ulcer patients in active stage 1, which was considered as an early stage of active open duodenal ulceration, did not differ statistically from that of normal subjects, whereas that of duodenal ulcer patients in active stage 2 began to show a significant increase (p less than 0.05), and the cholecystokinin-like activity in the duodenal mucosa of duodenal ulcer patients in healing stage 1 or healing stage 2 was significantly higher than that in normal subjects (p less than 0.01). The cholecystokinin-like activity in the duodenal mucosa of duodenal ulcer patients in the scarring stage, however, returned to the normal range. It is concluded that cholecystokinin may act physiologically in the cure of duodenal ulcer.     

Hypergastrinemia of antral origin in duodenal ulcer

A case of recurrent duodenal ulcer, basal gastric hypersecretion, and hypergastrinemia of antral origin is presented. The diagnosis was suggested preoperatively by stimulation tests with secretin and food. Billroth II antrectomy led to normalization of serum gastrin within half an hour. The gastrin content of the antral mucosa was not increased, neither was antral G-cell hyperplasia demonstrable. Postoperatively the basal gastric acid output and fasting serum gastrin levels were normal, without a postprandial increase in serum gastrin concentrations. The case does not support the existence of a specific disease called antral G-cell hyperplasia.     

Increased dopamine receptor binding in duodenal mucosa of duodenal ulcer patients

High-affinity and saturable membrane-bound dopamine binding sites have been characterized in rat and human gastrointestinal tissues. Although their role in experimental ulcerogenesis has been suggested, dopamine receptor activity in peptic ulcer disease has not been investigated. Radioligand binding studies were performed with mucosal tissue homogenates obtained from the antrum and duodenum of six male healthy volunteers and six male duodenal ulcer patients. The binding assay was performed in triplicate with a crude membrane fraction using [³H] dopamine as a ligand at a final concentration of 1 nM at 22 °C in the dark. Nonspecific binding (which usually comprised about 30% of total binding) was determined in the presence of a 100-fold excess of unlabeled dopamine. A significant (P<0.05) increase of [³H]dopamine binding was found in duodenal mucosa of duodenal ulcer patients. [³H]Dopamine binding in stomach (antrum) of normal and duodenal ulcer patients did not differ significantly. These findings provide preliminary evidence for a role of dopamine receptors in duodenal ulcer and suggest that biochemical abnormalities of gut dopamine function may be operative in the pathogenesis of peptic ulcer disease.     

Enzyme activities in the gastric mucosa in duodenal ulcer patients

In a series of 45 consecutive duodenal ulcer patients (DU) the activities of 10 marker enzymes from the brush border, basolateral membrane, mitochondria, and lysosomes were determined by analysis of homogenized material taken with biopsy forceps through an endoscope from the antral and body part of the stomach. They were compared with the enzyme activities determined in controls with similar types of gastritis but without any evidence of peptic ulcer disease. All the DU patients had gastritis in the antral mucosa. In the body part, about 30% had gastritis. In the antral mucosa of DU patients the activities of the membrane and lysosomal enzymes were mostly increased when compared with the controls. In the gastric body mucosa of DU patients the activities of the lysosomal enzymes were mostly increased, whereas most of the membrane enzymes showed unchanged activities when compared with the corresponding controls. Monoamine oxidase activities were decreased or unaltered in both regions in these patients. The finding of enzymatic changes in the gastric mucosa of DU patients gives further support to an altered mucosal metabolism in these patients.     

Gastric acid inhibits antral phase III activity in duodenal ulcer patients

Fourteen patients with duodenal ulcers and eight healthy volunteers were examined to measure interdigestive gastroduodenal motility and plasma motilin. In order to study the effects of gastric acid on the gastroduodenal motility, 20 mg of famotidine was administered intravenously. The motility index of the gastric antrum and the duodenum, as well as the pH in the duodenal bulb were calculated. The duodenal pH was significantly lower and the gastric motility index was significantly weaker before the duodenal interdigestive migrating complex (IMC) in the ulcer patients than in the controls. Motilin levels increased before the duodenal IMC and decreased afterwards in both groups. Famotidine significantly increased the duodenal pH and the gastric motility index before the IMC, but no changes in the motilin level were noted. We conclude that duodenal ulcer patients have duodenal hyperacidity that results from increased inflow from the antrum and antral hypomotility during the gastric IMC and that these changes are normalized by the administration of famotidine. These results suggest that gastric acid inhibits antral contraction during the gastric IMC.     

十二指肠溃疡伴Hp~ 胃窦炎时胃窦生长抑素含量与mRNA表达

目的探讨十二指肠溃疡（DU）伴幽门螺杆菌（Hp）相关性胃窦炎时胃实生长抑素（SS）含量与mRNA表达方法采用放免法测定26例活动期DU（Hp检查均阳性）及24例非溃疡对照组（Hp检查6例阳性）胃窦粘膜组织SS含量，应用免疫组织化学方法检查D细胞的数量SSmRNA基因表达采用Northernblot和斑点杂交方法分析测量结果活动期DU26例，胃窦粘膜湿重组织SS含量为266ng／g±56ng／g±56ng／g，非溃疡对照组胃窦粘膜SS含量为335ng／g±110ng／g，两者相比差异非常显著（P＜0．01）活动期DU胃窦粘膜D细胞计数为36±13／mm2，明显少于非溃疡对照组59±42／mm2（P＜0．01）活动期DuSSmRNA水平（A）为0．52±0．11，较非溃疡对照组3．26±0．84显著降低（P＜0．01）．结论Hp感染引起中重度胃窦炎导致胃窦粘膜D细胞数量减少，同时SSmRNA基因转录及合成功能降抵，粘膜组织中SS含量减低，进一步可导致DU的发生．     

Influence of RP 40749 on basal and meal-stimulated serum-gastrin,serum-pepsinogen I,and gastrin-content of the antral mucosa in duodenal ulcer patients

Eighteen patients with active duodenal ulcer were treated with a novel antisecretory drug, RP 40749, either 100 mg or 150 mg as a daily nocturnal dose for 28 days. In these patients we evaluated the clinical course, endoscopic healing rates after 28 days, routine laboratory parameters, basal serum gastrin and pepsinogen I levels, meal-stimulated serum gastrin concentration, and the gastrin content of the antral mucosa. All nine patients receiving 150 mg RP 40749 and eight of nine patients receiving 100 mg RP 40749 healed their ulcers completely within 28 days, becoming rapidly symptom-free after an average of three days. The basal (53.8±5.2 vs 99.8±11.4 pg/ml) and meal-stimulated serum gastrin levels (109.2±12.1 vs 189.2±16.7 pg/ml) rose significantly after treatment with RP 40749, as did the gastrin content of the antral mucosa (11.3±2.1 vs 26.0±5.1 g/g), suggesting increased synthesis and secretion of gastrin. Between the 100 mg and 150 mg groups, no significant differences in response were observed. Serum pepsinogen I levels (64.9±7.3 vs 147.9±17.9 ng/ml) increased after treatment; the increase after 150 mg RP 40749 was significantly greater than that after 100 mg RP 40749. The increased of serum pepsinogen levels are probably due to a spillover effect resulting from a blockade in exocrine secretion into the lumen. There were no relevant changes in routine laboratory parameters.     

Chronic antral gastritis in duodenal ulcer. Natural history and treatment with prostaglandin E1

The natural history of chronic antral gastritis in relation to the healing of duodenal ulcer and its response to treatment, if any, are unknown. We performed a double-blind controlled trial using an oral prostaglandin E1, misoprostol, in 229 patients with active duodenal ulcer randomized to receive placebo (n = 76), misoprostol 200 micrograms (n = 77), or misoprostol 300 micrograms (n = 76), q.i.d. orally. Healing of duodenal ulcer was assessed biweekly up to 12 wk by endoscopy, during which procedures at least two antral and two fundal biopsy specimens were taken. The activity and the degree of chronic inflammation of gastritis, as assessed histologically by the infiltration of polymorphs and chronic inflammatory cells, respectively, was graded blindly by two pathologists as nil, mild, moderate, or severe. Before treatment, 99% of patients had chronic antral gastritis and 1.5% had chronic fundal gastritis. In the placebo group, healed duodenal ulcer was associated with significantly (p less than 0.01, life table analysis) higher incidence of improvement of the activity of the antral gastritis (nil or mild as endpoint) than unhealed ulcer (30% vs. 4% at week 8). Irrespective of whether duodenal ulcer was healed or unhealed, significantly (p less than 0.01) more patients on misoprostol (50% at week 8) showed improvement (nil or mild as endpoint) than the placebo group. The degree of chronic inflammation of the antral gastritis showed similar significant changes in favor of misoprostol. Smoking and alcohol intake had no significant effect on the improvement of chronic antral gastritis. In conclusion, healing of duodenal ulcer was associated with improvement of the activity of chronic antral gastritis, which, as shown for the first time, could be further enhanced by a therapeutic agent--prostaglandin E1.     

Carboxyl terminal glycine extended progastrin (gastrin-G) in gastric antral mucosa of patients with gastric or duodenal ulcer and in gastrinomas

Recently, carboxyl terminal glycine extended progastrin (gastrin-G), the immediate biosynthetic precursor of amidated gastrin, was found in human gastric antral mucosa. To investigate in pathophysiological conditions, we examined gastrin and gastrin-G levels and their molecular forms in gastric antral mucosa of healthy controls and patients with gastric or duodenal ulcer and in gastrinomas. There were no significant differences between controls and gastric or duodenal ulcer patients in antral gastrin and gastrin-G levels, the ratio of gastrin-G to gastrin and the pattern of their molecular forms. In contrast, gastrin and gastrin-G levels and the ratio of gastrin-G to gastrin in gastrinomas were much higher than those in antral mucosa of controls or ulcer patients. The predominant molecular form of gastrin-G was different between two Zollinger-Ellison syndrome (ZES) cases. These results suggest that there are no significant differences between healthy controls and patients with gastric or duodenal ulcer in the nature of gastrin amidation, and that the nature of gastrin amination in gastrinomas is different from that in normal gastrointestinal tissues.     

Defective inhibition of gastrin release by antral distension in duodenal ulcer patients.

The gastrin response to a low and a high dose of gastrin-releasing peptide infusion was studied in healthy volunteers and in patients with duodenal ulcer disease. In duodenal ulcer patients, the gastrin response was exaggerated. Cholinergic blockade did not change the gastrin release in healthy volunteers. Antrum distension during neutralization of the gastric lumen was unable to stimulate gastrin release, also under cholinergic blockade. However, in healthy volunteers distension of the antrum significantly inhibited the gastrin response to gastrin-releasing peptide infusion. This inhibitory influence was most pronounced in patients given the lower dose of the neuropeptide. Cholinergic blockade counteracted the inhibitory effect exerted by antral distension. On the other hand, antral distension did not alter the gastrin response to gastrin-releasing peptide in patients with duodenal ulcer disease. These results suggest an additional defective inhibitory mechanism in duodenal ulcer patients.