Effect of cysteamine on gastroduodenal mucosal histamine in rat

Cysteamine administration to rats is followed by a high incidence of peptic ulceration. The aim of the present study was to investigate the effect of cysteamine on gastric and duodenal mucosal histamine and gastric mucosal histamine formation capacity. After a four hour fast, cysteamine in doses of 50, 100, 200, 300, 400, and 500 mg/kg bodyweight was injected subcutaneously to male Wistar rats; saline injection was used as control. After 24 hours the animals were killed; the stomach and duodenum were removed and examined for ulceration. Mucosal biopsies were taken for histamine studies. Gastric and duodenal ulceration tended to appear with increasing incidence with higher doses. A direct correlation was found between the dose of cysteamine and gastric mucosal histamine (p less than 0.02), and duodenal mucosal histamine (p less than 0.05). Further, a direct relationship was found between gastric mucosal histidine decarboxylase activity and the dose of cysteamine (p less than 0.05). Gastric mucosal histamine and histidine decarboxylase activity showed a direct correlation (p less than 0.001). Gastric and duodenal mucosal histamine and gastric mucosal histamine formation capacity were higher in rats with ulcers than in controls and rats without ulcers. In rat, cysteamine induces dose related changes in mucosal histamine and histidine decarboxylase activity. These changes are related to ulcer formation; histamine may be involved in the pathophysiology of cysteamine induced ulcer formation.     

Cysteamine-induced inhibition of acid neutralization and the increase in hydrogen ion back-diffusion in duodenal mucosa

To investigate the possible impairment of defensive mechanisms in cysteamine-induced duodenal ulceration, the effect of cysteamine on the neutralization of acid by the duodenum and the back-diffusion of hydrogen ions into the duodenal mucosa has been studied. The results obtained were as follows. (1) The intraduodenal pH started to decrease between 3 and 4 hr after cysteamine injection. (2) By perfusion of the duodenal loop excluding the opening of bile and pancreatic ducts, the amount of hydrogen ions (H⁺) neutralized was found to be significantly lower in cysteamine-treated animals than in the controls. (3) the back-diffusion of luminal H⁺ into the duodenal mucosa, estimated by measuring the H⁺ disappearance from the test solution including 100 mM HCl, was significantly increased by cysteamine. From these findings, it has been concluded that cysteamine reduces the resistance of duodenal mucosa to acid coming from the stomach.     

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.     

Duodenal ulcer prevalence: experimental evidence for the possible role of dietary lipids

BACKGROUND AND AIMS: Mapping the geographical distribution of duodenal ulcer in relation to staple diets, and experiments on animal peptic ulcer models suggested that the lipid fraction in certain foodstuffs had a protective effect which was most marked in the lipid obtained from Horse gram (Dolichos biflorus). Lipid obtained from stored polished rice or rice bran was ulcerogenic. Further animal experiments were designed to investigate the protective and healing effects of Horse gram lipid (HGL) against peptic ulceration. METHODS: Three effects were investigated in rats: (i) the protective effect of HGL on peptic ulceration produced by using pyloric ligation in combination with South Indian diet or rice bran oil, or by cysteamine, alcohol or aspirin; (ii) the effect of HGL on mast cell degranulation in response to pyloric ligation and rice bran oil; and (iii) the healing effect of HGL on acute gastric ulceration produced by alcohol, on chronic gastric ulceration produced by topical acetic acid or on chronic duodenal ulcer following cysteamine. RESULTS: Horse gram lipid was shown to be protective and to promote ulcer healing in all the models used. Mast cell degranulation was inhibited. CONCLUSION: The experiments confirm the presence of a lipid in certain staple foods that have protective and healing properties in experimental peptic ulcer animal models. The differences in the prevalence of duodenal ulceration between different regions in some developing countries with a high prevalence of Helicobacter pylori infection might be explained by the presence or absence of protective lipids or ulcerogenic factors in the staple diet.     

Biphasic effect of duodenal ulcerogens on gastric emptying in the rat

The effect of the duodenal ulcerogen cysteamine on gastric emptying of a liquid meal was compared to that of two newly identified duodenal ulcerogens, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and mepirizole. Emptying rates after acute and chronic treatment with duodenal ulcerogens were obtained. Acute administration of cysteamine, MPTP, or mepirizole significantly delayed gastric emptying of the meal. Chronically treated rats, however, showed either no change or accelerated gastric emptying after cysteamine, MPTP, or mepirizole. Gastric emptying in chronically treated animals was faster in rats that developed the most severe duodenal ulcers. These results indicate that delayed gastric emptying instead of accelerated emptying is a more common abnormality during duodenal ulceration. After the ulcer develops, however, unaltered or accelerated gastric emptying is observed experimentally, thus suggesting that accelerated gastric emptying in duodenal ulcers is an acquired alteration. The implications that these experimental findings may have in the pathogenesis of duodenal ulcer, in light of the clinical data available, are discussed.This study was supported by NIH grant AM25229.     

Intravenous Injection of Micafungin Counteracts Candida Albicans-Induced Aggravation of Duodenal Ulcers Caused by Cysteamine in Rats

Background We have reported previously that Candida albicans is involved in the pathogenesis of peptic ulcer perforation; it was shown that C. albicans aggravated the severity of duodenal ulceration and increased the rate of perforation. We considered it incumbent upon us to ascertain whether C. albicans is a virulence factor involved in peptic ulcer perforation. In the present study, we administered an antifungal drug (micafungin) intravenously to rats that had received intragastric (i.g.) administration of C. albicans and cysteamine, in order to examine that micafungin could counteract the C. albicans-aggravation of duodenal ulcers. Methods Cysteamine was administered thrice on day 1 to male Wistar rats. C. albicans was administered to the animals 1 h before, and 12 and 24 h after the first administration of cysteamine. Micafungin (n = 22) or saline (n = 24) was administered 12, 24, and 48 h after the administration of cysteamine. Results The area of the duodenal ulcers was also significantly smaller in the micafungin group (P < 0.05). In addition, the survival rate of the rats was significantly higher in the micafungin group (P < 0.05). While in the control group, the ulcer base was found to be colonized by C. albicans, there was no evidence of the presence of C. albicans in the micafungin group. Conclusion It was shown that intravenous injection of micafungin counteracted the aggravation by C. albicans of cysteamine-induced duodenal ulcers in rats. This finding supports the concept that C. albicans is an aggravating factor for peptic ulcers.     

Early myoelectrical activity changes during gastric or duodenal ulceration in dogs

Antroduodenal myoelectric activity and gastric transmural potential difference were recorded before and during fundic, antral, or duodenal ulceration in dogs. Gastric injury was obtained by electrocoagulation of the fundic or antral mucosa. Duodenal ulceration was induced by cysteamine injection which was accompanied by nausea or vomiting. Both antral electrocoagulation and cysteamine injection were also accompanied by antral dysrhythmia and a transient decrease of the gastric transmural potential difference. Effects of antral electrocoagulation were prevented by selective vagotomy. Since antral dysrhythmia disappeared as soon as the antral or duodenal ulcers became active, ie, within three days and 24 hr respectively, it is suggested that antral dysrhythmia is the result of antroduodenal stimulation and could thus not be assessed as a criterion of active ulceration.     

Epidermal growth factor inhibits cysteamine-induced duodenal ulcers

The effect of the duodenal ulcerogen cysteamine on secretion of epidermal growth factor from Brunner's gland pouches was studied in the rat. Total output of immunoreactive epidermal growth factor was reduced to approximately 55%, compared with controls, 5 h after administration of cysteamine (300 mg/kg, s.c.). Furthermore, measurements on tissue extracts of the pouches revealed that 5 h after cysteamine treatment, Brunner's glands were depleted of epidermal growth factor. The effect on ulcer development of intraduodenally applied exogenous epidermal growth factor (1 micrograms/kg . h) also was studied. Luminal epidermal growth factor significantly inhibited the formation of cysteamine-induced duodenal ulcer, compared with controls receiving saline. The effect was not due to inhibition of gastric acid secretion or stimulation of duodenal bicarbonate secretion since the dose of epidermal growth factor used, when tested on chronic fistula rats, had no effect on acid secretion and did not influence bicarbonate secretion from Brunner's gland pouches. These results demonstrate that epidermal growth factor has a cytoprotective effect on the duodenal mucosa, and it is suggested that inhibition of synthesis and secretion of endogenous epidermal growth factor may be a pathogenetic factor in cysteamine-induced duodenal ulcer.     

In vivo cell kinetics studies of the duodenum during and after healing of cysteamine-induced duodenal ulcer in rats using bromodeoxyuridine incorporation

The present study investigated the defect of duodenal defence responsible for the tendency of recurrence of duodenal ulcer. Male Wistar rats were treated with cysteamine-HCl subcutaneously to induce duodenal ulcer, and bromodeoxyuridine (BrdU) was given intraperitoneally 1 h before laparotomy. Serial tissue sections and immunocytochemical staining of BrdU were done to study the cell kinetics during and after healing. Deep ulcers developed in the proximal part of the duodenum 24 h after cysteamine injection, and the ulcer was replaced by scar tissue 1 week later. BrdU-labelling index of normal duodenal mucosa in control rats was 30-34%. On the peripheral part of the regenerative mucosa, BrdU-labelling index increased from 1.5% to 26-27%, 1-4 weeks after injection and remained at this level thereafter. On the central part, except the most central area, the labelling index remained at 0% until 3 weeks, and was 15% 6 weeks after cysteamine treatment. It never achieved the level seen in control normal mucosa. The labelling rate of fibrous cells in scar tissue decreased from 28% to nearly 0% 1-4 weeks after the injection. It is concluded that both the ulcer scar and the regenerative mucosa do not achieve a mature state in the initial scarred stage; they need more time to reach a relatively mature condition. Moreover, the regenerative mucosa will be the weak, easily damaged part of the duodenum.     

Mucosal cell proliferation in duodenal ulcer and duodenitis.

Mucosal cell proliferation in the first part of the duodenum was studied in 24 patients using a tissue culture technique in which endoscopic biopsies were subjected to autoradiography after exposure to tritiated thymidine. Eight patients had a normal duodenum, eight had duodenal ulcer, and eight had symptomatic chronic non-specific duodenitis. The mean crypt labelling index (LI) in normal duodenum was 8.8 0.4% (SEM). Increased labelling indices of 15.6 +/- 1.7% were found near the edge of duodenal ulcers and 17.8 1.8% in duodenitis. Treatment with cimetidine reduced both the severity of duodenitis and the mean crypt LI. The LI of histologically normal duodenal mucosa distal to ulcer of duodenitis was similar to that of the control subjects' mucosa. The increased mucosal cell proliferation seen in severe duodenitis, either alone or associated with duodenal ulceration, suggested that erosions and ulcers arose when the crypts passed into 'high output failure' and were unable to compensate for further epithelial cell loss. There was no evidence in out study for a generalised failure of mucosal cell proliferation in duodenal ulcer or duodenitis.     

Pathogenesis of duodenal ulceration produced by cysteamine or propionitrile

Insight into the pathogenesis and etiology of experimental duodenal ulceration was sought by studying the modulation of this disease in rats by selective vagotomy, chemical sympathectomy, histamine depletion, histamine H-2 receptor antagonists (eg, metiamide, cimetidine), or endocrine ablations. Gastric secretion was examined in intact and pylorusligated animals. The formation of duodenal ulcers induced by the administration of propionitrile or cysteamine was abolished by vagotomy, decreased by sympathectomy, histamine depletion, histamine H-2 receptor antagonists, hypophysectomy, thyroidectomy, or adrenalectomy. Cimetidine and metiamide exerted a dose-dependent antiulcer effect, but metiamide enhanced the mortality of rats given propionitrile or cysteamine. The nonulcerogen derivative of cysteamine, ethanolamine, did not increase mortality when given in combination with metiamide. The gastric hyperacidity elicited by cysteamine was reduced by metiamide or vagotomy, the latter being more effective in this respect. Thus, the chemically induced duodenal ulcer in rats resembles the human peptic ulcer disease in sensitivity to therapeutic modalities and may serve as an appropriate model to study the role of neural, hormonal, and other factors in the etiology and pathogenesis of this disorder.     

Disturbed gastroduodenal motility in patients with active and healed duodenal ulceration

Disordered gastroduodenal motility may promote duodenal ulceration by allowing prolonged acid contact with the duodenal mucosa. Using a multilumen perfused catheter incorporating 3 pH microelectrodes, antral and duodenal pH and antropyloroduodenal pressure activity were recorded in 36 subjects (10 with healed duodenal ulceration, 11 with active duodenal ulceration, and 15 healthy volunteers) during fasting and after a radiolabeled solid test meal. Correct pH probe/catheter position was continuously verified by recording transmucosal potential difference across the pylorus. Patients with active and healed duodenal ulcer had similarly disordered gastroduodenal motility. The chief abnormalities consisted of an increase in postprandial duodenal retroperistalsis (healed duodenal ulceration, 12 +/- 1 events per hour; active duodenal ulceration, 12 +/- 1; control, 6 +/- 1; mean +/- SEM: healed and active duodenal ulceration vs. control, P = 0.004 and P = 0.03, respectively), a reduction in pressure waves sweeping aborally through the duodenum after the meal (healed duodenal ulceration, 22 +/- 4 events per hour; active duodenal ulceration, 23 +/- 3; control, 34 +/- 4: healed and active duodenal ulceration vs. control, P = 0.04 and P less than 0.05, respectively), and an increased incidence of atypical, complex forms of coordinated duodenal motor activity throughout the study (postprandial data; healed duodenal ulceration, 8 +/- 1 events per hour; active duodenal ulceration, 10 +/- 1; control, 4 +/- 1: healed and active duodenal ulceration vs. control, P = 0.02 and P less than 0.02, respectively). In addition, gastric emptying of the solid test meal was significantly delayed in healed, but not active, duodenal ulceration [half-emptying time, healed duodenal ulceration 185 minutes (117-235); active duodenal ulceration 102 minutes (80-200); control 107 minutes (78-130): healed duodenal ulceration vs. control, P less than 0.009]. Duodenal bulb pH was similar in controls and patients with active duodenal ulceration; however, bulb pH was less than 4 for a significantly greater period of time in healed duodenal ulceration compared with active ulcer patients, particularly after the meal. In conclusion, duodenal ulcer disease is associated with disturbed gastroduodenal motility, even when the ulcer is quiescent and when intraduodenal acidity is low. In healed duodenal ulceration, disturbed motility may promote ulcer relapse by impairing acid clearance from the bulb. However, in active ulceration other factors such as mucosal bicarbonate secretion may have a more influential role in determining intraduodenal pH.     

Functional and structural changes in the jejunum of the rat following cysteamine and stress-induced duodenal ulcer.

The effects of cysteamine and stress-induced duodenal ulcer on the functional and structural properties of the rat jejunum were investigated. The absorptive capacity of the jejunum was determined using alanine as the permeant solute and the single-pass perfusion technique. A statistically significant decrease (p < 0.01) in alanine absorption was observed after 8 h and 3 days of duodenal ulcer induction by stress and cysteamine respectively. However, alanine transport measured 7 days after cysteamine or stress ulcer induction showed no significant change from control values. Cysteamine and stress-induced duodenal ulcer did not show any significant change in water absorption across the jejunum when measured after 8 h, 3 and 7 days of ulcer induction. Microscopically, the jejunum of rats with 3-day cysteamine-induced ulcer exhibited diffuse type of apical derangements with excessive swelling of the villi and progressive degenerative changes. No such changes were noticed on the 7th day nor in the jejunum of the rats with stress-induced duodenal ulcer. The results suggest that cysteamine-induced duodenal ulcer produces an inhibition in the absorptive capacity of the jejunum which is time-dependent and reversible.     

Effect of cysteamine on gastric nerve fibers containing gastrin-releasing peptide in the rat

In rats, changes in gastric nerve fibers containing gastrin-releasing peptide (GRP) in cysteamine-induced duodenal ulcer were investigated in relation to the dynamics of gastrin-producing cells (G-cells). Marked increases in gastric acid secretion and serum gastrin level were observed from 2h after the administration of cysteamine. The number of G-cells was significantly decreased from 2h after the injection of cysteamine. Two and 4h after the administration of cysteamine, the G-cells showed ultrastructural changes characterized by a markedly decreased number of secretory granules. Circulating GRP levels were significantly elevated from 2h after the administration of cysteamine. In the control group given vehicle only, nerve fibers showing immunoreaction for GRP formed a fine network in the gastric wall and were densely distributed in the oxyntic mucosa, located close to capillaries and demonstrated varicosities that contained either small clear vesicles or GRP-immunopositive vesicles with large cores. Eight h after the administration of cysteamine, there was depleted GRP immunoreactivity, evidenced by a markedly decreased number of vesicles, with large electron-dense cores, in the oxyntic mucosa. These findings suggest that, in cysteamine-induced doudenal ulcer, alterations in gastric nerve fibers containing GRP may be related to hypergastrinemia.     

Effect of oral epidermal growth factor on mucosal healing in rats with duodenal ulcer

AIM: To investigate the effect of epidermal growth factor (EGF) on mucosal healing in rats with duodenal ulcer.METHODS: Male Sprague-Dawley rats were randomly divided into sham operation without EGF, sham operation with EGF, duodenal ulcer without EGF, or duodenal ulcer with EGF groups. Additionally, normal rats without operation served as the control group. Duodenal ulcer was induced in rats by 300 mL/L acetic acid. Rats with EGF were orally administered at a dose of 60 μg/kg/day in drinking water on the next day of operation (day 1). Healing of duodenal ulcer was detected by haematoxylin and eosin staining. Cell growth of damaged mucosa was determined by the contents of nucleic acids and proteins. The level of EGF in duodenal mucosa was measured by ELISA.RESULTS: The pathological results showed that duodenal ulcer rats with EGF improved mucosal healing compared with those without EGF after day 5. Duodenal ulcer rats with EGF significantly increased duodenal DNA content compared with those without EGF on day 15 (6.44±0.54mg/g VS 1.45±0.52 mg/g mucosa, P＜0.05). Duodenal RNA and protein contents did not differ between duodenal ulcer rats with and without EGF during the experimental period.Sham operation and duodenal ulcer rats with EGF significantly increased duodenal mucosal EGF content compared with those without EGF on day 5 (76.0±13.7 ng/g VS 35.7±12.9ng/g mucosa in sham operation rats, and 68.3±10.9 ng/gVS 28.3±9.2 ng/g mucosa in duodenal ulcer rats, P＜0.05).CONCLUSION: Oral EGF can promote mucosal healing of the rats with duodenal ulcer by stimulating mucosal proliferation accompanied by an increase in mucosal EGF content.     

Effect of duodenal ulcerogens cysteamine,mepirizole, and MPTP on duodenal myoelectric activity in rats

Increased gastric acid secretion, enhanced acid delivery to the duodenum, and reduced alkaline secretion in the proximal duodenum are relatively well-established pathophysiologic abnormalities in duodenal ulcer. Impaired duodenal motility, however, may also contribute to duodenal ulceration by altering the distribution of acid and alkaline secretions along the upper digestive tract. We tested the hypothesis that the duodenal ulcerogens cysteamine, MPTP, and mepirizole modify duodenal motility in the rat and that motility changes might be a common and early alteration in experimental duodenal ulceration. All three duodenal ulcerogens rapidly produced extensive changes in duodenal myoelectric activity and reduced the frequency of myoelectric slow waves. Cysteamine induced marked hypermotility for at least 6 hr; MPTP rapidly decreased motility and fragmented the myoelectric migrating pattern. Mepirizole induced biphasic changes: an early hypermotility phase of about 30 min was followed by profound hypomotility. These results indicate that marked alterations of duodenal motility are common during experimental duodenal ulceration. In light of the differential effect of the ulcerogens on duodenal motility, it remains to be determined how these changes influence acid neutralization in the proximal duodenum. Nevertheless, our results suggest that all three duodenal ulcerogens, which are different in structure, alter duodenal motility.Dr. Mangla did this work while on sabbatical leave at Harvard Medical School.     

Progression of antral and body gastritis in patients with active and healed duodenal ulcer and duodenitis

The dynamics of the antral and body mucosa has been studied in biopsy specimens obtained during endoscopy of patients with duodenal ulcer (103 cases), patients with duodenal ulcer scars (108 cases), and patients with duodenitis (44 cases). A representative Finnish population sample consisting of 434 subjects was used as reference material. The antral mucosa of all patient series showed an increase in the severity and prevalence of gastritis similar to that of the general population, whereas virtually no progression of gastritis with age was seen in the body mucosa, which remained normal or at the stage of superficial gastritis up to geriatric age. In contrast, in the present controls and in all earlier population samples studied by us so far, there was a significant and steady increase in the severity and prevalence of body gastritis with age. It is concluded that the age behavior of the antral and body mucosa was in duodenal ulcer scars and duodenitis similar to that of patients with active duodenal ulcer. The persistence of normal conditions in the acid-secreting area may serve as one explanation of the strong tendency of the disease to recur. In addition, it is tentatively concluded that in duodenal ulcer disease there are factors that have a 'protecting' influence on the body glands and which are abolished by antrectomy, according to our earlier studies.     

Small-bowel obstruction due to bilharziasis

The dynamics of the antral and body mucosa has been studied in biopsy specimens obtained during endoscopy of patients with duodenal ulcer (103 cases), patients with duodenal ulcer scars (108 cases), and patients with duodenitis (44 cases). A representative Finnish population sample consisting of 434 subjects was used as reference material. The antral mucosa of all patient series showed an increase in the severity and prevalence of gastritis similar to that of the general population, whereas virtually no progression of gastritis with age was seen in the body mucosa, which remained normal or at the stage of superficial gastritis up to geriatric age. In contrast, in the present controls and in all earlier population samples studied by us so far, there was a significant and steady increase in the severity and prevalence of body gastritis with age. It is concluded that the age behaviour of the antral and body mucosa was in duodenal ulcer scars and duodenitis similar to that of patients with active duodenal ulcer. The persistence of normal conditions in the acid-secreting area may serve as one explanation of the strong tendency of the disease to recur. In addition, it is tentatively concluded that in duodenal ulcer disease there are factors that have a ‘protecting’ influence on the body glands and which are abolished by antrectomy, according to our earlier studies.     

Somatostatin in rat tissues is depleted by cysteamine administration

Administration of cysteamine (mercaptoethylamine) induces in rats severe perforating duodenal ulcers. Because the ulcerogenic properties of cysteamine are markedly reduced by treatment with somatostatin, we considered the possibility that cysteamine-induced duodenal ulcer might be mediated by depletion of tissue somatostatin, and thereby of its paracrine influences on gastrin and gastric acid secretion. To test this hypothesis, we measured the concentration of immunoreactive somatostatin (IR-somatostatin) in stomach and duodenal mucosa at intervals after administration of a single ulcerogenic dose (30 mg/kg by stomach tube). IR-somatostatin in these tissues fell rapidly to reach a minimum at 4 h (stomach 31%, duodenum 60% of control respectively). IR-somatostatin in hypothalamus and pancreas decreased gradually to a minimum at 7 h. Another duodenal ulcerogen, propionitrile (10 mg/100 g bw, s.c.) which is more toxic than cysteamine, and several stressful procedures including ether anesthesia, restraint and s.c. formalin did not lower stomach or duodenal IR-somatostatin. Gut, pancreas and hypothalamic VIP levels were not influenced by cysteamine. These findings suggest that cysteamine is a relatively specific depletor of tissue somatostatin. Because blood levels of somatostatin fell, and only trivial amounts of the peptide were found in the stomach lumen after cysteamine administration, it appears likely that this agent acts at the cellular level to cause breakdown of preformed somatostatin and/or to acutely reduce its synthesis.     

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.