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Gastric ulcer is a very common disease that represent an economic burden. Non-steroidal anti-inflammatory drugs induce ulcer in old patients and in patients with comorbidities. Indomethacin is widely used to induce gastric ulcer in animal models. Diabetic patients are highly susceptible to develop gastric ulcer. Metformin, the first line medication for the treatment of type II diabetes melilites that have many off label uses in non-diabetic patients, has been recently reported to have anti-inflammatory activities. Therefore, this research was conducted to assess the possible healing effects of metformin on gastric ulcers induced by indomethacin in rats. Indomethacin (48 mg/kg) single dose increased stomach acidity, ulcer index and induced histopathological changes. Indomethacin also decreased mucin levels and increased the activity of tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), Rho-associated protein kinas-1 (ROCK-1) and decreased the levels of the protective nitric oxide (NO). After the induction of ulcer, rats were treated by omeprazole (30 mg/kg) or metformin (50, 100 or 200 mg/kg). Omeprazole and metformin were found to decrease stomach acidity and ulcer index, restored the histological features and increased mucin levels. Both also decreased the levels of NF-κB, TNF-α, ROCK-1 and increased NO. Metformin exerted ulcer healing effects comparable to that of omeprazole. This can be attributed, at least partly, to its anti-inflammatory activity and increasing NO levels., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Multiple kinds of monoamine-based antidepressants have been shown prophylactic effects in experimentally induced gastric ulcer. The loss of redox homeostasis plays a principle role in the development of peptic mucosal damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are one of the most important sources of reactive oxygen species within the gastrointestinal tract. It is unclear whether there are some common NADPH oxidases modulated by monoamine-based antidepressants in different gastric mucosal damage models. We explored the effects of selective serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine on the reactive oxygen species production and antioxidant capacity in the gastric mucosa of water immersion restraint (WIRS) or indomethacin treated rats, and examined the role of NADPH oxidases in the protective effects. Pretreated duloxetine prevented the increase of gastric mucosal NADPH oxidase activity and NADPH oxidase inhibitor apocynin dose-dependently protected gastric mucosa from damage by the two factors. Furthermore, dual oxidase 2 (DUOX2) and NADPH oxidase4 (NOX4) are involved in the protective effects of duloxetine in both models. We then examined NADPH oxidases expression modulated by the other monoamine-based antidepressants including selective serotonin reuptake inhibitor (SSRIs) fluoxetine, tricyclic agent (TCAs) amitriptyline and monoamine oxidase inhibitor (MAOs) moclobemide in the two models, and all the three antidepressants reduced the DUOX2 expression in the gastric mucosa. So DUOX2 was a common modulator in the preventive effects of all the monoamine-based antidepressants on WIRS- and indomethacin-induced gastric lesion. Our work provided a peripheral joint molecular target for monoamine modulatory antidepressants, which may be helpful to reveal the mechanisms of this kind of drugs more than monoamine regulation., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Methylsulfonylmethane (MSM) is a natural organosulfur compound has been widely used as a dietary supplement. MSM has protective effects against various disorders through its anti-inflammatory and antioxidant properties however the effect of MSM on gastric mucosal injury remains unclear. The aim of the present study is to determine whether MSM has beneficial effects on ethanol/HCl-induced gastric ulcer in mice. Macroscopic and histopathological evaluation of gastric mucosa revealed that ethanol/HCl administration produced apparent mucosal injuries, while pretreatment with MSM (200 and 400mg/kg, orally) could effectively protect gastric mucosa against the injuries caused by acidified ethanol. MSM significantly increased the levels of glutathione (GSH), catalase (CAT) and prostaglandin E 2 (PGE 2 ), and decreased the levels of malondialdehyde (MDA), myeloperoxidase (MPO), carbonyl protein, and nitric oxide (NO) in gastric tissues compared with those in the ethanol group. MSM suppressed gastric inflammation by reducing the levels of proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9. Moreover, pretreatment of mice with MSM decreased the expression of nuclear factor kappa B (NF-κB) as a key regulator of inflammation in gastric mucosa. Taken together, these data suggest that MSM is able to decrease the severity of ethanol/HCl-induced gastric mucosal injury through inhibition of oxidative stress and inflammation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Ample of evidence proved the gastroprotective effect of thymoquinone (TQ), the main constituent of Nigella sativa oil; however, the full mechanistic cassette on the gastric ulcer etiopathogenesis is not fully elucidated. The aim of the present work is to unveil some of the possible mechanisms. Animals were injected with vehicle, TQ (10 & 20mg/kg), omeprazole (10 & 20mg/kg) or their combination (10mg/kg). Thirty minutes later, pyloric ligation was carried out and followed consequently with ischemia for another 30min, abided by reperfusion for 120min. The ischemia/reperfusion insult increased the gastric acid secretion, acid output, and pepsin, as well as the gastric mucosal content/activity of lipid peroxide, proton pump and myeloperoxidase, along with ulcer index. However, content/activity of gastric mucin, reduced glutathione, total nitric oxide, and superoxide dismutase were decreased. TQ, especially the high dose level, corrected the altered parameters in a comparable manner to that of the reference drug used, omeprazole. In addition, when the low doses were combined they add to each other to reach the effect of the high dose of either drug. These results showed that apart from its known antioxidant properties, TQ has novel gastroprotective mechanisms via inhibiting proton pump, acid secretion and neutrophil infiltration, while enhancing mucin secretion, and nitric oxide production., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Gastric ulcer is a multifaceted process that involves reactive oxygen species (ROS) generation, extracellular matrix degradation and mitochondrial damage. Mitochondria play a crucial role for homeostasis of ROS and cell survival. In our study, we investigated the efficacy and mechanism of polymeric nanocapsuled quercetin (NQC) over the free quercetin (QC) molecule in prevention of ethanol-induced gastric ulcer in rat. NQC possessed significantly higher efficacy (~20 fold) than free QC while preventing gastric ulcers. Our data show that prior administration of NQC and/or QC significantly blocked synthesis and secretion of matrix metalloproteinase (MMP)-9 as well as infiltration of inflammatory cells and oxidative damage in rat gastric tissues. As compared to free QC, NQC protected much better the mitochondrial integrity and size along with mitochondrial functions by controlling succinate dehydrogenase and NADH oxidase in rat gastric tissues. In addition, both free QC and NQC down regulated PARP-1 as well as apoptosis during protection against ethanol-induced gastric ulcer. Herein, the effect of NQC was greater than QC on expression of enzymes like cyclooxygenase and nitric oxidase synthase (NOS)-2. We conclude that NQC with greater bioavailability offers significantly higher potency in downregulating MMP-9 and NOS-2 as well as oxidative stress in blocking ethanol-induced gastric ulcer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The role of the ariginine-metabolism in the healing action of the Piper betle phenol, allylpyrocatechol (APC) and omeprazole against indomethacin-induced stomach ulceration in mouse was investigated. Indomethacin (18 mg/kg) was found to induce maximum stomach ulceration in Swiss albino mice on the 3rd day of its administration, which was associated with reduced arginase activity (21.6%, P<0.05), endothelial nitric oxide synthase (eNOS) expression (72%, P<0.001), and IL-4 and TGF-beta levels, along with increased inducible nitric oxide synthase (iNOS) (9.3 folds, P<0.001) expression, nitrite (2.29 folds, P<0.001), IL-1beta and IL-6 generation. Besides providing comparable healing as omeprazole (3 mg/kg x 3 days), APC (5 mg/kg x 3 days) shifted the iNOS/NO axis to the arginase/polyamine axis as revealed from the increased arginase activity (73.1%, P<0.001), eNOS expression (67.8%, P<0.001), and reduced iNOS expression (65.6%, P<0.001) and nitrite level (53.2%, P<0.001). These can be attributed to a favourable anti-/pro-inflammatory cytokines ratio, generated by APC. The healing by omeprazole was however, not significantly associated with those parameters.

We assessed the effect of novel selective thiopheneacetic acids on cyclooxygenase isoenzymes in vitro and in vivo. Thiopheneacetic acid Eltenac and derivatives were investigated in this study. In human whole blood experiments these derivatives were potent inhibitors of COX-2 (IC(50)=0.02-0.4 microM) with less pronounced effect on COX-1 (IC(50)=0.15-5.6 microM). With COX-1/COX-2 ratios between 7.5- and 16-fold they are in the range of Celecoxib (13-fold). The parent drug Eltenac demonstrated no selectivity for COX-2. In a rat paw edema model, these compounds showed reduction of edema volume in the range of 36-45% at 10 mg/kg (Eltenac 52%, Diclofenac 51%). However, the compounds were superior to Diclofenac and Eltenac with respect to their ulcerogenic and gastrointestinal properties. Introduction of a nitrate-ester moiety to either Eltenac or a derivative did neither improve selectivity or potency in vitro, nor ulcerogenicity in vivo. Molecular modeling of selective thiopheneacetic acid derivatives to the active site of human COX-2 suggested similar binding properties as Lumiracoxib and Diclofenac. In summary, modification of Eltenac generates moderately selective COX-2 drugs in the range of Celecoxib with respect to potency and selectivity. The drugs showed potent anti-inflammatory properties and significant improvement of animal survival in a sub-chronical experimental set up. Thiopheneacetic derivatives are characterized by low pK(a) values, short microsomal half-lives and binding mode to COX-2 similar to Diclofenac and Lumiracoxib. These properties may also have an impact on the transient inhibition of COX-2-dependent prostacyclin, thereby being less associated with vascular complications.

Gastric ulcer is a multifaceted process including acid secretion, reactive oxygen species generation, prostaglandin inhibition, and extracellular matrix (ECM) degradation. Matrix metalloproteinases (MMPs) have the ability to cleave and remodel the ECM. We investigated the activity and expression of MMP-9 and -2 in ethanol-induced acute gastric ulceration in rats. We found that severity of gastric ulcer was strongly correlated with increasing doses of ethanol and increased secretion of proMMP-9. ProMMP-9 was upregulated approximately 25-fold at maximum ulcer index. Increased secretion of proMMP-9 was associated with increased expression of tumor necrosis factor-alpha and interleukin-6. We examined the effect of H(2)-receptor antagonists and antioxidants on proMMP-9 secretion and synthesis during prevention of ethanol-induced gastric ulcer. Our data reveal that famotidine dose dependently blocked increased secretion and synthesis of proMMP-9 during gastroprotection and arrested infiltration of inflammatory cells as well as oxidative stress in rat gastric tissues. Similar to H(2)-receptor antagonists, N-acetylcysteine and dimethyl sulfoxide, well-known antioxidants, inhibited proMMP-9 upregulation to the control level. In conclusion, ethanol-induced gastric ulceration is associated with increased expression of proMMP-9 that can be attenuated by H(2)-receptor antagonists and antioxidants. These findings furnish a novel MMP-9-mediated pathway and its inhibition via proinflammatory cytokines by famotidine in ethanol-induced gastric ulceration.

Prostaglandin E(2) and D(2) (PGE(2) and PGD(2)) production and cyclooxygenase-2 (COX-2) expression during the resolution of acute and chronic gastric inflammatory lesions in Wistar rats have been investigated. Differences between ibuprofen, nonselective COX inhibitor, and rofecoxib, specific COX-2 inhibitor, on the development of the induced responses were also analysed. In an acute model, by instillation of HCL, the greatest injury was observed early with a rapid and progressive restoration. Maximal up-regulation of COX-2 protein was detected at 6 h and was accompanied by increase of PGE(2) synthesis but not PGD(2). Both drugs stimulated COX-2 expression in accordance to their capacity of inhibiting this enzymatic activity, driving to delay in the healing. In a chronic model, by acetic acid-induced gastric ulcers, COX-2 was expressed at 7 days and was also associated with PGE(2) increase. Ibuprofen and rofecoxib also augmented COX-2 protein and inhibited PGE(2) levels. However, PGD(2) production was augmented when none signal of COX-2 protein could be detected. Together, this study confirms the role played by COX-2 enzyme in the resolution of acute and chronic gastric inflammatory process, PGE(2) being the principal product. The antiinflammatory effect of nonsteroidal antiinflammatory drugs (NSAIDs) could be mediated not only through the inhibition of COX activity but also through the induction of antiinflammatory PGs production-such as PGD(2)-although further studies would be needed to clarify the mechanisms of this activity and the possible implicated processes.

Histamine is involved in the development of gastric lesions. To examine the contribution of the histamine-forming enzyme, histidine decarboxylase, to drug-induced gastric lesions, we compared the effects of aspirin, indomethacin and dexamethasone on histidine decarboxylase activity in mice. Administration of these drugs, orally or intraperitoneally, elevated histidine decarboxylase activity in the stomach but not in the liver, lung or spleen, dexamethasone being the most potent. In contrast, acetaminophen (a non-ulcerogenic drug) was inactive. These results and our previously reported findings (elevation of histidine decarboxylase activity by lipopolysaccharide, interleukin-1 and tumour necrosis factor, and by different types of stress) suggest that an elevation of histidine decarboxylase activity in the stomach may be a common feature of the responses to ulcerogenic stimuli. The possible participation of histidine decarboxylase in gastric lesions is discussed on the basis of the known actions of histamine, our findings and the effect of histamine H(2) receptor antagonists on histidine decarboxylase activity.

Gastroduodenal ulcerations have worldwide distribution and the infection with Helicobacter pylori (HP) has been implicated in pathogenesis of this disease. The HP infection is usually accompanied by hypergastrinemia and enhanced generation of prostaglandins (PG), both implicated in the pathogenesis of peptic ulcerations but no study has been undertaken to assess the relationship between the HP infection and coexpression of gastrin and cyclooxygenases (COX), the rate limiting enzymes in the PG production. Since HP infection, usually accompanying peptic ulcerations, results in increased release of gastrin, a potent gastric mitogen that might be capable to induce COX-2 and to generate PG, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric ulcer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) at the margin of gastric ulcer and in the mucosa of antrum and corpus before and after successful eradication of HP, 3) to assess the plasma levels and gastric luminal contents of gastrin before and after HP eradication and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 as well as the PGE2 generation in ulcer margin tissue and gastric antral and fundic mucosa before and after the HP eradication. The trial material included 20 patients with gastric ulcer and 40 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCK(B)-R, COX-1 and COX-2 were examined using RT-PCR with beta-actin as a reference and employing Western blotting for COX-2 expression, while gastrin and PGE2 were measured by RIA. All gastric ulcers were located at smaller curvature within the antral mucosal area. The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric ulcers (85%) than in controls (62.5%). Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in ulcer margin and gastrin mRNA was overexpressed in remaining antral mucosa, while CCK(B)-R mRNA was overexpressed in fundic mucosa of HP infected patients. Similarly, COX-2 mRNA and protein were found in margin of gastric ulcer and in the HP infected antral and fundic mucosa but not in the mucosa of HP eradicated patients in whom ulcers completely healed and gastrin was expressed only in antrum, CCK(B)-R only in corpus, while COX-1 was detected both in antrum and corpus. HP positive gastric ulcer patients showed about three times higher levels of plasma immunoreactive gastrin and about 50% higher luminal gastrin contents than the HP negative controls and this increased plasma and luminal gastrin was normalized following the HP eradication. A significant fall in gastrin and CCK(B)-R mRNA expression was noticed six weeks after HP eradication in gastric antral and fundic mucosa, while COX-2 mRNA completely disappeared after this treatment. We conclude that 1) HP infected gastric ulcer margin coexpresses gastrin, its receptors (CCK(B)-R), and COX-2; 2) HP infection may be implicated in gastric ulceration via increased release of gastrin that could be responsible for the overexpression of COX-2 that in turn could help ulcer healing through the stimulation of mucosal cell growth, restoration of the glandular structure and angiogenesis in the ulcer area and 3) gastrin produced in HP infected antral mucosa seems to be involved in the induction of COX-2 and PG production by this enzyme and this may contribute to the ulcer healing.

In this study, ischemia-reperfusion produced in rats by clamping the celiac artery for 0.5 h followed by 1 h of reperfusion was used to develop a new model of superficial gastric erosions progressing to deeper ulcers. Ischemia alone resulted in an immediate fall in gastric blood flow but no gross mucosal lesions were observed. When ischemia was followed by reperfusion, gastric erosive lesions occurred, reached a maximum at 12 h and then declined after 24 h. These acute erosions progressed into deeper lesions 24 h after ischemia-reperfusion and reached a peak after 3 days. Gastric blood flow and the mucosal generation of prostaglandin E(2) were significantly suppressed immediately following ischemia-reperfusion, but with the healing of deeper gastric ulcers, both gastric blood flow and prostaglandin E(2) generation were gradually restored. Cyclooxygenase-1 mRNA was detected by reverse transcription-polymerase chain reaction in intact gastric mucosa and throughout the recovery of the mucosa from acute ischemia-reperfusion lesions, whereas cyclooxygenase-2 mRNA, was recorded only after ischemia-reperfusion. NS-398 and rofecoxib, selective inhibitors of cyclooxyganase-2, failed to affect prostaglandin E(2) generation in the non-ulcerated gastric mucosa but inhibited it significantly in the ulcer area. The two cyclooxygenase-2 inhibitors as well as resveratrol, a specific cyclooxygenase-1 inhibitor and indomethacin and meloxicam, non-specific inhibitors of cyclooxygenase, augmented acute gastric erosions induced by ischemia-reperfusion and delayed significantly the progression of these lesions into deeper ulcers at each time interval after ischemia-reperfusion. We conclude that prostaglandins generated by both cyclooxygenase-1 and cyclooxygenase-2 contribute to the healing of gastric lesions induced by ischemia-reperfusion.

The development of cyclooxygenase (COX) deficient mice has allowed investigation into the individual physiological roles of the COX-1 and COX-2 isoforms. In the following article, the phenotypes of the two Ptgs (genes coding for COX-1 and COX-2) knockouts are summarized, and recent studies to investigate the effects of COX deficiency on cancer susceptibility, inflammatory response, gastric ulceration, and female reproductive processes are discussed. Also, the development and potential uses of mice deficient in both COX isoforms and mice containing only a single copy of one isoform are discussed. Additionally, when the data permit, the effects of genetic ablation of COX activity are compared with those of pharmacological inhibition of COX activity by nonsteroidal anti-inflammatory drugs. The data suggest that prostaglandins derived via the individual COX isoforms have separate as well as common functions. However, for the maintenance of normal physiology, it appears that deficiency of COX-2 has more profound effects than deficiency of COX-1.

The roles of neutrophil aggregation, inducible nitric oxide synthase activation and chemoattractant, leukotriene B4, in potentiation of the cigarette smoke effect on ethanol-induced gastric mucosal damage were studied. Smoke exposure markedly increased gastric lesion formation following ethanol administration and this was accompanied by substantial increase in gastric mucosal leukotriene B4 concentration, myeloperoxidase and inducible nitric oxide synthase activities. Antineutrophil serum or aminoguanidine pretreatment significantly attenuated both gastric mucosal lesion formation and inducible nitric oxide synthase activity. The increased myeloperoxidase activity was abolished by antineutrophil serum but not by aminoguanidine. These data indicated that both neutrophil mobilization and inducible nitric oxide synthase activation in the gastric mucosa play an important role in the potentiating action of cigarette smoke on ethanol-induced gastric mucosal lesion formation. Increased synthesis of nitric oxide from inducible nitric oxide synthase during gastric damage may be secondary to neutrophil infiltration in the gastric mucosa. Chemoattractant leukotriene B4 could also contribute to neutrophil recruitment in the tissue.

1. The effect of antiulcer agents, ebrotidine and sucralfate, on the expression of gastric mucosal proliferating cell nuclear antigen (PCNA) and cyclin-dependent kinase (p34Cdk2) during chronic ulcer healing was examined. 2. Rats with experimentally induced gastric ulcers were treated twice daily for 14 days with either ebrotidine at 100 mg/kg, sucralfate at 100 mg/kg or vehicle, and at different stages of treatment their stomachs were used for quantitization of gastric mucosal PCNA and Cdk2 expression. 3. The assays revealed that the ulcer healing was accompanied by a marked elevation in mucosal expression of PCNA and Cdk2. The maximum increase in PCNA (4.7-fold) occurred by the second day of healing, and the expression of Cdk2 reached a maximum increase (2.3-fold) by the fourth day. 4. Accelerated ulcer healing with ebrotidine (7 days) and sucralfate (8 days) treatments was reflected in a significant enhancement of PCNA and Cdk2 expression. By the second day of treatment, ebrotidine evoked a 15-fold increase in PCNA expression, and sucralfate produced an 11.8-fold enhancement. The mucosal expression of Cdk2 attained a maximum of 4.3-fold increase over that of the controls by the sixth day of healing with ebrotidine, and a fivefold increase in Cdk2 expression occurred by the fourth day of ulcer treatment with sucralfate. 5. The findings implicate cell cycle regulatory proteins in the processes to leading to mucosal repair and suggest that the two drugs exert a similar effect on the expression of proteins that control cell cycle progression.

Rebamipide, a novel antipeptic ulcer drug, 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinone-4-yl]-propionic acid, was studied for its inhibitory effect on gastric xanthine oxidase activity and type conversion of the enzyme that has a profound role in free radical generation. Intraperitoneal administration of rebamipide at 60 mg/kg body weight reduced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of rebamipide on alcohol-induced xanthine oxidase-type conversion and enzyme activity. It was also observed that the activity of xanthine oxidase was significantly inhibited by administration of rebamipide at 60 mg/kg body weight, leading to a significant reduction of lipid peroxide content in alcohol-treated rats. The results suggest that alcohol-induced gastric mucosal lesions might be, in part, due to the increased activity of xanthine oxidase and type conversion rate of the enzyme and the protective effect of rebamipide on gastric mucosal lesions would result from its ability to protect against oxidative stress on gastric mucosal lesions of alcohol-treated rats.

Helicobacter pylori are believed to play an important role in the formation of gastric ulcer in a syndrome characterized by a high urease activity. On the other hand, the production of oxygen radicals and platelet activating factor (PAF) is enhanced in gastric ulcers. The present study is designed to investigate the relationship between the different aspects of gastric mucosal injury, urease activity, oxygen radical production, and PAF content in gastric specimens. Biopsy specimens taken from 35 gastric ulcer patients were studied. Urease activity was detected by a rapid urease test (CLO). Oxygen radical production was measured as a value of luminol-dependent chemiluminescence (ChL) and PAF content was determined by radioimmunoassay in the biopsy samples. The CLO-positive rate was significantly higher in the gastric ulcer group in comparison with that in controls. ChL values and PAF content were significantly increased in gastric ulcers, especially in CLO-positive specimens. The CLO-positive rate, ChL values, and PAF content were also found to be increased at a distant site beyond the ulcer lesions. During the course of macroscopic ulcer healing of CLO-positive cases, the CLO positive level and the ChL values were not significantly decreased, although PAF content was significantly lower. Enhanced oxygen radical and PAF production were observed not only in the ulcer region but also at a distant site from the ulcer in the urease-positive gastric mucosa. The persistent enhancement of ChL values during the healing stage of urease-positive gastric ulcers suggests its involvement in the recurrence of gastric ulcers.

Adenosine deaminase activity was studied in gastric corpus mucosa close to an ulcer crater. It was found that 6 weeks of therapy with ranitidine was accompanied by a decrease in enzyme activity in the mucosa around healed ulcers and an increase around those which failed to heal. The different activities of adenosine deaminase in the vicinity of healed and unhealed ulcers may indicate its possible role in peptic ulcer healing.

Adenosine deaminase activity was studied in the gastric mucosa of patients with peptic ulcer in relation to ulcer localisation and treatment with ranitidine or sucralfate. Enzyme activities observed in the corpus mucosa were higher at a distance of over 2 cm from the ulcer margin than that recorded close to the ulcer. A significant decrease in adenosine deaminase activity was found after treatment with ranitidine but not with sucralfate. In the antral mucosa, enzyme activity was constant in all the groups observed. The evaluation of adenosine deaminase activity in gastric mucosa can be useful for studies of pathologic changes in the stomach.

Pepsinogens, proteolytic enzymes produced by peptic cells of the stomach and discharged into the gastric lumen as well as into the blood have been divided into two groups: PG-I, originating from chief cells, and PG-II, mainly from antrum peptic cells. Both total serum pepsinogen (s-Pg) and PG-I have been separately reported as being significantly increased in gastric (GU) and duodenal ulcer (DU) patients and related to maximal acid output. In order to ascertain the relationship between s-Pg measured by means of the colorimetric Uete method, and PG-I determined by RIA method, these were assayed in 72 control subjects, 35 GU and 95 DU patients. s-Pg was found to be significantly increased both in GU and DU patients in comparison with control subjects. Likewise PG-I was significantly enhanced in GU and DU patients as compared with controls. A significant direct correlation between s-Pg and PG-I was found in all the subjects studied (r = 0.732).

The role of pepsin proteolytic activity in the Exalto-Mann-Williamson ulcer has previously not been established. Our studies show that a potent inhibitor of pepsin activity, when administered orally to E-M-W dogs, reduced both the incidence and severity of jejunal ulceration. These results indicate that pepsin may play a major role in the development of ulceration in this model.