Reduction In Acid Output Research Articles

Autoimmune gastritis.

Autoimmune gastritis (AIG) is an increasingly prevalent, organ-specific, immune-mediated disorder characterized by the destruction of gastric parietal cells, leading to the loss of intrinsic factor and reduced acid output. These alterations result in malabsorption of iron, vitamin B12 (pernicious anaemia) and potentially other micronutrients. For several years, most studies have focused on pernicious anaemia only, generating confusion between the two entities. In AIG, the gastric proton pump, H+/K+ ATPase, is the major autoantigen recognized by autoreactive T cells. The T cell-dependent activation of B cells stimulates the production of anti-parietal cell antibodies, the serological hallmark of AIG. The role of Helicobacter pylori infection in activating or favouring the autoimmune process is still uncertain. Early histopathological alterations allowing a more precise and prompt recognition have recently been described. AIG is burdened by a substantial diagnostic delay as it can present with varied clinical signs including, among others, gastrointestinal symptoms and neuropsychiatric manifestations. In advanced stages, AIG might progress to neuroendocrine tumours and gastric adenocarcinoma. Management includes early detection through a proactive case-finding strategy, micronutrient supplementation and endoscopic surveillance. This Primer comprehensively describes the most important insights regarding the epidemiology, pathophysiology, diagnosis and management of AIG, focusing on the most controversial, outstanding issues and future directions.

World Gastroenterology Organisation Global Guidelines: GERD Global Perspective on Gastroesophageal Reflux Disease.

PROBIOTICS—THE CONCEPTHistory and DefinitionsA century ago, Elie Metchnikoff (a Russian scientist, Nobel laureate, and professor at the Pasteur Institute in Paris) postulated that lactic acid bacteria (LAB) offered health benefits capable of promoting longevity. He suggested that “intestinal autoint

Antiulcerogenic effect of some gastrointestinally acting plant extracts and their combination.

Extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, Silybum marianum and Chelidonium majus, singly and combined in the form of a commercial preparation, STW 5 (Iberogast) and a modified formulation, STW 5-II, lacking the last 3 constituents, were tested for their potential anti-ulcerogenic activity against indometacin induced gastric ulcers of the rat as well as for their antisecretory and cytoprotective activities. All extracts produced a dose dependent anti-ulcerogenic activity associated with a reduced acid output and an increased mucin secretion, an increase in prostaglandin E2 release and a decrease in leukotrienes. The effect on pepsin content was rather variable and did not seem to bear a relationship with the anti-ulcerogenic activity. The most beneficial effects were observed with the combined formulations STW 5 and STW 5-II in a dose of 10 ml/kg b.w., comparable with cimetidine in a dose of 100 mg/kg b.w. The anti-ulcerogenic activity of the extracts was also confirmed histologically. The cytoprotective effect of the extracts could be partly due to their flavonoid content and to their free radical scavenging properties.

Altered physiology of acid secretion in depression‐prone Flinders rats results in exacerbated NSAID and stress‐induced gastric damage

Flinders Sensitive Line (FSL) rats are characterized by hypersensitivity to cholinergic stimuli and have been extensively used for studying depressive disorders. A link between depression and peptic ulcers has long been established; however, there is a lack of data from animal models. We studied the physiology of acid secretion in FSL and Flinders Resistant Line (FRL) rats in vivo and in vitro. We also examined the susceptibility of Flinders rats to water immersion restraint stress (WIRS) or NSAID-induced gastric damage and explored the effect of an anticholinergic agent, atropine, in reversing this effect. Basal acid output was more than twofold greater in FSL compared with FRL rats in vivo, 213.5 and 92.8 μEq/3 h/100 g (P = 0.02), respectively. Carbachol was a more potent secretagog in vitro, and somatostatin was a less potent inhibitory agent, while paradoxically stimulating acid secretion over and above the carbachol response in gastric glands from FSL rats. The FSL rats were more susceptible to indomethacin and WIRS-induced gastric mucosal damage compared with FRL rats. Atropine reduced acid output, which resulted in a reduction in indomethacin and stress-induced gastric damage in FSL rats. Our study, for the first time, demonstrates that the altered vagally mediated physiology of acid secretion in depression-prone FSL rats contributes to gastric hypersecretion and, consequently, results in exacerbated stress and NSAID-induced gastric damage. Flinders rats may be a useful animal model for studying acid-related and also gastrointestinal functional disorders in depression.

Anti-ulcerogenic effect of aqueous propolis extract and the influence of radiation exposure

Purpose: To study the effect of aqueous propolis extract (AEP) against indomethacin (Indo)-induced gastric ulcers in irradiated and non-irradiated rats.Materials and methods: Animals were irradiated at different radiation dose levels before the induction of ulcers. AEP was injected orally 1 hour before induction of gastric ulcers and the effects compared with those of lansoprazole (Lanso), which was used as a reference anti-ulcerogenic drug.Results: Pretreatment of rats, either irradiated or non-irradiated, with AEP effectively protected against Indo-induced gastric ulceration. This was associated with a reduction in acid output and peptic activity and an increase in the secretion of mucin. The mucosal prostaglandin E2 (PGE2) level was also increased. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were suppressed to the same extent after treatment. Both propolis and Lanso were effective in reducing the number of gastric lesions as well as the plasma level of malondialdehyde (MDA).Conclusions: These findings indicate that the gastroprotective effect of AEP could be of value in the management of excessive gastric damage induced by radiation exposure.

Mechanisms involved in the gastro-protective effect of STW 5 (Iberogast®) and its components against ulcers and rebound acidity

The protective effect of a commercial preparation (STW 5, Iberogast), containing the extracts of bitter candy tuft, lemon balm leaf, chamomile flower, caraway fruit, peppermint leaf, liquorice root, Angelica root, milk thistle fruit and greater celandine herb, against the development of gastric ulcers was previously reported in an earlier publication (Khayyal et al., 2001). All extracts produced a dose dependent anti-ulcerogenic effect associated with a reduced acid output, an increased mucin secretion, an increase in prostaglandin E(2) release and a decrease in leukotrienes. The effect on pepsin content was not uniform and did not seem to bear a relationship with the anti-ulcerogenic activity. The best effects were observed with the combined formulation, STW 5. Furthermore, the effect of the latter in protecting against the development of rebound gastric acidity was examined experimentally in rats and compared with the effect of some commercial antacid preparations (Rennie, Talcid and Maaloxan). A model of testing rebound acidity was developed by inducing a marginal increase in gastric acidity through the administration of indomethacin, in such a way that it could be easily neutralized, allowing any eventual secondary increase in acidity to be measured within a few hours of administration. In addition, the serum gastrin level was measured after drug treatment to establish any correlation between it and any rebound acidity. The results obtained demonstrated that STW 5 did not only lower the gastric acidity as effectively as the commercial antacid, but it was more effective in inhibiting the secondary hyperacidity. Moreover, STW 5 was capable of inhibiting the serum gastrin level in rats, an effect which ran parallel to its lowering effect on gastric acid production.

The effect of vagotomy on the inhibition of gastric secretion by intraduodenal acid.

Abstract Acid in the duodenum is known to inhibit gastric secretion in man but whether this response is a humoral or a vagal phenomenon is unknown. If a vagal reflex is involved then selective and highly selective vagotomy, by preserving the duodenal nerve supply, could offer advantages over truncal division. This study was designed to investigate this claim. The effect of intraduodenal hydrochloric acid on pentagnstrin-stimulated gastric secretion was stimulated in 17 control subjects, 32 preoperative duodenal ulcer patients and 28 vagotomized patients (16 truncal vagotomy and pyloroplasty; 6 selective vagotomy and pyloroplasty; 6 highly selective vagotomy). Inhibition of acid output occurred in 15 control subjects, and the mean inhibition for the group was 2.68 + 0.39 mEq/10 minutes (P < 0.001). Inhibition occurred in 22 duodenal ulcer patients, and the mean reduction in acid output for the entire group was 2.26 ± 0.46 mEq/l0 minutes (P < 0.001). Intraduodenal acid failed to produce a response in the vagotomized patients irrespective of the presence or absence of a duodenal nerve supply. These results suggest that gastric secretory inhibition by intraduodenal acid is a vagal phenomenon in man; selective and highly selective vagotomy do not appear to carry any particular advantage over truncal section in terms of preserving this response.

Gastroprotective activity of Pradosia huberi on experimentally induced gastric lesions in rodents: Role of endogenous sulphydryls and nitric oxide

Pradosia huberi is a medicinal plant very common in the Amazonian forest population. The research interest in this plant is justifiable because of its potential medicinal value in gastritis and gastric ulcer mentioned in local folk medicine. In this paper, we evaluated the acute toxicity and antiulcerogenic effect of a hydroalcoholic extract (HAE) obtained from Pradosia huberi barks in rodents. No acute toxicological sign or symptom was observed in animals treated with the highest dose (5000 mg/kg, p.o.) of Pradosia huberi. In the HCl/EtOH-induced gastric ulcer model, HAE demonstrated significant inhibition of the ulcerative lesion index by 73% (500 mg/kg) and 88% (1000 mg/kg), respectively, in relation to the control value ( p < 0.05). The gastric damage induced by absolute ethanol in rats was effectively reduced by 84, 88 and 81% (250, 500 and 1000 mg/kg) when compared with the control group ( p < 0.01). In the NSAID-induced lesion model, HAE also showed antiulcerogenic effect with decrease in gastric lesions of 56% (250 mg/kg), 57% (500 mg/kg) and 67 % (1000 mg/kg) when compared with animals treated with vehicle ( p < 0.05). In the gastric ulcer induced by pylorus ligature model, the administration of HAE by oral and intraduodenal routes inhibited the gastric lesion index by 79 and 52% (500 mg/kg), respectively. HAE administered orally or intraduodenally was able to change gastric juice parameters (pH, volume and acid output) as well as those treated with cimetidine. The treatment with HAE (p.o.) significantly increased gastric volume, the pH values and promoted reduced acid output ( p < 0.01). By comparative effect (intraduodenal and oral route), we observed that HAE was better for local activity in gastric mucosa than in systemic action. HAE also has a non-specific activity when found to be the inhibitor of intestinal motility ( p > 0.01). The mechanism of action of HAE did not seem to be related to the NO-inhibitor but showed the participation of endogenous sulphydryl group in the gastroprotective action.

Preliminary studies of Mammea americana L. (Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice

Plant extracts are some of the most attractive sources of new drugs and have shown promising results for the treatment of gastric ulcers. Several folk medicinal plants and herbs have been used to treat gastrointestinal disorders, including gastric ulcers. Mammea americana L. (Guttiferae) fruit is very common in the diet of the population of northern South America. Our research interest in this plant arose because of its potential medicinal value as a tonic and against stomachache, as used in folk medicine. In this paper we evaluated three different extracts (ethanolic/EtOH, methanolic/MeOH and dichloromethane/DCM) obtained from M. americana L., for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH), hypothermic restraint stress, nonsteroidal anti-inflammatory drugs (NSAID, indomethacin) and pylorus ligation. In the HCl/EtOH-induced gastric-ulcer model, EtOH and DCM extracts demonstrated significant inhibition of the ulcerative lesion index by 54% (12.0 +/- 2.6 mm) and 86% (3.7 +/- 1.8 mm), respectively, in relation to the control value (26.0 +/- 1.4 mm) (p<0.0001). In the NSAID/cholinomimetic-induced lesion model, both EtOH and DCM extracts showed antiulcerogenic effects with significant reduction in the damage to these gastric lesions of 36% (8.3 +/- 2.0 mm) and 42% (7.5 +/- 1.4 mm), respectively, as compared to the control group (13.0 +/- 0.9 mm) (p<0.0001). In the gastric ulcer induced by hypothermic-restraint stress, both extracts also showed significant activity, and inhibited the gastric lesion index by 58% and 75%, respectively. The EtOH and DCM extracts also changed gastric juice parameters as well as those of cimetidine, decreased gastric acid secretion significantly (p<0.0001), increased pH values and promoted reduced acid output (p<0.0001). In all gastric-ulcer-induced models, MeOH extract did not show any significant antiulcerogenic activity, nor did it change gastric-juice parameters (p>0.05). The results suggest that EtOH and DCM extracts obtained from M. americana possess excellent antisecretory and/or gastrotective effect in all gastric ulcer models. These results suggest that the antiulcerogenic compound(s) present in M. americana may be clustered in the apolar fraction, which will be investigated by our group for the probable mechanisms of action.

Heightened susceptibility to chronic gastritis, hyperplasia and metaplasia in Kcnq1 mutant mice.

Increased susceptibility to gastric cancer has been associated with a wide range of host genetic and environmental factors, including Helicobacter pylori infection. Helicobacter pylori infection is postulated to initiate a progression through atrophic gastritis, metaplasia and dysplasia to cancer, and has been associated with reduction of acid output and dysregulation of stomach mucins. Here, we present the characterization of two mouse lines carrying mutant alleles of the gene encoding the Kcnq1 potassium channel, which very rapidly establish chronic gastritis in a pathogen-exposed environment. These mice develop gastric hyperplasia, hypochlorhydria and mucin dysregulation independent of infection. Metaplasia, dysplasia and pre-malignant adenomatous hyperplasia of the stomach have been observed in these Kcnq1 mutant mice, also independent of infection. The data presented here suggest that Kcnq1 mutant mice can be used both as an efficient model for the development of atrophic gastritis after infection and to determine the processes during the later stages of progression to gastric cancer independent of infection. Thus, Kcnq1 mutant mice are a powerful new tool for investigating the connection between acid balance, Helicobacter infection and mucin disruption in the progression to gastric cancer.

Presence of gastric autoantibodies impairs gastric secretory function in patients with Helicobacter pylori-positive duodenal ulcer.

Although the association between Helicobacter pylori infection and gastric autoimmunity is now well established, to date little is known about the significance of anticanalicular autoantibodies in patients with duodenal ulcer (DU). We therefore investigated the prevalence of serum antiparietal cell autoreactivity in DU patients as well as the relationship between these autoantibodies, gastric histopathology and gastric secretory function in this setting. Forty-one consecutive patients with H. pylori-positive DU were initially recruited. In all patients, basal (BAO) and pentagastrin stimulated acid output (PAO), fasting and meal-induced serum gastrin levels, as well as serum pepsinogen I concentrations, were measured. Antral and body gastritis was evaluated according to the Sydney system. Serum anticanalicular autoreactivity was determined by the indirect immunoperoxidase technique. Serum anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The presence of these antibodies was associated with a significantly higher grade of body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2) microg/ml versus 59.3 (20.5) microg/ml). In addition, PAO values were significantly lower in patients with gastric autoantibodies than in those without this autoreactivity (mean 0.35 (0.16) mmol kg(-1)h(-1) versus 0.49 (0.16)mmol kg(-1)h(-1)). In contrast, no significant differences were found between patients with and without anticanalicular autoantibodies as regards fasting serum pepsinogen I concentrations. Serum anticanalicular autoantibodies can be detected in 20% of patients with DU and are associated with a more severe pattern of body gastritis, higher gastrin levels and decreased peak acid secretion values. Their presence could account for the normal or reduced acid output which can be seen in a subset of DU patients.

Presence of Gastric Autoantibodies Impairs Gastric Secretory Function in Patients with Helicobacter pylori-positive Duodenal Ulcer

Background: Although the association between Helicobacter pylori infection and gastric autoimmunity is now well established, to date little is known about the significance of anticanalicular autoantibodies in patients with duodenal ulcer (DU). We therefore investigated the prevalence of serum antiparietal cell autoreactivity in DU patients as well as the relationship between these autoantibodies, gastric histopathology and gastric secretory function in this setting. Methods: Forty-one consecutive patients with H. pylori-positive DU were initially recruited. In all patients, basal (BAO) and pentagastrin stimulated acid output (PAO), fasting and meal-induced serum gastrin levels, as well as serum pepsinogen I concentrations, were measured. Antral and body gastritis was evaluated according to the Sydney system. Serum anticanalicular autoreactivity was determined by the indirect immunoperoxidase technique. Results: Serum anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The presence of these antibodies was associated with a significantly higher grade of body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2) pg/ml versus 59.3 (20.5) pg/ml). In addition, PAO values were significantly lower in patients with gastric autoantibodies than in those without this autoreactivity (mean 0.35 (0.16) mmol kg-1 h-1 versus 0.49 (0.16) mmol kg-1 h-1). In contrast, no significant differences were found between patients with and without anticanalicular autoantibodies as regards fasting serum pepsinogen I concentrations. Conclusions: Serum anticanalicular autoantibodies can be detected in 20% of patients with DU and are associated with a more severe pattern of body gastritis, higher gastrin levels and decreased peak acid secretion values. Their presence could account for the normal or reduced acid output which can be seen in a subset of DU patients.

Ethnic variations in the occurrence of gastroesophageal cancers.

Cancers of the esophagus, gastroesophageal junction (including the gastric cardia), and stomach represent three separate diseases with marked epidemiologic variations. The Department of Veterans Affairs computerized database records the ethnicity of all hospitalized patients throughout the United States, which provides an opportunity to study the influence of ethnicity on cancer rates in a uniform health-care system. All hospitalized patients, from 1980 through 1995, with a diagnosis of upper gastrointestinal cancer were identified. For each ethnic group and cancer type, hospitalization was expressed as an age-adjusted proportional rate per 10,000 hospitalizations from all causes. Hospitalization with gastric cancer was most frequent among Asians (48.4 per 10,000 hospitalizations) followed by blacks (33.3), Hispanics (28.7), American Indians (20.3), and whites (12.0). Adenocarcinoma of the gastroesophageal junction accounted for 5.9 per 10,000 hospitalizations among Asians, 4.5 among whites, and 4.5 among Hispanics. Gastroesophageal junction cancer was lowest among blacks (2.9) and American Indians (2.4). Finally, squamous cell carcinoma of the esophagus was frequent among blacks, 68.2 per 10,000, followed by Hispanics (36.4) and Asians (27.8), and was low among whites 24.0 and American Indians (21.5). Esophageal cancer rates remained stable in all ethnic groups from 1980 through 1995; gastroesophageal junction cancer rates increased particularly among whites, whereas gastric cancer rates declined in whites and blacks but not in Hispanics. There were significant ethnic differences in the occurrence of gastroesophageal malignancies among US military veterans. Environmental factors may explain some of these differences. Differential rates of Helicobacter pylori infection with resultant gastric atrophy and reduced acid output led to a greater risk for gastric cancer, but a reduced risk for reflux disease and cardiac cancer.

Rabeprazole: a review of its use in acid-related gastrointestinal disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate, to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.

Helicobacter pylori gastritis, peptic ulcer, and gastric cancer: clinical and molecular aspects.

Helicobacter pylori causes specific ultrastructural changes to the gastric mucosa. In developing countries a high percentage of infants acquire this infection, which initially causes a transient drop in stomach acid and thus allows transit of lower bowel pathogens, with consequent diarrhea and malnutrition. When infection occurs at an early age, the acid-producing cells of the stomach are involved in the inflammation, and the lifelong reduced acid output means a duodenal ulcer rarely develops. However, lifelong gastric inflammation leads in due course to atrophy, and in the presence of other factors gastric cancer may develop. People infected with H. pylori on average are of shorter stature than uninfected people. Adherence of H. pylori to the gastric mucosa is a prerequisite for infection, and a new binary model of adherence has been shown recently. Chaperonins of H. pylori induce macrophages to secrete cytokines, which leads to an immunologic cascade and inflammation.

Studies on the interrelation between Zollinger-Ellison syndrome, Helicobacter pylori, and proton pump inhibitor therapy

BACKGROUND & AIMS: The interrelation between Helicobacter pylori infection and proton pump inhibitor therapy in patients with Zollinger- Ellison syndrome is unknown. The aim of this study was to evaluate the influence of these factors on parameters of Zollinger-Ellison syndrome. METHODS: Prevalence of H. pylori was determined by biopsy and antibody testing in 84 patients. The influence of H. pylori status on clinical and laboratory parameters of Zollinger-Ellison syndrome was evaluated. Seroconversion after surgery was assessed retrospectively in infected patients. RESULTS: The prevalence of H. pylori exposure was 23% (10% with active infection). Acid output was higher in H. pylori-negative patients, but other clinical and biochemical parameters did not differ. Parameters were also similar for patients determined to be H. pylori positive by histology or antibody testing alone. Seroconversion rates did not differ between those rendered or not rendered disease free despite a significant reduction in acid output. CONCLUSIONS: H. pylori infection is not a risk factor for peptic ulceration in patients with Zollinger-Ellison syndrome. The prevalence is lower than in the general population and much lower than for patients with idiopathic peptic ulcer disease. Long-term omeprazole therapy in H. pylori-positive patients with Zollinger-Ellison syndrome may-lead to a reduction in parietal cell mass. (Gastroenterology 1997 Jan;112(1):84-91)

Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor-deficient mice

The cholecystokinin (CCK)-B/gastrin receptor is one of several regulators of gastric acid secretion and mucosal growth. To elucidate the contribution of this receptor relative to other trophic and secretory factors, mice that lack the CCK-B/gastrin receptor have been generated and studied. Both alleles of the CCK-B/gastrin receptor were inactivated by targeted gene disruption. Analysis of the mice included measurement of basal gastric pH and plasma gastrin levels. In addition, multiple gastric mucosal cell types were identified by immunostaining and quantified. Homozygous mutant mice were viable, fertile, and appeared grossly normal into adulthood. The receptor-deficient mice exhibited a marked increase in basal gastric pH (from 3.2 to 5.2) and an approximately 10-fold elevation in plasma gastrin concentration compared with wild-type controls. In the stomach of mutant animals, parietal and enterochromaffin-like cells were decreased, providing a likely explanation for the reduction in acid output. In the antrum, a decrease in somatostatin cell density and an increase in the gastrin cell number were observed, consistent with the concomitant elevation in circulating gastrin. Together, these findings demonstrate the importance of the CCK-B/gastrin receptor in maintaining the normal cellular composition and function of the gastric mucosa.

An interaction between glucose and estrogen in gastric acid secretion in the lateral hypothalamic area of female rats.

Gastric acid outputs caused by glucose injection into the lateral hypothalamic area (LHA) were examined in insulin hypoglycemia with or without estradiol-17 beta (EST) administration in bilaterally ovariectomized (OV) female rats. The basal level of acid output was higher in OV rats without EST than in OV rats with EST. When acid response was expressed as the percentage change, glucose injection into the LHA decreased acid output in a dose-dependent fashion in OV rats, while, in OV rats with EST, glucose injection into the LHA also reduced acid output without dose dependency. It was also noted that the threshold concentration of glucose that induced an acid response was lower in OV rats without EST than in OV rats with EST. These findings suggest that glucose-sensitive neurons responsible for gastric acid secretion can be modulated by estrogen at the LHA level.

Assessment and prediction of long-term cure in patients with the Zollinger-Ellison syndrome: the best approach.

To identify the best method for determining freedom from disease after gastrinoma resection and for predicting long-term disease-free status in patients with the Zollinger-Ellison syndrome. Prospective study in consecutive patients. Referral-based clinical research center. Eighty-one consecutive patients with the Zollinger-Ellison syndrome who underwent surgical exploration for gastrinoma resection. Patients were evaluated after gastrinoma resection, before discharge, 3 to 6 months after surgery, and yearly thereafter. Evaluation included secretin provocative testing and fasting serum gastrin determinations. Follow-up examinations after the initial postoperative evaluations included a clinical assessment, acid secretion studies, a calcium provocative test, and various imaging studies. Most patients (96%) had gastrinomas. Freedom from disease was defined by improved symptoms, reduced acid output and antisecretory drug requirements, and a normal gastrin level, normal imaging studies, and negative gastrin provocative studies. Fifty-two percent of patients (n = 42) were disease-free immediately after surgery, 44% at 3 to 6 months, 42% at 1 year, and 35% by 5 years (mean follow-up, 39 months). The secretin provocative test was the first test to become positive in 45% of patients with a recurrence, the serum gastrin determination was the first test to become positive in 36%, and both tests became positive at the same time in 18%. No recurrence was first detected by imaging studies or by calcium provocative testing. Fasting serum gastrin levels and secretin provocative test results at different postoperative times can be used to predict the probability of a patient remaining disease free at 3 years. Patients with a normal gastrin level and a normal secretin provocative test immediately after surgery had a 3-year disease-free probability of 75%, and normal results on both tests at 6 months, 1 year, and 2 years yielded respective probabilities of 88%, 95%, and 100%. Both the secretin provocative test and fasting serum gastrin determination are necessary for the early diagnosis of cases of recurrent disease after gastrinoma resection. The calcium provocative test and imaging studies do not detect any recurrences first. Fasting serum gastrin determinations and secretin provocative testing at different postoperative times can be used to predict the probability of a patient remaining disease free at 3 years.

Further investigations of omeprazole in obstetric patients

The routine use of antacid therapy during labour is controversial but most anaesthetists would agree that patients requiring regional or general anaesthesia should be treated. A recent survey’ has shown that suppression of acid secretion by Hz receptor blockade, supplemented by a saline antacid if operative obstetrics becomes necessary, is being widely used. Nevertheless H, receptor blockers by inhibiting liver enzymes and reducing hepatic blood flow could influence the pharmocokinetic pattern of other drugs. Omeprazole inhibits the proton pump of the parietal cell by way of a metabolite which is produced only in the highly acid milieu existing there.’ The parent drug in clinical doses has been shown to have no discemable effects elsewhere and the active metabolite has a very short half-life when absorbed. Nonobstetric studies indicated that a single dose provided a marked reduction in acid output for periods up to 24 h.3 Investigation of its effects as pre-anaesthetic antacid therapy was indicated and two investigations of its efficacy, side-effects and placental transfer in patients undergoing elective caesarean section were carried out.