Plasma Gastrin Levels Research Articles

Protective effect of palm vitamin E and α-tocopherol against gastric lesions induced by water immersion restraint stress in Sprague-Dawley rats.

Objective:Stress can lead to various changes in the gastrointestinal tract of rats. The present study was designed to compare the effect of palm vitamin E (PVE) and α-tocopherol (α-TF) supplementations on the gastric parameters important in maintaining gastric mucosal integrity in rats exposed to water immersion restraint stress (WRS). These parameters include gastric acidity, plasma gastrin level, gastric prostaglandin E2 (PGE2), and gastric lesions.Materials and Methods:Sixty male Sprague-Dawley rats (200-250 g) were divided into three equal groups: a control group, which received a normal rat diet (RC), and two treatment groups, receiving oral supplementation of either PVE or α-TF at 60 mg/kg body weight for 28 days. Each group was further divided into two groups: the nonstress and stress groups. The stress groups were subjected to 3.5 h of WRS once at the end of the treatment period. Blood samples were then taken to measure the gastrin level, after which the rats were killed. Gastric juice was collected for measurement of gastric acidity and gastric tissue was taken for measurement of gastric mucosal lesions and PGE2.Results:Exposure to stress resulted in the production of gastric lesions. PVE and α-TF lowered the lesion indices as compared to the stress control group. Stress reduced gastric acidity but pretreatment with PVE and α-TF prevented this reduction. The gastrin levels in the stress group were lower as compared to that in the nonstress control. However, following treatment with PVE and α-TF, gastrin levels increased and approached the normal level. There was also a significant reduction in the gastric PGE2 content with stress exposure, but this reduction was blocked with treatment with both PVE and α-TF.Conclusion:In conclusion, WRS leads to a reduction in the gastric acidity, gastrin level, and gastric PGE2 level and there is increased formation of gastric lesions. Supplementation with either PVE or α-TF reduces the formation of gastric lesions, possibly by blocking the changes in the gastric acidity, gastrin, and gastric PGE2 induced by stress. No significant difference between PVE and α-TF was observed.

Gastric secretion, proinflammatory cytokines and epidermal growth factor (EGF) in the delayed healing of lingual and gastric ulcerations by testosterone

Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins, as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha. Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha levels. Attenuation of plasma testosterone levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing, and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case of gastric ulcers, an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the deleterious effects of testosterone on ulcer healing.

Neurologic, Gastric, and Opthalmologic Pathologies in a Murine Model of Mucolipidosis Type IV

Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder caused by mutations in the MCOLN1 gene, which encodes the 65-kDa protein mucolipin-1. The most common clinical features of patients with MLIV include severe mental retardation, delayed motor milestones, ophthalmologic abnormalities, constitutive achlorhydria, and elevated plasma gastrin levels. Here, we describe the first murine model for MLIV, which accurately replicates the phenotype of patients with MLIV. The Mcoln1(-/-) mice present with numerous dense inclusion bodies in all cell types in brain and particularly in neurons, elevated plasma gastrin, vacuolization in parietal cells, and retinal degeneration. Neurobehavioral assessments, including analysis of gait and clasping, confirm the presence of a neurological defect. Gait deficits progress to complete hind-limb paralysis and death at age ~8 mo. The Mcoln1(-/-) mice are born in Mendelian ratios, and both male and female Mcoln1(-/-) mice are fertile and can breed to produce progeny. The creation of the first murine model for human MLIV provides an excellent system for elucidating disease pathogenesis. In addition, this model provides an invaluable resource for testing treatment strategies and potential therapies aimed at preventing or ameliorating the abnormal lysosomal storage in this devastating neurological disorder.

High gastrin cell activity and low ghrelin cell activity in high-anxiety Wistar Kyoto rats

Ghrelin is produced by gastric A-like cells and released in response to food deprivation. Interestingly, psychological stress also raises circulating ghrelin levels. This study compared plasma ghrelin levels in Sprague-Dawley (SPD) rats and high-anxiety Wistar Kyoto (WKY) rats. The two strains were also compared with respect to plasma gastrin, a gastric hormone with a pre- and postprandial release pattern opposite to that of ghrelin, and to the activity of the gastrin-dependent, histamine-forming ECL cells in the gastric mucosa. The rats were killed after being freely fed or after an over-night fast. The stomachs were weighed and tissue samples were collected for histological and biochemical analysis. Plasma ghrelin and gastrin levels were determined by RIA. While fasted SPD rats had higher plasma ghrelin levels than fasted WKY rats (P < 0.001), plasma ghrelin did not differ between freely fed rats of the two strains. Gastrin levels were higher in fed WKY rats than in fed SPD rats (P < 0.001). Despite the higher plasma gastrin level, the oxyntic mucosal histidine decarboxylase (HDC) activity (a marker of ECL-cell activity) in fed rats and the mucosal thickness did not differ between the two strains. In a subsequent study, rats were subjected to water-avoidance stress for 60 min, causing plasma gastrin to increase in WKY rats (P < 0.001) but not in SPD rats. In conclusion, high-anxiety WKY rats had lower circulating ghrelin and higher gastrin than SPD rats in both the fasted and fed state, while the ECL-cell activity (HDC activity) was only moderately affected.

Effects and mechanisms of electroacupuncture at PC6 on frequency of transient lower esophageal sphincter relaxation in cats

To investigate the effects of electroacupuncture (EA) at neiguan (PC6) on gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs) and discuss the mechanisms of this treatment. Protocol I: Twelve healthy cats underwent gastric distention for 60 min on the first day. Electrical acupoint stimulation was applied at the neiguan or a sham point on the hip in randomized order before gastric distention, on the third day and fifth day. Those cats that underwent EA at neiguan on the fifth day were named "Neiguan Group" and the cats that underwent EA at a sham acupoint on the fifth day were named "Sham Group" (control group). During the experiment the frequency of TLESRs and lower esophageal sphincter (LES) pressure were observed by a perfused sleeve assembly. Plasma levels of gastrin (GAS) and motilin (MTL) were determined by radioimmunoassay. Nitrite/nitrate concentration in plasma and tissues were measured by Griess reagent. The nuclei in the brain stem were observed by immunohistochemistry method of c-Fos and NADPH-d dyeing. Protocol II: Thirty six healthy cats were divided into 6 groups randomly. We gave saline (2 mL iv. control group), phaclofen (5 mg/kg iv. GABA-B antagonist), cholecystokinin octapeptide (CCK-8) (1 microg/kg per hour iv.), L-Arginine (200 mg/kg iv.), naloxone (2.5 micromol/kg iv.) and tacrine (5.6 mg/kg ip. cholinesterase inhibitor) respectively before EA at Neiguan and gastric distention. And the frequencies of TLESRs in experimental groups were compared with the control group. Protocol I: Not only the frequency of gastric distention-induced TLESR in 60 min but also the rate of common cavity during TLESRs were significantly decreased by EA at neiguan compared to that of sham acupoint stimulation. C-Fos immunoreactivity and NOS reactivity in the solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) were significantly decreased by EA at neiguan compared to that of the sham group. However, the positive nuclei of C-Fos and NOS in reticular formation of the medulla (RFM) were increased by EA at neiguan. Protocol II: The inhibited effect of EA at neiguan on TLESR's frequency was completely restored by pretreatment with CCK (23.5/h vs 4.5/h, P < 0.05), L-arginine (17.5/h vs 4.5/h, P < 0.05) and naloxone(12/h vs 4.5/h, P < 0.05). On the contrary, phaclofen (6/h vs 4.5/h, P > 0.05) and tacrine (9.5/h vs 4.5/h, P > 0.05) did not influence it. Electric acupoint stimulation at Neiguan significantly inhibits the frequency of TLESR and the rate of common cavity during TLESR in cats. This effect appears to act on the brain stem, and may be mediated through nitric oxide (NO), CCK-A receptor and mu-opioid receptors. But the GABAB receptor and acetylcholine may not be involved in it.

Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion

Gastric acid plays an important role in digesting food (especially protein), iron absorption, and destroying swallowed micro-organisms. H+ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms. Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like (ECL) cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, long-term hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastrin levels, leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concern, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and clinically in the regulation of gastric acid secretion.

H pyloriinfection causes chronic pancreatitis in Mongolian gerbils

To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type IV secretion system. Mongolian gerbils were infected with wild type (WT) H pylori type I strain B128 or its isogenic mutant B128 deltacagY (defective type IV secretion). After seven months of infection, H pylori was reisolated from antrum and corpus and H pylori DNA was analyzed by semi-nested polymerase chain reaction (PCR). Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals and those developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue, but not in the pancreas. H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type IV secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

Calcitonin gene-related peptide and somatostatin releases correlated with the area under the lafutidine concentration–time curve in human plasma

To examine the effects of the histamine H(2)-receptor antagonist, lafutidine, at clinical dosage (10 mg tablet after a standardized meal) on plasma levels of the gastrointestinal peptides, calcitonin gene-related peptide (CGRP), somatostatin and gastrin. Six healthy male volunteers ate a standardized meal, and received either lafutidine orally at a dose of 10 mg or water only (control). Blood samples were taken before and up to 4 h after the drug administration. Plasma lafutidine concentrations were determined by high pressure liquid chromatography. Pharmacokinetic analysis of lafutidine was performed using one-compartmental model. The levels of immunoreactive substances of plasma CGRP, somatostatin and gastrin were measured by enzyme immunoassay, and the amount of peptide release was calculated by the trapezoidal method. Lafutidine significantly increased plasma CGRP levels at 1, 1.5, 2.5 and 4 h and the total amount of CGRP release (192 +/- 14.0 pg.h/mL) compared with the control group (128 +/- 21.5 pg.h/mL). Lafutidine significantly increased the plasma somatostatin levels at 1 and 1.5 h, and the total amount of somatostatin released (107 +/- 18.2 pg.h/mL) compared with the control (78.4 +/- 7.70 pg.h/mL). The area under the drug concentration-time curve (AUC) from 0 to 4 h after administration correlated well with the Delta-CGRP and Delta-somatostatin release but not with total amount of gastrin released. However, plasma gastrin levels were significantly elevated at 1.5 h after drug administration. Lafutidine at clinical dosage increases plasma CGRP and the somatostatin. The amounts released correlated with the AUC of lafutidine in humans. These results suggest that the increased release of CGRP and somatostatin may contribute to its gastroprotective and anti-acid secretory effect.

Stimulatory effect of endogenous orexin A on gastric emptying and acid secretion independent of gastrin

Orexin A (OXA) increases food intake and inhibits fasting small bowel motility in rats. The aim of this study was to examine the effect of exogenous OXA and endogenous OXA on gastric emptying, acid secretion, glucose metabolism and distribution of orexin immunoreactivity in the stomach. Rats equipped with a gastric fistula were subjected to intravenous (IV) infusion of OXA or the selective orexin-1 receptor (OX1R) antagonist SB-334867-A during saline or pentagastrin infusion. Gastric emptying was studied with a liquid non-nutrient or nutrient, using 51Cr as radioactive marker. Gastric retention was measured after a 20-min infusion of OXA or SB-334867-A. Plasma concentrations of OXA, insulin, glucagon, glucose and gastrin were studied. Immunohistochemistry against OXA, OX1R and gastrin in gastric tissue was performed. OXA alone had no effect on either acid secretion or gastric emptying. SB-334867-A inhibited both basal and pentagastrin-induced gastric acid secretion and increased gastric retention of the liquid nutrient, but not PEG 4000. Plasma gastrin levels were unchanged by IV OXA or SB-334867-A. Plasma OXA levels decreased after intake of the nutrient meal and infusion of the OX1R antagonist. Only weak effects were seen on plasma glucose and insulin by OXA. Immunoreactivity to OXA and OX1R were found in the mucosa, myenteric cells bodies and varicose nerve fibers in ganglia and circular muscle of the stomach. In conclusion, endogenous OXA influences gastric emptying of a nutrient liquid and gastric acid secretion independent of gastrin. This indicates a role for endogenous OXA, not only in metabolic homeostasis, but also in the pre-absorptive processing of nutrients in the gut.

Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence

Ghrelin, identified in the gastric mucosa, has been involved in the control of food intake and growth hormone (GH) release, but whether this hormone influences the gastric secretion and gastric mucosal integrity has been little elucidated. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without suppression of nitric oxide (NO)-synthase or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by the H2-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. In addition, the gastric mucosal expression of mRNA for CGRP, the most potent neuropeptide released from the sensory afferent nerves, was analyzed in rats exposed to WRS with or without ghrelin pre-treatment. Ghrelin (5-80 microg/kg i.p. or 0.6-5 microg/kg i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS. This protective effect was accompanied by a significant rise in the gastric mucosal blood flow (GBF), luminal NO concentration and plasma ghrelin and gastrin levels. Ghrelin-induced protection was abolished by vagotomy and significantly attenuated by L-NNA and deactivation of afferent nerves with neurotoxic dose of capsaicin. The signal for CGRP mRNA was significantly increased in gastric mucosa exposed to WRS as compared to that in the intact gastric mucosa and this was further enhanced in animals treated with ghrelin. We conclude that central and peripheral ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol or WRS, and these effects depend upon vagal activity and hyperemia mediated by the NOS-NO system and CGRP released from sensory afferent nerves.

Serum Pepsinogen I: An Early Marker of Pernicious Anemia in Patients with Type 1 Diabetes

Pernicious anemia (PA) is an autoimmune organ disease much more common in type 1 diabetic patients (DM1) than in nondiabetic subjects, but it is clinically silent until its end stage. This study aimed to determine biochemical markers of latent PA in a population of DM1 patients attending the endocrinology outpatient clinic of a university hospital. The population studied consisted of 186 unselected patients (32.4 +/- 8.7 yr) and 118 healthy controls (30.9 +/- 9.4 yr). Plasma gastrin and pepsinogen I were determined in patients and controls, whereas hemoglobin A1c, serum cobalamin, hemoglobin, and organ-specific antibodies were determined only in patients. Latent PA was defined as serum pepsinogen I less than 30 microg/liter. In patients with low pepsinogen I concentrations and hypergastrinemia, esophagogastroduodenoscopy (EGD) was performed. DM1 patients showed significantly lower pepsinogen I concentrations (P < 0.001) and higher gastrinemia than controls. Latent PA was present in 12.4% of patients vs. 0.9% of controls. Among patients, more women than men showed low plasma pepsinogen I concentrations (P = 0.002) and thyroperoxidase antibody positivity (P < 0.001). Only the highest parietal cell antibody titers (> or =1:640) identified patients with significantly higher levels of plasma gastrin (P < 0.001) and lower levels of pepsinogen I (P < 0.001). The histopathological EGD findings confirmed different degrees of gastric body mucosa atrophy in all cases. The high prevalence of latent PA found in our DM1 patients leads us to recommend its screening using serum pepsinogen I concentrations. In patients with hypergastrinemia and high parietal cell antibody titers, EGD should be considered to confirm gastric mucosa atrophy.

Importance of the pineal gland, endogenous prostaglandins and sensory nerves in the gastroprotective actions of central and peripheral melatonin against stress‐induced damage

Melatonin attenuates acute gastric lesions induced by topical strong irritants because of scavenging of free radicals, but its role in the pathogenesis of stress-induced gastric lesions has been sparingly investigated. In this study we compared the effects of intragastric (i.g.) or intracerebroventricular (i.c.v.) administration of melatonin and its precursor, L-tryptophan, with or without concurrent treatment with luzindole, a selective antagonist of melatonin MT2 receptors, on gastric lesions induced by water immersion and restraint stress (WRS). The involvement of pineal gland, endogenous prostaglandins (PG) and sensory nerves in gastroprotective action of melatonin and L-tryptophan against WRS was studied in intact or pinealectomized rats or those treated with indomethacin or rofecoxib to suppress cyclooxygenase (COX)-1 and COX-2, respectively, and with capsaicin to induce functional ablation of the sensory nerves. In addition, the influence of i.c.v. and i.g. melatonin on gastric secretion was tested in a separate group of rats equipped with gastric fistulas. At 3.5 hr after the end of WRS, the number of gastric lesions was counted, the gastric blood flow (GBF) was determined by H2-gas clearance technique and plasma melatonin and gastrin levels were measured by specific radioimmunoassay (RIA). Biopsy mucosal samples were taken for determination of expression of mRNA for COX-1 and COX-2 by reverse transcriptase-polymerase chain reaction (RT-PCR) and of the mucosal generation of prostaglandin E2 (PGE2) by RIA. Melatonin applied i.g. (1.25-10 mg/kg) or i.c.v. (1.25-10 microg/kg) dose-dependently inhibited gastric acid secretion and significantly attenuated the WRS-induced gastric damage. This protective effect of melatonin was accompanied by a significant rise in the GBF and plasma melatonin and gastrin levels and in mucosal generation of PGE2. Pinealectomy, which suppressed plasma melatonin levels, aggravated the gastric lesions induced by WRS and these effects were counteracted by i.g. or i.c.v. application of melatonin. Luzindole abolished completely the gastroprotective effects of melatonin and L-tryptophan and attenuated significantly the rise in GBF evoked by the indoleamine and its precursor. Indomethacin and rofecoxib, which diminished PGE2 biosynthesis by c. 90 and 75% or capsaicin denervation, attenuated significantly melatonin- and L-tryptophan-induced protection and the rise in the GBF. Both the protection and the hyperemia were restored by addition of exogenous CGRP to capsaicin-denervated animals. COX-1 mRNA was detected by RT-PCR in the intact and melatonin-treated gastric mucosa, while COX-2 mRNA, which was undetectable in the intact gastric mucosa, appeared in WRS-exposed mucosa, especially in the melatonin-treated animals and this was accompanied by increased generation of PGE2 in gastric mucosa. Pinealectomy downregulated COX-2 mRNA and this effect was reversed by supplementation of pinealectomized animals with melatonin. We conclude that, (a) exogenous melatonin and its precursor, L-tryptophan, attenuates WRS-induced gastric lesions via interaction with MT2 receptors, (b) this protective action of melatonin is because of an enhancement of gastric microcirculation, probably mediated by PGE2 derived from COX-2 overexpression and activity, the activation of brain-gut axis involving CGRP released from sensory nerves, and the release of gastrin and (c) the pineal plays an important role in the limitation of WRS-induced gastric lesions via releasing melatonin, which exerts gastroprotective and hyperemic activities against stress ulcerogenesis.

Massage-like stroking influences plasma levels of gastrointestinal hormones, including insulin, and increases weight gain in male rats

The aim of the present study was to investigate the effects of repeated massage-like stroking on plasma levels of some gastrointestinal hormones, insulin included, glucose and weight gain. For this purpose, male rats were exposed to stroking on the ventral side of the abdomen for 3 or 14 times. The treatments were given every second day. Control rats were picked up at the same time but received no stroking. Body weight was measured regularly. Rats were decapitated 10 min after the last treatment. Hormone levels were radioimmunoassayed and glucose was measured by spectrophotometry. In rats exposed to 3 sessions of massage-like stroking plasma levels of insulin ( p < 0.05) and somatostatin ( p < 0.01) were significantly decreased 10 min after the last treatment. After 14 treatments of massage-like stroking, decreased plasma levels of insulin ( p < 0.01) and gastrin ( p < 0.01) as well as increased glucose levels ( p < 0.01) were observed 10 min after the last treatment. In addition, weight gain was significantly increased (ANOVA p < 0.0001) in rats exposed to 14 treatments. In conclusion, repeated massage-like stroking decreased plasma levels of gastrin, insulin and somatostatin, increased plasma levels of glucose and promoted weight gain. The effects were influenced by the number of treatments.

Helicobacter pylori cag-Type IV Secretion System Facilitates Corpus Colonization to Induce Precancerous Conditions in Mongolian Gerbils

Epidemiological studies suggest that atrophic corpus-dominant gastritis is an increased risk factor for gastric carcinogenesis. The role of the Helicobacter pylori type IV secretion system (T4SS) for pathogenesis in the Mongolian gerbil model was explored. Mongolian gerbils were infected for 32 weeks either with H. pylori type I strain B128 or with isogenic mutant strain B128delta cytotoxin-associated gene (cagY) or B128delta cagA , defective in T4SS or in the production of its effector protein CagA, respectively. Quantitative H. pylori reisolation was performed from the gastric antrum and corpus separately, cytokines were measured by quantitative reverse-transcription polymerase chain reaction, and gastric pH and hormones were determined. B128-infected gerbils harbored high numbers of bacteria in the gastric antrum and corpus, whereas B128delta cagY and B128delta cagA colonized the antrum more densely than the corpus. All infected animals showed a strong antral inflammation and epithelial cell proliferation. B128-infected, rather than mutant-infected, gerbils presented a severe transmural inflammation with huge lymph aggregates, increased proliferation, significant atrophy, and mucous gland metaplasia in the corpus. Plasma gastrin levels and gastric pH values were significantly increased only in B128-infected gerbils. In all infected animals, the expression of the proinflammatory cytokines interleukin 1beta, interferon gamma, and growth-regulated protein was considerably increased in the antrum, but only in wild type-infected animals was an increase seen in the corpus mucosa. The presence of an intact T4SS allows H. pylori to colonize the gastric corpus. This results in atrophic corpus-dominant gastritis, a severe precancerous condition, thus highlighting T4SS and CagA as major risk factors for gastric cancer development.

Gallbladder motility and gut hormone plasma levels in subjects with and without gallstones

Hormonal control of gallbladder motility is still unclear in patients with cholelithiasis. In a case-control study, we determined the characteristics of gallbladder emptying evaluated sonographically and the hormone levels of somatostatin, gastrin, and pancreatic polypeptide, before and after a fatty meal in 10 gallstone patients compared with 20 healthy subjects. Patients with lithiasis had a larger residual volume (median 12,0 ml vs 6,5 ml; P = 0.01) and a lower gallbladder ejection fraction (43% vs 70%, P = 0.02) than healthy subjects. During fasting, plasma pancreatic polypeptide concentrations were significantly higher in lithiasis patients (P < 0.03). In contrast, no differences between the two groups of patients were observed during the post prandial period. Somatostatin and gastrin plasma levels were similar in the two groups. Lastly, the serum bile salt levels were in the normal range and were not different between groups both during fasting and postprandial states. We conclude that large basal plasma concentrations of pancreatic polypeptide, a gut peptide inducing gallbladder relaxation, may constitute a factor facilitating lithogenesis.

Regular use of H2 blockers reduces the efficacy of roxatidine to control gastric pH and volume

H(2) antagonist premedication is common in surgical patients to control gastric pH and volume. However, several reports suggest that long-term medication may produce tolerance. Therefore, we studied the efficacy of a preanesthetic H(2) antagonist (oral roxatidine) in patients on regular H(2) antagonist therapy. Forty-eight patients undergoing elective surgery were studied and grouped according to medication: those on no medication (control group) and those receiving H(2)-antagonists for less than two weeks (< or =2 w group), between two and four weeks (2-4 w group) and for longer than four weeks (> or =4 w group; n =12 each). All patients were given oral roxatidine as anesthetic premedication. Gastric volume and pH were measured after induction of anesthesia. Arterial blood was simultaneously collected for measurement of plasma gastrin levels using an enzyme-linked immunosorbent assay We observed a significant decrease and increase in, respectively, gastric pH and volume (mL) in the < or =2 w group [6.50 +/- 0.43 (NS) and 11.6 +/- 10.3 (NS)], 2-4 w group [4.77 +/- 2.11 (P < 0.01) and 14.1 +/- 10.8 (P < 0.05)], > or =4 w group [2.32 +/- 1.46 (P < 0.01) and 22.2 +/- 14.2 (P < 0.01)] compared to patients in the control group (6.35 +/- 1.32 and 4.9 +/- 4.7). Plasma gastrin levels were decreased with increasing time on medication with a significant difference (46%) observed after two weeks' treatment. In addition, there was a significant correlation between gastric pH and plasma gastrin levels (r = 0.43, P < 0.01). These data suggest that regular H(2) antagonist treatment for longer than two weeks may produce tolerance to pre-anesthetic H(2) antagonist administration.

Influence of gastric colonization with Candida albicans on ulcer healing in rats: Effect of ranitidine, aspirin and probiotic therapy

Objective. Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. Material and methods. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg−1 day−1 s.c.) and 2) aspirin (ASA) (60 mg kg−1 day−1 i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1β and TNF-α and growth factors EGF and TGFα were assessed in the gastric mucosa. Results. Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1β, TNF-α, EGF and TGFα and a significant increment in plasma IL-1β and TNF-α levels. Conclusions. 1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1β and TNFα and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.

Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesionsviaactivation of prostaglandin, nitric oxide and sensory nerve pathways

Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 microg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves.

The Effect of Nichin-to on the Plasma Gut-Regulatory Peptide Level in Healthy Human Subjects

neuropeptides. In this study, we investigated the effects of Nichin-to on the plasma levels of gut-regulated peptides [gastrin, somatostatin, motilin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and substance P] in healthy human subjects. A single oral administration of Nichin-to caused significant (p < 0.05) increases in plasma levels of gastrin-, somatostatin-, VIP-, motilin-, CGRP- and substance P-immunoreactive substance (IS), compared with placebo group. In conclusion, these results might indicate that the pharmacological action of Nichinto is closely related to changes in these peptide levels in human plasma, and we hypothesize that the pharmacological effect of Nichin-to might be due to improvement of digestion, and accelerating the rate of gastric emptying and intestinal propulsion.

Gastrin (g) and enterochromaffin: Like (ecl) cells in the stomach of portocaval-shunted rats: Radioimmunological, immunocytochemical and ultrastructural study

The aim of the study was to monitor the changes observed in the concentration of gastrin, as well as the morphological and ultrastructural properties of pyloric G and fundic ECL cells in rats with a portocaval shunt (PCS). Eight weeks after surgery, plasma and pyloric tissue gastrin concentrations were determined by radioimmunoassay. Sections from pyloric mucosa were immunostained for the identification of G cells, while oxyntic mucosa specimens were processed for Sevier-Munger detection of ECL cells. In addition, ultrastructural properties of G and ECL cells were determined by standard transmission electron microscopy. The results showed that the plasma gastrin levels were unchanged, while the pyloric gastrin concentrations were significantly increased in rats with PCS compared to the control animals (p<0.01). The morphometric analysis showed a significant increase in the cell density of antral G cells (p<0.05) and fundic ECL cells (p<0.01), as well as an increased number of these cells per mm2 of mucosa (p<0.01). In addition the ECL cell profile area was increased in rats with PCS. The predominance of very large vesicles and the reduction of normal cytoplasmic granules and vesicles was a prominent subcellular feature of the ECL. G-cells in PCS rats showed the presence of secretory granules of all types (electron-dense electron-lucent and electron-pale). The number of electron dense granules was elevated. These ultrastructural patterns are compatible with the functional activation of G and ECL cells. The present study suggests that PCS results in hyperplasia of G cells, as well as in both hyperplasia and hypertrophia of ECL cells. It is highly probable that the PCS enchances the sensitivity of the ECL cells to gastrin, thereby enabling them to respond to gastrin in an exaggerated manner.