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Gastrin
Kinds of Gastrin Terms modified by Gastrin Selected AbstractsDevelopments in the inhibition of gastric acid secretionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2005J. Mössner Abstract Understanding the physiology of gastric acid secretion and the pathophysiology of acid-related diseases (e.g. gastrooesophageal reflux and peptic ulcer) has led to the development of numerous ways to decrease acid exposure. Pharmacologically one can try to neutralize secreted acid by antacids, prevent stimulation of the parietal cell, improve mucosal defences and block the functioning of the proton pump. Proton pump inhibitors (PPIs) inhibit the final step of acid secretion, and are currently the most potent acid inhibitors. Major therapeutic improvement within the PPI class appears unlikely, as agents in this class share similar chemistry, mode of action, and pharmacokinetic profiles. New approaches that block acid secretion are now being developed. Gastrin (CCK2) receptor antagonists and potassium-competitive acid blockers (P-CABs) are in clinical development. [source] Effect of Helicobacter pylori Infection on Gastric Acid Secretion and Meal-Stimulated Serum Gastrin in ChildrenHELICOBACTER, Issue 2 2004Seiichi Kato ABSTRACT Background., Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods., Thirty-six children aged 10,17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2,3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication. Results.,H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori- positive patients with duodenal ulcer than in gastritis-only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori- positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre- and post- H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions.,H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection. [source] Gastrin suppresses the interdependent expression of p16 and anion exchanger 1 favoring growth inhibition of gastric cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Hua Tian Abstract Our previous studies demonstrated that expression and interaction of p16 with anion exchanger 1 (AE1) in gastric cancer cells is correlated with progression and shorter survival of the cancer. In this article, the effects of gastrin on p16 and AE1 and its implication in prevention and treatment of gastric cancer were studied by molecular biology techniques, animal experiment and clinical analysis. The results showed that expression of p16 in human gastric body carcinoma was downregulated along with the progression of the cancer, suggesting the reverse correlations between gastrin and p16 in vivo. Further experiments indicated that gastrin suppressed the expression of p16 via the p16 promoter and thereafter resulted in the degradation of AE1 in gastric cancer cells. Silencing of AE1 or p16 significantly inhibited the proliferation of the cancer cells. Using a xenograft tumor model in nude mice, we showed that experimental systemic hypergastrinemia induced by the administration of omeprazole led to decreased expression of AE1 and p16 as well as to a marked growth inhibition of SGC7901 tumors. It is concluded that a moderate plasma gastrin level is beneficial to the growth inhibition of gastric cancer by suppressing the expression of AE1 and p16. This finding may have an important implication for the prevention and treatment of cancers arise in the gastric antrum. [source] The clinical safety of long-term lansoprazole for the maintenance of healed erosive oesophagitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009J. W. FRESTON Summary Background, The clinical safety of long-term lansoprazole therapy for the maintenance of healed erosive oesophagitis has not been extensively studied in clinical trials. Aim, To assess the long-term clinical safety of dose-titrated lansoprazole as maintenance therapy for up to 82 months in subjects with healed erosive oesophagitis. Methods, Clinical safety was assessed by monitoring adverse events (AEs), laboratory data including serum gastrin levels, and endoscopy. Results, Mean duration (± s.d.) of lansoprazole treatment during the titrated open-label period was 56 ± 24 months (range <1,82 months). Overall, 189 of 195 (97%) subjects experienced a total of 2825 treatment-emergent AEs. Most AEs occurred during the first year of treatment, were mild-to-moderate in severity and resolved while on treatment. Of 155 serious AEs (in 74 subjects), only two (colitis and rectal haemorrhage in one subject) were considered treatment-related. Sixty-nine of 195 subjects (35%) experienced 187 treatment-related AEs, with diarrhoea (10%), headache (8%) and abdominal pain (6%) being the most common. Gastrin levels ,400 pg/mL were seen in 9% of subjects; hypergastrinemia was not associated with gastro-intestinal AEs or nodules/polyps. Conclusions, Lansoprazole maintenance therapy for up to 6 years is safe and well tolerated in subjects with healed erosive oesophagitis. [source] Serum gastrin and pepsinogens do not correlate with the different grades of severity of gastro-oesophageal reflux disease: a matched case,control studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2008K. MONKEMULLER Summary Background, Gastrin and pepsinogens reflect the functional state of the gastric mucosa. Aim, To evaluate whether serum gastrin and pepsinogens correlate with the different grades of severity of gastro-oesophageal reflux disease (GERD). Methods, In all, 388 patients with heartburn not taking any form of acid suppressive therapy were matched-controlled for age and gender and sub-classified into four groups: group 1 non-erosive reflux disease (NERD); group 2, erosive reflux disease (ERD) Los Angeles (LA) A and B, group 3, ERD LA C and D; group 4 Barrett's oesophagus (BO). Fasting serum was analysed for gastrin 17, pepsinogen I, pepsinogen II und Helicobacter pylori using specific EIA tests (GastroPanel; Biohit, Plc). Statistics: Kruskal,Wallis test and analysis of variance. Results, There was a significant difference among the four groups with respect for pepsinogen I, but not for pepsinogen II, the pepsinogen I pepsinogen II ratio, H. pylori serology and gastrin levels. Pepsinogen I was the lowest in NERD and the highest in BO (median 91.6, mean ± standard deviation 106.2 ± 51.6 vs. median 114.7, mean ± standard deviation 130.4 ± 70.6; P = 0.046). Pepsinogen I levels were higher in H. pylori positive subjects. After adjusting for H. pylori status, the differences in pepsinogen I across patient groups were no longer statistically significant (P = 0.298). Conclusions, Serum gastrin and pepsinogen I and II do not correlate with the different grades of severity of GERD. The non-invasive GastroPanel is not useful for the differentiation of the various forms of GERD. [source] Gastrin reverses established cholangiocyte proliferation and enhanced secretin-stimulated ductal secretion of BDL rats by activation of apoptosis through increased expression of Ca2+ -dependent PKC isoformsLIVER INTERNATIONAL, Issue 2 2003Shannon Glaser Abstract: We posed these questions: (i) Does administration of gastrin to 1-week bile duct ligation (BDL) rats inhibits established cholangiocyte proliferation and ductal secretion? (ii) Is gastrin inhibition of cholangiocyte proliferation and secretion of BDL rats associated with enhanced apoptosis? (iii) Are gastrin's effects on cholangiocyte function associated with increased expression of protein kinase C (PKC) isoforms; and (iv) Is gastrin stimulation of cholangiocyte apoptosis regulated by the Ca2+ -dependent PKC pathway? Methods: Seven days after BDL, rats were treated with gastrin by minipumps for 14 days. Cholangiocyte proliferation was assessed by measurement of the number of PCNA and CK-19 positive cholangiocytes in sections, and PCNA expression in cholangiocytes. Ductal secretion was determined by measurement of secretin-induced cAMP levels and choleresis. Apoptosis was evaluated by TUNEL analysis in sections and annexin-V staining in cholangiocytes. The expression of PKC isoforms was determined by immunoblots. Results: Gastrin inhibits established cholangiocyte proliferation and enhanced secretin-stimulated ductal secretion of BDL rats. Gastrin's effects on cholangiocyte function were associated with enhanced apoptosis and increased expression of PKC alpha, and beta I and II. Gastrin increases in cholangiocyte apoptosis were blocked by BAPTA/AM and H7. Summary/conclusion: Gastrin inhibits cholangiocyte proliferation and secretin-induced ductal secretion in BDL rats by increasing apoptosis through a PKC-mediated mechanism. [source] Effect of Smoking on Serum Pepsinogen I Level Depends on Serological Status of Helicobacter pyloriCANCER SCIENCE, Issue 3 2001Masayuki Tatemichi Serum pepsinogen (sPG) levels are used in gastric cancer screening programs. However, modification of sPG levels by smoking habit, according to the status of Helicobacter pylori (H. pylori) infection has been little investigated. This study investigated the effects of smoking on serum levels of pepsinogen I (PG I), pepsinogen II (PG II), and gastrin by IgG titer of antibody against H. pylori (Hp-IgG titer) using the data from 356 current-smokers and 262 non-smokers (133 never-smokers and 129 ex-smokers) in a cross-sectional study of 618 men aged 40 to 49 years. PG I, PG II, PG I/PG II ratio and gastrin were significantly associated with Hp-IgG titer in never-smokers [Spearman's correlation coefficient (95% confidence interval): 0.23 (0.07, 0.39), 0.52 (0.41, 0.63), -0.40 (-0.54, -0.27), and 0.25 (0.10, 0.41), respectively]. However, the correlation coefficients of PG I and PG H decreased in current-smokers, 0.02 (-0.1, 0.13) and 0.32 (0.22, 0.42), respectively. In H. pylori seronegative and low titer cases, the mean PG I level was significantly (P<0.01) higher in current-smokers, compared with non-smokers. However, in high titer cases, the mean PG I level was lower in current-smokers. Mean PG II and gastrin levels, and PG I/PG II ratio did not differ according to smoking habits by Hp-IgG titer. The gastrin level was significantly correlated with PG H, but not PG I. These data indicate that current smoking influences the serum PG I level depending on Hp-IgG titer and the associations between sPGs and Hp-IgG titer. Gastrin is not involved in the modification of PG I levels by smoking. [source] Different effects of electroacupuncture on esophageal motility and serum hormones in cats with esophagitisDISEASES OF THE ESOPHAGUS, Issue 2 2008X. Shuai SUMMARY., We aim to investigate the effects of different electroacupuncture (EA) frequencies at ST-36 on esophageal motility, and to compare the effect of EA on serum gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP). Thirty-two cats were divided into four equal groups. All animals underwent a Heller myotomy. After esophagitis developed two frequencies (2/15 Hz or 2/100 Hz) of EA were delivered into ST-36 (LEA group [low EA], HEA group [high EA]). Animals submitted to EA on a non-point region (EANP) were used as controls (LEANP group, HEANP group), respectively. Esophageal motility was continuously monitored. The lower esophageal sphincter pressure (LESP) decreased significantly after myotomy. The LESP decreased in both LEA and LEANP cats, and in LEA cats the pressure decrease was greater. The LESP increased in the HEA group, which was higher than that in the HEANP group (P < 0.05). High-frequency EA significantly increased the peak amplitude in esophageal peristalsis. There was a decrease in serum GAS and MTL in LEA cats compared with LEANP cats (both P < 0.01). GAS and MTL were higher in the HEA group than in the HEANP group (both P < 0.01). Serum VIP decreased in the HEA group (P < 0.05), while it increased in the LEA group (P < 0.05), compared with EANP groups, respectively. EA with a high frequency at ST-36 enhances LESP as well as esophageal motility, while EA with a low frequency decreases LESP. The effect of EA is acupoint-specific, and this effect appears to be mediated through GAS, MTL and VIP. [source] Attack and defence in the gastric epithelium , a delicate balanceEXPERIMENTAL PHYSIOLOGY, Issue 4 2007Rod Dimaline The gastric epithelium is a complex structure formed into tubular branched gastric glands. The glands contain a wide variety of cell types concerned with the secretion of hydrochloric acid, proteases, mucus and a range of signalling molecules. All cell types originate from stem cells in the neck region of the gland, before migrating and differentiating to assume their characteristic positions and functions. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium, in the face of a hostile luminal environment. The first such mediator to be recognized, the hormone gastrin, was identified over a century ago and is now established as the major physiological stimulant of gastric acid secretion. Recent studies, including those using mice that overexpress or lack the gastrin gene, suggest a number of previously unrecognized roles for this hormone in the regulation of cellular proliferation, migration and differentiation. This review focuses on the identification of hitherto unsuspected gastrin-regulated genes and discusses the paracrine cascades that contribute to the maintenance of gastric epithelial architecture and secretory function. Helicobacter infection is also considered in cases where it shares targets and signalling mechanisms with gastrin. [source] Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitroFEBS JOURNAL, Issue 17 2009Suzana Kovac Transferrin is the main iron transport protein found in the circulation, and the level of transferrin saturation in the blood is an important indicator of iron status. The peptides amidated gastrin(17) (Gamide) and glycine-extended gastrin(17) (Ggly) are well known for their roles in controlling acid secretion and as growth factors in the gastrointestinal tract. Several lines of evidence, including the facts that transferrin binds gastrin, that gastrins bind ferric ions, and that the level of expression of gastrins positively correlates with transferrin saturation, suggest the possible involvement of the transferrin,gastrin interaction in iron homeostasis. In the present work, the interaction between gastrins and transferrin has been characterized by surface plasmon resonance and covalent crosslinking. First, an interaction between iron-free apo-transferrin and Gamide or Ggly was observed. The fact that no interaction was observed in the presence of the chelator EDTA suggested that the gastrin,ferric ion complex was the interacting species. Moreover, removal of ferric ions with EDTA reduced the stability of the complex between apo-transferrin and gastrins, and no interaction was observed between Gamide or Ggly and diferric transferrin. Second, some or all of glutamates at positions 8,10 of the Ggly molecule, together with the C-terminal domain, were necessary for the interaction with apo-transferrin. Third, monoferric transferrin mutants incapable of binding iron in either the N-terminal or C-terminal lobe still bound Ggly. These findings are consistent with the hypothesis that gastrin peptides bind to nonligand residues within the open cleft in each lobe of transferrin and are involved in iron loading of transferrin in vivo. Structured digital abstract ,,MINT-7212832, MINT-7212849: Apo-transferrin (uniprotkb:P02787) and Gamide (uniprotkb:P01350) bind (MI:0407) by surface plasmon resonance (MI:0107) ,,MINT-7212881, MINT-7212909: Ggly (uniprotkb:P01350) and Apo-transferrin (uniprotkb:P02787) bind (MI:0407) by cross-linking studies (MI:0030) ,,MINT-7212864: Apo-transferrin (uniprotkb:P02787) and Ggly (uniprotkb:P01350) bind (MI:0407) by competition binding (MI:0405) [source] Polyamines interact with DNA as molecular aggregatesFEBS JOURNAL, Issue 17 2002Luciano D'Agostino New compounds, named nuclear aggregates of polyamines, having a molecular mass of 8000, 4800 and <,1000 Da, were found in the nuclear extracts of several replicating cells. Their molecular structure is based on the formation of ionic bonds between polyamine ammonium and phosphate groups. The production of the 4800 Da compound, resulting from the aggregation of five or more <,1000 Da units, was increased in Caco-2 cells treated with the mitogen gastrin. Dissolving single polyamines in phosphate buffer resulted in the in vitro aggregation of polyamines with the formation of compounds with molecular masses identical to those of natural aggregates. After the interaction of the 4800 Da molecular aggregate with the genomic DNA at 37 °C, both the absorbance of DNA in phosphate buffer and the DNA mobility in agarose gel increased greatly. Furthermore, these compounds were able to protect the genomic DNA from digestion by DNase I, a phosphodiesterasic endonuclease. Our data indicate that the nuclear aggregate of polyamines interacts with DNA phosphate groups and influence, more efficaciously than single polyamines, both the conformation and the protection of the DNA. [source] Serum Levels of Leptin As Marker For Patients At High Risk of Gastric CancerHELICOBACTER, Issue 6 2009Lisette G. Capelle Abstract Background:, Serological screening for gastric cancer (GC) may reduce mortality. However, optimal serum markers for advanced gastric precursor lesions are lacking. Aim:, To evaluate in a case,control study whether serum leptin levels correlate with intestinal metaplasia (IM) and can serve as a tool to identify patients at high risk for GC. Materials and Methods:, Cases were patients with a previous diagnosis of IM or dysplasia, controls were patients without such a diagnosis. All patients underwent endoscopy. Fasting serum was collected for the measurement of leptin, pepsinogens I/II, gastrin, and Helicobacter pylori. Receiver operating characteristic (ROC) curves and their area under the curve (AUC) were provided to compare serum leptin levels with other serological markers. Results:, One hundred nineteen cases and 98 controls were included. In cases, the median leptin levels were 116.6 pg/mL versus 81.9 pg/mL in controls (p = .01). After adjustment for age, sex and BMI, leptin levels remained higher in cases than in controls (p < .005). In multivariate analysis, male sex (p = .002), age (<0.001), low pepsinogen levels (p = .004) and high leptin levels (p = .04) were independent markers for the presence of IM. In addition, a ROC curve including age, sex and pepsinogen I levels had an AUC of 0.79 (95% CI (0.73,0.85)). Adding serum leptin levels increased the AUC to 0.81 (95% CI (0.75,0.86)). Conclusions:, High leptin levels are associated with an increased risk of IM. Moreover, serum leptin levels are a significant independent marker for the presence of IM. However, in combination with the serological test for pepsinogen I the additional value of serum leptin levels is rather limited. [source] Gastric Acidity in Patients with Follicular Gastritis is Significantly Reduced, but Can be Normalized After Eradication for Helicobacter pyloriHELICOBACTER, Issue 3 2005Tomohiko Shimatani ABSTRACT Background., Follicular gastritis is thought to be caused by Helicobacter pylori infection. However, the pathophysiology of it remains unclear. Materials and methods., We assessed gastric acidity in 15 patients with follicular gastritis, aged 20,37 years, using a 24-hour intragastric pH-metry, as well as by histologic and serologic evaluations; and compared it with that in other age-matched groups: 18 cases of H. pylori -positive antrum-predominant gastritis, 12 of pangastritis, and 24 H. pylori -negative normals. In eight cases with follicular gastritis, it was re-assessed 6 months after the eradication therapy for H. pylori. Results., During nighttime, the percentage of time with intragastric pH above 3.0 in follicular gastritis was significantly higher than that in normals (p < .0001), and in antrum-predominant gastritis (p < .001), but was comparable with that in pangastritis. In the daytime period, this parameter in follicular gastritis was significantly higher than that in normal (p < .001), in antrum-predominant gastritis (p < .001), and in pangastritis (p < .05). Marked mononuclear cell and neutrophil infiltration but no apparent glandular atrophy were observed in both the antrum and corpus. Serum pepsinogen I/II ratio was significantly lower in follicular gastritis than that in normals (p < .0001) and in antrum-predominant gastritis (p < .001), whereas serum gastrin was significantly higher than that in normals (p < .0001), in antrum-predominant gastritis (p < .01) and in pangastritis (p < .05). After eradication for H. pylori, all of the parameters in follicular gastritis were altered to the same ranges as those in normals. Conclusions., In follicular gastritis, gastric acidity is significantly reduced, but can be normalized by eradication of H. pylori. It can thus be speculated that inflammatory cytokines or H. pylori -infection,induced prostaglandins might strongly inhibit gastric acid secretion in follicular gastritis. [source] Effect of Helicobacter pylori Infection on Gastric Acid Secretion and Meal-Stimulated Serum Gastrin in ChildrenHELICOBACTER, Issue 2 2004Seiichi Kato ABSTRACT Background., Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods., Thirty-six children aged 10,17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2,3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication. Results.,H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori- positive patients with duodenal ulcer than in gastritis-only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori- positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre- and post- H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions.,H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection. [source] Helicobacter pylori Infection and Gastric Autoimmune Diseases: Is There a Link?HELICOBACTER, Issue 6 2003Fabio Presotto ABSTRACT Background.,Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity. Patients and Methods., We studied 79 consecutive asymptomatic subjects with parietal cell antibodies, 24 patients with pernicious anemia, and 66 parietal cell antibody-negative controls. All patients underwent gastric biopsies for histology and detection of H. pylori. Red blood cell count and volume, serum levels of gastrin, pepsinogen I, iron, folic acid, vitamin B12, and circulating antibodies to H. pylori and to intrinsic factor were also determined. Results., We found an atrophic body gastritis in 14 of the 79 asymptomatic subjects with parietal cell antibodies (18%) and in 2 of the 66 controls (3%) (p = .01). Mean levels of gastrin were increased (p < .0001), while those of pepsinogen were reduced (p < .001) compared with controls. H. pylori was identified at the gastric level and/or circulating anti- H. pylori antibodies were detected in 46 parietal cell antibody-positive subjects (58%) compared with 26 controls (39%) (p = .03). In patients with pernicious anemia we found an atrophic body gastritis in 18 of 24 cases (75%) (p < .001 vs. controls). Mean levels of gastrin were markedly increased (p < .0001) and those of pepsinogen I decreased (p < .0001) relative to controls. Only five of these patients (21%) had evidence of H. pylori infection compared with 46 of the parietal cell antibody-positive subjects (58%) (p = .003) and 26 of the controls (39%). Considering all patients with gastric autoimmunity (i.e. with parietal cell antibodies and/or with pernicious anemia), H. pylori was found in 44 of 72 of those without atrophy (61%) but in 6 of 31 with gastric body atrophy (19%) (p < .001), indicating that H. pylori infection is greatly reduced when gastric acid secretion decreases. Conclusions., The frequent detection of H. pylori infection in subjects with early gastric autoimmunity, indicated by the presence of parietal cell antibodies, suggests that H. pylori could have a crucial role in the induction and/or the maintenance of autoimmunity at the gastric level. [source] Helicobacter pylori Infection Increases Serum Nitrate and Nitrite More Prominently Than Serum PepsinogensHELICOBACTER, Issue 1 2002Kanji Kodama Abstract Background.Helicobacter pylori infection causes chronic gastritis and results in increased serum concentrations of pepsinogens I and II as well as gastrin, while the ratio of pepsinogen I to II (I : II) is decreased. Inducible nitric oxide synthase (iNOS) is induced in H. pylori -associated gastritis and may modulate inflammation. However serum nitrate and nitrite (NOx) concentrations in patients with H. pylori -induced chronic gastritis have not been reported. We examined differences in serum NOx between H. pylori -negative and positive volunteers relative to differences in pepsinogens and gastrin. Materials and methods. Sera from 80 healthy asymptomatic volunteers younger than 36 years were analyzed for anti- H. pylori antibody, NOx, gastrin and pepsinogens. Results. In H. pylori antibody-positive subjects serum NOx concentrations were higher than in negative subjects (p < .005). In H. pylori -negative subjects, NOx correlated with pepsinogen II (r = .405, p < .05). In subjects with low pepsinogen I or II, NOx was higher in H. pylori -positive than negative subjects (p < .001). In subjects with high pepsinogen I : II (6 or higher), serum NOx was higher in H. pylori -positive than in negative subjects. Conclusions.H. pylori -induced gastritis increases serum NOx concentrations more prominently than those of pepsinogen. In H. pylori -negative subjects, serum correlates with serum pepsinogen II. [source] Helicobacter pylori Infection in the Cat: Evaluation of Gastric Colonization, Inflammation and FunctionHELICOBACTER, Issue 1 2001Kenneth W. Simpson Background. Further elucidation of the consequences of Helicobacter pylori infection on gastric mucosal inflammation and gastric secretory function would be facilitated by an animal model that is susceptible to infection with H. pylori, is broadly similar in gastric physiology and pathology to people, and is amenable to repeated non-invasive evaluation. The goal of this study was to examine the interrelationship of bacterial colonization, mucosal inflammation and gastric secretory function in cats with naturally acquired H. pylori infection. Materials and Methods. Twenty clinically healthy cats with naturally acquired H. pylori infection (cagA,, picB) and 19 Helicobacter -free cats were evaluated. Gastric colonization was determined by tissue urease activity, light microscopy, culture and PCR. The mucosal inflammatory response was evaluated by light microscopy, and by RT-PCR of the pro-inflammatory cytokines IL-1,, IL-1,, IL-8 and TNF-, in gastric mucosa. Gastric secretory function was assessed by measuring pentagastrin-stimulated acid secretion, fasting plasma gastrin, and antral mucosal gastrin and somatostatin immunoreactivity. Results. H. pylori colonized the pylorus, fundus and cardia in similar density. Bacteria were observed free in the lumen of gastric glands and were also tightly adherent to epithelial cells where they were associated with microvillus effacement. Mononuclear inflammation, lymphoid follicle hyperplasia, atrophy and fibrosis were observed primarily in H. pylori -infected cats, with the pylorus most severely affected. Neutrophilic and eosinophilic infiltrates, epithelial dysplasia, and up-regulation of mucosal IL-1, and IL-8 were observed solely in infected cats. Fasting plasma gastrin concentrations and pentagastrin-stimulated acid output were similar in both infected and uninfected cats. There was no relationship of bacterial colonization density or gastric inflammation to plasma gastrin concentrations or gastric acid output. Conclusions. The pattern of colonization and the mucosal inflammatory response in cats with naturally acquired H. pylori are broadly similar to those in infected people, particularly children, and non-human primates. The upregulation of IL-8 in infected cats was independent of cagA and picB. Our findings argue against a direct acid-suppressing effect of H. pylori on the gastric secretory-axis in chronically infected cats. Abbreviations: RT-PCR, reverse transcriptase polymerase chain reaction, HLO; Helicobacter -like organisms. [source] Negative Association Between Helicobacter pylori Infection and Reflux Esophagitis in Older Patients: Case-Control Study in JapanHELICOBACTER, Issue 1 2000Ken Haruma Background. Recent studies have clarified a close association between H. pylori infection and gastritis, peptic ulcer disease, and gastric cancer, but there is little information concerning the relationship between H. pylori infection and reflux esophagitis (RE). We investigated the relationship between H. pylori, RE, and corpus gastritis. Subjects and Methods. Ninety-five patients with RE and 190 sex- and age-matched asymptomatic healthy controls demonstrating no localized lesions in the upper GI tract were studied and evaluated for H. pylori infection, histologic gastritis, serum gastrin, and pepsinogens (PGs). Results.H. pylori infection was significantly lower in RE patients than in asymptomatic controls (41% vs. 76%, p < .01). Histologic gastritis of both the antrum and corpus was significantly less frequent (antrum; p < .01, corpus; p < .01), and serum levels of PGI and the PG I/II ratio were significantly higher in RE patients than in controls (PGI; p < .05, PG I/II ratio; p < .01). When the subjects were divided into two age groups (59 years of age and younger and 60 years of age and older), a significant difference was found only among patients over 60 years of age (29% vs. 85%, p < .01). Among subjects in this age group, gastritis in both the antrum and corpus were significantly milder in RE patients than in controls. Although the prevalence of H. pylori infection was similar between the two groups of patients under 59 years of age, corpus gastritis was significantly milder in patients than in controls (p < .05). Conclusions. A significantly low prevalence of H. pylori infection was found in RE patients over 60 years of age but not in those under 59 in comparison with sex- and age-matched controls. The relative lack of corpus gastritis might play a role in the pathogenesis of RE in our population through preservation of the acid secretion area. [source] Gastrin suppresses the interdependent expression of p16 and anion exchanger 1 favoring growth inhibition of gastric cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Hua Tian Abstract Our previous studies demonstrated that expression and interaction of p16 with anion exchanger 1 (AE1) in gastric cancer cells is correlated with progression and shorter survival of the cancer. In this article, the effects of gastrin on p16 and AE1 and its implication in prevention and treatment of gastric cancer were studied by molecular biology techniques, animal experiment and clinical analysis. The results showed that expression of p16 in human gastric body carcinoma was downregulated along with the progression of the cancer, suggesting the reverse correlations between gastrin and p16 in vivo. Further experiments indicated that gastrin suppressed the expression of p16 via the p16 promoter and thereafter resulted in the degradation of AE1 in gastric cancer cells. Silencing of AE1 or p16 significantly inhibited the proliferation of the cancer cells. Using a xenograft tumor model in nude mice, we showed that experimental systemic hypergastrinemia induced by the administration of omeprazole led to decreased expression of AE1 and p16 as well as to a marked growth inhibition of SGC7901 tumors. It is concluded that a moderate plasma gastrin level is beneficial to the growth inhibition of gastric cancer by suppressing the expression of AE1 and p16. This finding may have an important implication for the prevention and treatment of cancers arise in the gastric antrum. [source] Transgenic expression of CCK2 receptors sensitizes murine pancreatic acinar cells to carcinogen-induced preneoplastic lesions formationINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Anne Mathieu Abstract In humans, initial events of pancreatic carcinogenesis remain unknown, and the question of whether this cancer, which has a ductal phenotype, exclusively arises from duct cells has been raised. Previous studies have demonstrated that transgenic expression of the CCK2 receptor in acinar cells of ElasCCK2 mice plays a role in the development of pancreatic neoplasia. The aim of our study was to examine initial steps of carcinogenesis in ElasCCK2 mice, adding a supplementary defect by using a chemical carcinogen, azaserine. Results of posttreatment sequential immunohistochemical examinations and quantifications demonstrate that mice responded to azaserine. Transition of acinar cells into duct-like cells expressing Pdx1 and gastrin, as well as proliferation of acinar cells, were transiently observed in both transgenic and control mice. The carcinogen also induced formation of preneoplastic lesions, adenomas, exhibiting properties of autonomous growth. Importantly, expression of the CCK2 receptor increased the susceptibility of pancreas to azaserine. Indeed, treated ElasCCK2 mice exhibited larger areas of pancreatic acinar-ductal transition, increased cellular proliferation as well as larger adenomas areas vs. control mice. These amplified responses may be related to auto/paracrine stimulation of CCK2 receptor by gastrin expressed in newly formed duct-like cells. Our results demonstrate that activation of CCK2 receptor and azaserine result in cumulative effects to favor the emergence of a risk situation that is a potential site for initiation of carcinogenesis. © 2005 Wiley-Liss, Inc. [source] Factors affecting the serum gastrin 17 level: an evidence-based analysis of 3906 serum samples among ChineseJOURNAL OF DIGESTIVE DISEASES, Issue 2 2007Zhong ZHANG OBJECTIVE: To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum gastrin-17 level and to study the diagnostic value of serum gastrin-17 in gastric precancerous lesions and gastric cancer. METHODS: Serum gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology. RESULTS: Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum gastrin-17 level was markedly higher in people ,60 years old than that in younger age groups. The serum gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum gastrin-17 level was higher in the H. pylori -positive group than in the H. pylori -negative group. CONCLUSIONS: In people over 60 years of age, the serum gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum gastrin-17 level, whereas H. pylori infection is usually associated with its increment. [source] Vitamin C inhibits corpus gastritis in Helicobacter pylori -infected patients during acid-suppressive therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2001Masahiro Yoshinaga Abstract Background: Previous studies have shown that gastric acid suppression worsens corpus gastritis in Helicobacter pylori (H. pylori) -positive patients. We evaluated the effect of acid-suppressive therapy and vitamin C on H. pylori -associated gastritis. Methods: Forty patients with reflux esophagitis were divided into three groups by the status of H. pylori and therapy: group A (n = 15), H. pylori (+) and omeprazole 20 mg; group B (n = 15), H. pylori (+) and omeprazole 20 mg + vitamin C 1200 mg; and group C (n = 10), H. pylori (,) and omeprazole 20 mg. In all three groups, the mucosal interleukin (IL)-8 contents, H. pylori colonization density, neutrophil infiltration in the corpus, and serum gastrin were evaluated at entry and 2 weeks after starting therapy; in group B, serum vitamin C levels were also measured. Results: In group A, the IL-8 contents and the degree of neutrophil infiltration during therapy exceeded those at entry, whereas in groups B and C, these values did not change significantly with treatment. Helicobacter pylori colonization density during therapy was similar to that at entry in all three groups. The serum gastrin (in all groups) and vitamin C levels (in group B) during therapy exceeded those at entry. Conclusions: Potent acid suppression worsens H. pylori -associated corpus gastritis, although such worsening gastritis may be inhibited by vitamin C. [source] Clinical application of an enzyme immunoassay for cholecystokinin-like immunoreactive substance for determination of the human plasma levels: the effect of metoclopramide on gastrointestinal peptides and stress-related hormonesJOURNAL OF PEPTIDE SCIENCE, Issue 5 2006Fumihiko Katagiri Abstract Metoclopramide, a prokinetic drug, is widely used to treat vomiting and nausea. Delayed gastric emptying and continual stress are considered important factors, among others, that induce nausea and vomiting. One gastrointestinal motility regulatory factor has been assumed to be the induction of changes in the levels of peptides such as gastrin, somatostatin, motilin, and cholecystokinin (CCK) in plasma. In contrast, adrenocorticotropic hormone (ACTH) and cortisol are used as indicators of stress. Here, we studied the effects of metoclopramide on human plasma gastrin-, somatostatin-, motilin-, and CCK-like immunoreactive substances (ISs) and ACTH-IS and cortisol under stress conditions using repetitive blood sampling in healthy subjects. Metoclopramide hydrochloride at a dose of 30 mg or placebo was orally administered to five healthy male volunteers. Blood samples were taken before and 20, 40, 60, 90, 120, 180, and 240 min after administration, subject to extracting procedures, and submitted to a highly sensitive enzyme immunoassay system. A single administration of metoclopramide caused significant increases in plasma somatostatin-IS levels compared with the placebo. Metoclopramide significantly decreased plasma gastrin- and suppressed ACTH-IS and cortisol levels compared with the placebo. We hypothesize that metoclopramide might have an accelerating gastric-emptying effect and a modulatory effect on the hypothalamo-pituitary-adrenal (HPA) axis and the autonomic nervous function. These effects might be beneficial in stress-related diseases, which suggest that this medicine has clinicopharmacological activities. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Role of melatonin in mucosal gastroprotection against aspirin-induced gastric lesions in humansJOURNAL OF PINEAL RESEARCH, Issue 4 2010P. C. Konturek Abstract:, Melatonin and its precursor, l -tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l -tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E2, and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA-induced gastric lesions and microbleeding. Gastric mucosal generation of PGE2 was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan. [source] Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experienceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009D. A. PEURA Summary Background, Dexlansoprazole MR is a dual delayed release formulation of dexlansoprazole, an enantiomer of lansoprazole. Aim, To assess safety of dexlansoprazole MR in phase 3 clinical trials. Methods, Data from 4270 patients receiving dexlansoprazole MR 30 mg (n = 455), 60 mg (n = 2311) or 90 mg (n = 1864); lansoprazole 30 mg (n = 1363); or placebo (n = 896) in six randomized controlled trials and a 12-month safety study were pooled. Safety was assessed via adverse events, vital signs, electrocardiograms, clinical laboratory results and gastric biopsies. Adverse events were summarized per 100 patient-months of exposure to account for imbalances in study drug exposure. Results, The number of patients with ,1 treatment-emergent adverse event per 100 patient-months was higher in placebo (24.49) and lansoprazole (21.06) groups than in any dexlansoprazole MR (15.64,18.75) group. Fewer patients receiving dexlansoprazole MR discontinued therapy because of an adverse event (P , 0.05 vs. placebo). Seven patients died of events considered unrelated to study drug. Mean serum gastrin rose in all groups except placebo; increases were not dose-related. No clinically concerning trends were seen in gastric biopsy results. Endocrine cell hyperplasia, dysplasia and neoplasia were not observed. Conclusion, Dexlansoprazole MR 30,90 mg has a safety profile comparable to that of lansoprazole. [source] The clinical safety of long-term lansoprazole for the maintenance of healed erosive oesophagitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009J. W. FRESTON Summary Background, The clinical safety of long-term lansoprazole therapy for the maintenance of healed erosive oesophagitis has not been extensively studied in clinical trials. Aim, To assess the long-term clinical safety of dose-titrated lansoprazole as maintenance therapy for up to 82 months in subjects with healed erosive oesophagitis. Methods, Clinical safety was assessed by monitoring adverse events (AEs), laboratory data including serum gastrin levels, and endoscopy. Results, Mean duration (± s.d.) of lansoprazole treatment during the titrated open-label period was 56 ± 24 months (range <1,82 months). Overall, 189 of 195 (97%) subjects experienced a total of 2825 treatment-emergent AEs. Most AEs occurred during the first year of treatment, were mild-to-moderate in severity and resolved while on treatment. Of 155 serious AEs (in 74 subjects), only two (colitis and rectal haemorrhage in one subject) were considered treatment-related. Sixty-nine of 195 subjects (35%) experienced 187 treatment-related AEs, with diarrhoea (10%), headache (8%) and abdominal pain (6%) being the most common. Gastrin levels ,400 pg/mL were seen in 9% of subjects; hypergastrinemia was not associated with gastro-intestinal AEs or nodules/polyps. Conclusions, Lansoprazole maintenance therapy for up to 6 years is safe and well tolerated in subjects with healed erosive oesophagitis. [source] Serum gastrin and pepsinogens do not correlate with the different grades of severity of gastro-oesophageal reflux disease: a matched case,control studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2008K. MONKEMULLER Summary Background, Gastrin and pepsinogens reflect the functional state of the gastric mucosa. Aim, To evaluate whether serum gastrin and pepsinogens correlate with the different grades of severity of gastro-oesophageal reflux disease (GERD). Methods, In all, 388 patients with heartburn not taking any form of acid suppressive therapy were matched-controlled for age and gender and sub-classified into four groups: group 1 non-erosive reflux disease (NERD); group 2, erosive reflux disease (ERD) Los Angeles (LA) A and B, group 3, ERD LA C and D; group 4 Barrett's oesophagus (BO). Fasting serum was analysed for gastrin 17, pepsinogen I, pepsinogen II und Helicobacter pylori using specific EIA tests (GastroPanel; Biohit, Plc). Statistics: Kruskal,Wallis test and analysis of variance. Results, There was a significant difference among the four groups with respect for pepsinogen I, but not for pepsinogen II, the pepsinogen I pepsinogen II ratio, H. pylori serology and gastrin levels. Pepsinogen I was the lowest in NERD and the highest in BO (median 91.6, mean ± standard deviation 106.2 ± 51.6 vs. median 114.7, mean ± standard deviation 130.4 ± 70.6; P = 0.046). Pepsinogen I levels were higher in H. pylori positive subjects. After adjusting for H. pylori status, the differences in pepsinogen I across patient groups were no longer statistically significant (P = 0.298). Conclusions, Serum gastrin and pepsinogen I and II do not correlate with the different grades of severity of GERD. The non-invasive GastroPanel is not useful for the differentiation of the various forms of GERD. [source] Review article: From gastrin to gastro-oesophageal reflux disease , a century of acid suppressionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2006P. MALFERTHEINER Summary To commemorate Edkins' discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro-oesophageal reflux disease. Although initially ignored, Edkins' observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori. Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non-steroidal anti-inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid-suppressive agents. The major issue for the future resides within the epidemic of gastro-oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century. [source] Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-upALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2005M. Ito Summary Background :,It is controversial as to whether the development of gastric cancer is influenced by Helicobacter pylori eradication. If eradication itself influences the tumour morphology, this may affect the tumour discovery rate. Aim :,To investigate the morphological changes in the gastric neoplasm after H. pylori eradication. Methods :,We studied 37 patients with eradication therapy. After a 1-month follow-up, endoscopic re-evaluation was performed and the appearance was compared with first image. All lesions were resected endoscopically, and were subjected to histological assessment and to immunohistochemistry. Serum gastrin levels were determined before and after eradication. Results :,Twenty-nine of 37 patients underwent successful eradication. The appearance of 11 lesions (33% of 33 lesions) became indistinct after successful eradication. All lesions were of the superficial-elevated type and the height of the lesions decreased. We detected normal columnar epithelium over the neoplasm in eight of the lesions. Higher expression of single-stranded deoxyribonucleic acid in the deep area was characteristic in tumours with an indistinct appearance. These changes did not correlate with the serum gastrin levels. Conclusions :,The morphology of the gastric neoplasm change after eradication in the short-term. This may contribute to the decreased tumour discovery rate. [source] Gastrin reverses established cholangiocyte proliferation and enhanced secretin-stimulated ductal secretion of BDL rats by activation of apoptosis through increased expression of Ca2+ -dependent PKC isoformsLIVER INTERNATIONAL, Issue 2 2003Shannon Glaser Abstract: We posed these questions: (i) Does administration of gastrin to 1-week bile duct ligation (BDL) rats inhibits established cholangiocyte proliferation and ductal secretion? (ii) Is gastrin inhibition of cholangiocyte proliferation and secretion of BDL rats associated with enhanced apoptosis? (iii) Are gastrin's effects on cholangiocyte function associated with increased expression of protein kinase C (PKC) isoforms; and (iv) Is gastrin stimulation of cholangiocyte apoptosis regulated by the Ca2+ -dependent PKC pathway? Methods: Seven days after BDL, rats were treated with gastrin by minipumps for 14 days. Cholangiocyte proliferation was assessed by measurement of the number of PCNA and CK-19 positive cholangiocytes in sections, and PCNA expression in cholangiocytes. Ductal secretion was determined by measurement of secretin-induced cAMP levels and choleresis. Apoptosis was evaluated by TUNEL analysis in sections and annexin-V staining in cholangiocytes. The expression of PKC isoforms was determined by immunoblots. Results: Gastrin inhibits established cholangiocyte proliferation and enhanced secretin-stimulated ductal secretion of BDL rats. Gastrin's effects on cholangiocyte function were associated with enhanced apoptosis and increased expression of PKC alpha, and beta I and II. Gastrin increases in cholangiocyte apoptosis were blocked by BAPTA/AM and H7. Summary/conclusion: Gastrin inhibits cholangiocyte proliferation and secretin-induced ductal secretion in BDL rats by increasing apoptosis through a PKC-mediated mechanism. [source] | |||||||||||||||||||||||||||||||||||||