Correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease.

Oesophageal acidification induces dyspeptic symptoms in healthy individuals. This study aimed to evaluate the correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease. METHODS: A total of 68 patients with dominant symptoms of heartburn, negative upper gastrointestinal endoscopy and concomitant dyspeptic symptoms participated in the study. The severity of dyspepsia and reflux-related symptoms was evaluated, and 24-h gastro-oesophageal pH-monitoring study was performed in all patients at baseline and after 4 weeks of therapy with esomeprazole 40 mg. RESULTS: Oesophageal basal acid exposure was pathological in 43 patients and normal in 25 patients, with a similar prevalence and severity of individual dyspeptic symptoms in the two groups. A significant correlation between reflux and dyspepsia scores was observed in the subgroup of patients with normal, but not in those with abnormal pHmetry (r=0.4, P=0.04 and r=0.2 P=0.07, respectively). After esomeprazole, a reduction in severity of dyspepsia (>or=50% with respect to baseline) was observed, independent of improvement of reflux-associated symptoms. Improvement in dyspepsia was, however, similar in patients with normal and abnormal basal acid exposure (14/25 vs. 33/43, respectively, P=NS). CONCLUSION: Dyspeptic symptoms coexist in a subset of nonerosive reflux disease patients, but prevalence and severity of the symptoms seems to be independent of oesophageal acid exposure

Impaired duodenal Palmitoylethanolamide release underlies acid-induced mast cells activation in Functional Dyspepsia

Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process have not been systematically investigated. Palmitoylethanolamide (PEA) is an endogenous compound, able to modulate nociception and inflammation, but its role in FD has never been assessed

SPECIFIC DYSPEPTIC SYMPTOMS ARE ASSOCIATED WITH POOR RESPONSE TO THERAPY IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE

Background: In gastroesophageal reflux disease (GORD) patients, coexistence of functional dyspepsia (FD) is known to be associated with poor response to proton pump inhibitors (PPIs), but the contribution of specific dyspepsia symptoms has not been systematically investigated yet. Objective: To characterize the impact of dyspepsia symptoms on PPIs response in GORD patients. Methods:. The enrolled subjects were 100 patients with diagnosis of GORD. All patients underwent a 24 hour pH-impedance test, while on PPIs-therapy. Patients were divided into two groups, refractory and responders, according to the persistence of GORD symptoms. A standardized questionnaire for FD was also administered to assess presence of dyspepsia symptoms. Results: In the subgroup of refractory patients FD was more prevalent than in responder ones, with postprandial fullness, nausea, vomiting, early satiation and epigastric pain being significantly prevalent in refractory GORD-patients. In the multivariate analysis only early satiation and vomiting were significantly associated with poor response to PPIs Conclusion: Coexistence of FD is associated with refractory-GORD. We showed that only early satiation and vomiting are risk factors for poor response to PPIs therapy. Our findings suggest that symptoms of early satiation and vomiting would help to identify the subset of PPIs-refractory GORD patients

Gastric determinants of maximum satiety induced by standardized solid and liquid meal. An MRI study in non obese healthy subjects.

BACKGROUND: Gastric contribution to satiety has been mostly investigated by invasive methods and by the administration of liquid meals. Nonetheless, these conditions may alter the physiology of the stomach and do not reflect individual's alimentary habit, respectively. AIM: To study gastric determinant to satiety in a more physiological fashion by a non invasive method as MRI and by standardized solid (SM) and liquid (LM) meal. SUBJECTS AND METHODS: Ten healthy subjects (4 F; Age 22±3; BMI 23±1) underwent satiety tests by SM and LM on two separate occasions. Subjects were requested to maintain intake at regular rate (100 kcal/5 min). At five minute intervals, they scored their satiety using a graphic rating scale that combined verbal descriptors on a scale graded 0-5 (1=threshold, 5=maximum satiety). Kcal and time to reach maximum satiety (MS) were calculated. During the meal tests, a gastric 1.5 T MRI using a multi-receive parallel body-synergy-coil was performed. Three acquisitions were then recorded at baseline, maximum satiety and 120 min postprandially, in order to calculate total, proximal and distal gastric volumes at each time point. Also, residual volumes at 120 min were calculated and expressed as percentage respect to MS. Data are expressed as mean±SD. RESULTS: Kcals ingested and time to reach MS were significantly higher during SM (783±244 kcal; 44±14 min) than LM (630±353 p<0.01; 31±17 p<0.01). However, total, proximal and distal gastric volume were not different between the two meals (SM: 657±186, 110±40, 546±173 vs LM: 651±299, 143±64, 507±283). Correlation analysis between total and distal gastric volumes and kcal at MS revealed a more strong and significant correlation during LM (r=0.98, p<0.001; r=0.95, p<0.001) compared to SM (r=0.76, p<0.01; r=0.78, p<0.01). No correlations were found between proximal volumes and kcal at MS. Percentages of gastric retention at 120 min were significantly higher with SM than with LM in the distal stomach, but not in the proximal stomach (63±13 vs 38±14, p<0.01 and 14±5 vs 10±7 p=NS). In addition, a significant correlation between the percentage of gastric retention at 120min and MS was only observed by considering total and distal stomach with LM (r=0.73 and r=0.61, p<0.01, respectively). CONCLUSION: By using a non-invasive methodology we showed that a standardized SM is a reliable tool to assess maximum satiety in healthy subjects. The lack of correlation between proximal gastric volumes and Kcals ingested at maximum satiety is probably related to the different intragastric distribution and handling of the liquid and solid meal

Impaired Duodenal Palmitoylethanolamide Release Underlies Acid-Induced Mast Cell Activation in Functional Dyspepsia.

BACKGROUND & AIMS: Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process have not been investigated systematically. Palmitoylethanolamide (PEA) is an endogenous compound, able to modulate nociception and inflammation, but its role in FD has never been assessed. METHODS: Duodenal biopsy specimens from FD and control subjects, and peroxisome proliferator-activated receptor-α (PPARα) null mice were cultured at a pH of 3.0 and 7.4. Mast cell (MC) number, the release of their mediators, and the expression of transient receptor potential vanilloid receptor (TRPV)1 and TRPV4, were evaluated. All measurements also were performed in the presence of a selective blocker of neuronal action potential (tetradotoxin). FD and control biopsy specimens in acidified medium also were incubated in the presence of different PEA concentrations, alone or combined with a selective PPARα or PPAR-γ antagonist. RESULTS: An acid-induced increase in MC density and the release of their mediators were observed in both dyspeptic patients and controls; however, this response was amplified significantly in FD. This effect was mediated by submucosal nerve fibers and up-regulation of TRPV1 and TRPV4 receptors because pretreatment with tetradotoxin significantly reduced MC infiltration. The acid-induced endogenous release of PEA was impaired in FD and its exogenous administration counteracts MC activation and TRPV up-regulation. CONCLUSIONS: Duodenal acid exposure initiates a cascade of neuronal-mediated events culminating in MC activation and TRPV overexpression. These phenomena are consequences of an impaired release of endogenous PEA. PEA might be regarded as an attractive therapeutic strategy for the treatment of FD.status: Published onlin

The role of a pre-load beverage on gastric volume and food intake: comparison between non-caloric carbonated andnon-carbonated beverage

Background There is conflicting data on the effects of carbon dioxide contained in beverages on stomach functions. We aimed to verify the effect of a pre-meal administration of a 300 ml non-caloric carbonated beverage (B+CO2) compared to water or a beverage without CO2 (B-CO2), during a solid (SM) and a liquid meal (LM) on: a) gastric volume, b) caloric intake, c) ghrelin and cholecystokinin (CCK) release in healthy subjects. Methods After drinking the beverages (Water, B-CO2, B+CO2), ten healthy subjects (4 women, aged 22-30 years; BMI 23 ± 1) were asked to consume either an SM or an LM, at a constant rate (110 kcal/5 min). Total gastric volumes (TGV) were evaluated by Magnetic Resonance Imaging after drinking the beverage and at maximum satiety (MS). Total kcal intake at MS was evaluated. Ghrelin and CCK were measured by enzyme immunoassay until 120 min after the meal. Statistical calculations were carried out by paired T-test and analysis of variance (ANOVA). The data is expressed as mean ± SEM. Results TGV after B+CO2 consumption was significantly higher than after B-CO2 or water (p < 0.05), but at MS, it was no different either during the SM or the LM. Total kcal intake did not differ at MS after any of the beverages tested, with either the SM (Water: 783 ± 77 kcals; B-CO2: 837 ± 66; B+CO2: 774 ± 66) or the LM (630 ± 111; 585 ± 88; 588 ± 95). Area under curve of ghrelin was significantly (p < 0.05) lower (13.8 ± 3.3 ng/ml/min) during SM following B-CO2 compared to B+CO2 and water (26.2 ± 4.5; 27.1 ± 5.1). No significant differences were found for ghrelin during LM, and for CCK during both SM and LM after all beverages. Conclusions The increase in gastric volume following a 300 ml pre-meal carbonated beverage did not affect food intake whether a solid or liquid meal was given. The consistency of the meal and the carbonated beverage seemed to influence ghrelin release, but were unable, under our experimental conditions, to modify food intake in terms of quantity. Further studies are needed to verify if other food and beverage combinations are able to modify satiation

Clinical correlation and disease phenotype in patients with esophageal achalasia and comorbid autoimmune diseases

There is evidence that idiopathic achalasia has an autoimmune component and a significant association with several autoimmune comorbidities has been described. However, data regarding the prevalence of autoimmune diseases in achalasia are not well established, and few studies have explored this association