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Background: High-flow, heated, and humidified nasal oxygen therapy (HFNO) is frequently used in critical care and perioperative settings for a range of clinical applications. Much of the benefit of HFNO is attributed to generation of modest levels of positive airway pressure. Concern has been raised that this positive airway pressure may cause gastric insufflation, potentially increasing the risk of regurgitation and aspiration in an unprotected airway., Methods: A prospective, interventional, assessor-blinded study was undertaken to evaluate the effects of HFNO on gastric content and gastric distension in healthy fasted adult volunteers assessed by ultrasonography. The primary outcome was the volume of gastric secretions. The secondary outcomes were the incidence of gastric air insufflation and the distribution of gastric antral grades., Results: Sixty subjects were enrolled. No subject was found to have air gastric distension either at baseline or after treatment with HFNO. All subjects had either a Grade 0 or Grade 1 antrum, with similar distribution of antral grades and similar volume of gastric secretions before and after treatment with HFNO., Conclusions: There was no evidence that treatment with HFNO at flow rates of up to 70 L min -1 for 30 min resulted in gastric distension or an increase in gastric secretions in healthy individuals breathing spontaneously. The generalisability of these findings to subjects under anaesthesia and patients with incompetence of the lower oesophageal sphincter or impaired gastric emptying requires further investigation., Clinical Trial Registration: NCT03134937., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The link between food and human health is increasingly a topic of interest. One avenue of study has been to assess food disintegration and interactions within the gastrointestinal tract. In vitro digestion models have been widely used to overcome the constrictions associated with in vivo methodology. The COST Action INFOGEST developed an international, harmonised protocol for static simulation of digestion in the upper gastrointestinal tract of adults. This protocol is widely used; however, it is restricted to providing end-point assessment without considering the possible structural changes. On the other hand, there are dynamic models that provide more physiologically relevant data but are expensive and difficult to access. There is a gap between these models. The method outlined in this article provides an intermediate model; it builds upon the harmonised static model and now includes crucial kinetic aspects associated with the gastric phase of digestion, including gradual acidification, fluid and enzyme secretion and emptying. This paper provides guidance and standardised recommendations of a physiologically relevant semi-dynamic in vitro simulation of upper gastrointestinal tract digestion, with particular focus on the gastric phase. Adaptations of this model have already been used to provide kinetic data on nutrient digestion and structural changes during the gastric phase that impact on nutrient absorption. Moreover, it provides a simple tool that can be used in a wide range of laboratories.

Background: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are now accepted as suitable alternatives to antibiotics in the control of animal infections and improving animal production. Lactic acid bacteria (LAB) with remarkable functional properties have been evaluated in different studies as possible probiotic candidates. The purpose of this study was to isolate, characterize and assess the potentials of LAB from poultry gastrointestinal tract as potential poultry probiotics., Results: Potential LAB probiotics were isolated from broilers, characterized and evaluated for probiotic properties including antagonistic activity (against Escherichia coli, E. coli O157: H7, Enterococcus faecalis, Salmonella Typhimurium, S. Enteritidis and Listeria monocytogenes), survivability in simulated gastric juice, tolerance to phenol and bile salts, adhesion to ileum epithelial cells, auto and co-aggregation, hydrophobicity, α-glucosidase inhibitory activity, and antibiotic susceptibility tests. Most promising LAB strains with excellent probiotic potentials were identified by API 50 CHL and 16S rRNA sequencing as Lactobacillus reuteri I2, Pediococcus acidilactici I5, P. acidilactici I8, P. acidilactici c3, P. pentosaceus I13, and Enterococcus faecium c14. They inhibited all the pathogens tested with zones of inhibition ranging from 12.5 ± 0.71 to 20 ± 0 mm, and competitively excluded (P < 0.05) the pathogens examined while adhering to ileum epithelial cells with viable counts of 3.0 to 6.0 Log CFU/ml. The selected LAB strains also showed significant (P < 0.005) auto and co-aggregation abilities with α-glucosidase inhibitory activity ranging from 12.5 to 92.0%. The antibiotic susceptibility test showed 100.00% resistance of the LAB strains to oxacillin, with multiple antibiotic resistance indices above 0.5., Conclusion: The selected LAB strains are ideal probiotic candidates which can be applied in the field for the improvement of poultry performance and control of pathogens in poultry, hence curtailing further transmission to humans.

In vitro digestion models are a valid methodology to study nutrient hydrolysis by simulating standard physiological gastrointestinal conditions. However, there are pathologies in which some conditions are affected, which should be considered in the design of an in vitro digestion study. Our work aims at elucidating the role of different gastrointestinal conditions on lipolysis. In the context of exocrine pancreatic insufficiency, gastric pH, intestinal pH, bile salts composition, bile salts concentration, fat concentration in the digestion medium and volumetric ratio digestion fluid/food were the selected study parameters. The pH-stat method was applied to assess lipolysis extent and kinetics. Descriptive results were summarised in digestibility curves and beta regression models were used to explain the effect (odds ratio, OR) of the studied conditions on lipolysis. Additionally, distribution of emulsion droplets was measured and optical microscopy images of fat globules were taken in a selection of experimental conditions. Results showed that intestinal pH was the variable with the highest effect on lipolysis (OR 22.86, p < 0.001), followed by fat concentration in the digestion medium (OR 6.76, p < 0.001) and bile salts concentration (OR 1.56, p < 0.001). Overall, lipolysis was significantly associated with particle size (OR - 6.98, p < 0.001). We conclude that the assessment of lipolysis by means of in vitro digestion models is sensitive to the simulated gastrointestinal conditions, which should be adapted to the real physiological conditions occurring in altered health conditions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Study Objective: Perioperative fasting guidelines differ in their approaches to chewing gum in the preoperative period. Current recommendations range from canceling the surgery to proceeding with it. Given this lack of consensus, we performed gastric ultrasound assessments in healthy volunteers before and after a standardized period of chewing gum. The objective of our study was to determine if chewing gum for 1 h change the gastric volume., Design: Observational prospective analytical study., Setting: Bedside gastric ultrasound., Patients: Following institutional Review Board approval, 55 healthy (American Society of Anesthesiologists class I to II) fasted (non-surgical research) volunteers provided written informed consent to participate in the study. Morbid obesity, renal failure, diabetes mellitus, pregnancy and previous upper abdominal surgery were exclusion criteria., Interventions: Volunteers chewed gum for 1 h between the first and second assessment., Measurements: Four gastric ultrasound assessments were performed, the first one at baseline and then hourly thereafter., Main Results: Fifty-five healthy volunteers were studied. The proportion of subjects who presented a completely empty stomach (Grade 0 antrum) was similar at baseline and after 1 h of gum-chewing [81% vs. 84%, p = 0.19, CI 95% (-12%, 16%)]. Among those subjects who had visible fluid at baseline, the volume remained unchanged throughout the study period., Conclusions: One hour of gum-chewing had no significant effect on the gastric fluid volume of healthy volunteers, suggesting that it may be safe for healthy subjects to chew gum prior to elective surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (≥4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.

Background: Surgical patients are asked to fast for a sufficient duration to ensure that the amount of residual liquid in the stomach is within the safe range, thereby reducing the risk of gastric reflux perioperatively. The authors hypothesized that subjective hunger numerical rating scale (NRS) score could also help assess the process of gastric emptying and determine the amount of fluid remaining in the stomach., Methods: The current study consisted of healthy volunteers recruited by advertisement and mutual introduction. Participants were asked to rate their subjective hunger feeling every 30 min after oral administration of 8 mL/kg carbohydrate nutrient solution that contained 10% maltodextrin and 2.5% sucrose. Consecutively, the gastric residual fluid was measured by magnetic resonance imagining (MRI). The Spearman's correlation coefficient, the ROC curves and the stepwise regression were used to analyze the predictive value of NRS for the gastric emptying process., Results: The cohort consisted of 29 healthy volunteers enrolled in this study. The area under ROC curves estimated by the NRS score for the gastric residual volume of 2 mL/kg, 1 mL/kg, and 0.5 mL/kg were AUC 2.0  = 0.78, AUC 1.0  = 0.76, and AUC 0.5  = 0.72, respectively. The correlation coefficient between the NRS score and the residual liquid in the stomach was -0.57 (P < 0.01). The correlation coefficient between the increase of the NRS score and the decrease of gastric liquid residual volume was 0.46 (P < 0.01). The standardized estimate of NRS score for the residual volume was -0.18 (P < 0.01) and the standardized estimate of fasting time was -0.73 (P < 0.01)., Conclusions: The subjective hunger NRS score can not accurately predict the gastric residual volume, but it can provide a reference for clinicians to judge the gastric emptying process and it should be used as a second check after oral intake of clear fluids before surgery according to the new fasting protocol.

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and involves changes in reflux exposure, epithelial resistance, and visceral sensitivity. The gastric refluxate is a noxious material that injures the esophagus and elicits symptoms. Esophageal exposure to gastric refluxate is the primary determinant of disease severity. This exposure arises via compromise of the anti-reflux barrier and reduced ability of the esophagus to clear and buffer the refluxate, leading to reflux disease. However, complications and symptoms also occur in the context of normal reflux burden, when there is either poor epithelial resistance or increased visceral sensitivity. Reflux therefore develops via alterations in the balance of aggressive and defensive forces., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Mixing fluid in a container at low Reynolds number--in an inertialess environment--is not a trivial task. Reciprocating motions merely lead to cycles of mixing and unmixing, so continuous rotation, as used in many technological applications, would appear to be necessary. However, there is another solution: movement of the walls in a cyclical fashion to introduce a geometric phase. We show using journal-bearing flow as a model that such geometric mixing is a general tool for using deformable boundaries that return to the same position to mix fluid at low Reynolds number. We then simulate a biological example: we show that mixing in the stomach functions because of the "belly phase," peristaltic movement of the walls in a cyclical fashion introduces a geometric phase that avoids unmixing.

Gastric juice entering the mouth causes dental erosion. Common causes for the migration of gastric juice through the lower and upper oesophageal sphincters are reflux disease, laryngopharyngeal reflux, eating disorders, chronic alcoholism and pregnancy. Gastroesophageal reflux is a common condition affecting up to 65% of the Western population at some point in their lifetime. A typical clinical sign of acidic gastric juice entering the mouth is palatal dental erosion. As the condition becomes more chronic it becomes more widespread. There have been relatively few randomised studies investigating the aetiology of acids causing erosion. Of the few that have reported their findings, it appears that gastric acids have the potential to induce moderate-to-severe erosion. This literature review reports the conditions associated with the movement of gastric juice and dental erosion using medical and dental sources., (© 2014 S. Karger AG, Basel.)

Hyperspectral imaging system for diagnosing digestive diseases was newly developed in order to obtain information on pathology beyond morphology of lesions. In order to guide light reflected from a lesion, a baby fiber, which can be inserted in a forceps channel of the electronic endoscope, was also developed. The performance of the system was evaluated by animal experiment. Obtained hyperspectral data were found to have sufficient quality endurable to practical use. Harmful phenomena to a living body were not observed within the experiment. It was considered from the animal experiment that the present system could be practically used for humans.

Unlabelled: CF patients are often treated with proton pump inhibitors (PPIs) to reduce acidic gastro-esophageal reflux (GER) and bronchial aspiration of duodeno-gastric contents is common in CF. We have previously demonstrated that gastric juice (GJ) from patients "on" PPI can induce interleukin-8 (IL-8) production by bronchial epithelial cells in culture. We hypothesized that such effect would be more pronounced in CF patients known to have high inflammatory susceptibility. We aimed to evaluate the effect of GJ on IL-8 production by primary bronchial epithelial cells (PBEC), derived from a CF patient and a healthy subject., Methods: PBEC obtained from one donor (normal PBEC) and one receptor (CF-PBEC) for lung transplantation were stimulated with GJ from patients "off" and "on" PPI. IL-8 levels were measured in the supernatant., Results: GJ from patients "on" PPI provoked a significant higher IL-8 production compared to GJ from patients "off" PPI, both in normal PBEC [462 (200-1468) vs. 11 (4-28) pg/ml, p=0.0001] as in CF-PBEC [1468 (841-2449) vs. 85 (26-131) pg/ml, p<0.0001]. Exposure of the cells to GJ "off" PPI and "on" PPI provoked significantly higher IL-8 production in the CF-PBEC compared to the normal PBEC ["off" PPI 85 (26-131) vs. 11 (4-28) pg/ml, p=0.01; "on" PPI 1468 (841-2449) vs. 462 (200-1468) pg/ml, p=0.01]. Filtration (0.20 μm) of the GJ "on" PPI, to eliminate large particles and bacterial sub-products, resulted in a significant decrease of IL-8 production., Conclusion: Patients with CF, treated with PPIs, have GJ with high pH and high endotoxin levels. These patients often have GER and bronchial aspiration. The aspirated material (GJ "on" PPI) has a significantly enhanced inflammatory effect on CF bronchial epithelial cells in culture. As chronic PPI treatment in CF may result in a paradoxically increased inflammatory effect in the airways, alternative anti-reflux therapies should be considered in CF., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Purpose: To characterize human gastric fluid with regard to rheological properties and gastric lipase activity. In addition, traditional physicochemical properties were determined., Methods: Fasted HGA were collected from 19 healthy volunteers during a gastroscopic examination. Rheological characterization of the aspirates was conducted on a TA AR-G2 rheometer, using cone and plate geometry. Lipase activity was measured by continuous titration of released free fatty acid from tributyrate. Further, pH, osmolality, buffer capacity, and surface tension were measured and the total protein content and bile salt level were determined using assay kits., Results: Rheological examination of HGA showed non-Newtonian shear-thinning behavior with predominant elastic behavior in the linear range. The apparent viscosity was measured to be in the range of 1.7-9.3 mPas at a shear rate of 50s(-1). The FaSSGF and HCl pH 1.2 have no shear-thinning properties and showed lower viscosity (1.1 mPas at 50 s(-1)). The observed viscosity of the HGA will decrease the intrinsic dissolution rate of drugs. The activity of the gastric lipase was 7.4 ± 4.0 U/mL (N = 6, n = 3) and 99.0 ± 45.3 U/mL (N = 19, n = 3) at pH 2.8 and 5.4, respectively. pH, surface tension, buffer capacity, bile salt concentration, and osmolality were measured and compared with literature data., Conclusion: The rheological behavior and the mean apparent viscosity of HGA are significantly different from that of water and should therefore be considered important during development of gastric simulated media. Further, the activity of the HGL is active even under fasted gastric conditions and might contribute to the digestion and emulsification of lipid-based drug delivery systems in the entire gastrointestinal tract. HGL should therefore be considered in gastric evaluation of lipid-based drug delivery systems., (Copyright © 2013. Published by Elsevier B.V.)

Dietary glutamate (Glu) stimulates to evoke the umami taste, one of the five basic tastes, enhancing food palatability. But it is also the main gut energy source for the absorption and metabolism for each nutrient, thus, only a trace amount of Glu reaches the general circulation. Recently, we demonstrated a unique gut sensing system for free Glu (glutamate signaling). Glu is the only nutrient among amino acids, sugars and electrolytes that activates rat gastric vagal afferents from the luminal side specifically via metabotropic Glu receptors type 1 on mucosal cells releasing mucin and nitrite mono-oxide (NO), then NO stimulates serotonin (5HT) release at the enterochromaffin cell. Finally released 5HT stimulates 5HT3 receptor at the nerve end of the vagal afferent fiber. Functional magnetic resonance imaging (f-MRI, 4.7 T) analysis revealed that luminal sensing with 1 % (w/v) monosodium L-glutamate (MSG) in rat stomach activates both the medial preoptic area (body temperature controller) and the dorsomedial hypothalamus (basic metabolic regulator), resulting in diet-induced thermogenesis during mealing without changes of appetite for food. Interestingly, rats were forced to eat a high fat and high sugar diet with free access to 1 % (w/w) MSG and water in a choice paradigm and showed the strong preference for the MSG solution and subsequently, they displayed lower fat deposition, weight gain and blood leptin. On the other hand, these brain functional changes by the f-MRI signal after 60 mM MSG intubation into the stomach was abolished in the case of total vagotomized rats, suggesting that luminal glutamate signaling contributes to control digestion and thermogenesis without obesity.

A continuous leaching method, coupled online with inductively coupled plasma mass spectrometry (ICP-MS) was used on seafood samples to assess the maximum bioaccessibility of several trace elements. The method indeed involves continuous leaching of the food sample by artificial saliva and gastric juice, successively, where this exposition of the food to fresh reagent drives the dissolution equilibrium to the right. Leaching with intestinal juice had to be omitted because it resulted in clogging problems. The experimental apparatus includes a mini-column of powdered sample, which is directly connected to the nebulizer of an ICP-MS instrument. The on-line approach allows a quick assessment of the maximum bioaccessibility of elements of interest by monitoring the real-time release of elements by a given reagent. The method was applied to determine the bioaccessibility of four toxic elements (Al, Cd, Hg, and Pb) and of four essential elements (V, Mn, Cu, and Zn) in certified reference materials and in actual seafood samples. In all cases, mass balance was verified by carrying out the total digestion of the remaining residue from the mini-column and the relationship between total concentration and bioaccessibility was examined., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Recent data suggest that acid suppressive medications may alter factors central to the pathophysiology of inflammatory bowel diseases (IBD), whether through shifts in the intestinal microbiome due to acid suppression or effects on immune function., Aim: To assess the relationship between the use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2Ra) and incidence of 'flares' (hospitalisation/surgery and change in medication)., Methods: We conducted a new user cohort study including individuals diagnosed with IBD in British Columbia using linked healthcare utilisation databases (available from July 1996 through April 2006). Propensity-score matched incidence rates during a 6-month follow-up period and rate ratios (RR) and 95% CI were calculated., Results: Among 16 151 IBD patients, 1307 Crohn's disease (CD) and 996 ulcerative colitis (UC) patients experienced a new use of PPIs, whereas 741 CD and 738 UC used H2Ra. All IBD subgroups were matched separately to an equal number of unexposed IBD patients. H2Ra use in CD doubled the risk of hospitalisation/surgery (RR = 1.94; 95%CI 1.24-3.10) and numerically less so in UC patients (RR = 1.11) with widely overlapping CIs (0.61-2.03). Proton pump inhibitors use was associated with medication change in UC (RR = 1.39; 95%CI 1.20-1.62), but without meaningfully, increased risk of hospitalisation/surgery for UC or CD patients. Extending follow-up showed persistence, but attenuation, of all effects., Conclusions: Initiation of PPIs or H2Ra may be associated with short-term changes in the course of IBD. Although confounding by indication was adjusted using propensity score matching, residual confounding may persist and findings need to be interpreted cautiously., (© 2012 Blackwell Publishing Ltd.)

The viability of the probiotic strain Lactobacillus acidophilus DSM 20079, after its passage through the simulated gastric and pancreatic juices, was evaluated as function of its pre-growth in a medium containing the known prebiotics pectin or inulin, and was compared to glucose used as control. The presence of pectin or inulin did not affect the growth (12.11(log10) colony forming units/mL and 12.08(log10) colony forming units/mL for pectin and inulin respectively versus 12.22(log10) colony forming units/mL obtained for glucose). Pectin and inulin, in contrast to glucose, induced cell stress resistance against gastrointestinal juices (Δ(log10) 1 and 2 colony forming units/mL respectively, versus Δ(log10) 4.5 for glucose). The data were confirmed by the analysis of the protein pattern following stress treatments which, in the case of microbial cells grown with glucose, revealed a relevant protein degradation after the double passage through simulated gastric and intestinal juices. An impressive metabolic change, as function of the growth conditions, was demonstrated by analyzing the proteomic profile with a μ-2DE system, used herein for the first time as evaluation tool of prebiotic-probiotic interactions. The analysis revealed a different pH protein distribution that was mostly acidic in the presence of pectin and neutral-alkaline in the presence of inulin. Both prebiotics stimulated the production of butyrate, a relevant healthy bio-molecule not detectable in the presence of glucose, that was measured by HPLC analysis to be 14.5 fold higher after growth in the presence of inulin, as compared to pectin. Three specific proteins were detected at pH 6 after growth in the presence of pectin or inulin. They could be correlated to the stress resistance and/or to the production of butyrate, the common phenotypic characteristics induced in the bacterial strain by the two prebiotics., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Many ad hoc fasting guidelines for pre-anesthetic patients prohibit gum chewing. We find no evidence that gum chewing during pre-anesthetic fasting increases the volume or acidity of gastric juice in a manner that increases risk, nor that the occasional associated unreported swallowing of gum risks subsequent aspiration. On the contrary, there is evidence that gum chewing promotes gastrointestinal motility and physiologic gastric emptying. Recommendations against pre-anesthetic gum chewing do not withstand scrutiny and miss an opportunity to enhance comfort and sense of wellbeing for patients awaiting anesthesia. Gum chewing during the pre-anesthetic nil per os (NPO) period would also permit the development of gum-delivered premedications and should be permitted in children old enough to chew gum safely. Gum chewing should cease when sedatives are given and all patients should be instructed to remove any chewing gum from the mouth immediately prior to anesthetic induction., (© 2011 Blackwell Publishing Ltd.)

Objective: To investigate the intrinsic fluorescence spectrum of gastric juice as a diagnostic method for gastric cancer., Methods: We collected gastric juice by gastroscopy in 1,870 patients from May 2001 to March 2006, of whom 202 were involved in a preliminary test, 162 in experimental optimization and 1,506 in clinical verification. The best dilution and pH value were chosen in the experimental optimization phase. Clinical verification was based on optimized samples. Intrinsic fluorescence spectra were measured in all samples with a fluorescence spectrophotometer using an excitation wavelength of 288 nm., Results: The first peak of fluorescence intensity (P(1) FI) of the intrinsic fluorescence spectrum was significantly higher in gastric juice from patients with gastric cancer than from those with benign lesions. There was no significant difference in the P(1) FI differences between patients with benign and malignant lesions with samples diluted by 20-fold to 80-fold and from pH 9 to pH 11. Clinical verification in 1,506 patients showed that P(1) FI ≥ 76.5 was the optimal cut-off on the receiver operating characteristic curve for diagnosing gastric cancers: sensitivity was 83.2%, specificity 80.7% and accuracy 82.0%., Conclusions: P(1) FI of the intrinsic fluorescence at 288 nm is significantly higher in patients with gastric cancers than in individuals with benign lesions. As a clinical indicator of gastric cancer, its sensitivity, specificity and accuracy were high., (© 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.)

Aim: To search the independent factors determining gastric juice acidity and to investigate the acidity of gastric juices in various benign and malignant upper gastrointestinal diseases., Methods: Fasting gastric juice acidity of 165 healthy subjects and 346 patients with esophageal ulcer (n = 21), gastric ulcer (n = 136), duodenal ulcer (n = 100) or gastric cancer (n = 89) were measured and compared. Additionally, gastric specimens were taken from the antrum and body for rapid urease test and histological examination., Results: Multivariate analysis revealed that bile stain of gastric juice, high acute inflammatory score of the corpus, and atrophy of the corpus were independent risk factors for the development of gastric hypoacidity with odds ratios of 3.1 (95% CI: 1.3-7.3), 3.1 (95% CI: 1.2-7.9) and 3.5 (95% CI: 1.3-9.2). Esophageal ulcer and duodenal ulcer patients had a lower pH level (1.9 and 2.1 vs 2.9, both P < 0.05) of gastric juices than healthy subjects. In contrast, gastric ulcer and gastric cancer patients had a higher pH level (3.4 and 6.6 vs 2.9, both P < 0.001) than healthy controls. Hypoacidity existed in 22%, 5%, 29%, 5% and 88% of healthy subjects, esophageal ulcer, gastric ulcer, duodenal ulcer and gastric cancer patients, respectively., Conclusion: Bile reflux, atrophy and dense neutrophil infiltrate of the corpus are three independent factors determining the acidity of gastric juice.

Background: There is a paucity of studies comparing stress ulcer prophylaxis (SUP) agents in high-risk neurosurgical patients., Methods: In this prospective, randomized study, critically ill neurosurgical patients received lansoprazole 30 mg suspension via NG/NJ tube daily or famotidine 20 mg IV q12 h for SUP. Gastric pH and residual volumes were recorded for 3 days and adverse events for 7 days after admission., Results: There were 51 patients randomized to lansoprazole (n = 28) or famotidine (n = 23) who received SUP for ≥ 3 days. All patients had at least two risk factors for SRMD, and 75% had a baseline GCS < 9. On day 1 of therapy, more famotidine patients had a gastric pH ≥ 4 at least 80% of the time as compared to lansoprazole patients (74 vs. 36%, P = 0.01, respectively); however, there was no difference on days 2 and 3. Enteral feedings on day 1 predicted a pH ≥ 4 (P = 0.01). There were no significant differences in the percentages of time gastric residual volumes < 28 ml (P = NS). Heme-positive aspirates were present in 18-39% of patients (P = NS); one patient receiving famotidine met the criteria for overt bleeding. Thrombocytopenia occurred in 17% in the famotidine group and 4% in the lansoprazole group (P = NS)., Conclusions: Neurosurgery ICU patients receiving famotidine for SUP achieved a gastric pH ≥ 4 more often than lansoprazole-treated patients, but only on day 1 of the 3-day study period. Both agents were equally effective in reducing gastric acid production. There was no difference in the incidence of mucosal damage and thrombocytopenia.

Background and Aims: The lower esophageal sphincter (LES) in patients with gastroesophageal reflux disease often has a low resting pressure and a short abdominal length. The mechanism by which this occurs is unknown. We hypothesize that gastric distension causes progressive effacement of the abdominal portion of the LES, exposing it to acid injury resulting in mucosal and sphincter damage. Our aim was to assess in normal subjects the effect of gastric distension on the LES length and pressure and its exposure to acid gastric juice., Methods: Eleven asymptomatic volunteers had their LES length and pressure measured before and during gastric distension. The location of the pH step-up point (shift from gastric pH to a pH >4) was also measured before and after distension., Results: Progressive gastric distension with air resulted in progressive shortening of LES (R = 0.89, P < 0.0001). After infusion of 750 cc of air there was a significant reduction in the median LES length from 4 to 2.6 cm (P = 0.001). This change occurred in the abdominal length of the LES (2.6-1.4 cm [P = 0.001]) and not in the thoracic length. At rest the pH step-up point was 0.5 cm above the lower border of the LES and with distension moved a median of 1 cm cephalad within the LES. Simultaneously with the loss of length there was a reduction in LES pressure (27.4-23.4 mm Hg, P = 0.02)., Conclusions: Gastric distension causes progressive shortening of the abdominal length of the LES and a reduction in its pressure. The process exposes the effaced mucosa and sphincter to acid gastric juice.

The research of novel probiotic strains is important in order to satisfy the increasing request of the market and to obtain functional products in which the probiotic cultures are more active and have better probiotic characteristics than those already on the market. In this study, the probiotic potential of Lactobacillus and Enterococcus strains isolated from human feces was investigated. One hundred seven strains of lactic acid bacteria were isolated from the fecal samples of 19 adult volunteers with stomach problems and the fecal samples of 12 healthy adult volunteers. The strains were identified by 16S rRNA analysis and examined for resistance to gastric acidity (pH 3.5) and bile salts (0.3% bile salt). The antibiotic susceptibility of the strains was also determined. The counts of lactic acid bacteria in the fecal samples ranged from 1.7 x 10(7) to 3.1 x 10(10) CFU/g. The species present in those samples were found to be Lactobacillusplantarum, L. fermentum, Enterococcus faecium and E. durans. Results indicated that L. plantarum (AA1-2, AA17-73, AC18-88, AK4-11, and AK7-28), L. fermentum (AB5-18, BB16-75, and AK4-180), E. faecium (AB20-98 and BK11-50) and E. durans (AK4-14 and BK9-40) showed good pH and bile tolerance. These strains are potentially good candidates for use as health-promoting bacteria., (Copyright 2010 S. Karger AG, Basel.)

This study aimed to assess variations in the human gastrointestinal transit tolerance of Lactobacillus plantarum strain No. 14 after culture with glucose and with fructose. Transit tolerance was determined at 37 degrees C against simulated gastric juices at pH values of 2.5, 3.0, and 3.5, and against simulated small intestinal juices containing 0%, 0.2%, or 0.4% oxgall. The simulated gastrointestinal transit tolerance of Lactobacillus plantarum strain No. 14 varied with the carbon source. Hence we compared the amounts of exopolysaccharide from Lactobacillus plantarum strain No. 14 cultured in various carbon sources. The exopolysaccharide levels were 146.5+/-8.1 mg/l (culture) with glucose, and 20.1+/-17.0 mg/l (culture) with fructose. When exopolysaccharide was removed by centrifugation, the simulated gastric tolerance of Lactobacillus plantarum strain No. 14 cultured with glucose decreased markedly, but that with fructose did not decrease. These results suggest that the gastrointestinal transit tolerance of Lactobacillus plantarum strain No. 14 is related to exopolysaccharide contents.

Salivary nitrite plays a role in the lipid peroxidation process of muscle tissue in simulated gastric fluid. The objectives of our study were to elucidate the fate of nitrite in the presence of reducing compounds and to evaluate its effect on lipid peroxidation during digestion. Nitrite at pH 3 (possibly NO(2.), not NO.) can oxidize beta-carotene, but the addition of reducing compounds, ascorbic acid or polyphenols, alters its effect. Ascorbic acid alone promoted the formation of NO. from nitrite only up to pH 3, but the addition of iron ions facilitated the formation of NO. up to pH 5.5. NO prevented membranal lipid peroxidation under stomach conditions. Nitrite, only in the presence of reducing compounds, achieved the same goal but at much higher concentrations. Addition of polyphenols to nitrite synergistically improved its antioxidant effect. Therefore, to promote NO. production and to achieve better control of the lipid peroxidation process in the stomach, a nitrite-rich meal should be consumed simultaneously with food rich in polyphenols.

Aims: Lactobacilli should resist stress environments in industry process and gastrointestinal tract before exerting their beneficial effects. To explore the possible stabilizers in probiotic products, prebiotic oligosaccharides were investigated., Methods and Results: We investigated the effect of four selected oligosaccharides on the survival of probiotic Lactobacillus plantarum and L. acidophilus to simulated stress conditions. It was found that the tolerance of lactobacilli to simulated artificial gastrointestinal juice, heat treatment and phenol solution was obviously enhanced in fructo-oligosaccharides (FOS) and xylo-oligosaccharides (XOS) group. In addition, chito-oligosaccharides (COS), manno-oligosaccharides (MOS) and glucose also had positive effect compared with control group (without sugar)., Conclusions: Prebiotic oligosaccharides, especially XOS and FOS added in medium have protection function to lactobacilli in stress environments. The protection function of oligosaccharides may correlate with the bacteria growth, which was stimulated by these oligosaccharides., Significance and Impact of the Study: Prebiotic oligosaccharides may be used as stabilizers in probiotic products.

Disorders of haemostasis and haemocoagulation are often seen in cancer patients as a part of the paraneoplastic syndrome. This study describes a novel compound that activates coagulation and also inhibits fibrinolytic system and fibrin degradation products in the gastric juice of 33 patients with gastric cancer. Similar, but less pronounced changes have been found in gastric juice of patients with gastric precancerosis. Procoagulant activity, induced by pathologically changed cells or monocytes, macrophages from tumor stroma, indicates the activation of local coagulation with the production of fibrin. It can be concluded that the local changes of coagulation and fibrinolysis may precede coagulopathies in cancer patients (Tab. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

Objective: Although aspiration pneumonitis is a severe complication in patients hospitalized in intensive care units, its pathogenesis is poorly understood. The aim of this study was to determine whether the intensity of lung injury and inflammation developing after aspiration during mechanical ventilation differed depending on the inflammatory activity of intensive care unit patients' gastric fluid., Design: In vitro study on human gastric juice and randomized controlled animal study., Setting: Research laboratories of academic institutions., Subjects: Male New-Zealand white rabbits., Interventions: Proinflammatory activity of gastric juice from 17 intensive care unit patients and 12 controls undergoing elective surgery was measured based on a target cell activation assay. Two gastric juices from intensive care unit patients with similar pH but differing for their in vitro proinflammatory activity (high and low) were further instilled into the trachea of ventilated rabbits. Lung function, mechanics, pathology, leukocyte infiltration, and local cytokine levels were measured after 6 hrs., Measurements and Main Results: Gastric juice from intensive care unit patients, even buffered at pH 7.4, stimulated human type II-like A549 epithelial cells to up-regulate intercellular adhesion molecule-1 and interleukin-8, significantly more than juice obtained in controls. Gastric juice from an intensive care unit patient supporting high proinflammatory activity in vitro also induced a more severe and persistent drop in PaO2/FIO2 and respiratory system compliance in ventilated rabbits, a worse histologic score, higher lung lavage concentrations of inflammatory cells, interleukin-8 (p < 0.01), and growth-related oncogene-alpha (p < 0.01) than one fluid with low proinflammatory activity., Conclusion: Gastric juice from critically ill patients is proinflammatory and stimulates human pulmonary cells in vitro. A human gastric juice with high proinflammatory activity is more "toxic" to the lung than one with low proinflammatory activity in a ventilated rabbit model, an effect that is independent of pH and particulate matter content.

Gastroesophageal reflux has become a major health concern in industrialized countries, with drugs aimed at blocking acid production being more frequently prescribed than any other drug. Damage to lung tissue as a result of chronic aspiration of gastric fluid is a primary health risk associated with gastro-esophageal reflux, with such aspiration being suspected in the induction or exacerbation of asthma and other lung diseases. In this study, a rodent model of chronic aspiration was used to characterize the pulmonary histopathology produced by repetitive aspiration events and to investigate the pathologic roles of individual gastric fluid components such as acid and particulate food matter. Rats exposed to chronic aspiration of whole gastric fluid developed a pathology distinct from that of acute lung injury, characterized by granulomatous interstitial pneumonitis with prominent formation of multinucleated giant cells. This pattern of injury could be reproduced with chronic aspiration of particulate food matter and with chronic aspiration of pH-neutralized gastric fluid, but not with chronic aspiration of hydrochloric acid. Thus, since acid-neutralizing therapy is currently the mainstay of treatment for patients with reflux-associated respiratory symptoms, these results strongly suggest that alternative therapeutic approaches aimed at preventing chronic-aspiration induced lung injury may be warranted.

Trypanosoma cruzi infection by oral route constitutes the most important mode of transmission in some geographical regions, as illustrated by reports on microepidemics and outbreaks of acute Chagas' disease acquired by ingestion of food contaminated with parasites from triatomine insects. In the mouse model, T. cruzi metacyclic trypomastigotes invade the gastric mucosal epithelium, a unique portal of entry for systemic infection. High efficiency of metacyclic forms in establishing infection by oral route is associated with expression of gp82, a stage-specific surface molecule that binds to gastric mucin and to epithelial cells. Gp82 promotes parasite entry by triggering the signaling cascades leading to intracellular Ca(2+) mobilization. T. cruzi strains deficient in gp82 can effectively invade cells in vitro, by engaging the Ca(2+) signal-inducing surface glycoprotein gp30. However, they are poorly infective in mice by oral route because gp30 has low affinity for gastric mucin. Metacyclic forms also express gp90, a stage-specific surface glycoprotein that binds to host cells and acts as a negative regulator of invasion. T. cruzi strains expressing gp90 at high levels, in addition to gp82 and gp30, are all poor cell invaders in vitro. Notwithstanding, their infectivity by oral route may vary because, unlike gp82 and gp30, which resist degradation by pepsin in the gastric milieu, the gp90 isoforms of different strains have varying susceptibility to peptic digestion. For instance, in a T. cruzi isolate, derived from an acute case of Chagas' disease acquired by oral route, gp90 is extensively degraded by gastric juice in the mouse stomach and this renders the parasite highly invasive towards target cells. If such an exacerbation of infectivity occurs in humans, it may be responsible for the severity of the disease reported in outbreaks of oral infection.

Background: The pathogenesis of multiple organ failure (MOF) in trauma patients may involve the gastrointestinal tract, but its exact origins remain elusive. In a prospective study, the gastric fluid of major torso trauma patients was examined for evidence of duodenogastric reflux and potential gastric injury, and was compared with patient outcomes regarding MOF., Methods: Patient samples were collected daily for 4 days by nasogastric tube and analyzed for pH, hemoglobin, and bile acid. Blood was collected for analysis of C-reactive protein (CRP). Outcomes were recorded for the presence or absence of MOF., Results: The results showed that most patients exhibited alkaline gastric contents (pH >/=4.9) and elevated levels of hemoglobin immediately after the trauma. Although non-MOF patients demonstrated a decline of both mean gastric pH and bleeding by day 4, MOF patients maintained significant elevations in pH during this time period. Mean total bile acid levels were increased in all patients, signifying the presence of duodenogastric reflux. However, there were no clear differences in mean bile acid concentrations between MOF and non-MOF patients over time, although MOF patients tended to exhibit higher levels. All patients showed a progressive rise in serum CRP during the first 24 hours after trauma, which was maintained for 4 days. The initial rise in serum CRP in MOF patients was delayed compared with that in non-MOF patients., Conclusions: We conclude that duodenogastric reflux occurs in trauma patients in the first few days after trauma and may contribute to elevated gastric pH and bleeding. Further study is needed to verify whether monitoring the gastric juice of trauma patients during the first several days of hospitalization, for alkaline pH and excessive blood in the gastric lumen, could lead to better assessments of patient status.

Systematic procedures were used to evaluate the probiotic properties of Lactobacillus fermentum (L. fermentum) strains isolated from swine and poultry. The major properties included their capabilities to adhere to the intestinal epithelium of swine and poultry, the inhibition on pathogenic bacteria, and their tolerance to the gastric juice and bile salts. Results showed that L. fermentum strains from poultry digestive tract showed better adherence to the swine intestine and chicken crop epithelial cells as compared to those strains from the swine origin. In addition, six strains from poultry and one strain from swine showed adhesion specificity to their own intestinal epithelium. Four poultry isolates and one swine isolate were able to adhere to the epithelial cells from both swine and chicken. For gastric juice and bile tolerance, most of the strains isolated from swine or poultry were acid tolerant but less strains were bile intolerant. The spent culture supernatant (SCS) of these L. fermentum strains showed antagonistic effect against the indicator bacteria, such as Escherichia coli, Salmonella spp., Shigella sonnei and some enterotoxigenic Staphylococcus aureus. From the above studies, some L. fermentum strains isolated from poultry were found to have the probiotic properties required for use in animal feed supplement. This study suggested that poultry digestive tract may serve as potential source for the isolation of probiotic lactic acid bacteria.

Acid challenge of the gastric mucosa is signaled to the brainstem. This study examined whether mild gastritis due to dextrane sulfate sodium (DSS) or iodoacetamide (IAA) enhances gastric acid-evoked input to the brainstem and whether this effect is related to gastric myeloperoxidase activity, gastric histology, gastric volume retention or cyclooxygenase stimulation. The stomach of conscious mice was challenged with NaCl (0.15 M) or HCl (0.15 and 0.25 M) administered via gastric gavage. Two hours later, activation of neurons in the nucleus tractus solitarii (NTS) was visualized by c-Fos immunocytochemistry. Gastritis was induced by DSS (molecular weight 8000; 5%) or IAA (0.1%) added to the drinking water for 7 days. Relative to NaCl, intragastric HCl increased the number of c-Fos protein-expressing cells in the NTS. Pretreatment with DSS or IAA for 1 week did not alter the c-Fos response to NaCl but significantly enhanced the response to HCl by 54 and 74%, respectively. Either pretreatment elevated gastric myeloperoxidase activity and induced histological injury of the mucosal surface. In addition, DSS caused dilation of the gastric glands and damage to the parietal cells. HCl-induced gastric volume retention was not altered by IAA but attenuated by DSS pretreatment. Indomethacin (5 mg/kg) failed to significantly alter HCl-evoked expression of c-Fos in the NTS of control, DSS-pretreated and IAA-pretreated mice. We conclude that the gastritis-evoked increase in the gastric acid-evoked c-Fos expression in the NTS is related to disruption of the gastric mucosal barrier, mucosal inflammation, mucosal acid influx and enhanced activation of the afferent stomach-NTS axis.

To purpose of this paper is to study the relation between normal lung maturation signal and changes in intensity ratios (SIR) and to determine which magnetic resonance imaging sequence provides the strongest correlation of normal lung SIs with gestational age. 126 normal singleton pregnancies (20-37 weeks) were examined with a 1.5 Tesla unit. Mean SIs for lungs, liver, and gastric fluid were assessed on six different sequences, and SIRs of lung/liver (LLSIR) and lung/gastric fluid (LGSIR) were correlated with gestational age for each sequence. To evaluate the feasibility of SIRs in the prediction of the state of the lung maturity, accuracy of the predicted SIRs (D*) was measured by calculating relative residuals (D*-D)/D for each sequence. LLSIRs showed significant changes in every sequence (p<0.05), while LGSIRs only on two sequences. Significant differences were shown for the mean of absolute residuals for both LLSIRs (p<0.001) and for LGSIRs (p=0.003). Relative residuals of LLSIRs were significantly smaller on T1-weighted sequence, whereas they were significantly higher for LGSIRs on FLAIR sequence. Fetal liver seems to be adequate reference for the investigation of lung maturation. T1-weighted sequence was the most accurate for the measurement of the lung SIs; thus, we propose to determine LLSIR on T1-weighted sequence when evaluating lung development.

Some transient lower oesophageal sphincter relaxations (TLOSRs) are accompanied by gastro-oesophageal reflux and others are not. We aimed to investigate what factors determine the occurrence and type of reflux during TLOSRs. In 12 healthy subjects prolonged high-resolution manometry was performed. Reflux was detected using pH-impedance monitoring. A total of 219 TLOSRs were detected; no differences were observed between the duration of TLOSRs with liquid-containing reflux (20.2 +/- 1.0 s), gas reflux (17.0 +/- 1.0 s) and no reflux (19.0 +/- 1.0 s). Trans-sphincteric pressure gradient was similar in TLOSRs with liquid reflux (1.6 +/- 0.1 kPa), gas reflux (1.5 +/- 0.1 kPa) and no reflux (1.7 +/- 0.3 kPa). Prevalence, duration and amplitude of oesophageal pre-contractions and sphincteric after-contractions were not different for TLOSRs with and without reflux. The total number of TLOSRs decreased significantly from 8.2 +/- 0.8 in the first to 5.7 +/- 0.5 in the second and 4.4 +/- 0.6 in the third 70-min recording period. The number of TLOSRs accompanied by liquid-containing reflux decreased from 4.7 +/- 0.9 to 3.0 +/- 0.4 to 1.6 +/- 0.4, while the numbers of TLOSRs with gas reflux remained unchanged (2.1 +/- 0.6-2.1 +/- 0.7-2.2 +/- 0.6). Besides, time after the meal, no differences were observed in the characteristics of TLOSRs with and without gastro-oesophageal reflux. We conclude that factors, other than TLOSR characteristics, are important of whether or not a TLOSR is reflux-related.

Both human and H. pylori populations are polymorphic for the expression of Lewis antigens. Using an experimental H. pylori challenge of rhesus monkeys of differing Lewis phenotypes, we aimed to determine whether H. pylori populations adapt their Lewis phenotypes to those of their hosts. After inoculation of four monkeys with a mixture of seven strains identified by RAPD-polymerase chain reaction, H. pylori Lewis expression was followed in 86 isolates obtained over 40 wk. Host Lewis(a/b) secretion status was characterized by immunological assays. Fingerprints of the predominating strain (J166) were identical in all four animals after 40 wk, but its Lewis phenotype had substantial variability in individual hosts. At 40 wk, J166 populations from two Lewis(a-b+) animals predominantly expressed Lewis(y). In contrast, J166 populations had switched to a Lewis(x) dominant phenotype in the two Lewis(a+b-) animals; a frame shift in futC, regulating conversion of Lewis(x) to Lewis(y), accounted for the phenotypic switch. The results indicate that individual cells in H. pylori populations can change Lewis phenotypes during long-term colonization of natural hosts to resemble those of their hosts, providing evidence for host selection for bacterial phenotypes.

The effect of taurine on gastric hemorrhage and mucosal erosion in the brain ischemia (BI) is unknown. The aim of the research was to study the involvement of gastric oxidative stress in hemorrhagic erosion produced in BI rats. The protective effect of taurine on this erosion model was evaluated. Male Wistar rats were deprived of food for 24 h. Under chloral hydrate -anesthesia, bilateral carotid artery ligation (BCAL) was performed 12, 18 and 21 h after removal of food to obtain 12, 6 and 3 h of BI duration. The pylorus and carotid esophagus of rats also were ligated. The stomachs were then irrigated for 3 h with normal saline or simulated gastric juice containing 100 mM HCl plus 17.4 mM pepsin and 54 mM NaCl. The stomach was dissected. Gastric samples were harvested. The rat brain was dissected for examination of ischemia by using triphenyltetrazolium chloride staining method. Changes in gastric ulcerogenic parameters, such as decreased mucosal GSH level as well as enhanced gastric acid back-diffusion, mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin content and mucosal erosion in gastric samples were measured. The results indicated that BCAL could produce severe BI in rats. Moreover, a BI- duration-dependent exacerbation of various ulcerogenic parameters also was observed in these rats. Intraperitoneal taurine (0-300 mg/kg) dose-dependently ameliorated gastric oxidative stress and hemorrhagic erosion in BI rats. Taken together, BI could produce gastric oxidative stress and hemorrhagic erosions that was ameliorated by taurine through stimulation of GSH biosynthesis and inhibition of oxidative stress.

Background: The Bravo system was designed mainly to monitor esophageal pH, and there have been no reports on gastric pH monitoring using this system., Objective: To place the Bravo capsule on the gastric wall and monitor gastric pH., Design: Experimental clinical trial with the cooperation of volunteers., Setting: Academic medical center., Patients: Eleven volunteers (9 men, 2 women; mean age 38 years; 3 had symptoms of GERD)., Interventions: The Bravo system was introduced into the esophagus and stomach along a thin endoscope and capsules were attached, one each to the esophageal and gastric walls under direct vision through the endoscope. Esophageal and gastric pHs were simultaneously monitored., Results: The 2 capsules were successfully placed in 10 of the 11 subjects, and both esophageal and gastric pHs were monitored for 48 hours in 9 subjects. Mild to moderate precordial pain was observed in 7 subjects, but no other complications or side effects were observed in this study. The gastric pH of 10 subjects increased after meals and returned to baseline pH 2 hours later. Decrease of esophageal pH was observed 1 hour after a meal in the symptomatic subjects and corresponded to the time when gastric pH decreased secondary to the increase of pH with meals., Conclusions: The Bravo capsule is easily placed on the gastric wall under endoscopic assistance and enables long ambulatory monitoring of gastric pH.

Leptin is a hormone secreted by the gastric mucosa into the lumen of the stomach. It is present in its intact form in the intestine where it regulates nutrient absorption and intestinal mucosa integrity. We have identified the binding protein that protects leptin from the harsh conditions of the gastric juice. Immunoprecipitations and Western blot analyses demonstrated that leptin is present in the gastric mucosa and the gastric juice, bound to a protein corresponding to the extracellular domain of the leptin receptor. In the absence of this soluble receptor, leptin is rapidly degraded. Immunocytochemistry on rat gastric mucosa identified the cells and intracellular compartments involved in secretion of this complex. Leptin receptor extracellular domain and leptin are present along the rough endoplasmic reticulum-Golgi-granules secretory pathways and form a complex in the secretory granules of Chief and specific endocrine cells. The long-form membrane leptin receptor OB-Rb, the protease activator furin, and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells. The shedding of the receptor occurs in the immature granules. It is concluded that in the immature secretory granules of Chief cells, furin activates proprotein convertase 7 that, in turn, cleaves the extracellular portion of membrane-bound leptin receptors. Leptin bound to its soluble receptor forms a complex that is resistant to the gastric juice. Endocrine cells, on the other hand, generate a soluble leptin receptor by mechanisms different from those of the exocrine cells.

All vertebrates produce gastric acid. Its main function is inactivation of ingested microorganisms. The majority of microbiological pathogens ingested never reaches the intestine because of the gastric barrier. Although gastric hypochlorhydria is fairly common due to atrophic gastritis, gastric surgery or use of inhibitors of gastric acid secretion, the resulting susceptibility to infection has not been studied extensively. Drug-induced blockade of acid secretion leads to gastrointestinal bacterial overgrowth; the clinical significance of this is still controversial. Gastric acidity is known to protect against non-typhoid salmonellosis and cholera and it is suspected that it protects against several parasitic diseases as giardiasis and strongyloides. There is a lack of studies focusing on the impact of the gastric acidic barrier on viral infections. Concerning prion infections only a single study has been performed, demonstrating a possible role of gastric acidity in the protection against foodborne prion disease in mice. The combination of malnutrition and hypochlorhydria may contribute to the high prevalence of gastrointestinal infections in developing countries. Further studies are needed to evaluate the clinical consequences of impaired gastric acidity with respect to susceptibility to infections.

The fed human stomach displays regular peristaltic contraction waves that originate in the proximal antrum and propagate to the pylorus. High-resolution concurrent manometry and magnetic resonance imaging (MRI) studies of the stomach suggest a primary function of antral contraction wave (ACW) activity unrelated to gastric emptying. Detailed evaluation is difficult, however, in vivo. Here we analyse the role of ACW activity on intragastric fluid motions, pressure, and mixing with computer simulation. A two-dimensional computer model of the stomach was developed with the 'lattice-Boltzmann' numerical method from the laws of physics, and stomach geometry modelled from MRI. Time changes in gastric volume were specified to match global physiological rates of nutrient liquid emptying. The simulations predicted two basic fluid motions: retrograde 'jets' through ACWs, and circulatory flow between ACWs, both of which contribute to mixing. A well-defined 'zone of mixing', confined to the antrum, was created by the ACWs, with mixing motions enhanced by multiple and narrower ACWs. The simulations also predicted contraction-induced peristaltic pressure waves in the distal antrum consistent with manometric measurements, but with a much lower pressure amplitude than manometric data, indicating that manometric pressure amplitudes reflect direct contact of the catheter with the gastric wall. We conclude that the ACWs are central to gastric mixing, and may also play an indirect role in gastric emptying through local alterations in common cavity pressure.