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American Journal of Physiology.... Aug 2013Previous studies have identified differences in the expression of proteins that regulate myosin light chain phosphorylation and contraction in tonic and phasic smooth... (Comparative Study)
Comparative Study
Previous studies have identified differences in the expression of proteins that regulate myosin light chain phosphorylation and contraction in tonic and phasic smooth muscle. cGMP plays a critical role in smooth muscle relaxation and is important for optimal function of phasic and tonic smooth muscle. The intracellular cGMP levels are regulated by its hydrolysis via phosphodiesterase 5 (PDE5) and efflux via novel multidrug resistance protein 5 (MRP5). In the present study we tested the hypothesis that the differences in the phasic and tonic behavior of smooth muscles may be related to differences in mechanisms that terminate cGMP signaling. Expression of PDE5 and MRP5 was significantly (more than 2-fold) higher in fundus compared with antrum. The NO donor S-nitrosoglutathione (GSNO) caused an increase in PDE5 activity and intra- and extracellular cGMP levels in both fundus and antrum. Stimulation of PDE5 activity and increase in extracellular cGMP were significantly higher in fundus, whereas increase in intracellular cGMP was significantly higher in antrum. GSNO-induced increase in extracellular cGMP was blocked in dispersed cells by the cyclic nucleotide export blocker probenecid and in cultured muscle cells by depletion of ATP or suppression of MRP5 by siRNA, providing evidence that cGMP efflux was mediated by ATP-dependent export via MRP5. Consistent with the higher expression and activity levels of PDE5 and MRP5, GSNO-induced PKG activity and muscle relaxation were significantly lower in muscle cells from fundus compared with antrum. Thus higher expression of PDE5 and MRP5 in muscle cells from fundus correlates with tonic phenotype of muscle.
Topics: Adenosine Triphosphate; Animals; Cells, Cultured; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Gastric Fundus; Hydrolysis; Multidrug Resistance-Associated Proteins; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Myocytes, Smooth Muscle; Nitric Oxide; Nitric Oxide Donors; Phenotype; Pyloric Antrum; RNA Interference; RNA, Messenger; Rabbits; Second Messenger Systems; Time Factors; Transfection
PubMed: 23764893
DOI: 10.1152/ajpgi.00457.2012 -
American Journal of Physiology.... Jun 2009Slow waves are known to originate orally in the stomach and to propagate toward the antrum, but the exact location of the pacemaker and the precise pattern of...
Slow waves are known to originate orally in the stomach and to propagate toward the antrum, but the exact location of the pacemaker and the precise pattern of propagation have not yet been studied. Using assemblies of 240 extracellular electrodes, simultaneous recordings of electrical activity were made on the fundus, corpus, and antrum in open abdominal anesthetized dogs. The signals were analyzed off-line, pathways of slow wave propagation were reconstructed, and slow wave velocities and amplitudes were measured. The gastric pacemaker is located in the upper part of the fundus, along the greater curvature. Extracellularly recorded slow waves in the pacemaker area exhibited large amplitudes (1.8 +/- 1.0 mV) and rapid velocities (1.5 +/- 0.9 cm/s), whereas propagation in the remainder of the fundus and in the corpus was slow (0.5 +/- 0.2 cm/s) with low-amplitude waveforms (0.8 +/- 0.5 mV). In the antrum, slow wave propagation was fast (1.5 +/- 0.6 cm/s) with large amplitude deflections (2.0 +/- 1.3 mV). Two areas were identified where slow waves did not propagate, the first in the oral medial fundus and the second distal in the antrum. Finally, recordings from the entire ventral surface revealed the presence of three to five simultaneously propagating slow waves. High resolution mapping of the origin and propagation of the slow wave in the canine stomach revealed areas of high amplitude and rapid velocity, areas with fractionated low amplitude and low velocity, and areas with no propagation; all these components together constitute the elements of a gastric conduction system.
Topics: Animals; Biological Clocks; Dogs; Electromyography; Electrophysiological Phenomena; Female; Gastric Fundus; Gastrointestinal Motility; Male; Models, Biological; Pyloric Antrum; Pylorus; Stomach
PubMed: 19359425
DOI: 10.1152/ajpgi.90581.2008 -
Neurogastroenterology and Motility Jul 2020Vagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS...
BACKGROUND
Vagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS parameters and polarity on postprandial gastric motility remain incompletely characterized.
METHODS
In anesthetized rats (N = 3), we applied monophasic electrical stimuli to the left cervical vagus and recorded compound nerve action potential (CNAP) as a measure of nerve response. We evaluated to what extent afferent or efferent pathway could be selectively activated by monophasic VNS. In a different group of rats (N = 13), we fed each rat a gadolinium-labeled meal and scanned the rat stomach with oral contrast-enhanced magnetic resonance imaging (MRI) while the rat was anesthetized. We evaluated the antral and pyloric motility as a function of pulse amplitude (0.13, 0.25, 0.5, 1 mA), width (0.13, 0.25, 0.5 ms), frequency (5, 10 Hz), and polarity of VNS.
KEY RESULTS
Monophasic VNS activated efferent and afferent pathways with about 67% and 82% selectivity, respectively. Primarily afferent VNS increased antral motility across a wide range of parameters. Primarily efferent VNS induced a significant decrease in antral motility as the stimulus intensity increased (R = -.93, P < .05 for 5 Hz, R = -.85, P < .05 for 10 Hz). The VNS with either polarity tended to promote pyloric motility to a greater extent given increasing stimulus intensity.
CONCLUSIONS AND INFERENCES
Monophasic VNS biased toward the afferent pathway is potentially more effective for facilitating occlusive contractions than that biased toward the efferent pathway.
Topics: Action Potentials; Afferent Pathways; Animals; Duodenum; Efferent Pathways; Gastrointestinal Motility; Magnetic Resonance Imaging; Male; Pyloric Antrum; Pylorus; Rats, Sprague-Dawley; Vagus Nerve; Vagus Nerve Stimulation
PubMed: 32297404
DOI: 10.1111/nmo.13853 -
Brazilian Journal of Anesthesiology... 2022Pulmonary aspiration is one of the most important complications in anesthesiology. Assessment of gastric content by ultrasound is a good method to quantify gastric... (Observational Study)
Observational Study
BACKGROUND
Pulmonary aspiration is one of the most important complications in anesthesiology. Assessment of gastric content by ultrasound is a good method to quantify gastric volume and to determine the risk of intraoperative pulmonary aspiration. The aim of this study is to determine the accuracy of the gastric ultrasonography in the qualitative analysis of gastric content, mainly in the analysis of small amounts of liquid content.
METHODS
Gastric ultrasound was performed to 36 patients before upper gastrointestinal endoscopy (UGI), making two longitudinal scans at the epigastric level, one in supine position and the other in right lateral decubitus position, measuring two diameters and the area of the gastric antrum and assessing the content characteristics determining whether it was an empty stomach or contained fluid or solid content. Subsequently, the ultrasound findings were compared with UGI findings.
RESULTS
Gastric areas were analyzed by the trace and the lengths of the craniocaudal and anteroposterior axes concluding that there are no significant differences between the two methods. No statistically significant difference was found between UGI and US assessment technics. No statistically significant difference was found between the estimated volume by UGI and US.
CONCLUSIONS
Though our study has some limitations, qualitative analysis of gastric content using ultrasound followed by endoscopy enabled the conclusion that there are no differences in the qualitative assessment regarding these two techniques, supporting the important role of point-of-care gastric ultrasound (POCGUS) in the assessment of pulmonary aspiration risk by the anesthesiologist in the perioperative period.
Topics: Humans; Prospective Studies; Stomach; Gastrointestinal Contents; Pyloric Antrum; Ultrasonography
PubMed: 34324937
DOI: 10.1016/j.bjane.2021.07.008 -
Journal of Gastrointestinal and Liver... Dec 2015Appropriate biopsy sampling is important for the classification of gastritis, yet the extent of inflammation and atrophy of different regions of the stomach with chronic... (Comparative Study)
Comparative Study
BACKGROUND AND AIMS
Appropriate biopsy sampling is important for the classification of gastritis, yet the extent of inflammation and atrophy of different regions of the stomach with chronic gastritis have been addressed only in a few studies. The aim of our study was to analyze the inflammatory, atrophic and metaplastic changes in the greater and lesser curvature of the antrum and corpus mucosa.
METHODS
420 patients undergoing upper endoscopy were enrolled in the study. Four expert gastrointestinal pathologists graded biopsy specimens according to the updated Sydney classification.
RESULTS
The obtained results showed that the mononuclear and granulocyte inflammatory cells were more prominent in the corpus lesser curvature compared to the corpus greater curvature (p=0.01 and p=0.0001, respectively). In addition, the extent and degree of atrophy and intestinal metaplasia were more prominent in the corpus lesser compared to the greater curvature (p=0.002 and p=0.0065, respectively). The frequency of distribution of H. pylori did not differ throughout both the corpus and antrum greater and lesser curvature. However, the degree of H. pylori colonization in the corpus was higher in the lesser than in the greater curvature. The interobserver agreement was significantly higher for corpus atrophy compared to antrum atrophy.
CONCLUSIONS
These findings demonstrated that the more severe atrophic, metaplastic and inflammatory changes were observed in the lesser compared to the greater curvature of the stomach. In routine clinical settings, corpus and antral biopsies should be obtained from both lesser and greater curvature. Analysis of the incisura biopsy is also important.
Topics: Adult; Aged; Biopsy; Female; Gastric Mucosa; Gastritis, Atrophic; Granulocytes; Helicobacter pylori; Humans; Male; Metaplasia; Middle Aged; Observer Variation; Predictive Value of Tests; Prospective Studies; Pyloric Antrum; Reproducibility of Results; Severity of Illness Index
PubMed: 26697568
DOI: 10.15403/jgld.2014.1121.244.ptt -
American Journal of Physiology.... Mar 2006Enterally administered lipid modulates antropyloroduodenal motility, gut hormone release, appetite, and energy intake. We hypothesized that these effects would be... (Randomized Controlled Trial)
Randomized Controlled Trial
Enterally administered lipid modulates antropyloroduodenal motility, gut hormone release, appetite, and energy intake. We hypothesized that these effects would be dependent on both the load, and duration, of small intestinal exposure to lipid. Eleven healthy men were studied on four occasions in a double-blind, randomized, fashion. Antropyloroduodenal motility, plasma CCK and peptide YY (PYY) concentrations, and appetite perceptions were measured during intraduodenal infusion of lipid (Intralipid) at 1) 1.33 kcal/min for 50 min, 2) 4 kcal/min for 50 min, and 3) 1.33 kcal/min for 150 min, or 4) saline for 150 min. Immediately after the infusions, energy intake was quantified. Pressure wave sequences (PWSs) were suppressed, and basal pyloric pressure, isolated pyloric pressure waves (IPPWs), plasma CCK and PYY stimulated (all P < 0.05), during the first 50 min of lipid infusion, in a load-dependent fashion. The effect of the 4 kcal/min infusion was sustained so that the suppression of antral pressure waves (PWs) and PWSs and increase in PYY remained evident after cessation of the infusion (all P < 0.05). The prolonged lipid infusion (1.33 kcal/min for 150 min) suppressed antral PWs, stimulated CCK and PYY and basal pyloric pressure (all P < 0.05), and tended to stimulate IPPWs when compared with saline throughout the entire infusion period. There was no significant effect of any of the lipid infusions on appetite or energy intake, although nausea was slightly higher (P < 0.05) with the 4 kcal/min infusion. In conclusion, both the load, and duration, of small intestinal lipid influence antropyloroduodenal motility and patterns of CCK and PYY release.
Topics: Adult; Cholecystokinin; Dietary Fats; Dose-Response Relationship, Drug; Double-Blind Method; Duodenum; Energy Intake; Enteral Nutrition; Humans; Infusions, Parenteral; Lipids; Male; Peptide YY; Pyloric Antrum; Reference Values; Time Factors
PubMed: 16210415
DOI: 10.1152/ajpregu.00606.2005 -
World Journal of Gastroenterology Jan 2014To examine the effect of intra-gastric triacetin on both upper gastrointestinal motility and proximal gastric tone in conscious dogs.
AIM
To examine the effect of intra-gastric triacetin on both upper gastrointestinal motility and proximal gastric tone in conscious dogs.
METHODS
Three beagle dogs under sedation were surgically implanted with gastrocutaneous fistula in the gastric body and force transducers in the gastric antrum and duodenum. Beginning at week-2 after insertion, the animals were either fasted for 24 h or fed a liquid meal 2-3 h before the experiment. With the animals fully conscious, a polyethylene bag was inserted into the proximal stomach through the gastrocutaneous fistula, followed by 15 min of air inflation (minimal distending pressure of +2 mmHg) and then 20 mL of a low-, mid- or high-concentration triacetin solution (0.5%, 1.0% and 2.0%) or warm water (vehicle control). The proximal stomach receptive volume and gastric antral and duodenal contractions were measured over 10 min. The experiment was repeated twice per week over several months, with each animal receiving at least one infusion of the various triacetin solutions and the vehicle at different times. Intergroup differences were assessed by ANOVA and Bonferroni-Dunn post-hoc testing.
RESULTS
Intra-gastric infusion of mid- and high-concentration triacetin induced an increase in the proximal stomach receptive volume, and the average increase induced by the high-concentration at 0-4 min after infusion was significantly greater than that induced by the vehicle control (62.4 ± 9.8 vs 18.4 ± 4.7, P < 0.01). The mid- and high-concentration triacetin also produced a temporary inhibition of the gastric antral contractions at 2 min after infusions; however, only the fasted group showed triacetin-induced antral contractile inhibition that was significantly greater than that in the vehicle control group (P < 0.05). In addition, only the fasted group showed a high-concentration triacetin-induced increase in duodenal contractions at 9-10 min that was significantly different from that in the vehicle control group (P < 0.05).
CONCLUSION
Intra-gastric infusion of 1.0%-2.0% triacetin delays gastric emptying by increasing proximal stomach receptive volume, temporarily inhibiting gastric antral contractions and facilitating duodenal contractions.
Topics: Animals; Consciousness; Dogs; Dose-Response Relationship, Drug; Duodenum; Female; Gastric Emptying; Gastrointestinal Motility; Gastrointestinal Transit; Pyloric Antrum; Time Factors; Triacetin
PubMed: 24574778
DOI: 10.3748/wjg.v20.i4.1054 -
Alimentary Pharmacology & Therapeutics Jan 2002To assess non-invasively the dose-response relations for the effects of exogenous motilin on antrum contraction frequency, gall-bladder volume and gastric myoelectrical... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
AIM
To assess non-invasively the dose-response relations for the effects of exogenous motilin on antrum contraction frequency, gall-bladder volume and gastric myoelectrical activity.
METHODS
In a double-blind, randomized, placebo-controlled, five-way crossover study, 10 fasted healthy volunteers were infused intravenously with synthetic human motilin (0.5, 1, 2 and 4 pmol x min/kg) or placebo for 60 min. Gall-bladder volume and antrum contractions were assessed by ultrasonography and gastric myoelectrical activity by electrogastrography. Motilin concentrations were measured using a radioimmunoassay.
RESULTS
Baseline plasma motilin levels (60 pmol/L) were similar for all treatments. Motilin levels increased upon the start of infusion and rapidly returned to baseline after cessation of the infusion. At motilin doses of 2 and 4 pmol.min/kg, the antrum contraction frequency was significantly augmented, with maximum differences of two contractions per 2-min interval compared to placebo, while no changes in gastric myoelectrical activity were observed. Changes in gall-bladder volume were not significantly different for any of the motilin doses compared to placebo.
CONCLUSIONS
Motilin increased antrum contraction frequency, whereas no effect on gastric myoelectrical activity was observed. Antrum contraction frequency appears to be a useful biomarker for motilin efficacy, and motilin doses of 2 and 4 pmol x min/kg were equally effective.
Topics: Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Electrophysiology; Female; Gallbladder; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Male; Motilin; Muscle, Smooth; Pyloric Antrum
PubMed: 11856087
DOI: 10.1046/j.1365-2036.2002.01142.x -
Laboratory Investigation; a Journal of... Dec 2019Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide and is strongly associated with chronic Helicobacter pylori (Hp) infection. The ability...
Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide and is strongly associated with chronic Helicobacter pylori (Hp) infection. The ability of Hp to closely adhere to the gastric surface protective mucous layer containing mucins (MUC in humans and Muc in animals), primarily Muc5ac, is integral in the stepwise pathogenesis from gastritis to cancer. To probe the role of Muc5ac in Hp-induced gastric pathology, Muc5ac and Muc5ac (WT) mice were experimentally infected with Hp Sydney strain (SS1). At 16 weeks and 32 weeks post infection (wpi), groups of mice were euthanized and evaluated for the following: gastric histopathological parameters, immunohistochemical expression of mucins (Muc5ac, Muc1, Muc2), Trefoil factor family proteins (Tff1 and Tff2), Griffonia (Bandeiraea) simplicifolia lectin II (GSL II) (mucous metaplasia marker) and Clusterin (Spasmolytic Polypeptide Expressing Metaplasia (SPEM) marker), Hp colonization density by qPCR and gastric cytokine mRNA levels. Our results demonstrate that Muc5ac mice developed spontaneous antro-pyloric proliferation, adenomas and in one case with neuroendocrine differentiation; these findings were independent of Hp infection along with strong expression levels of Tff1, Tff2 and Muc1. Hp-infected Muc5ac mice had significantly lowered gastric corpus mucous metaplasia at 16 wpi and 32 wpi (P = 0.0057 and P = 0.0016, respectively), with a slight reduction in overall gastric corpus pathology. GSII-positive mucous neck cells were decreased in Hp-infected Muc5ac mice compared to WT mice and clusterin positivity was noted within metaplastic glands in both genotypes following Hp infection. Additionally, Hp colonization densities were significantly higher in Muc5ac mice compared to WT at 16 wpi in both sexes (P = 0.05) along with a significant reduction in gastric Tnfα (16 wpi-males and females, P = 0.017 and P = 0.036, respectively and 32 wpi-males only, P = 0.025) and Il-17a (16 wpi-males) (P = 0.025). Taken together, our findings suggest a protective role for MUC5AC/Muc5ac in maintaining gastric antral equilibrium and inhibiting Hp colonization and associated inflammatory pathology.
Topics: Adenoma; Animals; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Hyperplasia; Male; Metaplasia; Mice, Inbred C57BL; Mucin 5AC; Mucins; Pyloric Antrum; Stomach Neoplasms; Trefoil Factors
PubMed: 31399638
DOI: 10.1038/s41374-019-0293-y -
Gut Jan 1993Stimulation of localised pyloric contractions may be an important mechanism in the slowing of gastric emptying by cholecystokinin infusion. The effect of cholecystokinin... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Stimulation of localised pyloric contractions may be an important mechanism in the slowing of gastric emptying by cholecystokinin infusion. The effect of cholecystokinin octapeptide on fasting pyloric motility was investigated in 14 healthy volunteers. Antral, pyloric, and duodenal pressure responses to normal saline and graded injections of cholecystokinin octapeptide (5, 10, and 20 ng/kg) were measured. Injections were given double blind and in randomised order. All doses of cholecystokinin octapeptide initially stimulated (p < 0.05 cf saline) phasic pressure waves localised to the pylorus--the median number of pyloric pressure waves in the 5 minutes after injection being 0, 3.5, 6, and 7 for the saline and the 5, 10, 20 ng/kg cholecystokinin octapeptide injections respectively. The phasic pyloric motor response to 20 ng/kg cholecystokinin octapeptide injection was greater than that to 5 ng/kg (p < 0.05). Basal pyloric pressure increased after 20 ng/kg (1.0 v 0.2 mm Hg, p < 0.05 cf saline). Antral and duodenal pressure waves were suppressed initially by all doses of cholecystokinin (p < 0.05 cf saline). Subsequently, 20 of the 42 cholecystokinin octapeptide, injections but none of the saline injections, were followed by antropyloric pressure waves. Atropine, 15 micrograms/kg iv as a bolus, and then 4 micrograms/kg/hour iv as an infusion, had no effect on the stimulation of localised phasic pyloric pressure waves by cholecystokinin octapeptide 10 ng/kg. It is concluded that stimulation of pyloric contractions and suppression of antral and proximal duodenal motility may contribute to the slowing of gastric emptying produced by cholecystokinin.
Topics: Adolescent; Adult; Double-Blind Method; Duodenum; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Injections; Male; Pressure; Pyloric Antrum; Sincalide; Stimulation, Chemical
PubMed: 8432448
DOI: 10.1136/gut.34.1.33