vasoactive-intestinal-peptide and Gastroesophageal-Reflux

Infantile colic is a widespread clinical condition in the first 3 months of life, which is easily recognized, but incompletely understood and difficult to solve. The available evidence suggests that infantile colic might have several independent causes. The medical hypotheses include food hypersensitivity or allergy, immaturity of gut function and dysmotility, and the behavioural hypotheses include inadequate maternal-infant interaction, anxiety in the mother and difficult infant temperament. Other recent hypotheses, such as hormone alterations and maternal smoking, still need confirmation, whereas the new concept of alterations in the gut microflora, have been reported. A number of interventions, including pharmacological agents, are discussed, but it is probable that infants with colic require a graded strategy.. Considering the favourable clinical course and the wide range of manifestations, a safe approach should be adopted, which is proportional to the intensity of the infantile colic. However, further research and guidelines are still needed.

Topics: Colic; Diet; Feeding Behavior; Food Hypersensitivity; Gastroesophageal Reflux; Gastrointestinal Motility; Gastrointestinal Tract; Glucose Solution, Hypertonic; Humans; Infant; Lactose Intolerance; Phytotherapy; Probiotics; Psychology; Severity of Illness Index; Vasoactive Intestinal Peptide

Proximal gastric relaxation is a vago-vagal reflex upon food intake. The efferent neurons involved at the level of the stomach are nonadrenergic noncholinergic. Deficient proximal gastric relaxation is observed in a portion of patients with functional dyspepsia, while exaggerated relaxation might contribute to the development of gastroesophageal reflux disease via triggering of transient lower esophageal sphincter relaxations. Nitric oxide (NO) is mediating, together with vasoactive intestinal polypeptide (VIP) as parallel cotransmitter, the nonadrenergic noncholinergic neurotransmission of the proximal stomach. Evidence for a sequential link between VIP as neurotransmitter and muscular NO generation was obtained when studied in isolated gastric smooth muscle cells; inducible NO synthase seems expressed. The endogenous gastric nitrergic neurotransmitter is not sensitive to superoxide anion generators and NO scavengers, that reduce the relaxation to exogenous NO. This is not due to the release of a nerve-derived hyperpolarizing factor in addition of NO, nor to binding to thiols, but Cu/Zn superoxide dismutase is involved in the protection of endogenous NO versus superoxide anions and scavenging. The release of NO from gastric nitrergic neurons is not sensitive to negative feedback but is inhibited via presynaptic alpha 2-adrenoceptors. Nitric oxide functionally antagonizes acetylcholine in the smooth muscle cells but does not influence the release of acetylcholine at the cholinergic varicosities. Stimulating or inhibiting the gastric nitrergic neurons might be a target for drug therapy in functional dyspepsia or gastro-esophageal reflux, respectively.

Topics: Dyspepsia; Free Radical Scavengers; Gastroesophageal Reflux; Humans; Muscle Relaxation; Neural Pathways; Neurotransmitter Agents; Nitric Oxide; Stomach; Superoxide Dismutase; Vasoactive Intestinal Peptide

Topics: Animals; Atropine; Cats; Dogs; Esophageal and Gastric Varices; Esophageal Diseases; Esophageal Neoplasms; Esophagitis; Esophagogastric Junction; Esophagoscopy; Esophagus; Gastroesophageal Reflux; Hexamethonium Compounds; Humans; Opossums; Papio; Peristalsis; Rats; Swine; Vasoactive Intestinal Peptide

To observe the effect of repeated esophageal acid infusion on specific airway resistance (sRaw) and airway reactivity in the guinea pigs and explore the mechanism.. sRaw and airway reactivity were measured by double-chamber plethysmography in normal control group (group N), saline control group (group NS), and repeated acid irrigation group (group H). The initial measurement was used as the baseline sRaw and airway reactivity (1d1), and 2 h after the initial measurement, sRaw and airway reactivity were measured again (1d2). Similarly, such measurements were repeated on the 15th day for all the guinea pigs (15d1, 15d2) with a 2-h interval. The content of Substance P (SP) and vasoactive intestinal peptide (VIP) in lung tissue, trachea, BALF and ganglion were detected by ELISA.. The percent change of sRaw, (15d2-1d1)/1d1 in group H was significantly higher than that in group N. The differences in the airway reactivity of the group N, group NS, and group H were not statistically significant. The SP content in the lung, trachea, ganglion and bronchoalveolar lavage fluid (BALF) in group H was significantly higher than those in group N. The SP content in ganglion showed a significant positive correlation to that in the trachea. No significant differences were found in the VIP content in the lung, trachea, ganglion or BALF between the groups.. Repeated esophageal acid infusion increases the airway resistance, but not the airway reactivity in normal guinea pigs. SP may be involved in development of high sRaw through the esophageal-tracheobronchial reflex.

Topics: Airway Resistance; Animals; Bronchoalveolar Lavage Fluid; Esophagus; Gastroesophageal Reflux; Guinea Pigs; Lung; Male; Respiratory System; Substance P; Trachea; Vasoactive Intestinal Peptide

Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum of achalasia patients could reproduce the phenotype and functional changes that occur with disease progression in an ex vivo human model.. Specimens of normal human fundus were maintained in culture in the presence of serum from patients with achalasia, gastro-oesophageal reflux disease (GORD), or healthy subjects (controls). Immunohistochemical detection of choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), and substance P was carried out in whole mounts of gastric fundus myenteric plexus. In addition, the effects of achalasia serum on electrical field stimulation (EFS) induced contractions were measured in circular muscle preparations.. Serum from achalasia patients did not affect the number of myenteric neurones. Tissues incubated with serum from achalasia patients showed a decrease in the proportion of NOS (-26% of NSE positive neurones; p=0.016) and VIP (-54%; p=0.09) neurones, and a concomitant increase in ChAT neurones (+16%; p<0.001) compared with controls. In contrast, GORD serum did not modify the phenotype of myenteric neurones. Area under the curve of EFS induced relaxations (abolished by N-nitro-L-arginine methyl ester) was significantly decreased following incubation with serum from achalasia patients compared with controls (-7.6 (2.6) v -14.5 (5.0); p=0.036).. Serum from achalasia patients can induce phenotypic and functional changes which reproduce the characteristics of the disease. Further identification of putative seric factors and mechanisms involved could lead to the development of novel diagnostic and/or therapeutic strategies in achalasia.

Topics: Adult; Aged; Aged, 80 and over; Choline O-Acetyltransferase; Disease Progression; Electric Stimulation; Esophageal Achalasia; Female; Ganglia; Gastric Fundus; Gastroesophageal Reflux; Humans; Male; Middle Aged; Myenteric Plexus; Nitrergic Neurons; Nitric Oxide; Nitric Oxide Synthase; Phenotype; Tissue Culture Techniques; Vasoactive Intestinal Peptide

The normal esophageal motility is a balance between excitatory cholinergic "muscarinic" innervations and noncholinergic nonadrenergic inhibitory innervations. The latter is mediated by nitric oxide (NO) and/or vasoactive intestinal polypeptide (VIP).. The study included 50 patients with gastro-esophageal reflux disease (GERD), and 10 healthy controls of matched age and sex. Patients were divided into five groups according to the degree of lower end esophagitis (Savary-Miller classification). Serum VIP was measured using enzyme immunoassay after peptide purification. Serum nitrate as an index of nitric oxide generation was determined biochemically.. Serum nitrate and VIP levels were significantly higher in GERD patients than the control group (p < 0.001). Grade 0 serum nitrates was significantly higher than the control group (p < 0.05) with some overlap between the individual values of the two groups. Serum VIP was significantly higher in grade 0 group compared to control group (p < 0.001) with no overlap in the individual values. There was a significant positive correlation between the grade of lower end esophagitis and each of serum nitrate and VIP (p < 0.001), as well as between serum nitrate and each of serum VIP, cigarette smoking index (CSI) and BMI (p < 0.001).. Abnormally high levels of serum VIP and NO may have a role in the pathogenesis of GERD. Exposure of esophageal mucosa to noxious effect of acid refluxed due to the relaxant effect of VIP on lower esophageal sphincter may cause increased NO levels. BMI and CSI are risk factors for GERD progression.

Topics: Adult; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Nitrates; ROC Curve; Smoking; Statistics, Nonparametric; Vasoactive Intestinal Peptide

We evaluated the effect of graded exercise on esophageal motility and gastroesophageal reflux. We studied eight trained cyclists using a catheter with three strain-gauge transducers connected to a solid-state datalogger and an ambulatory intraesophageal pH monitor. Each study lasted 4 hr during which subjects exercised on a stationary bike for 1 hr at 60% of peak O2 uptake (O2 max), 45 min at 75% of O2 max, and for 10 min at 90% of O2 max. Subjects rested 1 hr before exercise (control period) and for 30 min between exercise sessions. Studies were performed after an overnight fast and subjects received only intravenous infusion of 5% glucose solution during the study. Plasma concentrations of gastrin, motilin, glucagon, pancreatic polypeptide (PP), and vasoactive intestinal peptide (VIP) were determined at rest and before and after each exercise session. The duration, amplitude, and frequency of esophageal contractions declined with increasing exercise intensity, and the differences were significant (P < or = 0.05) for all three variables at 90% O2 max. The number of gastroesophageal reflux episodes and the duration of esophageal acid exposure were significantly (P < or = 0.05) increased during exercise at 90% O2 max. Plasma hormone concentrations showed no significant changes between rest and the various exercise sessions. Thus, exercise has profound effects on esophageal contractions and gastroesophageal reflux which are intensity dependent. These effects are not mediated by the hormones measured.

Topics: Adult; Analysis of Variance; Bicycling; Esophagus; Exercise; Exercise Test; Gastrins; Gastroesophageal Reflux; Glucagon; Humans; Hydrogen-Ion Concentration; Male; Manometry; Motilin; Pancreatic Polypeptide; Peristalsis; Reference Values; Vasoactive Intestinal Peptide

The distribution of nerve fibers and cell bodies reactive for the peptides enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide were studied in biopsies of external muscle taken from the gastric body and antrum of 17 patients undergoing surgery for gastroesophageal reflux, and in regions of healthy stomach resected as part of gastric cancer operations. The results were correlated with preoperative measurements of liquid and solid emptying from the stomach in the patients with gastro-esophageal reflux. In three cases, no delay was detected in either liquid or solid emptying, and the distribution of peptide immunoreactive fibers in the external muscle was similar to that of healthy muscle. In 14 cases, the emptying of either liquids or solids or both was delayed, and in eight of these clearcut changes in the distribution of peptide-immunoreactive fibers occurred. In six cases, the number of enkephalin-immunoreactive fibers was fewer than normal in the biopsy from the gastric body (in one of these samples the number of substance P-immunoreactive fibers was also reduced). In another cae, the number of substance P-immunoreactive fibers in the antrum was reduced, and in another the number of vasoactive intestinal peptide and neuropeptide Y-immunoreactive fibers in the antral biopsy was reduced. It is concluded that in patients with gastroesophageal reflux who have delayed gastric emptying, a proportion demonstrate abnormalities of the peptide-immunoreactive fibers that innervate the gastric external muscle.

Topics: Enkephalins; Esophagus; Female; Fluorescent Antibody Technique; Gastric Emptying; Gastroesophageal Reflux; Humans; Male; Middle Aged; Nerve Fibers; Neuropeptide Y; Peristalsis; Stomach; Substance P; Vasoactive Intestinal Peptide

In children with chronic renal failure (CRF) anorexia, nausea, and vomiting are common yet poorly understood symptoms. We studied oesophageal and gastric motor function in 12 children (age 7 months-6.8 years) with severe CRF not undergoing dialysis who had persistent anorexia and vomiting. Eight of 12 patients had significant gastro-oesophageal reflux (reflux index 5.2% to 21.9%, mean 11.3%; controls < 5%), 7/10 had altered gastric half emptying times (T1/2) for 5% glucose or milk (glucose meal--controls: 8-14 min, two CRF patients: 18-25 min; milk meal--controls: 48-72 min, five CRF patients 27, 28, 82, 83, and 110 min). Gastric antral electrical control activity was abnormal in 6/11 patients, with different types of gastric dysrhythmias whereas the remainder and controls showed a regular dominant frequency of 0.05 Hz. In 7/9 patients fasting serum gastrin concentration was raised (53 to > 400, mean 168 pmol/l, controls < 40 pmol/l). All CRF patients with anorexia and vomiting had one or more disorder of foregut motility. The nature and variety of the motor disorders and the raised concentrations of circulating gastrin suggest that the normal environment generated by CRF affects the function of the smooth muscle of the foregut.

Topics: Child; Child, Preschool; Electrophysiology; Esophagus; Female; Gastric Emptying; Gastroesophageal Reflux; Humans; Infant; Kidney Failure, Chronic; Male; Muscle, Smooth; Stomach; Vasoactive Intestinal Peptide

We have evaluated the correlation between vasoactive intestinal polypeptide (VIP) plasma concentration and severity of gastroesophageal reflux in patients with Barrett's esophagus and the possible differences in the VIP values of these patients compared with healthy volunteers. We also evaluated the relation between VIP plasma concentration and lower esophageal sphincter (LES) pressure in 24 patients with Barrett's esophagus. The mean VIP plasma concentration in 14 patients with severe gastroesophageal reflux was 25.6 +/- 0.75 pg/ml, significantly higher than the mean value observed in 10 patients with moderate reflux (18.9 +/- 0.67 pg/ml) (p less than 0.01). The mean LES resting pressure was significantly lower in the group of patients with severe gastroesophageal reflux than that observed in patients with moderate reflux (3 +/- 0.64 and 10.3 +/- 0.69 mm Hg, respectively; p less than 0.01). The mean VIP plasma concentration in 11 healthy volunteers (20.6 +/- 0.65 pg/ml) was significantly lower than the mean value observed in the subgroup of patients with severe gastroesophageal reflux (p less than 0.01). VIP values in patients with moderate reflux were not significantly different from those observed in our volunteers. There was a significant correlation between LES pressure and VIP plasma level (r = -0.9253; p less than 0.01). In conclusion, it is possible that the decreased LES resting pressure observed in patients with Barrett's esophagus and severe gastroesophageal reflux may be due to impairment of the VIPergic innervation, resulting in an increased local VIP release with possible overflow to peripheral plasma.

Topics: Adult; Aged; Aged, 80 and over; Barrett Esophagus; Esophagogastric Junction; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Peristalsis; Pressure; Vasoactive Intestinal Peptide

Twenty patients with gastroesophageal reflux disease (10 with compensated and 10 with decompensated gastroesophageal incompetence) were examined to determine if there was a correlation between the ability of physiological stimuli to tonicize the lower esophageal sphincter (LES) and the response to pentagastrin stimulation (Gastrodiagnost). The pressure of the lower esophageal sphincter as well as blood levels of the hormones/neurotransmitters gastrin, PP and VIP were determined after giving a 300 ml intragastral bolus of either 0.9% NaCl or 20% peptone solution. All patients exhibited per definitionem a positive common-cavity phenomenon on abdominal compression. Intravenous pentagastrin stimulated the LES in patients with compensated gastroesophageal incompetence (GI) but not in those with decompensated GI (p less than or equal to 0.0005). Esophagoscopy revealed a severe esophagitis in 80% of the patients with decompensated GI but in only 10% of the patients with compensated GI. Peptone stimulated the LES in patients with compensated GI (p less than or equal to 0.005) at 5, 10 and 15 minutes, pepton vs. NaCl). Neither NaCl nor peptone increased the tone of the LES in patients with decompensated GI. Peptone but not NaCl caused a significant increase of serum gastrin in all patients: there was no difference between the two groups. Neither NaCl nor peptone influenced VIP levels in peripheral blood. PP levels increased significantly in both groups following peptone. Physiological responsiveness of the LES can be inferred from the manometric data and the results of the pentagastrin test. A negative reaction to pentagastrin is associated with a loss of response to physiological stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Esophagitis, Peptic; Esophagogastric Junction; Esophagoscopy; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Male; Manometry; Middle Aged; Pancreatic Polypeptide; Peptones; Vasoactive Intestinal Peptide

The oesophageal pH was recorded for 3 h after a test-meal in 27 healthy control subjects (group I), 40 patients with alcoholic cirrhosis (group II), and 22 patients with a normal liver and symptoms of gastro-oesophageal reflux (control refluxers). Gastro-oesophageal reflux was observed in 10 of the cirrhotic patients. Marked reflux episodes lasted longer in cirrhotic refluxers than in control refluxers (P less than 0.05). The frequency of ascites, bleeding from ruptured oesophageal varices, peripheral neuropathy and hepatic encephalopathy were not significantly different according to presence or absence of reflux. Plasma concentrations of gastrin, somatostatin, motilin and vasoactive intestinal peptide (VIP) were measured in groups I and II. Fasting plasma motilin levels, and the release of motilin and of VIP after the meal were higher in group II than in group I. Basal levels and post-prandial profiles of the four peptides tested did not differ between cirrhotics with or without gastro-oesophageal reflux. We conclude that in patients with alcoholic cirrhosis: gastro-oesophageal reflux is frequent (25%) and characterized by prolonged reflux episodes; reflux is not correlated with the degree of liver failure and plays no significant role in the rupture of oesophageal varices; and raised plasma motilin and VIP levels cannot account for the high incidence of reflux in cirrhotics.

Topics: Adult; Aged; Aged, 80 and over; Female; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Motilin; Somatostatin; Vasoactive Intestinal Peptide