Gastroduodenal Motility Research Articles

A comparison of the VASP index between patients with hemodynamically complicated and uncomplicated acute myocardial infarction

Critically-ill patients with ST-segment elevation myocardial infarction (STEMI) often present with insufficient gastroduodenal motility, liver hypoperfusion, and higher levels of circulating catecholamines. All of these factors can lead to reduced efficacy of clopidogrel, which is only available as a p.o. medication. The aim of the study was to compare clopidogrel effectiveness in unstable STEMI patients on mechanical ventilation with stable STEMI patients. Two groups of twenty patients with STEMI were enrolled. One group (unstable) consisted of 20 hemodynamically unstable patients on mechanical ventilation and catecholamine support. The other group (stable) consisted of 20 control patients (all patients with STEMI in Killip I class). All patients were treated by primary Percutaneous coronary intervention. Blood samples were drawn before (baseline), at 4h (4h+), 24h (1d+) and 2 days (2d+) after clopidogrel administration. Clopidogrel efficacy was assessed by measurement of vasodilator-stimulated phosphoprotein phosphorylation index. The decrease in the vasodilator-stimulated phosphoprotein (VASP) index was substantially less in unstable patients compared with stable ones (ANOVA, P < 0.001). In stable patients, the VASP index decreased significantly by 20% at 4h+ and by 34% at 1d+, and remained significantly decreased by 31% at 2d+. In unstable patients, the VASP decreased nonsignificantly by 8% at 4h+, and no further decrease of VASP was present (-7% at 1d+, -11% at 2d+). Laboratory clopidogrel efficacy is lower in patients with MI and severe hemodynamic instability, probably due to splanchnic and liver hypoperfusion and catecholamine use.

New method of manometric measurement of gastroduodenal motility in conscious mice: effects of ghrelin and Y2 depletion

Since no previous studies have reported dual measurements of stomach and duodenal motility in conscious mice, we developed a manometric method to measure the gastroduodenal motility in the physiological fed and fasted states of conscious mice. By this method we measured, for the first time, the gastroduodenal motility in Y2 knockout mice and analyzed the effects of ghrelin on the gastroduodenal motility in conscious mice. To evaluate this new method, we provide the comparison on the effects of CCK-8 examined by present and previous methods. In the fasted state of mice, phase III-like contractions with frequencies of 7.8 +/- 0.5 contractions/h in the antrum and 6.6 +/- 0.7 contractions/h in the duodenum were observed. This fasted pattern was disrupted and replaced by the fed pattern after feeding, with an increase of the motor index (MI) immediately after feeding. Intravenous injection of ghrelin induced the fasted pattern in the duodenum when injected in the fed state and increased %MI (114.3 +/- 9.8%) compared with saline-injected controls (64.4 +/- 9.6%) in the antrum. Intravenous injection of CCK-8 disrupted phase III-like contractions in both antrum and duodenum, which were replaced by fed-like motor patterns accompanied with the elevation of baseline pressure. In Y2 knockout mice, the frequency of phase III-like contractions was decreased in the antrum compared with wild-type mice and the immediate increase of MI after feeding seen in wild-type mice was disrupted in Y2 knockout mice. Our model provides a new method for studies of gastrointestinal motility in various mouse models, including transgenic and knockout ones.

Upper gastrointestinal promotility drugs: not all uniform?

The pathophysiology of functional gastrointestinal (GI) disorders has been under broad investigation in the past two decades; dysmotility remains one of the main focuses of the research. Numerous studies have documented abnormal gastroduodenal motility in patients with functional dyspepsia, irritable bowel syndrome, and other functional GI disorders. In functional dyspepsia, the abnormalities range from delayed to accelerated gastric emptying, abnormal antral and fundic contractions, and disordered accommodation in the fundus and antrum. Some of the functional GI symptoms may be explained by disturbed motility both during and after the meal. Less is known about small bowel dysmotility. Alterations in small bowel transit time, proximal small bowel accommodation, and abnormal contractions may play a role in pathophysiology of symptoms of the functional disorders. Currently, we have witnessed rapidly accumulating knowledge about the functional characteristics of GI tract motility. Some new tools are available such as a wireless motility capsule 1 or impedance pH test. These tests can give additional information about the relationships between GI transit and contractility as measured by manometry. But antroduodenal manometry, though uncommonly performed, still provide fascinating insights into upper GI motility. Using promotility agents to treat functional GI disorders is very attractive, given that they may target some of the underlining pathophysiologic mechanisms. Unfortunately, most of them are only modestly effective. This may be due to the fact that normal gut motility is a complex interaction between multiple neurotransmitters, while available drugs usually target only one neurotransmitter or receptor involved in the maintaining of normal GI motility function.

GLP‐1 regulates gastroduodenal motility involving cholinergic pathways

The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9-39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9-39), atropine, exendin(9-39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9-39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9-39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9-39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9-39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9-39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.

Effects of intraluminal local anesthetic on upper gastrointestinal motor, sensory, and peptide hormone responses to intraduodenal glucose

Enterally administered glucose modifies gut sensation, diminishes hunger, and slows gastric emptying by suppressing antral motility and stimulating pyloric pressures. We aimed to clarify the mechanism of small intestinal glucose sensing. We studied eight healthy males twice, in random order. An antroduodenal manometry catheter was positioned with a sleeve sensor across the pylorus. Benzocaine, or vehicle alone, was given into the proximal duodenum as a bolus, followed by continuous infusion for 105 min (T=-15 to 90 min). Glucose was also infused into the proximal duodenum at 3 kcal/min for 90 min (T=0-90 min). Sensations of hunger, bloating, and nausea were assessed with visual analog questionnaires, blood was sampled at intervals, and energy intake at a buffet meal (T=90-120 min) was measured. Perceptions of bloating and nausea were markedly less with benzocaine when compared with vehicle (P<0.05 for each), with no difference in hunger, or energy intake. In contrast, the suppression of antral waves and stimulation of phasic and tonic pyloric pressures, duodenal waves, and propagated duodenal wave sequences by intraduodenal glucose infusion did not differ between the 2 days. No difference in blood glucose, plasma insulin, or plasma glucagon-like peptide 1 between benzocaine and control was observed, whereas glucose-dependent insulinotropic polypeptide and cholecystokinin concentrations were slightly higher with benzocaine (P<0.05 for both). Mucosal anesthesia ameliorates unpleasant sensations induced by enteral glucose, but does not inhibit the release of gut peptides that feed back on appetite and gastroduodenal motility.

Effect of clarithromycin on esophageal motility

As clarithromycin (CLA), an antibiotic commonly used for Helicobacter pylori eradication, stimulates gastroduodenal motility, we investigated whether it also stimulates esophageal motility. In 15 normal subjects, esophageal motility was recorded using a low-compliance manometric system with two ports in the esophageal body, one port in the lower esophageal sphincter (LES), and five ports in the antroduodenal tract to monitor the occurrence of phases I-III of the migrating motor complex. Thirty minutes after the occurrence of a duodenal phase III, we infused intravenously, randomly, and in a double-blind manner, CLA 100 mg in five subjects (group A), CLA 250 mg in five subjects (group B), and normal saline in the remaining five subjects (group C). LES tone and post-deglutitive residual pressure, as well as the amplitude and duration of the esophageal contractions, were measured each minute and averaged over a post-infusion period of 30 min. Both group A and B showed a LES tone significantly higher than that of group C after CLA infusion, whereas the post-deglutitive residual pressure was not significantly different from that of group C. The LES tone of group B was significantly higher than that of group A. Group B, but not group A, showed a wave amplitude and duration significantly higher than that of group C. In conclusion, CLA is able to stimulate LES tone and esophageal contractions with a dose-related effect.

Effect of Distal Subtotal Gastrectomy With Preservation of the Celiac Branch of the Vagus Nerve to Gastrointestinal Function

To evaluate the effects of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve on gastrointestinal function. The operative procedure of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve is now in the spotlight in Japan with the goal of finding a function-preserving surgical technique. However, there has been no analysis of the effect of this type of surgery on gastrointestinal function. In this article, we describe the results of a fundamental experiment on distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve. Twenty conscious dogs were divided into 2 groups, each subdivided into 2 groups of 5: a normal intact dog group (NG) divided into 2 groups, with preservation (PNG) and resection (RNG; these dogs were truncally vagotomized including transaction of the celiac branch) of the celiac branch, and a gastrectomy dog group (GG) divided into 2 groups, with preservation (PGG) and resection (RGG) of the celiac branch. The motility of the dogs was recorded using strain gauge force transducers. The effects of the preservation of the celiac branch of the vagus nerve on gastrointestinal motility, gastric emptying, and pancreatic insulin release were evaluated. The motility index of gastrointestinal motility with preservation of the celiac branch was higher than the motility index with resection of the celiac branch in fasted and fed of NG and GG. In gastric emptying, significant differences were found between the PNG and RNG but not between the PGG and RGG. In the fasted state for 80 minutes of the PNG and PGG, the serum insulin concentration reached a peak during the early phase III at 20 minutes in the gastric body and the antrum. This study has shown that it is effective to preserve the celiac branch of the vagus nerve for gastroduodenal motility, gastric emptying, and pancreatic insulin release after a gastrectomy.

Obestatin inhibits motor activity in the antrum and duodenum in the fed state of conscious rats

Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its effects on gastrointestinal motility remain controversial. Here we have examined the effects of obestatin on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. We examined the effects of intravenous (IV) injection of obestatin on the percentage motor index (%MI) and phase III-like contractions in the antrum and duodenum. The brain mechanism mediating the action of obestatin on gastroduodenal motility and the involvement of vagal afferent pathway were also examined. Between 30 and 90 min after IV injection, obestatin decreased the %MI in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing factor- and urocortin-2-containing neurons in the paraventricular nucleus in the hypothalamus were activated by IV injection of obestatin. Intracerebroventricular injection of CRF type 1 and type 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of obestatin on duodenal motility but not on antral motility. Obestatin failed to antagonize ghrelin-induced stimulation of gastroduodenal motility. These results suggest that, in the fed state, obestatin inhibits motor activity in the antrum and duodenum and that CRF type 1 and type 2 receptors in the brain might be involved in these effects of obestatin on gastroduodenal motility.

Obestatin inhibits gastroduodenal motility in conscious fed rats via POMC pathway and CRF receptors in the brain

Obestatin is a novel peptide identified from the gene of ghrelin precursor in mice and reported to suppress food intake and gastrointestinal functions and antagonize the effects of ghrelin. Since the inhibitory effects of obestatin have been controversial, we aimed to study the effects of obestatin on the gastroduodenal motility by conscious rat models.

Existe-t-il encore une place pour la dopamine en réanimation pédiatrique ?

Dopamine is mostly used in patients with cardiogenic or septic shock, but its place in critical care medicine is often questioned. Dopamine, of which pharmacology in children is variable, is prescribed for its inotropic effect, associated with an increase in cardiac output and at a lesser degree blood pressure. Beneficial effects (need for renal replacement therapy and mortality) of low dose in patients at risk of, or with acute renal failure are not demonstrated. Dopamine has numerous potential deleterious effects on local circulations (pulmonary, cerebral, coronary and cutaneous), respiratory function, gastroduodenal motility, endocrine function (further depression of the hypothalamic-pituitary axis induced by stress) and immunity (partially due to decreased production of prolactin). Finally, in shocked adults dopamine infusion might be associated with an increase in mortality rate. Dopamine remains the most prescribed catecholamine, either in adults or children. It still is one of the first line drug included in the recent recommendations for the treatment of septic shock (norepinephrine tends to replace it), cardiogenic shock (dobutamine is the first drug), severe head trauma, and organ donor in cerebral death. In conclusion, if dopamine is today less used, there is no proof that its deleterious effects are associated with an excess of mortality. Thus, dopamine still is part of the stock of drugs that act on the cardiocirculatory system (but for how long?).

Perfluorooctane sulfonate influences feeding behavior and gut motility via the hypothalamus

Perfluorinated compounds (PFCs) have been employed as surface treatment agents in a variety of products. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the two most commonly found PFCs in the environment and human blood. We investigated the effects of PFOS and PFOA on feeding behavior. PFOS or PFOA was administered intracerebroventricularly in mice or rats. Following administration, food intake, gastroduodenal motility, gastric emptying, gene expression of hypothalamic neuropeptides, and c-Fos expression along with immunoreaction for urocortin 2 in the paraventricular nucleus (PVN) were determined. Centrally administered PFOS and PFOA decreased food intake. Administration of PFOS decreased gastric emptying and disrupted the fasted motor activity in the antrum and duodenum. The gene expression of urocortin 2 in the hypothalamus and c-Fos expression and immunoreaction for urocortin 2 in the PVN were increased by the action of PFOS. A centrally administered corticotropin-releasing factor type 2 receptor (CRFR2) antagonist blocked PFOS-induced anorexia. These findings indicate that PFOS and PFOA influence feeding behavior. This effect is mediated via the activation of hypothalamic urocortin 2 and CRFR2, and the suppression of gastroduodenal motor activity. These observations indicate that PFCs may act centrally to influence behavior and physiological functions in humans.

Alan Godfrey Johnson

Alan Godfrey Johnson

Study of the duodenal contractile activity during antral contractions

To investigate the hypothesis that duodenal bulb (DB) inhibition on pyloric antrum (PA) contraction is reflex. Balloon (condom)-tipped tube was introduced into 1(st) duodenum (DD) and a manometric tube into each of PA and DD. Duodenal and antral pressure response to duodenal and then PA balloon distension with saline was recorded. These tests were repeated after separate anesthetization of DD and PA. Two and 4 mL of 1(st) DD balloon distension produced no pressure changes in DD or PA (10.7 +/- 1.2 vs 9.8 +/- 1.2, 11.2 +/- 1.2 vs 11.3 +/- 1.2 on H(2)O respectively, P > 0.05). Six mL distension effected 1(st) DD pressure rise (30.6 +/- 3.4 cm H(2)O, P < 0.01) and PA pressure decrease (6.2 +/- 1.4 cm H(2)O, P < 0.05); no response in 2(nd), 3(rd) and 4(th) DD. There was no difference between 6, 8, and 10 mL distensions. Ten mL PA distension produced no PA or 1(st) DD pressure changes (P > 0.05). Twenty mL distension increased PA pressure (92.4 +/- 10.7 cm H(2)O, P < 0.01) and decreased 1(st) DD pressure (1.6 +/- 0.3 cm H(2)O, P < 0.01); 30, 40, and 50 mL distension produced the same effect as the 20 mL distension (P > 0.05). PA or DD distension after separate anesthetization produced no significant pressure changes in PA or DD. Large volume DD distension produced DD pressure rise denoting DD contraction and PA pressure decline denoting PA relaxation. PA relaxation upon DD contraction is postulated to be mediated through a reflex which we call duodeno-antral reflex. Meanwhile, PA distension effected DD relaxation which we suggest to be reflex and termed antro-duodenal reflex. It is suggested that these 2 reflexes, could act as investigative tools in diagnosis of gastroduodenal motility disorders.

Stepped assessment of gastric emptying of a solid meal using the 13C-octanoic acid breath test

The (13)C-octanoic acid breath test is widely used for evaluating gastric emptying of solids. Since the results of this test are influenced by multiple factors such as the time required to grind the solid meal into smaller particles, the gastroduodenal transport time of the ground meal, and the time required for bowel drug absorption and drug dispersion, the administration of a test meal by the oral route alone cannot result in an accurate measurement of the complicated process of emptying the stomach of solids. The aim of the present study was to evaluate each phase of gastric emptying of solids by varying the administration route of the test meal. Six healthy male volunteers (mean age: 33.2 yr) participated in the study. The test meal consisted of a bowl of rice topped with a mixture of boiled chicken and eggs admixed with 100 mg of (13)C-octanoic acid (total: 273 kcal). All subjects were given the test meal by each of the following three methods: 1. Normal oral intake of the test meal, 2. Feeding of the ground test meal through a nasogastric tube, 3. Feeding of the ground test meal through a duodenal tube. For each set of examinations, the mean residence time (MRT), half-emptying time (T(1/2)), gastric emptying coefficient (GEC), lag phase (L-breath), and measured maximum (13)C excretion time (Tmax-measured) were calculated. The data was analyzed to determine the time for each phase of gastric emptying as follows: mean grinding time (MGT) = MRT(oral) - MRT(nasogastric), mean gastroduodenal transport time (MGDTT) = MRT(nasogastric) - MRT (nasoduodenal). Data was expressed as the mean +/- SE. The values of the parameters of MGT were 0.82 +/- 0.50 hr (MRT), 0.64 +/- 0.18 hr (T(1/2)), 0.51 +/- 0.24 hr (L-breath), -0.45 +/- 0.30 hr (GEC), and 49.2 +/- 8.0 min (Tmax-measured). The values of the parameters of MGDTT were 0.87 +/- 0.38 hr (MRT), 0.26 +/- 0.29 hr (T(1/2)), 0.92 +/- 0.36 hr (L-breath), 0.55 +/- 0.23 hr (GEC), and 63.33 +/- 8.16 min (Tmax-measured). The times required for the drug absorption and disposition were 1.60 0.20 hr (MRT), 1.03 +/- 0.24 hr (T(1/2)), 0.10 +/- 0.08 hr (L-breath), 3.72 +/- 0.46 hr (GEC), and 19.67 +/- 2.11 min (Tmax-measured). By varying the administration route of a test meal containing (13)C-octanoic acid, we may be able to assess each phase of the emptying of gastric solids in detail, thus leading to a better understanding of gastroduodenal motility.

Gastric longitudinal shortening may occur during gastric phase III activities in man

The aim of this study was to determine whether the gastric longitudinal shortening occurs during the gastric phase III in man. Intragastric pH and gastroduodenal motility were simultaneously measured by means of a 24-h ambulatory recording system in 14 healthy volunteers. In nine subjects (group A), the catheter assembly was endoscopically clipped to the gastric mucosa with the middle transducer and the distal pH sensor in the antrum. In the remaining five subjects (group B), measurements were performed without securing the assembly. In 23 of the 25 gastrointestinal interdigestive migrating complexes in group A, the distal and middle transducers showed characteristic duodenal contractions (11-12 c.p.m.). Neutralization was noted at the distal pH sensor. Similar phenomena were observed during all 15 gastrointestinal interdigestive migrating complexes in group B. The catheter assemblies escaped into the duodenum despite the fact that they were secured to the stomach. This may be explained by gastric longitudinal shortening during gastric phase III activities. Studies of intragastric physiology with test catheters must take the effect of gastric longitudinal shortening during phase III into consideration.

Acylated ghrelin and des-acyl ghrelin exert different effects on the gastrointestinal motility in conscious rats

Acylated ghrelin and des-acyl ghrelin exert opposite effects on the gastroduodenal motility, the former induces fasted motor activity in the duodenum but the latter disrupts the fasted motor activity in the antrum. Different brain mechanisms seem to be involved in these effects, NPY might be involved in the action of acylated ghrelin, while CRF type 2 receptor might be involved in the action of des-acyl ghrelin.

Antireflux Surgery: New Era's, New Results

INTRODUCTION In the past, surgical treatment for gastroesophageal reflux disease has known its ups and downs. Substantial morbidity in Nissen fundoplication made many pediatricians and also some pediatric surgeons reluctant to propose surgery in GERD.When alternative techniques with less complications, but with the same effect, became available, a number of pediatric surgeons became less restrained to offer surgery as a means of therapy for GERD (1). The advent of in particular protonpump inhibitors (PPIs) has revolutionized the approach to acid-related disorders, reducing the indications for surgery again (2). However, putting children on lifelong PPIs is a dilemma for both doctor and parents. The safety of long-term administration of acid blocking medication needs to be considered in relation to potential consequences of prolonged acid suppression, such as hypergastrinemia, proliferation of gastric flora, enterochromaffin-like cell hyperplasia theoretically leading to gastric cancer (3), and nosocomial infections. As almost half of the pediatric population with GERD is mentally handicapped, nosocomial infections are a non-neglectable thread. When the laparoscopic surgical approach to GERD was introduced in pediatric surgery in the nineties of the last century, it became apparent that this approach was beneficial for the pediatric patient (4). In particular the group of mentally handicapped children, which in the past had always been a complication prone population in regard to postoperative morbidity, duration of hospitalization, and cure of GERD, seemed to benefit from the laparoscopic approach and showed no increase in postoperative morbidity, had a reduced hospital stay and showed an equal cure of GERD as did children in the not-mentally handicapped group (5). In a group of 149 children, operated between 1993 and 2002 laparoscopically according to Thal for GERD, 49% was mentally handicapped. Follow-up ranged from 6 months to 9 years (median 4.5y). Nineteen children died. All but one were not related with the antireflux procedure. Immediate relief of symptoms occurred in 120 children (80,5%). In 29 children the results were less than optimal. Eight patients underwent a laparoscopic redo-procedure (5,4%). However, none of the children with a follow-up of more than five years showed any symptoms anymore. It was concluded from this study that the laparoscopic Thal fundoplication was a safe procedure and that results in the long run were favorable, irrespective of the nature of the cause, i.e. mental retardation (5). Close examination of the subgroup that did not do well directly after the operation, showed that in particular children with motility disorders of the esophagus or gastroduodenal motility disorder continued to have problems. It is therefore of great importance to identify these children during preoperative work-up for GERD. Alternative therapeutic strategies for these patient groups are warranted.

Insulin modulates duodenal vagal afferents basal activity

Hyperglycemia markedly modifies gastro-duodenal motility. The question was raised whether hyperinsulinaemia, which is usually concomitant to hyperglycemia, could be the factor responsible for this effect through alteration of gastro-duodenal sensitivity. Indeed, vagal receptors are directly activated by insulin in lambs. However, insulin action significantly differs in ruminants and non-ruminants. The aim of our study was therefore to check (i) if insulin per se was able to modulate basal and distension induced discharges of duodenal vagal afferents in a monogatric animal model and (ii) if its action was direct or indirect through changes in gut compliance. Fourteen duodenal mechanoreceptors were studied in anaesthetized curarized pigs using the “single-fiber” method performed on the left cervical vagus. The characteristics of the vagal receptors were studied before (Control), and after (i) local insulin infusion in the gastroepiploic artery (IA), (ii) IV insulin perfusion inducing systemic hypoglycemia (IV), and (iii) during an euglycemic hyperinsulinemic clamp (EH). Basal recording, isobaric and isovolumetric distensions were performed in all experimental conditions. Basal discharge was significantly increased during IA (5.8 ± 0.28 spikes/5 s), IV (6.6 ± 0.30 spikes/5 s) and EH (5.7 ± 0.25 spikes/5 s) compared to Control (4.4 ± 0.27 spikes/5 s, p < 0.05). Responses during isobaric and isovolumetric distensions were identical irrespective of the experimental condition. Gut compliance and intraluminal pressure during basal recording were not modified ( p > 0.05). In conclusion, insulin increased duodenal vagal mechanoreceptors basal activity but did not modulate the mechanosensitivity of the vagal units. Insulin-induced increase in basal discharge rate was due to hyperinsulinemia per se since it persisted during the euglycemic hyperinsulinemic clamp.

Des-acyl Ghrelin Acts by CRF Type 2 Receptors to Disrupt Fasted Stomach Motility in Conscious Rats

Although it has been shown that des-acyl ghrelin decreases food intake and gastric emptying, no previous studies have examined the effects of des-acyl ghrelin on physiologic fed and fasted motor activity in the gastrointestinal tract. We examined the effects of intraperitoneal (IP) administration of des-acyl ghrelin on food intake and the effects of intracerebroventricular (ICV) or intravenous (IV) administration of des-acyl ghrelin on gastroduodenal motility using freely moving conscious rat models. The brain nuclei responding to these effects were examined by c- fos immunohistochemistry of the brain sections. IP injection of des-acyl ghrelin decreased food intake, and this effect was not altered by capsaicin treatment. IP injection of des-acyl ghrelin enhanced c- fos expression in the arcuate and paraventricular nucleus but not in the nucleus of the solitary tract. Both ICV and IV injection of des-acyl ghrelin disrupted fasted motor activity in the antrum but not in the duodenum. Changes in gastric motility induced by IV injection of des-acyl ghrelin were completely antagonized by ICV injection of a selective corticotropin-releasing factor (CRF) 2 receptor antagonist; however, the CRF 1 receptor antagonist had no effects. The results suggest that des-acyl ghrelin decreases food intake and disrupts the fasted motor activity of the antrum in freely moving conscious rats. Peripheral des-acyl ghrelin may induce this function by direct activation of brain receptor by crossing the blood-brain barrier but not by the activation of vagal afferent pathways. In the brain, CRF 2 receptor, but not CRF 1 receptor, is involved in this action.

Mechanisms underlying duodeno‐gastric reflux in man

Recent studies suggest that duodeno-gastro-oesophageal reflux (DGER) contributes to the occurrence of reflux oesophagitis and Barrett's oesophagus. The mechanisms underlying duodeno-gastric reflux (DGR), a prerequisite for DGER, are poorly understood. To study the occurrence of DGR in relation to interdigestive and postprandial gastroduodenal motility. Ten healthy subjects underwent stationary gastroduodenal manometry with simultaneous duodenal and antral Bilitec recording 4 h before and 5 h after ingestion of a liquid meal. Eight volunteers underwent the same study, with administration of erythromycin postprandially. During the interdigestive phase II, all volunteers had short DGR episodes. Postprandially, DGR occurred in all subjects, on average 39 +/- 28 min after the start of the meal, and was cleared from the stomach after 242 +/- 23 min. Induction of increased antral motility and of a premature phase III, by administration of erythromycin, was associated with faster gastric DGR clearance. However, there was no direct temporal relationship between erythromycin-induced gastric phase III and erythromycin-induced DGR clearance. In healthy subjects, duodenogastric reflux occurs sporadically in the interdigestive state and is a normal phenomenon in the postprandial period. Erythromycin induces faster clearance of DGR from the stomach, which depends on enhanced antral contractile activity rather than premature phase III.