Neurogastroenterology and Motility via MedWorm.com

Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system

Neurogastroenterology and Motility — Sat, 13 Mar 2010 00:00:00 +0100

Conclusions & Inferences G protein coupled bile acid receptor 1 is unexpectedly expressed in enteric neurons. Bile acids activate GpBAR1 on inhibitory motor neurons to release nitric oxide and suppress motility, revealing a novel mechanism for the actions of BAs on intestinal motility. (Source: Neurogastroenterology and Motility)

Cisplatin-induced gastrointestinal dysmotility is aggravated after chronic administration in the rat. Comparison with pica

Neurogastroenterology and Motility — Fri, 12 Mar 2010 00:00:00 +0100

Conclusions & Inferences Whereas gastric dysmotility induced by cisplatin is parallel to the development of acute pica and might underlie facilitation of pica throughout chronic treatment, it does not explain its long-term maintenance. These findings should be taken into account in the search for new antiemetic strategies. (Source: Neurogastroenterology and Motility)

Enhancement of intestinal inflammation in mice lacking interleukin 10 by deletion of the serotonin reuptake transporter

Neurogastroenterology and Motility — Mon, 08 Mar 2010 00:00:00 +0100

Conclusions & Inferences Our observations indicate that colitis associated with IL-10 deficient mice is enhanced when the IL-10 deficiency is combined with a SERT deficiency. The data support the concept that 5-HT is a pro-inflammatory mediator in the gut. (Source: Neurogastroenterology and Motility)

Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons

Neurogastroenterology and Motility — Thu, 04 Mar 2010 00:00:00 +0100

Conclusions & Inferences These observations suggest that chronic colonic inflammation is ameliorated by the systemic administration of S/OT, which probably explains the parallel ability of systemic S/OT to inhibit the colitis-associated activation of forebrain neurons. It is possible that S and OT, which are endogenous to the colon, might normally combine to restrict the severity of colonic inflammatory responses and that advantage might be taken of this system to develop novel means of treating inflammation-associated intestinal disorders. (Source: Neurogastroenterology and Motility)

Bowel preparation affects the amplitude and spatiotemporal organization of colonic propagating sequences

Neurogastroenterology and Motility — Thu, 25 Feb 2010 00:00:00 +0100

Conclusions & Inferences The overall frequency of PSs, the colonic responses to physiological stimuli such a meal and morning waking and nocturnal suppression, are not influenced by prior bowel preparation. However, investigators wishing to study HAPS frequency, or the more complex spatiotemporal relationships among consecutive PSs, should control for bowel preparation when making comparisons among study groups. (Source: Neurogastroenterology and Motility)

Differential effects of CB1 neutral antagonists and inverse agonists on gastrointestinal motility in mice

Neurogastroenterology and Motility — Wed, 24 Feb 2010 00:00:00 +0100

Conclusions & Inferences Cannabinoid type 1 receptors regulate small intestinal and colonic motility, but not GI secretion under physiological conditions. Cannabinoid type 1 inverse agonists and CB1 neutral antagonists have different effects on intestinal motility. The ability of the neutral antagonist not to affect whole gut transit may be important for the future development of CB1 receptor antagonists as therapeutic agents. (Source: Neurogastroenterology and Motility)

Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors

Neurogastroenterology and Motility — Wed, 17 Feb 2010 00:00:00 +0100

Conclusions & Inferences The present results suggest that GLP-1 is able to act in the enteric nervous system by decreasing the excitatory cholinergic neurotransmission through presynaptic GLP-1Rs, which modulate NO release. (Source: Neurogastroenterology and Motility)

Cannabinoid 1 receptors modulate intestinal sensory and motor function in rat

Neurogastroenterology and Motility — Tue, 16 Feb 2010 00:00:00 +0100

Conclusions & Inferences Activation of the CB1 receptor differentially alters afferent intestinal nerve sensitivity to bradykinin, 5-HT, and noxious mechanical distension, while it strengthens ascending neuronal contractions. Further studies are needed to determine the physiological relevance of these observations. (Source: Neurogastroenterology and Motility)

Anorectal function in patients with collagenous colitis in active and clinically quiescent phase, in comparison with healthy controls

Neurogastroenterology and Motility — Sat, 13 Feb 2010 00:00:00 +0100

Conclusions & Inferences Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC. (Source: Neurogastroenterology and Motility)

Stress-induced barrier disruption of rat follicle-associated epithelium involves corticotropin-releasing hormone, acetylcholine, substance P, and mast cells

Neurogastroenterology and Motility — Wed, 10 Feb 2010 00:00:00 +0100

Conclusions & Inferences Corticotropin-releasing hormone and acetylcholine signaling affect mainly transcellular permeability while SP seems more selective toward the paracellular pathways. Our findings may be of importance for the understanding of the pathogenesis of stress-related intestinal disorders. (Source: Neurogastroenterology and Motility)

Localization of muscarinic receptors M1R, M2R and M3R in the human colon

Neurogastroenterology and Motility — Tue, 09 Feb 2010 00:00:00 +0100

Conclusions & Inferences In the human colon, subtypes of MRs were present on multiple cell types within the enteric circuits underlying motility, secretory and vasoactive reflexes. The cellular distribution for MRs found in this study agrees with data from functional studies, providing insight into the role MRs have in mediating enteric cholinergic neurotransmission. (Source: Neurogastroenterology and Motility)

A 5-HT4-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult

Neurogastroenterology and Motility — Mon, 08 Feb 2010 00:00:00 +0100

Conclusions & Inferences These results indicate that activation of enteric neural 5-HT4-receptors promotes reconstruction of an enteric neural circuit leading to the recovery of the defecation reflex in the distal gut, and that this reconstruction involves possibly neural stem cells. These findings indicate that treatment with 5-HT4 agonists could be a novel therapy for generating new enteric neurons to rescue aganglionic gut disorders. (Source: Neurogastroenterology and Motility)

The cannabinoid antagonist SR144528 enhances the acute effect of WIN 55,212-2 on gastrointestinal motility in the rat

Neurogastroenterology and Motility — Wed, 03 Feb 2010 00:00:00 +0100

Conclusions & Inferences X-ray analyses confirm that cannabinoids inhibit GI motility via CB1 receptors; in addition, cannabinoids could influence motility through interaction with a SR144528-sensitive site. Further studies are needed to verify if such site of action is the CB2 receptor. (Source: Neurogastroenterology and Motility)

Increased colonic motility in a rat model of irritable bowel syndrome is associated with up-regulation of L-type calcium channels in colonic smooth muscle cells

Neurogastroenterology and Motility — Mon, 01 Feb 2010 00:00:00 +0100

Conclusion These results suggest that NMS lead to up-regulation of L-type Ca2+ channels expression in the colon, which contributes to the colonic motility disorder. Our findings provide direct evidence to help understanding the underlying mechanism of chronic stress-induced colonic motility disorder in IBS. (Source: Neurogastroenterology and Motility)

Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule

Neurogastroenterology and Motility — Sat, 30 Jan 2010 00:00:00 +0100

Conclusions & Inferences The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles. (Source: Neurogastroenterology and Motility)

Effect of proximal gastric volume on hiatal hernia

Neurogastroenterology and Motility — Thu, 28 Jan 2010 00:00:00 +0100

Conclusions & Inferences (i) In GERD patients a postprandial increase in proximal gastric volume is accompanied by a decrease in hernia prevalence, which can be explained by a reduction of the intra-thoracic part of the stomach. (ii) A temporal hernia profile also occurs in healthy subjects. (iii) During the hernia profile, acid reflux is more prevalent, especially after meal ingestion. (Source: Neurogastroenterology and Motility)

Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain

Neurogastroenterology and Motility — Thu, 21 Jan 2010 00:00:00 +0100

Conclusion & Inferences Bowel disorders including chronic abdominal pain and NBS are common in patients taking opioids for CNCP. Decreased HRQoL in patients with CNCP is driven by chronic abdominal pain. (Source: Neurogastroenterology and Motility)

Acid-induced CGRP release from the stomach does not depend on TRPV1 or ASIC3

Neurogastroenterology and Motility — Thu, 21 Jan 2010 00:00:00 +0100

Conclusions & Inferences Adequate proton concentrations inhibit prostaglandin and stimulate CGRP release from the stomach wall, however, the transduction mechanism in the gastric sensory neurons remains unclear. (Source: Neurogastroenterology and Motility)

Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

Neurogastroenterology and Motility — Thu, 21 Jan 2010 00:00:00 +0100

Conclusions & Inferences The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders. (Source: Neurogastroenterology and Motility)

Assessment of symptoms during gastric emptying scintigraphy to correlate symptoms to delayed gastric emptying

Neurogastroenterology and Motility — Mon, 18 Jan 2010 00:00:00 +0100

Conclusions & Inferences Stomach fullness, bloating, and abdominal pain recorded during GES were higher in patients with delayed gastric emptying than in patients with normal gastric emptying. Symptoms recorded during GES correlated with those during daily life by patient recall. (Source: Neurogastroenterology and Motility)

The role of neural activity in the migration and differentiation of enteric neuron precursors

Neurogastroenterology and Motility — Mon, 18 Jan 2010 00:00:00 +0100

Conclusions & Inferences (i) Some enteric neuron sub-types are present very early during the development of the enteric nervous system. (ii) The rate of differentiation of some sub-types of enteric neurons appears to be influenced by TTX- and tetanus toxin-sensitive mechanisms. (Source: Neurogastroenterology and Motility)

Effects of autonomic nerve stimulation on colorectal motility in rats

Neurogastroenterology and Motility — Wed, 13 Jan 2010 00:00:00 +0100

Conclusions & Inferences Vagal innervation extends to the distal colon, while the PN has projections in the distribution of the rectum through the mid colon. This suggests a pattern of dual parasympathetic innervation in the left colon. Parasympathetic fibers regulate colorectal contractions via muscarinic receptors. The HGN mainly regulates colorectal relaxations via beta-adrenoceptors. (Source: Neurogastroenterology and Motility)

Investigation of esophageal sensation and biomechanical properties in functional chest pain

Neurogastroenterology and Motility — Tue, 12 Jan 2010 00:00:00 +0100

Conclusions & Inferences Seventy-five per cent of subjects with FCP demonstrate esophageal hypersensitivity. Visceral hyperalgesia and sensori-motor dysfunction of the esophagus play a key role in the pathogenesis of chest pain. (Source: Neurogastroenterology and Motility)

Varying postprandial abdominovagal and cardiovagal activity in normal subjects

Neurogastroenterology and Motility — Fri, 08 Jan 2010 00:00:00 +0100

Conclusions & Inferences These findings suggest that HRV reflects cardiac, but not equivalently, abdominovagal activity. Therefore, HRV as an abdominovagal activity measurement in patients with GI functional problems should be used with caution, and other markers such as PP should be included. (Source: Neurogastroenterology and Motility)

Non-peristaltic patterns of motor activity in the guinea-pig proximal colon

Neurogastroenterology and Motility — Thu, 07 Jan 2010 00:00:00 +0100

Conclusions & Inferences The interaction of myogenic 'ripples' with neurogenic 'abrupt contractions' generates localized alternating rings of contractions and dilatation, well suited to effective mixing of contents. (Source: Neurogastroenterology and Motility)

Riser's reflux – an eye-opening experience

Neurogastroenterology and Motility — Tue, 05 Jan 2010 00:00:00 +0100

Conclusions & Inferences Riser's reflux is very common among GORD patients and possibly may explain reports of early-morning GORD symptoms. (Source: Neurogastroenterology and Motility)

ICC-MY coordinate smooth muscle electrical and mechanical activity in the murine small intestine

Neurogastroenterology and Motility — Tue, 05 Jan 2010 00:00:00 +0100

Conclusions & Inferences These results show how dominance of pacemaking by ICC-MY coordinates propagating con-tractions and regulates the spontaneous activity of smooth muscle. (Source: Neurogastroenterology and Motility)

Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia – 100 mg t.i.d. is an optimal dosage

Neurogastroenterology and Motility — Tue, 05 Jan 2010 00:00:00 +0100

Conclusions & Inferences These results suggest that acotiamide possesses efficacy on FD and more specifically its meal-related symptoms of FD. (Source: Neurogastroenterology and Motility)

NK-1 receptor is involved in the decreased movement in a rat chronic acid reflux oesophagitis model

Neurogastroenterology and Motility — Tue, 05 Jan 2010 00:00:00 +0100

Conclusions & Inferences The NK-1R and related neuropeptides are possibly involved in the decrease in voluntary movement of RE. (Source: Neurogastroenterology and Motility)

Impaired intestinal gas propulsion in manometrically proven dysmotility and in irritable bowel syndrome

Neurogastroenterology and Motility — Tue, 29 Dec 2009 00:00:00 +0100

Conclusion & Inferences Patients with manometric dysmotility have markedly impaired intestinal gas propulsion. In IBS patients, impaired gas propulsion is less pronounced but associated with concomitant sensory dysfunction and poor tolerance of gas retention. (Source: Neurogastroenterology and Motility)

The contractile deceleration point: an important physiologic landmark on oesophageal pressure topography

Neurogastroenterology and Motility — Mon, 28 Dec 2009 00:00:00 +0100

Conclusions & Inferences The deceleration point in the CFV on OPT plots accurately demarcated the early region in which the CFV reflects peristaltic velocity (CFVfast) from the later region where it reflects the progression of ampullary emptying (CFVslow). These distinctions should help objectify definitions of disordered peristalsis, especially spasm, and improve understanding of impaired bolus transit across the oesophagogastric junction. (Source: Neurogastroenterology and Motility)

Diverticular disease is associated with an enteric neuropathy as revealed by morphometric analysis

Neurogastroenterology and Motility — Thu, 24 Dec 2009 00:00:00 +0100

Conclusions & Inferences Patients with DD show substantial structural alterations of the ENS mainly characterized by myenteric and submucosal oligo-neuronal hypoganglionosis which may account for intestinal motor abnormalities reported in DD. The morphometric data give evidence that DD is associated with structural alterations of the ENS which may complement established pathogenetic concepts. (Source: Neurogastroenterology and Motility)

Delayed gastric emptying and disruption of the interstitial cells of Cajal network after gastric ischaemia and reperfusion

Neurogastroenterology and Motility — Wed, 23 Dec 2009 00:00:00 +0100

Conclusions & Inferences Gastric I/R evokes transient gastroparesis with delayed gastric emptying, associated with disruption of the ICC network and nNOS-positive neurons. (Source: Neurogastroenterology and Motility)

Serum correlates of the placebo effect in irritable bowel syndrome

Neurogastroenterology and Motility — Tue, 22 Dec 2009 00:00:00 +0100

Conclusions & Inferences These two measurable biological parameters associated with placebo, namely serum OPG and TWEAK, provide a proof of principle for discovering putative molecular signatures of placebo response in IBS and perhaps in other illnesses with patient self-reported outcomes. (Source: Neurogastroenterology and Motility)

Lower functional gastrointestinal disorders: evidence of abnormal colonic transit in a 287 patient cohort

Neurogastroenterology and Motility — Mon, 21 Dec 2009 00:00:00 +0100

Conclusions & Inferences Abnormal transit is documented non-invasively with scintigraphy in 30% of lower FGID patients; transit measurement may help document pathophysiology and inform selection of therapy in lower FGID. (Source: Neurogastroenterology and Motility)

Performance characteristics of scintigraphic colon transit measurement in health and irritable bowel syndrome and relationship to bowel functions

Neurogastroenterology and Motility — Fri, 18 Dec 2009 00:00:00 +0100

Conclusions & Inferences Despite inter-subject variation in scintigraphic colonic transit results, the intra-subject measurements are reproducible over time in healthy volunteers and patients with IBS; significant changes in colonic transit at 24 h were observed only in IBS-D. Colonic transit is associated with stool form, frequency and ease of passage. (Source: Neurogastroenterology and Motility)

Influence of 5-HT4 receptor activation on acetylcholine release in human large intestine with endometriosis

Neurogastroenterology and Motility — Fri, 18 Dec 2009 00:00:00 +0100

Conclusions & inferences Large intestinal endometriosis does not lead to a systematic interference with the cholinergic facilitating effect of prucalopride. (Source: Neurogastroenterology and Motility)

Glucagon-like peptide-1 inhibits voltage-gated potassium currents in mouse nodose ganglion neurons

Neurogastroenterology and Motility — Fri, 11 Dec 2009 00:00:00 +0100

Conclusions & Inferences These experiments indicate that GLP-1 receptor activation results in vagal afferent excitation, due at least in part to inhibition of sustained and inactivating potassium currents. This mechanism may be important in satiety and glucose homeostatic signals arising from the gastrointestinal tract. (Source: Neurogastroenterology and Motility)

Heightened central affective response to visceral sensations of pain and discomfort in IBS

Neurogastroenterology and Motility — Fri, 11 Dec 2009 00:00:00 +0100

Conclusion&Inferences This work points to alterations in the central response to visceral pain and discomfort in IBS, highlighting diminished modulation and heightened internalization of affective reactions. (Source: Neurogastroenterology and Motility)

Gastroparesis and functional dyspepsia: excerpts from the AGA/ANMS meeting

Neurogastroenterology and Motility — Wed, 09 Dec 2009 00:00:00 +0100

Background Despite the relatively high prevelance of gastroparesis and functional dyspepsia, the aetiology and pathophysiology of these disorders remain incompletely understood. Similarly, the diagnostic and treatment options for these two disorders are relatively limited despite recent advances in our understanding of both disorders.Purpose This manuscript reviews the advances in the understanding of the epidemiology, pathophysiology, diagnosis, and treatment of gastroparesis and functional dyspepsia as discussed at a recent conference sponsored by the American Gastroenterological Association (AGA) and the American Neurogastroenterology and Motility Society (ANMS). Particular focus is placed on discussing unmet needs and areas for future research. (Source: Neurogastroenterology and Motili...

5-HT2B receptors modulate visceral hypersensitivity in a stress-sensitive animal model of brain-gut axis dysfunction

Neurogastroenterology and Motility — Wed, 09 Dec 2009 00:00:00 +0100

Conclusions & Inferences Taken together, blockade of 5-HT2B receptors offers an exciting novel therapeutic target for pain relief in stress-related gastrointestinal disorders such as IBS. (Source: Neurogastroenterology and Motility)

Inhibition of p38 MAPK improves intestinal disturbances and oxidative stress induced in a rabbit endotoxemia model

Neurogastroenterology and Motility — Wed, 09 Dec 2009 00:00:00 +0100

Conclusions & Inferences Lipopolysaccharide decreases the duodenal contractility in rabbits and increases the production of free radicals. p38 MAPK is a mediator of these effects. (Source: Neurogastroenterology and Motility)

Lack of serotonin 5-HT2B receptor alters proliferation and network volume of interstitial cells of Cajal in vivo

Neurogastroenterology and Motility — Thu, 26 Nov 2009 00:00:00 +0100

Conclusions & Inferences Interstitial cells of Cajal proliferate in adult mice and activation of 5-HT2B receptors results in increased proliferation of ICC in vivo. Furthermore, lack of 5-HT2B receptor signaling reduces the density of ICC networks in mature mice. These data suggest that 5-HT2B receptor signaling is required for maintenance of ICC networks, adding 5-HT to the growing number of factors shown to regulate ICC networks. (Source: Neurogastroenterology and Motility)

Prokineticin-1 evokes secretory and contractile activity in rat small intestine

Neurogastroenterology and Motility — Wed, 25 Nov 2009 00:00:00 +0100

Conclusions & Inferences These results demonstrate that PROK1 has oral prokinetic and secretogogue activity and that it acts on the intestinal mucosa via PK-R1 and prostaglandin receptors to mediate these effects. (Source: Neurogastroenterology and Motility)

Rumination or belching–regurgitation? Differential diagnosis using oesophageal impedance–manometry

Neurogastroenterology and Motility — Wed, 25 Nov 2009 00:00:00 +0100

Conclusions & Inferences Postprandial impedance[ndash]manometry monitoring improves diagnosis of rumination because it allows distinction between rumination and postprandial belching and regurgitation. During rumination, oesophageal liquid retrograde flow is first driven by an early small rise in intragastric pressure preceding the peak pressure observed during straining. (Source: Neurogastroenterology and Motility)

The microenvironment in chronic pancreatitis and pancreatic cancer induces neuronal plasticity

Neurogastroenterology and Motility — Thu, 12 Nov 2009 00:00:00 +0100

Conclusions & Inferences Intrapancreatic microenvironment in CP and PCa induces neuroplastic alterations under in-vitro conditions, leading to increased neural density and hypertrophy. Thus, due to its neurotrophic attributes, the intrapancreatic microenviroment in CP and PCa seems to be a key player in the generation of pancreatic neuropathy and neuroplasticity. (Source: Neurogastroenterology and Motility)

Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome

Neurogastroenterology and Motility — Tue, 10 Nov 2009 00:00:00 +0100

Conclusions & Inferences These results support the hypothesis that both fecal microbiota and organic acids are altered in IBS patients. A combination of Veillonella and Lactobacillus is known to produce acetic and propionic acid. High levels of acetic and propionic acid may associate with abdominal symptoms, impaired QOL and negative emotions in IBS. (Source: Neurogastroenterology and Motility)

Long pulse gastric electrical stimulation induces regeneration of myenteric plexus synaptic vesicles in diabetic rats

Neurogastroenterology and Motility — Mon, 02 Nov 2009 00:00:00 +0100

Conclusions & Inferences The longer duration of diabetes, the more significant damages to myenteric neurons and synaptic vesicles of diabetic rats; long pulse GES could induce regeneration of myenteric plexus synaptic vesicles, thereby reform gastric motility. (Source: Neurogastroenterology and Motility)

Laser microdissection as a new tool to investigate site-specific gene expression in enteric ganglia of the human intestine

Neurogastroenterology and Motility — Fri, 23 Oct 2009 23:00:00 +0100

Conclusions & Inferences Laser microdissection combined with real-time RT-PCR is a novel technique to reliably detect and quantify site-specific expression of low-abundance mRNAs (e.g. growth factors, neurotransmitter receptors) related to the human enteric nervous system. This technical approach expands the spectrum of available tools to characterize enteric neuropathologies underlying human gastrointestinal motility disorders at the molecular biological level. (Source: Neurogastroenterology and Motility)

Decrease in nerve fibre density in human sigmoid colon circular muscle occurs with growth but not aging

Neurogastroenterology and Motility — Thu, 15 Oct 2009 23:00:00 +0100

Conclusions & Inferences In human sigmoid colon circular muscle, there are reductions in nNOS-, VIP- and SP-IR nerve fibre density with growth from newborn to late adolescence but little further change with aging. The reduction in nerve density is due to an increase in circular muscle thickness rather than a loss of nerve fibres. (Source: Neurogastroenterology and Motility)

Unexplained gastrointestinal symptoms and joint hypermobility: is connective tissue the missing link?

Neurogastroenterology and Motility — Wed, 14 Oct 2009 23:00:00 +0100

Conclusions & Inferences In a preliminary retrospective study, we have found a high incidence of JHM in patients referred to tertiary neurogastroenterology care with unexplained GI symptoms and in a proportion of these a diagnosis of BJHS is made. Symptoms and functional tests suggest GI dysmotility in a number of these patients. The possibility that a proportion of patients with unexplained GI symptoms and JHM may share a common pathophysiological disorder of connective tissue warrants further investigation. (Source: Neurogastroenterology and Motility)

Involvement of cannabinoid-1 and cannabinoid-2 receptors in septic ileus

Neurogastroenterology and Motility — Wed, 14 Oct 2009 23:00:00 +0100

Conclusions & Inferences The LPS model of septic ileus impairs jejunal myoelectrical activity and delays GI transit in vivo. Antagonists at the CB1 receptor or the CB2 receptor prevent the delay of GI transit and thus may be powerful tools in the future treatment of septic ileus. (Source: Neurogastroenterology and Motility)

Ghrelin stimulates gastric motility of the guinea pig through activation of a capsaicin-sensitive neural pathway: in vivo and in vitro functional studies

Neurogastroenterology and Motility — Wed, 14 Oct 2009 23:00:00 +0100

Conclusions & Inferences Ghrelin stimulates gastric motility of the guinea pig through activation of capsaicin-sensitive vago-vagal reflex pathway including efferent cholinergic neurons. Peripheral ghrelin receptors on enteric nitrergic nerves might affect the ghrelin-induced gastric action by releasing nitric oxide. (Source: Neurogastroenterology and Motility)

Site-specific differences in central processing of visceral stimuli from the rectum and the descending colon in men

Neurogastroenterology and Motility — Mon, 12 Oct 2009 23:00:00 +0100

Conclusions & Inferences These findings suggest that central projections of painful visceral stimulation from the rectum and descending colon differ in affective, cognitive and nociceptive processing in the brain, which may result in different perceptions of visceral stimulation from different sites. (Source: Neurogastroenterology and Motility)

Is there any association between disturbed gastrointestinal visceromotor and sensory function and impaired quality of life in functional dyspepsia?

Neurogastroenterology and Motility — Thu, 08 Oct 2009 23:00:00 +0100

Conclusions & Inferences In EPS and PDS, delayed gastric empting and altered sensory function are disease markers but not directly linked to the severity of HRQOL impairment or clinical presentation of FD. (Source: Neurogastroenterology and Motility)

Does body position modify the results of oesophageal high resolution manometry?

Neurogastroenterology and Motility — Wed, 07 Oct 2009 23:00:00 +0100

Conclusions & Inferences Body position can affect OGJ morphology and oesophageal motility assessment by HRM in some patients. Normal values in the sitting position should thus be determined. Inter-observer variation for the proposed classification of OGJ morphology must also be taken into account. (Source: Neurogastroenterology and Motility)

Enteric circular muscle dysfunction in the cystic fibrosis mouse small intestine

Neurogastroenterology and Motility — Wed, 07 Oct 2009 23:00:00 +0100

Conclusions & Inferences These results suggest that the enteric microbiota modulates PGE2 levels in a complex manner, which affects enteric smooth muscle activity and contributes to slower small intestinal transit in CF. (Source: Neurogastroenterology and Motility)

The ageing gut: diminished symptom response to a standardized nutrient stimulus

Neurogastroenterology and Motility — Wed, 07 Oct 2009 23:00:00 +0100

Background The prevalence of dyspepsia and the severity of reflux symptoms decreases with advancing age. We postulate that advancing age influences sensory function and this will be associated with a diminished symptom response to a standardized meal stimulus.Our aim was to assess the influence of age on visceral sensory function.Methods Baseline gastrointestinal symptoms and anxiety and depression were assessed in 53 healthy volunteers using validated questionnaires. After an 8-h fast, subjects received 200 mL of a standardized enteral feeding solution every 5 min up to a cumulative volume of 800 mL. After each 200 mL drink, five key symptoms were assessed (fullness, abdominal pain, retrosternal/abdominal burning, nausea and regurgitation) using a standardized instrument on visual analogu...

Differential stress-induced alterations of colonic corticotropin-releasing factor receptors in the Wistar Kyoto rat

Neurogastroenterology and Motility — Mon, 05 Oct 2009 23:00:00 +0100

Conclusions & Inferences This study demonstrates that psychological and physical stressors alter colonic CRF receptor expression and further support a role for local colonic CRF signalling in stress-induced changes in GI function. (Source: Neurogastroenterology and Motility)

Prolonged IL-1β exposure alters neurotransmitter and electrically induced Ca2+ responses in the myenteric plexus

Neurogastroenterology and Motility — Thu, 01 Oct 2009 23:00:00 +0100

Conclusions & Inferences In this study, IL-1[beta] differentially modulates the neuronal response to eFTS and neurotransmitter application in the myenteric plexus of guinea pigs. This cytokine could be implicated in the motility disturbances observed during gastrointestinal inflammation. (Source: Neurogastroenterology and Motility)

Lactobacillus reuteri ingestion and IKCa channel blockade have similar effects on rat colon motility and myenteric neurones

Neurogastroenterology and Motility — Mon, 28 Sep 2009 23:00:00 +0100

Conclusions & Inferences The present results are consistent with L. reuteri enhancing tonic inhibition of colon contractile activity by acting via the IKCa channel current in AH cells. (Source: Neurogastroenterology and Motility)

Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies

Neurogastroenterology and Motility — Tue, 22 Sep 2009 23:00:00 +0100

Conclusions & Inferences Age and an absence of Et-3 from the recipient gut both significantly reduced but did not prevent ENCC migration, but the presence of neurones almost totally prevented ENCC migration. (Source: Neurogastroenterology and Motility)

Constipation: a potential cause of pelvic floor damage?

Neurogastroenterology and Motility — Thu, 17 Sep 2009 23:00:00 +0100

Conclusions & Inferences Constipation appears to be as important as obstetric trauma in the development of pelvic floor damage. Thus, a more proactive approach to recognizing and treating constipation might significantly reduce the prevalence of this distressing problem. (Source: Neurogastroenterology and Motility)

Psychometric performance and clinical meaningfulness of the Patient Assessment of Constipation – Quality of Life questionnaire in prucalopride (RESOLOR®) trials for chronic constipation

Neurogastroenterology and Motility — Wed, 16 Sep 2009 23:00:00 +0100

Conclusions & Inferences The PAC-QOL questionnaire is a useful measurement tool to assess, from a patient perspective, the potential therapeutic value of chronic constipation treatments in clinical trials and, by directly reflecting the patient's own perspective on constipation and its treatment, eventually also for informing daily medical practice. (Source: Neurogastroenterology and Motility)

Somatostatin receptor subtypes 2 and 5 mediate inhibition of egg yolk-induced gall bladder emptying in mice

Neurogastroenterology and Motility — Tue, 15 Sep 2009 23:00:00 +0100

Conclusions & Inferences Our study provides evidence for the role of SSTR2 and SSTR5 in regulating gall bladder emptying in mice. (Source: Neurogastroenterology and Motility)

Safety assessment of prucalopride in elderly patients with constipation: a double-blind, placebo-controlled study

Neurogastroenterology and Motility — Sun, 13 Sep 2009 23:00:00 +0100

AbstractChronic constipation is common among nursing home residents. The aim of this study was to evaluate safety, tolerability and pharmacokinetics of the selective 5HT4 receptor agonist prucalopride in elderly, chronically constipated patients in nursing homes. A multicentre, phase II, randomized, double-blind dose-escalation study in 89 elderly constipated nursing home residents treated with placebo, 0.5, 1 or 2 mg prucalopride once daily for 28 days was analysed. Adverse events, vital signs, ECG, Holter monitor and pharmacokinetics were assessed (Clinicaltrials.gov identifier: NCT00627692). Patients' mean age was 83 years; 88% had a history of cardiovascular diseases. Most frequent adverse events, at least possibly related to prucalopride, were diarrhoea and abdominal pain. Relative to...

The effect of esomeprazole 20 mg twice daily on acoustic and perception parameters of the voice in laryngopharyngeal reflux

Neurogastroenterology and Motility — Tue, 08 Sep 2009 23:00:00 +0100

Conclusions & Inferences Use of more specific laryngeal functional parameters such as voice-related acoustic measures of pitch range, fundamental frequency and intensity also failed to demonstrate a significant response to proton pump inhibitor treatment as compared to placebo in patients with suspected LPR. (Source: Neurogastroenterology and Motility)

A selective, high affinity 5-HT2B receptor antagonist inhibits visceral hypersensitivity in rats

Neurogastroenterology and Motility — Tue, 08 Sep 2009 23:00:00 +0100

Conclusions & Inferences These results suggest that 5-HT2Breceptors are involved in signaling from the colon in rats in which there is visceral hypersensitivity and that a selective 5-HT2Breceptor antagonist could have therapeutic potential for the treatment of gut disorders characterized by visceral hypersensitivity. (Source: Neurogastroenterology and Motility)

Proteinase-activated receptor-2 activation evokes oesophageal longitudinal smooth muscle contraction via a capsaicin-sensitive and neurokinin-2 receptor-dependent pathway

Neurogastroenterology and Motility — Tue, 08 Sep 2009 23:00:00 +0100

Conclusions & Inferences Longitudinal smooth muscle contraction induced by trypsin involves capsaicin-sensitive neurons and subsequent activation of NK-2, which is identical to the pathway involved in acid-induced LSM contraction and oesophageal shortening. This suggests that acid-induced LSM contraction may involve mast cell-derived mediators that activate capsaicin-sensitive neurons via PAR-2. (Source: Neurogastroenterology and Motility)

CaM kinase II in colonic smooth muscle contributes to dysmotility in murine DSS-colitis

Neurogastroenterology and Motility — Mon, 07 Sep 2009 23:00:00 +0100

Conclusions & Inferences These results suggest that disruptions in intracellular Ca2+ mobilization due to down-regulation of SERCA2 and phospholamban expression lead to increased CaM kinase II activity and cytosolic HDAC4 that may contribute to the dysmotility of colonic smooth muscles in colitis by enhancing NF-[kappa]B activity. (Source: Neurogastroenterology and Motility)

Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy

Neurogastroenterology and Motility — Sun, 06 Sep 2009 23:00:00 +0100

Conclusions & Inferences Intestinal muscle hypercontractility in remission is maintained at the smooth muscle cell level. Th2 cytokines and 5-HT in the small intestine contribute to the maintenance of the altered muscle function in recovery phase. (Source: Neurogastroenterology and Motility)

Motility of the oesophagus and small bowel in adults treated for Hirschsprung's disease during early childhood

Neurogastroenterology and Motility — Sun, 06 Sep 2009 23:00:00 +0100

Conclusions & Inferences This study demonstrates that adult patients with HD have preserved essential patterns of oesophageal and small bowel motility. However, abnormalities mainly characterized by increased contractile activity of the small bowel during fasting and postprandially are evident. These findings indicate alterations in neuronal control of motility and persistent involvement of the upper GI tract in this disease. (Source: Neurogastroenterology and Motility)

Gastric emptying of enterally administered liquid meal in conscious rats and during sustained anaesthesia

Neurogastroenterology and Motility — Thu, 03 Sep 2009 23:00:00 +0100

Conclusions & Inferences Our data indicate that Inactin® anaesthesia does not significantly affect gastric emptying while urethane anaesthesia profoundly impairs gastric emptying. We suggest that Inactin®, not urethane, is the more suitable anaesthetic for gastrointestinal research. (Source: Neurogastroenterology and Motility)

N-Methyl-d-aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat

Neurogastroenterology and Motility — Wed, 02 Sep 2009 23:00:00 +0100

Conclusions & Inferences These data demonstrate a potential modulatory mechanism of NMDA-R in altered colonic motility in TNBS colitis. Inhibition of the enteric NMDA-Rs may provide a therapeutic option via which to influence intestinal hypermotility, microcirculatory changes and inflammatory activation simultaneously. (Source: Neurogastroenterology and Motility)

Mechanisms of symptomatic improvement after gastric electrical stimulation in gastroparetic patients

Neurogastroenterology and Motility — Thu, 27 Aug 2009 23:00:00 +0100

Abstract The aims were to investigate the effects of gastric electrical stimulation (GES) on autonomic function, gastric distention and tone, and central control mechanisms in gastroparetic patients. Ten gastroparetic patients refractory to standard medical therapy participated in this study and data were collected at baseline, within two weeks before surgery for implantation of GES system, and at follow-up sessions between 6 and 12 weeks after GES therapy was initiated. In each session, electrocardiogram, electrogastrogram (EGG) and gastric barostat measurements were conducted before and after a caloric liquid meal. Positron Emission Tomography (PET) brain scans were performed on a separate day. During GES therapy there was a significant increase in the discomfort threshold for mean press...

Functional protease-activated receptors in the dorsal motor nucleus of the vagus

Neurogastroenterology and Motility — Thu, 27 Aug 2009 23:00:00 +0100

Conclusions & Inferences Our results indicate that PAR-1 and PAR-2 are present in the DMV neurons, and their activation leads to increases in intracellular calcium via signal transduction mechanism that involves activation of PLC and the production of IP3. (Source: Neurogastroenterology and Motility)

Rectal motility after sacral nerve stimulation for faecal incontinence

Neurogastroenterology and Motility — Wed, 26 Aug 2009 23:00:00 +0100

Abstract Sacral nerve stimulation (SNS) is effective against faecal incontinence, but the mode of action is obscure. The aim of this study was to describe the effects of SNS on fasting and postprandial rectal motility. Sixteen patients, 14 women age 33[ndash]73 (mean 58), with faecal incontinence of various aetiologies were examined. Before and during SNS, rectal cross-sectional area (CSA) and ano-rectal pressures were determined with impedance planimetry and manometry for 1 h during fast and 1 h postprandially. Neither in the fasting state nor postprandially did SNS affect the number of single rectal contractions, total time with cyclic rectal contractions, the number of aborally and orally propagating contractions, the number of anal sampling reflexes or rectal wall tension during contra...

Loss of enteric neurons accompanied by decreased expression of GDNF and PI3K/Akt pathway in diabetic rats

Neurogastroenterology and Motility — Tue, 25 Aug 2009 23:00:00 +0100

Abstract To investigate the enteric neuropathy in diabetic rats and the role of glia cell line-derived neurotrophic factor (GDNF) and its signalling pathway PI3K/Akt in regulating enteric neurons survival. Male Sprague[ndash]Dawley (SD) rats were randomly divided into normal control group, diabetic groups (rats with diabetes for 4, 8 and 12 weeks respectively). Proximal and distal colon specimens were obtained from each rat. Phosphoinositol-3-kinase signalling pathway was analysed by Akt phosphorylation. Protein gene product 9.5 (PGP9.5) used as a pan-neuronal marker. The expressions of GDNF, phospho-Akt (p-Akt), neuronal nitric oxide synthase (nNOS) neurons, cholinergic [choline acetyltransferase (CHAT) stained] neurons and total neurons were measured by immunohistochemical streptavidin-b...

Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain

Neurogastroenterology and Motility — Mon, 24 Aug 2009 23:00:00 +0100

Conclusions & Inferences These findings indicate that linaclotide has potent anti-nociceptive effects in several mechanistically different rodent models of visceral hypersensitivity and that these pharmacological properties of linaclotide are exerted through the activation of the GC-C receptor. Therefore, linaclotide may be capable of decreasing abdominal pain in patients suffering from IBS-C. (Source: Neurogastroenterology and Motility)

Reproducibility of axial force and manometric recordings in the oesophagus during wet and dry swallows

Neurogastroenterology and Motility — Sun, 23 Aug 2009 23:00:00 +0100

Conclusions & Inferences The system provided a more complete description of primary oesophageal peristalsis. Axial force and manometry were both reproducible but force measurements had increased dynamic range. As manometry and axial force generally are not associated, they each provide different information, and in combination they may be useful to better characterize oesophageal motor function. (Source: Neurogastroenterology and Motility)

Distention of the colon is associated with initiation of propagated contractions in children

Neurogastroenterology and Motility — Sun, 23 Aug 2009 23:00:00 +0100

Abstract The presence of high-amplitude propagating contractions (HAPCs) has been identified as a marker of colonic neuromuscular integrity. The physiologic mechanisms of HAPCs initiation have yet to be determined. Distention secondary to colonic filling has been hypothesized as physiologic initiator. The aim of this study was to study the effect of intraluminal balloon distention in the colon of children with defecatory disorders. Colonic manometry was performed with a polyethylene balloon situated at the proximal end of the catheter, which was placed in the most proximal colonic segment reached during colonoscopy. A stepwise pressure controlled distention of the balloon was performed using barostat computer (10[ndash]50 mmHg). Propagated contractions were defined as those that migrated o...

Impact of nadir lower oesophageal sphincter pressure on bolus clearance assessed by combined manometry and multi-channel intra-luminal impedance measurement

Neurogastroenterology and Motility — Thu, 20 Aug 2009 23:00:00 +0100

This study aimed to assess the relationship between nadir lower oesophageal sphincter pressure (LOSP) and wave amplitude (WA) in oesophageal bolus clearance. Concurrent oesophageal manometry and impedance were performed in 146 subjects [41 healthy, 24 non-obstructive dysphagia (NOD) and 81 gastro-oesophageal reflux (GOR)]. Patients with achalasia and diffuse oesophageal spasm were excluded. Swallow responses were categorized by nadir LOSP. For each category of nadir LOSP, WA at the distal 2 recording sites were grouped into bins of 10 mmHg and the proportion of waves in each bin associated with a normal bolus presence time (BPT) was determined. Nadir LOSP, distal BPT, total bolus transit time and the proportion of impaired oesophageal clearance in patients with NOD were greater than those ...

Proteinase-activated receptors 1and 2 mediate contraction of human oesophageal muscularis mucosae

Neurogastroenterology and Motility — Wed, 19 Aug 2009 23:00:00 +0100

Abstract Proteinase-activated receptors 1 and 2 mediate contraction of the human gallbladder. In the present study, we investigated effects mediated by proteinase-activated receptors (PARs) in the human oesophagus by measuring contraction of muscularis mucosae strips isolated from the human oesophagus. Both PAR1 agonists (thrombin, SFLLRN-NH2 and TFLLR-NH2) and PAR2 agonists (trypsin, 2-furoyl-LIGRLO-NH2 and SLIGKV-NH2) caused concentration-dependent contraction. In contrast, PAR1 and PAR2 control peptides did not cause contraction. The existence of PAR1 and PAR2 in the human oesophageal muscularis mucosae was confirmed by immunohistochemistry and reverse transcription-polymerase chain reaction. On the other hand, PAR4 agonists, GYPGKF-NH2, GYPGQV-NH2 and AYPGKF-NH2, did not cause contract...

Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation

Neurogastroenterology and Motility — Tue, 18 Aug 2009 23:00:00 +0100

Abstract Velusetrag (TD-5108) is a potent, selective high intrinsic activity serotonin 5-HT4 receptor agonist. We assessed effects of Velusetrag on gastrointestinal transit and compared its pharmacokinetics in healthy volunteers (HV) and chronic constipation (CC) patients. Sixty HV were randomly assigned, double-blind to placebo, 5, 15, 30 or 50 mg Velusetrag (single and 6-day dosing). Primary endpoints were colonic transit (geometric centre at 24 h, GC24) and ascending colon emptying (ACE) T1/2 after first dose. Secondary endpoints included gastric emptying (GE) T1/2 and colonic filling at 6 h (CF6). Single dose Velusetrag significantly accelerated GC24, ACE T1/2, and CF6; 30 and 50 mg Velusetrag accelerated all three endpoints. With multiple doses, Velusetrag 30 mg accelerated GC24, and ...

The participation of the sympathetic innervation of the gastrointestinal tract in disease states

Neurogastroenterology and Motility — Fri, 14 Aug 2009 23:00:00 +0100

Abstract Knowledge of neural circuits, neurotransmitters and receptors involved in the sympathetic regulation of gastrointestinal (GI) function is well established. However, it is only recently that the interaction of sympathetic neurons, and of sympathetic transmitters, with the GI immune system and with gut flora has begun to be explored. Changes in the behaviour of sympathetic nerves when gut function is compromised, for example in ileus and in inflammation, have been observed, but the roles of the sympathetic innervation in these and other pathologies are not adequately understood. In this article, we first review the principal roles of the sympathetic innervation of the GI tract in controlling motility, fluid exchange and gut blood flow in healthy individuals. We then discuss the evid...

Mucosal mast cells mediate motor response induced by chronic oral exposure to ovalbumin in the rat gastrointestinal tract

Neurogastroenterology and Motility — Thu, 13 Aug 2009 23:00:00 +0100

In this study, the objective was to determine the mechanism of action of OVA and the role of mucosal mast cells in the regulation of motor activity in this model. Rats were orally exposed to OVA during 6 weeks. Intestinal mucosal mast cells (IMMCs) were counted and rat mast cell protease II (RMCPII) measured in duodenum, jejunum, ileum and colon. Anti-OVA IgE, IgG, and IL-4 were measured in serum. Eosinophils and IgE+ cells were counted in jejunum. In an additional study rats were treated with the mast cell stabilizer ketotifen and mast cell number, RMCPII concentration and motor activity in vitro were evaluated. OVA exposed rats showed an increase in mucosal mast cell number and in RMCPII content in small intestine and colon. However, variables of a Th2 type response were not affected by ...

Relationship between symptom pattern, assessed by the PAGI-SYM© questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia

Neurogastroenterology and Motility — Tue, 04 Aug 2009 23:00:00 +0100

Abstract The patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire was recently developed and validated for the evaluation of therapeutic responsiveness in functional dyspepsia (FD). Functional dyspepsia is a heterogeneous disorder, with different pathophysiological mechanisms underlying the symptom pattern. The relationship between PAGI-SYM scores and putative pathophysiological mechanisms has not been studied. The aim of this study was to evaluate the relationship between PAGI-SYM subscales and gastric emptying, gastric sensitivity and gastric accommodation in FD. A total of 161 consecutive FD patients underwent Helicobacter pylori (HP), gastric barostat and standardized gastric emptying testing (n = 126), and completed the PAGI-SYM questionnaire. R...

Differential expression of enteric neuroimmune-network in invasive and acute watery diarrhoea

Neurogastroenterology and Motility — Sun, 02 Aug 2009 23:00:00 +0100

Abstract We aimed to evaluate the changes of nerve morphology and distribution of neurotransmitters and neuropeptides in the rectum of Shigella flexneri-infected patients and in the duodenum of Vibrio cholerae O1-infected patients. Nerve morphology was observed by transmission electron microscopy. Immunoreactivity of nerve growth factor (NGF), neurotransmitters and neuropeptides in tissues were studied by immunohistochemistry. Ultrastructural analysis of intestinal biopsy revealed persisting axons degeneration throughout the study period in all patients. Regeneration was already evident at the acute stage with marked increase at late convalescence. Both acute shigellosis and cholera were accompanied by increased expression of NGF and histamine and decreased expression of serotonin that was...

Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function

Neurogastroenterology and Motility — Tue, 28 Jul 2009 23:00:00 +0100

Abstract Tryptophan is the precursor of a wide array of metabolites, which are involved in a variety of aspects of human nutrition and metabolism. Accumulating evidence suggests a role of tryptophan metabolites, especially serotonin (5-hydroxytryptamin) in intestinal (patho) physiology, although mechanisms of action are still poorly understood. Alterations of serotonin metabolism may give rise to gastrointestinal dysfunction. Recently, it has been postulated that other metabolites of tryptophan, mostly of the kynurenine pathway, also play a role in regulating gut function. This review analyses the current knowledge of the interrelationship between tryptophan metabolic pathways and summarizes the existing scientific evidence regarding the role of tryptophan metabolites in intestinal functio...

Speech therapy in patients with excessive supragastric belching – a pilot study

Neurogastroenterology and Motility — Mon, 27 Jul 2009 23:00:00 +0100

Abstract In patients whose main symptom is excessive belching, supragastric belching appears to be the predominant mechanism. This belch pattern is characterized by a rapid influx of air into the oesophagus, immediately followed by rapid air expulsion. The rate at which supragastric belching occurs is influenced by attention and distraction, suggesting a behavioural disorder and speech therapy may be of benefit to these patients. In 17 consecutive patients with excessive belching, concurrent impedance monitoring and high-resolution manometry were performed to ascertain the mechanism of belching. Patients with supragastric belches were referred to a speech therapist, who was familiar with the concept of supragastric belching. Before and after treatment by the speech therapist, patients fill...

Salvinorin A inhibits colonic transit and neurogenic ion transport in mice by activating κ-opioid and cannabinoid receptors

Neurogastroenterology and Motility — Wed, 22 Jul 2009 23:00:00 +0100

Abstract The major active ingredient of the plant Salvia divinorum, salvinorin A (SA) has been used to treat gastrointestinal (GI) symptoms. As the action of SA on the regulation of colonic function is unknown, our aim was to examine the effects of SA on mouse colonic motility and secretion in vitro and in vivo. The effects of SA on GI motility were studied using isolated preparations of colon, which were compared with preparations from stomach and ileum. Colonic epithelial ion transport was evaluated using Ussing chambers. Additionally, we studied GI motility in vivo by measuring colonic propulsion, gastric emptying, and upper GI transit. Salvinorin A inhibited contractions of the mouse colon, stomach, and ileum in vitro, prolonged colonic propulsion and slowed upper GI transit in vivo. S...

Routine colonic biopsies as a new tool to study the enteric nervous system in living patients

Neurogastroenterology and Motility — Tue, 21 Jul 2009 23:00:00 +0100

Abstract Better characterization of enteric neuropathies during the course of gastrointestinal diseases could be of great diagnostic and/or therapeutic interest. However, studies using whole mounts of the enteric nervous system (ENS) are restricted to specific diseases requiring surgery and are also limited by the small number of specimens available. Therefore, we here describe a novel method to obtain whole mounts of submucosal plexus in routine colonic biopsies. We show that a single biopsy displays a substantial number of submucosal ganglia and neurons and that it can be reliably used to perform morphometric and neurochemical analysis and Western Blots quantification of neuronal or glial markers. This method of analysis of the human ENS will enable us to gain better insight into the cha...

Modulation of inhibitory neurotransmission in brainstem vagal circuits by NPY and PYY is controlled by cAMP levels

Neurogastroenterology and Motility — Sun, 19 Jul 2009 23:00:00 +0100

Abstract Pancreatic polypeptides such as neuropeptide Y (NPY) and peptide YY (PYY) exert profound, vagally mediated effects on gastrointestinal (GI) motility. Vagal efferent outflow to the GI tract is determined principally by tonic GABAergic synaptic inputs onto dorsal motor nucleus of the vagus (DMV) neurons, yet neither peptide modulates GABAergic transmission. We showed recently that opioid peptides appear similarly ineffective because of the low resting cAMP levels. Using whole cell recordings from identified DMV neurons, we aimed to correlate the influence of brainstem cAMP levels with the ability of pancreatic polypeptides to modulate GABAergic synaptic transmission. Neither NPY, PYY, nor the Y1 or Y2 receptor selective agonists [Leu,Pro]NPY or NPY(3-36) respectively, inhibited evok...

Small bowel motility in functional chronic constipation

Neurogastroenterology and Motility — Wed, 15 Jul 2009 23:00:00 +0100

Abstract In functional constipation, three pathophysiological subgroups have been identified: slow-transit constipation (STC); normal-transit constipation (NTC) and outlet delay (OD). Extracolonic manifestations, especially disturbed small bowel motility, are well known to occur in STC, but have rarely been studied in NTC and OD. To perform 24-h-ambulatory jejunal manometry in a large prospective series of clinical patients with chronic constipation of all subtypes. A total of 61 consecutive patients, referred to our tertiary gastroenterologic centre for chronic constipation (48 female, 13 male; mean age 57 (range 20[ndash]87) years), underwent jejunal 24-h-ambulatory manometry (standardized meal) after a transit-time study (radio-opaque markers), anorectal manometry, defecography and colo...

Neuropeptide S receptor 1 expression in the intestine and skin – putative role in peptide hormone secretion

Neurogastroenterology and Motility — Mon, 13 Jul 2009 23:00:00 +0100

In conclusion, similar to other neuropeptides and their receptors, NPSR1 signalling might play a dual role along the gut[ndash]brain axis. The NPS/NPSR1 pathway may participate in the regulation of the peptide hormone production in enteroendocrine cells of the small intestine. (Source: Neurogastroenterology and Motility)

Understanding measurements of intestinal permeability in healthy humans with urine lactulose and mannitol excretion

Neurogastroenterology and Motility — Sun, 12 Jul 2009 23:00:00 +0100

Abstract Our aim was to understand the information from differential two-sugar excretion (2-SE) in measuring intestinal permeability. In a crossover study in 12 healthy volunteers, we compared urinary excretion ratios of lactulose (L) to mannitol [(M) LMR] after ingestion in liquid formulation (LF) or in delayed-release, methacrylate-coated capsules (CAP). Both formulations were radiolabelled. Urine was collected every 2 h from 0 to 8 h, and from 8 to 24 h. Two hours after LF, gastric residual was 15.9 ± 6.2% (SEM), and the percentage in colon was 49.6 ± 7.8%; in 11/12 participants, liquid had entered colon within 2 h. Average CAP arrival time in colon was 5.16 ± 0.46 h (mode 6 h). After LF, mannitol was extensively absorbed in the first 8 h; lactulose absorption was low thoughout the 2...

Intestinal motor activity, endoluminal motion and transit

Neurogastroenterology and Motility — Sun, 12 Jul 2009 23:00:00 +0100

Abstract A programme for evaluation of intestinal motility has been recently developed based on endoluminal image analysis using computer vision methodology and machine learning techniques. Our aim was to determine the effect of intestinal muscle inhibition on wall motion, dynamics of luminal content and transit in the small bowel. Fourteen healthy subjects ingested the endoscopic capsule (Pillcam, Given Imaging) in fasting conditions. Seven of them received glucagon (4.8 [mu]g kg[minus]1 bolus followed by a 9.6 [mu]g kg[minus]1 h[minus]1 infusion during 1 h) and in the other seven, fasting activity was recorded, as controls. This dose of glucagon has previously shown to inhibit both tonic and phasic intestinal motor activity. Endoluminal image and displacement was analyzed by means of a c...

Swallowing and respiratory pattern in young healthy individuals recorded with high temporal resolution

Neurogastroenterology and Motility — Sun, 12 Jul 2009 23:00:00 +0100

In this study, we have examined young healthy individuals with simultaneous videofluoroscopy, videomanometry and respiratory recording, all with high temporal resolution. The onset of 13 predetermined swallowing and respiratory events and the surrounding respiratory phase pattern were studied in different body positions and during different respiratory drives. An increased respiratory drive was induced by breathing 5% CO2. The results demonstrated a highly repeatable and fixed temporal coordination of the swallowing pattern despite body position and respiratory drive. Previous studies have demonstrated a period of centrally controlled apnoea during swallowing. This apnoea period has a variable length, varying from 1 to 5 s. During increased respiratory drive, we could demonstrate a signifi...

Differential afferent sensitivity to mucosal lipopolysaccharide from Salmonella typhimurium and Escherichia coli in the rat jejunum

Neurogastroenterology and Motility — Sun, 12 Jul 2009 23:00:00 +0100

Abstract Postinfectious irritable bowel syndrome may develop subsequent to acute bacterial enteritis. We therefore hypothesized that intestinal afferents may develop hypersensitivity upon exposure to luminal lipopolysaccharide (LPS) from pathogens but not from commensal bacteria and that this may be prostaglandin mediated. Extracellular recordings of jejunal afferents were obtained in vivo from male Wistar rats (n = 5 per group; 300[ndash]400 g). Lipopolysaccharide from Escherichia coli (E-LPS), Salmonella typhimurium (S-LPS) or vehicle were infused into the intestinal lumen at 5 mg mL[minus]1. The selective 5-HT3-receptor agonist 2-methyl-5-HT (2m5-HT, 15 [mu]gkg[minus]1, i.v.) was administered at 15-min intervals before and up to 2 h after S-LPS administration. Intraluminal E-LPS had no ...

An endoscopic method for thermal and chemical stimulation of the human oesophagus

Neurogastroenterology and Motility — Sun, 12 Jul 2009 23:00:00 +0100

Abstract Previous methods for visceral thermal stimulation have lacked control of the temperature rate and visual inspection of the organ. The aims of this study was to develop a method for linear control of heat stimulation in the human oesophagus combined with endoscopy, to assess the reproducibility of this method and to investigate sensitivity to thermal stimulation of the distal oesophagus before and after acid perfusion. A probe with a 2.8 mm endoscope inside was constructed permitting heat and chemical stimulation. Three different temperature ramps were applied in the distal oesophagus in 12 healthy subjects by recirculation of heated water in a bag. Endoscopy of the oesophageal mucosa was performed prior to experimental stimulation. The temperature, the time of stimulation and the ...

Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis

Neurogastroenterology and Motility — Sun, 12 Jul 2009 23:00:00 +0100

Abstract Our goal was to investigate associations between the status of interstitial cells of Cajal (ICC) and electrogastrogram (EGG) parameters, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty-one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c-kit and scored for the presence of ICC based on criteria obtained from 10 controls. All patients underwent EGG recordings, a 4-h standardized scintigraphic gastric emptying study and symptom assessment prior to the surgery. Based on antral biopsy, 15 patients (36%) had almost no ICC (ICC[minus] group) and 26 patients had adequate ce...

Electrical colonic stimulation reduces mean transit time in a porcine model

Neurogastroenterology and Motility — Wed, 08 Jul 2009 23:00:00 +0100

This study aimed to demonstrate the effect of direct electrical colonic stimulation on mean transit time in a chronic porcine model. The impact of stimulation and implanted material on the colonic wall was also assessed. Three pairs of electrodes were implanted into the caecal wall of 12 anaesthetized pigs. Reference colonic transit time was determined by radiopaque markers for each pig before implantation. It was repeated 4 weeks after implantation with sham stimulation and 5 weeks after implantation with electrical stimulation. Aboral sequential trains of 1-ms pulse width (10 V; 120 Hz) were applied twice daily for 6 days, using an external battery operated stimulator. For each course of markers, a mean value was computed from transit times obtained from individual pig. Microscopic exami...

Dehydroepiandrosterone sulphate improves cholestasis-associated fatigue in bile duct ligated rats

Neurogastroenterology and Motility — Tue, 07 Jul 2009 23:00:00 +0100

In this study, we tested the effect of DHEAS on whole body fatigue in rats following bile duct ligation (BDL). Fatigue was estimated by the time spent on an electrified grid as a result of falling off a treadmill and by performance of rats on an infrared beam monitor which allows the assessment of travelled distance and stereotypic movement activities. On day 5 after BDL surgery, cholestatic rats exhibited increased whole body fatigue as reflected by significantly increased time spent on the electrified grid, reduced travelled distance and reduced stereotypic movements. Administration of 5 mg kg[minus]1 of DHEAS to BDL rats for three consecutive days significantly normalized their behaviour. Fatigue scores were also found to be reduced in cirrhotic rats 4 weeks after BDL surgery, and DHEAS...

Selective stimulation of intrinsic excitatory and inhibitory motor pathways in porcine lower oesophageal sphincter

Neurogastroenterology and Motility — Sat, 04 Jul 2009 23:00:00 +0100

Abstract The mechanisms of stimulation of inhibitory and excitatory motor neurons (MNs) in the lower oesophageal sphincter (LOS) are not fully understood. The aim of this study was to assess the effect of selective stimulation of inhibitory and excitatory MNs in porcine LOS through nicotinic acetylcholine receptors (nAChRs), 5-HT3 and P2X receptors. Circular LOS strips from adult pigs were studied in organ baths. We compared the effects of stimulation of MNs by electrical field stimulation (26 V, 0.3[ndash]20 Hz); nicotine (1[ndash]300 [mu]mol L[minus]1); 5-HT and 2-Me-5-HT (1 nmol[minus]1[ndash]30 [mu]mol L[minus]1); and [alpha],[beta]-methylene ATP ([alpha],[beta]-meATP 1[ndash]100 [mu]mol L[minus]1); in standard Krebs solution; a non-adrenergic non-nitrergic non-purinergic (NANNNP) solu...

Catecholamine and cortisol levels during sleep in women with irritable bowel syndrome

Neurogastroenterology and Motility — Tue, 30 Jun 2009 23:00:00 +0100

This study compared serum cortisol and plasma catecholamine levels during sleep between women with IBS (n = 30) and healthy controls (n = 31), and among subgroups within the IBS sample based on predominant stool patterns, IBS-diarrhoea (n = 14), IBS-constipation (n = 7) and IBS-alternators (n = 9). Cortisol was measured from serial blood samples drawn every 20 min, and catecholamines every hour, in a sleep laboratory from 8 pm until awakening. Because of the varied sleep schedules of the individual participants, each subject's hormone series time base was referenced with respect to their onset of Stage 2 sleep. Overall, there were no significant differences in cortisol or catecholamine patterns between women with IBS and controls, nor were there any group by time interactions. However, wom...

Time-course of recovery of gastric emptying and motility in rats with experimental spinal cord injury