Medicine JournalFeeds

Upregulation of mucosal 5-HT(3) receptors is involved in restoration of colonic transit after pelvic nerve transection.

Neurogastroenterol Motil. 2012 Feb 3;

Authors: Gribovskaja-Rupp I, Takahashi T, Ridolfi T, Kosinski L, Ludwig K

Abstract

Background  Colonic dysfunction occurs after pelvic autonomic nerve damage. The enteric nervous system can compensate. We investigated the role of mucosal serotonin receptors, 5-HT(3) and 5-HT(4) , in the colonic motility restoration over 2 weeks after parasympathetic pelvic nerve transection in a rat model. Methods  Male Sprague-Dawley rats underwent pelvic nerve transection or sham operation. Colonic transit was expressed as the geometric center of (51) Cr distribution. Mucosal 5-HT(3) and 5-HT(4) receptor expression was evaluated by Western blot. Intraluminal pressure increase was measured after 5-HT(3) (ondansetron) or 5-HT(4) receptor antagonist (GR125487) administration in vitro in sham and denervated distal colons. Key Results  At 2 weeks, colonic transit in the denervated group was 30% slower compared to the sham group (P < 0.01). At 1 and 2 weeks, 5-HT(3) receptor expression was increased two-fold in the denervated group, compared to shams (P < 0.05). A three-fold smaller dose of ondansetron was required in denervated tissues to inhibit intraluminal pressure rise than in sham colons (P < 0.01). There was no difference in the expression of 5-HT(4) receptor or the response to GR125487 in denervated vs sham colons. Conclusions & Inferences  Colonic motility was restored to approximately 70% normal over 1 week without further improvement at 2 weeks. Enteric nervous system compensated by upregulating mucosal 5-HT(3,) but not 5-HT(4,) receptors.

PMID: 22304456 [PubMed - as supplied by publisher]

Role of Lactobacillus acidophilus loaded floating beads in chronic fatigue syndrome: behavioral and biochemical evidences.

Neurogastroenterol Motil. 2012 Feb 1;

Authors: Singh PK, Chopra K, Kuhad A, Kaur IP

Abstract

Background  In recent years the interface between neuropsychiatry and gastroenterology has converged in to a new discipline referred to as enteric neuroscience. Implications of brain-gut communication in the pathogenesis of psychiatric disorders indicate a possible role of suitably packaged/delivered probiotics as newer therapeutic options. In the present study probable role of per-oral administration of free Lactobacillus acidophilus (LAB) and LAB loaded alginate beads in attenuation of the symptoms associated with chronic fatigue syndrome (CFS) were evaluated. Methods  Chronic fatigue syndrome following physical fatigue was induced in rats by forcing them to swim (forced swim test; FST) in water till exhaustion, after weighing them down with 10% their body weight, daily for 28 days. Immobility (I) and postswim fatigue time (PSF) were taken as suitable markers. Free LAB and LAB loaded floating beads (FBs) were administered, from 21 to 28 days. Key Results  Immobility and PSF were found to increase considerably in FST rats (665 ± 22 s and 196 ± 6 s) as compared with the naïve (32 ± 7 s and 22 ± 2 s) at 20 days, establishing severe fatigue like behavior. FST control group exhibited significant (P < 0.05) hypertrophy of spleen, hypotrophy of thymus, and increased oxido-nitrosative stress in brain and tumor necrosis factor-α (TNF-α) levels in serum. Treatment with LAB and LAB FBs significantly decreased I and PSF and attenuated (P < 0.05) oxido-nitrosative stress and TNF-α levels. Spleen and thymus were also restored to their original size in this group. Conclusions & Inferences  The findings suggest a valuable therapeutic role of LAB especially when incorporated into alginate beads for the treatment of CFS.

PMID: 22296294 [PubMed - as supplied by publisher]

Duodenal lipid-induced symptom generation in gastroesophageal reflux disease: role of apolipoprotein A-IV and cholecystokinin.

Neurogastroenterol Motil. 2012 Feb 2;

Authors: van Boxel OS, Ter Linde JJ, Oors J, Otto B, Feinle-Bisset C, Smout AJ, Siersema PD

Abstract

Background  Duodenal lipid intensifies the perception of esophageal acid perfusion. Recently, we showed that genes implicated in lipid absorption were upregulated in the duodenum of fasting gastro-esophageal reflux disease (GERD) patients. This suggests that chylomicron production and secretion may be enhanced and, consequently, the release of apolipoprotein A-IV (apoA-IV), a chylomicron-derived signaling protein. ApoA-IV may stimulate release of cholecystokinin (CCK), an activator of vagal afferents. This study evaluated putative involvement of abnormal apoA-IV and CCK responses to lipid in GERD. Methods  Ten GERD patients and 10 healthy volunteers (HV) underwent duodenal perfusion with Intralipid 20%, 2 kcal min(-1) , for 60 min. Symptoms were scored, blood samples collected every 15 min during lipid perfusion and 15 min after discontinuation when duodenal biopsies were taken. Plasma and mucosal concentrations of apoA-IV and CCK and transcript levels of 21 genes implicated in lipid absorption, differentially expressed under fasting conditions, were quantified. Key Results  Heartburn (P = 0.003), abdominal discomfort (P = 0.037) and nausea (P = 0.008) only increased significantly during lipid infusion in GERD patients. Following lipid infusion mean mucosal apoA-IV concentration was lower in GERD patients compared with HV (P = 0.023), whereas plasma concentration tended to be elevated (P = 0.068). Mean mucosal CCK concentration was also lower in GERD patients (P = 0.009). Two genes, HIBADH and JTB, were upregulated in GERD patients (P = 0.008 and P = 0.038, respectively). Conclusions & Inferences  Our results suggest excessive duodenal lipid-induced release of apoA-IV and CCK in GERD. We postulate that the resulting heightened activation of duodenal vagal afferents may underlie central sensitization, thereby increasing the perception of reflux events.

PMID: 22300015 [PubMed - as supplied by publisher]

Randomized pharmacodynamic and pharmacogenetic trial of dronabinol effects on colon transit in irritable bowel syndrome-diarrhea.

Neurogastroenterol Motil. 2012 Jan 30;

Authors: Wong BS, Camilleri M, Eckert D, Carlson P, Ryks M, Burton D, Zinsmeister AR

Abstract

Background  Genetic variation in endocannabinoid metabolism is associated with colonic transit in irritable bowel syndrome (IBS) with diarrhea (IBS-D). The nonselective cannabinoid (CB) receptor agonist, dronabinol (DRO), reduced fasting colonic motility in nonconstipated IBS. FAAH and CNR1 variants influenced DRO’s effects on colonic motility. Our aims were: (i) to compare dose-related effects of DRO to placebo (PLA) on gut transit in IBS-D, and (ii) to examine influence of genetic variations in CB mechanisms on DRO’s transit effects. Methods  Thirty-six IBS-D volunteers were randomized (double-blind, concealed allocation) to twice per day PLA (n = 13), DRO 2.5 mg (n = 10), or DRO 5 mg (n = 13) for 2 days. We assessed gastric, small bowel, and colonic transit by validated radioscintigraphy and genotyped the single nucleotide polymorphisms CNR1 rs806378 and FAAH rs324420. Data analysis utilized a dominant genetic model. Key Results  Overall treatment effects of DRO on gastric, small bowel, or colonic transit were not detected. CNR1 rs806378 CT/TT was associated with a modest delay in colonic transit at 24 h compared with CC (P = 0.13 for differential treatment effects on postminus pretreatment changes in colonic transit by genotype). No significant interaction of treatment with FAAH rs324420 was detected. Conclusions & Inferences  Overall, DRO 2.5 or 5 mg twice per day for 2 days had no effect on gut transit in IBS-D. There appears to be a treatment-by-genotype effect, whereby DRO preferentially delays colonic transit in those with the CNR1 rs806378 CT/TT genotypes. Further study of CB pharmacogenetics may help identify a subset of IBS-D patients most likely to benefit from CB agonist therapy.

PMID: 22288893 [PubMed - as supplied by publisher]

Cascade stomach is associated with upper gastrointestinal symptoms: a population-based study.

Neurogastroenterol Motil. 2012 Jan 30;

Authors: Kusano M, Hosaka H, Moki H, Shimoyama Y, Kawamura O, Kuribayashi S, Mori M, Akuzawa M

Abstract

Background  Cascade stomach (CS) is recognized by characteristic findings on barium studies. We prospectively investigated the relationship between CS and upper gastrointestinal (GI) symptoms. Methods  In subjects undergoing health screening, CS was diagnosed by barium studies. Consecutive persons (500 men and 127 women) with CS were identified and the same number of age-matched subjects without CS were selected as controls. Upper GI symptoms were classified as reflux symptoms, dyspepsia symptoms, or epigastralgia symptoms. Then, we prospectively analyzed barium studies to classify the gastric morphology and also assessed upper GI symptoms in consecutive 5008 men and 2736 women. Key Results  BMI was significantly higher in men with CS than in controls, and also in women with CS than in controls. Upper GI symptoms were significantly more frequent in the CS group than the controls among both men and women, especially reflux symptoms. In men, logistic regression analysis identified CS as an independent risk factor for upper GI symptoms (odds ratio = 1.771, P = 0.005) and for reflux symptoms (odds ratio = 2.07, P = 0.009). In women, CS was also significantly related to upper GI symptoms (odds ratio = 2.544, P = 0.020). The prevalence of CS was significantly higher (P < 0.0001) among symptomatic men than among those with no symptoms. Conclusions & Inferences  Gastric morphology is related to upper GI symptoms in both men and women. Cascade stomach should be reconsidered as a pathophysiological factor associated with upper GI symptoms.

PMID: 22288935 [PubMed - as supplied by publisher]

Comparative analysis of phase III migrating motor complexes in stomach and small bowel using wireless motility capsule and antroduodenal manometry.

Neurogastroenterol Motil. 2012 Jan 31;

Authors: Brun R, Michalek W, Surjanhata BC, Parkman HP, Semler JR, Kuo B

Abstract

Background  Assessment of phase III MMC is often not performed due to the invasive nature of antroduodenal manometry used to detect it. The aim of the study was to evaluate the ability of wireless motility capsule (WMC) to detect phase III MMC and correlate it with the simultaneous measurements by antroduodenal manometry (ADM). Methods  Eighteen patients underwent simultaneous ADM and WMC. MMCs were identified first on ADM and then correlated with WMC events occurring simultaneously. Frequency of contractions per min, AUC, MI, and criteria for amplitude thresholds of contractions representing MCCs on WMC tracings were defined. Key Results  In 18 patients, a total of 29 MMCs were recorded by ADM. WMC detected 86% of MMC events measured by ADM. Hundred percent (10/10) of MMCs in stomach were detected by WMC, whereas 79% (15/19) of MMCs were detected in SB. The sensitivity and specificity of WMC high amplitude contractions to represent phase III MMC were 90% and 71.8% in the stomach; 73.7% and 84.7% in SB, respectively, and negative predictive value was 99.9% in both regions. Conclusions & Inferences  Wireless motility capsule was able to detect the phase III MMCs as the high amplitude contractions with good fidelity. WMC does not detect the propagation of MMC. Using the pressure thresholds, WMC can detect high amplitude contraction representing phase III MMC with favorable sensitivity/specificity profile and 99.9% negative predictive value. This observation may have clinical significance, as the absence of high amplitude contractions recorded by WMC during fasting state suggests absence of MMCs.

PMID: 22292793 [PubMed - as supplied by publisher]

Life style in persons with functional gastrointestinal disorders – large-scale internet survey of lifestyle in Japan.

Neurogastroenterol Motil. 2012 Jan 31;

Authors: Miwa H

Abstract

Background  Care of patients with functional gastrointestinal disorders (FGIDs) commonly includes offering guidance on diet, exercise, and other lifestyle factors, but there is little information available on the actual lifestyles of FGID sufferers. Methods  An internet questionnaire survey of 15 000 adult members of the general public in Japan who were screened for functional dyspepsia (FD) and irritable bowel syndrome (IBS) using the Rome III adult FGID questionnaire was conducted. Key Results  The prevalence of FD and IBS was 6.5% and 14.0%, respectively, and 3.0% of the subjects met the criteria for both FD and IBS. The prevalence of both FD and IBS was higher in women than in men. The lifestyles of 2 547 subjects who met the Rome III criteria for FD, IBS, or both were compared with the lifestyles of 1 000 control subjects who did not meet the criteria for FD or the criteria for IBS. Compared to the control subjects, a significantly lower percentage of subjects with FD, IBS, or both exercised frequently, and a significantly higher percentage thought that their sleep was insufficient, ate meals irregularly, did not have an appetite, did not like meat, thought that their vegetable consumption was insufficient, felt stress in their daily lives, and regarded themselves as being highly susceptible to stress. Conclusions & Inferences  Persons with FGIDs are affected by impairment of sleep, eating habits, diet, exercise and other lifestyle factors, and feel excessive stress. This suggests that offering lifestyle guidance to FGID patients may be useful.

PMID: 22292849 [PubMed - as supplied by publisher]

Short-term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease.

Neurogastroenterol Motil. 2012 Jan 31;

Authors: Rodríguez L, Rodríguez P, Neto MG, Ayala JC, Saba J, Berel D, Conklin J, Soffer E

Abstract

Background  Electrical stimulation (ES) of the lower esophageal sphincter (LES) increases resting LES pressure (LESP) in animal models. Our aims were to evaluate the safety of such stimulation in humans, and test the hypothesis that ES increases resting LESP in patients with gastroesophageal reflux disease (GERD). Methods  A total of 10 subjects (nine female patients, mean age 52.6 years), with symptoms of GERD responsive to PPIs, low resting LES pressure, and abnormal 24-h intraesophageal pH test were enrolled. Those with hiatal hernia >2 cm and/or esophagitis >Los Angeles Grade B were excluded. Bipolar stitch electrodes were placed longitudinally in the LES during an elective laparoscopic cholecystectomy, secured by a clip and exteriorized through the abdominal wall. Following recovery, an external pulse generator delivered two types of stimulation for periods of 30 min: (i) low energy stimulation; pulse width of 200 μs, frequency of 20 Hz and current of 5-15 mA (current was increased up to 15 mA if LESP was less than 15 mmHg), and (ii) high energy stimulation; pulse width of 375 ms, frequency of 6 cpm, and current 5 mA. Resting LESP, amplitude of esophageal contractions and residual LESP in response to swallows were assessed before and after stimulation. Symptoms of chest pain, abdominal pain, and dysphagia were recorded before, during, and after stimulation and 7-days after stimulation. Continuous cardiac monitoring was performed during and after stimulation. Key Results  All patients were successfully implanted nine subjects received high frequency, low energy, and four subjects received low frequency, high energy stimulation. Both types of stimulation significantly increased resting LESP: from 8.6 mmHg (95% CI 4.1-13.1) to 16.6 mmHg (95% CI 10.8-19.2), P < 0.001 with low energy stimulation and from 9.2 mmHg (95% CI 2.0-16.3) to 16.5 mmHg (95% CI 2.7-30.1), P = 0.03 with high energy stimulation. Neither type of stimulation affected the amplitude of esophageal peristalsis or residual LESP. No subject complained of dysphagia. One subject had retrosternal discomfort with stimulation at15 mA that was not experienced with stimulation at 13 mA. There were no adverse events or any cardiac rhythm abnormalities with either type of stimulation. Conclusions & Inferences  Short-term stimulation of the LES in patients with GERD significantly increases resting LESP without affecting esophageal peristalsis or LES relaxation. Electrical stimulation of the LES may offer a novel therapy for patients with GERD.

PMID: 22292889 [PubMed - as supplied by publisher]

Ca(2+) sensitivity of the maxi chloride channel in interstitial cells of Cajal.

Neurogastroenterol Motil. 2012 Feb 1;

Authors: Wright GW, Parsons SP, Huizinga JD

Abstract

Background  Interstitial cells of Cajal (ICC) associated with the myenteric plexus of the small intestine express maxi chloride channels. Our aim was to investigate whether or not these channels would be activated by increases in intracellular Ca(2+) , as that would strengthen evidence for their potential role in ICC pacemaking. A further aim was to examine whether inwardly and outwardly rectifying maxi chloride currents signify different channels. Methods  We used Fluo-4 AM Ca(2+) imaging and patch clamp electrophysiology (cell-attached and inside-out) on isolated ICC in short term culture. Key Results  Increasing intracellular Ca(2+) by three functionally distinct mechanisms (blocking sarcoplasmic reticulum Ca(2+) refilling, creating membrane Ca(2+) pores and a solution designed to block plasmalemmal Ca(2+) extrusion) was followed by inwardly rectifying maxi chloride channel activation assessed in the cell-attached configuration. Furthermore, in the inside-out configuration, increased outwardly rectifying maxi-chloride channel activity followed an increase in Ca(2+) to 2 mmol L(-1) at the cytoplasmic face of the channel. Conclusions & Inferences  Increase in intracellular Ca(2+) will activate the maxi chloride channels. Maxi chloride currents are inwardly rectifying in the cell-attached patch clamp configuration under physiological conditions and are outwardly rectifying in the inside-out configuration. The same channel is responsible for both currents. Ca(2+) does not appear to regulate the rectification.

PMID: 22292914 [PubMed - as supplied by publisher]

A comparison between colonic submucosa and mucosa to detect Lewy pathology in Parkinson’s disease.

Neurogastroenterol Motil. 2012 Jan 31;

Authors: Pouclet H, Lebouvier T, Coron E, Des Varannes SB, Neunlist M, Derkinderen P

Abstract

Background  Lewy bodies and neurites (LN), the two pathological hallmarks of Parkinson’s disease (PD), are found in the enteric nervous system (ENS). Previously, we have shown that whole mounts of submucosa obtained after microdissection of colonic biopsies can be used for the detection of LN in the submucosal plexus (SMP) of PD patients. Recent reports suggest that Lewy pathology may extend beyond the submucosa to involve the digestive mucosa. The aim of the present research was to determine whether the analysis of the mucosa obtained after microdissection may help improve the sensitivity of colonic biopsies to detect Lewy pathology in the colon of PD patients. Methods  Nine PD patients and 10 controls were included. Four biopsies were taken from the sigmoid/descending colon junction during the course of a rectosigmoidoscopy (short colonoscopy) in PD patients and during a total colonoscopy for colorectal screening in controls. Biopsies were microdissected, the mucosa was separated from the submucosa and both structures were analyzed by immunohistochemistry. Immunohistochemical analysis was performed using antibodies against phosphorylated alpha-synuclein to detect LN and neurofilaments NF200 kDa to label the neuronal structures. Key Results  Lewy neurites were present in the SMP of four patients and in the mucosa of three patients. Remarkably, among the patients who displayed LN within their mucosa, one was devoid of Lewy pathology in his SMP. No LN were observed in the mucosa and the SMP of controls. Conclusions & Inferences  The parallel analysis of colonic mucosa, along with the SMP, can help detect Lewy pathology in PD.

PMID: 22292943 [PubMed - as supplied by publisher]