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1.
Am J Physiol Gastrointest Liver Physiol ; 327(2): G306-G315, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38860287

ABSTRACT

Data are limited regarding gastrointestinal motility disturbance in disorders of gut-brain interaction (DGBI). This study aimed to characterize antroduodenal motor alterations in patients with high-resolution antroduodenal manometry (HR-ADM). HR-ADM was performed in patients with severe DGBI and compared with healthy volunteers (HV). HR-ADM used a commercially available probe composed of 36 electronic sensors spaced 1 cm apart and positioned across the pylorus. Antral and duodenal motor high-resolution profiles were analyzed, based on the frequency, amplitude, and contractile integral/sensor (CI/s) calculated for each phase of the migrating motor complex (MMC). Eighteen HV and 64 patients were investigated, 10 with irritable bowel syndrome (IBS), 24 with functional dyspepsia (FD), 15 with overlap IBS-FD, and 15 with other DGBI. Compared with HV, patients had a lower frequency of phase II duodenal contractions (27 vs. 51 per hour; P = 0.002) and a lower duodenal phase II contraction amplitude (70 vs. 100 mmHg; P = 0.01), resulting in a lower CI/s of phase II (833 vs. 1,901 mmHg·cm·s; P < 0.001) in the duodenum. In addition, the frequency of phase II propagated antroduodenal contractions was lower (5 vs. 11 per hour; P < 0.001) in patients compared with HV. Interestingly, the antral CI/s of phase III was decreased in FD patients but not in IBS patients. Patients with severe DGBI display alterations in antral and intestinal motility assessed by commercially available HR-ADM. Whether these alterations may explain symptom profiles in such patients remains to be confirmed (NCT04918329 and NCT01519180).NEW & NOTEWORTHY Gastrointestinal dysmotility has been assessed poorly in disorders of gut-brain interaction (DGBI), especially with high-resolution antroduodenal manometry. Plots of DGBI patients showed lower duodenal contractions during phase II regarding amplitude, frequency, and contractile integral/sensor (CI/s) compared with healthy volunteers. A lower frequency of propagated antroduodenal contractions was also reported. Finally, antral CI/s was lower in patients with functional dyspepsia during phase III. Further studies are needed to assess the clinical significance of these alterations.


Subject(s)
Duodenum , Gastrointestinal Motility , Manometry , Pyloric Antrum , Humans , Manometry/methods , Male , Female , Adult , Gastrointestinal Motility/physiology , Middle Aged , Duodenum/physiopathology , Pyloric Antrum/physiopathology , Dyspepsia/physiopathology , Irritable Bowel Syndrome/physiopathology , Aged , Myoelectric Complex, Migrating/physiology , Case-Control Studies , Muscle Contraction
2.
Neurogastroenterol Motil ; 33(11): e14144, 2021 11.
Article in English | MEDLINE | ID: mdl-33881203

ABSTRACT

BACKGROUND: The gastroparetic syndrome encompasses antral hypomotility, gastric dysrhythmia, impaired antroduodenal coordination, pyloric dysfunction, and abnormal duodenal motility; the last three collectively referred to as pylorospasms. We hypothesized that antroduodenal motility is diminished and transition time is prolonged in adults with type 1 diabetes (T1D) and polyneuropathy. METHODS: This cross-sectional study included 124 participants, of which 21 were healthy, 53 had T1D and 50 had T1D with distal symmetrical polyneuropathy (T1D + DSPN). We used the wireless motility capsule to assess antroduodenal transition time, gastric emptying time, gastric and small bowel motility indices (MI), and numbers of alkalic/acidic exposures. RESULTS: In comparison with controls, patients with T1D had prolonged antroduodenal transition time (1.85±1.5 vs. 6.6±4.8 minutes; p=0.02), which was even more pronounced in patients with T1D+DSPN (1.85±1.5 vs. 17.8±28.5 minutes; p<0.008. T1D+DSPN tended to have diminished gastric MI (11.9±2.4 vs. 12.7±1.0, p=0.07) and small bowel MI (13.1±1.4 vs. 13.6±0.6, p=0.05) and experienced more antral/pyloric alkalic episodes (1.2±1.3 vs. 2.0±2.1, p=0.02) compared with controls. CONCLUSION: The current method may assess a proxy for severity of pylorospasms in patients with diabetes and other diseases associated with upper gastrointestinal motility disorders, which ultimately may optimize future management.


Subject(s)
Diabetes Mellitus, Type 1/physiopathology , Duodenum/physiopathology , Gastrointestinal Motility , Cross-Sectional Studies , Gastric Emptying , Humans , Pyloric Antrum/physiopathology
3.
J Gastrointest Surg ; 24(1): 188-197, 2020 01.
Article in English | MEDLINE | ID: mdl-31637625

ABSTRACT

INTRODUCTION: Severe burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular mechanism of these pathologic changes remains largely unknown. METHODS: Male Sprague Dawley rats approximately 3 months old and weighing 300-350 g were randomized to either a 60% total body surface area full-thickness scald burn or sham procedure and were sacrificed 24 h after the procedure. Gastric emptying, gastric antrum contractility ileal smooth muscle contractility, and colonic contractility were measured. Muscularis externa was isolated from the ileal segment to prepare smooth muscle protein extracts for Western blot analysis. RESULTS: Compared with sham controls, the baseline rhythmic contractile activities of the antral, ileal, and colonic smooth muscle strips were impaired in the burned rats. Simultaneously, our data showed that ileal muscularis ECM proteins fibronectin and laminin were significantly up-regulated in burned rats compared with sham rats. TGF-ß signaling is an important stimulating factor for ECM protein expression. Our results revealed that TGF-ß signaling was activated in the ileal muscle of burned rats evidenced by the activation of Smad2/3 expression and phosphorylation. In addition, the total and phosphorylated AKT, which is an important downstream factor of ECM signaling in smooth muscle cells, was also up-regulated in burned rats' ileal muscle. Notably, these changes were not seen in the colonic or gastric tissues. CONCLUSION: Deposition of fibrosis-related proteins after severe burn is contributors to decreased small intestinal motility.


Subject(s)
Burns/metabolism , Extracellular Matrix Proteins/metabolism , Ileum/metabolism , Intestinal Pseudo-Obstruction/metabolism , Muscle Contraction/physiology , Muscle, Smooth/metabolism , Animals , Burns/complications , Burns/physiopathology , Colon/metabolism , Colon/physiopathology , Disease Models, Animal , Extracellular Matrix Proteins/biosynthesis , Fibronectins/biosynthesis , Fibronectins/metabolism , Fibrosis/etiology , Fibrosis/metabolism , Fibrosis/physiopathology , Gastric Emptying/physiology , Gastrointestinal Motility/physiology , Ileum/physiopathology , Ileus/metabolism , Ileus/physiopathology , Inflammation/etiology , Inflammation/metabolism , Inflammation/physiopathology , Intestinal Pseudo-Obstruction/etiology , Intestinal Pseudo-Obstruction/physiopathology , Laminin/biosynthesis , Laminin/metabolism , Male , Muscle, Smooth/physiopathology , Phosphorylation , Pyloric Antrum/metabolism , Pyloric Antrum/physiopathology , Rats , Rats, Sprague-Dawley , Signal Transduction/physiology , Stomach/physiopathology
4.
Neurogastroenterol Motil ; 32(5): e13766, 2020 05.
Article in English | MEDLINE | ID: mdl-31773831

ABSTRACT

BACKGROUND: Enteric nervous system (ENS) abnormalities have been implicated in delayed gastric emptying but studies exploring potential treatment options are limited by the lack of an experimental animal model. We examined the ENS abnormalities in the mouse stomach associated with aging, developed a novel model of gastroparesis, and established a new approach to measure gastric emptying. METHODS: A modified gastric emptying assay was developed, validated in nNOS -/- mice, and tested in mice at multiple ages. Age-related changes in ENS structure were analyzed by immunohistochemistry. Gastric aganglionosis was generated in Wnt1-iDTR mice using focal administration of diphtheria toxin (DT) into the anterior antral wall. KEY RESULTS: Older mice (>5 months) exhibit hypoganglionosis in the gastric antrum and a decreased proportion of nNOS neurons as compared to younger mice (age 5-7 weeks). This was associated with a significant age-dependent decrease in liquid and solid gastric emptying. A novel model of gastric antrum hypoganglionosis was established using neural crest-specific expression of diphtheria toxin receptor. In this model, a significant reduction in liquid and solid gastric emptying is observed. CONCLUSIONS & INFERENCES: Older mice exhibit delayed gastric emptying associated with hypoganglionosis and a reduction in nNOS-expressing neurons in the antrum. The causal relationship between antral hypoganglionosis and delayed gastric emptying was verified using a novel experimental model of ENS ablation. This study provides new information regarding the pathogenesis of delayed gastric emptying and provides a robust model system to study this disease and develop novel treatments.


Subject(s)
Enteric Nervous System/physiopathology , Gastric Emptying , Gastroparesis/physiopathology , Pyloric Antrum/physiopathology , Aging/physiology , Animals , Disease Models, Animal , Enteric Nervous System/pathology , Female , Gastroparesis/pathology , Male , Mice, Inbred C57BL , Mice, Knockout , Neurons/pathology , Nitric Oxide Synthase Type I/genetics , Pyloric Antrum/pathology
5.
Sci Rep ; 9(1): 8683, 2019 06 18.
Article in English | MEDLINE | ID: mdl-31213634

ABSTRACT

The structural organization of intestinal blood flow is such as to allow for intramural collateral flow. Redistribution phenomena due to different local metabolic demands may lead to an impaired perfusion of parts of the intestinal wall which will display a characteristic pattern. Based on Ohm's and Kirchhoff's laws, a differential analysis of the gastric vascular bed bridges the gap between basic physiological concepts and traditional anatomical, pathological and clinical knowledge. An ulcer of the intestinal wall becomes understandable as a non-occlusive infarct based on a supply/demand conflict in an anisotropic structure as it can be found in the upper and lower gastrointestinal tract of man.


Subject(s)
Gastrointestinal Tract/physiopathology , Microvessels/physiopathology , Peptic Ulcer/physiopathology , Stomach Ulcer/physiopathology , Stomach/physiopathology , Algorithms , Blood Flow Velocity , Gastrointestinal Tract/blood supply , Gastrointestinal Tract/pathology , Humans , Models, Biological , Peptic Ulcer/diagnosis , Pyloric Antrum/blood supply , Pyloric Antrum/pathology , Pyloric Antrum/physiopathology , Stomach/blood supply , Stomach/pathology , Stomach Ulcer/diagnosis
7.
Neurogastroenterol Motil ; 31(3): e13521, 2019 03.
Article in English | MEDLINE | ID: mdl-30537362

ABSTRACT

BACKGROUND: We evaluated the changes in antroduodenal manometry (ADM) parameters and interpretation when the test is performed the day of catheter placement and the following day. METHODS: Catheter was placed endoscopically under anesthesia and recorded on day 1 and repeated on day 2. Study parameters including antrum and small bowel motility index (MI) during fasting, meal, postprandial, erythromycin (EES), and octreotide (OCT) challenge phases, the presence of the phase III of the migrating motor complex (MMC), visual postprandial response, and study interpretation were compared between both days. KEY RESULTS: Twenty patients were studied. Antrum and small bowel MI during fasting, postprandial, and EES challenge phases were significantly higher on day 2 than on day 1 (P < 0.05). The proportion of patients having a phase III of the MMC was significantly higher on day 2 compared to day 1 (65% vs 15%; P = 0.006). Study interpretation changed from day 1 to day 2. On day 1, 70% of the patients had a normal study and 30% had an abnormal study. On day 2, 67% of the patients with an abnormal study on day 1 changed to normal and 33% remained abnormal. All patients with a normal study on day 1 remained normal on day 2. CONCLUSIONS AND INFERENCES: ADM parameters are affected the day of catheter placement. The MI and presence of the phase III of the MMC were significantly higher on day 2 compared to day 1. Overall, ADM study interpretation changed from day 1 to day 2 in 20% of the patients.


Subject(s)
Duodenum/physiopathology , Gastrointestinal Diseases/physiopathology , Manometry/methods , Pyloric Antrum/physiopathology , Adolescent , Catheterization/methods , Child , Child, Preschool , Female , Humans , Infant , Male , Myoelectric Complex, Migrating , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , Upper Gastrointestinal Tract
8.
Neurogastroenterol Motil ; 30(7): e13360, 2018 07.
Article in English | MEDLINE | ID: mdl-29717796

ABSTRACT

BACKGROUND: Well-developed galaninergic gastric intramural nerve system is known to regulate multiple stomach functions in physiological and pathological conditions. Stomach ulcer, a disorder commonly occurring in humans and animals, is accompanied by inflammatory reaction. Inflammation can cause intramural neurons to change their neurochemical profile. Galanin and its receptors are involved in inflammation of many organs, however, their direct participation in stomach reaction to ulcer is not known. Therefore, the aim of the study was to investigate adaptive changes in the chemical coding of galaninergic intramural neurons and mRNA expression encoding Gal, GalR1, GalR2, GalR3 receptors in the region of the porcine stomach directly adjacent to the ulcer location. METHODS: The experiment was performed on 24 pigs, divided into control and experimental groups. In 12 experimental animals, stomach antrum ulcers were experimentally induced by submucosal injection of acetic acid solution. Stomach wall directly adjacent to the ulcer was examined by: (1) double immunohistochemistry-to verify the changes in the number of galaninergic neurons (submucosal, myenteric) and fibers; (2) real-time PCR to verify changes in mRNA expression encoding galanin, GalR1, GalR2, GalR3 receptors. KEY RESULTS: In the experimental animals, the number of Gal-immunoreactive submucosal perikarya was increased, while the number of galaninergic myenteric neurons and fibers (in all the stomach wall layers) remained unchanged. The expression of mRNA encoding all galanin receptors was increased. CONCLUSIONS & INTERFERENCES: The results obtained unveiled the participation of galanin and galanin receptors in the stomach tissue response to antral ulcerations.


Subject(s)
Galanin/physiology , Gastric Mucosa/physiopathology , Neurons/physiology , Pyloric Antrum/physiopathology , Receptors, Galanin/physiology , Stomach Ulcer/physiopathology , Animals , Female , Gastric Mucosa/innervation , Gastric Mucosa/pathology , Pyloric Antrum/innervation , Pyloric Antrum/pathology , Stomach Ulcer/pathology , Swine
9.
Crit Care ; 21(1): 248, 2017 Sep 26.
Article in English | MEDLINE | ID: mdl-28950897

ABSTRACT

BACKGROUND: Various special techniques for blind bedside transpyloric tube placement have been introduced into clinical practice. However, transpyloric spiral tube placement facilitated by a blind bedside method has not yet been reported. The objective of this prospective study was to evaluate the safety and efficiency of blind bedside postpyloric placement of a spiral tube as a rescue therapy subsequent to failed spontaneous transpyloric migration in critically ill patients. METHODS: This prospective, tricentric, observational study was conducted in the intensive care units (ICUs) of three tertiary hospitals. A total of 127 consecutive patients with failed spontaneous transpyloric spiral tube migration despite using prokinetic agents and still required enteral nutrition for more than 3 days were included. The spiral tube was inserted postpylorically using the blind bedside technique. All patients received metoclopramide intravenously prior to tube insertion. The exact tube tip position was determined by radiography. The primary efficacy endpoint was the success rate of postpyloric spiral tube placement. Secondary efficacy endpoints were success rate of a spiral tube placed in the third portion of the duodenum (D3) or beyond, success rate of placement in the proximal jejunum, time to insertion, length of insertion, and number of attempts. Safety endpoints were metoclopramide-related and major adverse tube-associated events. RESULTS: In 81.9% of patients, the spiral feeding tubes were placed postpylorically; of these, 55.1% were placed in D3 or beyond and 33.9% were placed in the proximal jejunum, with a median time to insertion of 14 min and an average number of attempts of 1.4. The mean length of insertion was 95.6 cm. The adverse event incidence was 26.0%, and no serious adverse event was observed. CONCLUSIONS: Blind bedside postpyloric placement of a spiral tube, as a rescue therapy subsequent to failed spontaneous transpyloric migration in critically ill patients, is safe and effective. This technique may facilitate the early initiation of postpyloric feeding in the ICU. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OPN-16008206 . Registered on 1 April 2016.


Subject(s)
Critical Illness/therapy , Intubation, Gastrointestinal/methods , Pyloric Antrum/physiology , Aged , Antiemetics/therapeutic use , Enteral Nutrition/instrumentation , Enteral Nutrition/methods , Female , Humans , Intensive Care Units/organization & administration , Male , Metoclopramide/therapeutic use , Middle Aged , Prospective Studies , Pyloric Antrum/physiopathology
10.
Neurogastroenterol Motil ; 29(11)2017 Nov.
Article in English | MEDLINE | ID: mdl-28585346

ABSTRACT

BACKGROUND: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. METHODS: The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2-null mice were analyzed and compared with their wild type (wt) littermates. KEY RESULTS: Increased food retention was detected in Tacr2-/- mice. The stomach of Tacr2-/- mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS)-induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up-regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2-/- mice. Intraperitoneal application of 7-nitroindazole (7-NI) to Tacr2-/- mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF-κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. CONCLUSIONS & INFERENCES: Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP, enhanced NO signaling and changed the Creb and NF-κB signalings, finally leading to the gastric emptying disturbance of Tacr2-/- mice.


Subject(s)
Gastric Emptying , Gastric Mucosa/metabolism , Receptors, Neurokinin-2/physiology , Stomach/physiopathology , Animals , Cyclic AMP Response Element-Binding Protein/metabolism , Female , Gastric Fundus/physiopathology , Gene Expression Regulation , Intestine, Small/physiopathology , Male , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/metabolism , Phenotype , Pyloric Antrum/physiopathology , Receptors, Neurokinin-2/genetics , Receptors, Neurokinin-2/metabolism , Signal Transduction , Stomach/pathology , Vasoactive Intestinal Peptide/metabolism
11.
Postgrad Med ; 129(3): 312-317, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28299959

ABSTRACT

OBJECTIVES: Although a common cause of intestinal blood loss, the pathophysiology of gastric antral vascular ectasia (GAVE) is not well understood. We aimed to evaluate gastric antral and body mucosal flow in GAVE patients compared to a control population using laser Doppler flowmetry. METHODS: 27 patients with GAVE and 11 control patients without GAVE were evaluated using an endoscopic LDF probe. The probe was placed in the gastric antrum and body in order to calculate standardized mucosal flow rates recorded as perfusion units (PU). RESULTS: Despite its hyperemic appearance and propensity to bleed, antral blood flow was not increased in GAVE: 115.5 PU (IQR: [94.4, 135.9 PU]) in GAVE versus 123.7 PU (IQR: [109.7, 186.5 PU]) in controls. There was a significant gradient between the gastric body and antral blood flow in GAVE (p < 0.001) that was not evident in controls. CONCLUSION: These results indicate that antral mucosal blood flow is not increased in GAVE despite its grossly hyperemic appearance. A mild but statistically significant gradient was noted between the gastric antrum and body in patients with GAVE compared to controls. The pathophysiological significance of this finding is uncertain.


Subject(s)
Gastric Antral Vascular Ectasia/physiopathology , Gastric Mucosa/physiopathology , Aged , Diabetes Complications , Female , Fibrosis/complications , Gastric Antral Vascular Ectasia/drug therapy , Gastric Mucosa/drug effects , Gastroscopy , Humans , Laser-Doppler Flowmetry , Male , Middle Aged , Prospective Studies , Proton Pump Inhibitors/pharmacology , Pyloric Antrum/drug effects , Pyloric Antrum/physiopathology , Stomach/physiopathology
12.
Exp Mol Pathol ; 102(1): 7-14, 2017 02.
Article in English | MEDLINE | ID: mdl-27939576

ABSTRACT

Excessive production of advanced glycation end products (AGE) has been implicated in the pathogenesis of diabetic complications. Smooth muscle (SM) phenotype transition is involved in diabetes-associated gastric motility dysfunction. We investigated whether AGE interfere with gastric antral SM contractile marker expression. Sixteen Sprague-Dawley rats were randomly divided into control and streptozotocin-induced diabetic groups. Sixteen weeks after streptozotocin administration, gastric antral SM strip contractility in the groups were measured. The gastric tissue expression of AGE was tested. Primary cultured gastric smooth muscle cells (SMCs) were used in complementary in vitro studies. In the presence and absence of AGE, SMCs were transfected with myocardin plasmid or treated with nuclear factor-κB (NF-κB) inhibitor or anti-RAGE antibody. Diabetic rats showed weakness of SM strip contractility and decreased expression of SM contractile marker genes (myosin heavy chains [MHC], α-actin, calponin) as compared with the control group. Gastric antral SM layer Nε-(carboxymethyl) lysine (CML) level, the major AGE compound, were increased in the diabetic rats. AGE downregulated SM contractile markers and myocardin expression in a concentration-dependent manner. Myocardin overexpression prevented these results. AGE treatment activated NF-κB in SMCs. The NF-κB inhibitor BAY 11-7082 and anti-RAGE antibody blocked the effects of AGE on myocardin downregulation. AGE may induce the development of gastric dysmotility by downregulating SM contractile proteins and myocardin expression via the AGE/RAGE/NF-κB pathway.


Subject(s)
Biomarkers/metabolism , Glycation End Products, Advanced/pharmacology , Muscle Contraction , NF-kappa B/metabolism , Receptor for Advanced Glycation End Products/metabolism , Signal Transduction/drug effects , Actins/genetics , Actins/metabolism , Animals , Blotting, Western , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Cells, Cultured , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Dose-Response Relationship, Drug , Gastric Emptying , Gene Expression/drug effects , Male , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Muscle, Smooth/drug effects , Muscle, Smooth/metabolism , Muscle, Smooth/physiopathology , Myocytes, Smooth Muscle/metabolism , Myosin Heavy Chains/genetics , Myosin Heavy Chains/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Pyloric Antrum/metabolism , Pyloric Antrum/physiopathology , Random Allocation , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Trans-Activators/genetics , Trans-Activators/metabolism , Calponins
13.
PLoS One ; 11(12): e0166638, 2016.
Article in English | MEDLINE | ID: mdl-27930657

ABSTRACT

BACKGROUD: Interstitial cells of Cajal (ICCs) and nNOS play a crucial role in diabetic gastrointestinal dysmotility(DGD). Our previous study found that electro-acupuncture(EA) on ear point 'stomach' could repair the gastric dysrhythmias in rats induced by rectal distention(RD) after meal. However, little were known about the possible effect of auricular electro-acupuncture (AEA) on diabetic rats. Thus, we designed this study to investigate the effect of AEA on streptozotocin(STZ)-induced diabetic rats. METHOD: Forty male Sprague_Dawley (SD) rats were injected with STZ, at the end of 8th week after injection, animals were randomly divided into four groups and received 2 weeks-treatment(10 times) respectively: control group(CON,n = 10, no stimulation), sham auricular electro-acupuncture group(SEA,n = 10, low frequency EA on earlobes), auricular eletro-acupuncture group(AEA,n = 10, low frequency EA on ear point 'stomach'), and ST-36 group(ST-36,n = 10, low frequency EA on ST-36). Gastrointestinal (GI) motility was measured by GI transit rate. ICCs(c-kit+ expression) in antrum were analyzed by Immunohistochemistry and western blotting. NO level in blood serum were detected by Griess Reagent, and nNOSmRNA expression in antrum were determined by Real-time PCR. RESULTS: GI transit rate and ICCs(c-kit+ expression) in antrum of AEA group have the tendency to increase compared with CON group, but had no statistics difference (P>0.05). nNOSmRNA expression in antrum of AEA group was dramatically increased compared with CON group (P = 0.037). CONCLUSIONS: Low frequency EA on ear 'stomach' point could significantly up-regulate nNOS mRNA expression and ameliorate the ICCs networks partly in gastric antrum of STZ -induced diabetic rats, which may has benefits on regulating the GI motility.


Subject(s)
Acupuncture, Ear , Diabetes Mellitus, Experimental/therapy , Interstitial Cells of Cajal/physiology , Nitric Oxide Synthase Type I/metabolism , Pyloric Antrum/metabolism , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Gene Expression/physiology , Male , Pyloric Antrum/physiopathology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley
14.
BMC Gastroenterol ; 16: 26, 2016 Feb 29.
Article in English | MEDLINE | ID: mdl-26924750

ABSTRACT

BACKGROUND: Approximately 0.2-1 % of children suffers from abdominal migraine (AM). Pathophysiology of AM has not been adequately studied. This study evaluated gastric motility in children with AM. METHODS: Seventeen children (6 boys), within an age range of 4-15 years, referred to a tertiary care paediatric unit, North Colombo Teaching Hospital Ragama, Sri Lanka, from 2007 to 2012, were screened. Those fulfilling Rome III criteria for AM were recruited after obtaining parental consent. None had clinical or laboratory evidence of organic disorders. Twenty healthy children (8 boys), with an age range of 4-14 years, were recruited as controls. Liquid gastric emptying rate (GE) and antral motility parameters were assessed using an ultrasound method. RESULTS: Average GE (41.6 % vs. 66.2 %, in controls), amplitude of antral contractions (A) (57.9 % vs. 89.0 %) and antral motility index (MI) (5.0 vs. 8.3) were lower and fasting antral area (1.8 cm(2) vs. 0.6 cm(2)) was higher in children with AM (p < 0.01). No significant difference in the frequency of antral contractions (F) (8.8/3 min vs. 9.3/3 min, p = 0.08) was found between the two groups. Scores obtained for severity of abdominal pain had a negative correlation with A (r = -0.55, p = 0.03). Average duration of abdominal pain episodes correlated with GE (r = -0.58, p = 0.02). Negative correlations were observed between duration of AM and A (r = -0.55), F (r = -0.52), and MI (r = -0.57) (p < 0.05). CONCLUSIONS: GE and antral motility parameters were significantly lower in children with AM. A significant correlation was found between symptoms and gastric motility. These findings suggest a possible role of abnormal gastric motility in the pathogenesis of AM.


Subject(s)
Gastric Emptying/physiology , Migraine Disorders/physiopathology , Pyloric Antrum/physiopathology , Adolescent , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Female , Gastrointestinal Motility/physiology , Humans , Male , Migraine Disorders/diagnostic imaging , Muscle Contraction/physiology , Pyloric Antrum/diagnostic imaging , Severity of Illness Index , Sri Lanka , Stomach/diagnostic imaging , Stomach/physiopathology , Ultrasonography
15.
Gut ; 65(7): 1110-8, 2016 07.
Article in English | MEDLINE | ID: mdl-25986945

ABSTRACT

OBJECTIVE: Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. DESIGN: Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. RESULTS: Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. CONCLUSIONS: Motilin may be an important regulator involved in the pathogenesis of obesity.


Subject(s)
Hunger/physiology , Motilin/blood , Myoelectric Complex, Migrating , Obesity/blood , Obesity/surgery , Adult , Case-Control Studies , Duodenum/physiopathology , Erythromycin/pharmacology , Female , Gastric Bypass , Gastrointestinal Agents/pharmacology , Ghrelin/blood , Humans , Hunger/drug effects , Male , Postoperative Period , Preoperative Period , Pyloric Antrum/physiopathology , Surveys and Questionnaires
16.
Am J Clin Nutr ; 102(6): 1323-31, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26561615

ABSTRACT

BACKGROUND: In lean individuals, intraduodenal protein and lipid modulate gastrointestinal motor and hormone functions and reduce energy intake in a load-dependent manner; protein also stimulates insulin, with modest effects on reducing blood glucose. The effect of intraduodenal lipid on gastrointestinal motor and hormone responses is diminished in obesity; whether the effects of protein are also attenuated remains unclear. OBJECTIVES: The objectives of this study were to characterize the load-dependent effects of intraduodenal whey protein hydrolysate on antropyloroduodenal pressures, gut hormones, glycemia, appetite, and energy intake in obese subjects and to compare the responses to the higher protein load with those in lean subjects. DESIGN: We measured antropyloroduodenal pressures, plasma cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, blood glucose, appetite, and energy intake in 12 nondiabetic obese men on 3 separate occasions, in a double-blind, randomized order, during 60-min intraduodenal infusions of hydrolyzed whey protein at either 0 (saline control), 1.5, or 3 kcal/min. Twelve age-matched lean individuals received a 3-kcal/min infusion only. Immediately after the infusions, energy intake from a buffet lunch was quantified. RESULTS: In obese subjects, protein suppressed antral and duodenal pressures; stimulated plasma CCK, GLP-1, GIP, insulin, and glucagon (all r > 0.57, P < 0.01); and tended to reduce energy intake (r = -10.38, P = 0.057) in a dose-dependent manner. In response to the 3-kcal/min protein load, antropyloroduodenal pressures, CCK, GLP-1, and glucagon did not differ between lean and obese subjects. Insulin release was greater, and GIP release less, in obese than in lean subjects (both P < 0.05), whereas the reduction in glucose was comparable. Energy intake tended to be higher in obese subjects (P = 0.08). CONCLUSIONS: The gastrointestinal effects of hydrolyzed whey protein remain relatively intact in obesity; however, the observed changes in insulin and GIP suggest early disturbances in the insulin-incretin axis. This study was registered at www.anzctr.org.au as ACTRN 12612000203853.


Subject(s)
Duodenum/physiopathology , Enteral Nutrition , Intubation, Gastrointestinal , Obesity/therapy , Protein Hydrolysates/therapeutic use , Pyloric Antrum/physiopathology , Whey Proteins/therapeutic use , Adolescent , Adult , Appetite Regulation , Body Mass Index , Double-Blind Method , Duodenum/metabolism , Energy Intake , Gastric Mucosa/metabolism , Gastric Mucosa/physiopathology , Gastrointestinal Hormones/blood , Gastrointestinal Hormones/metabolism , Gastrointestinal Motility , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/physiopathology , Lunch , Male , Middle Aged , Obesity/blood , Obesity/metabolism , Obesity/physiopathology , Protein Hydrolysates/administration & dosage , Pyloric Antrum/metabolism , Whey Proteins/administration & dosage , Young Adult
17.
Neurogastroenterol Motil ; 27(3): 339-46, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25521513

ABSTRACT

BACKGROUND: Studies of symptomatic gastroparetics consistently find poor correlation with gastric emptying. We hypothesized that concomitant small bowel dysmotility may play a role in symptom causation in gastroparesis and sought to test this hypothesis by using wireless motility capsule (WMC) testing to simultaneously measure antral and duodenal area under pressure curve (AUC) in patients with delayed gastric emptying. METHODS: Using a cohort from a multicenter clinical trial and a separate tertiary clinical database, we identified gastroparetics that underwent concurrent WMC testing and completed the Gastroparesis Cardinal Symptom Index, a validated questionnaire. Our study included 35 gastroparetics defined by a gastric emptying time (GET) ≥ 5 h. Antral and duodenal AUC were assessed at 1-h windows pre-GET and post-GET, respectively. KEY RESULTS: We found moderate correlations between duodenal AUC and symptom severity in the combined cohort (n = 35; R = -0.42; p = 0.01; 95% CI -0.7, -0.1). Removing patients with colonic delay resulted in a stronger correlation of duodenal AUC to symptom severity (n = 21; R = -0.63; p < 0.01; 95% CI -0.81, -0.31). The multicenter trial (n = 20) and clinical practice cohorts (n = 15) had significantly different symptom severity and exclusion criteria. When analyzed separately, significant correlations between duodenal AUC and symptom severity were observed (R = -0.71; p < 0.01; 95% CI -0.9, -0.4 and R = -0.72; p < 0.01; 95% CI -0.9, -0.3, respectively). Symptom severity and antral motility showed no correlation. CONCLUSIONS & INFERENCES: We found significant correlations between duodenal AUC and symptom severity in two cohorts of gastroparetics. Small bowel motility may contribute to symptom generation in gastroparetic patients and this may inform therapeutic considerations.


Subject(s)
Duodenum/physiopathology , Gastroparesis/physiopathology , Pyloric Antrum/physiopathology , Female , Humans , Male , Muscle Contraction , Severity of Illness Index
18.
Curr Gastroenterol Rep ; 16(8): 398, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25064317

ABSTRACT

Rumination syndrome is the non-purposeful regurgitation of recently ingested food from the stomach to the mouth, where it is either expelled or reswallowed. Adolescent rumination syndrome (ARS) is a rare condition of which many physicians are unaware. Patients often are misdiagnosed or undergo costly testing, and as a result, diagnosis and treatment are often delayed. While ARS is not life-threatening, it does have medical and emotional effects on the patient and the patient's family. Diagnosis of ARS is based upon the Rome III diagnostic criteria. Antroduodenal manometry, while not required for a diagnosis, can be helpful to confirm the diagnosis. The pathogenesis of this disorder is complex and not well understood. However, because of its behavioral component, treatment of ARS requires a multidisciplinary approach that includes both medical management of symptoms and implementation of strategies that address behavioral, psychological, and general quality-of-life components of the disorder.


Subject(s)
Feeding and Eating Disorders of Childhood/diagnosis , Vomiting/psychology , Adolescent , Duodenum/physiopathology , Feeding and Eating Disorders of Childhood/etiology , Feeding and Eating Disorders of Childhood/therapy , Humans , Manometry/methods , Pyloric Antrum/physiopathology , Syndrome , Vomiting/physiopathology
19.
J Gastroenterol Hepatol ; 29(3): 469-73, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24712047

ABSTRACT

BACKGROUND AND AIM: Patients with gastroesophageal reflux disease (GERD) are often advised to avoid large meals, based on their complaints of increased symptoms after eating too much, and epidemiological evidence of a link between high volume intake and the presence of GERD. However, the precise effects of meal volume on gastroesophageal reflux have not been well studied. We aimed to clarify the effect of meal volume on acid regurgitation and symptoms in patients with GERD. METHODS: Fifteen patients (10 female, 5 male; mean 54 ± 10 years old) with GERD were studied twice each in random order, during 24 h ambulatory pH monitoring. On one day, they consumed a 600 mL liquid test meal three times (breakfast, lunch, and dinner), and on the other, they consumed a 300 mL test meal six times (breakfast, snack, lunch, snack, dinner, and snack). Gastric fundus and antral areas and antral contractions were measured by transabdominal ultrasound. Symptoms were recorded using questionnaires. RESULTS: During the 600 mL regimen, there were more reflux episodes (17 ± 4 vs 10 ± 2, P = 0.03) and a greater total acid reflux time (12.5 ± 5.9% vs 5.5 ± 3.6%; P = 0.045) than the 300 mL regimen. Both the cross-sectional area of the gastric fundus (P = 0.024) and the number of antral contractions (P = 0.014) were greater for the 600 mL regimen. CONCLUSIONS: Larger meals are associated with distension of the gastric fundus and an increase in gastroesophageal reflux when compared with smaller, more frequent meals.


Subject(s)
Eating/physiology , Gastroesophageal Reflux/etiology , Meals , Adult , Disease Progression , Esophageal pH Monitoring , Female , Gastric Fundus/physiopathology , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/physiopathology , Gastroesophageal Reflux/prevention & control , Gastrointestinal Motility , Humans , Male , Middle Aged , Pyloric Antrum/physiopathology , Surveys and Questionnaires
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