Tu1809 Intestinal Manipulation Induces Degranulation of Peritoneal Mast Cells and Activates Dorsal...
Transcript of Tu1809 Intestinal Manipulation Induces Degranulation of Peritoneal Mast Cells and Activates Dorsal...
Figure 1. Effects of Rikkunshito on plasma acylated ghrelin level in aged male and femalemice exposed novelty environment stress.
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Duodenal Nutrient Sensitivity During Enteral Lipid and CarbohydrateInfusion in Functional Dyspepsia (FD): A Role for Enteral HormonesAdil E. Bharucha, Michael Camilleri, Alan R. Zinsmeister
Background. Approximately 20% of patients with FD have rapid gastric emptying (RGE).Accelerated duodenal delivery of nutrients and/or increased duodenal sensitivity may explainGI symptoms in these patients. Indeed, FD patients report severe symptoms during duodenallipid (LIP)) but not carbohydrate (CHO) infusion. The mechanisms of this increased sensitiv-ity are poorly understood. While enteral hormones are implicated, there is limited evidence,only for CCK, based on a study of 8 functional dyspepsia patients and 8 controls (Pilichiewicz2008). Hypotheses. Patients with FD have increased nutrient sensitivity and concentrationsof plasma enteral hormones mediating satiety during duodenal enteral lipid or CHO infusion.Methods. Enteral hormonal responses during duodenal nutrient infusion were comparedin 35 healthy subjects (41 ± 3 years, 24 females, BMI 26.4 ± 0.7 kg/m2) and 30 FD patients(40 ± 3 years, 26 female, BMI 26.4 ± 0.7 kg/m2) with previously documented idiopathicRGE for solids. Isocaloric (222 kcal) and isovolumic (222 mL) carbohydrate (CHO, Limeon-dex®, 75 gm) and lipid infusions (Microlipid® 66.7 mL diluted to 222 mL, 0.5 gm/mL)were administered in randomized order over 120 minutes separated by a 120 minute washoutperiod. These nutrients were given at a variable rate, approximating that at which oralglucose enters the systemic circulation in healthy subjects. During infusions, symptoms wereevaluated by a VAS scale (0=none, 1=light, 2=moderate, 3=severe, 4=intolerable). Associationsbetween plasma hormones (AUC) and subject status (ie, control vs functional dyspepsia)and separately with any moderate symptoms or worse were evaluated by univariate tests.Results. 30 controls and 24 pts completed studies. During lipid (6 controls, 14 pts) andcarbohydrate infusion (1 control, 14 pts) the presence of one or more symptoms of at leastmoderate severity was more common (p ≤ 0.01) in patients than controls. Compared tosubjects with mild or no symptoms, a higher proportion of subjects with moderate ormore severe symptoms had abnormal (ie, >90th %tile values in controls) plasma hormoneconcentrations during the corresponding nutrient infusion ie (a) higher GLP-1 (p = 0.005)concentration during CHO infusion and (b) higher GIP (p = 0.01) and CCK (p=0.03)concentration during lipid infusion. Other hormones (PYY, ghrelin, glucagon, and insulin)were not associated with increased sensitivity. Conclusions. During enteral carbohydrateor lipid infusions, patients with FD and RGE have increased symptoms which is associatedwith higher plasma concentrations of GLP-1 during carbohydrate as also CCK and GIPconcentrations during lipid infusion compared to controls. These data suggest that amongpatients with FD, enteral hormones mediate exaggerated increased intestinal sensitivity tonutrients in a nutrient-specific manner.Comparison of Plasma Hormone Concentration in Subjects with and without Moderate/Severe/Intolerable Symptoms during Carbohydrate or Lipd Infusion
Values are Median (IQ range)Association between Plasma Hormone Concentrations and Duodenal Sensitivity
S-849 AGA Abstracts
α p = 0.005, β p = 0.01, γ p = 0.03 for Fisher's exact or Chi-Square test
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Intestinal Manipulation Induces Degranulation of Peritoneal Mast Cells andActivates Dorsal Root Ganglia in Postoperative IleusSergio Berdún, Patri Vergara
Background: Mast cells (MC) have been demonstrated to play a role in the pathogenesis ofpostoperative ileus (POI) in mice and humans. We aimed to investigate if such mechanismscould be related to activation of afferent neural pathways in the rat. Methods: Male Sprague-Dawley rats (8-9 wo) were subjected to laparotomy plus intestinal manipulation (IM, N=12) or only laparotomy (SHAM, N=8). Intestinal manipulation was performed by touchingdistal jejunum, ileum, caecum and proximal colon with cotton swabs under sterile surgicalconditions. 20 min later, peritoneal lavage was collected for the assessment of levels of rat mastcell protease 6 (RMCP-6). In vivo intestinal transit and gastric emptying and inflammation ofileum wall (PCR; IL-6, IL-10) were evaluated at 24h. Toraco-lumbar (T10-L2) dorsal rootganglia (DRG) were collected and used for the assessment of CGRP, CGRP receptor, SP,PAR-2, NGF, TrkA and TRPV-1 expression (PCR). In another study, following laparotomy,ileum was incubated with either Compound 48/80 (0.6mg/ml, N=6) or saline (controlgroup, N=6) for 1min. At 3 hours, peritoneal RMCP-6, gastrointestinal transit, intestinalinflammation and activation of DRG were also evaluated. Results: Upon intestinal manipula-tion, absorbance for RMCP-6 in peritoneal fluid increased (0.35 ± 0.02 vs 0.27 ± 0.01 inSHAM group, P<0.05). Furthermore, intestinal manipulation delayed intestinal transit (GCIM: 3.98 ± 0.29 vs GC SHAM: 6.20 ± 0.33, P<0.0001) but did not alter gastric emptying(GE IM: 65.30 ± 8.05 % vs GE SHAM: 84.07 ± 8.20 %, P=0.07) at 24 h and induced up-regulation of IL-6 and IL-10 mRNA expression by 4.72 and 3.34 folds respectively (P<0.05)in the intestinal wall. Likewise expression of CGRP, PAR-2 and TrkA in DRG were increasedin manipulated rats by 1.41, 1.29 and 1.21 folds respectively (P<0.05). Compound 48/80decreased absorbance for peritoneal RMCP-6 (0.14 ± 0.01 vs 0.20 ± 0.02 in control group,P<0.05), evoked delayed intestinal transit and gastric emptying (GC C48/80: 3.99 ± 0.32vs GC CONTROL: 5.16 ± 0.29, P<0.05 and GE C48/80: 44.34 ± 9.09% vs GE CONTROL:78.12 ± 5.89%, P<0.01) and also increased expression of IL-6 (2.20± 0.45 vs 1.03±0.10fold change in control group, P<0.05). Nevertheless, there were no differences in theexpression of CGRP, CGRP receptor, NGF, TrkA, PAR-2, TRPV-1 in DRG (P<0.05) afterincubation with C48/80. Conclusions: Our results show that intestinal manipulation isfollowed by activation of peritoneal mast cells and splanchnic afferents as demonstrated bythe activation of toraco-lumbar DRG. The mast cell degranulator C48/80 reduced intestinalmotility and induced inflammation resembling the effects of intestinal manipulation. None-theless it failed to activate DRG indicating that intestinal manipulation involves multifactorialmechanisms leading to afferent activation.
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Vesopressin-Induced Nausea and Vomiting Present With Distinct GastricMotility Patterns in DogsYan Sun, Geng-Qing Song, Yang Bin, Xiaohua Hou, Richard W. McCallum
Background: The correlation among gastrointestinal symptoms (such as nausea and vomit-ing), gastric motility, gastric myoelectrical activity (GMA) is poorly understood. Aims: Theaim of this study was to assess the association of gastric motility (postprandial antralcontractions and gastric emptying of liquids) and GMA with vomiting induced by vasopressin.Methods: 14 female beagle dogs with either a gastric (for measuring antral contractions(AC)) or duodenal cannula (for recording gastric emptying of liquids (GE)) and 4 pairs ofgastric serosa electrodes for gastric slow waves recording were studied. The protocol included2 experiments (AC and GE), each consisting of two sessions (saline and vasopressin). Eachsession was conducted sequentially as follows: 30-min baseline, ingestion of a liquid meal(for GE) or a solid meal (for AC), 30-min intravenous infusion of vasopressin (0.75 U/kg,in 30 ml of 154 mmol NaCl, 1ml/min) or saline (30 ml of 154 mmol NaCl, 1ml/min), andtwo 30-min postprandial recordings. Emetic symptoms and GMA were recorded in eachsession. Antral contractions were measured by a water perfused manometry system. Gastricemptying contents were collected every 15 min via the cannula for a period of 90 min.Results: Vasopressin induced episodes of nausea and vomiting in all animals. 1) Whenvomiting occurred, it was accompanied by increased amplitude of antral contractions andthe propagation of the contraction wave was completely uncoupled. the major contractionpattern was hypo-motility during the remaining time period of 30-min infusion of vasopressin(4.6 ± 0.8, P < 0.01 vs. the corresponding period in saline control (7.5 ± 1.3)). 2) Duringinfusion of vasopressin, the pattern of dysrhythmia immediately before vomiting was tachyar-rhythmia and the gastric slow wave was completely uncoupled before and after vomiting.However, the pattern returned quickly to brandygastria which was the main dysrhythmiaoverall during the 30-min infusion of vasopressin (59.7 % ± 6.3 %, P < 0.01 vs. thecorresponding period in saline control (2.5 ± 1.1 %)). (3) The increase of antral contraction
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