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W2051 Electroacupuncture (EA) Improves Impaired Gastric Accommodation, Gastric Dysrhythmia and Delayed Gastric Emptying via the Opioid Pathway in Diabetic Rats Induced By Streptozotocin (STZ)
Exp.3: In order to investigate the effect of UCN on secretion and production of ghrelin, stomach and plasma were collected after ICV injection of saline or UCN (300pmol/head). The levels of acyl-ghrelin and des-acyl ghrelin in stomach and plasma were measured by enzyme-linked immunosorbent assay. Ghrelin gene expression in stomach was measured by real-time RT-PCR. Results: Exp.1:ICV injection of UCN inhibited feeding and gastric empting in rats. Exp.2:The amplitude of contraction is decreased in the antrum but increased in the duodenum after ICV injection of UCN. Exp.3:The levels of acyl-ghrelin and des-acyl ghrelin in stomach were increased at 1 h-2 hrs after ICV injection of UCN. The levels of acyl-ghrelin and des-acyl ghrelin in plasma were decreased at 4 hrs after ICV injection of UCN. The levels of pre-pro ghrelin mRNA in stomach were decreased at 2hrs after ICV injection of UCN. Conclusion: These results suggest that UCN-induced anorexic effects may be mediated partly via inhibition of ghrelin secretion and production. This relation between UCN and ghrelin strongly suggest the involvement of brain-gut axis in anorexia caused by the state of stress.
Response to Acetylcholine and Electrical Field Stimulation On Human Gastric Fundus and Corpus Is Different with That of Human Gastric Antrum Dong Hyun Sinn, Eun Ran Kim, Eun-ju Ko, Hee Jung Son, Jae J Kim, Jong Chul Rhee, Jae Hyung Noh, Tae Sung Sohn, Sung Kim, Sean M. Ward, Poong-Lyul Rhee Introduction: Motor functions of the stomach have traditionally been regarded to differ by stomach region. However, to date there have been few studies on the gastric contractility of the human stomach. Objectives: The aim of the present study was therefore to examine the response to acetylcholine and electrical field stimulation (EFS) of the human fundus, corpus and antrum. Methods: Gastric muscles were obtained from 71 patients (44 males, 27 females with an average age of 60.7 yrs; 34 - 85 yrs) undergoing gastric cancer surgery. Muscle strips (n = 71) were isolated and attached to a fixed mount and to an isometric strain gauge. The muscle strips were studied In Vitro for their contractile responses to acetylcholine (n=25) and electrical field stimulation (EFS, n=46). N-nitro-L-arginine (L-NA), atropine and tetrodotoxin (TTX) were added to assess the nitro oxide-mediated changes and cholinergic neural pathway involved in EFS-induced contractions. Results: Spontaneous contractile activity was observed in muscle strips of stomach regions. In the antrum, acetylcholine induced increase in contraction frequency and peak contraction in dose dependent pattern, but no significant change was noticed in muscle tone. In corpus and fundus, acetylcholine induced dose-dependent increase in peak contraction and muscle tone, but there was no significant change in frequency. The response to EFS also differed by stomach region. EFS produced no significant change in contractile activity in 22 of 46 muscle strips. When EFS evoked frequency-dependent contraction or relaxation in muscle strips, contraction was primarily observed in the muscle strips from the antrum, and relaxation was primarily observed in the muscle strips of the corpus and fundus. The addition of LNA (100 uM) to the muscle bath converted the EFS-induced relaxation to contractions and increased the EFS-induced contractions. EFS-induced contractions were abolished by atropine (1uM) or TTX (1uM). Conclusions: Our study demonstrated that the response to acetylcholine and electrical field stimulation on human gastric fundus and corpus is different with that of human gastric antrum.
W2053 The Impact of Using Different Standardized Meals in the Assessment of Motility of Upper Gastrointestinal Tract Maria C. Bucur, Whitney Michalek, Richard McCallum, Kenneth L. Koch, Michael D. Sitrin, William D. Chey, William L. Hasler, Leonard A. Katz, Henry P. Parkman, Satish S. Rao, John R. Semler, Braden Kuo Introduction: Understanding the motor function of the upper gastrointestinal (UGI) tract in normal subjects and patients with gastroparesis (GP) is crucial for research into new therapies of dysmotility syndromes. Different meal compositions could have an effect on the UGI motility. Development of standardized test meals which can be uniformly adopted across study sites without extensive clinician preparation will facilitate multicenter investigation of motor patterns in health and disease. The SmartPill (SP) wireless capsule is a validated method for quantifying UGI pressure activity. Aim: To determine if UGI pressure patterns before and after the gastric emptying time (GET) vary with the ingestion of different standardized meals. Methods: Healthy subjects (GET<5h) and GP patients (GET>5h) swallowed SP capsule after ingesting 120cc of water and a standardized meal [SmartBar (SB) (260kcal, 2% fat, 2g fiber, 105 cc volume) or Egg beater (EB) meal (255kcal, 2% fat, 1g fiber, 180 cc volume)]. GET of SP from stomach to duodenum is defined as an abrupt rise in pH >3units above baseline pH. Frequencies of contractions (Ct) and pressure amplitudes defined as area under the curve (AUC) were compared 20 minutes before and after GET in those who consumed EB vs. SB. Results: There were no differences in Ct and AUC before and after GET in both healthy and GP subjects after ingesting the EB vs. the SB (presented in table). Conclusions: Parameters of UGI motor function are similar for both healthy volunteers and gastroparetic patients after ingestion of a test meal commonly used with gastric scintigraphic versus a prepackaged bar of comparable nutrient content. The use of the SB meal with a long shelf life that does not require clinician preparation will promote standardization of testing across institutions and will facilitate multicenter investigation of UGI motor disturbances in patients with dysmotility syndromes. Normal Subjects (GET<5h)
W2051 Electroacupuncture (EA) Improves Impaired Gastric Accommodation, Gastric Dysrhythmia and Delayed Gastric Emptying via the Opioid Pathway in Diabetic Rats Induced By Streptozotocin (STZ) Jieyun Yin, Jie Chen, Jiande Chen Impaired gastric accommodation, gastric dysrhythmia and delayed gastric emptying are common in diabetes. The Aim of this study was to investigate the effects and mechanisms of EA on gastric accommodation, gastric dysrhythmia and gastric emptying in STZ-induced diabetic rats. Methods: Ten rats chronically implanted with one pair of gastric serosal electrodes were used in acute experiments (6 weeks after induction of diabetes) of EA on gastrointestinal motility. In the fasting state, gastric slow waves were recorded for 30-min at baseline, 30-min during EA at bilateral ST36 and 30-min during recovery. Then the rats were fed with 1.5ml phenol red solution mixed with methycellulose and EA was performed for 30min immediately after feeding. In a separated session, Naloxone (3mg/kg) was injected 20 min before EA in the fasting state. Gastric retention was assessed by calculating the phenol red amount in the stomach; small intestinal transit was assessed using geometric center (GC) of 10 small intestinal segments. In the control session, sham EA was performed. In another experiment, a gastric balloon was implanted 5 days prior to the test. Gastric accommodation was measured by barostat using ramp distension in three randomized sessions (EA, Sham EA and EA plus Naloxone (3mg/kg)). Results: 1). EA improved gastric dysrhythmia in the diabetic rats. The normal percentage of slow waves was 54.7 ± 4.0% at baseline and significantly increased to 68.4 ± 3.6% with EA (P < 0.01) and sustained at 67.8 ± 2.3% during the recovery period and 67.1 ± 5.2 after the test meal (P < 0.01). Naloxone blocked the improvement of gastric dysrhythmia by EA. 2). EA resulted in a 21.4% increase in gastric emptying and 18.2% increase in small intestinal transit in the diabetic rats. Gastric emptying at 30 min was significantly increased from 75.1 ± 5.0% with sham-EA to 91.2 ± 1.5% with EA (P = 0.01); The GC of intestinal transit was significantly increased from 4.4 ± 0.2 with sham-EA to 5.2 ± 0.2 with EA (P = 0.01). 3). EA restored diabetes-induced impaired gastric accommodation. Gastric accommodation was 0.98 ± 0.13ml with sham-EA and significantly increased to 1.21 ± 0.15ml with EA (P = 0.01); and this effect was blocked when Naloxone was applied together with EA (0.97 ± 0.12ml, P = 0.01 vs. EA). Conclusions: EA at ST 36 improves impaired gastric accommodation, gastric dysrhythmia and delayed gastric emptying and small intestinal transit in STZ-induced diabetic rats; and the improvement is mediated via the opioid pathway. EA may have a promising therapeutic potential for diabetic gastroparesis.
Gastroparetic Subjects (GET>5h)
W2054 Non-Invasive Measurement of Early Postprandial Volume and Accommodation Response in Health and Functional Dyspepsia Using Magnetic Resonance Imaging Jeoffrey J. Haans, Ingrid M. de Zwart, Albert de Roos, Ad Masclee
W2052
Background: Impaired accommodation is considered to be one of the pathophysiological mechanisms in functional dyspepsia. Several studies using the invasive barostat technique have found impaired accommodation in response to a meal in up to 40% of patients with functional dyspepsia. Magnetic Resonance Imaging is an alternative, non-invasive technique to measure volume changes in response to a meal. Methods: Measurements were performed in 21 healthy subjects (HS) and 18 patients with functional dyspepsia (FD). Magnetic Resonance Imaging was used to obtain data prior to and up to 30 minutes after intake of a meglumine gadoterate labeled 200 ml liquid meal (300 kcal). Intragastric air and intragastric meal volumes were obtained using volume scans. Total volume (intragastric air plus contents), accommodation volume (mean total volume over 30 min minus fasting total volume) and accommodation ratio (accommodation volume divided by fasting total volume) were calculated. All data are provided as mean±SD. Results: Healthy subjects and patients with functional dyspepsia (endoscopy negative) did not differ significantly in age, gender or BMI. Fasting total volume did not differ significantly (p=0.38) between both groups, 39±24 ml and 45±16 ml for HS and FD resp. Immediately after meal intake total volume increased to 304±51 and 315±63 ml for HS and FD resp. Accommodation volume did not differ significantly
Urocortin Reduces Food Intake via Inhibition of Ghrelin Secretion in Rats Shino Ohno, Shoki Ro, Tsuneko Onouchi, Mitsuko Ochiai, Shingo Kato, Masamichi Noguchi, Mitsutoshi Yuzurihara, Tomohisa Hattori, Koji Yakabi Background/Aim: The effects of stress on feeding and the involvement of CRF family in modulating the anorexia are well recognized. Urocortin (UCN), a member of CRF family, inhibits feeding behavior. On the other hand, ghrelin promotes feeding behavior. Although the both play an important role in the control of food intake in brain-gut axis,involvement of ghrelin in mechanism underlying anorexia induced by UCN has not been understood. To clarify mechanism underlying anorexia induced by urocortin, ghrelin gene expression in the stomach and ghrelin levels in stomach and plasma were examined after ICV injection of UCN. Methods: Exp.1:Effects of ICV injection of UCN (30-300 pmol/head) on the 24 hrs food and water intake and gastric empting were examined in fasted rats. Exp.2:The effect of ICV injection of UCN on gastroduodenal motor activity was measured in the conscious rats by a strain gauge force transducer method. After the gastroduodenal motility was ascertained to be changed into the fed pattern, ICV injection of UCN was performed.
A-781
AGA Abstracts
AGA Abstracts
W2050
Response to Acetylcholine and Electrical Field Stimulation On Human Gastric Fundus and Corpus Is Different with That of Human Gastric Antrum Dong Hyun Sinn, Eun Ran Kim, Eun-ju Ko, Hee Jung Son, Jae J Kim, Jong Chul Rhee, Jae Hyung Noh, Tae Sung Sohn, Sung Kim, Sean M. Ward, Poong-Lyul Rhee Introduction: Motor functions of the stomach have traditionally been regarded to differ by stomach region. However, to date there have been few studies on the gastric contractility of the human stomach. Objectives: The aim of the present study was therefore to examine the response to acetylcholine and electrical field stimulation (EFS) of the human fundus, corpus and antrum. Methods: Gastric muscles were obtained from 71 patients (44 males, 27 females with an average age of 60.7 yrs; 34 - 85 yrs) undergoing gastric cancer surgery. Muscle strips (n = 71) were isolated and attached to a fixed mount and to an isometric strain gauge. The muscle strips were studied In Vitro for their contractile responses to acetylcholine (n=25) and electrical field stimulation (EFS, n=46). N-nitro-L-arginine (L-NA), atropine and tetrodotoxin (TTX) were added to assess the nitro oxide-mediated changes and cholinergic neural pathway involved in EFS-induced contractions. Results: Spontaneous contractile activity was observed in muscle strips of stomach regions. In the antrum, acetylcholine induced increase in contraction frequency and peak contraction in dose dependent pattern, but no significant change was noticed in muscle tone. In corpus and fundus, acetylcholine induced dose-dependent increase in peak contraction and muscle tone, but there was no significant change in frequency. The response to EFS also differed by stomach region. EFS produced no significant change in contractile activity in 22 of 46 muscle strips. When EFS evoked frequency-dependent contraction or relaxation in muscle strips, contraction was primarily observed in the muscle strips from the antrum, and relaxation was primarily observed in the muscle strips of the corpus and fundus. The addition of LNA (100 uM) to the muscle bath converted the EFS-induced relaxation to contractions and increased the EFS-induced contractions. EFS-induced contractions were abolished by atropine (1uM) or TTX (1uM). Conclusions: Our study demonstrated that the response to acetylcholine and electrical field stimulation on human gastric fundus and corpus is different with that of human gastric antrum.
W2053 The Impact of Using Different Standardized Meals in the Assessment of Motility of Upper Gastrointestinal Tract Maria C. Bucur, Whitney Michalek, Richard McCallum, Kenneth L. Koch, Michael D. Sitrin, William D. Chey, William L. Hasler, Leonard A. Katz, Henry P. Parkman, Satish S. Rao, John R. Semler, Braden Kuo Introduction: Understanding the motor function of the upper gastrointestinal (UGI) tract in normal subjects and patients with gastroparesis (GP) is crucial for research into new therapies of dysmotility syndromes. Different meal compositions could have an effect on the UGI motility. Development of standardized test meals which can be uniformly adopted across study sites without extensive clinician preparation will facilitate multicenter investigation of motor patterns in health and disease. The SmartPill (SP) wireless capsule is a validated method for quantifying UGI pressure activity. Aim: To determine if UGI pressure patterns before and after the gastric emptying time (GET) vary with the ingestion of different standardized meals. Methods: Healthy subjects (GET<5h) and GP patients (GET>5h) swallowed SP capsule after ingesting 120cc of water and a standardized meal [SmartBar (SB) (260kcal, 2% fat, 2g fiber, 105 cc volume) or Egg beater (EB) meal (255kcal, 2% fat, 1g fiber, 180 cc volume)]. GET of SP from stomach to duodenum is defined as an abrupt rise in pH >3units above baseline pH. Frequencies of contractions (Ct) and pressure amplitudes defined as area under the curve (AUC) were compared 20 minutes before and after GET in those who consumed EB vs. SB. Results: There were no differences in Ct and AUC before and after GET in both healthy and GP subjects after ingesting the EB vs. the SB (presented in table). Conclusions: Parameters of UGI motor function are similar for both healthy volunteers and gastroparetic patients after ingestion of a test meal commonly used with gastric scintigraphic versus a prepackaged bar of comparable nutrient content. The use of the SB meal with a long shelf life that does not require clinician preparation will promote standardization of testing across institutions and will facilitate multicenter investigation of UGI motor disturbances in patients with dysmotility syndromes. Normal Subjects (GET<5h)
W2051 Electroacupuncture (EA) Improves Impaired Gastric Accommodation, Gastric Dysrhythmia and Delayed Gastric Emptying via the Opioid Pathway in Diabetic Rats Induced By Streptozotocin (STZ) Jieyun Yin, Jie Chen, Jiande Chen Impaired gastric accommodation, gastric dysrhythmia and delayed gastric emptying are common in diabetes. The Aim of this study was to investigate the effects and mechanisms of EA on gastric accommodation, gastric dysrhythmia and gastric emptying in STZ-induced diabetic rats. Methods: Ten rats chronically implanted with one pair of gastric serosal electrodes were used in acute experiments (6 weeks after induction of diabetes) of EA on gastrointestinal motility. In the fasting state, gastric slow waves were recorded for 30-min at baseline, 30-min during EA at bilateral ST36 and 30-min during recovery. Then the rats were fed with 1.5ml phenol red solution mixed with methycellulose and EA was performed for 30min immediately after feeding. In a separated session, Naloxone (3mg/kg) was injected 20 min before EA in the fasting state. Gastric retention was assessed by calculating the phenol red amount in the stomach; small intestinal transit was assessed using geometric center (GC) of 10 small intestinal segments. In the control session, sham EA was performed. In another experiment, a gastric balloon was implanted 5 days prior to the test. Gastric accommodation was measured by barostat using ramp distension in three randomized sessions (EA, Sham EA and EA plus Naloxone (3mg/kg)). Results: 1). EA improved gastric dysrhythmia in the diabetic rats. The normal percentage of slow waves was 54.7 ± 4.0% at baseline and significantly increased to 68.4 ± 3.6% with EA (P < 0.01) and sustained at 67.8 ± 2.3% during the recovery period and 67.1 ± 5.2 after the test meal (P < 0.01). Naloxone blocked the improvement of gastric dysrhythmia by EA. 2). EA resulted in a 21.4% increase in gastric emptying and 18.2% increase in small intestinal transit in the diabetic rats. Gastric emptying at 30 min was significantly increased from 75.1 ± 5.0% with sham-EA to 91.2 ± 1.5% with EA (P = 0.01); The GC of intestinal transit was significantly increased from 4.4 ± 0.2 with sham-EA to 5.2 ± 0.2 with EA (P = 0.01). 3). EA restored diabetes-induced impaired gastric accommodation. Gastric accommodation was 0.98 ± 0.13ml with sham-EA and significantly increased to 1.21 ± 0.15ml with EA (P = 0.01); and this effect was blocked when Naloxone was applied together with EA (0.97 ± 0.12ml, P = 0.01 vs. EA). Conclusions: EA at ST 36 improves impaired gastric accommodation, gastric dysrhythmia and delayed gastric emptying and small intestinal transit in STZ-induced diabetic rats; and the improvement is mediated via the opioid pathway. EA may have a promising therapeutic potential for diabetic gastroparesis.
Gastroparetic Subjects (GET>5h)
W2054 Non-Invasive Measurement of Early Postprandial Volume and Accommodation Response in Health and Functional Dyspepsia Using Magnetic Resonance Imaging Jeoffrey J. Haans, Ingrid M. de Zwart, Albert de Roos, Ad Masclee
W2052
Background: Impaired accommodation is considered to be one of the pathophysiological mechanisms in functional dyspepsia. Several studies using the invasive barostat technique have found impaired accommodation in response to a meal in up to 40% of patients with functional dyspepsia. Magnetic Resonance Imaging is an alternative, non-invasive technique to measure volume changes in response to a meal. Methods: Measurements were performed in 21 healthy subjects (HS) and 18 patients with functional dyspepsia (FD). Magnetic Resonance Imaging was used to obtain data prior to and up to 30 minutes after intake of a meglumine gadoterate labeled 200 ml liquid meal (300 kcal). Intragastric air and intragastric meal volumes were obtained using volume scans. Total volume (intragastric air plus contents), accommodation volume (mean total volume over 30 min minus fasting total volume) and accommodation ratio (accommodation volume divided by fasting total volume) were calculated. All data are provided as mean±SD. Results: Healthy subjects and patients with functional dyspepsia (endoscopy negative) did not differ significantly in age, gender or BMI. Fasting total volume did not differ significantly (p=0.38) between both groups, 39±24 ml and 45±16 ml for HS and FD resp. Immediately after meal intake total volume increased to 304±51 and 315±63 ml for HS and FD resp. Accommodation volume did not differ significantly
Urocortin Reduces Food Intake via Inhibition of Ghrelin Secretion in Rats Shino Ohno, Shoki Ro, Tsuneko Onouchi, Mitsuko Ochiai, Shingo Kato, Masamichi Noguchi, Mitsutoshi Yuzurihara, Tomohisa Hattori, Koji Yakabi Background/Aim: The effects of stress on feeding and the involvement of CRF family in modulating the anorexia are well recognized. Urocortin (UCN), a member of CRF family, inhibits feeding behavior. On the other hand, ghrelin promotes feeding behavior. Although the both play an important role in the control of food intake in brain-gut axis,involvement of ghrelin in mechanism underlying anorexia induced by UCN has not been understood. To clarify mechanism underlying anorexia induced by urocortin, ghrelin gene expression in the stomach and ghrelin levels in stomach and plasma were examined after ICV injection of UCN. Methods: Exp.1:Effects of ICV injection of UCN (30-300 pmol/head) on the 24 hrs food and water intake and gastric empting were examined in fasted rats. Exp.2:The effect of ICV injection of UCN on gastroduodenal motor activity was measured in the conscious rats by a strain gauge force transducer method. After the gastroduodenal motility was ascertained to be changed into the fed pattern, ICV injection of UCN was performed.
A-781
AGA Abstracts
AGA Abstracts
W2050