- Email: [email protected]
Mo1161 Serum Micronutrient Level and Gastric Motility: Delayed Gastric Emptying and Nutritional Deficiencies in Patients With Gastroparesis
contains 1.4% rikkunshito (a traditional Japanese medicine, R group), 0.04% domperidone (D group) and 0.02% mosapride which is serotonin 5-HT4 receptor agonist (M group) for 2 weeks (4 mice for each groups). RNA was extracted from the stomach, duodenum, proximal jejunum and mid-jejunum, and each cDNA was synthesized. We measured mRNA levels of T1R2, T1R3, G-protein α-gustducin (Gαgust) and proglucagon by real-time PCR method and the expression level of each gene was expressed as the ratio compared with that of control group (C group). (2) We also administered free access to water contain 0.02% mosapride to adult male C57BL/KsJ-db/db Jcl mice aged 9 weeks which are type 2 diabetes model mice (DM-M group) and analyzed them in the same way. Results: The expression of T1R2 did not change significantly in R group and D group. Otherwise, the expression of T1R2 of proximal jejunum and mid-jejunum were significantly high in M group [4.1 ± 1.8 times and 3.1 ± 1.6 times (p≤0.05)] and in DM-M group [3.5 ± 2.5 times and 3.6 ± 1.2 times (p≤0.05)], respectively. The expression of T1R3 of any digestive tract were significantly lower in R group and D group [0.1-0.2 times (p≤0.05)], but there were no significant difference in M group and DM-M group. While the expressions of Gαgust of stomach, duodenum, and proximal jejunum were significantly lower in R group and D group, those of stomach, proximal jejunum, and mid-jejunum in M group were significantly high [3.2 ± 0.7 times, 4.6 ± 0.8 times and 3.1 ± 0.9 times, respectively]. However, there was no its elevation in DM-M group. Conclusions: The expression of T1R2 and Gαgust of gastrointestinal tract of mice administered mosapride were significantly increased. In contrast, the expression of T1R3 and Gαgust were significantly decreased after the administration of rikkunshito and domperidone. The fact that the expression of gastrointestinal taste receptor was affected by administration of drugs for FGIDs might help us to understand the mechanisms of these drugs' effects.
Mo1158 IL-1 Receptor Signaling Mediates Postoperative Ileus in a Mouse Model of Intestinal Manipulation Burkhard Stoffels, Sjoerd H. van Bree, Mariola Lysson, Kristof J. Hupa, Wouter de Jonge, Joerg C. Kalff, Sven Wehner INTRODUCTION: Abdominal surgery commonly leads to a transient postoperative intestinal dysmotility, known as postoperative ileus (POI). We have previously shown that activation of resident muscularis externa (ME) macrophages and an innate immune response is a crucial step in the initiation of POI. Herein, we studied the role of innate immune receptor signaling in POI development. AIMS & METHODS: C57BL6 wildtype, TLR-/-, MyD88-/-, Trif-/-, IL-1R-/- and IL-18-/- mice underwent a standardized intestinal manipulation (IM). After 3 h and 24 h, cytokine gene expression, neutrophil levels and the geometric center (GC) of gastrointestinal transit (GIT) were assessed. Results: IM led to a significant induction of cytokine expression (IL-6: 115±50 vs. 1.1±1, IL-1beta 49±6 vs. 1±0.1-fold) and neutrophil influx (805±184 vs. 2±1 cells/mm2) compared to unoperated controls (C) after surgery in the ME. GIT was also significantly decelerated by IM (GC: IM 3.4±0.5 vs. C 9.3±0.3). POI was dependent on MyD88 but not Trif deficiency, as neutrophils (333±17 cells/mm2) and proinflammatory gene expression (IL-6: 21±5; IL-1beta: 6±1) was significantly reduced, while GIT was accelerated (GC: 5.4±0.3). Upstream MyD88-/- signaling was dependent on IL-R but not TLR or IL-18 signaling, as IL-1R, but not TLR-2 or -4 or -9 and IL-18 deficient mice, demonstrated reduced ME inflammation (556±34 cells/mm2) and improved GIT (GC: 6.4±0.5). Additionally, ASC-/-mice demonstrated no changes in postoperative ME inflammation and dysmotility, indicating that IL-1R signaling is independent from ASC depending inflammasome IL-1 beta production. Conclusion: Upstream innate immune activation of Myd88 signaling via IL-1, but not TLR or IL-18 dependent mechanisms, is involved in POI development. Perioperative targeting of IL-1 signaling could be a promising strategy in prevention of POI.
Mo1161 Serum Micronutrient Level and Gastric Motility: Delayed Gastric Emptying and Nutritional Deficiencies in Patients With Gastroparesis Archana Kedar, Yana Nikitina, Katherine B. Abell, Vetta Vedanarayanan, William A. Rock, Michael Griswold, Thomas L. Abell Background: Nutritional abnormalities are common in patients with gastroparesis (Gp), a disorder that may affect gastric motility and delay emptying. Objective: Identify relationships between serum nutrition markers and gastric motility measures in Gp patients. Design, Setting, and Patients: Enrolled 59 consecutive gastric motility clinic patients (48 female, 11 male; mean age 44yrs; 42 Idiopathic; 17 Diabetes Mellitus) with Gp symptoms. Intervention: Assessed baseline serum nutrition markers and gastric emptying times (GET); recorded baseline prescription medications and nutrition supplements. Main Outcome Measurements: Examined serum nutrition and GET measures for associations. Results: Vitamin D levels, for most patients slightly above the lower limit of normal (38.68 ± 25.05 ng/mL), were lowest in diabetic (DM) (30.32 ±13.71 ng/mL) versus idiopathic (ID) (42.12 ± 27.89 ng/ mL) gastroparesis. First hour GET: A 10 ng/Dl vitamin D level increase was associated for all patients with a 2.7% improvement (95% CI -5.46, -0.01) p=0.056; this association, although marked in ID Gp, -3.4% (95% CI -6.4, -0.3) p=0.033, was extremely weak in DM Gp, 5.2 [-11.7, 22.1], p=0.536. Fouth hour GET: A 10 ng/Dl increase of vitamin D, associated with significant improvement for all patients, -2.8% [-5.7, 0.4] p=0.053, was weaker in ID, -2.8 [-6.1, 0.4] p=0.086, and absent in DM, 7.3 [-17.3, 18.8] p=0.935, gastroparesis. Limitations: No food intake history. Conclusions: Vitamin D levels may be associated with gastric emptying, with potentially differing roles across Gp etiologies. Vitamin D contributions to enteric nerve function should be explored, particularly where metabolic comorbidities exist.
Mo1159 Inhibitory Effects and Sympathetic Mechanisms of Distension in the Distal Organs on Small Bowel Motility and Slow Waves in Dogs Jun Song, Jieyun Yin, Hanaa Sallam, Jiande Chen BACKGROUND AND AIMS: Rectal distension (RD) is known to induce intestinal dysmotilily. Few studies were performed to compare effects of RD, colon distension (CD) and duodenal distension (DD) on small bowel motility. This study aimed to investigate effects and underlying mechanisms of distensions in these regions on intestinal motility and slow waves in the dogs. METHODS: Six female dogs chronically implanted with a duodenal fistula, a proximal colon fistula and intestinal serosal electrodes were studied in six randomized sessions on separate days: control, RD, CD, DD, RD + guanethidine and CD + guanethidine. We recorded intestinal slow waves and intestinal manometry 15 cm distal to the site of DD, and the ECG in three periods (30 min baseline, 30 min distension and 30 min recovery) immediately after a standard test meal (solid canned dog food). All distensions were performed using a barostat with a constant pressure of 30 mmHg. RESULTS: 1) Isobaric RD and CD suppressed intestinal contractions (contractile index or CI: 6.0 ± 0.4 with RD vs. 9.9 ± 0.9 at baseline, P = 0.009, 5.3 ± 0.2 with CD vs. 7.7± 0.8 at baseline, P = 0.008). Guanethidine 3 mg/kg iv was able to partly block the suppressed contractions. 2) RD and CD reduced the percentage of normal intestinal slow waves from 92.1 ± 2.8% to 64.2 ± 3.4 (P < 0.001) and from 90 ± 2.7% to 69.2 ± 3.7% (P = 0.01) respectively. Guanethidine could eliminate these inhibitory effects. 3) DD didn't induce any changes in small intestinal contractions or intestinal slow waves (P > 0.05). 4) The spectral analysis of the heart rate variability signal derived from the ECG showed both RD and CD increased sympathetic activity (LF) (0.47 ± 0.08 with RD vs. 0.31 ± 0.08 at baseline, P = 0.02, 0.56 ± 0.14 with CD vs. 0.45 ± 0.14 at baseline, P = 0.01) and reduced vagal activity (HF) (0.53 ± 0.06 with RD vs. 0.78 ± 0.09 at baseline, P = 0.04, 0.52 ± 0.07 with CD vs. 0.82 ± 0.09 at baseline, P = 0.03). CONCLUSION: Isobaric RD and CD inhibited postprandial intestinal motility and impaired intestinal slow waves mediated via the sympathetic pathway. However, lumen distention (DD) at a site proximal to the measurement site does not seem to impair small intestinal contractions or slow waves. Mo1160
Mo1162
The Gene Expression of Taste Receptors in Gastrointestinal Tract After the Administration of Drugs for Functional Gastrointestinal Disorders Daisuke Maruoka, Makoto Arai, Tomoaki Matsumura, Tomoo Nakagawa, Tatsuro Katsuno, Fumio Imazeki, Osamu Yokosuka
Scn10a Gene Polymorphisms are Closely Associated With the Risk of Functional Dyspepsia in Japan Nobuhiko Hayashi, Hisakazu Shiroeda, Ranji Hayashi, Kazuhiro Matsunaga, Atsushi Fukumura, Kazuaki Ozaki, Tomomitsu Tahara, Tomoyuki Shibata, Tomiyasu Arisawa
Aims: Taste receptors, type 1, member 2 / member 3 (T1R2 / T1R3), which is G-protein coupled receptor located in taste bud and act as a receptor for sweet tastants, were reported to exist in mucosa of the gastrointestinal tract and attract attention recently. Various drugs were administered for functional gastrointestinal disorders (FGIDs), but these drugs' effects to sweet tastants' receptors have not been known exactly. We analyzed the change of these genes expression in mucosa of the gastrointestinal tract after the administration of drugs for FGIDs in this study. Materials and Methods: (1) Adult male C57BL/6 mice aged 9 weeks which had free access to water and a standard diet. We administered free access to water
[Background] The role of genetics in the susceptibility to functional dyspepsia (FD) remains unclear. Visceral sensory is transmitted via C-fiber from gastrointestinal tract to CNS. SNS, a TTX-resistant voltage gated Na+ channel, was identified on C-fiber (Akopian AN et al., Nature 1996). Thereafter, it has been demonstrated that SNS null mutant mice lowered thresholds of electrical activation of C-fiber (Akopian AN et al., Nature Nurosci, 1999). Recently, mutant allele of V1073A variation in SCN10A gene, coding SNS, is revealed to be a gain of function allele (Chambers JC et al., Nat Genet, 2010). We attempted to
S-609
AGA Abstracts
AGA Abstracts
well as its duration and amplitude. CONCLUSIONS: Acute thermal cooling affects colonic neuromuscular function by increasing basal tone and response to cholinergic stimulus. These effects are not reversible after short-term observation. It is known that temperature affects both the ionic conductances and the rate constants modulating the action potential propagation in giant squid axon. We hypothesize that temperature gradients, by changing the ion dynamics, could influence the electrochemical behaviour of intestinal muscle, with a memory effect which should require long time to be deleted. Further studies are needed to establish the exact involved mechanisms in order to better understand clinical consequences of hypothermia during abdominal surgery.
Mo1158 IL-1 Receptor Signaling Mediates Postoperative Ileus in a Mouse Model of Intestinal Manipulation Burkhard Stoffels, Sjoerd H. van Bree, Mariola Lysson, Kristof J. Hupa, Wouter de Jonge, Joerg C. Kalff, Sven Wehner INTRODUCTION: Abdominal surgery commonly leads to a transient postoperative intestinal dysmotility, known as postoperative ileus (POI). We have previously shown that activation of resident muscularis externa (ME) macrophages and an innate immune response is a crucial step in the initiation of POI. Herein, we studied the role of innate immune receptor signaling in POI development. AIMS & METHODS: C57BL6 wildtype, TLR-/-, MyD88-/-, Trif-/-, IL-1R-/- and IL-18-/- mice underwent a standardized intestinal manipulation (IM). After 3 h and 24 h, cytokine gene expression, neutrophil levels and the geometric center (GC) of gastrointestinal transit (GIT) were assessed. Results: IM led to a significant induction of cytokine expression (IL-6: 115±50 vs. 1.1±1, IL-1beta 49±6 vs. 1±0.1-fold) and neutrophil influx (805±184 vs. 2±1 cells/mm2) compared to unoperated controls (C) after surgery in the ME. GIT was also significantly decelerated by IM (GC: IM 3.4±0.5 vs. C 9.3±0.3). POI was dependent on MyD88 but not Trif deficiency, as neutrophils (333±17 cells/mm2) and proinflammatory gene expression (IL-6: 21±5; IL-1beta: 6±1) was significantly reduced, while GIT was accelerated (GC: 5.4±0.3). Upstream MyD88-/- signaling was dependent on IL-R but not TLR or IL-18 signaling, as IL-1R, but not TLR-2 or -4 or -9 and IL-18 deficient mice, demonstrated reduced ME inflammation (556±34 cells/mm2) and improved GIT (GC: 6.4±0.5). Additionally, ASC-/-mice demonstrated no changes in postoperative ME inflammation and dysmotility, indicating that IL-1R signaling is independent from ASC depending inflammasome IL-1 beta production. Conclusion: Upstream innate immune activation of Myd88 signaling via IL-1, but not TLR or IL-18 dependent mechanisms, is involved in POI development. Perioperative targeting of IL-1 signaling could be a promising strategy in prevention of POI.
Mo1161 Serum Micronutrient Level and Gastric Motility: Delayed Gastric Emptying and Nutritional Deficiencies in Patients With Gastroparesis Archana Kedar, Yana Nikitina, Katherine B. Abell, Vetta Vedanarayanan, William A. Rock, Michael Griswold, Thomas L. Abell Background: Nutritional abnormalities are common in patients with gastroparesis (Gp), a disorder that may affect gastric motility and delay emptying. Objective: Identify relationships between serum nutrition markers and gastric motility measures in Gp patients. Design, Setting, and Patients: Enrolled 59 consecutive gastric motility clinic patients (48 female, 11 male; mean age 44yrs; 42 Idiopathic; 17 Diabetes Mellitus) with Gp symptoms. Intervention: Assessed baseline serum nutrition markers and gastric emptying times (GET); recorded baseline prescription medications and nutrition supplements. Main Outcome Measurements: Examined serum nutrition and GET measures for associations. Results: Vitamin D levels, for most patients slightly above the lower limit of normal (38.68 ± 25.05 ng/mL), were lowest in diabetic (DM) (30.32 ±13.71 ng/mL) versus idiopathic (ID) (42.12 ± 27.89 ng/ mL) gastroparesis. First hour GET: A 10 ng/Dl vitamin D level increase was associated for all patients with a 2.7% improvement (95% CI -5.46, -0.01) p=0.056; this association, although marked in ID Gp, -3.4% (95% CI -6.4, -0.3) p=0.033, was extremely weak in DM Gp, 5.2 [-11.7, 22.1], p=0.536. Fouth hour GET: A 10 ng/Dl increase of vitamin D, associated with significant improvement for all patients, -2.8% [-5.7, 0.4] p=0.053, was weaker in ID, -2.8 [-6.1, 0.4] p=0.086, and absent in DM, 7.3 [-17.3, 18.8] p=0.935, gastroparesis. Limitations: No food intake history. Conclusions: Vitamin D levels may be associated with gastric emptying, with potentially differing roles across Gp etiologies. Vitamin D contributions to enteric nerve function should be explored, particularly where metabolic comorbidities exist.
Mo1159 Inhibitory Effects and Sympathetic Mechanisms of Distension in the Distal Organs on Small Bowel Motility and Slow Waves in Dogs Jun Song, Jieyun Yin, Hanaa Sallam, Jiande Chen BACKGROUND AND AIMS: Rectal distension (RD) is known to induce intestinal dysmotilily. Few studies were performed to compare effects of RD, colon distension (CD) and duodenal distension (DD) on small bowel motility. This study aimed to investigate effects and underlying mechanisms of distensions in these regions on intestinal motility and slow waves in the dogs. METHODS: Six female dogs chronically implanted with a duodenal fistula, a proximal colon fistula and intestinal serosal electrodes were studied in six randomized sessions on separate days: control, RD, CD, DD, RD + guanethidine and CD + guanethidine. We recorded intestinal slow waves and intestinal manometry 15 cm distal to the site of DD, and the ECG in three periods (30 min baseline, 30 min distension and 30 min recovery) immediately after a standard test meal (solid canned dog food). All distensions were performed using a barostat with a constant pressure of 30 mmHg. RESULTS: 1) Isobaric RD and CD suppressed intestinal contractions (contractile index or CI: 6.0 ± 0.4 with RD vs. 9.9 ± 0.9 at baseline, P = 0.009, 5.3 ± 0.2 with CD vs. 7.7± 0.8 at baseline, P = 0.008). Guanethidine 3 mg/kg iv was able to partly block the suppressed contractions. 2) RD and CD reduced the percentage of normal intestinal slow waves from 92.1 ± 2.8% to 64.2 ± 3.4 (P < 0.001) and from 90 ± 2.7% to 69.2 ± 3.7% (P = 0.01) respectively. Guanethidine could eliminate these inhibitory effects. 3) DD didn't induce any changes in small intestinal contractions or intestinal slow waves (P > 0.05). 4) The spectral analysis of the heart rate variability signal derived from the ECG showed both RD and CD increased sympathetic activity (LF) (0.47 ± 0.08 with RD vs. 0.31 ± 0.08 at baseline, P = 0.02, 0.56 ± 0.14 with CD vs. 0.45 ± 0.14 at baseline, P = 0.01) and reduced vagal activity (HF) (0.53 ± 0.06 with RD vs. 0.78 ± 0.09 at baseline, P = 0.04, 0.52 ± 0.07 with CD vs. 0.82 ± 0.09 at baseline, P = 0.03). CONCLUSION: Isobaric RD and CD inhibited postprandial intestinal motility and impaired intestinal slow waves mediated via the sympathetic pathway. However, lumen distention (DD) at a site proximal to the measurement site does not seem to impair small intestinal contractions or slow waves. Mo1160
Mo1162
The Gene Expression of Taste Receptors in Gastrointestinal Tract After the Administration of Drugs for Functional Gastrointestinal Disorders Daisuke Maruoka, Makoto Arai, Tomoaki Matsumura, Tomoo Nakagawa, Tatsuro Katsuno, Fumio Imazeki, Osamu Yokosuka
Scn10a Gene Polymorphisms are Closely Associated With the Risk of Functional Dyspepsia in Japan Nobuhiko Hayashi, Hisakazu Shiroeda, Ranji Hayashi, Kazuhiro Matsunaga, Atsushi Fukumura, Kazuaki Ozaki, Tomomitsu Tahara, Tomoyuki Shibata, Tomiyasu Arisawa
Aims: Taste receptors, type 1, member 2 / member 3 (T1R2 / T1R3), which is G-protein coupled receptor located in taste bud and act as a receptor for sweet tastants, were reported to exist in mucosa of the gastrointestinal tract and attract attention recently. Various drugs were administered for functional gastrointestinal disorders (FGIDs), but these drugs' effects to sweet tastants' receptors have not been known exactly. We analyzed the change of these genes expression in mucosa of the gastrointestinal tract after the administration of drugs for FGIDs in this study. Materials and Methods: (1) Adult male C57BL/6 mice aged 9 weeks which had free access to water and a standard diet. We administered free access to water
[Background] The role of genetics in the susceptibility to functional dyspepsia (FD) remains unclear. Visceral sensory is transmitted via C-fiber from gastrointestinal tract to CNS. SNS, a TTX-resistant voltage gated Na+ channel, was identified on C-fiber (Akopian AN et al., Nature 1996). Thereafter, it has been demonstrated that SNS null mutant mice lowered thresholds of electrical activation of C-fiber (Akopian AN et al., Nature Nurosci, 1999). Recently, mutant allele of V1073A variation in SCN10A gene, coding SNS, is revealed to be a gain of function allele (Chambers JC et al., Nat Genet, 2010). We attempted to
S-609
AGA Abstracts
AGA Abstracts
well as its duration and amplitude. CONCLUSIONS: Acute thermal cooling affects colonic neuromuscular function by increasing basal tone and response to cholinergic stimulus. These effects are not reversible after short-term observation. It is known that temperature affects both the ionic conductances and the rate constants modulating the action potential propagation in giant squid axon. We hypothesize that temperature gradients, by changing the ion dynamics, could influence the electrochemical behaviour of intestinal muscle, with a memory effect which should require long time to be deleted. Further studies are needed to establish the exact involved mechanisms in order to better understand clinical consequences of hypothermia during abdominal surgery.