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M2020 Influence of Sleep On Esophago-UES Contractile Reflex and Secondary Peristalsis in the Elderly
AGA Abstracts
M2019 Phonation-Induced UES Contractile Reflex Is Preserved in the Elderly Benjamin Schneeberger, Lilani P. Perera, Sri Naveen Surapaneni, Shiko Kuribayashi, Linda Tatro, Muhammad Hafeezullah, Reza Shaker
M2021
INTRODUCTION: Earlier studies have documented the presence of UES contractile response during phonation in young healthy individuals. Magnitude of the UES pressure increase during phonation was found to be significantly higher than phonation related pressure increases in the distal esophagus, LES, and stomach. The aim of this study was to determine the effects of aging on phonation-induced UES contraction. METHODS: We studied 6 (2M & 4F) healthy elderly volunteers (75+/-4.3 yrs) by concurrent high resolution manometry (Manoscan, Sierra Scientific) to record the upper GI tract pressure and voice analysis (Praat, University of Amsterdam). We tested high and low pitch vowels (AA, EE) (30-60dB) for durations of 10 seconds. Each vowel was repeated X3. RESULTS: High pitch vowels had a significantly higher frequencies (Hz) compared to low pitched vowels (#P<0.05) (Table). Median UES pressures during all tested vowels were significantly higher compared to the median resting baseline UES pressure for all of the studied pitches (71 mmHg High EE, 61 mmHg Low EE, 109 mmHg High AA, 71 mmHg Low AA vs 21 mmHg Baseline, UES pressures). The absolute change in pressure (phonation - prephonation pressure) was significantly higher in UES compared to the rest of the studied upper GI tract (Table). CONCLUSIONS: The phonation-induced UES contractile reflex is preserved in the elderly. The magnitude of UES pressure increase due to activation of this reflex is significantly higher than phonation-induced pressure increase in the distal esophagus, LES, and stomach. Supported in part by research grants 1PO1DKO68061-01A1, 5RO1DKO25731-28 and T32 DK61923.
Increased Expression of Interleukin 17 in Celiac Disease Mucosa Ivan Monteleone, Massimiliano Sarra, Iris Cardolini, Giovanna Del Vecchio Blanco, Omero Alessandro Paoluzi, Eleonora Franzè, Daniele Fina, Thomas T. MacDonald, Francesco Pallone, Giovanni Monteleone BACKGROUND: Celiac disease (CD) is a gluten sensitive enteropathy associated with a marked infiltration of the mucosa with T cells secreting interferon-gamma (IFN-gamma) and IL-21. Recently a novel subset of T helper (Th) cells, namely Th17 cells, producing the pro-inflammatory cytokine IL-17A have been reported to play important roles in various inflammatory diseases. OBJECTIVE: Since Th17 cell differentiation can be facilitated by IL21, we assessed whether IL-17A expression is enhanced in CD, and if this production relies on IL-21 activity. METHODS: IL-17A RNA was assessed in CD (both treated and untreated) and normal control duodenal biopsies by real-time PCR. IL-17A and IFN-gamma were examined in intestinal Lamina Propria T lymphocytes (T-LPL) of CD patients and normal control by flow cytometry. To assess the role of IL-21 in the control of IL-17 expresison, a neutralizing IL-21 ab was added to ex vivo organ cultures of biopsies taken from untreated CD biopsies or peptic-tryptic digest of gliadin (PT)-stimulated treated CD biopsies. After 24 hours, IL-17A RNA was evaluated by real-time PCR. RESULTS: Enhanced IL-17 RNA was seen in untreated CD in comparison to treated CD and normal biopsies. Flow cytometry analysis of T-LPL confirmed that IL-17A is over-produced in CD mucosa, and that both CD4+ and CD8+ cells were major sources of IL-17A (Table). Of the IL-17-producing cells, more than 50% co-expressed IFN-gamma. Blockade of IL-21 activity reduced IL-17A expression in cultures of both untreated CD and PT-stimulated treated CD biopsies.CONCLUSIONS: Data indicate that IL-17A expression is up-regulated in CD mucosa, and that IL-21 contributes to sustain IL-17 production. . Percentages of cytokine-producing T-LPL isolated from CD patients and normal controls. Numbers indicate mean ± SD of 3 separate experiments in which cells isolated form 3 CD patients and 4 controls were examined
M2020 Influence of Sleep On Esophago-UES Contractile Reflex and Secondary Peristalsis in the Elderly Kulwinder S. Dua, Sri Naveen Surapaneni, Shiko Kuribayashi, Muhammad Hafeezullah, Reza Shaker Introduction:Esophago-UES Contractile Reflex (EUCR) and Secondary Peristalsis (SP) protect the airways by preventing entry of refluxate into the pharynx during retrograde transit of gastric contents. In a prior study we showed that frequency elicitation (FE) of these reflexes by proximal esophageal water perfusion (as a surrogate for proximal reflux event) was 100% in young healthy individuals during the awake and sleep states (Bajaj et al. Gastroenterology 2006;130:17-25). The frequency elicitation of these reflexes in the elderly, especially during sleep is not known. Aims:To study the effect of sleep on EUCR and SP in the elderly. Methods:Seven healthy elderly volunteers (74.9±4 SD yr; 1 male) were studied during awake and stage II sleep in supine position by concurrent polysomnography, EMG and UES/ esophageal (sleeve) manometry. Sleep state was determined in real time prior to proximal esophageal stimulation by perfusion of water through a dedicated port below UES at a rate of 2.7 ml/min (similar to what was used during our previous study on young subjects). Results: During the awake state, the FE of EUCR and SP was 38 % and 52% respectively (compared to 100% in historical young subjects). The threshold volume to elicit SP was significantly higher than the threshold volume to elicit EUCR (5.65±2.43, 2.15±0.88 respectively in ml, p< 0.001). Only 5 of 7 subjects were able to reach sleep stage II; therefore only 5 subjects were used in the comparative analysis. Contrary to historical results in young (100% elicitation), in stage II sleep, EUCR could not be elicited in any elderly subjects (0%). FE of 2P during awake and stage II sleep were similar. (52% Vs 44% respectively, p=0.26) Contrary to young where arousal was not noted in stage II, proximal esophageal stimulation in elderly in stage II elicited EEG evidence of arousal in 56% of infusions. Conclusions:Sleep significantly reduces the frequency elicitation of EUCR, but not 2P in elderly. Frequency elicitation of both EUCR and 2P in awake and sleep in elderly is diminished compared to young. These findings may have implications in the pathogenesis of aspiration in the elderly during retrograde transit of gastric contents. Frequency Elicitation of Esophago-UES Contractile Reflex (EUCR) and Secondary Peristalsis (2P) in Awake and Sleep in the elderly
AGA Abstracts
M2022 Gliadin Activates Monocytes, Macrophages and Dendritic Cells In Vitro and In Vivo via Toll Like Receptor 4 Yvonne Junker, Daniel A. Leffler, Herbert Wieser, Detlef Schuppan Background: Celiac disease is a small intestinal enteropathy caused by a Th1 mediated inflammatory response to certain gluten peptides after binding to HLA-DQ2/-DQ8. However, only 2-5% of individuals expressing DQ2/DQ8 develop celiac disease, indicating that additional mechanisms such as an innate immune response to gluten might be involved in disease pathogenesis. Yet, the specificity and nature of this response remains controversial. Methods: Gliadin and zein (Sigma) were digested with pepsin and trypsin. Human monocytic cell lines (HL-60, THP-1, U-937), mouse peritoneal macrophages and human monocyte derived dendritic cells from healthy controls and celiac disease patients were stimulated overnight with digests of gliadin and zein and cytokine levels of IL-8, TNF-α and MCP-1 in culture supernatants were measured by ELISA. To test their stimulatory capacity In Vivo gliadin, zein and lipopolysaccharide (LPS) were injected intraperitoneally in C57BL/6, Rag1-/and MyD88-/- mice. Serum was taken 2h after injection and chemokine levels were measured by ELISA. Results: Upon stimulation with the peptic tryptic digest of gliadin but not zein all tested cell lines secreted high amounts of IL-8, MCP-1 and TNF-α. Gliadin of the pure wheat strain Rektor had identical effects. Peritoneal macrophages from MyD88-/- or C3H/ HeJ mice that lack TLR-4 responses did not secrete these cytokines upon gliadin stimulation as compared to macrophages from wild type mice. Dendritic cells (DCs) of celiac disease patients on a gluten free diet stimulated with gliadin secreted IL-8 and TNF-alpha comparable to those from non-celiac controls. Cytokine secretion in DCs was significantly decreased by preincubation with TLR4 neutralizing antibody. Furthermore, intraperitoneal injection of gliadin led to increased serum levels of TNF-alpha and KC (IL-8) similarly in C57BL/6 and Rag1-/- but not in MyD88-/- mice. Conclusion: Gliadin peptides can elicit an innate immune response In Vitro and In Vivo and TLR-4 is its major innate immune receptor.
A-468
M2019 Phonation-Induced UES Contractile Reflex Is Preserved in the Elderly Benjamin Schneeberger, Lilani P. Perera, Sri Naveen Surapaneni, Shiko Kuribayashi, Linda Tatro, Muhammad Hafeezullah, Reza Shaker
M2021
INTRODUCTION: Earlier studies have documented the presence of UES contractile response during phonation in young healthy individuals. Magnitude of the UES pressure increase during phonation was found to be significantly higher than phonation related pressure increases in the distal esophagus, LES, and stomach. The aim of this study was to determine the effects of aging on phonation-induced UES contraction. METHODS: We studied 6 (2M & 4F) healthy elderly volunteers (75+/-4.3 yrs) by concurrent high resolution manometry (Manoscan, Sierra Scientific) to record the upper GI tract pressure and voice analysis (Praat, University of Amsterdam). We tested high and low pitch vowels (AA, EE) (30-60dB) for durations of 10 seconds. Each vowel was repeated X3. RESULTS: High pitch vowels had a significantly higher frequencies (Hz) compared to low pitched vowels (#P<0.05) (Table). Median UES pressures during all tested vowels were significantly higher compared to the median resting baseline UES pressure for all of the studied pitches (71 mmHg High EE, 61 mmHg Low EE, 109 mmHg High AA, 71 mmHg Low AA vs 21 mmHg Baseline, UES pressures). The absolute change in pressure (phonation - prephonation pressure) was significantly higher in UES compared to the rest of the studied upper GI tract (Table). CONCLUSIONS: The phonation-induced UES contractile reflex is preserved in the elderly. The magnitude of UES pressure increase due to activation of this reflex is significantly higher than phonation-induced pressure increase in the distal esophagus, LES, and stomach. Supported in part by research grants 1PO1DKO68061-01A1, 5RO1DKO25731-28 and T32 DK61923.
Increased Expression of Interleukin 17 in Celiac Disease Mucosa Ivan Monteleone, Massimiliano Sarra, Iris Cardolini, Giovanna Del Vecchio Blanco, Omero Alessandro Paoluzi, Eleonora Franzè, Daniele Fina, Thomas T. MacDonald, Francesco Pallone, Giovanni Monteleone BACKGROUND: Celiac disease (CD) is a gluten sensitive enteropathy associated with a marked infiltration of the mucosa with T cells secreting interferon-gamma (IFN-gamma) and IL-21. Recently a novel subset of T helper (Th) cells, namely Th17 cells, producing the pro-inflammatory cytokine IL-17A have been reported to play important roles in various inflammatory diseases. OBJECTIVE: Since Th17 cell differentiation can be facilitated by IL21, we assessed whether IL-17A expression is enhanced in CD, and if this production relies on IL-21 activity. METHODS: IL-17A RNA was assessed in CD (both treated and untreated) and normal control duodenal biopsies by real-time PCR. IL-17A and IFN-gamma were examined in intestinal Lamina Propria T lymphocytes (T-LPL) of CD patients and normal control by flow cytometry. To assess the role of IL-21 in the control of IL-17 expresison, a neutralizing IL-21 ab was added to ex vivo organ cultures of biopsies taken from untreated CD biopsies or peptic-tryptic digest of gliadin (PT)-stimulated treated CD biopsies. After 24 hours, IL-17A RNA was evaluated by real-time PCR. RESULTS: Enhanced IL-17 RNA was seen in untreated CD in comparison to treated CD and normal biopsies. Flow cytometry analysis of T-LPL confirmed that IL-17A is over-produced in CD mucosa, and that both CD4+ and CD8+ cells were major sources of IL-17A (Table). Of the IL-17-producing cells, more than 50% co-expressed IFN-gamma. Blockade of IL-21 activity reduced IL-17A expression in cultures of both untreated CD and PT-stimulated treated CD biopsies.CONCLUSIONS: Data indicate that IL-17A expression is up-regulated in CD mucosa, and that IL-21 contributes to sustain IL-17 production. . Percentages of cytokine-producing T-LPL isolated from CD patients and normal controls. Numbers indicate mean ± SD of 3 separate experiments in which cells isolated form 3 CD patients and 4 controls were examined
M2020 Influence of Sleep On Esophago-UES Contractile Reflex and Secondary Peristalsis in the Elderly Kulwinder S. Dua, Sri Naveen Surapaneni, Shiko Kuribayashi, Muhammad Hafeezullah, Reza Shaker Introduction:Esophago-UES Contractile Reflex (EUCR) and Secondary Peristalsis (SP) protect the airways by preventing entry of refluxate into the pharynx during retrograde transit of gastric contents. In a prior study we showed that frequency elicitation (FE) of these reflexes by proximal esophageal water perfusion (as a surrogate for proximal reflux event) was 100% in young healthy individuals during the awake and sleep states (Bajaj et al. Gastroenterology 2006;130:17-25). The frequency elicitation of these reflexes in the elderly, especially during sleep is not known. Aims:To study the effect of sleep on EUCR and SP in the elderly. Methods:Seven healthy elderly volunteers (74.9±4 SD yr; 1 male) were studied during awake and stage II sleep in supine position by concurrent polysomnography, EMG and UES/ esophageal (sleeve) manometry. Sleep state was determined in real time prior to proximal esophageal stimulation by perfusion of water through a dedicated port below UES at a rate of 2.7 ml/min (similar to what was used during our previous study on young subjects). Results: During the awake state, the FE of EUCR and SP was 38 % and 52% respectively (compared to 100% in historical young subjects). The threshold volume to elicit SP was significantly higher than the threshold volume to elicit EUCR (5.65±2.43, 2.15±0.88 respectively in ml, p< 0.001). Only 5 of 7 subjects were able to reach sleep stage II; therefore only 5 subjects were used in the comparative analysis. Contrary to historical results in young (100% elicitation), in stage II sleep, EUCR could not be elicited in any elderly subjects (0%). FE of 2P during awake and stage II sleep were similar. (52% Vs 44% respectively, p=0.26) Contrary to young where arousal was not noted in stage II, proximal esophageal stimulation in elderly in stage II elicited EEG evidence of arousal in 56% of infusions. Conclusions:Sleep significantly reduces the frequency elicitation of EUCR, but not 2P in elderly. Frequency elicitation of both EUCR and 2P in awake and sleep in elderly is diminished compared to young. These findings may have implications in the pathogenesis of aspiration in the elderly during retrograde transit of gastric contents. Frequency Elicitation of Esophago-UES Contractile Reflex (EUCR) and Secondary Peristalsis (2P) in Awake and Sleep in the elderly
AGA Abstracts
M2022 Gliadin Activates Monocytes, Macrophages and Dendritic Cells In Vitro and In Vivo via Toll Like Receptor 4 Yvonne Junker, Daniel A. Leffler, Herbert Wieser, Detlef Schuppan Background: Celiac disease is a small intestinal enteropathy caused by a Th1 mediated inflammatory response to certain gluten peptides after binding to HLA-DQ2/-DQ8. However, only 2-5% of individuals expressing DQ2/DQ8 develop celiac disease, indicating that additional mechanisms such as an innate immune response to gluten might be involved in disease pathogenesis. Yet, the specificity and nature of this response remains controversial. Methods: Gliadin and zein (Sigma) were digested with pepsin and trypsin. Human monocytic cell lines (HL-60, THP-1, U-937), mouse peritoneal macrophages and human monocyte derived dendritic cells from healthy controls and celiac disease patients were stimulated overnight with digests of gliadin and zein and cytokine levels of IL-8, TNF-α and MCP-1 in culture supernatants were measured by ELISA. To test their stimulatory capacity In Vivo gliadin, zein and lipopolysaccharide (LPS) were injected intraperitoneally in C57BL/6, Rag1-/and MyD88-/- mice. Serum was taken 2h after injection and chemokine levels were measured by ELISA. Results: Upon stimulation with the peptic tryptic digest of gliadin but not zein all tested cell lines secreted high amounts of IL-8, MCP-1 and TNF-α. Gliadin of the pure wheat strain Rektor had identical effects. Peritoneal macrophages from MyD88-/- or C3H/ HeJ mice that lack TLR-4 responses did not secrete these cytokines upon gliadin stimulation as compared to macrophages from wild type mice. Dendritic cells (DCs) of celiac disease patients on a gluten free diet stimulated with gliadin secreted IL-8 and TNF-alpha comparable to those from non-celiac controls. Cytokine secretion in DCs was significantly decreased by preincubation with TLR4 neutralizing antibody. Furthermore, intraperitoneal injection of gliadin led to increased serum levels of TNF-alpha and KC (IL-8) similarly in C57BL/6 and Rag1-/- but not in MyD88-/- mice. Conclusion: Gliadin peptides can elicit an innate immune response In Vitro and In Vivo and TLR-4 is its major innate immune receptor.
A-468