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Viscosity and parameters of the peristaltic reflex in the isolated guinea pig ileum
GASTROENTEROLOGY "Col. 114, No. 4
A784 AGA ABSTRACTS G3228
OROCECAL TRANSIT TIME IS PROLONGED IN PATIENTS WITH HEART FAILURE. C.Langner, J.Barnert, A.Majewicz, M.Wienbeck. Department of Medicine III, Zentralklinikum Augsburg, Germany. Patients with heart failure often complain of gastrointestinal symptoms, But little is known about the influence of cardiovascular dysfunction on gastrointestinal motility. The aim of this study was test for any influence of heart failure on orocecal transit time. Methods: 19 patients (13 male/6 female) suffering from various degrees of heart failure (NYHA I-III) were studied. They were aged 47-85 yrs. (mean 68 yrs.). 18 inpatients (4m/14f) aged 47-86 yrs. (mean 64 yrs) without cardiovascular or gastrointestinal disease served as controls. None was on any medication influencing gastrointestinal motility including calciumantagonists. Patients with diabetes were excluded. Orocecal transit time was assessed by the breath hydrogen test. After an overnight fast the subjects took 10 gm of lactulose solved in 100ml of tap water. End expiratory air was tested for hydrogen concentration every 10 min. up to 400 min. using an electrochemical H2-monitor (Clinical Microlyzer, Stimotron, Germany). A rise of 15 ppm Hz over baseline was taken as significant. Statistical analvsis was performed using Student's t-test and Spearman's correlation coefficient. Data are given as means _ SD. Results: The orocecal transit time of the patients with heart failure was significantly prolonged compared to the control group (260-+ 118 vs. 169-+95 min.; p<0.014). The grading of the heart failure showed no statistically significant influence on the orocecal transit time. In the control group the age of the patients correlated (r=0.73; p<0.05) with the 0rocecal transit time whereas in the heart failure group this phenomenon was not overt (r=0.23; p>0.05). Conclusions: These data suggest that (I) orocecal transit time is prolonged in patients with heart failure and (2) in contrast to age-matched controls orocecal transit time shows no correlation with age in these patients.
Manning and Rome criteria and to compare these data to those obtained in a selected group of patients with a clinical diagnosis of IBS. Methods. The BDQ was administered in a cross-sectional study to 1520 residents of LoianoMonghidoro, Bologna, Italy, (age range 18-88 yr, 90% of all residents), and to 100 outpatients in which the diagnosis of IBS was made after full laboratory investigation. In both groups symptoms-based diagnosis of IBS was made according to the presence of >_2 Manning criteria and Rome criteria. Results. Cross-sectional study: A total of 1493 subjects answered to the BDQ (774 males, 719 females, mean age 52 yr, response rate 98%). 409 subjects (27.3%) were affected by IBS according to the Manning criteria with a higher prevalence in females (35%) than in males (20.5%, p<0.0001). When evaluated according to the Rome criteria, 148 subjects (9.9%) were diagnosed IBS (females 13.6.% vs. males 6.4%, p<0.0001). Prevalence of IBS in females, but not in males, progressively declined starting to be significant in the fifth decade (p<0,005). All patients affected by IBS according to Rome criteria were also diagnosed IBS according to Manning criteria. IBS patients: All patients (28 males, 72 females, mean age 35 yr) reported > 2 Manning criteria. When evaluated according to the Rome criteria, 81 patients met the criteria for IBS (females 82%); no change in the prevalence of IBS was observed across age with both criteria. Summary. Compared to the Manning criteria, the Rome criteria are less sensitive in identifying IBS patients in a population-based study than in a clinical setting. Conclusions. In the absence of a definite indication to use either Manning or Rome criteria, our data suggest that in population-based studies Rome criteria are more reliable in identifying patients that would be encountered in an hospital setting. • G3231 SNAP-23, SNAP-25 AND VAMP-2 ARE FOUND IN FELINE ESOPHAGEAL SMOOTH MUSCLE. H Lau, AMP Salapatek, L Sheu, HY Gaisann, NE Diamant. The Toronto Hospital and Department of Medicine, University of Toronto, Toronto, Canada. Background Studies into neuroexocytosis and yeast secretory pathways have
• G3229 VISCOSITY AND PARAMETERS OF THE PERISTALTIC REFLEX IN THE ISOLATED GUINEA PIG ILEUM. M Larson, T Wolf and K Schulze-Delrieu. Gastroenterology Research Labs, VAMC, Iowa City, IA. We have previously shown that increases in bolus volume or in outflow resistance increase the length of the contraction which isolated loops of guinea pig ileum generate (Gastroenterology 108:A673, 1995). Here we examined how visual parameters of the contraction are affected when the viscosity of the bolus is increased by addition of 1.5, 2.0 or 2.5% cellulose. We injected 1.6 ml boluses into 10 cm preparations of guinea pig ileum and recorded luminal pressures and outflow. From videotapes we measured the length of the contracting segment, its propagation velocity and the delay from the end of the injection to the onset of the visual contraction. We found that outflow and the propagation velocity of the contraction was less with the viscous solutions than with the aqueous Krebs' solution (Table). Also, viscous solutions generated a greater length of the contracting segment and greater delay until the contraction started. Effects were seen with all concentrations of cellulose; statistically, the response was not greater with 2.5% cellulose which had the consistency of thin pudding than with 1.5% cellulose which had the consistency of thin syrup. We conclude therefore that the ileum responds to bolus consistency not with a unique contraction pattern but to an increase in volume or outflow resistance. Increases in load (be it from volume, resistance or viscosity) increase the duration of the initial inhibition of the intestine and the length of intestine which is recruited for contraction. Viscosity of.. Krebs 1.5%
Pressure (mmHg) 20.8 -+ 13.9 17.9 + 9.7 16.2 + 4.2 17.5 -+ 6.5
Length (mm) 56.6+9.7 67.9-+14.4" 76.3_+8.7* 72.5-+19.6"
Velocity (mm/s) 47.3-+15.7 26.5-+9.6" 22.8-+3.1" 16.9+5.2"
2.0% 2.5% n=6 * p < 0.05 when compared to Krebs. Supported by Merit Review Grant from VAMC
Delay (see) 1.1-+0.8 2.7_+9.6 22.8-+3.1 2.5_+1.0
Outflow (ml) 0.9-+0.3 0.3-+0.2 0.3-+0.2 0.2-+0.2
• G3230 MANNING CRITERIA AND ROME CRITERIA IN THE DIAGNOSIS OF IRRITABLE BOWEL SYNDROME: A COMPARISON BETWEEN A POPULATION-BASED STUDY AND A SELECTED PATIENTS POPULATION, F Laterza, M Neff, F Romano, M Ricciuti, F Carbone, F Schioppa, Chieti, Italy; F Bazzoli, E Roda, G Mazzella, Bologna, Italy; D Panuccio, Loiano, Italy; D Festi, Universit~t G.D' Annunzio, Chieti, Italy. Symptom-based diagnosis of Irritable Bowel Syndrome (IBS) in epidemiological studies is based on the presence of Manning criteria and/or Rome criteria, the latter being characterized by the presence of abdominal pain as discriminant symptom. However, it has never been evaluated whether the two symptoms complexes identify different patients populations. Aim. To evaluate by a validated questionnaire (BDQ, Talley et al, Ann Intern Med 1989) the prevalence of IBS in an Italian population according to both
demonstrated that SNAREs (soluble N-ethylmaleimide sensitive factors attachment protein receptors) are well conserved through evolution in all cell types to mediate targeted vesicular transport. The general model is that vesicle (v-) SNAREs (vesicle-associated membrane proteins -VAMP (-1, -2 and -3)) interact with target (t-) membrane SNAREs (synaptosomal-associated membrane protein of 25kDa - SNAP-25 and syntaxins) in a step-wise manner to form multi-molecular complexes. More recently, it was shown that SNARE proteins bind to Ca2+ channels and are involved with Ca2+ channel kinetics and Ca2+ homeostasis. Functionally, SNAREs could be manipulated as different Botulinum neurotoxins (BoNT) cleave different SNAREs specifically. The presence and functions of SNAREs in GI smooth muscle have not been investigated. Hypothesis We propose that SNAREs are present in esophageal smooth muscle and that differential expression are likely to be observed along different regions of the esophagus, which may in part explain the known as well as undefined functional differences among the muscle groups of the esophageal body and lower esophageal sphincter (LES). Methods The esophagus from each of 9 healthy adult cats was excised. 2 mm3 smooth muscle strips from circular smooth muscle 4 cm above the LES, longitudinal smooth muscle from 4 cm above the LES, LES sling muscle and LES clasp muscle were excised and dissociated into single cells by enzymatic digestion and mechanical tituration. Dissociated cells were fixed with 100% methanol and incubated overnight at 4oc with primary antibodies against SNAP-25, SNAP-23 (a recently reported novel SNAP-25 isoform), VAMP-2 and double labeled with a-actin. The cells were then labeled with the appropriate secondary antibodies and the cellular locations of these proteins were detected using a laser scanning confocal imaging system (Carl Zeiss). Quantification of immunofluorescence were determined using standard software (NIH Image v 1.6). Signal intensity was analyzed by single factor ANOVA. Results Feline esophageal smooth muscles of all regions examined possess SNAP-23, SNAP-25 and VAMP-2. SNAP-23 was most strongly detected in body circular smooth muscle, whereas SNAP-25 was most strongly detected in body longitudinal smooth muscle. No differential expression was found for VAMP-2. SNAP-23 SNAP-25 VAMP2
Circular 166.49 146.79 198.12
Longitudinal 140.93 203.20 191.48
LES clasp 136.14 157.92 174.89
LES sling 143.01 177.66 173.44
p < 0.01 < 0.01 0.07
Signal intensity is expressed as sum of gray values of all pixels per pm2. Conclusions We report the novel presence of SNAREs in esophageal smooth
muscle. This is the first demonstration of two SNAP-25 isoforms in a single cell type. The distinct expression of SNAP-25 isoforms along different regions of the esophagus may reflect their role in esophageal muscle groups specialization. The ability to cleave different SNAREs with Botulinum neurotoxins (BoNT/A cleave SNAP-25 but not SNAP-23) has implications for the treatment of esophageal disorders.
A784 AGA ABSTRACTS G3228
OROCECAL TRANSIT TIME IS PROLONGED IN PATIENTS WITH HEART FAILURE. C.Langner, J.Barnert, A.Majewicz, M.Wienbeck. Department of Medicine III, Zentralklinikum Augsburg, Germany. Patients with heart failure often complain of gastrointestinal symptoms, But little is known about the influence of cardiovascular dysfunction on gastrointestinal motility. The aim of this study was test for any influence of heart failure on orocecal transit time. Methods: 19 patients (13 male/6 female) suffering from various degrees of heart failure (NYHA I-III) were studied. They were aged 47-85 yrs. (mean 68 yrs.). 18 inpatients (4m/14f) aged 47-86 yrs. (mean 64 yrs) without cardiovascular or gastrointestinal disease served as controls. None was on any medication influencing gastrointestinal motility including calciumantagonists. Patients with diabetes were excluded. Orocecal transit time was assessed by the breath hydrogen test. After an overnight fast the subjects took 10 gm of lactulose solved in 100ml of tap water. End expiratory air was tested for hydrogen concentration every 10 min. up to 400 min. using an electrochemical H2-monitor (Clinical Microlyzer, Stimotron, Germany). A rise of 15 ppm Hz over baseline was taken as significant. Statistical analvsis was performed using Student's t-test and Spearman's correlation coefficient. Data are given as means _ SD. Results: The orocecal transit time of the patients with heart failure was significantly prolonged compared to the control group (260-+ 118 vs. 169-+95 min.; p<0.014). The grading of the heart failure showed no statistically significant influence on the orocecal transit time. In the control group the age of the patients correlated (r=0.73; p<0.05) with the 0rocecal transit time whereas in the heart failure group this phenomenon was not overt (r=0.23; p>0.05). Conclusions: These data suggest that (I) orocecal transit time is prolonged in patients with heart failure and (2) in contrast to age-matched controls orocecal transit time shows no correlation with age in these patients.
Manning and Rome criteria and to compare these data to those obtained in a selected group of patients with a clinical diagnosis of IBS. Methods. The BDQ was administered in a cross-sectional study to 1520 residents of LoianoMonghidoro, Bologna, Italy, (age range 18-88 yr, 90% of all residents), and to 100 outpatients in which the diagnosis of IBS was made after full laboratory investigation. In both groups symptoms-based diagnosis of IBS was made according to the presence of >_2 Manning criteria and Rome criteria. Results. Cross-sectional study: A total of 1493 subjects answered to the BDQ (774 males, 719 females, mean age 52 yr, response rate 98%). 409 subjects (27.3%) were affected by IBS according to the Manning criteria with a higher prevalence in females (35%) than in males (20.5%, p<0.0001). When evaluated according to the Rome criteria, 148 subjects (9.9%) were diagnosed IBS (females 13.6.% vs. males 6.4%, p<0.0001). Prevalence of IBS in females, but not in males, progressively declined starting to be significant in the fifth decade (p<0,005). All patients affected by IBS according to Rome criteria were also diagnosed IBS according to Manning criteria. IBS patients: All patients (28 males, 72 females, mean age 35 yr) reported > 2 Manning criteria. When evaluated according to the Rome criteria, 81 patients met the criteria for IBS (females 82%); no change in the prevalence of IBS was observed across age with both criteria. Summary. Compared to the Manning criteria, the Rome criteria are less sensitive in identifying IBS patients in a population-based study than in a clinical setting. Conclusions. In the absence of a definite indication to use either Manning or Rome criteria, our data suggest that in population-based studies Rome criteria are more reliable in identifying patients that would be encountered in an hospital setting. • G3231 SNAP-23, SNAP-25 AND VAMP-2 ARE FOUND IN FELINE ESOPHAGEAL SMOOTH MUSCLE. H Lau, AMP Salapatek, L Sheu, HY Gaisann, NE Diamant. The Toronto Hospital and Department of Medicine, University of Toronto, Toronto, Canada. Background Studies into neuroexocytosis and yeast secretory pathways have
• G3229 VISCOSITY AND PARAMETERS OF THE PERISTALTIC REFLEX IN THE ISOLATED GUINEA PIG ILEUM. M Larson, T Wolf and K Schulze-Delrieu. Gastroenterology Research Labs, VAMC, Iowa City, IA. We have previously shown that increases in bolus volume or in outflow resistance increase the length of the contraction which isolated loops of guinea pig ileum generate (Gastroenterology 108:A673, 1995). Here we examined how visual parameters of the contraction are affected when the viscosity of the bolus is increased by addition of 1.5, 2.0 or 2.5% cellulose. We injected 1.6 ml boluses into 10 cm preparations of guinea pig ileum and recorded luminal pressures and outflow. From videotapes we measured the length of the contracting segment, its propagation velocity and the delay from the end of the injection to the onset of the visual contraction. We found that outflow and the propagation velocity of the contraction was less with the viscous solutions than with the aqueous Krebs' solution (Table). Also, viscous solutions generated a greater length of the contracting segment and greater delay until the contraction started. Effects were seen with all concentrations of cellulose; statistically, the response was not greater with 2.5% cellulose which had the consistency of thin pudding than with 1.5% cellulose which had the consistency of thin syrup. We conclude therefore that the ileum responds to bolus consistency not with a unique contraction pattern but to an increase in volume or outflow resistance. Increases in load (be it from volume, resistance or viscosity) increase the duration of the initial inhibition of the intestine and the length of intestine which is recruited for contraction. Viscosity of.. Krebs 1.5%
Pressure (mmHg) 20.8 -+ 13.9 17.9 + 9.7 16.2 + 4.2 17.5 -+ 6.5
Length (mm) 56.6+9.7 67.9-+14.4" 76.3_+8.7* 72.5-+19.6"
Velocity (mm/s) 47.3-+15.7 26.5-+9.6" 22.8-+3.1" 16.9+5.2"
2.0% 2.5% n=6 * p < 0.05 when compared to Krebs. Supported by Merit Review Grant from VAMC
Delay (see) 1.1-+0.8 2.7_+9.6 22.8-+3.1 2.5_+1.0
Outflow (ml) 0.9-+0.3 0.3-+0.2 0.3-+0.2 0.2-+0.2
• G3230 MANNING CRITERIA AND ROME CRITERIA IN THE DIAGNOSIS OF IRRITABLE BOWEL SYNDROME: A COMPARISON BETWEEN A POPULATION-BASED STUDY AND A SELECTED PATIENTS POPULATION, F Laterza, M Neff, F Romano, M Ricciuti, F Carbone, F Schioppa, Chieti, Italy; F Bazzoli, E Roda, G Mazzella, Bologna, Italy; D Panuccio, Loiano, Italy; D Festi, Universit~t G.D' Annunzio, Chieti, Italy. Symptom-based diagnosis of Irritable Bowel Syndrome (IBS) in epidemiological studies is based on the presence of Manning criteria and/or Rome criteria, the latter being characterized by the presence of abdominal pain as discriminant symptom. However, it has never been evaluated whether the two symptoms complexes identify different patients populations. Aim. To evaluate by a validated questionnaire (BDQ, Talley et al, Ann Intern Med 1989) the prevalence of IBS in an Italian population according to both
demonstrated that SNAREs (soluble N-ethylmaleimide sensitive factors attachment protein receptors) are well conserved through evolution in all cell types to mediate targeted vesicular transport. The general model is that vesicle (v-) SNAREs (vesicle-associated membrane proteins -VAMP (-1, -2 and -3)) interact with target (t-) membrane SNAREs (synaptosomal-associated membrane protein of 25kDa - SNAP-25 and syntaxins) in a step-wise manner to form multi-molecular complexes. More recently, it was shown that SNARE proteins bind to Ca2+ channels and are involved with Ca2+ channel kinetics and Ca2+ homeostasis. Functionally, SNAREs could be manipulated as different Botulinum neurotoxins (BoNT) cleave different SNAREs specifically. The presence and functions of SNAREs in GI smooth muscle have not been investigated. Hypothesis We propose that SNAREs are present in esophageal smooth muscle and that differential expression are likely to be observed along different regions of the esophagus, which may in part explain the known as well as undefined functional differences among the muscle groups of the esophageal body and lower esophageal sphincter (LES). Methods The esophagus from each of 9 healthy adult cats was excised. 2 mm3 smooth muscle strips from circular smooth muscle 4 cm above the LES, longitudinal smooth muscle from 4 cm above the LES, LES sling muscle and LES clasp muscle were excised and dissociated into single cells by enzymatic digestion and mechanical tituration. Dissociated cells were fixed with 100% methanol and incubated overnight at 4oc with primary antibodies against SNAP-25, SNAP-23 (a recently reported novel SNAP-25 isoform), VAMP-2 and double labeled with a-actin. The cells were then labeled with the appropriate secondary antibodies and the cellular locations of these proteins were detected using a laser scanning confocal imaging system (Carl Zeiss). Quantification of immunofluorescence were determined using standard software (NIH Image v 1.6). Signal intensity was analyzed by single factor ANOVA. Results Feline esophageal smooth muscles of all regions examined possess SNAP-23, SNAP-25 and VAMP-2. SNAP-23 was most strongly detected in body circular smooth muscle, whereas SNAP-25 was most strongly detected in body longitudinal smooth muscle. No differential expression was found for VAMP-2. SNAP-23 SNAP-25 VAMP2
Circular 166.49 146.79 198.12
Longitudinal 140.93 203.20 191.48
LES clasp 136.14 157.92 174.89
LES sling 143.01 177.66 173.44
p < 0.01 < 0.01 0.07
Signal intensity is expressed as sum of gray values of all pixels per pm2. Conclusions We report the novel presence of SNAREs in esophageal smooth
muscle. This is the first demonstration of two SNAP-25 isoforms in a single cell type. The distinct expression of SNAP-25 isoforms along different regions of the esophagus may reflect their role in esophageal muscle groups specialization. The ability to cleave different SNAREs with Botulinum neurotoxins (BoNT/A cleave SNAP-25 but not SNAP-23) has implications for the treatment of esophageal disorders.