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Brush border sugar transporter expression is altered following massive small bowel resection
AM AGA ABSTRACTS
GASTROENTEROLOGY Vol. 118, No.4
523
525
BRUSH BORDER SUGAR TRANSPORTER EXPRESSION IS ALTERED FOLLOWING MASSIVE SMALL BOWEL RESECTION. Brian M. Chung, Laurie E. Wallace, Bob Winkfein, James A. Hardin, Ted V. 0' Loughlin, Donald G. Gall, Univ of Calgary, Calgary, AB, Canada; New Childrens Hosp, Sydney, Australia. Following resection, the distal remnant small bowel displays decreased in vitro net glucose transport and brush border membrane (BBM) glucose uptake kinetics. Oral epidermal growth factor (EGF) returns in vitro net glucose transport to control levels despite having no effect on BBM glucose uptake kinetics. Hypothesis: Small bowel resection alters the expression of the BBM sugar transporters SGLTI and GLUT5. Methods: NZW rabbits (lkg) underwent a 70% small bowel resection. One group of resected animals received oral EGF (40 J.Lglkg, days 3-8 post surgery), and were compared to untreated resected, and unmanipulated controls. 10 days post-surgery, in separate experiments, BBM were prepared from distal remnant tissue for Western immunoblots, whole mucosa for Northern blots, or tissue fixed for microscopic localization of SGLTl and GLUT5 along the villus. Results: Resection decreased BBM SGLTl content compared to controls and was not altered by oral EGF (SGLTl CON .56::'::.03, RES .42::'::.02, R-EGF .41::'::.03, n=5, p<.05). Resection also decreased BBM GLUT5 levels (CON .45::'::.05, RES .28::'::.04 p<.05). In contrast to SGLTI, oral EGF returned GLUT5 content to control levels (R-EGF .38::'::.03 n.s. compared to CON, n=5). SGLTl or GLUT5 mRNA levels did not differ between groups. Immuno-Iocalization of SGLTl indicated less staining in the upper villus, and increased staining in the mid-villus region in remnant tissue. Oral EGF returned SGLTl staining patterns normal. GLUT5 expression was decreased on the lower 2/3 villus. EGF had no effect on GLUT5 distribution. Conclusion: Resection causes decreased BBM SGLTl and GLUT5 content in the distal remnant, and alters their expression along the viJIus. Oral EGF normalizes the pattern of SGLTl expression along the villus but has no effect on BBM SGLTl content. EGF returns BBM GLUT5 to normal levels. The data suggest the defect in nutrient transport following resection is due to alterations in the post transcriptional expression of transport proteins.
ESOPHAGEAL ATRESIA AND ASSOCIATED CARDIOVASCULAR ANOMALIES. Denis A. Cozzi, Francesco Morini, Alessandra Casati, Lucia Oriolo, Michele Ilari, Daniela Camanni, Gemma Trimarco, Francesco Cozzi, Pediatric Surg Unit, Universita' La Sapienza, Rome, Italy. Aim: Patients with exemplary cephalic neurocristopathies present with a striking pattern of associated cardiovascular anomalies (CVA). Therefore, to support the hypothesis that esophageal atresia (EA) may be related with cephalic neurocristopathies we studied the pattern of CVA associated with EA. Methods: Medical records of 99 patients (pts) with EA, 101 pts with anorectal malformations (ARM) and 15 pts with both EA and ARM, consecutively admitted to our unit were reviewed. The prevalence and pattern of CVA associated with EA and/or ARM were compared on the assumption that the cranial or caudal location of a major anomaly is correlated with different associated anomalies. Data were analysed with ltest applying Yate's correction. Results: The prevalence of eVA was 39.4% in infants with EA and 6.9% in infants with ARM (p
524 PATTERN OF ESOPHAGEAL MUSCLE IN INFANTS WITH ESOPHAGEAL ATRESIA. Denis A. Cozzi, Alessandra Casati, Francesco Morini, Michele Ilari, Lucia Oriolo, Antonietta Pisera', Maurizio Pacilli, Francesco Cozzi, Pediatric Surg Unit, Universita' La Sapienza, Rome, Italy. Aim: Striated muscles which compose the human proximal esophagus are thought to derive from myoblasts of the caudal branchial arches.In this study we tested the hypothesis that esophageal atresia (EA) may interfere with myoblast migration. Methods: We examined microscopically serial sections of 37 specimens from the tip of the upper pouch and 15 specimens from the proximal end of the lower esophagus from 40 infants with EA. Those were compared with serial sections of esophagus and trachea removed en bloc from 10 infants who died for disease not related to the gut. Results: Infants without EA had a complete transition from striated to smooth muscles in the esophagus caudal to the tracheal bifurcation, whereas in infants with EA this transition occurred above the carina(see table). Conclusion: The difference in distribution of striated muscle between normal or atretic esophagus, suggests that the reduction in striated muscle component in EA is more probably a concomitant anomaly, rather than the result of an interference from EA. Implication: In infants with repaired EA, a congenital anomaly of esophageal striated muscle arrangement may impair the organization of peristalsis and the defence mechanism against esophago-pharyngeal reflux. Esophageal muscles arrangement ininfants with esophageal atresia
Upper pouch Lower fistula' Lower stump
All Striated
Mixed
All smooth
8 specimens
16specimens 3specimens
13specimens 10specimens 2specimens
, ending above the carina inall cases
526 THE INFLUENCE OF ENTERAL FEEDING ON GROWTH FACTORS, INFLAMMATION AND NUTRITION IN CHILDREN WITH CROHN'S DISEASE. Kaushik Bannerjee, Nicholas M. Croft, Kasha Babinska, Cecilia Camachno-Hubner, Martin O. Savage, Ian R. Sanderson, Children's Service, Barts and the London NHS Trust, London, United Kingdom; Paediatric Gastroenterology, Queen Mary & Westfield Coli, London, United Kingdom; Acad Service, Barts and the London NHS Trust, London, United Kingdom; Paediatric Endocrinology, Queen Mary and Westfield Coli, London, United Kingdom. Background Exclusive enteral feeding reduces inflammation and improves clinical well being and nutritional status in children with active small bowel Crohn' s disease I. It has also been found that this treatment leads to increase in serum growth factors (IGF-1 and IGFBP-3)'. Whether the changes in growth factors are a consequence of suppression of inflammation or improved nutrition is not known. This study was undertaken to test the hypothesis that changes in growth factors and related proteins are temporally related to a decrease in inflammation rather than improvement in nutrition. Methods 13 children with active small bowel Crohn's disease being treated with a six week course of enteral feed (ALl 10, Nestle, UK) were recruited and studied at day 0,3,7, 14,21,28 and 2 and 4 months. The weight, paediatric Crohn's disease activity index (PCDAl), triceps skinfold thickness (TSFT), mid-upper arm circumference (MUAC) were measured at each visit. Serum inflammatory parameters (CRP, ESR), growth factors and related proteins (lGF-I, IGFBP-3, acid labile subunit (ALS)) and a serum marker of fat stores (Leptin) were also measured at each visit. Data from day three onwards were compared with day zero data using the wilcoxon matched pairs signed rank test. Results Thus far 7 children have completed the study and had their data analysed. There were significant improvements (P
GASTROENTEROLOGY Vol. 118, No.4
523
525
BRUSH BORDER SUGAR TRANSPORTER EXPRESSION IS ALTERED FOLLOWING MASSIVE SMALL BOWEL RESECTION. Brian M. Chung, Laurie E. Wallace, Bob Winkfein, James A. Hardin, Ted V. 0' Loughlin, Donald G. Gall, Univ of Calgary, Calgary, AB, Canada; New Childrens Hosp, Sydney, Australia. Following resection, the distal remnant small bowel displays decreased in vitro net glucose transport and brush border membrane (BBM) glucose uptake kinetics. Oral epidermal growth factor (EGF) returns in vitro net glucose transport to control levels despite having no effect on BBM glucose uptake kinetics. Hypothesis: Small bowel resection alters the expression of the BBM sugar transporters SGLTI and GLUT5. Methods: NZW rabbits (lkg) underwent a 70% small bowel resection. One group of resected animals received oral EGF (40 J.Lglkg, days 3-8 post surgery), and were compared to untreated resected, and unmanipulated controls. 10 days post-surgery, in separate experiments, BBM were prepared from distal remnant tissue for Western immunoblots, whole mucosa for Northern blots, or tissue fixed for microscopic localization of SGLTl and GLUT5 along the villus. Results: Resection decreased BBM SGLTl content compared to controls and was not altered by oral EGF (SGLTl CON .56::'::.03, RES .42::'::.02, R-EGF .41::'::.03, n=5, p<.05). Resection also decreased BBM GLUT5 levels (CON .45::'::.05, RES .28::'::.04 p<.05). In contrast to SGLTI, oral EGF returned GLUT5 content to control levels (R-EGF .38::'::.03 n.s. compared to CON, n=5). SGLTl or GLUT5 mRNA levels did not differ between groups. Immuno-Iocalization of SGLTl indicated less staining in the upper villus, and increased staining in the mid-villus region in remnant tissue. Oral EGF returned SGLTl staining patterns normal. GLUT5 expression was decreased on the lower 2/3 villus. EGF had no effect on GLUT5 distribution. Conclusion: Resection causes decreased BBM SGLTl and GLUT5 content in the distal remnant, and alters their expression along the viJIus. Oral EGF normalizes the pattern of SGLTl expression along the villus but has no effect on BBM SGLTl content. EGF returns BBM GLUT5 to normal levels. The data suggest the defect in nutrient transport following resection is due to alterations in the post transcriptional expression of transport proteins.
ESOPHAGEAL ATRESIA AND ASSOCIATED CARDIOVASCULAR ANOMALIES. Denis A. Cozzi, Francesco Morini, Alessandra Casati, Lucia Oriolo, Michele Ilari, Daniela Camanni, Gemma Trimarco, Francesco Cozzi, Pediatric Surg Unit, Universita' La Sapienza, Rome, Italy. Aim: Patients with exemplary cephalic neurocristopathies present with a striking pattern of associated cardiovascular anomalies (CVA). Therefore, to support the hypothesis that esophageal atresia (EA) may be related with cephalic neurocristopathies we studied the pattern of CVA associated with EA. Methods: Medical records of 99 patients (pts) with EA, 101 pts with anorectal malformations (ARM) and 15 pts with both EA and ARM, consecutively admitted to our unit were reviewed. The prevalence and pattern of CVA associated with EA and/or ARM were compared on the assumption that the cranial or caudal location of a major anomaly is correlated with different associated anomalies. Data were analysed with ltest applying Yate's correction. Results: The prevalence of eVA was 39.4% in infants with EA and 6.9% in infants with ARM (p
524 PATTERN OF ESOPHAGEAL MUSCLE IN INFANTS WITH ESOPHAGEAL ATRESIA. Denis A. Cozzi, Alessandra Casati, Francesco Morini, Michele Ilari, Lucia Oriolo, Antonietta Pisera', Maurizio Pacilli, Francesco Cozzi, Pediatric Surg Unit, Universita' La Sapienza, Rome, Italy. Aim: Striated muscles which compose the human proximal esophagus are thought to derive from myoblasts of the caudal branchial arches.In this study we tested the hypothesis that esophageal atresia (EA) may interfere with myoblast migration. Methods: We examined microscopically serial sections of 37 specimens from the tip of the upper pouch and 15 specimens from the proximal end of the lower esophagus from 40 infants with EA. Those were compared with serial sections of esophagus and trachea removed en bloc from 10 infants who died for disease not related to the gut. Results: Infants without EA had a complete transition from striated to smooth muscles in the esophagus caudal to the tracheal bifurcation, whereas in infants with EA this transition occurred above the carina(see table). Conclusion: The difference in distribution of striated muscle between normal or atretic esophagus, suggests that the reduction in striated muscle component in EA is more probably a concomitant anomaly, rather than the result of an interference from EA. Implication: In infants with repaired EA, a congenital anomaly of esophageal striated muscle arrangement may impair the organization of peristalsis and the defence mechanism against esophago-pharyngeal reflux. Esophageal muscles arrangement ininfants with esophageal atresia
Upper pouch Lower fistula' Lower stump
All Striated
Mixed
All smooth
8 specimens
16specimens 3specimens
13specimens 10specimens 2specimens
, ending above the carina inall cases
526 THE INFLUENCE OF ENTERAL FEEDING ON GROWTH FACTORS, INFLAMMATION AND NUTRITION IN CHILDREN WITH CROHN'S DISEASE. Kaushik Bannerjee, Nicholas M. Croft, Kasha Babinska, Cecilia Camachno-Hubner, Martin O. Savage, Ian R. Sanderson, Children's Service, Barts and the London NHS Trust, London, United Kingdom; Paediatric Gastroenterology, Queen Mary & Westfield Coli, London, United Kingdom; Acad Service, Barts and the London NHS Trust, London, United Kingdom; Paediatric Endocrinology, Queen Mary and Westfield Coli, London, United Kingdom. Background Exclusive enteral feeding reduces inflammation and improves clinical well being and nutritional status in children with active small bowel Crohn' s disease I. It has also been found that this treatment leads to increase in serum growth factors (IGF-1 and IGFBP-3)'. Whether the changes in growth factors are a consequence of suppression of inflammation or improved nutrition is not known. This study was undertaken to test the hypothesis that changes in growth factors and related proteins are temporally related to a decrease in inflammation rather than improvement in nutrition. Methods 13 children with active small bowel Crohn's disease being treated with a six week course of enteral feed (ALl 10, Nestle, UK) were recruited and studied at day 0,3,7, 14,21,28 and 2 and 4 months. The weight, paediatric Crohn's disease activity index (PCDAl), triceps skinfold thickness (TSFT), mid-upper arm circumference (MUAC) were measured at each visit. Serum inflammatory parameters (CRP, ESR), growth factors and related proteins (lGF-I, IGFBP-3, acid labile subunit (ALS)) and a serum marker of fat stores (Leptin) were also measured at each visit. Data from day three onwards were compared with day zero data using the wilcoxon matched pairs signed rank test. Results Thus far 7 children have completed the study and had their data analysed. There were significant improvements (P