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An association between Barrett's esophagus and celiac sprue
April 2000
AGAAtl23
5178
5180
ROLE OF HSP70I IN HEAT STRESS AND G LUTAMINE PROTECTION AGAINST MESENTERIC ISCHEMIAJREPERFUSION (IR)INDUCED INJURY IN VIVO . Sherry D. Fleming, Benjamin W. Starnes. Gary Wheeler, Daniel Mulloy, Julianne Kiang, George Tsokos, Scott T. Rehrig, Terez Shea-Donohue , Usuhs, Bethesda, MD; Walter Reed Army Institute of Research. Washington. DC. Previously we showed that heat-induction of HSP70i protein protects the intestine against IR-induced microscopic damage. Others showed that glutamine protects against oxidative injury ill vitro by inducing HSP70i protein. Aim: To determine the I) ability of glutamine to prevent IRinduced injury via HSP-70i in vivo and 2) effects of heat stress on lR-induced changes in epithelial cell function. Methods: Rats were subjected to either whole body hypertherm ia (heat) to a core temperature of 42°C for 5 min or given 2 mM glutamine intraluminally 2.5 hr before 30 min occlusion of the superior mesenteric artery. After I hr reperfusion, sections of stripped mucosa were mounted in Ussing chambers . Basal resistance and concentration-dependent changes in Isc to glucose (GLU) and acetylcholine (ACH)were determ ined. Microscopic mucosal injury was scored from 0 (normal) to 5 (severe). Results: Glutamine increased intestinal HSP-70 mRNA expression, but did not alter HSP-70i protein levels. The lR-induced microscopic injury (4.5:t 0.3)and decreased mucosal resistance were not prevented by glutamine (4.2:t0.3). Both glutamine and heat stress alone elevated Isc in response to ACH. Heat prevented and glutamine attenuated the IR suppressed responses to ACH. Heat stress and glutamine were unable to block IR-induced depression of responses to GLU. Conclusions: The protective effect of heat stress, but not glutamine , against lR-induced injury in vivo is correlated with elevation of HSP-70i. The lR-induced inhibition of epithelial secretion (ACH), but not absorption (GLU), were improved by both heat stress and gluatmine. Thus, heat stress induction of HSP-70i provides both microscopic and functional protection . The partial mucosal protection afforded by glutamine is independent of HSP.
THE PROTECTIVE EFFECT OF RECOMBINANT INTERLEU· KIN-ll PRETREATEMENT ON RADIATION INDUCED COLITIS WITH RATS. Eiichiro Fukuda, Masahiro Nakashima, Kazuko Shichijo , Mutsumi Matsuu, Masahiro Ito, Ichiro Sekine, Atomic Bomb Disease Inst, Nagasaki Univ Sch of Medicine , Nagasaki, Japan. Background : It is well known that interleukin- I I (lL-II ) is a multifunctional cytokine involved in the regulation of cell proliferati on and differentiation in a variety of cells and tissues in vitro and in vivo. Because several different lines suggest that IL-II processes the anti-inflammatory effects in inflammtory bowel disease models, we tried to evaluate the effect of IL-II on radiation induced colitis with rats and demonstrate the localization of IL-II receptor ( IL-II R ) expression in colonic mucosa. Materials and Methods : Eight-week male WKY rats were used in this study. Distal colon were exposed and then received a focal 30 Gy irradiation. These animals were divided into two groups. The first group ( early-treated group ) was pretreated with 200p.gIkg Iday IL-II s. c. before irradiation and until 10th day after irradiation when ulceration was occurred. The second group ( late-treated group ) was treated with IL-II as well 10-21st day after irradiation when mucosa was re-epithelized . As a control study, 0.1% bovine serum albumin used as a vehicle in IL-II treatment was infused s.c, in each group. Distal colons were resected at I, 3,5,7, 10 and 21st days after the irradiation, respective ly. The tissues were examined histologically with HE stained section. To evaluate the degree of tissue injury and inflammatory response, we counted the number of TUNEL positive cells and myeloperoxidase ( MPO ) immunopositive cells in irradiated portion. Furthermore, to confirm the target cells for IL-Il, both Western blots and in situ hybridization ( ISH) for IL-II Ra-subunit were carried out on control colon. Results : The numbers of both TUNEL positive cells and MPO immunopo sitive cells were decreased in irradiated co lon after IL-II treatment . The ulcer index ( the regenerative epithelium I irradiated site) was significantly ( P < 0.05) higher at the 21st day after irradiation in the early-treated group than in control group, although there were no significant differences of ulcer index between the late-treated group and its control. Western blots with both stripped colonic mucosa and submucosal tissue demonstrated immunore activity IL-Il Ro- subunit. lL-11 R mRNA was predominantl y localized in both mucosal crypt and capillary endothelial cells by ISH. Conclusion : These results indicate that [L-II pretreatment enhance the epitheliali zation by inhibition of inflammation and apoptosis in irradiated colonic mucosa. IL-II may play a protective role in radiation colitis via IL-11 R expressed in colonic mucosa.
Treabnent Control Glutamine Heat Control lR Glutamine IR HeatlR
Resistance (n-crn»
ACH (flicnY)
Glucose(flicrn»
26± 2 24 ± 2 _25± 2 11 ± 210 ± 123 ± 1
128 ± 24 205 ± 17 197 ±19 7 ± 651 ± 9-$ 93± 11
94± 17 84± 8 77± 11 O±0O± 027 ± 13-
5179 REVERSAL OF LACTOSE MALABSORPTION WITH PREBIOTIC AND PROBIOTIC THERAPY. Gerald Friedman, Mount Sinai Sch of Medicine, New York City, NY. Background : Lactose malabsorption is defined as the development of intestinal symptoms of maldigestion after the intake of lactose-containing substances. Lacotse malabsorption is due to a moderate deficiency of lactase, a disaccharidase in the glycocalyx of the small intestine . Symptoms include abdominal discomfort, bloating, flatulence, nausea and diarrhea following the ingestion of milk or milk-con taining products. The combined use of prebiotics and probiotics ameliorate symptoms of lactose malabsorption by reducing the populations of bacteria which are hydrogenergic and methanogenergic. Methods : Ten patients with symptoms suggestive of lactose intolerance (eight females) were tested for lactose malabsorption following a 10 hour fast. After the baseline (control) sample had been collected, a 25 gram dose of lactose was ingested by the patient. At 30 minute intervals samples of alveolar air were collected and analyzed for H2 and CH4. If the patient is a lactose malabsorber, the breath H2 concentration will increase over 20 PPM within the test period following the ingestion of the lactose. Following the demonstration of lactose malabsorption (eg excessive production of Hydrogen and/or Methane ), the patients were treated for one month with one capsule twice daily of probiotic Lactobacillus GG and prebiotic FOS (fructooligosaccharide, "Pure."). The lactose tolerance test was then repeated employing the same technique as initially. Results: I. Most patients demonstrated initial abnormal hydrogen production, some had abnormal hydrogen and methane production , and others had solely increased methane product ion. 2. In all instances s the symptoms of lactose malabsorpti on were ameliorated or completel y abrogated , in association with a dramatc reduction of hydrogen and/or methane production. Conclusions: Pre and probiotic therapy employing Lactobacillus GG and FOS can reverse lactose malabsorption.
5181 AN ASSOCIATION BETWEEN BARRETT'S ESO PHAGUS AND CELIAC SPRUE. Gehad Ghaith, Tusar K. Desai, Thomas J. Alexander, Michael H. Piper, Peter DeRidder, William Beaumont Hosp, Royal Oak, MI. An association between Barrell ' s esophagus and celiac sprue has been reported in children , and esophageal motility disorders have been reported in adults with celiac sprue. We have noted a heretofore unreported association between Barrell' s esophagus and celiac sprue in adults. Celiac sprue was diagnosed in 8 of the last 225 patients with Barrell' s esophagus encountered since January 1998, drawn from the private practice of four community gastroenterologists. The 8 patients were drawn from a total of 105 patients with celiac sprue encountered over that period. The two conditions were diagnosed simultaneously in 7 of 8 patients. In the eighth patient, celiac sprue was diagnosed first, and this was the only patient on a gluten-free diet at the time of Barrett 's diagnosis. Clinical characteri stics are described below. Conclusion: Barrett' s esophagus was found in 8 of 105 patients with celiac sprue, suggesting a prevalence of Barrett' s esophagus of approximately 7.6% among patients with celiac sprue. Conversely, celiac sprue was found in 8 of 225 patients with Barrell ' s esophagus, suggesting a prevalence of celiac sprue of 3.5% among patients with Barrett' s esophagus . Age (years) Sex Presenting symptom· Indication for Endoscopy Iron deficiencyanemiaHeartburn/Dysphagia • Diarrhea Short Segment Barrett's · LongSegment Barrett's -
64±5 7 maies/ 1female 4
6 6 6 2
AGAAtl23
5178
5180
ROLE OF HSP70I IN HEAT STRESS AND G LUTAMINE PROTECTION AGAINST MESENTERIC ISCHEMIAJREPERFUSION (IR)INDUCED INJURY IN VIVO . Sherry D. Fleming, Benjamin W. Starnes. Gary Wheeler, Daniel Mulloy, Julianne Kiang, George Tsokos, Scott T. Rehrig, Terez Shea-Donohue , Usuhs, Bethesda, MD; Walter Reed Army Institute of Research. Washington. DC. Previously we showed that heat-induction of HSP70i protein protects the intestine against IR-induced microscopic damage. Others showed that glutamine protects against oxidative injury ill vitro by inducing HSP70i protein. Aim: To determine the I) ability of glutamine to prevent IRinduced injury via HSP-70i in vivo and 2) effects of heat stress on lR-induced changes in epithelial cell function. Methods: Rats were subjected to either whole body hypertherm ia (heat) to a core temperature of 42°C for 5 min or given 2 mM glutamine intraluminally 2.5 hr before 30 min occlusion of the superior mesenteric artery. After I hr reperfusion, sections of stripped mucosa were mounted in Ussing chambers . Basal resistance and concentration-dependent changes in Isc to glucose (GLU) and acetylcholine (ACH)were determ ined. Microscopic mucosal injury was scored from 0 (normal) to 5 (severe). Results: Glutamine increased intestinal HSP-70 mRNA expression, but did not alter HSP-70i protein levels. The lR-induced microscopic injury (4.5:t 0.3)and decreased mucosal resistance were not prevented by glutamine (4.2:t0.3). Both glutamine and heat stress alone elevated Isc in response to ACH. Heat prevented and glutamine attenuated the IR suppressed responses to ACH. Heat stress and glutamine were unable to block IR-induced depression of responses to GLU. Conclusions: The protective effect of heat stress, but not glutamine , against lR-induced injury in vivo is correlated with elevation of HSP-70i. The lR-induced inhibition of epithelial secretion (ACH), but not absorption (GLU), were improved by both heat stress and gluatmine. Thus, heat stress induction of HSP-70i provides both microscopic and functional protection . The partial mucosal protection afforded by glutamine is independent of HSP.
THE PROTECTIVE EFFECT OF RECOMBINANT INTERLEU· KIN-ll PRETREATEMENT ON RADIATION INDUCED COLITIS WITH RATS. Eiichiro Fukuda, Masahiro Nakashima, Kazuko Shichijo , Mutsumi Matsuu, Masahiro Ito, Ichiro Sekine, Atomic Bomb Disease Inst, Nagasaki Univ Sch of Medicine , Nagasaki, Japan. Background : It is well known that interleukin- I I (lL-II ) is a multifunctional cytokine involved in the regulation of cell proliferati on and differentiation in a variety of cells and tissues in vitro and in vivo. Because several different lines suggest that IL-II processes the anti-inflammatory effects in inflammtory bowel disease models, we tried to evaluate the effect of IL-II on radiation induced colitis with rats and demonstrate the localization of IL-II receptor ( IL-II R ) expression in colonic mucosa. Materials and Methods : Eight-week male WKY rats were used in this study. Distal colon were exposed and then received a focal 30 Gy irradiation. These animals were divided into two groups. The first group ( early-treated group ) was pretreated with 200p.gIkg Iday IL-II s. c. before irradiation and until 10th day after irradiation when ulceration was occurred. The second group ( late-treated group ) was treated with IL-II as well 10-21st day after irradiation when mucosa was re-epithelized . As a control study, 0.1% bovine serum albumin used as a vehicle in IL-II treatment was infused s.c, in each group. Distal colons were resected at I, 3,5,7, 10 and 21st days after the irradiation, respective ly. The tissues were examined histologically with HE stained section. To evaluate the degree of tissue injury and inflammatory response, we counted the number of TUNEL positive cells and myeloperoxidase ( MPO ) immunopositive cells in irradiated portion. Furthermore, to confirm the target cells for IL-Il, both Western blots and in situ hybridization ( ISH) for IL-II Ra-subunit were carried out on control colon. Results : The numbers of both TUNEL positive cells and MPO immunopo sitive cells were decreased in irradiated co lon after IL-II treatment . The ulcer index ( the regenerative epithelium I irradiated site) was significantly ( P < 0.05) higher at the 21st day after irradiation in the early-treated group than in control group, although there were no significant differences of ulcer index between the late-treated group and its control. Western blots with both stripped colonic mucosa and submucosal tissue demonstrated immunore activity IL-Il Ro- subunit. lL-11 R mRNA was predominantl y localized in both mucosal crypt and capillary endothelial cells by ISH. Conclusion : These results indicate that [L-II pretreatment enhance the epitheliali zation by inhibition of inflammation and apoptosis in irradiated colonic mucosa. IL-II may play a protective role in radiation colitis via IL-11 R expressed in colonic mucosa.
Treabnent Control Glutamine Heat Control lR Glutamine IR HeatlR
Resistance (n-crn»
ACH (flicnY)
Glucose(flicrn»
26± 2 24 ± 2 _25± 2 11 ± 210 ± 123 ± 1
128 ± 24 205 ± 17 197 ±19 7 ± 651 ± 9-$ 93± 11
94± 17 84± 8 77± 11 O±0O± 027 ± 13-
5179 REVERSAL OF LACTOSE MALABSORPTION WITH PREBIOTIC AND PROBIOTIC THERAPY. Gerald Friedman, Mount Sinai Sch of Medicine, New York City, NY. Background : Lactose malabsorption is defined as the development of intestinal symptoms of maldigestion after the intake of lactose-containing substances. Lacotse malabsorption is due to a moderate deficiency of lactase, a disaccharidase in the glycocalyx of the small intestine . Symptoms include abdominal discomfort, bloating, flatulence, nausea and diarrhea following the ingestion of milk or milk-con taining products. The combined use of prebiotics and probiotics ameliorate symptoms of lactose malabsorption by reducing the populations of bacteria which are hydrogenergic and methanogenergic. Methods : Ten patients with symptoms suggestive of lactose intolerance (eight females) were tested for lactose malabsorption following a 10 hour fast. After the baseline (control) sample had been collected, a 25 gram dose of lactose was ingested by the patient. At 30 minute intervals samples of alveolar air were collected and analyzed for H2 and CH4. If the patient is a lactose malabsorber, the breath H2 concentration will increase over 20 PPM within the test period following the ingestion of the lactose. Following the demonstration of lactose malabsorption (eg excessive production of Hydrogen and/or Methane ), the patients were treated for one month with one capsule twice daily of probiotic Lactobacillus GG and prebiotic FOS (fructooligosaccharide, "Pure."). The lactose tolerance test was then repeated employing the same technique as initially. Results: I. Most patients demonstrated initial abnormal hydrogen production, some had abnormal hydrogen and methane production , and others had solely increased methane product ion. 2. In all instances s the symptoms of lactose malabsorpti on were ameliorated or completel y abrogated , in association with a dramatc reduction of hydrogen and/or methane production. Conclusions: Pre and probiotic therapy employing Lactobacillus GG and FOS can reverse lactose malabsorption.
5181 AN ASSOCIATION BETWEEN BARRETT'S ESO PHAGUS AND CELIAC SPRUE. Gehad Ghaith, Tusar K. Desai, Thomas J. Alexander, Michael H. Piper, Peter DeRidder, William Beaumont Hosp, Royal Oak, MI. An association between Barrell ' s esophagus and celiac sprue has been reported in children , and esophageal motility disorders have been reported in adults with celiac sprue. We have noted a heretofore unreported association between Barrell' s esophagus and celiac sprue in adults. Celiac sprue was diagnosed in 8 of the last 225 patients with Barrell' s esophagus encountered since January 1998, drawn from the private practice of four community gastroenterologists. The 8 patients were drawn from a total of 105 patients with celiac sprue encountered over that period. The two conditions were diagnosed simultaneously in 7 of 8 patients. In the eighth patient, celiac sprue was diagnosed first, and this was the only patient on a gluten-free diet at the time of Barrett 's diagnosis. Clinical characteri stics are described below. Conclusion: Barrett' s esophagus was found in 8 of 105 patients with celiac sprue, suggesting a prevalence of Barrett' s esophagus of approximately 7.6% among patients with celiac sprue. Conversely, celiac sprue was found in 8 of 225 patients with Barrell ' s esophagus, suggesting a prevalence of celiac sprue of 3.5% among patients with Barrett' s esophagus . Age (years) Sex Presenting symptom· Indication for Endoscopy Iron deficiencyanemiaHeartburn/Dysphagia • Diarrhea Short Segment Barrett's · LongSegment Barrett's -
64±5 7 maies/ 1female 4
6 6 6 2