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Published in: Digestive Diseases and Sciences 12/2012

01-12-2012 | Original Article

Neuroprotective Effect of Quercetin on the Duodenum Enteric Nervous System of Streptozotocin-Induced Diabetic Rats

Authors: Cláudia Regina Pinheiro Lopes, Paulo Emílio Botura Ferreira, Jacqueline Nelisis Zanoni, Angela Maria Pereira Alves, Éder Paulo Belato Alves, Nilza Cristina Buttow

Published in: Digestive Diseases and Sciences | Issue 12/2012

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Abstract

Background

In diabetes mellitus (DM), hyperglycemia promotes changes in biochemical mechanisms that induce oxidative stress. Oxidative stress has been closely linked to adverse consequences that affect the function of the gastrointestinal tract caused by injuries to the enteric nervous system (ENS) that in turn cause neurodegeneration and enteric glial loss. Therapeutic approaches have shown that diet supplementation with antioxidants, such as quercetin, reduce oxidative stress.

Aims

This work sought to evaluate neurons and enteric glial cells in the myenteric and submucosal plexuses of the duodenum in diabetic rats supplemented with quercetin.

Methods

The duodenum of 24 rats, including a control group (C), control quercetin supplementation group (CQ), diabetic group (D), and diabetic quercetin supplementation group (DQ), were used to investigate whole mounts of muscular and submucosal layers subjected to immunohistochemistry to detect vasoactive intestinal peptide in the myenteric layer and double-staining for HuC-D/neuronal nitric oxide synthase (nNOS) and HuC-D/S100.

Results

A reduction of the general neuronal population (HuC/D) was found in the myenteric and submucosal plexuses (p < 0.001) in the D and DQ groups. The nitrergic subpopulation (nNOS) decreased only in the myenteric plexus (p < 0.001), and glial cells decreased in both plexuses (p < 0.001) in the D and DQ groups. In diabetic rats, quercetin supplementation reduced neuronal and glial loss. Diabetes promoted an increase in the cell body area of both the general and nitrergic populations. Quercetin supplementation only prevented neuronal hypertrophy in the general population.

Conclusion

Supplementation with quercetin eased the damage caused by diabetes, promoting a neuroprotective effect and reducing enteric glial loss in the duodenum.
Literature
1.
go back to reference Rolo AP, Palmeira CM. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol. 2006;212:167–178.PubMedCrossRef Rolo AP, Palmeira CM. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol. 2006;212:167–178.PubMedCrossRef
2.
go back to reference Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–820.PubMedCrossRef Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–820.PubMedCrossRef
3.
go back to reference Hoeldtke RD, Bryner KD, VanDyke K. Oxidative stress and autonomic nerve function in early type 1 diabetes. Clin Auton Res. 2011;21:19–28.PubMedCrossRef Hoeldtke RD, Bryner KD, VanDyke K. Oxidative stress and autonomic nerve function in early type 1 diabetes. Clin Auton Res. 2011;21:19–28.PubMedCrossRef
4.
go back to reference Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev. 2004;25:612–628.PubMedCrossRef Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev. 2004;25:612–628.PubMedCrossRef
5.
go back to reference Izbeki F, Wittman T, Rosztoczy A, et al. Immediate insulin treatment prevents gut motility alterations and loss of nitrergic neurons in the ileum and colon of rats with streptozotocin-induced diabetes. Diabetes Res Clin Pract. 2008;80:192–198.PubMedCrossRef Izbeki F, Wittman T, Rosztoczy A, et al. Immediate insulin treatment prevents gut motility alterations and loss of nitrergic neurons in the ileum and colon of rats with streptozotocin-induced diabetes. Diabetes Res Clin Pract. 2008;80:192–198.PubMedCrossRef
6.
go back to reference Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Int Med. 2001;161:1989–1996.CrossRef Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Int Med. 2001;161:1989–1996.CrossRef
7.
go back to reference Obrosova IG, Van Huysen C, Fathallah L, Cao XC, Greene DA, Stevens MJ. An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense. FASEB J. 2002;16:123–125.PubMed Obrosova IG, Van Huysen C, Fathallah L, Cao XC, Greene DA, Stevens MJ. An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense. FASEB J. 2002;16:123–125.PubMed
8.
go back to reference Formica JV, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol. 1995;33:1061–1080.PubMedCrossRef Formica JV, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol. 1995;33:1061–1080.PubMedCrossRef
9.
go back to reference Shirai M, Yamanishi R, Moon JH, Murota K, Terao J. Effect of quercetin and its conjugated metabolite on the hydrogen peroxide-induced intracellular production of reactive oxygen species in mouse fibroblasts. Biosci Biotechnol Biochem. 2002;66:1015–1021.PubMedCrossRef Shirai M, Yamanishi R, Moon JH, Murota K, Terao J. Effect of quercetin and its conjugated metabolite on the hydrogen peroxide-induced intracellular production of reactive oxygen species in mouse fibroblasts. Biosci Biotechnol Biochem. 2002;66:1015–1021.PubMedCrossRef
10.
go back to reference Arredondo F, Echeverry C, Abin-Carriquiry JA, Blasina F, Antunez K, Jones DP, Go YM, Liang YL, Dajas F. After cellular internalization, quercetin causes nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult. Free Radic Biol Med. 2010;49:738–747. Arredondo F, Echeverry C, Abin-Carriquiry JA, Blasina F, Antunez K, Jones DP, Go YM, Liang YL, Dajas F. After cellular internalization, quercetin causes nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult. Free Radic Biol Med. 2010;49:738–747.
11.
go back to reference De Freitas P, Natali MR, Pereira RV, Miranda Neto MH, Zanoni JN. Myenteric neurons and intestinal mucosa of diabetic rats after ascorbic acid supplementation. World J Gastroenterol. 2008;14:6518–6524.PubMedCrossRef De Freitas P, Natali MR, Pereira RV, Miranda Neto MH, Zanoni JN. Myenteric neurons and intestinal mucosa of diabetic rats after ascorbic acid supplementation. World J Gastroenterol. 2008;14:6518–6524.PubMedCrossRef
12.
go back to reference Pereira RV, de Miranda-Neto MH, da Silva Souza ID, Zanoni JN. Vitamin e supplementation in rats with experimental diabetes mellitus: analysis of myosin-v and nnos immunoreactive myenteric neurons from terminal ileum. J Mol Histol. 2008;39:595–603.PubMedCrossRef Pereira RV, de Miranda-Neto MH, da Silva Souza ID, Zanoni JN. Vitamin e supplementation in rats with experimental diabetes mellitus: analysis of myosin-v and nnos immunoreactive myenteric neurons from terminal ileum. J Mol Histol. 2008;39:595–603.PubMedCrossRef
13.
go back to reference Fregonesi CE, Molinari SL, Alves AM, et al. Morphoquantitative aspects of nitrergic myoenteric neurons from the stomach of diabetic rats supplemented with acetyl-l-carnitine. Anat Histol Embryol. 2005;34:93–97.PubMedCrossRef Fregonesi CE, Molinari SL, Alves AM, et al. Morphoquantitative aspects of nitrergic myoenteric neurons from the stomach of diabetic rats supplemented with acetyl-l-carnitine. Anat Histol Embryol. 2005;34:93–97.PubMedCrossRef
14.
go back to reference da Silva GG, Zanoni JN, Buttow NC. Neuroprotective action of ginkgo biloba on the enteric nervous system of diabetic rats. World J Gastroenterol. 2011;17:898–905.PubMedCrossRef da Silva GG, Zanoni JN, Buttow NC. Neuroprotective action of ginkgo biloba on the enteric nervous system of diabetic rats. World J Gastroenterol. 2011;17:898–905.PubMedCrossRef
15.
go back to reference Tashima CM, Tronchini EA, Pereira RV, Bazotte RB, Zanoni JN. Diabetic rats supplemented with l-glutamine: a study of immunoreactive myosin-v myenteric neurons and the proximal colonic mucosa. Dig Dis Sci. 2007;52:1233–1241.PubMedCrossRef Tashima CM, Tronchini EA, Pereira RV, Bazotte RB, Zanoni JN. Diabetic rats supplemented with l-glutamine: a study of immunoreactive myosin-v myenteric neurons and the proximal colonic mucosa. Dig Dis Sci. 2007;52:1233–1241.PubMedCrossRef
16.
go back to reference Roldi LP, Pereira RV, Tronchini EA, et al. Vitamin e (alpha-tocopherol) supplementation in diabetic rats: effects on the proximal colon. BMC Gastroenterol. 2009;9:88.PubMedCrossRef Roldi LP, Pereira RV, Tronchini EA, et al. Vitamin e (alpha-tocopherol) supplementation in diabetic rats: effects on the proximal colon. BMC Gastroenterol. 2009;9:88.PubMedCrossRef
17.
go back to reference Chandrasekharan B, Srinivasan S. Diabetes and the enteric nervous system. Neurogastroenterol Motil. 2007;19:951–960.PubMed Chandrasekharan B, Srinivasan S. Diabetes and the enteric nervous system. Neurogastroenterol Motil. 2007;19:951–960.PubMed
19.
go back to reference Kuyvenhoven JP, Meinders AE. Oxidative stress and diabetes mellitus: pathogenesis of long-term complications. Eur J Internal Med. 1999;10:9–19.CrossRef Kuyvenhoven JP, Meinders AE. Oxidative stress and diabetes mellitus: pathogenesis of long-term complications. Eur J Internal Med. 1999;10:9–19.CrossRef
20.
go back to reference Shirpoor A, Ansari MH, Salami S, Pakdel FG, Rasmi Y. Effect of vitamin e on oxidative stress status in small intestine of diabetic rat. World J Gastroenterol. 2007;13:4340–4344.PubMed Shirpoor A, Ansari MH, Salami S, Pakdel FG, Rasmi Y. Effect of vitamin e on oxidative stress status in small intestine of diabetic rat. World J Gastroenterol. 2007;13:4340–4344.PubMed
21.
go back to reference Myhrstad MC, Carlsen H, Nordstrom O, Blomhoff R, Moskaug JO. Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med. 2002;32:386–393.PubMedCrossRef Myhrstad MC, Carlsen H, Nordstrom O, Blomhoff R, Moskaug JO. Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med. 2002;32:386–393.PubMedCrossRef
22.
go back to reference Hollman PC, Gaag VDM, Mengelers MJ, van Trijp JM, de Vries JH, Katan MB. Absorption and disposition kinetics of the dietary antioxidant quercetin in man. Free Radic Biol Med. 1996;21:703–707.PubMedCrossRef Hollman PC, Gaag VDM, Mengelers MJ, van Trijp JM, de Vries JH, Katan MB. Absorption and disposition kinetics of the dietary antioxidant quercetin in man. Free Radic Biol Med. 1996;21:703–707.PubMedCrossRef
23.
go back to reference Hollman PC, Katan MB. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed Pharmacother. 1997;51:305–310.PubMedCrossRef Hollman PC, Katan MB. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed Pharmacother. 1997;51:305–310.PubMedCrossRef
24.
go back to reference Takahashi T, Nakamura K, Itoh H, Sima AA, Owyang C. Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats. Gastroenterology. 1997;113:1535–1544.PubMedCrossRef Takahashi T, Nakamura K, Itoh H, Sima AA, Owyang C. Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats. Gastroenterology. 1997;113:1535–1544.PubMedCrossRef
25.
go back to reference Wrzos HF, Cruz A, Polavarapu R, Shearer D, Ouyang A. Nitric oxide synthase (nos) expression in the myenteric plexus of streptozotocin-diabetic rats. Dig Dis Sci. 1997;42:2106–2110.PubMedCrossRef Wrzos HF, Cruz A, Polavarapu R, Shearer D, Ouyang A. Nitric oxide synthase (nos) expression in the myenteric plexus of streptozotocin-diabetic rats. Dig Dis Sci. 1997;42:2106–2110.PubMedCrossRef
26.
go back to reference Yoneda S, Kadowaki M, Kuramoto H, Fukui H, Takaki M. Enhanced colonic peristalsis by impairment of nitrergic enteric neurons in spontaneously diabetic rats. Auton Neurosci. 2001;92:65–71.PubMedCrossRef Yoneda S, Kadowaki M, Kuramoto H, Fukui H, Takaki M. Enhanced colonic peristalsis by impairment of nitrergic enteric neurons in spontaneously diabetic rats. Auton Neurosci. 2001;92:65–71.PubMedCrossRef
27.
go back to reference Belai A, Cooper S, Burnstock G. Effect of age on nadph-diaphorase-containing myenteric neurones of rat ileum and proximal colon. Cell Tissue Res. 1995;279:379–383.PubMedCrossRef Belai A, Cooper S, Burnstock G. Effect of age on nadph-diaphorase-containing myenteric neurones of rat ileum and proximal colon. Cell Tissue Res. 1995;279:379–383.PubMedCrossRef
28.
go back to reference Santer RM. Survival of the population of nadph-diaphorase stained myenteric neurons in the small intestine of aged rats. J Auton Nerv Syst. 1994;49:115–121.PubMedCrossRef Santer RM. Survival of the population of nadph-diaphorase stained myenteric neurons in the small intestine of aged rats. J Auton Nerv Syst. 1994;49:115–121.PubMedCrossRef
29.
go back to reference Zanoni JN, Hernandes L, Bazotte RB, Miranda Neto MH. Terminal ileum submucous plexus: study of the vip-ergic neurons of diabetic rats treated with ascorbic acid. Arq Neuropsiquiatr. 2002;60:32–37.PubMedCrossRef Zanoni JN, Hernandes L, Bazotte RB, Miranda Neto MH. Terminal ileum submucous plexus: study of the vip-ergic neurons of diabetic rats treated with ascorbic acid. Arq Neuropsiquiatr. 2002;60:32–37.PubMedCrossRef
30.
go back to reference Nagahama M, Semba R, Tsuzuki M, Aoki E. l-arginine immunoreactive enteric glial cells in the enteric nervous system of rat ileum. Biol Signals Recept. 2001;10:336–340. Nagahama M, Semba R, Tsuzuki M, Aoki E. l-arginine immunoreactive enteric glial cells in the enteric nervous system of rat ileum. Biol Signals Recept. 2001;10:336–340.
31.
go back to reference Porter AJ, Wattchow DA, Brookes SJ, Costa M. Projections of nitric oxide synthase and vasoactive intestinal polypeptide-reactive submucosal neurons in the human colon. J Gastroenterol Hepatol. 1999;14:1180–1187.PubMedCrossRef Porter AJ, Wattchow DA, Brookes SJ, Costa M. Projections of nitric oxide synthase and vasoactive intestinal polypeptide-reactive submucosal neurons in the human colon. J Gastroenterol Hepatol. 1999;14:1180–1187.PubMedCrossRef
32.
go back to reference Lin Z, Sandgren K, Ekblad E. Increased expression of nitric oxide synthase in cultured neurons from adult rat colonic submucous ganglia. Auton Neurosci. 2004;114:29–38.PubMedCrossRef Lin Z, Sandgren K, Ekblad E. Increased expression of nitric oxide synthase in cultured neurons from adult rat colonic submucous ganglia. Auton Neurosci. 2004;114:29–38.PubMedCrossRef
33.
go back to reference Zucoloto S, Diaz JA, Oliveira JS, Muccilo G, Sales Neto VN, Kajiwara JK. Effect of chemical ablation of myenteric neurones on intestinal cell proliferation. Cell Tissue Kinet. 1988;21:213–219.PubMed Zucoloto S, Diaz JA, Oliveira JS, Muccilo G, Sales Neto VN, Kajiwara JK. Effect of chemical ablation of myenteric neurones on intestinal cell proliferation. Cell Tissue Kinet. 1988;21:213–219.PubMed
34.
go back to reference Montaner B, Asbert M, Perez-Tomas R. Immunolocalization of transforming growth factor-alpha and epidermal growth factor receptor in the rat gastroduodenal area. Dig Dis Sci. 1999;44:1408–1416.PubMedCrossRef Montaner B, Asbert M, Perez-Tomas R. Immunolocalization of transforming growth factor-alpha and epidermal growth factor receptor in the rat gastroduodenal area. Dig Dis Sci. 1999;44:1408–1416.PubMedCrossRef
35.
go back to reference Yoshikawa I. Effects of epidermal growth factor on alkaline secretion and mucus formation in rat duodenum exposed to luminal acid. Gastroenterol Jpn. 1993;28:496–504.PubMedCrossRef Yoshikawa I. Effects of epidermal growth factor on alkaline secretion and mucus formation in rat duodenum exposed to luminal acid. Gastroenterol Jpn. 1993;28:496–504.PubMedCrossRef
36.
go back to reference Moriez R, Abdo H, Chaumette T, Faure M, Lardeux B, Neunlist M. Neuroplasticity and neuroprotection in enteric neurons: role of epithelial cells. Biochem Biophys Res Commun. 2009;382:577–582.PubMedCrossRef Moriez R, Abdo H, Chaumette T, Faure M, Lardeux B, Neunlist M. Neuroplasticity and neuroprotection in enteric neurons: role of epithelial cells. Biochem Biophys Res Commun. 2009;382:577–582.PubMedCrossRef
37.
go back to reference Cabarrocas J, Savidge TC, Liblau RS. Role of enteric glial cells in inflammatory bowel disease. Glia. 2003;41:81–93.PubMedCrossRef Cabarrocas J, Savidge TC, Liblau RS. Role of enteric glial cells in inflammatory bowel disease. Glia. 2003;41:81–93.PubMedCrossRef
38.
go back to reference Bassotti G, Villanacci V. Can “Functional” constipation be considered as a form of enteric neuro-gliopathy? Glia. 2011;59:345–350. Bassotti G, Villanacci V. Can “Functional” constipation be considered as a form of enteric neuro-gliopathy? Glia. 2011;59:345–350.
39.
go back to reference Wang L, Colodner KJ, Feany MB. Protein misfolding and oxidative stress promote glial-mediated neurodegeneration in an alexander disease model. J Neurosci. 2011;31:2868–2877.PubMedCrossRef Wang L, Colodner KJ, Feany MB. Protein misfolding and oxidative stress promote glial-mediated neurodegeneration in an alexander disease model. J Neurosci. 2011;31:2868–2877.PubMedCrossRef
40.
go back to reference Shih AY, Johnson DA, Wong G, et al. Coordinate regulation of glutathione biosynthesis and release by nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci. 2003;23:3394–3406.PubMed Shih AY, Johnson DA, Wong G, et al. Coordinate regulation of glutathione biosynthesis and release by nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci. 2003;23:3394–3406.PubMed
41.
go back to reference Belai A, Calcutt NA, Carrington AL, Diemel LT, Tomlinson DR, Burnstock G. Enteric neuropeptides in streptozotocin-diabetic rats; effects of insulin and aldose reductase inhibition. J Auton Nerv Syst. 1996;58:163–169.PubMedCrossRef Belai A, Calcutt NA, Carrington AL, Diemel LT, Tomlinson DR, Burnstock G. Enteric neuropeptides in streptozotocin-diabetic rats; effects of insulin and aldose reductase inhibition. J Auton Nerv Syst. 1996;58:163–169.PubMedCrossRef
42.
go back to reference Spangeus A, Suhr O, El-Salhy M. Diabetic state affects the innervation of gut in an animal model of human type 1 diabetes. Histol Histopathol. 2000;15:739–744.PubMed Spangeus A, Suhr O, El-Salhy M. Diabetic state affects the innervation of gut in an animal model of human type 1 diabetes. Histol Histopathol. 2000;15:739–744.PubMed
43.
go back to reference Eaker EY, Sallustio JE, Marchand SD, Sahu A, Kalra SP, Sninsky CA. Differential increase in neuropeptide y-like levels and myenteric neuronal staining in diabetic rat intestine. Regul Pept. 1996;61:77–84.PubMedCrossRef Eaker EY, Sallustio JE, Marchand SD, Sahu A, Kalra SP, Sninsky CA. Differential increase in neuropeptide y-like levels and myenteric neuronal staining in diabetic rat intestine. Regul Pept. 1996;61:77–84.PubMedCrossRef
44.
go back to reference Shotton HR, Lincoln J. Diabetes only affects nitric oxide synthase-containing myenteric neurons that do not contain heme oxygenase 2. Brain Res. 2006;1068:248–256.PubMedCrossRef Shotton HR, Lincoln J. Diabetes only affects nitric oxide synthase-containing myenteric neurons that do not contain heme oxygenase 2. Brain Res. 2006;1068:248–256.PubMedCrossRef
45.
go back to reference Shotton HR, Adams A, Lincoln J. Effect of aminoguanidine treatment on diabetes-induced changes in the myenteric plexus of rat ileum. Auton Neurosci. 2007;132:16–26.PubMedCrossRef Shotton HR, Adams A, Lincoln J. Effect of aminoguanidine treatment on diabetes-induced changes in the myenteric plexus of rat ileum. Auton Neurosci. 2007;132:16–26.PubMedCrossRef
46.
go back to reference Cellek S. Point of no return for nitrergic nerves in diabetes: a new insight into diabetic complications. Curr Pharm Des. 2004;10:3683–3695.PubMedCrossRef Cellek S. Point of no return for nitrergic nerves in diabetes: a new insight into diabetic complications. Curr Pharm Des. 2004;10:3683–3695.PubMedCrossRef
47.
go back to reference Courderot-Masuyer C, Lahet JJ, Verges B, Brun JM, Rochette L. Ascorbyl free radical release in diabetic patients. Cell Mol Biol. 2000;46:1397–1401.PubMed Courderot-Masuyer C, Lahet JJ, Verges B, Brun JM, Rochette L. Ascorbyl free radical release in diabetic patients. Cell Mol Biol. 2000;46:1397–1401.PubMed
48.
go back to reference Kumari K, Umar S, Bansal V, Sahib MK. Monoaminoguanidine inhibits aldose reductase. Biochem Pharmacol. 1991;41:1527–1528.PubMedCrossRef Kumari K, Umar S, Bansal V, Sahib MK. Monoaminoguanidine inhibits aldose reductase. Biochem Pharmacol. 1991;41:1527–1528.PubMedCrossRef
Metadata
Title
Neuroprotective Effect of Quercetin on the Duodenum Enteric Nervous System of Streptozotocin-Induced Diabetic Rats
Authors
Cláudia Regina Pinheiro Lopes
Paulo Emílio Botura Ferreira
Jacqueline Nelisis Zanoni
Angela Maria Pereira Alves
Éder Paulo Belato Alves
Nilza Cristina Buttow
Publication date
01-12-2012
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 12/2012
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-012-2300-7

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