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Larazotide Acetate Regulates Epithelial Tight Junctions in Vitro and in Vivo

Reference: Gopalakrishnan S, Durai M, Kitchens K, Tamiz AP, Somerville R, Ginski M, Paterson BM, Murray JA, Verdu EF, Alkan SS, Pandey NB. Larazotide Acetate Regulates Epithelial Tight Junctions in Vitro and in Vivo. Peptides. 2012 Feb 27.

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Larazotide Acetate Promotes Tight Junction Assembly in Epithelial Cells

Reference: Gopalakrishnan S, Tripathi A, Tamiz AP, Alkan SS, Pandey NB. Larazotide Acetate Promotes Tight Junction Assembly in Epithelial Cells. Peptide. 2012 May.

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Key publications in the field of barrier function and its role in the pathogenesis of disease:

Permeability
1  Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut 2006;55:1512-20.
2  Arnott ID, Kingstone K, Ghosh S. Abnormal intestinal permeability predicts relapse in inactive Crohn disease. Scand J Gastroenterol 2000;35:1163-9.
3  Barbara G. Mucosal barrier defects in irritable bowel syndrome. Who left the door open? The American journal of gastroenterology 2006;101:1295-8.
4  Baumgart DC, Dignass AU. Intestinal barrier function. Current opinion in clinical nutrition and metabolic care 2002;5:685-94.
5  Clayburgh DR, Shen L, Turner JR. A porous defense: the leaky epithelial barrier in intestinal disease. Laboratory investigation; a journal of technical methods and pathology 2004;84:282-91.
6  Clemente MG, De Virgiliis S, Kang JS, et al. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut. Feb 2003;52(2):218-223.
7  DeMeo MT, Mutlu EA, Keshavarzian A, et al. Intestinal permeation and gastrointestinal disease. Journal of clinical gastroenterology 2002;34:385-96.
8  Damci T, Nuhoglu I, Devranoglu G, et al. Increased intestinal permeability as a cause of fluctuating postprandial blood glucose levels in Type 1 diabetic patients. European journal of clinical investigation 2003;33:397-401.
9  Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nature clinical practice 2005;2:416-22.
10 Meddings JB, Jarand J, Urbanski SJ, et al. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. The American journal of physiology 1999;276:G951-7.
11 Neu J, Reverte CM, Mackey AD, et al. Changes in intestinal morphology and permeability in the biobreeding rat before the onset of type 1 diabetes. J Pediatr Gastroenterol Nutr. May 2005;40(5):589-595.
12 Secondulfo M, Iafusco D, Carratu R, et al. Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients. Dig Liver Dis 2004;36:35-45.

Disease models
1  Blair SA, Kane SV, Clayburgh DR, et al. Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Laboratory investigation; a journal of technical methods and pathology 2006;86:191-201.
2  Chakir H, Lefebvre DE, Wang H, Caraher E, Scott FW. Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats. Diabetologia. Aug 2005;48(8):1576-1584.
3  Fasano A, Uzzau S. Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model. The Journal of clinical investigation 1997;99:1158-64.
4  Karyekar CS, Fasano A, Raje S, et al. Zonula occludens toxin increases the permeability of molecular weight markers and chemotherapeutic agents across the bovine brain microvessel endothelial cells. Journal of pharmaceutical sciences 2003;92:414-23.
5  Katouzian F, Sblattero D, Not T, et al. Dual sugar gut-permeability testing on blood drop in animal models. Clinica chimica acta; international journal of clinical chemistry 2005;352:191-7.
6  Korzenik JR, Podolsky DK. Evolving knowledge and therapy of inflammatory bowel disease. Nat Rev Drug Discov 2006;5:197-209.
7  Malaisse WJ, Courtois P, Scott FW. Insulin-dependent diabetes and gut dysfunction: the BB rat model. Horm Metab Res. Sep 2004;36(9):585-594.
8  Marinaro M, Fasano A, De Magistris MT. Zonula occludens toxin acts as an adjuvant through different mucosal routes and induces protective immune responses. Infect Immun 2003;71:1897-902.
9  Meddings JB, Jarand J, Urbanski SJ, et al. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. The American journal of physiology 1999;276:G951-7.
10 Rossi M, Maurano F, Luongo D, et al. Zonula occludens toxin (Zot) interferes with the induction of nasal tolerance to gliadin. Immunology letters 2002;81:217-21.
11 Scott FW. Food-induced type 1 diabetes in the BB rat. Diabetes Metab Rev. Dec 1996;12(4):341-359.
12 Watts T, Berti I, Sapone A, et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proceedings of the National Academy of Sciences of the United States of America 2005;102:2916-21.
13 Weber CR, Turner JR. Inflammatory bowel disease: is it really just another break in the wall? Gut 2007;56:6-8.

Clinical medicine
1  Bjarnason I, Takeuchi K, Bjarnason A, et al. The G.U.T. of gut. Scand J Gastroenterol 2004;39:807-15.
2  Bosi E, Molteni L, Radaelli MG, et al. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia 2006;49:2824-7.
3  Bruewer M, Samarin S, Nusrat A. Inflammatory bowel disease and the apical junctional complex. Annals of the New York Academy of Sciences 2006;1072:242-52.
4  Catassi C, Bearzi I, Holmes GK. Association of celiac disease and intestinal lymphomas and other cancers. Gastroenterology 2005;128:S79-86.
5  Dewar DH, Ciclitira PJ. Clinical features and diagnosis of celiac disease. Gastroenterology 2005;128:S19-24.
6  Fasano A. Celiac disease--how to handle a clinical chameleon. The New England journal of medicine 2003;348:2568-70.
7  Isaacs KL, Lewis JD, Sandborn WJ, et al. State of the art: IBD therapy and clinical trials in IBD. Inflammatory bowel diseases 2005;11 Suppl 1:S3-12.
8  Loftus EV, Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 2004;126:1504-17.
9  Murray JA. Celiac disease in patients with an affected member, type 1 diabetes, iron-deficiency, or osteoporosis? Gastroenterology 2005;128:S52-6.
10 NIH. National Institutes of Health Consensus Development Conference Statement on Celiac Disease, June 28-30, 2004. Gastroenterology 2005;128:S1-9.
11 Norris JM, Barriga K, Klingensmith G, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. Jama. Oct 1 2003;290(13):1713-1720.
12 Norris JM, Barriga K, Hoffenberg EJ, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. Jama. May 18 2005;293(19):2343-2351.
13 Sapone A, de Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 2006;55:1443-9.
14 Ziegler AG, Schmid S, Huber D, Hummel M, Bonifacio E. Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. Jama. Oct 1 2003;290(13):1721-1728.

Triggers
1  Akerblom HK, Vaarala O, Hyoty H, et al. Environmental factors in the etiology of type 1 diabetes. American journal of medical genetics 2002;115:18-29.
2  Catassi C, Fabiani E, Iacono G, et al. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr 2007;85:160-6.
3  Chamberlin WM, Naser SA. Integrating theories of the etiology of Crohn's disease. On the etiology of Crohn's disease: questioning the hypotheses. Med Sci Monit 2006;12:RA27-33.
4  Collin P, Thorell L, Kaukinen K, et al. The safe threshold for gluten contamination in gluten-free products. Can trace amounts be accepted in the treatment of coeliac disease? Aliment Pharmacol Ther 2004;19:1277-83.
5  Couper JJ. Environmental triggers of type 1 diabetes. Journal of paediatrics and child health 2001;37:218-20.
6  Dewar DH, Ciclitira PJ. Clinical features and diagnosis of celiac disease. Gastroenterology. Apr 2005;128(4 Suppl 1):S19-24.
7  Di Cagno R, De Angelis M, Auricchio S, et al. Sourdough bread made from wheat and nontoxic flours and started with selected lactobacilli is tolerated in celiac sprue patients. Appl Environ Microbiol. Feb 2004;70(2):1088-1096.
8  Di Pierro M, Lu R, Uzzau S, et al. Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain. The Journal of biological chemistry 2001;276:19160-5.
9  Drago S, El Asmar R, Di Pierro M, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol 2006;41:408-19.
10  Fasano A, Baudry B, Pumplin DW, et al. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proceedings of the National Academy of Sciences of the United States of America 1991;88:5242-6.
11  Fasano A. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Annals of the New York Academy of Sciences 2000;915:214-22.
12 Lefebvre DE, Powell KL, Strom A, Scott FW. Dietary proteins as environmental modifiers of type 1 diabetes mellitus. Annu Rev Nutr. 2006;26:175-202.
13 Thomas KE, Sapone A, Fasano A, et al. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease. J Immunol 2006;176:2512-21.
14 Schuppan D. Current concepts of celiac disease pathogenesis. Gastroenterology. Jul 2000;119(1):234-242.

Genetics
1  Honeyman MC, Harrison LC, Drummond B, et al. Analysis of families at risk for insulin-dependent diabetes mellitus reveals that HLA antigens influence progression to clinical disease. Molecular medicine (Cambridge, Mass 1995;1:576-82.
2  Hugot JP. Inflammatory bowel disease: a complex group of genetic disorders. Best practice & research 2004;18:451-62.
3  Loftus EV, Jr., Schoenfeld P, Sandborn WJ. The epidemiology and natural history of Crohn's disease in population-based patient cohorts from North America: a systematic review. Aliment Pharmacol Ther 2002;16:51-60.
4  Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001;411:603-6.
5  Papadopoulos GK, Wijmenga C, Koning F. Interplay between genetics and the environment in the development of celiac disease: perspectives for a healthy life. The Journal of clinical investigation 2001;108:1261-6.
6  Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nature clinical practice 2006;3:390-407.
7  Sumnik Z, Kolouskova S, Malcova H, et al. High prevalence of coeliac disease in siblings of children with type 1 diabetes. European journal of pediatrics 2005;164:9-12.
8  Takeuchi K, Maiden L, Bjarnason I. Genetic aspects of intestinal permeability in inflammatory bowel disease. Novartis Foundation symposium 2004;263:151-8; discussion 9-63, 211-8.
9  Vader W, Stepniak D, Kooy Y, et al. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. Proceedings of the National Academy of Sciences of the United States of America 2003;100:12390-5.
10  van Heel DA, Hunt K, Greco L, et al. Genetics in coeliac disease. Best practice & research 2005;19:323-39.

Immunology
1  Auricchio R, Paparo F, Maglio M, et al. In vitro-deranged intestinal immune response to gliadin in type 1 diabetes. Diabetes. Jul 2004;53(7):1680-1683.
2  Dewar DH, Amato M, Ellis HJ, et al. The toxicity of high molecular weight glutenin subunits of wheat to patients with coeliac disease. Eur J Gastroenterol Hepatol. May 2006;18(5):483-491
3  Kagnoff MF. Mucosal inflammation in celiac disease: interleukin-15 meets transforming growth factor beta-1. Gastroenterology. Mar 2007;132(3):1174-1176.
4  Koning F. The molecular basis of celiac disease. J Mol Recognit. Sep-Oct 2003;16(5):333-336.
5  Thomas KE, Sapone A, Fasano A, Vogel SN. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease. J Immunol. Feb 15 2006;176(4):2512-2521.