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Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model

BACKGROUND: Intestinal transplantation (ITx) faces many challenges due to the complexity of surgery and to the multiple immunological reactions that lead to the necessity of rigorous follow-up for early detection of acute cellular rejection (ACR). Our aim was to determine the kinetics of ACR using a...

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Autores principales: Stringa, Pablo, Romanin, David, Lausada, Natalia, Papa Gobbi, Rodrigo, Zanuzzi, Carolina, Martín, Pedro, Abate, Juan Cruz, Cabanne, Ana, Arnal, Nathalie, Vecchio, Leandro, Milesi, Verónica, Portiansky, Enrique, Gondolesi, Gabriel, Rumbo, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682765/
https://www.ncbi.nlm.nih.gov/pubmed/29184909
http://dx.doi.org/10.1097/TXD.0000000000000718
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author Stringa, Pablo
Romanin, David
Lausada, Natalia
Papa Gobbi, Rodrigo
Zanuzzi, Carolina
Martín, Pedro
Abate, Juan Cruz
Cabanne, Ana
Arnal, Nathalie
Vecchio, Leandro
Milesi, Verónica
Portiansky, Enrique
Gondolesi, Gabriel
Rumbo, Martin
author_facet Stringa, Pablo
Romanin, David
Lausada, Natalia
Papa Gobbi, Rodrigo
Zanuzzi, Carolina
Martín, Pedro
Abate, Juan Cruz
Cabanne, Ana
Arnal, Nathalie
Vecchio, Leandro
Milesi, Verónica
Portiansky, Enrique
Gondolesi, Gabriel
Rumbo, Martin
author_sort Stringa, Pablo
collection PubMed
description BACKGROUND: Intestinal transplantation (ITx) faces many challenges due to the complexity of surgery and to the multiple immunological reactions that lead to the necessity of rigorous follow-up for early detection of acute cellular rejection (ACR). Our aim was to determine the kinetics of ACR using an experimental ITx model, with emphasis in the characterization of the process using different approaches, including the use of functional assays of absorptive and barrier function. METHODS: ITx in rats conducting serial sampling was performed. Clinical monitoring, graft histology, proinflammatory gene expression, and nitrosative stress determination were performed. Also, glucose absorption, barrier function using ovalbumin translocation, and contractile function were analyzed. RESULTS: The model used reproduced the different stages of ACR. Allogeneic ITx recipients showed signs of rejection from postoperative day (POD) 5, with increasing severity until 12 POD. Histological evaluation showed mild rejection in early sampling and severe rejection at late stages, with alterations in all graft layers. IL-6, CXCL 10, IFNg, and nitrite plasmas levels showed behavior coincident with histopathology. Remarkably, allogeneic grafts showed a marked alteration of glucose absorptive capacity from POD 5 that was sustained until endpoint. Coincidently, barrier function alteration was evidenced by luminal ovalbumin translocation to serum. Contractile function was progressively impaired along ACR. CONCLUSIONS: Glucose absorption and barrier function are altered at early stages of ACR when histological alterations or gene expression changes were much subtle. This observation may provide simple evaluation tools that could be eventually translated to the clinics to contribute to early ACR diagnosis.
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spelling pubmed-56827652017-11-28 Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model Stringa, Pablo Romanin, David Lausada, Natalia Papa Gobbi, Rodrigo Zanuzzi, Carolina Martín, Pedro Abate, Juan Cruz Cabanne, Ana Arnal, Nathalie Vecchio, Leandro Milesi, Verónica Portiansky, Enrique Gondolesi, Gabriel Rumbo, Martin Transplant Direct Basic Science BACKGROUND: Intestinal transplantation (ITx) faces many challenges due to the complexity of surgery and to the multiple immunological reactions that lead to the necessity of rigorous follow-up for early detection of acute cellular rejection (ACR). Our aim was to determine the kinetics of ACR using an experimental ITx model, with emphasis in the characterization of the process using different approaches, including the use of functional assays of absorptive and barrier function. METHODS: ITx in rats conducting serial sampling was performed. Clinical monitoring, graft histology, proinflammatory gene expression, and nitrosative stress determination were performed. Also, glucose absorption, barrier function using ovalbumin translocation, and contractile function were analyzed. RESULTS: The model used reproduced the different stages of ACR. Allogeneic ITx recipients showed signs of rejection from postoperative day (POD) 5, with increasing severity until 12 POD. Histological evaluation showed mild rejection in early sampling and severe rejection at late stages, with alterations in all graft layers. IL-6, CXCL 10, IFNg, and nitrite plasmas levels showed behavior coincident with histopathology. Remarkably, allogeneic grafts showed a marked alteration of glucose absorptive capacity from POD 5 that was sustained until endpoint. Coincidently, barrier function alteration was evidenced by luminal ovalbumin translocation to serum. Contractile function was progressively impaired along ACR. CONCLUSIONS: Glucose absorption and barrier function are altered at early stages of ACR when histological alterations or gene expression changes were much subtle. This observation may provide simple evaluation tools that could be eventually translated to the clinics to contribute to early ACR diagnosis. Lippincott Williams & Wilkins 2017-10-06 /pmc/articles/PMC5682765/ /pubmed/29184909 http://dx.doi.org/10.1097/TXD.0000000000000718 Text en Copyright © 2017 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Basic Science
Stringa, Pablo
Romanin, David
Lausada, Natalia
Papa Gobbi, Rodrigo
Zanuzzi, Carolina
Martín, Pedro
Abate, Juan Cruz
Cabanne, Ana
Arnal, Nathalie
Vecchio, Leandro
Milesi, Verónica
Portiansky, Enrique
Gondolesi, Gabriel
Rumbo, Martin
Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model
title Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model
title_full Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model
title_fullStr Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model
title_full_unstemmed Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model
title_short Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model
title_sort gut permeability and glucose absorption are affected at early stages of graft rejection in a small bowel transplant rat model
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682765/
https://www.ncbi.nlm.nih.gov/pubmed/29184909
http://dx.doi.org/10.1097/TXD.0000000000000718
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