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Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates

A limitation of currently used preclinical models of colitis is that disease and treatment assessment methods differ from clinically used methods. Thus, a modified Mayo score and an endoscopic index (EI) were developed for use in cynomolgus macaques with 0.25% dextran sulfate sodium (DSS)-induced ul...

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Autores principales: Takahashi, Nobuyuki, Kitazawa, Chinatsu, Itani, Yoshitaka, Awaga, Yuji, Hama, Aldric, Hayashi, Ikuo, Takamatsu, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953712/
https://www.ncbi.nlm.nih.gov/pubmed/31938753
http://dx.doi.org/10.1016/j.heliyon.2020.e03178
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author Takahashi, Nobuyuki
Kitazawa, Chinatsu
Itani, Yoshitaka
Awaga, Yuji
Hama, Aldric
Hayashi, Ikuo
Takamatsu, Hiroyuki
author_facet Takahashi, Nobuyuki
Kitazawa, Chinatsu
Itani, Yoshitaka
Awaga, Yuji
Hama, Aldric
Hayashi, Ikuo
Takamatsu, Hiroyuki
author_sort Takahashi, Nobuyuki
collection PubMed
description A limitation of currently used preclinical models of colitis is that disease and treatment assessment methods differ from clinically used methods. Thus, a modified Mayo score and an endoscopic index (EI) were developed for use in cynomolgus macaques with 0.25% dextran sulfate sodium (DSS)-induced ulcerative colitis. Macaques were treated with water with DSS for two weeks followed by water without DSS for two weeks. Disease activity was classified according to a modified Mayo score: stool consistency, rectal bleeding, colonoscopy examination and global assessment. Findings on colonoscopy were further graded according the Rachmilewitz EI. To demonstrate the sensitivity of the modified Mayo score and EI to therapeutic intervention, macaques were treated with the anti-inflammatory steroid prednisolone followed eight weeks later by the integrin antibody vedolizumab. Before DSS treatment, normal stool consistency and no rectal bleeding were observed. Colonoscopy demonstrated no mucosal abnormalities. Following the first DSS treatment, Mayo score and EI indicated signs of mild colitis. Following subsequent DSS treatments, mild to moderate colitis emerged with each DSS treatment and reduced signs of colitis were observed 2 weeks after DSS treatment termination. Prednisolone treatment during DSS treatment suppressed the emergence of colitis. Vedolizumab reduced signs of colitis during DSS treatment and further reduced signs of colitis that persisted after termination of DSS treatment. The current study demonstrated the potential of utilizing clinical outcome measures to assess experimentally-induced colitis in the macaque. Furthermore, signs of colitis, as assessed with the current methods, were reduced following therapeutic treatment. The current findings suggest that clinically relevant outcome measures in the macaque model of ulcerative colitis could be used to test novel treatments.
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spelling pubmed-69537122020-01-14 Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates Takahashi, Nobuyuki Kitazawa, Chinatsu Itani, Yoshitaka Awaga, Yuji Hama, Aldric Hayashi, Ikuo Takamatsu, Hiroyuki Heliyon Article A limitation of currently used preclinical models of colitis is that disease and treatment assessment methods differ from clinically used methods. Thus, a modified Mayo score and an endoscopic index (EI) were developed for use in cynomolgus macaques with 0.25% dextran sulfate sodium (DSS)-induced ulcerative colitis. Macaques were treated with water with DSS for two weeks followed by water without DSS for two weeks. Disease activity was classified according to a modified Mayo score: stool consistency, rectal bleeding, colonoscopy examination and global assessment. Findings on colonoscopy were further graded according the Rachmilewitz EI. To demonstrate the sensitivity of the modified Mayo score and EI to therapeutic intervention, macaques were treated with the anti-inflammatory steroid prednisolone followed eight weeks later by the integrin antibody vedolizumab. Before DSS treatment, normal stool consistency and no rectal bleeding were observed. Colonoscopy demonstrated no mucosal abnormalities. Following the first DSS treatment, Mayo score and EI indicated signs of mild colitis. Following subsequent DSS treatments, mild to moderate colitis emerged with each DSS treatment and reduced signs of colitis were observed 2 weeks after DSS treatment termination. Prednisolone treatment during DSS treatment suppressed the emergence of colitis. Vedolizumab reduced signs of colitis during DSS treatment and further reduced signs of colitis that persisted after termination of DSS treatment. The current study demonstrated the potential of utilizing clinical outcome measures to assess experimentally-induced colitis in the macaque. Furthermore, signs of colitis, as assessed with the current methods, were reduced following therapeutic treatment. The current findings suggest that clinically relevant outcome measures in the macaque model of ulcerative colitis could be used to test novel treatments. Elsevier 2020-01-09 /pmc/articles/PMC6953712/ /pubmed/31938753 http://dx.doi.org/10.1016/j.heliyon.2020.e03178 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Takahashi, Nobuyuki
Kitazawa, Chinatsu
Itani, Yoshitaka
Awaga, Yuji
Hama, Aldric
Hayashi, Ikuo
Takamatsu, Hiroyuki
Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates
title Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates
title_full Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates
title_fullStr Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates
title_full_unstemmed Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates
title_short Exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates
title_sort exploratory clinical characterization of experimentally-induced ulcerative colitis nonhuman primates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953712/
https://www.ncbi.nlm.nih.gov/pubmed/31938753
http://dx.doi.org/10.1016/j.heliyon.2020.e03178
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