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Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout

INTRODUCTION: Gout is an inflammatory condition induced by the deposition of monosodium urate (MSU) crystals in the joints and soft tissues that can produce acute or chronic arthritis. Several animal models of crystal-induced inflammation have been proposed that involve direct injection of MSU-cryst...

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Autores principales: Pineda, Carlos, Fuentes-Gómez, Arturo J, Hernández-Díaz, Cristina, Zamudio-Cuevas, Yessica, Fernández-Torres, Javier, López-Macay, Ambar, Alba-Sánchez, Ismael, Camacho-Galindo, Javier, Ventura, Lucio, Gómez-Quiróz, Luis E, Gutiérrez-Ruíz, María Concepción, García-Vázquez, Francisco, Reginato, Anthony M, Gutiérrez, Marwin, López-Reyes, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363186/
https://www.ncbi.nlm.nih.gov/pubmed/25889158
http://dx.doi.org/10.1186/s13075-015-0550-4
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author Pineda, Carlos
Fuentes-Gómez, Arturo J
Hernández-Díaz, Cristina
Zamudio-Cuevas, Yessica
Fernández-Torres, Javier
López-Macay, Ambar
Alba-Sánchez, Ismael
Camacho-Galindo, Javier
Ventura, Lucio
Gómez-Quiróz, Luis E
Gutiérrez-Ruíz, María Concepción
García-Vázquez, Francisco
Reginato, Anthony M
Gutiérrez, Marwin
López-Reyes, Alberto
author_facet Pineda, Carlos
Fuentes-Gómez, Arturo J
Hernández-Díaz, Cristina
Zamudio-Cuevas, Yessica
Fernández-Torres, Javier
López-Macay, Ambar
Alba-Sánchez, Ismael
Camacho-Galindo, Javier
Ventura, Lucio
Gómez-Quiróz, Luis E
Gutiérrez-Ruíz, María Concepción
García-Vázquez, Francisco
Reginato, Anthony M
Gutiérrez, Marwin
López-Reyes, Alberto
author_sort Pineda, Carlos
collection PubMed
description INTRODUCTION: Gout is an inflammatory condition induced by the deposition of monosodium urate (MSU) crystals in the joints and soft tissues that can produce acute or chronic arthritis. Several animal models of crystal-induced inflammation have been proposed that involve direct injection of MSU-crystals into different anatomical structures; however, only a few of these models reflect a true diarthrodial joint microenvironment in which an acute gouty attack takes place. The aim of this study was to assess the inflammatory and structural joint changes in a rabbit model of acute gout attack by ultrasound (US), synovial fluid (SF) and histopathological analyses. METHODS: Under US guidance, 42 rabbit knees were randomly injected with a suspension of 50 mg/ml of either MSU or allopurinol synthetic crystals. The control group received intra-articular vehicle of phosphate-buffered saline (PBS). US evaluation, SF and histopathological analyses were performed at days 1, 3, and 7. RESULTS: A total of 21 rabbit knees were assigned to the control group, 12 to the MSU-crystals group, and 9 to the allopurinol crystals group. By US, the MSU crystals group displayed the double contour sign and bright stippled aggregates in 67% and 75% of joints, respectively. Neither control knees nor allopurinol crystals group displayed these US signs. Power Doppler (PD) signal was moderate to intense in the MSU-crystals group and greater than both the allopurinol crystal and control groups at day 1 (P <0.001) and 3 (P <0.05), with its practical disappearance by day 7. SF leukocyte count was 40,312 ± 6,369 cells/mm(3) in the MSU-crystals group, higher than in controls (P = 0.004) and allopurinol crystal group (P = 0.006). At day 7, SF leukocyte count decreased in both MSU and allopurinol crystal groups reaching the non-inflammatory range. Histologically, at day 3 intense synovial polymorphonuclear cells infiltration and MSU aggregates were identified. CONCLUSION: The rabbit model of MSU crystal-induced acute arthritis efficiently reproduces the inflammatory, US, SF and histopathological changes of the human acute gouty attack. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-015-0550-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-43631862015-03-19 Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout Pineda, Carlos Fuentes-Gómez, Arturo J Hernández-Díaz, Cristina Zamudio-Cuevas, Yessica Fernández-Torres, Javier López-Macay, Ambar Alba-Sánchez, Ismael Camacho-Galindo, Javier Ventura, Lucio Gómez-Quiróz, Luis E Gutiérrez-Ruíz, María Concepción García-Vázquez, Francisco Reginato, Anthony M Gutiérrez, Marwin López-Reyes, Alberto Arthritis Res Ther Research Article INTRODUCTION: Gout is an inflammatory condition induced by the deposition of monosodium urate (MSU) crystals in the joints and soft tissues that can produce acute or chronic arthritis. Several animal models of crystal-induced inflammation have been proposed that involve direct injection of MSU-crystals into different anatomical structures; however, only a few of these models reflect a true diarthrodial joint microenvironment in which an acute gouty attack takes place. The aim of this study was to assess the inflammatory and structural joint changes in a rabbit model of acute gout attack by ultrasound (US), synovial fluid (SF) and histopathological analyses. METHODS: Under US guidance, 42 rabbit knees were randomly injected with a suspension of 50 mg/ml of either MSU or allopurinol synthetic crystals. The control group received intra-articular vehicle of phosphate-buffered saline (PBS). US evaluation, SF and histopathological analyses were performed at days 1, 3, and 7. RESULTS: A total of 21 rabbit knees were assigned to the control group, 12 to the MSU-crystals group, and 9 to the allopurinol crystals group. By US, the MSU crystals group displayed the double contour sign and bright stippled aggregates in 67% and 75% of joints, respectively. Neither control knees nor allopurinol crystals group displayed these US signs. Power Doppler (PD) signal was moderate to intense in the MSU-crystals group and greater than both the allopurinol crystal and control groups at day 1 (P <0.001) and 3 (P <0.05), with its practical disappearance by day 7. SF leukocyte count was 40,312 ± 6,369 cells/mm(3) in the MSU-crystals group, higher than in controls (P = 0.004) and allopurinol crystal group (P = 0.006). At day 7, SF leukocyte count decreased in both MSU and allopurinol crystal groups reaching the non-inflammatory range. Histologically, at day 3 intense synovial polymorphonuclear cells infiltration and MSU aggregates were identified. CONCLUSION: The rabbit model of MSU crystal-induced acute arthritis efficiently reproduces the inflammatory, US, SF and histopathological changes of the human acute gouty attack. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-015-0550-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-02-26 2015 /pmc/articles/PMC4363186/ /pubmed/25889158 http://dx.doi.org/10.1186/s13075-015-0550-4 Text en © Pineda et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Pineda, Carlos
Fuentes-Gómez, Arturo J
Hernández-Díaz, Cristina
Zamudio-Cuevas, Yessica
Fernández-Torres, Javier
López-Macay, Ambar
Alba-Sánchez, Ismael
Camacho-Galindo, Javier
Ventura, Lucio
Gómez-Quiróz, Luis E
Gutiérrez-Ruíz, María Concepción
García-Vázquez, Francisco
Reginato, Anthony M
Gutiérrez, Marwin
López-Reyes, Alberto
Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout
title Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout
title_full Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout
title_fullStr Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout
title_full_unstemmed Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout
title_short Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout
title_sort animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363186/
https://www.ncbi.nlm.nih.gov/pubmed/25889158
http://dx.doi.org/10.1186/s13075-015-0550-4
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