Nonerosive reflux disease (NERD) is a highly prevalent phenotype of the gastroesophageal reflux disease. In this study, we developed a novel murine model of NERD in mice with microscopic inflammation and impairment in the epithelial esophageal barrier. Female Swiss mice were subjected to the following surgical procedure: the transitional region between the forestomach and the glandular portion of the stomach was ligated, and a nontoxic ring was placed around the duodenum near the pylorus. The control group underwent sham surgery. The animals were euthanized at 1, 3, 7, and 14 days after surgery. Survival and body weight were monitored daily. Esophageal wet weight, macroscopic lesion, histopathological alterations, myeloperoxidase (MPO) activity, cytokine levels, transepithelial electrical resistance (TEER), and mucosal permeability were evaluated. The survival rate was 78% at 14 days, with mild loss in body weight. Surgery did not induce erosive esophagitis but instead induced microscopic inflammation and increased esophageal wet weight, IL-6, keratinocyte-derived cytokine (KC) levels, and MPO activity with maximal peak between 3 and 7 days and resolution at 14 days postsurgery. Epithelial esophageal barrier was evaluated in operated mice at 7 and 14 days postsurgery; a decrease in TEER and increase in the esophageal epithelial permeability were observed compared with the sham-operated group. In addition, the inhibition of acid secretion with omeprazole significantly prevented the esophageal inflammation and impairment of barrier function at 7 days postsurgery. Thus we established a novel experimental model of NERD in mice, which can contribute to understanding the pathophysiological events associated with NERD. In this study, we standardized an experimental model of nonerosive reflux disease (NERD) in mice. This model involves an acute inflammatory response followed by impaired esophageal mucosal integrity, even in the absence of inflammation. Thus this model can serve for evaluation of pathophysiological aspects of NERD and open new perspectives for therapeutic strategies for patients with this disorder.
The TRPV1 receptor has a critical role in esophageal inflammation and mucosal barrier impairment in NERD mice, suggesting that TRPV1 might be a pharmacological target in patients with NERD.
ResumoA periostite reativa florida é uma lesão benigna e rara que constitui um problema recorrente de diagnóstico. Sua etiopatogênese permanece desconhecida. A periostite reativa florida caracteriza-se por ser uma reação periosteal agressiva e inflamatória de tecido mole e por ser um tumor portador de fibrose e produtor de cartilagem. Ocorre em adolescentes e adultos jovens, com predomínio no sexo feminino, e acomete com frequência os ossos das mãos e pés, podendo acometer também ossos longos. O diagnóstico permanece um grande desafio devido à enorme possibilidade de diagnósticos diferenciais. Por isso, uma cuidadosa avaliação clínica, radiológica e patológica é necessária para fechar o diagnóstico. Relata-se o caso de um paciente com periostite reativa florida na falange proximal do segundo dedo da mão direita, que foi submetida à excisão cirúrgica com margem ampla do segundo raio até o terço proximal do segundo metacarpo, e evoluiu sem queixas, com amplitude de movimento e força satisfatória.
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