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- ItemAcesso aberto (Open Access)Estágio de desenvolvimento renal tem papel fundamental na fisiopatologia da uropatia obstrutiva(Universidade Federal de São Paulo (UNIFESP), 2017-10-25) Geminiani, Julio José [UNIFESP]; Ribeiro, Cassio Andreoni [UNIFESP]; http://lattes.cnpq.br/2915020488175752; http://lattes.cnpq.br/2801196536985579; Universidade Federal de São Paulo (UNIFESP)INTRODUCTION: Inflammation and fibrosis are widely accepted as the key processes driving the progression of obstruction-induced renal injuries to kidney disease in the mature kidney. However, it is likely that there are significant differences in the developing kidney, which have important implications for the treatment of congenital urinary tract obstruction. In this study, we provide the first direct comparison of injury responses during each of the critical stages of kidney development. METHODS: Disease progression was examined in a murine model of unilateral ureteral obstruction (UUO) at (1) P1, during nephrogenesis/nephron maturation and corresponding to the third trimester in humans, (2) P14, during the proliferative growth phase and corresponding to 1-2 years of infancy in humans, and (3) P60, in the mature kidney. Renal pathology was evaluated by performing immunostaining for molecular markers of key processes in the pathogenesis of renal injury and kidney development. The activation of pro-fibrotic signaling pathways and nephron differentiation programs was assessed by using quantitative PCR to monitor changes in gene expression. RESULTS: UUO at either P1 or P14 in the developing kidney leads to decreased kidney growth, reduced proliferative expansion of nephrons, increased apoptosis in progenitor cells, and impaired nephron differentiation. However, there is a notable absence of fibroblast and macrophage recruitment, inflammation, and fibrosis in the developing kidney following injury. This starkly contrasts the mature kidney where there are dramatic increases in proliferation, inflammation, and fibrosis following injury. In comparing these distinct outcomes at the molecular level, we found that injury responses in the developing kidney are characterized by the inhibition of nephron differentiation programs rather than the activation of pro-fibrotic signaling pathways (TGF-b, Renin-Angiotensin, WNT, PDGF) previously implicated as potential therapeutic targets by studies performed in the mature kidney. CONCLUSIONS: This study reveals that developmental context has a significant impact on the pathogenesis of renal injuries. In contrast to the mature kidney, injury in the developing kidney is characterized by profound developmental deficits and a distinct absence of inflammation and fibrosis. This suggests the treatment of patients with obstructive uropathies can be optimized by tailoring therapeutic strategies that are specific to the developmental context. More aggressive surgical intervention at early developmental stages may be necessary to prevent impaired renal maturation. Additionally, it may be beneficial to design adjuvant therapies to stimulate proliferation and minimize apoptosis at early stages of development while targeting inflammation and fibrosis at later stages of development.
- ItemAcesso aberto (Open Access)Tendências em experimentação animal(Sociedade Brasileira de Cirurgia Cardiovascular, 2009-12-01) Monteiro, Rosangela; Brandau, Ricardo; Gomes, Walter José [UNIFESP]; Braile, Domingo Marcolino; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); FAMERP; Universidade Estadual de Campinas (UNICAMP)INTRODUCTION: The search of the understanding of etiological factors, mechanisms and treatment of the diseases has been taking to the development of several animal models in the last decades. OBJECTIVE: To discuss aspects related to animal models of experimentation, animal choice and current trends in this field in our country. In addition, this study evaluated the frequency of experimental articles in medical journals. METHODS: Five Brazilian journals indexed by LILACS, SciELO, MEDLINE, and recently incorporate for Institute for Scientific Information Journal of Citation Reports were analyzed. All the papers published in those journals, between 2007 and 2008, that used animal models, were selected based on the abstracts. RESULTS: Of the total of 832 articles published in the period, 92 (11.1%) experimentation papers were selected. The number of experimental articles ranged from 5.2% to 17.9% of the global content of the journal. In the instructions to the authors, four (80%) journals presented explicit reference to the ethical principles in the conduction of studies with animals. The induced animal models represented 100% of the articles analyzed in this study. The rat was the most employed animal in the analyzed articles (78.3%). CONCLUSIONS: The present study can contribute, supplying subsidies for adoption of future editorials policies regarding the publication of animal research papers in Brazilian Journal of Cardiovascular Surgery.
- ItemAcesso aberto (Open Access)Treinamento em microcirurgia vascular: é economicamente viável?(Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia, 2002-05-01) Webster, Ronaldo; Ely, Pedro Bins [UNIFESP]; CHSCPA Sociedade Brasileira de Cirurgia Plástica SBCP; Universidade Federal de São Paulo (UNIFESP)The authors describe their experience at the Experimental Microsurgery Lab of the Plastic Surgery Service of Irmandade Santa Casa de Misericórdia de Porto Alegre Hospital -- Fundação Faculdade Federal de Ciências Médicas de Porto Alegre Medical School, highlighting initial low cost microsurgery training alternatives. They present the experimental results obtained.