Exercise and Caloric Restriction Alter the Immune System of Mice Submitted to a High-Fat Diet

As the size of adipocytes increases during obesity, the establishment of resident immune cells in adipose tissue becomes an important source of proinflammatory mediators. Exercise and caloric restriction are two important, nonpharmacological tools against body mass increase. To date, their effects on the immune cells of adipose tissue in obese organisms, specifically when a high-fat diet is consumed, have been poorly investigated. Thus, after consuming a high-fat diet, mice were submitted to chronic swimming training or a 30% caloric restriction in order to investigate the effects of both interventions on resident immune cells in adipose tissue. These strategies were able to reduce body mass and resulted in changes in the number of resident immune cells in the adipose tissue and levels of cytokines/chemokines in serum. While exercise increased the number of NK cells in adipose tissue and serum levels of IL-6 and RANTES, caloric restriction increased the CD4+/CD8+ cell ratio and MCP-1 levels. Together, these data demonstrated that exercise and caloric restriction modulate resident immune cells in adipose tissues differently in spite of an equivalent body weight reduction. Additionally, the results also reinforce the idea that a combination of both strategies is better than either individually for combating obesity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniv São Paulo, Sch Arts Sci & Humanities, BR-03828000 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Lab Transplantat Immunobiol, Dept Immunol, BR-05508900 São Paulo, BrazilUniv Fed Pelotas, Sch Nutr, Dept Nutr, BR-96010610 Pelotas, RS, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilFAPESP: 2011/03528-0Web of Scienc

Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation

The antineoplastic drug cisplatin promotes renal injury, which limits its use. Protocols that reduce renal cisplatin toxicity will allow higher doses to be used in cisplatin treatment. Here, we compare physical exercise and caloric restriction (CR) as protocols to reduce cisplatin renal injury in mice. Male C57BL/6 were divided into four groups: Control, cisplatin, exercise + cisplatin, and 30% CR + cisplatin. Animals were injected with a single dose of cisplatin (20 mg/kg i.p.) and sacrificed 96 h after injection. Quantitative real time PCR, histological analyses, immunohistochemistry, and biochemical measurements were performed to investigate renal injury, necrosis, apoptosis, and inflammatory mechanisms. Both protocols protected against cisplatin renal injury, but CR was more effective in reducing uraemia and renal necrosis. The CR + Cisplatin group exhibited reduced serum IL-1 beta and INF-alpha levels. No differences were noted in the renal mRNA expression of cytokines. Both interventions reduced apoptosis, but only the CR + Cisplatin group decreased TNFR2 protein expression. PPAR-ci was activated in mice after CR. An antagonist of PPAR-alpha blocked the protective effect of CR. Both interventions attenuated the nephrotoxicity caused by cisplatin injection, but CR + Cisplatin showed a better response by modulating TNFR2. Moreover, part of the CR benefit depends on PPAR-alpha activation.FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)CAPES/DAADUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Med, Disciplina Nefrol, Sao Paulo, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Immunol, Sao Paulo, BrazilUniv Sao Paulo, Dept Clin Med, Sao Paulo, BrazilUniv Fed Pelotas, Escola Nutr, Dept Nutr, Pelotas, BrazilMax Delbruck Ctr Mol Med, Berlin, GermanyUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Med, Disciplina Nefrol, Sao Paulo, BrazilFAPESP: 2013/06207-6FAPESP: 2015/20082-7CAPES/DAAD: 427/15Web of Scienc

Kinin B-2 receptor deletion and blockage ameliorates cisplatin-induced acute renal injury

Cisplatin treatment has been adopted in some chemotherapies; however, this drug can induce acute kidney injury due its ability to negatively affect renal function, augment serum levels of creatinine and urea, increase the acute tubular necrosis score and up-regulate cytokines (e.g., IL-1 beta and TNF-alpha). the kinin B2 receptor has been associated with the inflammation process, as well as the regulation of cytokine expression, and its deletion resulted in an improvement in the diabetic nephropathy status. To examine the role of the kinin B2 receptor in cisplatin-induced acute kidney injury, kinin B2 receptor knockout mice were challenged with cisplatin. Additionally, WT mice were treated with a B2 receptor antagonist after cisplatin administration. B2 receptor-deficient mice were less sensitive to this drug than the WT mice, as shown by reduced weight loss, better preservation of kidney function, down regulation of inflammatory cytokines and less acute tubular necrosis. Moreover, treatment with the kinin B2 receptor antagonist effectively reduced the levels of serum creatinine and blood urea after cisplatin administration. Thus, our data suggest that the kinin B2 receptor is involved in cisplatin-induced acute kidney injury by mediating the necrotic process and the expression of inflammatory cytokines, thus resulting in declined renal function.These results highlight the kinin B2 receptor antagonist treatment in amelioration of nephrotoxicity induced by cisplatin therapy. (C) 2014 Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Biophys, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, BR-04023900 São Paulo, BrazilUniv São Paulo, Sch Arts Sci & Humanities, BR-03828000 São Paulo, BrazilUniv São Paulo, Dept Clin Med, BR-05403000 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Immunol, Lab Transplantat Immunobiol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, BR-04023900 São Paulo, BrazilFAPESP: 2011/03528-0Web of Scienc

Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by modulating immune cell migration

Cisplatin is a chemotherapeutic agent that causes severe renal dysfunction. the kinin B1 receptor has been associated with the migration of immune cells to injured tissue as well as with renal inflammation. To examine the role of the kinin B1 receptor in cisplatin-induced acute kidney injury, we used kinin B1 receptor knockout mice and treatment with a receptor antagonist before and after cisplatin administration. Cisplatin injection caused exacerbation of renal macrophage and neutrophil migration, higher levels of serum creatinine and blood urea, upregulation of B1 receptor mRNA and an increase in pro-inflammatory cytokines expression. B1 receptor knockout mice exhibited a reduction in serum creatinine and blood urea levels, diminished apoptosis, and decreased cisplatin-induced upregulation of inflammatory components. Moreover, treatment with the B1 receptor antagonist prior to cisplatin administration normalized serum creatinine, blood urea levels, protected from acute tubular necrosis, apoptosis-related genes, and prevented upregulation of pro-inflammatory cytokines. Thus, we propose that kinins have an important role in cisplatin-induced acute kidney injury by impairing immune cells migration to renal tissue during cisplatin nephrotoxicity. Kinin B1 receptor is upregulated after cisplatin exposure.Kinin B1 receptor deficiency diminishes the nephrotoxicity caused by cisplatin.Kinin B1 receptor deficiency ameliorates the inflammatory response.Kinin B1 receptor deficiency diminishes apoptosis caused by cisplatin.Kinin B1 receptor antagonism ameliorates renal function after cisplatin injection.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Dept Med, BR-04023062 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 São Paulo, BrazilUniv São Paulo, Dept Clin Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nutr, Escola Nutr, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Dept Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nutr, Escola Nutr, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilFAPESP: 2011/03528-0Web of Scienc

Estudios curriculares: desafíos teóricos y metodológicos

Com fronteiras disciplinares muito permeáveis, os estudos curriculares têm enfrentado alguns desafios teóricos e metodológicos. Argumento, neste artigo, que a construção complexa da identidade e a análise de diversas abordagens, por vezes, contraditórias, dos estudos curriculares são desafios que necessitam de ser debatidos criticamente. Inclui-se, ainda, uma breve referência às tradições curriculares e aos desafios metodológicos centrados na pesquisa curricular, em Portugal. A leitura deste artigo torna-se, assim, fundamental para alunos de cursos de graduação e pós-graduação, bem como para professores e educadores ligados quer às questões da educação e formação, em geral, quer às questões do currículo, que inclui também uma referência à didática e à pedagogia.With strong permeable disciplinary boundaries, the curriculum studies have addressed some theoretical and methodological challenges. In this article, I argument that the complex construction of curriculum studies’ identity and the analysis of different approaches, occasionally contradictory, are challenges that need to be critically analyzed. The article also includes a brief review of the curriculum studies’ traditions in Portugal and a particular approach about methodological challenges. Therefore, reading this article is crucial for undergraduate and postgraduate students as well as teachers and educators related either to the issues of education and training in general, and to the issues of curriculum, which includes also a reference to teaching and pedagogy.Con las fronteras disciplinares muy permeables, los estudios curriculares han enfrentado algunos desafíos teóricos y metodológicos. En este artículo se argumenta que la construcción de la identidad y el análisis de diversos abordajes, a veces contradictorios, sobre los estudios curriculares son desafíos que necesitan discutirse críticamente. Se incluye una breve referencia a las tradiciones curriculares y a los desafíos metodológicos centrados en la investigación curricular, en Portugal. La lectura de este artículo adquiere gran importancia para los estudiantes de pregrado y posgrado, así como para profesores y educadores vinculados tanto a las cuestiones de la educación y la formación en general, como a los temas del plan de estudios, lo que incluye una referencia a la didáctica y la pedagogía.(undefined

Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by modulating immune cell migration

Cisplatin is a chemotherapeutic agent that causes severe renal dysfunction. the kinin B1 receptor has been associated with the migration of immune cells to injured tissue as well as with renal inflammation. To examine the role of the kinin B1 receptor in cisplatin-induced acute kidney injury, we used kinin B1 receptor knockout mice and treatment with a receptor antagonist before and after cisplatin administration. Cisplatin injection caused exacerbation of renal macrophage and neutrophil migration, higher levels of serum creatinine and blood urea, upregulation of B1 receptor mRNA and an increase in pro-inflammatory cytokines expression. B1 receptor knockout mice exhibited a reduction in serum creatinine and blood urea levels, diminished apoptosis, and decreased cisplatin-induced upregulation of inflammatory components. Moreover, treatment with the B1 receptor antagonist prior to cisplatin administration normalized serum creatinine, blood urea levels, protected from acute tubular necrosis, apoptosis-related genes, and prevented upregulation of pro-inflammatory cytokines. Thus, we propose that kinins have an important role in cisplatin-induced acute kidney injury by impairing immune cells migration to renal tissue during cisplatin nephrotoxicity. Kinin B1 receptor is upregulated after cisplatin exposure.Kinin B1 receptor deficiency diminishes the nephrotoxicity caused by cisplatin.Kinin B1 receptor deficiency ameliorates the inflammatory response.Kinin B1 receptor deficiency diminishes apoptosis caused by cisplatin.Kinin B1 receptor antagonism ameliorates renal function after cisplatin injection.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Dept Med, BR-04023062 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 São Paulo, BrazilUniv São Paulo, Dept Clin Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nutr, Escola Nutr, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Dept Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nutr, Escola Nutr, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilFAPESP: 2011/03528-0Web of Scienc