Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.Univ Fed Sao Paulo, Disciplina Nefrol, Dept Med, Sao Paulo, SP, BrazilUniv Cruzeiro Sul, Programa Interdisciplinar Ciencias Saude, Inst Ciencias Atividade Fis & Esporte, Sao Paulo, SP, BrazilUniv Sao Paulo, LEMA, Escola Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Enfermagem Clin & Cirurg, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Nefrol, Dept Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Enfermagem Clin & Cirurg, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilWeb of Scienc

A radical freedom? Gianni Vattimo's ‘emancipatory nihilism’

What scope is there for emancipatory politics in light of the postmodern critique of philosophical foundations? This paper examines the response to this question by Italian philosopher, Gianni Vattimo, who for over two decades has defended the emancipatory prospects of what he terms ‘nihilism’. Vattimo conceives the retreat of metaphysics as a progressive weakening of ontological claims and an opening towards new and diverse modes of being. In his view, far from an exclusively tragic experience of loss or meaninglessness, nihilism is a steadily expanding narrative that invites us to face up to our own radical freedom. The paper sets out Vattimo's central arguments and contrasts the ethical thrust of his ‘emancipatory nihilism’ with the distinctly political take on emancipation presented by Ernesto Laclau. While the two converge on the withdrawal of metaphysics as the premise for a radical and democratic freedom, Vattimo's vision remains insufficiently focused on the dynamics of contestation that a generalized nihilism implies

A Educação Ambiental frente aos desafios apresentados pelos discursos contemporâneos sobre a natureza Environmental Education and the challenges presented by the contemporary discourses about nature

A noção de natureza tem tido papel importante na filosofia e também na Educação Ambiental. Filósofos contemporâneos como Gianni Vattimo e Newton Aquiles von Zuben afirmam que uma noção única de natureza contribuiu para a difusão da metafísica dogmática, que por sua vez, solidificou totalitarismos políticos e religiosos. A Educação Ambiental latino-americana tem constituído um campo teórico e espaço público privilegiado para a difusão de noções de natureza, não dogmáticas, nem totalitárias, em estreitas relações com a diversidade cultural e social. Num primeiro momento da Educação Ambiental a noção de natureza estava relacionada aos recursos naturais. Desde que temas específicos relacionados com os discursos contemporâneos sobre a natureza, como a biodiversidade e os transgênicos ganharam o espaço público, argumentamos que a Educação Ambiental se viu diante de novos desafios teóricos, políticos, ecológicos, sociais, culturais e pedagógicos. Neste artigo procuramos identificar e analisar alguns desses desafios tendo como apoio teórico o pensamento do filósofo italiano Gianni Vattimo e do filósofo brasileiro Newton Aquiles von Zuben, nos aspectos relacionados à bioética e ao papel político da educação, na formação de cidadãos e cidadãs. Concluímos que a abordagem dos discursos contemporâneos sobre a natureza possibilita que o diálogo entre a Educação Ambiental e a bioética tende a se ampliar e a se concretizar em práticas sociais e pedagógicas cotidianas, apresentando-se, assim, como alternativa concreta para que cidadãos e cidadãs possam enfrentar os desafios trazidos com a biodiversidade e com os transgênicos, com argumentos científicos, éticos e políticos.<br>The notion of nature has played an important role in philosophy and also in Environmental Education. Contemporary philosophers such as Gianni Vattimo and Newton Aquiles von Zuben declare that the notion of a single nature has contributed to the growth of a dogmatic metaphysics that has crystallized political and religious totalitarianisms. Environmental Education in Latin America has constituted a theoretical field and a privileged public space for the diffusion of non-dogmatic, non-totalitarian, notions of nature in close relationship to cultural and social diversity. At a first moment of Environmental Education the notion of nature was linked to natural resources. However, after specific themes related to the contemporary discourses about nature, such as transgenetics and biodiversity, have gained the public sphere we argue that Environmental Education has been facing new theoretical, political, ecological, social, cultural and pedagogical challenges. In the present article we try to identify and analyze some of these challenges, having as our theoretical foundation the ideas of Italian thinker Gianni Vattimo, and of Brazilian philosopher Newton Aquiles von Zuben, on the aspects related to bioethics and to the political role of education in the formation of citizens. We conclude that the approach to nature present in contemporary discourses helps to open out the dialogue between Environmental Education and bioethics, and to materialize it in daily social and pedagogical practices, thus representing a concrete alternative to allow citizens to face up to the challenges brought about by biodiversity and the transgenics with scientific, ethical and political arguments