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Molecular, cellular and pathophysiological mechanisms on acute renal failure

Grant number: 04/08311-6
Support type:Research Projects - Thematic Grants
Duration: December 01, 2004 - December 31, 2009
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Nestor Schor
Grantee:Nestor Schor
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Co-Principal Investigators:Alvaro Pacheco e Silva Filho ; Miguel Cendoroglo Neto
Associated grant(s):09/02492-2 - World Congress of nephrology 2009, AR.EXT
Associated scholarship(s):08/06219-6 - Evaluation of NF-kB intracellular signaling pathway and endostatin on human mesangial cell in endotoxic acute kidney injury during diabetes mellitus, BP.PD

Abstract

Despite impressive advances in the field of acute renal failure (ARF), mortality rates (about 50%) are still toa high. Maintenance of this figure in the past 4 decades is a consequence of different factors. Improvement in health care and medical progress allowed severely ill patients to be kept alive long enough to develop ARF. Mas, também, a manutenção desta elevada mortalidade é decorrente do incompleto conhecimento das etapas da cascata fisiopatológica desta doença, desde os fatores desencadeantes intracelulares, passando pelos aspectos de estabelecimento e manutenção até os fatores de correção biológica das alterações induzidas nas células renais.On the other hand, incomplete knowledge of the pathophysiology of ARF, from its origin at the cellular level to development and maintenance of the factors that participate in the resolution renal alterations, are responsible for this unsucefull outcome. Our laboratory has been developing studies in the field for more than 25 years, employing models of toxic or ischemic ARF and different research tools including but not limited to systemic and glomerular heamodynamics analysis, and cell and molecular biology. Thus, this thematic project. aims to study different stages of the pathophysiology of ARF, by means of gene and protein expression analysis, and evaluation of inflammatory and immunologic players in the scenario of toxic or ischemic aggression of renal cells. It also explores new models for ARF induction, as well as experimental protective strategies applicable to clinical practice. In addition, the relevance of experimental findings will be challenged in clinical studies that will concentrate on patients prone to develop ARF. This project was structured to cover different aspects of the pathophysiology of ARF, as a RESEARCH FIELD, with various strategies, aiming a global understanding and with the intention to identify new approaches to interfering with the development and maintenance of this disease. (AU)

Scientific publications (18)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CHRISTO, JOELMA SANTINA; RODRIGUES, ADELSON MARCAL; MOURO, MARGARET GORI; CENEDEZE, MARCOS ANTONIO; SIMOES, MANUEL DE JESUS; SCHOR, NESTOR; SUEMITSU HIGA, ELISA MIEKO. Nitric oxide (NO) is associated with gentamicin (GENTA) nephrotoxicity and the renal function recovery after suspension of GENTA treatment in rats. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 24, n. 2, p. 77-83, MAR 15 2011. Web of Science Citations: 27.
MEI WANG, PAMELLA HUEY; SCHWINDT, TELMA T.; BARNABE, GABRIELA FILOSO; MOTTA, FABIANA L. T.; SEMEDO, PATRICIA; BERALDO, FELIPE CAETANO; MAZZALI, MARILDA; DOS REIS, MARLENE ANTONIA; ANTUNES TEIXEIRA, VICENTE DE PAULA; PACHECO-SILVA, ALVARO; DE MELLO, LUIS EUGENIO A.; CAMARA, NIELS O. S. Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury. NEPHRON EXPERIMENTAL NEPHROLOGY, v. 112, n. 1, p. E20-E28, 2009. Web of Science Citations: 7.
NAKA‚ E.L.; PONCIANO‚ V.C.; CENEDEZE‚ M.A.; PACHECO-SILVA‚ A.; SARAIVA CÂMARA‚ N.O. Detection of the Tim-3 ligand‚ galectin-9‚ inside the allograft during a rejection episode. International Immunopharmacology, v. 9, n. 6, p. 658-662, 2009.
NOGUEIRA‚ E.; PONCIANO‚ V.C.; NAKA‚ É.L.; MARQUES‚ G.D.M.; CENEDEZE‚ M.A.; C{\=A}MARA‚ N.O.S.; PACHECO-SILVA‚ A. Toll-like receptors-related genes in kidney transplant patients with chronic allograft nephropathy and acute rejection. International Immunopharmacology, v. 9, n. 6, p. 673-676, 2009.
PONCIANO‚ V.C.; SOARES‚ M.F.; NAKA‚ É.L.; ARRUDA‚ É.F.; CENEDEZE‚ M.A.; FRANCO‚ M.F.; PACHECO-SILVA‚ A.; C{\=A}MARA‚ N.O.S. Urinary CD20 mRNA as a surrogate of CD20-positive cells infiltration during allograft dysfunction in renal transplant patients. International Immunopharmacology, v. 9, n. 6, p. 663-667, 2009.
WANG‚ P.H.M.; CENEDEZE‚ M.A.; CAMPANHOLLE‚ G.; MALHEIROS‚ D.M.A.C.; DE MOURA TORRES‚ H.A.; PESQUERO‚ J.B.; PACHECO-SILVA‚ A.; C{\=A}MARA‚ N.O.S. Deletion of bradykinin B1 receptor reduces renal fibrosis. International Immunopharmacology, v. 9, n. 6, p. 653-657, 2009.
FERNANDES BERTOCCHI, ANA PAULA; CAMPANHOLE, GABRIELA; MEI WANG, PAMELLA HUEY; GONCALVES, GISELLE MARTINS; DAMIAO, MARCIO JOSE; CENEDEZE, MARCOS ANTONIO; BERALDO, FELIPE CAETANO; ANTUNES TEIXEIRA, VICENTE DE PAULA; DOS REIS, MARLENE ANTONIA; MAZZALI, MARILDA; PACHECO-SILVA, ALVARO; SARAIVA CAMARA, NIELS OLSEN. A Role for galectin-3 in renal tissue damage triggered by ischemia and reperfusion injury. Transplant International, v. 21, n. 10, p. 999-1007, OCT 2008. Web of Science Citations: 43.
MACIEL, THIAGO T.; COUTINHO, ENIA L.; SOARES, DEBORA; ACHAR, EDUARDO; SCHOR, NESTOR; BELLINI, MARIA H. Endostatin, an antiangiogenic protein, is expressed in the unilateral ureteral obstruction mice model. JOURNAL OF NEPHROLOGY, v. 21, n. 5, p. 753-760, SEP-OCT 2008. Web of Science Citations: 15.
WANG, PAMELLA H. M.; CAMPANHOLLE, GABRIELA; CENEDEZE, MARCOS A.; FEITOZA, CARLA Q.; GONCALVES, GISELLE M.; LANDGRAF, RICHARDT G.; JANCAR, SONIA; PESQUERO, JOAO B.; PACHECO-SILVA, ALVARO; CAMARA, NIELS O. S. Brabykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury. PLoS One, v. 3, n. 8, p. e3050, 2008. Web of Science Citations: 23.
H.S. PINHEIRO; N.O.S. CAMARA; I.L. NORONHA; I.L. MAUGERI; M.F. FRANCO; J.O.A.P. MEDINA; A. PACHECO-SILVA. Contribution of CD4+ T cells to the early mechanisms of ischemia- reperfusion injury in a mouse model of acute renal failure. Brazilian Journal of Medical and Biological Research, v. 40, n. 4, p. 557-568, Abr. 2007.
PONCIANO‚ V.C.; RENESTO‚ P.G.; NOGUEIRA‚ E.; RANGEL‚ É.B.; CENEDEZE‚ M.A.; FRANCO‚ M.F.; CÂMARA‚ N.O.S.; PACHECO-SILVA‚ A. Tim-3 expression in human kidney allografts. TRANSPLANT IMMUNOLOGY, v. 17, n. 3, p. 215-222, 2007.
GONÇALVES‚ G.M.; CENEDEZE‚ M.A.; FEITOZA‚ C.Q.; BATISTA DE PAULA‚ C.; MACUSSO‚ G.D.; PINHEIRO‚ H.S.; TEIXEIRA‚ V.P.A.; DOS REIS‚ M.A.; PACHECO-SILVA‚ A.; CÂMARA‚ N.O.S. Heme oxygenase 1 and renal ischemia and reperfusion injury: The impact of immunosuppressive drug. International Immunopharmacology, v. 6, n. 13, p. 1966-1972, 2006.
M.A. GLORIA; M.A. CENEDEZE; A. PACHECO-SILVA; N.O.S. CÂMARA. The blockade of cyclooxygenases-1 and -2 reduces the effects of hypoxia on endothelial cells. Brazilian Journal of Medical and Biological Research, v. 39, n. 9, p. 1189-1196, Set. 2006.
MARQUES‚ V.P.; GONÇALVES‚ G.M.; FEITOZA‚ C.Q.; CENEDEZE‚ M.A.; FERNANDES BERTOCCHI‚ A.P.; DAMIAO‚ M.J.; PINHEIRO‚ H.S.; ANTUNES TEIXEIRA‚ V.P.; DOS REIS‚ M.A.; PACHECO-SILVA‚ A.; OTHERS. Influence of TH1/TH2 switched immune response on renal ischemia-reperfusion injury. NEPHRON EXPERIMENTAL NEPHROLOGY, v. 104, n. 1, p. e48-e56, 2006.
NOGUEIRA‚ E.; OZAKI‚ K.S.; TOMIYAMA‚ H.; GRANATO‚ C.F.H.; CAMARA‚ N.O.S.; OTHERS. The emergence of cytomegalovirus resistance to ganciclovir therapy in kidney transplant recipients. International Immunopharmacology, v. 6, n. 13, p. 2031-2037, 2006.
PEREIRA‚ M.G.; CÂMARA‚ N.O.S.; CAMPAHOLLE‚ G.; CENEDEZE‚ M.A.; DE PAULA ANTUNES TEIXEIRA‚ V.; DOS REIS‚ M.A.; PACHECO-SILVA‚ A. Pioglitazone limits cyclosporine nephrotoxicity in rats. International Immunopharmacology, v. 6, n. 13, p. 1943-1951, 2006.
R. CHINEN; N.O.S. CÂMARA; S. NISHIDA; M.S. SILVA; D.A. RODRIGUES; A.B. PEREIRA; A. PACHECO-SILVA. Determination of renal function in long-term heart transplant patients by measurement of urinary retinol-binding protein levels. Brazilian Journal of Medical and Biological Research, v. 39, n. 10, p. 1305-1313, Out. 2006.
WANG‚ P.H.M.; CENEDEZE‚ M.A.; PESQUERO‚ J.B.; PACHECO-SILVA‚ A.; CÂMARA‚ N.O.S. Influence of bradykinin B1 and B2 receptors in the immune response triggered by renal ischemia-reperfusion injury. International Immunopharmacology, v. 6, n. 13, p. 1960-1965, 2006.

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