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Neuroendocrine mechanisms of the regulation of the hypothalamic-pituitary-adrenal axis in clinical and experimental models of resistance to glycocorticoids and sepsis

Grant number: 03/09857-0
Support type:PRONEX Research - Thematic Grants
Duration: July 01, 2004 - March 31, 2008
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: CNPq - Pronex
Principal Investigator:Ayrton Custodio Moreira
Grantee:Ayrton Custodio Moreira
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Acute inflammatory and infectious processes induce the activation of the immune system and the hypothalamic-pituitary-adrenal axis (HPA), developing fever and alterations in feeding behavior and ingestion of liquids. Sensitivity to glycocorticoids (GC) will be studied in normal individuals, patients with nephrotic idiopathic syndrome and renal transplants, using in vitro study of the inhibition of the proliferation of lymphocytes by dexametasone, bonding test of the GCs to their receptor (GR) and quantification of the expression of the mRNAs of the gene by PCR in real time. We will also investigate in these individuals the presence of polymorphisms in the gene of the GR (subproject 1.1, 1.2, 1.3). We will use administration of LPS to ascertain the participation of different neuromodulators in the neuroendocrine mechanisms in response to infection (subproject 2 and 3). We will evaluate the role of the nitrergic system in the tolerance to LPS in iNOS-KO mice (sub-project 4) and the interaction of the HPA axis and the central melanocortin system in response to the LPS (subproject 5). (AU)

Scientific publications
(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)
DE LUCA, JR., LAURIVAL A.; ALMEIDA, ROBERTO L.; DAVID, RICHARD B.; DE PAULA, PATRICIA M.; ANDRADE, CARINA A. F.; MENANI, JOSE V. Participation of alpha(2)-adrenoceptors in sodium appetite inhibition during sickness behaviour following administration of lipopolysaccharide. JOURNAL OF PHYSIOLOGY-LONDON, v. 594, n. 6, p. 1607-1616, MAR 15 2016. Web of Science Citations: 0.
CHRIGUER, ROSANGELA SOARES; ROSELINO, ANA MARIA; DE CASTRO, MARGARET. Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus. JOURNAL OF CLINICAL IMMUNOLOGY, v. 32, n. 4, p. 786-793, AUG 2012. Web of Science Citations: 12.
DE ANTONIO‚ S.R.; SABER‚ L.T.S.; CHRIGUER‚ R.S.; DE CASTRO‚ M. Glucocorticoid resistance in dialysis patients may impair the kidney allograft outcome. Nephrology Dialysis Transplantation, v. 23, n. 4, p. 1422-1428, 2008.

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