IRINEU TADEU VELASCO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Phagocytic activity of LPS tolerant macrophages(2014) LIMA, Thais Martins de; SAMPAIO, Sandra Coccuzzo; PETRONI, Ricardo; BRIGATTE, Patricia; VELASCO, Irineu Tadeu; SORIANO, Francisco GarciaEndotoxin tolerance is defined as a reduced capacity of the host to respond to LPS activation following a first exposure to this stimulus. It affects all leukocytes and regarding macrophages, most studies focus on the reduced ability of these cells to secrete pro-inflammatory cytokines. Therefore, we evaluated other macrophages functions (fungicidal capacity, reactive oxygen species production and antigen presentation) in cells from tolerant mice. We have performed a tolerance model in our laboratory that does not stimulate directly the place from where the cells will be removed (peritoneal cavity). Mouse received subcutaneous injections of LPS in the scruff for 5 days and we analyze the capacity of peritoneal macrophages to phagocyte using three different receptors: Fc, C3b and mannose receptors. We found a reduction in the phagocytosis of erythrocytes and Candida albicans related to the Fc and mannose receptors. These differences can be due to a macrophage reprogramming, as demonstrated by altered expression of cytokines and chemokines. Despite this reduction in phagocytosis capacity, macrophages from tolerant animals exhibited enhanced hydrogen peroxide production and expression of antigen presentation molecules, suggesting that their ability to combat an infection is improved. In summary, our data indicates that LPS tolerance drives macrophages from a predominant release of proinflammatory mediators that amplify inflammation and host damage toward a better killing and antigen presentation state.
conferenceObject Identification of E. coli mimetics proteins that can inhibit phagocytosis mechanisms(2014) BEPPLER, J.; GIORDANO, R.; MONTEIRO, R.; VELASCO, I. T.; SILVA, F. Pinheiro da- PGC-1 alpha Expression Is Increased in Leukocytes in Experimental Acute Pancreatitis(2014) LLIMONA, Flavia; LIMA, Thais Martins de; MORETTI, Ana Iochabel; THEOBALDO, Mariana; JUKEMURA, Jose; VELASCO, Irineu Tadeu; MACHADO, Marcel C. C.; SOUZA, Heraldo PossoloSevere acute pancreatitis (AP) induces a systemic inflammatory disease that is responsible for high mortality rates, particularly when it is complicated by infection. Therefore, differentiating sepsis from the systemic inflammation caused by AP is a serious clinical challenge. Considering the high metabolic rates of leukocytes in response to stress induced by infection, we hypothesized that the transcription coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1 alpha), a master regulator of mitochondrial biogenesis and function, would be distinctly expressed during inflammation or infection and, therefore, could constitute a useful marker to differentiate between these two conditions. Rats were subjected to injection of taurocholate into the main pancreatic duct, which caused a severe AP with high amylase levels and white blood cell counts. In these animals, a marked increase in PGC-1 alpha mRNA levels in circulating leukocytes was observed 48 h after the surgical procedure, a time when bacteremia is present. Antibiotic treatment abolished PGC-1 alpha up-regulation. Moreover, PGC-1 alpha expression was higher in peritoneal macrophages from animals subjected to a bacterial insult (cecal ligation and puncture) than in animals with AP. In isolated macrophages, we also observed that PGC-1 alpha expression is more prominent in the presence of a phagocytic stimulus (zymosan) when compared to lipopolysaccharide-induced aseptic inflammation. Moreover, abolishing PGC-1 alpha expression with antisense oligos impaired zymosan phagocytosis. Together, these findings suggest that PGC-1 alpha is differentially expressed during aseptic inflammation and infection and that it is necessary for adequate phagocytosis. These results could be useful in developing new tests for differentiating infection from inflammation for clinical purposes in patients with AP.
- Neuropeptide Downregulation in Sepsis(2014) SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira Cesar; SALLET, Paulo Clemente; ZAMPIERI, Fernando Godinho; GOULART, Alessandra Carvalho; TORGGLER FILHO, Francisco; BARBEIRO, Hermes Vieira; VELASCO, Irineu Tadeu; CRUZ NETO, Luiz Monteiro da; SOUZA, Heraldo Possolo deNeuropeptides are an extremely conserved arm of neurobiology. Despite their effects as neurohormones and neurotransmitters, a multitude of other effects have been described, putting in evidence their importance as regulators of immune responses, such as chemotaxis, oxidative burst, pro-inflammatory signaling, and many others. The effects of neuropeptides in the pathophysiology of sepsis, however, remain poorly investigated. A prospective cohort study to investigate the effects of neuropeptides in sepsis was carried out. Here, we describe that neuropeptides are downregulated during septic shock. We propose that it may be a protective mechanism of the host to avoid further inflammatory injury.
conferenceObject Lipid structures as biomarkers in septic shock: a new road to travel(2014) SILVA, F. Pinheiro Da; CATALDI, T.; LIMA, T. M. de; STARZYNSKI, P. N.; BARBEIRO, H. V.; LABATE, M. V.; MACHADO, M. C. C.; VELASCO, I. T.; SOUZA, H. P. de; LABATE, C. A.- O impacto das soluções hipertônica e salina fisiológica na reperfusão do trato gastrintestinal pós-isquemia em ratos(2014) CHIMABUCURO, Wilson Kohama; SILVA JUNIOR, Bomfim Alves da; MORETTI, Ana Iochabel Soares; VELASCO, Irineu Tadeu; RIOS, Ester Correia Sarmento; SORIANO, Francisco GarciaObjetivo: Investigar o papel de duas diferentes soluções salinas nos mecanismos de lesão após isquemia intestinal: estresse oxidativo e respostas inflamatórias. Métodos: Ratos Wistar foram submetidos a oclusão transitória da artéria mesentérica superior e estudados durante as 6 horas seguintes à reperfusão. Após randomização, os animais foram divididos em quatro grupos: Falso; Solução Hipertônica, os quais receberam infusão de solução salina hipertônica a 7,5% (4mL/kg de peso corpóreo); Solução Fisiológica, os quais receberam infusão de solução salina a 0,9% (33mL/kg); e Sem Tratamento. A infusão foi realizada imediatamente antes da reperfusão. Foram realizadas dosagens sequenciais de interleucina 6 e interleucina 10 no plasma. Foram coletadas amostras de tecidos (pulmão, fígado e intestino) para medir malondialdeído, mieloperoxidase e interleucina. Resultados: Em comparação ao Grupo Sem Tratamento, os animais que receberam volume (Grupos Solução Hipertônica e Solução Fisiológica) mostraram níveis tissulares mais baixos de malondialdeído, mieloperoxidase, interleucina 6 e interleucina 10. As concentrações plasmáticas de interleucina 6 e interleucina 10 foram mais altas nos animais tratados com solução hipertônica do que nos tratados com solução fisiológica e nos sem tratamento. Conclusão: Neste modelo de isquemia intestinal transitória, a manutenção adequada de volume intravascular diminuiu o estresse oxidativo e a síntese de marcadores de inflamação. Tanto a solução hipertônica quanto a fisiológica atenuaram os efeitos deletérios observados após isquemia intestinal.
conferenceObject Increased Bacterial Translocation in Aging Animals Is Not Related to Decreased Intestinal Antimicrobial Peptide Expression in Acute Pancreatitis(2014) CUNHA, Debora G.; SILVA, Fabiano Pinheiro da; BARBEIRO, Denise F.; KOIKE, Marcia K.; MACHADO, Marcel C.; VELASCO, Irineu T.- ENDOTOXIN TOLERANCE DRIVES NEUTROPHIL TO INFECTIOUS SITE(2014) ARIGA, Suely Kubo; ABATEPAULO, Fatima Bernardes; MELO, Edielle Sant Anna; VELASCO, Irineu Tadeu; SILVA, Fabiano Pinheiro da; LIMA, Thais Martins de; SORIANO, Francisco GarciaThe objective of this randomized animal study and laboratory investigation was to investigate whether lipopolysaccharide tolerance redirects neutrophil migration between organs. Male BALB/c mice received subcutaneous injections of lipopolysaccharide (1 mg/kg) for 5 days, followed by cecal ligation and puncture (CLP). Cytokines and adhesion molecules were measured after tolerance and CLP challenge. Increased numbers of neutrophils were observed in the peritoneal cavity of tolerant mice, which was associated with increased levels of adhesion molecules and chemokines. In contrast, nontolerant mice accumulated higher numbers of neutrophils in the lungs compared with those in the peritoneal cavity. Neutrophil function accessed by hydrogen peroxide production from neutrophils recovered from peritoneal cavity showed that tolerance increased the capacity to produce hydrogen peroxide. Mortality was reduced in tolerant animals. This study demonstrated that tolerance reduces leukocyte accumulation in the lung after CLP by redirecting neutrophils to the site of infection.