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
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Septic shock in older people: a prospective cohort study(2013) SILVA, Fabiano Pinheiro da; ZAMPIERI, Fernando Godinho; BARBEIRO, Denise Frediani; BARBEIRO, Hermes Vieira; GOULART, Alessandra Carvalho; TORGGLER FILHO, Francisco; VELASCO, Irineu Tadeu; CRUZ NETO, Luiz Monteiro da; SOUZA, Heraldo Possolo de; MACHADO, Marcel Cerqueira CesarBackground: Septic shock is the first cause of death in Intensive Care Units. Despite experimental data showing increased inflammatory response of aged animals following infection, the current accepted hypothesis claims that aged patients are immunocompromised, when compared to young individuals. Results: Here, we describe a prospective cohort study designed to analyze the immune profile of this population. Conclusion: Older people are as immunocompetent as the young individual, regarding the cytokines, chemokines and growth factors response to devastating infection.
- Septic Shock in Advanced Age: Transcriptome Analysis Reveals Altered Molecular Signatures in Neutrophil Granulocytes(2015) PELLEGRINA, Diogo Vieira da Silva; SEVERINO, Patricia; BARBEIRO, Hermes Vieira; ANDREGHETTO, Flavia Maziero; VELASCO, Irineu Tadeu; SOUZA, Heraldo Possolo de; MACHADO, Marcel Cerqueira Cesar; REIS, Eduardo Moraes; SILVA, Fabiano Pinheiro daSepsis is one of the highest causes of mortality in hospitalized people and a common complication in both surgical and clinical patients admitted to hospital for non-infectious reasons. Sepsis is especially common in older people and its incidence is likely to increase substantially as a population ages. Despite its increased prevalence and mortality in older people, immune responses in the elderly during septic shock appear similar to that in younger patients. The purpose of this study was to conduct a genome-wide gene expression analysis of circulating neutrophils from old and young septic patients to better understand how aged individuals respond to severe infectious insult. We detected several genes whose expression could be used to differentiate immune responses of the elderly from those of young people, including genes related to oxidative phosphorylation, mitochondrial dysfunction and TGF-a signaling, among others. Our results identify major molecular pathways that are particularly affected in the elderly during sepsis, which might have a pivotal role in worsening clinical outcomes compared with young people with sepsis.
- Cathelicidin LL-37 bloodstream surveillance is down regulated during septic shock(2013) BARBEIRO, Denise Frediani; BARBEIRO, Hermes Vieira; ZAMPIERI, Fernando Godinho; MACHADO, Marcel Cerqueira Cesar; TORGGLER FILHO, Francisco; CUNHA, Debora Maria Gomes; GOULART, Alessandra Carvalho; VELASCO, Irineu Tadeu; CRUZ NETO, Luiz Monteiro da; SOUZA, Heraldo Possolo de; SILVA, Fabiano Pinheiro daHost defense peptides are ancient weapons of the innate immunity. The human cathelicidin LL-37 protects the epithelial barrier against infection and is constitutively secreted in the bloodstream by immune cells. Current knowledge claims that LL-37 is up regulated upon infection. LL-37 can protect against bacterial infections and possesses many immunomodulatory properties. Here, we show that the human host defense peptide LL-37 is down regulated during septic shock. Furthermore, we show that these effects are not related to vitamin D serum levels, a potent inducer of LL-37 gene expression, pointing out the complex regulation of cathelicidins during septic shock.
- 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.
- Neutrophils LL-37 migrate to the nucleus during overwhelming infection(2013) SILVA, Fabiano Pinheiro da; MEDEIROS, Maria Cristina Rodrigues; SANTOS, Angela Batista Gomes dos; FERREIRA, Marcelo Alves; GARIPPO, Ana Lucia; CHAMMAS, Roger; CALDINI, Elia; VELASCO, Irineu Tadeu; SOUZA, Heraldo Possolo de; MACHADO, Marcel Cerqueira CesarLL-37 is the only cathelicidin produced by human cells. It is secreted by a variety of cell types, including monocyte/macrophages, neutrophils, mast cells, keratinocytes and epithelial cells, acting on the extracellular milieu by directly killing bacteria or boosting innate immunity. Here, we show that LL-37 translocates to the nucleus following overwhelming infection, putting in evidence that its role may be even broader, with new potential important implications to cell biology. Future studies are necessary to address if LL-37 is able to induce or affect transcription, since it can lead to a novel cell signaling pathway that probably will contribute to the understanding of complex diseases.
- 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.- Antimicrobial peptide LL-37 participates in the transcriptional regulation of melanoma cells(2016) MUNOZ, Mindy; CRASKE, Madeleine; SEVERINO, Patricia; LIMA, Thais Martins de; LABHART, Paul; CHAMMAS, Roger; VELASCO, Irineu Tadeu; MACHADO, Marcel Cerqueira Cesar; EGAN, Brian; NAKAYA, Helder I.; SILVA, Fabiano Pinheiro daAntimicrobial peptides are an ancient family of molecules that emerged millions of years ago and have been strongly conserved during the evolutionary process of living organisms. Recently, our group described that the human antimicrobial peptide LL-37 migrates to the nucleus, raising the possibility that LL-37 could directly modulate transcription under certain conditions. Here, we showed evidence that LL-37 binds to gene promoter regions, and LL-37 gene silencing changed the transcriptional program of melanoma A375 cells genes associated with histone, metabolism, cellular stress, ubiquitination and mitochondria.
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.- Neuropeptides in sepsis: From brain pathology to systemic inflammation(2013) SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira Cesar; VELASCO, Irineu TadeuSeptic encephalopathy is frequently diagnosed in critically ill patients and in up to 70% of patients with severe systemic infection [19]. The syndrome is defined by diffuse cerebral dysfunction or structural abnormalities attributed to the effects of systemic infection, rather than a direct central nervous system cause. The clinical characteristics can range from mild delirium to deep coma, but patients are often medically sedated making the diagnosis difficult. Any manifestation, however, is specific and markers of disease are lacking [43]. Sepsis survivors present long term cognitive impairment, including alterations of memory, attention and concentration [10,54]. Here, we propose that neuropeptides may play a key role in septic encephalopathy, leading to a vicious circle characterized by brain disease and systemic inflammation.