DENISE FREDIANI BARBEIRO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- Gastrin-Releasing Peptide Receptor Antagonism Induces Protection from Lethal Sepsis: Involvement of Toll-like Receptor 4 Signaling(2012) PETRONILHO, Fabricia; VUOLO, Francieli; GALANT, Leticia Selinger; CONSTANTINO, Larissa; TOMASI, Cristiane Damiani; GIOMBELLI, Vinicius Renne; SOUZA, Cldudio Teodoro de; SILVA, Sabrina da; BARBEIRO, Denise Frediani; SORIANO, Francisco Garcia; STRECK, Emilio Luiz; RITTER, Cristiane; ZANOTTO-FILHO, Alfeu; PASQUALI, Matheus Augusto; GELAIN, Daniel Pens; RYBARCZYK-FILHO, Jose Luiz; MOREIRA, Jose Claudio Fonseca; BLOCK, Norman L.; ROESLER, Rafael; SCHWARTSMANN, Gilberto; SCHALLY, Andrew V.; DAL-PIZZOL, FelipeIn sepsis, toll-like receptor (TLR)-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis, organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide (GRP) receptor (GRPR) antagonist RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha and RC-3095 (10 ng/mL), Male Wistar rats were subjected to cecal ligation and puncture (CLP), and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 h, we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h, and plasma was collected before and after RC-3095 administration and, in a different set of patients with systemic inflammatory response syndrome (SIRS) or sepsis. GRP plasma levels were determined. RC-3095 inhibited TLR-4, extracellular-signal-related kinase (ERK)-1/2, Jun NH2-terminal kinase (JNK) and Akt and decreased activation of activator protein 1 (AP-1), nuclear factor (NF)-kappa B and interleukin (IL)-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-alpha. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung and reduced systemic cytokines and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving at least inhibition of TLR-4 signaling. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00083
conferenceObject Obesity protects heart but increases lung injury by endotoxin inflammation(2014) LIMA, T. M. D.; MALDONADO, M. C.; PETRONI, R.; BARBEIRO, D.; SORIANO, F. G.; SILVA, F. Pinheiro da- Evolution of Biomarkers of Atherogenic Risk in Liver Transplantation Recipients(2018) LINHARES, L. M. C.; OLIVEIRA, C. P.; ALVARES-DA-SILVA, M. R.; STEFANO, J. T.; BARBEIRO, H. V.; BARBEIRO, D. F.; TERRABUIO, D. R. B.; ABDALA, E.; SORIANO, F. G.; CARRILHO, F. J.; FARIAS, A. Q.; SIDDIQUI, M. S.; D'ALBUQUERQUE, L. A. C.Background. Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). Methods. This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). Results. The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 +/- 0.44 ng/mL to 9.10 +/- 5.82 ng/mL (P < .001) and 0.23 +/- 0.09 ng/mL to 2.7 +/- 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 +/- 0.07 ng/mL to 3.46 +/- 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 +/- 40.7 ng/mL at entry to 91.5 +/- 143.6 ng/mL at end of study (P < .001). Conclusion. No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.
- Hypertonic saline solution reduces the inflammatory response in endotoxemic rats(2012) THEOBALDO, Mariana Cardillo; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; PETRONI, Ricardo; SORIANO, Francisco GarciaOBJECTIVE: Volume replacement in septic patients improves hemodynamic stability. This effect can reduce the inflammatory response. The objective of this study was to evaluate the effect of 7.5% hypertonic saline solution versus 0.9% normal saline solution for volume replacement during an inflammatory response in endotoxemic rats. METHODS: We measured cytokines (serum and gut), nitrite, and lipid peroxidation (TBARS) as indicators of oxidative stress in the gut. Rats were divided into four groups: control group (C) that did not receive lipopolysaccharide; lipopolysaccharide injection without treatment (LPS); lipopolysaccharide injection with saline treatment (LPS + S); and lipopolysaccharide injection with hypertonic saline treatment (LPS + H). Serum and intestine were collected. Measurements were taken at 1.5, 8, and 24 h after lipopolysaccharide administration. RESULTS: Of the four groups, the LPS + H group had the highest survival rate. Hypertonic saline solution treatment led to lower levels of IL-6, IL-10, nitric oxide, and thiobarbituric acid reactive substances compared to 0.9% normal saline. In addition, hypertonic saline treatment resulted in a lower mortality compared to 0.9% normal saline treatment in endotoxemic rats. Volume replacement reduced levels of inflammatory mediators in the plasma and gut. CONCLUSION: Hypertonic saline treatment reduced mortality and lowered levels of inflammatory mediators in endotoxemic rats. Hypertonic saline also has the advantage of requiring less volume replacement.
- Crotoxin modulates inflammation and macrophages? functions in a murine sepsis model(2022) BRETONES, Marisa Langeani; SAMPAIO, Sandra Coccuzzo; BARBEIRO, Denise Frediani; ARIGA, Suely K. Kubo; SORIANO, Francisco Garcia; LIMA, Thais Martins deSepsis is a syndrome of physiological and biochemical abnormalities induced by an infection that represents a major public health concern. It involves the early activation of inflammatory responses. Crotoxin (CTX), the major toxin of the South American rattlesnake Crotalus durissus terrificus venom, presents longstanding antiinflammatory properties. Since immune system modulation may be a strategic target in sepsis management, and macrophages' functional and secretory activities are related to the disease's progression, we evaluated the effects of CTX on macrophages from septic animals. Balb/c male mice submitted to cecal ligation and puncture (CLP) were treated with CTX (0.9 mu g/animal, subcutaneously) 1 h after the procedure and euthanized after 6 h. We used plasma samples to quantify circulating cytokines and eicosanoids. Bone marrow differentiated macrophages (BMDM) were used to evaluate the CTX effect on macrophages' functions. Our data show that CTX administration increased the survival rate of the animals from 40% to 80%. Septic mice presented lower plasma concentrations of IL-6 and TNF-alpha after CTX treatment, and higher concentrations of LXA4, PGE2, and IL-1 beta. No effect was observed in IL-10, IFN-gamma, and RD1 concentrations. BMDM from septic mice treated with CTX presented decreased capacity of E. coli phagocytosis, but sustained NO and H2O2 production. We also observed higher IL-6 concentration in the culture medium of BMDM from septic mice, and CTX induced a significant reduction. CTX treatment increased IL-10 production by macrophages as well. Our data show that the protective effect of CTX in sepsis mortality involves modulation of macrophage functions and inflammatory mediators' production.
- Pro-atherosclerotic markers and cardiovascular risk factors one year after liver transplantation(2014) ALVARES-DA-SILVA, Mario Reis; OLIVEIRA, Claudia Pinto Marques Souza de; STEFANO, Jose Tadeu; BARBEIRO, Hermes V.; BARBEIRO, Denise; SORIANO, Francisco G.; FARIAS, Alberto Queiroz; CARRILHO, Flair Jose; D'ALBUQUERQUE, Luiz Augusto CarneiroAIM: To investigate pro-atherosclerotic markers (endothelial dysfunction and inflammation) in patients one year after liver transplantation. METHODS: Forty-four consecutive liver transplant (LT) outpatients who were admitted between August 2009 and July 2010, were followed-up by for 1 year, exhibited no evidences of infection or rejection, all of them underwent tacrolimus-based immunosuppressive regimens were consecutively enrolled. Inflammatory cytokines (TNF alpha, IFN gamma, IL-8, and IL-10), endothelial biomarkers (sVCAM-1, sICAM-1, MPO, adiponectin, PAI-1, SAP, SAA, E-selectin, and MMP-9), high sensitive C-reactive protein, and Framingham risk score (FRS) were assessed. The anthropometric data, aminotransferases, metabolic syndrome features, glucose and lipid profiles, and insulin resistance data were also collected. The LT recipients were compared to 22 biopsy-proven non-alcoholic steatohepatitis (NASH) patients and 20 healthy controls (non-obese, non-diabetics, and non-dyslipidemic). RESULTS: The LT recipients had significantly younger ages and lower body mass indices, aminotransferases, fasting glucose and insulin levels, glucose homeostasis model and metabolic syndrome features than the NASH patients. Classic cardiovascular risk markers, such as Hs-CRP and FRS [2.0 (1.0-8.75)], were lower in the LT patients compared to those observed in the NASH patients (P = 0.009). In contrast, the LT recipients and NASH patients had similar inflammatory and endothelial serum markers compared to the controls (pg/mL): lower IL-10 levels (32.3 and 32.3 vs 62.5, respectively, P = 0.019) and higher IFN gamma (626.1 and 411.9 vs 67.9, respectively, P < 0.001), E-selectin (48.5 and 90.03 vs 35.7, respectively, P < 0.001), sVCAM-1 (1820.6 and 1692.4 vs 1167.2, respectively, P < 0.001), and sICAM-1 (230.3 and 259.7 vs 152.9, respectively, P = 0.015) levels. CONCLUSION: Non-obese LT recipients have similar pro-atherosclerotic serum profiles after a short 1-year follow-up period compared to NASH patients, suggesting a high risk of atherosclerosis in this population.
- Hypertonic solution-induced preconditioning reduces inflammation and mortality rate(2019) PIMENTEL, Rosangela Nascimento; PETRONI, Ricardo Costa; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; ANDRADE, Mariana Macedo; ARIGA, Suely Kumini; SORIANO, Francisco GarciaBackgroundDysregulated inflammatory response is common cause of organ damage in critical care patients. Preconditioning/tolerance is a strategy to prevent exacerbated inflammation. The aim of this study is to analyze hypertonic saline 7.5% as a potential inducer of preconditioning that protect from a lethal dose of LPS and modulates systemic inflammatory profile in mice.MethodsMale Balb/C mice received intravenous (i.v.) injections of Hypertonic solution (NaCl 7.5%) (0.8ml) for 3days, on day 8th was challenged with LPS 15mg/kg. Controls with Saline 0.9%, urea and sorbitol were performed. Microarray of mRNA expression was analyzed from HS versus saline from macrophages to identified the pathways activated by HS.ResultsHS preconditioning reduced mortality after LPS injection as well reduced the cytokines release in plasma of the animals challenged by LPS. In order to check how HS induces a preconditioning state we measured plasma cytokines after each HS infusion. Repeated HS injections induced a state of preconditioning that reprograms the inflammatory response, resulting in reduced inflammatory cytokine production. A microarray of mRNA demonstrated that Hypertonic solution increased the expression of several genes in special Mapkbp1 and Atf3.Conclusionhypertonic solution induces preconditioning/tolerance reducing mortality and inflammatory response after LPS challenge.
conferenceObject Obesity alters sepsis induced pulmonary inflammation(2012) LIMA-SALGADO, T.; FUNGARO, T. P.; PETRONI, R. C.; OLIVEIRA, S. J. S.; BARBEIRO, D. F.; SORIANO, F. G.Purpose/Objective: Sepsis is a severe disease that represents a significant healthcare burden worldwide, while obesity has reached epidemic proportions over the last few decades. Although the mechanism is uncharted, it is known that obesity increases morbidity and mortality in sepsis through its multiple effects on many organ systems, including pulmonary function. Our aim was to investigate the effects of obesity in systemic and pulmonary inflammatory process in an experimental model of endotoxemic shock. Materials and methods: Animals were fed a high fat diet (30% of fat) for 6 weeks and then injected with 15 mg/kg LPS i.p. They were euthanatized after 6, 24 and 48 h. Inflammation was characterized by measurement of plasma and pulmonary cytokines. The mRN expression of cytokines and tissue remodeling proteins was determined by real time PCR. Results: Obesity decreased the survival rate of the animals 24 h after LPS injection. There was higher plasma concentration of IL1-beta, IL-6and TNF-alpha in these animals. Furthermore, there was higher concentration of IL-6 in the obese mice’s lungs after 6 h of endotoxemia. However, the mRNA expression of pro-inflammatory factors (IL-6, TNF-alpha, IL-1beta and MMP9) was lower, suggesting they may be converted to proteins. Obese mice presented higher mRNA expression of TGF-beta after 6 h, indicating a reparative process. Conclusions: Obesity may be an additional complication factor in sepsis induced pulmonary inflammation.conferenceObject Cardiovascular risk and coronary artery calcium score after liver transplantation: study at fouth year(2017) LINHARES, L. M.; OLIVEIRA, C. P.; ALVARES-DA-SILVA, M. R.; STEFANO, J. T.; GEBRIM, E. M.; BARBEIRO, H. V.; BARBEIRO, D. F.; TERRABUIO, D. R.; ABDALA, E.; SORIANO, F. G.; CARRILHO, F. J.; FARIAS, A. Q.; AUGUSTO, L.; ALBUQUERQUE, C. D'- Sepsis: Future role of omics in diagnosis and therapy(2019) BARBEIRO, H. V.; BARBEIRO, D. F.; SORIANO, F. G.Protocoled interventions for sepsis have dominated the guidelines of international societies. Treatment has to start quickly. In sepsis as in other emergencies, it has been demonstrated that time since emergency room admission and antibiotic prescription determine clinical evolution. Precision medicine-based sepsis management faces a specific problem. In addition to being accurate, diagnosis has to be fast. In a matter of hours, a patient may have died from an infection that has turned into sepsis. Techniques for proteomics, genomics, metabolomics, and all omics are indeed becoming more accurate and fast. Yet time to receive laboratory results is the limiting factor for implementing such advances in clinical practice. In this chapter we review recent data about omics, and how they can help for better diagnosis and treatment. © 2020 Elsevier Inc. All rights reserved.