FABIANO PINHEIRO DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
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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- Increased intestinal production of alpha-defensins in aged rats with acute pancreatic injury(2014) CUNHA, Debora Maria Gomes; KOIKE, Marcia Kiyomi; BARBEIRO, Denise Frediani; BARBEIRO, Hermes Vieira; HAMASAKI, Mike Yoshio; COELHO NETO, Guilherme Tude; MACHADO, Marcel Cerqueira Cesar; SILVA, Fabiano Pinheiro daAcute pancreatitis is a life-threatening situation, frequently associated with uncontrolled local and systemic inflammation, and aging is associated with a worst prognosis. Antimicrobial peptides are ancient molecules that belong to innate immunity, produced by epithelial and immune cells, and are able to trigger a myriad of effector responses. We have hypothesized that antimicrobial peptides could play an important role during serious pancreatic injury. To investigate our hypothesis, alpha-defensin-5, alpha-defensin-7 and CRAMP gene expression levels were measured in the intestinal tissue of old and young rats submitted to chemical pancreatic damage. We found significantly higher levels of alpha-defensin-5 and alpha-defensin-7, but not CRAMP, in the samples from old mice. This increase was not associated with a worse systemic inflammatory response. We conclude that alpha-defensins may have a pivotal role during acute pancreatitis and that the elderly develops a more severe local, but not systemic inflammatory process.
- Beneficial effects of adenosine triphosphate-sensitive K+ channel opener on liver ischemia/reperfusion injury(2014) NOGUEIRA, Mateus Antunes; COELHO, Ana Maria Mendonca; SAMPIETRE, Sandra Nassa; PATZINA, Rosely Antunes; SILVA, Fabiano Pinheiro da; D'ALBUQUERQUE, Luiz Augusto Carneiro; MACHADO, Marcel Cerqueira CesarAIM: To investigate the effect of diazoxide administration on liver ischemia/reperfusion injury. METHODS: Wistar male rats underwent partial liver ischemia performed by clamping the pedicle from the medium and left anterior lateral segments for 1 h under mechanical ventilation. They were divided into 3 groups: Control Group, rats submitted to liver manipulation, Saline Group, rats received saline, and Diazoxide Group, rats received intravenous injection diazoxide (3.5 mg/kg) 15 min before liver reperfusion. 4 h and 24 h after reperfusion, blood was collected for determination of aspartate transaminase (AST), alanine transaminase (ALT), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), nitrite/nitrate, creatinine and tumor growth factor-beta 1 (TGF-beta 1). Liver tissues were assembled for mitochondrial oxidation and phosphorylation, malondialdehyde (MDA) content, and histologic analysis. Pulmonary vascular permeability and myeloperoxidase (MPO) were also determined. RESULTS: Four hours after reperfusion the diazoxide group presented with significant reduction of AST (2009 +/- 257 U/L vs 3523 +/- 424 U/L, P = 0.005); ALT (1794 +/- 295 U/L vs 3316 +/- 413 U/L, P = 0.005); TNF-alpha (17 +/- 9 pg/mL vs 152 +/- 43 pg/mL, P = 0.013; IL-6 (62 +/- 18 pg/mL vs 281 +/- 92 pg/mL); IL-10 (40 +/- 9 pg/mL vs 78 +/- 10 pg/mL P = 0.03), and nitrite/nitrate (3.8 +/- 0.9 mu mol/L vs 10.2 +/- 2.4 mu mol/L, P = 0.025) when compared to the saline group. A significant reduction in liver mitochondrial dysfunction was observed in the diazoxide group compared to the saline group (P < 0.05). No differences in liver MDA content, serum creatinine, pulmonary vascular permeability and MPO activity were observed between groups. Twenty four hours after reperfusion the diazoxide group showed a reduction of AST (495 +/- 78 U/L vs 978 +/- 192 U/L, P = 0.032); ALT (335 +/- 59 U/L vs 742 +/- 182 U/L, P = 0.048), and TGF-beta 1 (11 +/- 1 ng/mL vs 17 +/- 0.5 ng/mL, P = 0.004) serum levels when compared to the saline group. The control group did not present alterations when compared to the diazoxide and saline groups. CONCLUSION: Diazoxide maintains liver mitochondrial function, increases liver tolerance to ischemia/reperfusion injury, and reduces the systemic inflammatory response. These effects require further evaluation for using in a clinical setting.
- An increase in mean platelet volume after admission is associated with higher mortality in critically ill patients(2014) ZAMPIERI, Fernando G.; RANZANI, Otavio T.; SABATOSKI, Viviane; SOUZA, Heraldo Possolo de; BARBEIRO, Hermes; DA NETO, Luiz Monteiro Cruz; PARK, Marcelo; SILVA, Fabiano Pinheiro daBackground: Platelet activation and consumption are common in critically ill patients and are associated with poorer prognosis. Mean platelet volume is a simple surrogate for platelet activation, with higher MPV being associated with worse clinical condition on a large array of clinical diagnoses. We therefore aimed to investigate associations between changes in platelet count and mean platelet volume (MPV) with prognosis and inflammatory cytokine values in critically ill patients. Methods: This study prospectively included 84 critically ill patients. Patients were stratified into four groups according to proportional changes in MPV (Delta MPV24h) and platelet count (Delta Plat(24h)) in the first 24 hours after admission. Mortality between groups was compared using the chi(2) test. Logistic regression was performed using hospital mortality as outcome and Simplified Acute Physiology Score (SAPS 3), Delta Plat(24h) and Delta MPV24h as covariates. Concentrations of the following inflammatory mediators were measured using Miliplex (R) technology: IL1 beta, IL6, IL8, IL10, epidermal growth factor, vascular endothelial growth factor, TNF alpha and IFN alpha. Cytokine concentrations were compared between groups using the Kruskal-Wallis test with Bonferroni correction. Results: Patients in whom MPV increased and platelet count decreased had higher mortality rates (46%). According to logistic regression, Delta MPV24h was independently associated with increased mortality (OR 1.28 per 1% increase; 95% CI 1.08 to 1.48). No strong associations between inflammatory mediators and changes in MPV and platelet count were found. Conclusion: An increase in MPV after admission to an ICU is independently associated with higher hospital mortality.
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- 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.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.- Relationship between acid-base status and inflammation in the critically ill(2014) ZAMPIERI, Fernando G.; KELLUM, John A.; PARK, Marcelo; RANZANI, Otavio T.; BARBEIRO, Hermes V.; SOUZA, Heraldo P. de; CRUZ NETO, Luiz Monteiro da; SILVA, Fabiano Pinheiro daIntroduction: There is a complex interplay between changes in acid base components and inflammation. This manuscript aims to explore associations between plasma cytokines and chemokines and acid base status on admission to intensive care. Methods: We conducted a prospective cohort study in a 13-bed ICU in a tertiary-care center in Brazil. 87 unselected patients admitted to the ICU during a 2-year period were included. We measured multiple inflammatory mediators in plasma using multiplex assays and evaluated the association between mediator concentrations and acid base variables using a variety of statistical modeling approaches, including generalized linear models, multiadaptive regression splines and principal component analysis. Results: We found a positive association between strong ion gap (SIG) and plasma concentrations of interleukin (IL)6, 8, 10 and tumor necrosis factor (TNF); whereas albumin was negatively associated with IL6, IL7, IL8, IL10, TNF and interferon (IFN)alpha. Apparent strong ion difference (SIDa) was negatively associated with IL10 and IL17. A principal component analysis including SAPS 3 indicated that the association between acid base components and inflammatory status was largely independent of illness severity, with both increased SIG and decreased SIDa (both drivers of acidosis) associated with increased inflammation. Conclusion: Acid base variables (especially increased SIG, decreased albumin and decreased SIDa) on admission to ICU are associated with immunological activation. These findings should encourage new research into the effects of acid base status on inflammation.
- 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.