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
65 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 65
- Cathelicidin protects mice from Rhabdomyolysis-induced Acute Kidney Injury(2021) SILVA, Beatriz Helena Cermaria Soares da; ARIGA, Suely Kubo; BARBEIRO, Hermes Vieira; VOLPINI, Rildo Aparecido; BARBEIRO, Denise Frediani; SEGURO, Antonio Carlos; SILVA, Fabiano Pinheiro daBackground: Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity. Rhabdomyolysis is a major trigger of AKI. Objectives: Here, we investigated the role of cathelicidins in non-infectious Acute kidney Injury (AKI). Method: Using an experimental model of rhabdomyolysis, we induced AKI in wild-type and cathelicidin-related AMP knockout (CRAMP(-/-)) mice. Results: We previously demonstrated that CRAMP(-/-) mice, as opposed wild-type mice, are protected from AKI during sepsis induced by cecal ligation and puncture. Conversely, in the current study, we show that CRAMP(-/-) mice are more susceptible to the rhabdomyolysis model of AKI. A more in-depth investigation of wild-type and CRAMP(-/-) mice revealed important differences in the levels of several inflammatory mediators. Conclusion: Cathelicidins can induce a varied and even opposing repertoire of immune-inflammatory responses depending on the subjacent disease and the cellular context.
- Cathelicidin-deficient mice exhibit increased survival and upregulation of key inflammatory response genes following cecal ligation and puncture(2017) SEVERINO, Patricia; ARIGA, Suely Kubo; BARBEIRO, Hermes Vieira; LIMA, Thais Martins de; SILVA, Elisangela de Paula; BARBEIRO, Denise Frediani; MACHADO, Marcel Cerqueira Cesar; NIZET, Victor; SILVA, Fabiano Pinheiro daAntimicrobial peptides possess a myriad of molecular properties including bacterial killing and the regulation of many aspects of innate immunity. Cathelicidins are a group of antimicrobial peptides widely investigated by the scientific community. Many studies have focused on the bactericidal and pro-inflammatory roles of cathelicidins. Because the role of endogenous cathelicidin expression remains obscure in deep-seated systemic infections, we induced sepsis in cathelicidin knockout and wild-type (WT) mice by cecal ligation and puncture, performing transcriptome screening by DNA micro-array in conjunction with other immunologic assays. Cathelicidin-deficient mice showed increased survival compared to WT mice in this established experimental model of polymicrobial sepsis, in association with upregulation of certain key inflammatory response genes. Therefore, cathelicidins can exert both pro- and anti-inflammatory activities depending on the disease and cellular context.
- Ânion gap corrigido para albumina, fosfato e lactato é um bom preditor de íon gap forte em pacientes enfermos graves: estudo de coorte em nicho(2013) ZAMPIERI, Fernando Godinho; PARK, Marcelo; RANZANI, Otavio Tavares; MACIEL, Alexandre Toledo; SOUZA, Heraldo Possolo de; CRUZ NETO, Luiz Monteiro da; SILVA, Fabiano Pinheiro daOBJECTIVE: Corrected anion gap and strong ion gap are commonly used to estimate unmeasured anions. We evaluated the performance of the anion gap corrected for albumin, phosphate and lactate in predicting strong ion gap in a mixed population of critically ill patients. We hypothesized that anion gap corrected for albumin, phosphate and lactate would be a good predictor of strong ion gap, independent of the presence of metabolic acidosis. In addition, we evaluated the impact of strong ion gap at admission on hospital mortality. METHODS: We included 84 critically ill patients. Correlation and agreement between the anion gap corrected for albumin, phosphate and lactate and strong ion gap was evaluated by the Pearson correlation test, linear regression, a Bland-Altman plot and calculating interclass correlation coefficient. Two subgroup analyses were performed: one in patients with base-excess <-2mEq/L (low BE group - lBE) and the other in patients with base-excess >-2mEq/L (high BE group - hBE). A logistic regression was performed to evaluate the association between admission strong ion gap levels and hospital mortality. RESULTS: There was a very strong correlation and a good agreement between anion gap corrected for albumin, phosphate and lactate and strong ion gap in the general population (r2=0.94; bias 1.40; limits of agreement -0.75 to 3.57). Correlation was also high in the lBE group (r2=0.94) and in the hBE group (r2=0.92). High levels of strong ion gap were present in 66% of the whole population and 42% of the cases in the hBE group. Strong ion gap was not associated with hospital mortality by logistic regression. CONCLUSION: Anion gap corrected for albumin, phosphate and lactate and strong ion gap have an excellent correlation. Unmeasured anions are frequently elevated in critically ill patients with normal base-excess. However, there was no association between unmeasured anions and hospital mortality.
conferenceObject Intestinal Barrier Dysfunction in Ageing Animals With Acute Pancreatitis: Increased Intestinal Inflammation?(2015) MACHADO, Marcel C.; SILVA, Fabiano Pinheiro da; CUNHA, Debora G.; BARBEIRO, Denise F.; COELHO, Ana Maria M.; SOUZA, Heraldo P.conferenceObject LL-37 upregulates genes related to stemness in breast cancer cells(2016) SILVA, F. Pinheiro da; LIMA, T. Martins de; COELHO NETO, G. Tude; MACHADO, M. Cesar- Diazoxide reduces local and remote organ damage in a rat model of intestinal ischemia reperfusion(2018) DOURADO, Saulo Fernandes de Mattos; BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; BARBEIRO, Hermes Vieira; SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira CesarBackground: Intestinal ischemia reperfusion is a common clinical condition that causes functional impairment. Once tight junctions are damaged, barrier function is compromised, and the intestines become a source for entry of bacterial and inflammatory mediators into the circulation, leading to systemic inflammatory response syndrome, multiple organ failure, and death. It is possible that diazoxide could protect the intestines against ischemia reperfusion. The aim of this study is to determine whether diazoxide can provide protection in a rat model of intestinal ischemia reperfusion. Methods: A total of 32 adult male specific pathogen-free Wistar rats were randomized into three groups: a control group, n = 6; a saline group, n = 13; and a diazoxide group, n = 13. The saline and diazoxide groups underwent clamping of the superior mesenteric artery for 1 h, with samples in all the groups being collected 12 h later. Results: Intestinal histology showed greater damage in the intestinal ischemia reperfusion groups. mRNA expression of zonula occludens-1 and occludin (tight junction proteins) and interleukin-6 and cyclooxygenase-2 was the highest in the Saline group. The Diazoxide group showed a reduction in aspartate aminotransferase serum levels compared with the other groups. Conclusions: Increased expression of zonula occludens-1, occludin, and cyclooxygenase-2 suggested a greater regenerative effort because ofmore severe lesions in the saline group. In addition, increased expression of interleukin-6 in the saline group was suggestive of inflammation, indicating that diazoxide had protective effects in the diazoxide group. Reduced aspartate aminotransferase in the diazoxide group suggested liver protection. Diazoxide protects the intestines and liver fromintestinal ischemia reperfusion lesions in rats.
- Microarray gene expression analysis of neutrophils from elderly septic patients(2015) PELLEGRINA, Diogo Vieira da Silva; SEVERINO, Patricia; MACHADO, Marcel Cerqueira; SILVA, Fabiano Pinheiro da; REIS, Eduardo MoraesSepsis is an especially common affliction in the elderly and despite its increased prevalence and mortality in older people, the immune response of the elderly during septic shock appears similar to that of younger patients. In the original study we conducted a global gene expression analysis of circulating neutrophils from elderly and young septic patients, as well as from age-matched healthy controls, to better understand how elder individuals respond to severe infectious insult (Pellegrina et al., 2015). Here we provide additional details pertaining processing and statistical analysis of the microarray data. Raw and normalized datasets linked to this project have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE67652. (C) 2015 Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Antimicrobial peptides in the gut-brain axis: A straightforward review to unravel some missing links(2020) SILVA, Fabiano Pinheiro da; BRUZAFERRO, Ewerton Vinicius Macarini; CAMARA, Niels Olsen SaraivaAntimicrobial peptides (AMPs) are intriguing molecules, able to directly kill several microorganisms and to regulate multiple aspects of the immune response. Despite the extensive studies on the role of AMPs in the epithelial barrier, placing them as a pivotal line of defense against pathogen invasion, little attention has been directed to their role in the maintenance and modulation of the gut microbiota and, by consequence, of the homeostasis of extra intestinal tissues. Here, we review the recent literature about the microbiome-gut-brain axis, focusing on the role of AMPs in this scenario. We provide a straightforward revision of current data in order to provide an overview of the subject, discussing more in depth some points that, in our opinion, are crucial and have received little attention.
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- Influence of Body Mass Index on Inflammatory Profile at Admission in Critically Ill Septic Patients(2015) ZAMPIERI, Fernando G.; JACOB, Vanessa; SILVA, Fabiano Pinheiro da; SOUZA, Heraldo P. deIntroduction. Inflammation is ubiquitous during sepsis and may be influenced by body mass index (BMI). We sought to evaluate if BMIwas associated with serumlevels of several cytokinesmeasured at intensive care unit admission due to sepsis. Methods. 33 septic patients were included. An array of thirty-two cytokines and chemokines was measured using Milliplex technology. We assessed the association between cytokine levels and BMI by generalized additive model that also included illness severity (measured by SAPS 3 score); one model was built for each cytokine measured. Results. We found that levels of epidermal growth factor, vascular endothelial growth factor, and interleukins 4, 5, and 13 were associated with BMI in a complex, nonlinear way, independently of illness severity. Higher BMI was associated with higher levels of anti-inflammatory interleukins. Conclusion. BMI may influence host response to infection during critical illness. Larger studies should confirm these findings.