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
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conferenceObject URINARY BIOMARKER NGAL IN PATIENTS WITH HEPATORENAL SYNDROME: ACCURACY STUDY IN PREDICTION OF NO RESPONSE TO THERAPY WITH ALBUMIN AND TERLIPRESSIN(2016) XIMENES, R. O.; HELOU, C.; DINIZ, M.; BARBEIRO, D.; SOUZA, H.; D'ALBUQUERQUE, L. A.; CARRILHO, F.; FARIAS, A.- 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.
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.- 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.
- High-fat diet inhibits PGC-1 alpha suppressive effect on NF kappa B signaling in hepatocytes(2018) BARROSO, Wermerson Assuncao; VICTORINO, Vanessa Jacob; JEREMIAS, Isabela Casagrande; PETRONI, Ricardo Costa; ARIGA, Suely Kunimi Kubo; SALLES, Thiago A.; BARBEIRO, Denise Frediani; LIMA, Thais Martins de; SOUZA, Heraldo Possolo deThe peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1 alpha exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1 alpha expression in mice. In this study, we investigated the role of PGC-1 alpha in the inflammatory changes observed in steatohepatitis induced by high-fat diet. C57black/6 mice were fed a high-fat diet containing 30% fat for 10 weeks. After euthanasia, liver morphology was examined by HE staining and inflammation was determined by IL-6, TNF-alpha, and IL-1 beta quantification. Liver gene expression of PGC-1 isoforms was evaluated by real-time PCR and p65 NF kappa B nuclear translocation by Western blotting. HepG2 cells were treated with linoleic acid overload for 72 h to create an in vitro model of steatohepatitis. RNA interference (RNAi) was used to evaluate the involvement of PGC-1 alpha on inflammatory mediators' production by hepatocytes. The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. Mice liver also exhibited increased proinflammatory cytokines' levels, decreased PGC-1 alpha expression, and marked increase in p65 NF kappa B nuclear translocation. Linoleic acid treated cells also presented increased expression of proinflammatory cytokines and decreased PGC-1 alpha expression. The knockdown of PGC-1 alpha content caused an increase in IL-6 expression and release via enhanced I kappa B alpha phosphorylation and subsequent increase of p65 NF kappa B nuclear translocation. High-fat diet induces liver inflammation by inhibiting PGC-1 alpha expression and its suppressive effect in NF kappa B pathway.
- Sodium Taurocholate Induced Severe Acute Pancreatitis in C57BL/6 Mice(2021) SERRA, Mariana B.; KOIKE, Marcia K.; BARBEIRO, Denise F.; MACHADO, Marcel C. C.; SOUZA, Heraldo P. deBiliary acute pancreatitis induction by sodium taurocholate infusion has been widely used by the scientific community due to the representation of the human clinical condition and reproduction of inflammatory events corresponding to the onset of clinical biliary pancreatitis. The severity of pancreatic damage can be assessed by measuring the concentration, speed, and volume of the infused bile acid. This study provides an updated checklist of the materials and methods used in the protocol reproduction and shows the main results from this acute pancreatitis (AP) model. Most of the previous publications have limited themselves to reproducing this model in rats. We have applied this method in mice, which provides additional advantages (i.e., the availability of an arsenal of reagents and antibodies for these animals along with the possibility of working with genetically modified strains of mice) that may be relevant to the study. For acute pancreatitis induction in mice, we present a systematic protocol, with a defined dose of 2.5% sodium taurocholate at an infusion speed 10 mu L/min for 3 min in C57BL/6 mice that reaches its maximal level of severity within 12 h of induction and highlight results with outcomes that validate the method. With practice and technique, the total estimated time, from the induction of anesthesia to the completion of the infusion, is 25 min per animal.
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.
- Neuropeptides in the brain defense against distant organ damage(2016) HAMASAKI, Mike Yoshio; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; CUNHA, Debora Maria Gomes; KOIKE, Marcia Kiyomi; MACHADO, Marcel Cerqueira Cesar; SILVA, Fabiano Pinheiro daDelirium, or acute confusional state, is a common manifestation in diseases that originate outside the central nervous system, affecting 30-40% of elderly hospitalized patients and up to 80% of the critically ill, even though it remains unclear if severe systemic inflammation is able or not to induce cellular disturbances and immune activation in the brain. Neuropeptides are pleotropic molecules heterogeneously distributed throughout the brain and possess a wide spectrum of functions, including regulation of the inflammatory response, so we hypothesized that they would be the major alarm system in the brain before overt microglia activation. In order to investigate this hypothesis, we induced acute pancreatitis in 8-10 week old rats and collected brain tissue, 12 and 24 h following pancreatic injury, to measure neuropeptide and cytokine tissue levels. We found significantly higher levels of beta-endorphin, orexin and oxytocin in the brain of rats submitted to pancreatic injury, when compared to healthy controls. Interestingly, these differences were not associated with increased local cytokine levels, putting in evidence that neuropeptide release occurred independently of microglia activation and may be a pivotal alarm system to initiate neurologic reactions to distant inflammatory non-infectious aggression.
conferenceObject Inflammatory and antioxidant response in obese septic shock patients(2013) VICTORINO, Vanessa Jacob; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; SILVA, Fabiano Pinheiro; SOUZA, Heraldo PossoloThere is no consensus about the influence of obesity on sepsis. Hence, we evaluated the inflammatory and antioxidant response in obese patients (body mass index > 30) with septic shock compared to non-infected obese and non-obese septic patients. Blood samples were obtained from 27 critically ill patients admitted to ICUs in Clinics Hospital, Universidade de Sao Paulo. Cytokines were measured by ELISA Milliplex and antioxidant activity by colorimetric methods. There are small differences in the cytokine profiles in obese septic patients (n=6), compared to obese non-infected ones (n=10). Only FGF2, TGF-α, IFN-α2, IFN-{gamma}, IL-10, MCP-3, IL-13 and IL-15 presented significantly higher levels in septic patients. Interestingly, there was a marked increase in superoxide dismutase (SOD) and catalase (CAT) activity in erythrocytes from the septic group. Compared to their non-obese septic counterparts, septic obese patients presented significantly lower levels of FGF2, IL-4, TNF-β and VEGF. SOD activity was higher in this group, compared to non-obese patients. We concluded that obese patients with septic shock maintain cytokine levels similar to the ones observed in their non-obese counterparts, while increasing their antioxidant activity.