MARCEL CERQUEIRA CESAR MACHADO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cirurgia, Faculdade de Medicina - Docente
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Effects of diazoxide in experimental acute necrotizing pancreatitis(2017) ANDRADE, Roberta de Oliveira; KUNITAKE, Tiago; KOIKE, Marcia Kiyomi; MACHADO, Marcel C. C.; SOUZA, Heraldo PossoloOBJECTIVE: We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis. METHODS: Male Wistar rats (200-400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n= 38) was observed for 72 h and analyzed by the Mantel-Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt's scale. Cytokine expression in plasma was evaluated by the multiplex method. RESULTS: Mortality at 72 h was 33% in the control group and 60% in the treatment group (p = 0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p = 0.015). CONCLUSIONS: Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h.
- 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 Salmonella in Sausage, Frankfurter and Meat Sausage, Not Only in Raw or Undercooked but Also Found in Smoked and Cooked Ones: An Alert for Public Health and Traveler's Health Problem, Including Aerospace Medicine?(2017) MORIOKA, Cintia Y.; OLIVEIRA, Luiz G. P.; CREPALDI FILHO, Rene; PEREIRA, Nixon A.; SILVA, Joelmir L. V.; MENQUINI, Alfredo F.; SANDOVAL, Alexandre A. B.; GARCIA, Marcelo E.; LIMA, Edgard M. R.; BORGES, Gustavo; OTOCH, Jose Pinhata; MACHADO, Marcel C. C.- Reduction of venous pressure during the resection of liver metastases compromises enteric blood flow: IGFBP-1 as a novel biomarker of intestinal barrier injury(2017) BARBEIRO, Hermes Vieira; MACHADO, Marcel Autran Cesar; SOUZA, Heraldo Possolo de; SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira CesarOBJECTIVES: Disruption of the intestinal barrier and bacterial translocation commonly occur when intestinal blood flow is compromised. The aim of this study was to determine whether liver resection induces intestinal damage. METHODS: We investigated intestinal fatty-acid binding protein and insulin-like growth factor binding protein levels in the plasma of patients who underwent liver resection. RESULTS: We show that liver resection is associated with significant intestinal barrier injury, even if the Pringle maneuver is not performed. CONCLUSION: We propose the use of insulin-like growth factor binding protein-1 as a novel biomarker of intestinal damage in such situations.
- Septic Shock and the Aging Process: A Molecular Comparison(2017) SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira CesarAging is a continuous process promoted by both intrinsic and extrinsic factors that each trigger a multitude of molecular events. Increasing evidence supports a central role for inflammation in this progression. Here, we discuss how the low-grade chronic inflammation that characterizes aging is tightly interconnected with other important aspects of this process, such as DNA damage, mitochondrial dysfunction, and epigenetic changes. Similarly, inflammation also plays a critical role in many morbid conditions that affect patients who are admitted to Intensive Care. Although the inflammatory response is low grade and persistent in healthy aging while it is acute and severe in critically ill states, we hypothesize that both situations have important interconnections. Here, we performed an extensive review of the literature to investigate this potential link. Because sepsis is the most extensively studied disease and is the leading cause of death in Critical Care, we focus our discussion on comparing the inflammatory profile of healthy older people with that of patients in septic shock to explain why we believe that both situations have synergistic effects, leading to critically ill aged patients having a worse prognosis when compared with critically ill young patients.
- Cytokine and chemokine levels in the heart tissue of aged rats following severe acute pancreatitis(2017) AMARAL, Rizia Callou; BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; MADY, Charles; MACHADO, Marcel Cerqueira Cesar; SILVA, Fabiano Pinheiro daSevere acute pancreatitis (AP) is a disease associated with high mortality and characterized by overwhelming systemic inflammation. Older people have a prolonged hospital stay and worst prognosis, when affected by this disease. Our group hypothesized, thus, that the systemic inflammatory response in the elderly would promote more organ damage when compared to the young. We sought to investigate the effect of systemic inflammation on the gene expression of cytokines, chemokines, and growth factors in the hearts of older and younger rats in an animal model of AP. AP was induced in all rats by injection of 0.5 mL of 2.5% taurocholate. There were two healthy age-matched control groups. An array of 79 cytokines, chemokines, and growth factors was measured in samples of cardiac tissue taken from the AP rats after 10 h, and from control rats. Older healthy rats had significantly higher levels of interleukin-10 (IL-10) and CCL1 gene expression than younger ones (P < 0.05), but all other measurements were similar among the study groups. This study indicates the systemic inflammation may show unique features for different organs in the body, but older animals with systemic inflammation are similar to the young regarding the cardiac inflammatory response.
- Effect of parenteral infusion of fish oil-based lipid emulsion on systemic inflammatory cytokines and lung eicosanoid levels in experimental acute pancreatitis(2017) GARLA, Priscila; GARIB, Ricardo; TORRINHAS, Raquel S.; MACHADO, Marcel C. C.; CALDER, Philip C.; WAITZBERG, Dan L.Parenteral fish oil lipid emulsion (FOLE) might mitigate inflammation after injury. Acute pancreatitis (AP) can occur following major surgery and is characterized by tissue and systemic release of inflammatory mediators that contributes to the systemic inflammatory response syndrome and multiple organ failure. Aim: We evaluated the effect of short-term FOLE infusion before experimental induction of AP on systemic cytokine and lung eicosanoid profiles. Methods: Lewis rats (n = 72) received parenteral infusion of FOLE (FO group) or saline (SS group), or remained without parenteral infusion (CG group) for 48 h. Thereafter, AP was induced by retrograde injection of sodium taurocholate into the pancreatic duct. Animals were sacrificed after 2, 12 and 24 h. Blood and lung samples were collected to assess serum inflammatory cytokines (Luminex) and tissue eicosanoids (ELISA), respectively. Results: Serum TNF-alpha increased over time and serum IL-10 decreased from 12 to 24 h in CG group. In SS group serum TNF-alpha increased from 12 to 24 h (p = 0.039) and serum IL-10 decreased over time. Both CG and SS groups exhibited increased IL-6/IL-10 ratio (p = 0.040). From 12 to 24 h animals from FO group showed decreased serum IL-1 (p < 0.001), IL-4 (p < 0.002) and IL-6 (p = 0.050), and a trend towards increased IL-10 (p = 0.060). All experimental groups showed a trend towards increased PGE(2) and decreased LTB4 in the lung at 24 compared with 12 h Conclusion: Parenteral infusion of FOLE for 48 h before the induction of experimental AP appears to favorably influence the cytokine response without affecting lung eicosanoids at the time points measured. The use of FOLE to prevent and treat AP following major surgery needs to be further explored.
- The dual role of cathelicidins in systemic inflammation(2017) SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira CesarAntimicrobial peptides are key components of the innate immune system. They act as broad-spectrum antimicrobial agents against Gram-positive and negative bacteria, viruses, and fungi. More recently, antimicrobial peptides have been ascribed immunomodulatory functions, including roles in wound healing, induction of cytokines, and altering host gene expression. Cathelicidins are a class of antimicrobial peptide found in humans, mice, and rats, among others. Known as LL-37 in humans and cathelin-related antimicrobial peptide (CRAMP) in rodents, cathelicidins are produced by many different cells, including macrophages, neutrophils, and epithelial cells. The role of cathelicidins is somewhat confounding, as they exhibit both pro-and anti-inflammatory activity. A major obstacle in the study of cathelicidins is the inability of exogenous LL-37 or CRAMP to mimic the activity of their endogenous counterparts. Nevertheless, studies have shown that LL-37 is recognized by multiple receptors, and may stabilize or modulate Toll-like receptor signaling. In addition, cathelicidins play a role in apoptosis, inflammasome activation, and phagocytosis. However, many studies are revealing the dual effects of cathelicidins. For example, CRAMP appears to be protective in models of group A Streptococcus skin infection, pneumonia, and meningitis, but detrimental in cases of severe bacterial infection, such as septic shock. It is becoming increasingly clear that the activity of cathelicidins is modulated by complex interactions with the microenvironment, as well as the disease background. This article reviews what is currently known about the activity of cathelicidins in an attempt to understand their complex roles in systemic diseases. (C)2017 European Federation of Immunological Societies.
conferenceObject LIVER RESECTION INDUCES ACUTE INTESTINAL BARRIER DYSFUNCTION IGFBP-1 AS A NOVEL BIOMARKER OF INTESTINAL INJURY(2017) MACHADO, Marcel C. C.; BARBEIRO, Hermes; SOUZA, Heraldo P.; PINHEIRO, Fabiano; MACHADO, Marcel AutranconferenceObject RESECTABLE PANCREATIC NEUROENDOCRINE NEOPLASMS: CLINICOPATHOLOGICAL CHARACTERISTICS AND IMMUNOHISTOCHEMICAL CORRELATION(2017) NAVA, Carolin D.; COUDRY, Renata; MACHADO, Marcel C. C.; MEIRELLES, Luciana; GONCALVES, Marianne de Castro; PADUANI, Gabriela F.; CABRAL, Joao Guilherme G.; HYBNER, Luciano D.; ARDENGH, Jose Celso