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
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- Penetrance of Functioning and Nonfunctioning Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 in the Second Decade of Life(2014) GONCALVES, Tatiana D.; TOLEDO, Rodrigo A.; SEKIYA, Tomoko; MATUGUMA, Sergio E.; MALUF FILHO, Fauze; ROCHA, Manoel S.; SIQUEIRA, Sheila A. C.; GLEZER, Andrea; BRONSTEIN, Marcelo D.; PEREIRA, Maria A. A.; JUREIDINI, Ricardo; BACCHELLA, Telesforo; MACHADO, Marcel C. C.; TOLEDO, Sergio P. A.; LOURENCO JR., Delmar M.Context: Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. Apotential positive correlation between tumor size and malignancy (2-3 cm, 18%; >3 cm, 43%) has greatly influenced the management of MEN1 adults with NF-PETs. Objective: The aim of the study was to estimate the penetrance of NF-PETs, insulinomas, and gastrinomas in young MEN1 carriers. Design: The data were obtained from a screening program (1996-2012) involving 113 MEN1 patients in a tertiary academic reference center. Patients: Nineteen MEN1 patients (aged 12-20 y; 16 patients aged 15-20 y and 3 patients aged 12-14 y) were screened for NF-PETs, insulinomas, and gastrinomas. Methods: Magnetic resonance imaging/computed tomography and endoscopic ultrasound (EUS) were performed on 10 MEN1 carriers, magnetic resonance imaging/computed tomography was performed on five patients, and four other patients underwent an EUS. Results: The overall penetrance of PETs during the second decade of life was42%(8 of 19). All eight PET patients had NF-PETs, and half of those tumors were multicentric. One-fifth of the screened patients (21%; 4 of 19) harbored at least one large tumor (>2.0 cm). Insulinoma was detected in two NF-PET patients (11%) at the initial screening; gastrinoma was not present in any cases. Six of the 11 (54%) screened patients aged 15-20 years who underwent an EUS had NF-PETs. Potential false-positive EUS results were excluded based on EUS-guided biopsy results, the reproducibility of the NF-PET findings, or the observation of increased tumor size during follow-up. Distal pancreatectomy and the nodule enucleation of pancreatic head tumors were conducted on three patients with large tumors (>2.0 cm; T2N0M0) that were classified as grade 1 neuroendocrine tumors (Ki-67 < 2%). Conclusions: Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group.
- 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.
- Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress(2014) ROCHA-SANTOS, Vinicius; FIGUEIRA, Estela R. R.; ROCHA-FILHO, Joel A.; COELHO, Ana M. M.; PINHEIRO, Rafael Soraes; BACCHELLA, Telesforo; MACHADO, Marcel C. C.; D'ALBUQUERQUE, Luiz A. C.BACKGROUND: Liver ischemia reperfiision (IR) injury triggers a systemic inflammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver surgery. Pentoxifylline (PTX) and h-ypertonic saline solution (HTS) have been identified to have beneficial effects against IR injury This study aimed to investigate if the addition of PTX to HTS is superior to HTS alone for the prevention of liver IR injury. METHODS: Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes. of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaC1 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaC1 plus 25 mg/kg of PTX 15 minutes before reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-alpha, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase. RESULTS: HPTX significantly decreased TNF-alpha 30 minutes after reperfusion. HPTX and HTS significantly decreased ALT, AST, IL-6, mitochondrial dysfunction and pulmonary myeloperoxidase 4 hours after reperfusion. Compared with HTS only, HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion. CONCLUSION: This study showed that PTX added the beneficial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.
- 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.
conferenceObject Totally Laparoscopic Right Hepatectomy With Roux-en-Y Hepaticojejunostomy(2014) MACHADO, Marcel C.; SURJAN, Rodrigo C.; MAKDISSI, Fabio F.; MACHADO, Marcel Autran- PGC-1 alpha Expression Is Increased in Leukocytes in Experimental Acute Pancreatitis(2014) LLIMONA, Flavia; LIMA, Thais Martins de; MORETTI, Ana Iochabel; THEOBALDO, Mariana; JUKEMURA, Jose; VELASCO, Irineu Tadeu; MACHADO, Marcel C. C.; SOUZA, Heraldo PossoloSevere acute pancreatitis (AP) induces a systemic inflammatory disease that is responsible for high mortality rates, particularly when it is complicated by infection. Therefore, differentiating sepsis from the systemic inflammation caused by AP is a serious clinical challenge. Considering the high metabolic rates of leukocytes in response to stress induced by infection, we hypothesized that the transcription coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1 alpha), a master regulator of mitochondrial biogenesis and function, would be distinctly expressed during inflammation or infection and, therefore, could constitute a useful marker to differentiate between these two conditions. Rats were subjected to injection of taurocholate into the main pancreatic duct, which caused a severe AP with high amylase levels and white blood cell counts. In these animals, a marked increase in PGC-1 alpha mRNA levels in circulating leukocytes was observed 48 h after the surgical procedure, a time when bacteremia is present. Antibiotic treatment abolished PGC-1 alpha up-regulation. Moreover, PGC-1 alpha expression was higher in peritoneal macrophages from animals subjected to a bacterial insult (cecal ligation and puncture) than in animals with AP. In isolated macrophages, we also observed that PGC-1 alpha expression is more prominent in the presence of a phagocytic stimulus (zymosan) when compared to lipopolysaccharide-induced aseptic inflammation. Moreover, abolishing PGC-1 alpha expression with antisense oligos impaired zymosan phagocytosis. Together, these findings suggest that PGC-1 alpha is differentially expressed during aseptic inflammation and infection and that it is necessary for adequate phagocytosis. These results could be useful in developing new tests for differentiating infection from inflammation for clinical purposes in patients with AP.
- 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.- Antisense Oligonucleotides Targeted to KRAS Gene Could Inhibit the Tumor Growth, Invasion, and MMP-2 and MMP-9 Expression in Hamster Pancreatic Cancer Model In Vitro and In Vivo(2014) MORIOKA, Cintia; OTOCH, Jose; SAITO, Seiji; MACHADO, Marcel; WATANABE, Akiharu; HUANG, Cheng; COSTA, Frederico
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.