THAIS MARTINS DE LIMA
Projetos de Pesquisa
Unidades Organizacionais
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
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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. CesarconferenceObject Cathelicidin binds to transcriptional complexes in cancer cells(2016) SILVA, F. Pinheiro da; MUNOZ, M.; LIMA, T. Martins de; SEVERINO, P.; MACHADO, M. Cerqueira Cesar; REIS, E. Moraes; NAKAYA, H.; IRINEU, V- Effect of medium/omega-6 long chain triglyceride-based emulsion on leucocyte death and inflammatory gene expression(2011) CURY-BOAVENTURA, M. F.; GORJAO, R.; LIMA, T. Martins de; FIAMONCINI, J.; GODOY, A. B. P.; DESCHAMPHS, F. C.; SORIANO, F. G.; CURI, R.Lipid emulsion (LE) containing medium/omega-6 long chain triglyceride-based emulsion (MCT/omega-6 LCT LE) has been recommended in the place of omega-6 LCT-based emulsion to prevent impairment of immune function. The impact of MCT/omega-6 LCT LE on lymphocyte and neutrophil death and expression of genes related to inflammation was investigated. Seven volunteers were recruited and infusion of MCT/omega-6 LCT LE was performed for 6 h. Four volunteers received saline and no change was found. Blood samples were collected before, immediately afterwards and 18 h after LE infusion. Lymphocytes and neutrophils were studied immediately after isolation and after 24 and 48 h in culture. The following determinations were carried out: plasma-free fatty acids, triacylglycerol and cholesterol concentrations, plasma fatty acid composition, neutral lipid accumulation in lymphocytes and neutrophils, signs of lymphocyte and neutrophil death and lymphocyte expression of genes related to inflammation. MCT/omega-6 LCT LE induced lymphocyte and neutrophil death. The mechanism for MCT/omega-6 LCT LE-dependent induction of leucocyte death may involve changes in neutral lipid content and modulation of expression of genes related to cell death, proteolysis, cell signalling, inflammatory response, oxidative stress and transcription.
conferenceObject Obesity alters sepsis induced pulmonary inflammation(2012) LIMA-SALGADO, T.; FUNGARO, T. P.; PETRONI, R. C.; OLIVEIRA, S. J. S.; BARBEIRO, D. F.; SORIANO, F. G.Purpose/Objective: Sepsis is a severe disease that represents a significant healthcare burden worldwide, while obesity has reached epidemic proportions over the last few decades. Although the mechanism is uncharted, it is known that obesity increases morbidity and mortality in sepsis through its multiple effects on many organ systems, including pulmonary function. Our aim was to investigate the effects of obesity in systemic and pulmonary inflammatory process in an experimental model of endotoxemic shock. Materials and methods: Animals were fed a high fat diet (30% of fat) for 6 weeks and then injected with 15 mg/kg LPS i.p. They were euthanatized after 6, 24 and 48 h. Inflammation was characterized by measurement of plasma and pulmonary cytokines. The mRN expression of cytokines and tissue remodeling proteins was determined by real time PCR. Results: Obesity decreased the survival rate of the animals 24 h after LPS injection. There was higher plasma concentration of IL1-beta, IL-6and TNF-alpha in these animals. Furthermore, there was higher concentration of IL-6 in the obese mice’s lungs after 6 h of endotoxemia. However, the mRNA expression of pro-inflammatory factors (IL-6, TNF-alpha, IL-1beta and MMP9) was lower, suggesting they may be converted to proteins. Obese mice presented higher mRNA expression of TGF-beta after 6 h, indicating a reparative process. Conclusions: Obesity may be an additional complication factor in sepsis induced pulmonary inflammation.- High serum levels of fatty acid-binding protein 7 in diabetic rats with experimental sepsis(2018) MARTINS, Emerson R.; LIMA, Thais M. de; V, Hermes Barbeiro; MACHADO, Marcel C. Cesar; SILVA, Fabiano Pinheiro daSepsis is a disease that affects a wide variety of individuals, including the young, the elderly, and those admitted to the hospital with diverse acute or chronic conditions. Because sepsis is such a heterogeneous disease, some researchers believe that personalized medicine may represent a promising means of improving the prognosis for certain patients. Of those who develop sepsis, diabetic patients remain a significant proportion, because diabetes is a metabolic disorder that is associated with disturbances in the immune system, which facilitates bacterial infections. Fatty acid-binding proteins (FABPs) are a family of transport proteins with an important role in metabolism; therefore, we decided to measure their levels in diabetic rats, as part of a search for a novel biomarker of sepsis. Diabetes was experimentally induced in male Wistar rats, some of which then underwent cecal ligation and puncture, and the levels of FABP4 and FABP7 were measured in their serum and key tissues. Serum FABP7 levels in diabetic septic rats were significantly higher than those in non-diabetic septic rats. Consequently, we propose that FABP7 should be further investigated as a potential biomarker of sepsis in diabetic patients.
- Phagocytic activity of LPS tolerant macrophages(2014) LIMA, Thais Martins de; SAMPAIO, Sandra Coccuzzo; PETRONI, Ricardo; BRIGATTE, Patricia; VELASCO, Irineu Tadeu; SORIANO, Francisco GarciaEndotoxin tolerance is defined as a reduced capacity of the host to respond to LPS activation following a first exposure to this stimulus. It affects all leukocytes and regarding macrophages, most studies focus on the reduced ability of these cells to secrete pro-inflammatory cytokines. Therefore, we evaluated other macrophages functions (fungicidal capacity, reactive oxygen species production and antigen presentation) in cells from tolerant mice. We have performed a tolerance model in our laboratory that does not stimulate directly the place from where the cells will be removed (peritoneal cavity). Mouse received subcutaneous injections of LPS in the scruff for 5 days and we analyze the capacity of peritoneal macrophages to phagocyte using three different receptors: Fc, C3b and mannose receptors. We found a reduction in the phagocytosis of erythrocytes and Candida albicans related to the Fc and mannose receptors. These differences can be due to a macrophage reprogramming, as demonstrated by altered expression of cytokines and chemokines. Despite this reduction in phagocytosis capacity, macrophages from tolerant animals exhibited enhanced hydrogen peroxide production and expression of antigen presentation molecules, suggesting that their ability to combat an infection is improved. In summary, our data indicates that LPS tolerance drives macrophages from a predominant release of proinflammatory mediators that amplify inflammation and host damage toward a better killing and antigen presentation state.
- 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.
- Short-term Obesity Worsens Heart Inflammation and Disrupts Mitochondrial Biogenesis and Function in an Experimental Model of Endotoxemia(2022) PETRONI, Ricardo Costa; OLIVEIRA, Suelen Jeronymo Souza de; FUNGARO, Thais Pineda; ARIGA, Suely K. K.; BARBEIRO, Hermes Vieira; SORIANO, Francisco Garcia; LIMA, Thais Martins deCardiomyopathy is a well-known complication of sepsis that may deteriorate when accompanied by obesity. To test this hypothesis we fed C57black/6 male mice for 6 week with a high fat diet (60% energy) and submitted them to endotoxemic shock using E. coli LPS (10 mg/kg). Inflammatory markers (cytokines and adhesion molecules) were determined in plasma and heart tissue, as well as heart mitochondrial biogenesis and function. Obesity markedly shortened the survival rate of mouse after LPS injection and induced a persistent systemic inflammation since TNF alpha, IL-1 beta, IL-6 and resistin plasma levels were higher 24 h after LPS injection. Heart tissue inflammation was significantly higher in obese mice, as detected by elevated mRNA expression of pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF alpha). Obese animals presented reduced maximum respiratory rate after LPS injection, however fatty acid oxidation increased in both groups. LPS decreased mitochondrial DNA content and mitochondria biogenesis factors, such as PGC1 alpha and PGC1 beta, in both groups, while NRF1 expression was significantly stimulated in obese mice hearts. Mitochondrial fusion/fission balance was only altered by obesity, with no influence of endotoxemia. Obesity accelerated endotoxemia death rate due to higher systemic inflammation and decreased heart mitochondrial respiratory capacity.
conferenceObject Epigenetic profile in lipopolysaccharide-stimulate macrophages(2012) RIOS, E. C. S.; LIMA-SALGADO, T. M.; SORIANO, F. G.Purpose/Objective: Sepsis remains a clinical challenge for the intensive care units. However, it is known that the tolerance mechanism using low doses of lipopolysaccharide (LPS) reduces the expression of proinflammatory genes and involves epigenetic regulation. The chromatin openness is regulated by Histone Acetyltransferases (HATs) and these enzymes could be modulated by Nitric Oxide (NO) interaction. In the present work, we demonstrate the pathway of tolerance to LPS from HAT activity and level of histone openness to production of cytokines as well as the influence of NO inhibition. Materials and methods: THP1 differentiated into macrophages (with 2.5 nM PMA treatment) were cultivated in RPMI medium (Control group), submitted to tolerance (500 ng/ml of LPS 24 h before challenge with 1000 ng/ml of LPS * Tolerant group) and challenge (1000 ng/ml of LPS * D group) during 24 h. NO production was inhibited by addition of 100 l M of LNAME. The HAT activity and cytokine production (IL-6) were measured with biochemistry kits. Histone acetylated H3 and H4 were analyzed by western blotting. Results: Tolerance reduced HAT activity compared with group directly challenged (P< 0.05). The H4 acetylated was maintained at basal levels in the tolerant group and increased in the D group (P< 0.05). However, the tolerance increases the acetylation of Histone H3 in a NO-dependent response. Similarly, the IL-6 release was reduced by induction of tolerance (P< 0.05 versus D). However, this effect was abolished by inhibition of NO production. Conclusions: The induction of tolerance reduces HAT activity and cytokine production. The tolerance triggers a complex epigenetic modulation dependent of Nitric Oxide.- Hypertonic Saline (NaCl 7.5 %) Reduces LPS-Induced Acute Lung Injury in Rats(2015) PETRONI, Ricardo Costa; BISELLI, Paolo Jose Cesare; LIMA, Thais Martins de; THEOBALDO, Mariana Cardillo; CALDINI, Elia Tamaso; PIMENTEL, Rosangela Nascimento; BARBEIRO, Hermes Vieira; KUBO, Suely Ariga; VELASCO, Irineu Tadeu; SORIANO, Francisco GarciaAcute respiratory distress syndrome (ARDS) is the most severe lung inflammatory manifestation and has no effective therapy nowadays. Sepsis is one of the main illnesses among ARDS causes. The use of fluid resuscitation is an important treatment for sepsis, but positive fluid balance may induce pulmonary injury. As an alternative, fluid resuscitation with hypertonic saline ((HS) NaCl 7.5 %) has been described as a promising therapeutical agent in sepsis-induced ARDS by the diminished amount of fluid necessary. Thus, we evaluated the effect of hypertonic saline in the treatment of LPS-induced ARDS. We found that hypertonic saline (NaCl 7.5 %) treatment in rat model of LPS-induced ARDS avoided pulmonary function worsening and inhibited type I collagen deposition. In addition, hypertonic saline prevented pulmonary injury by decreasing metalloproteinase 9 (MMP-9) activity in tissue. Focal adhesion kinase (FAK) activation was reduced in HS group as well as neutrophil infiltration, NOS2 expression and NO content. Our study shows that fluid resuscitation with hypertonic saline decreases the progression of LPS-induced ARDS due to inhibition of pulmonary remodeling that is observed when regular saline is used.