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
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
conferenceObject Increase of splenic lymphocyte apoptosis in septic encephalopathy(2014) JEREMIAS, Isabela; VICTORINO, Vanessa; LIMA, Thais; SORIANO, FranciscoconferenceObject Effect of low level laser therapy on lung mechanics and inflammatory response(2013) CURY, Vivian; LIMA, Thais; ARIGA, Suely; BARBEIRO, Denise; PINHEIRO, Nathalia; PRADO, Carla Maximo; MORETTI, Ana Iochabel; SOUZA, Heraldo PossoloconferenceObject Late remodeling of extracellular matrix after acute inflammatory injury or chronic distension(2012) PRIST, Iryna Hirata; SALLES, Alessandra Grassi; SALGADO, Thais M. de Lima; SOUZA, Heraldo Possolo DeExtracellular matrix remodeling is a crucial step in the healing process after inflammatory or infectious insult. We studied the role of matrix metalloproteinases in models of disease secondary to an acute inflammatory injury (burned skin) or chronic aggression (skin from obese patients submitted to gastroplasty). Skin samples were extracted using a 4 mm punch from abdomen of patients in late post-operative of bariatric surgery, recovered from third degree burns or control subjects. RNA was extracted by TRIzol and evaluated by quantitative PCR. MMPs activity was determined by zymography. In skin from burned patients, MMPs 2 and 9 expression was not different from control subjects. Obese patients present a higher MMP2 expression, compared to controls (2.4±0.56 x 1.0±0.1, respectively, p<0.05), however MMP9 mRNA was not detectable in these patients, even when conventional PCR was used. Interestingly, in spite of higher mRNA amounts, MMP2 activity was reduced in burned patients compared to controls (1.3±0.1 x 2.6±0.5 A.U., respectively, p<0.05), while MMP9 activity had a large variability, preventing any conclusion. We conclude that an acute inflammatory stimulus leads to late decreased MMP2 activity, what can explain the extensive fibrosis observed in these patients. In a more prolonged injury, due to chronic skin distension caused by obesity, MMP9 expression is affected leading to flabby skin deposits.- Molecular Mechanisms by Which Saturated Fatty Acids Modulate TNF-alpha Expression in Mouse Macrophage Lineage(2011) LIMA-SALGADO, Thais Martins de; ALBA-LOUREIRO, Tatiana C.; NASCIMENTO, Caroline S. do; NUNES, Maria T.; CURI, RuiMany macrophage functions are modulated by fatty acids (FAs), including cytokine release, such as tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is of great interest due to its role in the inflammation process observed in several diseases such as rheumatoid arthritis, atherosclerosis, and obesity. However, the mechanisms by which FA effects occur have not been completely elucidated yet. In this study, we used a mouse monocyte lineage (J774 cells) to evaluate the effect of 50 and 100 mu M of saturated (palmitic and stearic acids), monounsaturated (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-alpha production. Alterations in gene expression, poly(A) tail length and activation of transcription factors were evaluated. Oleic and linoleic acids, usually known as neutral or pro-inflammatory FA, inhibited LPS-induced TNF-alpha secretion by the cells. Saturated FAs were potent inducers of TNF-alpha expression and secretion under basal and inflammatory conditions (in the presence of LPS). Although the effect of the saturated FA was similar, the mechanism involved in each case seem to be distinct, as palmitic acid increased EGR-1 and CREB binding activity and stearic acid increased mRNA poly(A) tail. These results may contribute to the understanding of the molecular mechanisms by which saturated FAs modulate the inflammatory response and may lead to design of associations of dietary and pharmacological strategies to counteract the pathological effects of TNF-alpha.
- Sepsis Induces Telomere Shortening: a Potential Mechanism Responsible for Delayed Pathophysiological Events in Sepsis Survivors?(2016) OLIVEIRA, Naara Mendes; RIOS, Ester C. S.; LIMA, Thais Martins de; VICTORINO, Vanessa Jacob; BARBEIRO, Hermes; SILVA, Fabiano Pinheiro da; SZABO, Csaba; SORIANO, Francisco GarciaSepsis survivors suffer from additional morbidities, including higher risk of readmissions, nervous system disturbances and cognitive dysfunction, and increased mortality, even several years after the initial episode of sepsis. In many ways, the phenotype of sepsis survivors resembles the phenotype associated with accelerated aging. Since telomere shortening is a hallmark of aging, we investigated whether sepsis also leads to telomere shortening. Male balb/c mice were divided into two groups: the control group received 100 mu l of normal saline intraperitoneally (i.p.) and the sepsis group received 15 mg/kg of bacterial lipopolysaccharide i.p. After 48 h, animals were euthanized to collect blood, spleen and kidney. The human component of our study utilized blood samples obtained from patients in the trauma department and samples collected 7 d later in those patients who developed sepsis. Telomere length was measured by quantitative polymerase chain reaction. Since oxidative stress is a known inducer of telomere shortening, thiobarbituric acid-reactive substances and superoxide dismutase activity were analyzed to evaluate oxidative stress burden. Induction of endotoxemia in mice resulted in significant telomere shortening in spleen and kidney. Blood cells from patients who progressed to sepsis also exhibited a statistically significant reduction of telomere length. Endotoxemia in mice also induced an early-onset increase in oxidative stress markers but was not associated with a downregulation of telomerase protein expression. We conclude that endotoxemia and sepsis induce telomere shortening in various tissues and hypothesize that this may contribute to the pathogenesis of the delayed pathophysiological events in sepsis survivors.
- Novel role of TLR4 in NAFLD development: Modulation of metabolic enzymes expression(2015) FERREIRA, Darkiane Fernandes; FIAMONCINI, Jarlei; PRIST, Iryna Hirata; ARIGA, Suely Kubo; SOUZA, Heraldo Possolo de; LIMA, Thais Martins deThe rise in the prevalence of obesity and metabolic syndrome turned NAFLD as the most common cause of chronic liver diseases worldwide. Although the role of toll like receptors, especially TLR4, as activators of inflammatory pathways in liver diseases is well established, our goal was to investigate if TLR4 activation could modulate metabolic lipid pathways and alter the onset of NAFLD. We used LDL receptor-deficient mice (LDLrKO) fed with an atherogenic diet as a model. The role of TLR4 activation was evaluated by crossing LDLrKO mice with the TLR4 knockout mice. Animals were fed for 12 weeks with high-fat high-cholesterol diet (HFD) containing 18% saturated fat and 1.25% cholesterol. TLR4/LDLr KO mice presented lower triacylglyceride (TAG) plasma levels when compared to LDLrKO, despite the type of diet ingested. HFD induced TAG and cholesterol accumulation in the liver of all mice genotypes studied, but TLR4/LDLr KO presented lower TAG accumulation than LDLrKO mice. Gene expression of TAG synthesis enzymes (ApoB100, MTTP, GPAT1 and GPAT4) was not differentially altered in TLR4/LDLr KO and LDLrKO mice. On the other hand, TLR4 deficiency enhanced the expression of several enzymes involved in the oxidation of fatty acids, as follows: ACOX, CPT-1, MTPa, MTBb, PBE and 3-ketoacyl-CoA thiolase. Acyl-camitine plasma profile showed an increase in C0 and C2 concentration in TLR4/LDLr KO group, corroborating the hypothesis of increased fat oxidation. Our results indicate that TLR4 may have an important role in the onset of steatosis, once its depletion enhances fatty acid oxidation in the liver of mice, preventing triglyceride accumulation.
conferenceObject Effect of low level laser therapy on acute lung injury(2012) CURY, Vivian; LIMA-SALGADO, Thais; PINHEIRO, Natalia; PRADO, Carla Maximo; ASSIS, Livia; MORETTI, Ana Iochabel; SOUZA, Heraldo PossoloLow level laser therapy (LLLT) is prescribed as adjuvant therapy for inflammatory diseases. Hence, we examined whether LLLT may ameliorate acute lung injury (ALI) induced by intratracheal LPS instillation. C57 black mice (n=10 per group) were treated with intratracheal LPS (5mg/kg) or PBS. Six hours after instillation, two groups (PBS and LPS) were irradiated with laser at 660 nm, power output 30mW, fluency 10J/cm2. We observed a marked decrease in the number of cells recovered by bronchoalveolar lavage in LPS + LLLT animals compared to LPS alone (2.0±0.8 x 4.4±1.3, respectively p<0.05). LLLT also decreased the number of inflammatory cells infiltrated in lung interstitium (49.6±3.15 x 71.8±3.92), p<0.05). There was also a decrease in the expression of F4/80 (macrophage surface marker) and MCP-1 (monocyte chemoattractant protein-1), detected by quantitative PCR, in animals submitted to LPS + LLLT, when compared to animals that received only LPS. A marked decrease in cytokines secretion (IL1β, TNFα, IL6, IL10) was also observed in LPS+LLLT group. No difference was observed in animals that received PBS, regardless of LLLT. Therefore, LLLT decreases pulmonary inflammatory cell infiltration, cytokines and chemokines secretion in an experimental model of ALI, supporting the notion that laser therapy attenuates inflammatory intensity, what can contribute to accelerate ALI resolution.- 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 Expression of peroxisome proliferator activated receptor gamma coactivator 1 (PGC-1) on the immune response to bacteria(2012) NERO, Luis Guilherme Del; MARTA, Guilherme; LIMA-SALGADO, Thais; KUBO, Sueli; LLIMONA, Flavia; VELASCO, Irineu Tadeu; SOUZA, HeraldoIntroduction/Objective: Inflammatory response during sepsis requires energy expenditure from immune cells. Since the transcription coactivator PGC-1 controls cell energy homeostasis, we aimed to determine whether PGC-1 may modulate the immune response in an experimental model of sepsis. Methods: Live bacteria were injected intraperitoneally in Balb/C mice and PGC-1β expression was evaluated by quantitative PCR in peritoneal macrophages. Further, mice (20 animals in each group) were submitted to cecal ligation and puncture (CLP). Group 1 received intraperitoneal injections of antisense oligonucleotide (ASO) against PGC-1β (3,0 nmol) three days before and three days after CLP. Group 2 was given no specific treatment. The animals were followed for 72 hours and mortality was evaluated every 12 hours. Results: Increased PGC-1β expression was observed in macrophages from animals exposed to bacteria compared to controls (2.7±0.5 vs. 1.0±0.2, respectively, p<0.05). We further evaluated whether PGC-1β absence would interfere with the response to acute bacterial aggression in vivo. Mice from Group 1, where PGC-1β expression was blocked, showed an 80% mortality after 72 hours, while animals from Group 2 had a mortality rate of 63% (p=0,7714). Conclusions: PGC-1β is up-regulated during bacterial infection, however, abolishing PGC-1β expression did not affect mortality of septic mice.