Navegando por Autor "Teixeira, Mauro Martins"
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Item Acute exercise modulates the inflammatory response in adipose tissue of lean and obese mice.(2023) Lacerda, Débora Romualdo; Silva, Albená Nunes da; Silveira, Ana Letícia Malheiros; Costa, Kátia Anunciação; Rodrigues, Débora Fernandes; Moraes, Michele Macedo; Pinho, Vanessa; Menezes, Gustavo Batista; Teixeira, Mauro Martins; Wanner, Samuel Penna; Soares, Danusa Dias; Ferreira, Adaliene Versiani MatosAcute physical exercise act as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodelling process. In addition, some cytokines have important functions in lipolysis. Since chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein, we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. Lean mice were fed a standard chow diet, whereas obese mice were fed a high- refined carbohydrate (HC) diet for 8 weeks. Both groups were subjected to 60 min of moderately-intensity exercise. In the epididymal adipose tissue (EAT) of lean mice, exercise enhanced IL-6 and TNF-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of EAT vessels revealed higher recruitment of neutrophils following exercise. Also, the number of leucocytes expressing CD11b+F480– was elevated 6 h after exercise. Similarly, the CXCL-1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity were increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in EAT from obese mice considering pro-inflammatory cytokines (IL-6 and TNF-). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. These data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodelling. In contrast, acute exercise promotes an anti-inflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostatic.Item Aerobic training modulates the increase in plasma concentrations of cytokines in response to a session of exercise.(2021) Fonseca, Tatiana Ramos; Mendes, Thiago Teixeira; Ramos, Guilherme Passos; Cabido, Christian Emmanuel Torres; Morandi, Rodrigo Figueiredo; Ferraz, Fernanda Oliveira; Miranda, Aline Elizabeth da Silva; Mendonça, Vanessa Amaral; Teixeira, Antônio Lúcio; Garcia, Emerson Silami; Silva, Albená Nunes da; Teixeira, Mauro MartinsAcute physical exercise can modulate immune function. For example, acute exercise is known to increase the circulating concentration of cytokines. Exercise is also known to modulate immune function chronically. It is not known whether exercise training can result in training of the immune system. Here, we investigated the effects of six weeks of aerobic training on cytokine responses induced by acute exercise until fatigue. Twelve healthy men performed a fatiguing exercise at the anaerobic threshold (AT) intensity. After the training period, the participants performed another bout of acute exercise at the same duration and intensity of the pretraining situation. ,e analysis was made at the beginning, end, and at 10, 30, and 60 minutes during the recovery period. Training at AT induced a gain of 11.2% of exercise capacity. Before training, a single bout of acute exercise induced a significant increase in plasma levels of cytokines, including IL-6, TNF-α, sTNFR1, IL-10, CXCL10, BDNF, leptin, resistin, and adiponectin. After six weeks of aerobic training, levels of IL-6, sTNFR1, BDNF, and leptin increased to a lesser extent after an acute bout exercise at the same absolute intensity as the pretraining period. Responses to the same relative exercise intensity were similar to those observed before exercise. ,ese results show that aerobic training is associated with training of acute immune responses to acute exercise until fatigue.Item Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice.(2018) Lacerda, Débora Romualdo; Moraes, Michele Macedo; Silva, Albená Nunes da; Costa, Kátia Anunciação; Rodrigues, Débora Fernandes; Sabino, Josiana Lopes; Cordeiro, Letícia Maria de Souza; Pinho, Vanessa; Teixeira, Mauro Martins; Wanner, Samuel Penna; Soares, Danusa Dias; Ferreira, Adaliene Versiani MatosObesity is associated with an energy imbalance that results from excessive energy intake, low diet quality and a sedentary lifestyle. In this regard, the increased consumption of a high-refined carbohydrate diet (HC) is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known non-pharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by the HC diet need to be further investigated. Herein, our hypothesis was that aerobic training would decrease the recruitment of leukocytes in the adipose tissue thereby reducing the levels of cytokines and improving metabolism in mice fed the HC diet. Male Balb/c were assigned to the following groups: control non-trained (C-NT), control trained (C-T), HC-NT and HC-T. Mice were submitted to moderate-intensity training sessions that consisted of running 60 min/day for 8 weeks. The intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, HC-T mice showed an increased resting energy expenditure, a decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition relative to HC-NT mice. Collectively, our data enhance the understanding about the antiinflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.Item Bj-PRO-5a and Bj-PRO 10c found at c-type natriuretic peptide precursor of bothrops jararaca change renal function of hypertensive rats.(2017) Custódio, Carlos Henrique Xavier; Miranda, José Rodolfo Rubini; Yamaguchi, Juliana; Silveira, Kátia Daniela da; Teixeira, Mauro Martins; Chianca Júnior, Deoclécio Alves; Silva, Ana Cristina Simões e; Santos, Robson Augusto Souza dos; Camargo, Antônio Carlos Martins de; Ianzer, Danielle AlvesProline-rich oligopeptides from Bothrops jararaca (Bj-PROs) produce potent and long-lasting antihypertensive effect through mechanisms that go beyond ACE inhibition. In this study we evaluated the renal function parameters of spontaneously hypertensive rats (SHR) injected with Bj-PRO-5a and -10c (0.47, 71 or 710 nmol/ kg) found in the CNP-precursor of the snake. At 71 and 710 nmol/kg, Bj-PROs increased urinary flow rate (18.1– 43.5%). At 71 nmol/kg, Bj-PRO 5a and 10c elevated sodium excretion (68.1 and 40.9%, respectively) and Bj- PRO-5a also increased urinary sodium/creatinine ratio (56.5%). At 0.47 nmol/kg, Bj-PROs did not change renal function. All doses of Bj-PROs reduced blood pressure (Δ = −13 to −24mmHg). We conclude that Bj-PROs reduce blood pressure and improve renal functiItem Brain natriuretic peptide based strategy to detect left ventricular dysfunction in Chagas disease : a comparison with the conventional approach.(2006) Ribeiro, Antônio Luiz Pinho; Teixeira, Mauro Martins; Reis, Adelina Martha dos; Silva, André Talvani Pedrosa da; Perez, Amanda Arantes; Barros, Márcio Vinicius Lins; Rocha, Manoel Otávio da CostaBackground: Left ventricular dysfunction (LVd) is the main predictor of mortality in Chagas disease (ChD). Aims: To compare the diagnostic performance of the conventional approach (ECG and chest X-ray) in the recognition of LVd in ChD, with a new strategy, in which BNP is measured in patients with an abnormal ECG. Methods: Consecutive ChD patients recruited at an Outpatient Reference Center in Belo Horizonte, Brazil, without other systemic diseases, in 1998–99 (sample 1, n =165) and in 2001–02 (sample 2, n =62) underwent ECG, chest X-ray, BNP measurement and echocardiography. Results: The prevalence of LVd (ejection fraction _0.40) was 9.1% in the sample 1. The conventional strategy recognized all patients with LVd (sensitivity: 100%, 95% CI: 79.6–100% and negative predictive value _PV 100%, 92.1–100%), but with low specificity (30%, 95% CI: 23.2–37.8) and +PV (12.5%, 95% IC: I7.7–19.6). The BNP/ECG strategy showed significantly better specificity (96.0%, 95% CI: 91.5–98.2, p <0.001) and +PV (66.7%, 95% CI: 43.7–83.7, p <0.001), and non-significantly lower sensitivity (80.0%, 95% CI: 54.8–93.0, p =0.25) and _PV (98.0%,95% CI: 94.2–99.3, p =0.08). Overall accuracy was improved with the new strategy. (94.5%,95% CI: 90.0– 97.1_36.4%, 95% CI: 29.4–43.9, p <0.001). Similar results were obtained for the sample 2. Conclusions: The BNP-based strategy was more accurate than the conventional approach in the detection of LVd in ChD patients and should be considered as a valid option.Item Cyclic AMP decreases the production of NO and CCL2 by macrophages stimulated with Trypanosoma cruzi GPI-mucins.(2009) Silva, André Talvani Pedrosa da; Coutinho, Sibele Ferreira; Barcelos, Luciola da Silva; Teixeira, Mauro MartinsGlycosylphosphatidylinositol-anchored mucinlike glycoproteins (tGPI-mucin) present on the surface of the cellular membrane of Trypanosoma cruzi forms activate toll-like receptors 2 (TLR2) on the surface of immune cells and induce the release of several mediators of inflammation which may be relevant in the context of Chagas disease. Here, we evaluated the ability of tGPI-mucins to activate murine peritoneal macrophages to induce nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1/CCL2). We also investigated the ability of compounds which increase or mimic cyclic adenosine monophosphate (AMP) to modulate the production of NO and CCL2. Our data show that elevation of intracellular levels of cyclic AMP prevents the release of NO and CCL2 induced by tGPI-mucins in macrophages. Overall, the release of CCL2 was decreased to a greater extent and at lower concentrations of cyclic AMP-modifying agents than the production of NO. It is suggested that the elevation of cyclic AMP during T. cruzi infection may modify the release of proinflammatory mediators and alter significantly the course of T. cruzi infection.Item Deposição e uniformidade de distribuição da calda de aplicação em plantas de café utilizando a pulverização eletrostática.(2013) Sasaki, Robson Shigueaki; Teixeira, Mauro Martins; Fernandes, Haroldo Carlos; Monteiro, Paulo Marcos de Barros; Rodrigues, Denilson EduardoNo âmbito da tecnologia de aplicação de agrotóxicos, a pulverização eletrostática é um sistema disponível comercialmente, no entanto, pouco empregado, devido à existência de algumas divergências quanto à efi ciência desse sistema, razão pela qual o entendimento dessa tecnologia e suas interações com a planta tornam-se necessários. Nesse contexto, objetivouse avaliar a utilização da pulverização eletrostática na cultura do café quanto à efi ciência de deposição e a uniformidade de distribuição da calda de aplicação. Utilizou-se um pulverizador eletrostático, marca Electrostatic Spraying Systems, modelo ESS MBP 4.0. O experimento foi instalado no delineamento de parcelas subsubdivididas (2x3x6), com dois sistemas de pulverização (sistema eletrostático ligado e desligado), três partes da planta (superior, médio e inferior) e seis posições de coleta das folhas, com quatro repetições. Quanto à uniformidade de distribuição, observou-se que houve maior variabilidade na deposição, quando o sistema eletrostático permaneceu ligado, com maior deposição na parte externa do dossel. Os valores de coefi ciente de variação para o sistema eletrostático ligado e desligado foi de 40,3 e 33,08%, respectivamente. O sistema eletrostático foi efi ciente na pulverização em plantas de café e proporcionou aumento de 37% na deposição da calda de aplicação em relação ao sistema eletrostático desligado.Item Does Croton argyrophyllus extract has an effect on muscle damage and lipid peroxidation in rats submitted to high intensity strength exercise?(2019) Araújo, Silvan Silva de; Martins, Felipe José Aidar; Matos, Dihogo Gama de; Santos, Jymmys Lopes dos; Souza, Lúcio Marques Vieira; Silva, Albená Nunes da; Santos, Rodrigo Miguel dos; Marçal, Anderson Carlos; Mourão, Daniella Mota; Júnior, Amário Lessa; Durães, Geraldo Magela; Carneiro, André Luiz Gomes; Silva, Rodrigo Gonçalves da; Teixeira, Mauro Martins; Estevam, Charles dos SantosMany species of the genus Croton have been used for anti-inflammatory, antiproliferative, antidiabetic, and antitumor purposes. The objective was to evaluate the e ect of a hydroethanolic extract (HEE) from the inner bark of Croton argyrophyllus (Euphorbiaceae) on muscle damage and oxidative stress in rats after high intensity exercise. The animals were divided into four groups: (i) the sedentary group (SV; n = 7), (ii) the exercise vehicle group (EV, n = 7), (iii) the sedentary group HEE (SHG; n = 7) composed of sedentary animals and treated with the hydroethanolic extract of C. argyrophyllus (200 mg/kg, v.o.), and (iv) the HEE exercise group (HEE; n = 7) composed of animals submitted to resistance exercise (RE) and treated with the hydroethanolic extract of C. argyrophyllus (200 mg/kg, v.o.). In the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) test, the HEE showed lower values of inhibition potential (IP%) at 39.79% compared to gallic acid, 87.61%, and lipoperoxidation inhibition at 27.4% (100 µg/mL) or 28.6% (200 µg/mL) (p < 0.001). There was inhibition in free radicals in vivo. The HEE of C. argyrophyllus partially reduced the biomarkers of oxidative stress in muscle tissue and muscular damage (creatine kinase (CK) and Lactate Dehydrogenase (LDH)) (p < 0.05) in rats, and in this sense it can be an aid to the recovery process after exhaustive e orts.Item Effect of early treatment with Hydroxychloroquine or Lopinavir and Ritonavir on risk of hospitalization among patients with COVID-19.(2021) Reis, Gilmar; Silva, Eduardo Augusto dos Santos Moreira; Silva, Daniela Carla Medeiros; Thabane, Lehana; Singh, Gurmit; Park, Jay J. H.; Forrest, Jamie I.; Harari, Ofir; Santos, Castilho Vitor Quirino dos; Almeida, Ana Paula Figueiredo Guimarães de; Figueiredo Neto, Adhemar Dias de; Savassi, Leonardo Cançado Monteiro; Milagres, Aline Cruz; Teixeira, Mauro Martins; Simplicio, Maria Izabel Campos; Ribeiro, Luciene Barra; Oliveira, Rosemary; Mills, Edward J.IMPORTANCE Data on the efficacy of hydroxychloroquine or lopinavir-ritonavir for the treatment of high-risk outpatients with COVID-19 in developing countries are needed. OBJECTIVE To determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial was conducted in Brazil. Recently symptomatic adults diagnosed with respiratory symptoms from SARS-CoV-2 infection were enrolled between June 2 and September 30, 2020. The planned sample size was 1476 patients, with interim analyses planned after 500 patients were enrolled. The trial was stopped after the interim analysis for futility with a sample size of 685 patients. Statistical analysis was performed in December 2020. INTERVENTIONS Patients were randomly assigned to hydroxychloroquine (800 mg loading dose, then 400 mg daily for 9 days), lopinavir-ritonavir (loading dose of 800 mg and 200 mg, respectively, every 12 hours followed by 400 mg and 100 mg, respectively, every 12 hours for the next 9 days), or placebo. MAIN OUTCOMES AND MEASURES The primary outcomes were COVID-19–associated hospitalization and death assessed at 90 days after randomization. COVID-19–associated hospitalization was analyzed with a Cox proportional hazards model. The trial included the following secondary outcomes: all-cause hospitalization, viral clearance, symptom resolution, and adverse events. RESULTS Of 685 participants, 632 (92.3%) self-identified as mixed-race, 377 (55.0%) were women, and the median (range) age was 53 (18-94) years. A total of 214 participants were randomized to hydroxychloroquine; 244, lopinavir-ritonavir; and 227, placebo. At first interim analysis, the data safety monitoring board recommended stopping enrollment of both hydroxychloroquine and lopinavir-ritonavir groups because of futility. The proportion of patients hospitalized for COVID-19 was 3.7% (8 participants) in the hydroxychloroquine group, 5.7% (14 participants) in the lopinavir ritonavir group, and 4.8% (11 participants) in the placebo group. We found no significant differences between interventions for COVID-19–associated hospitalization (hydroxychloroquine: hazard ratio [HR], 0.76 [95% CI, 0.30-1.88]; lopinavir-ritonavir: HR, 1.16 [95% CI, 0.53-2.56] as well as for the secondary outcome of viral clearance through day 14 (hydroxychloroquine: odds ratio [OR], 0.91 [95% CI, 0.82-1.02]; lopinavir-ritonavir: OR, 1.04 [95% CI, 0.94-1.16]). At the end of the trial, there were 3 fatalities recorded, 1 in the placebo group and 2 in the lopinavir-ritonavir intervention group. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, neither hydroxychloroquine nor lopinavir-ritonavir showed any significant benefit for decreasing COVID-19–associated hospitalization or other secondary clinical outcomes. This trial suggests that expedient clinical trials can be implemented in low-income settings even during the COVID-19 pandemic.Item Effect of physical training on exercise-induced inflammation and performance in mice.(2021) Barcellos, Luiz Alexandre Medrado de; Gonçalves, William Antonio; Oliveira, Marcos Paulo Esteves de; Guimarães, Juliana Bohnen; Queiroz Júnior, Celso Martins; Resende, Carolina Braga de; Russo, Remo de Castro; Coimbra, Cândido Celso; Silva, Albená Nunes da; Teixeira, Mauro Martins; Gonçalves, Barbara Maximino Rezende; Silva, Vanessa Pinho daAcute exercise increases the amount of circulating inflammatory cells and cytokines to maintain physiological homeostasis. However, it remains unclear how physical training regulates exercise-induced inflammation and performance. Here, we demonstrate that acute high intensity exercise promotes an inflammatory profile characterized by increased blood IL-6 levels, neutrophil migratory capacity, and leukocyte recruitment to skeletal muscle vessels. Moreover, we found that physical training amplified leukocyte– endothelial cell interaction induced by acute exercise in skeletal muscle vessels and diminished exercise-induced inflammation in skeletal muscle tissue. Furthermore, we verified that disruption of the gp-91 subunit of NADPH-oxidase inhibited exerciseinduced leukocyte recruitment on skeletal muscle after training with enhanced exercise time until fatigue. In conclusion, the training was related to physical improvement and immune adaptations. Moreover, reactive oxygen species (ROS) could be related to mechanisms to limit aerobic performance and its absence decreases the inflammatory response elicited by exercise after training.Item Effects of resistance training and Bowdichia virgilioides hydroethanolic extract on oxidative stress markers in rats submitted to peripheral nerve injury.(2020) Costa, Luana Santos; Martins, Felipe José Aidar; Matos, Dihogo Gama de; Oliveira, José Uilien de; Santos, Jymmys Lopes dos; Almeida Neto, Paulo Francisco de; Souza, Raphael Fabrício de; Pereira, Danielle Dutra; Garrido, Nuno Domingos; Silva, Albená Nunes da; Marçal, Anderson Carlos; Estevam, Charles dos Santos; Cabral, Breno Guilherme de Araújo Tinôco; Reis, Victor Machado; Teixeira, Mauro MartinsThe objective of this study was to analyze the effects of the combination of resistance training (RT) and the hydroethanolic extract (EHE) of Bowdichia virgilioides as markers of oxidative stress (OS) in rats with peripheral nerve injury (PNI). Rats were allocated into six groups (n = 10): animals without interventions (C), animals with an exposed nerve but without injury, injured animals, trained and injured animals, injured animals that received EHE, and animals that received a combination of RT and EHE. RT comprised the climbing of stairs. EHE was orally administered (200 mg/kg) for 21 days after PNI induction. RT reduced the amount of lipoperoxidation in plasma (14.11%). EHE reduced lipoperoxidation in the plasma (20.72%) and the brain (41.36). RT associated with the extract simultaneously reduced lipoperoxidation in the plasma (34.23%), muscle (25.13%), and brain (43.98%). There was an increase in total sulhydrilyl levels (a) in the brain (33.33%) via RT; (b) in the brain (44.44%) and muscle (44.51%) using EHE; and (c) in the plasma (54.02%), brain (54.25%), and muscle using the combination of RT + EHE. These results suggest that RT associated with oral EHE results in a decrease in OS.Item Enalapril prevents cardiac immune-mediated damage and exerts anti- Trypanosoma cruzi activity during acute phase of experimental Chagas disease.(2010) Costa, Guilherme de Paula; Silva, Rafael Rodrigues; Pedrosa, Michelle Cristine; Silva, Vanessa Pinho da; Lima, Wanderson Geraldo de; Teixeira, Mauro Martins; Bahia, Maria Terezinha; Silva, André Talvani Pedrosa daChagas heart disease (CHD), caused by Trypanosoma cruzi infection, is a significant cause of morbidity and mortality in South and Central America. Enalapril, an angiotensin converting enzyme (ACE) inhibitor, is an important drug used to ameliorate heart functional capacity and its remodelling in individuals presenting CHD. In this study, we evaluated the effects of enalapril on systemic and cardiac immune response during experimental acute CHD. C57BL ⁄ 6 mice infected with 50 trypomastigote forms of T. cruzi (Colombian strain) were treated daily with enalapril (25 mg ⁄ kg) and, after 30 days, a reduction in seric levels of IFNgamma, TNF-alpha, CCL5⁄RANTES and nitric oxide, but not in that of IL-10, was detected. This imbalance of cytokines reflects in a reduction of heart mononuclear infiltration and in an increasing of cardiac mast cells. Enalapril also presents a new and interesting in vitro and in vivo anti- T. cruzi activity probably acting on parasite oxidative pathway via cytochrome-P450. Our data show that enalapril exerts an important anti-T. cruzi and anti-inflammatory activity during acute CHD reducing inflammatory cells and, possibly, preventing fibrotic process in the chronic phase. Nevertheless, further studies are still necessary to clarify the mechanisms by which this drug is acting on the parasites and on the immune pathways.Item Experimental Trypanosoma cruzi infection and chagas disease : a word of caution.(2023) Silva, André Talvani Pedrosa da; Teixeira, Mauro MartinsItem In vivo inhibitory effect of anti-muscarinic autoantibodies on the parasympathetic function in Chagas disease.(2010) Ribeiro, Antônio Luiz Pinho; Carvalho, Antônio Carlos Campos de; Lombardi, Federico; Silva, André Talvani Pedrosa da; Teixeira, Mauro Martins; Rocha, Manoel Otávio da CostaItem Involvement of the chemokine RANTES (CCL5) in resistance to experimental infection with Leishmania major.(2004) Santiago, Helton da Costa; Oliveira, Carolina Ferreira; Santiago, Luciana; Ferraz, Fernanda Oliveira; Souza, Daniele da Glória de; Freitas, Luiz Antônio Rodrigues de; Afonso, Luís Carlos Crocco; Teixeira, Mauro Martins; Gazzinelli, Ricardo Tostes; Vieira, Leda QuerciaThe expression and putative role of chemokines during infection with Leishmania major in mice were investigated. CCL5 expression correlates with resistance, and blockade of CCL5 rendered mice more susceptible to infection. CCL5 is part of the cascade of events leading to efficient parasite control in L. major infection.Item Mechanisms underlying fat pad remodeling induced by fasting : role of PAF receptor.(2019) Lacerda, Débora Romualdo; Soares, Danusa Dias; Costa, Kátia Anunciação; Silva, Albená Nunes da; Rodrigues, Débora Fernandes; Sabino, Josiana Lopes; Silveira, Ana Letícia Malheiros; Pinho, Vanessa; Vieira, Érica Leandro Marciano; Menezes, Gustavo Batista; Antunes, Maísa Mota; Teixeira, Mauro Martins; Ferreira, Adaliene Versiani MatosObjectives: Fasting has long been practiced for political and religious reasons and to lose weight. However, biological responses during fasting have yet to be fully understood. Previous studies have shown that cytokines may control fat pad expansion, at least in part, owing to the induction of lipolysis. Indeed, we have previously shown that mice with a lower inflammatory response, such as platelet-activating factor receptor knockout mice (PAFR / ), are prone to gain weight and adiposity. The aims of this study were to determine whether adipose tissue becomes inflamed after fasting and to evaluate whether the PAF signaling is a fator in the fat loss induced by fasting. Methods: Wild-type (WT) and PAFR / mice were fasted for 24 h. Adiposity, leukocyte recruitment, and cytokine levels were evaluated. Multiple comparisons were performed using two-way analysis of variance and post hoc Fisher exact test. Results: After fasting, male WT mice showed lower adiposity (P < 0.001), higher recruitment of immune cells (P < 0.001), and increased cytokine levels (P < 0.05) in adipose tissue. Although WT mice lost ~79% of their adipose tissue mass, PAFR / mice lost only 36%. Additionally, PAFR / mice did not show enhanced cytokine and chemokine levels after fasting (P > 0.05). Conclusion: Despite low-grade inflammation being associated with metabolic syndrome, at least in part, the inflammatory milieu is also important to induce proper fat mobilization and remodeling of adipose tissue.Item Molecular mechanisms of myocarditis caused by Trypanosoma cruzi.(2015) Esper, Lísia; Silva, André Talvani Pedrosa da; Pimentel, Pollyana; Teixeira, Mauro Martins; Machado, Fabiana SimãoAmerican trypanosomiasis, or Chagas disease, is a lifelong and persistent infection caused by the protozoan Trypanosoma cruzi and is the most significant cause of morbidity and mortality in South and Central America. Owing to immigration and additional risks from blood transfusion and organ transplantation, the number of reported cases of Chagas disease has increased recently in Europe and the USA. The disease is caused by a moderate to intense lasting inflammatory response that triggers local expression of inflammatory mediators and activates and recruits leukocytes to various tissues to eliminate the parasites.Item Oral formulation of Angiotensin-(1-7) promotes therapeutic actions in a model of eosinophilic and meutrophilic asthma.(2021) Magalhães, Giselle Santos; Gregório, Juliana Fabiana; Ribeiro, Arthur Tonani Pereira Cançado; Baroni, Isis Felippe; Vasconcellos, Ana Victoria de Oliveira; Nakashima, Gabriela Pansanato; Oliveira, Isabel Fusaro Aguiar; Matos, Natália Alves de; Castro, Thalles de Freitas; Bezerra, Frank Silva; Sinisterra, Ruben Dario; Pinho, Vanessa; Teixeira, Mauro Martins; Santos, Robson Augusto Souza dos; Machado, Maria da Glória Rodrigues; Santos, Maria José Campagnole dosThe presence of eosinophils and neutrophils in the lungs of asthmatic patients is associated with the severity of the disease and resistance to corticosteroids. Thus, defective resolution of eosinophilic and neutrophilic inflammation is importantly related to exacerbation of asthma. In this study, we investigated a therapeutic action of angiotensin-(1-7) (Ang-(1-7)) in a model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS). Balb-c mice were sensitized and challenged with OVA. Twentythree hours after the last OVA challenge, experimental groups received LPS, and 1 h and 7 h later, mice were treated with oral formulation of Ang-(1-7). On the next day, 45 h after the last challenge with OVA, mice were subjected to a test of motor and exploratory behavior; 3 h later, lung function was evaluated, and bronchoalveolar lavage fluid (BALF) and lungs were collected. Motor and exploratory activities were lower in OVA + LPSchallenged mice. Treatment with Ang-(1-7) improved these behaviors, normalized lung function, and reduced eosinophil, neutrophil, myeloperoxidase (MPO), eosinophilic peroxidase (EPO), and ERK1/2 phosphorylation (p-ERK1/2) in the lungs. In addition, Ang-(1-7) decreased the deposition of mucus and extracellular matrix in the airways. These results extended those of previous studies by demonstrating that oral administration of Ang-(1-7) at the peak of pulmonary inflammation can be valuable for the treatment of neutrophil- and eosinophil-mediated asthma. Therefore, these findings potentially provide a new drug to reverse the natural history of the disease, unlike the current standards of care that manage the disease symptoms at best.Item Plasma concentrations of tumour necrosis factor-alpha, tumour necrosis factor-related apoptosis-inducing ligand, and FasLigand/CD95L in patients with Chagas cardiomyopathy correlate with left ventricular dysfunction.(2009) Lula, Jamille Fernandes; Rocha, Manoel Otávio da Costa; Nunes, Maria do Carmo Pereira; Ribeiro, Antônio Luiz Pinho; Teixeira, Mauro Martins; Bahia, Maria Terezinha; Silva, André Talvani Pedrosa daCardiomyocyte apoptosis is reported to be involved in the pathogenesis of human chronic Chagas cardiomyopathy (CCC). Members of the tumour necrosis factor (TNF) superfamily (TNF-a, FasLigand/CD95L, and TNF-related apoptosis-inducing ligand) are known to activate the death receptor pathway. We therefore investigated whether levels of TNF-a, FasLigand/CD95L, and TRAIL correlated with changes in heart function of patients with Chagas disease (n ¼ 31). Concentrations of TNF-a and TRAIL were clearly augmented in individuals with severe form CCC (n ¼ 16). Levels of FasLigand/CD95L were greater in chagasic patients than in non-infected individuals (n ¼ 15) but did not differentiate between clinical forms of Chagas disease. There was a good correlation between TNF-a (r ¼ 0.85 and r ¼ 0.68, P , 0.0001) or TRAIL (r ¼ 0.68 and r ¼ 0.60, P , 0.001) and left ventricular ejection fraction (LVEF) and left ventricular diastolic diameter (LVDD), respectively. In addition, TNF-a (r ¼ 0.57, P ¼ 0.0001), TRAIL (r ¼ 0.56, P ¼ 0.001), and FasLigand/CD95L (r ¼ 0.51, P ¼ 0.001) showed a good correlation with brain natriuretic peptide, a well-known parameter of ventricular dysfunction in CCC. There was a weak correlation between levels of FasLigand/CD95L (r ¼ 0.50, P , 0.004) and both LVEF and LVDD. There was no correlation between levels of TNF superfamily ligands and chronotropic incompetence, maximal heart rate, or number of ventricular premature beats in 24 h. Plasma levels of TNF superfamily ligands are elevated in patients with functional but not arrhythmogenic disturbances, and these death receptor ligands may be potential markers of ventricular dysfunction in CCC.Item Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.(2023) Silva, Juliana Priscila Vago da; Zaidan, Isabella; Perucci, Luiza Oliveira; Brito, Larissa Froede; Teixeira, Lívia Cristina Ribeiro; Silva, Camila Meirelles Souza; Miranda, Thaís Cristina de; Melo, Eliza Mathias; Bruno, Alexandre Santos; Queiroz Júnior, Celso Martins; Sugimoto, Michelle Adriane Amantéa; Tavares, Luciana Padua; Ferreira, Lais Cunha Grossi; Borges, Isabela Nascimento; Schneider, Ayda Henriques; Baik, Nagyung; Silva, André Talvani Pedrosa da; Ferreira, Raphael Gomes; Alves Filho, José Carlos Farias; Nobre Junior, Vandack Alencar; Teixeira, Mauro Martins; Parmer, Robert J.; Miles, Lindsey A.; Sousa, Lirlândia Pires deSepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla– afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.