MILTON DE ARRUDA MARTINS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
43 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 43
- Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice (vol 8, 12636, 2018)(2018) GENARO, Isabella Santos de; ALMEIDA, Francine Maria de; HIZUME-KUNZLER, Deborah Camargo; MORIYA, Henrique Takachi; SILVA, Ronaldo Aparecido; CRUZ, Joao Carlos Goncalves; LOPES, Renan Boeira; RIGHETTI, Renato Fraga; VIEIRA, Rodolfo de Paula; SAIKI, Mitiko; MARTINS, Milton Arruda; TIBERIO, Iolanda de Fatima Lopes Calvo; ARANTES-COSTA, Fernanda Magalhaes; SARAIVA-ROMANHOLO, Beatriz Mangueira
- Treatment with proteinase inhibitor from Enterolobium contortisiliquum in mice with asthma-COPD(2020) BARBOSA, Jessica Anastacia Silva; SILVA, Luana Laura Sales Da; JOAO, Juliana Morelli Lopes Goncalves; SANTOS, Tabata Maruyama Dos; CAMARGO, Leandro Nascimento; CAMPOS, Elaine Cristina De; GALLI, Thiago Tafarel; SARAIVA-ROMANHOLO, Beatriz Mangueira; BEZERRA, Suellen Karoline Moreira; HAMAGUCHI, Sara Sumie Sobral; LEICK, Edna Aparecida; PRADO, Carla Maximo; MARTINS, Milton De Arruda; OLIVO, Maria Luiza Vilela; RIGHETTI, Renato Fraga; TIBERIO, Iolanda De Fatima Lopes Calvo
- Anti-IL17 treatment control responses in lung injury induced by elastase(2018) FUKUZAKI, Silvia; GARRIDO, Aurelio C.; RIGHETTI, Renato F.; SANTOS, Tabata M.; CAMARGO, Leandro N.; ARISTOTELES, Luciana R. C. R. B.; SOUZA, Flavia C. R.; SARAIVA-ROMANHOLO, Beatriz M.; LEICK, Edna A.; PRADO, Carla M.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.
- Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases(2016) SANTANA, Fernanda Paula R.; PINHEIRO, Nathalia M.; MERNAK, Marcia Isabel B.; RIGHETTI, Renato F.; MARTINS, Milton A.; LAGO, Joao H. G.; LOPES, Fernanda D. T. Q. dos Santos; TIBERIO, Iolanda F. L. C.; PRADO, Carla M.Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.
- iNOS Inhibition Reduces Lung Mechanical Alterations and Remodeling Induced by Particulate Matter in Mice(2019) PRADO, Carla Maximo; RIGHETTI, Renato Fraga; LOPES, Fernanda Degobbi Tenorio Quirino dos Santos; LEICK, Edna Aparecida; ARANTES-COSTA, Fernanda Magalhaes; ALMEIDA, Francine Maria de; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; TIBERIO, Iolanda de Fatima Lopes Calvo; MARTINS, Milton de ArrudaBackground. The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and acute lung damage is well known. However, the mechanism involved in the effects of repeated exposures of PM in the lung injury is poorly documented. This study tested the hypotheses that chronic nasal instillation of residual oil fly ash (ROFA) induced not only distal lung and airway inflammation but also remodeling. In addition, we evaluated the effects of inducible nitric oxide inhibition in these responses. For this purpose, airway and lung parenchyma were evaluated by quantitative analysis of collagen and elastic fibers, immunohistochemistry for macrophages, neutrophils, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and alveolar septa 8-iso prostaglandin F2 (8-iso-PGF-2) detection. Anesthetized in vivo (airway resistance, elastance, H, G, and Raw) respiratory mechanics were also analyzed. C57BL6 mice received daily 60ul of ROFA (intranasal) for five (ROFA-5d) or fifteen days (ROFA-15d). Controls have received saline (SAL). Part of the animals has received 1400W (SAL+1400W and ROFA-15d+1400W), an iNOS inhibitor, for four days before the end of the protocol. A marked neutrophil and macrophage infiltration and an increase in the iNOS, nNOS, and 8-iso-PGF2 expression was observed in peribronchiolar and alveolar wall both in ROFA-5d and in ROFA-15d groups. There was an increment of the collagen and elastic fibers in alveolar and airway walls in ROFA-15d group. The iNOS inhibition reduced all alterations induced by ROFA, except for the 8-iso-PGF2 expression. In conclusion, repeated particulate matter exposures induce extracellular matrix remodeling of airway and alveolar walls, which could contribute to the pulmonary mechanical changes observed. The mechanism involved is, at least, dependent on the inducible nitric oxide activation.
- Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice(2018) GENARO, Isabella Santos de; ALMEIDA, Francine Maria de; HIZUME-KUNZLER, Deborah Camargo; MORIYA, Henrique Takachi; SILVA, Ronaldo Aparecido; CRUZ, Joao Carlos Goncalves; LOPES, Renan Boeira; RIGHETTI, Renato Fraga; VIEIRA, Rodolfo de Paula; SAIKI, Mitiko; MARTINS, Milton Arruda; TIBERIO, Iolanda de Fatima Lopes Calvo; ARANTES-COSTA, Fernanda Magalhaes; SARAIVA-ROMANHOLO, Beatriz MangueiraWork-exacerbated asthma (WEA) is defined as preexisting asthma that worsens with exposure to irritants [e.g., chlorine (Cl-2) derivatives] in the workplace. The maximum allowable concentration in the workplace of Cl-2 exposure is 3 mg/m(3) (described in OSHA). We investigated in an experimental asthma model in mice the effects of a single exposure to a sodium hypochlorite dose with this allowed chlorine concentration and a tenfold higher dose. Acute chlorine exposure at 3.3 mg/m(3) in the OVA-sensitized group increased eosinophils in the peribronquial infiltrate, cytokine production, nasal mucus production and the number of iNOS positive cells in the distal lung compared to only sensitized mice. The exposure to a higher dose of 33.3 mg/m(3) in the OVA-sensitized group resulted in an increase in respiratory system elastance, in the total and differential numbers of inflammatory cells in bronchoalveolar lavage fluid, IL-4, IL-5, and IL-17 in the lungs, eosinophils in peribronquial infiltrate and mucus content in nasal compared to non-exposed and sensitized animals. In this asthma model, chorine exposures at an allowable dose, contributed to the potentiation of Th2 responses. The functional alterations were associated with increased iNOS and ROCK-2 activation in the distal lung.
- Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma(2018) SANTOS, Tabata M. dos; RIGHETTI, Renato F.; CAMARGO, Leandro do N.; SARAIVA-ROMANHOLO, Beatriz M.; ARISTOTELES, Luciana R. C. R. B.; SOUZA, Flavia C. R. de; FUKUZAKI, Silvia; ALONSO-VALE, Maria I. C.; CRUZ, Maysa M.; PRADO, Carla M.; LEICK, Edna A.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.Background: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for the treatment of this disease. Objective: To study the effects of an anti-IL17 neutralizing antibody and ROCK inhibitor treatments, separately and in combination, in a murine model of chronic allergy-induced lung inflammation. Methods: Sixty-four BALBc mice, were divided into eight groups (n = 8): SAL (saline-instilled); OVA (exposed-ovalbumin); SAL-RHOi (saline and ROCK inhibitor), OVA-RHOi (exposed-ovalbumin and ROCK inhibitor); SAL-anti-IL17 (saline and anti-IL17); OVA-anti-IL1 7 (exposed-ovalbumin and anti-IL1 7); SAL-RHOi-anti-IL17 (saline, ROCK inhibitor and anti-IL17); and OVA-RHOi-anti-IL17 (exposed-ovalbumin, anti-IL17, and ROCK inhibitor). A 28-day protocol of albumin treatment was used for sensitization and induction of pulmonary inflammation. The anti-IL17A neutralizing antibody (7.5 mu g per treatment) was administered by intraperitoneal injection and ROCK inhibitor (Y-27632) intranasally (10 mg/kg), 1 h prior to each ovalbumin challenge (days 22, 24, 26, and 28). Results: Treatment with the anti-IL17 neutralizing antibody and ROCK inhibitor attenuated the percentage of maximal increase of respiratory system resistance and respiratory system elastance after challenge with methacholine and the inflammatory response markers evaluated (CD4(+), CD8(+), ROCK1, ROCK2, IL-4, IL-5, IL-6, IL-10 IL-13, IL-17, TNF-alpha, TGF-beta, NF-kappa B, dendritic cells, iNOS, MMP-9, MMP-12, TIMP-1, FOXP3, isoprostane, biglycan, decorin, fibronectin, collagen fibers content and gene expression of IL-17, VAChT, and arginase) compared to the OVA group (p < 0.05). Treatment with anti-IL17 and the ROCK inhibitor together resulted in potentiation in decreasing the percentage of resistance increase after challenge with methacholine, decreased the number of IL-5 positive cells in the airway, and reduced, IL-5, TGF beta, FOXP3, ROCK1 and ROCK2 positive cells in the alveolar septa compared to the OVA-RHOi and OVA-anti-IL17 groups (p < 0.05). Conclusion: Anti-IL17 treatment alone or in conjunction with the ROCK inhibitor, modulates airway responsiveness, inflammation, tissue remodeling, and oxidative stress in mice with chronic allergic lung inflammation.
conferenceObject Rho Kinase Inhibition Associated To Corticosteroid Treatment Decreases Th1/th2 Responses, Nfkappa B, Mmp-9 And Timp-1 On Airways And Distal Lung Tissue In Animals With Chronic Allergic Inflammation(2013) PIGATI, P. A. Da Silva; RIGHETTI, R. F.; POSSA, S. S.; RODRIGUES, A. P. D.; XISTO, D. G.; LEICK, E. A.; PRADO, C. M.; MARTINS, M. A.; ROCCO, P. R. M.; TIBERIO, I. F. L. C.- Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS(2018) CAMARGO, Leandro do Nascimento; RIGHETTI, Renato Fraga; ARISTOTELES, Luciana Ritha de Cassia Rolim Barbosa; SANTOS, Tabata Maruyama dos; SOUZA, Flavia Castro Ribas de; FUKUZAKI, Silvia; CRUZ, Maysa Mariana; ALONSO-VALE, Maria Isabel Cardoso; SARAIVA-ROMANHOLO, Beatriz Mangueira; PRADO, Carla Maximo; MARTINS, Milton de Arruda; LEICK, Aparecida; TIBERIO, Iolanda de Fatima Lopes CalvoInflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-kappa B, and Rho kinase 1-and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.
- Bronchial Vascular Remodeling Is Attenuated by Anti-IL-17 in Asthmatic Responses Exacerbated by LPS(2020) CAMARGO, Leandro do Nascimento; SANTOS, Tabata Maruyama dos; ANDRADE, Felipp Costa Pinto de; FUKUZAKI, Silvia; LOPES, Fernanda Degobbi Tenorio Quirino dos Santos; MARTINS, Milton de Arruda; PRADO, Carla Maximo; LEICK, Edna Aparecida; RIGHETTI, Renato Fraga; TIBERIO, Iolanda de Fatima Lopes CalvoIntroduction Although the major alterations associated with asthma are related to the airways, there is also evidence of the importance of peribronchial vascular inflammation and remodeling in its pathophysiology. Objectives To determine the effects of anti-IL-17 therapy on peribronchial vessels of an asthma model exacerbated by lipopolysaccharide. Methods We evaluated several factors, including lung function, inflammation, oxidative stress, vascular remodeling, and signaling pathways present in the peribronchial vessels of 66 male BALB/c mice exposed to ovalbumin and treated (or not) treated with anti-IL-17. Twenty-four hours before the end of the experimental protocol, groups of sensitized animals (OVA-LPS and OVA-LPS anti-IL-17) also received LPS. Results The OVA-LPS-anti-IL-17 group presented a decrease in several factors [airway resistance and elastance, bronchoalveolar lavage fluid (BALF) cell counts, inflammatory response, eosinophils, TSLP, IL-33, TARC, TNF-alpha, CD4+, CD8+, IL-4, IL-6, IL-10, IL-17, and VEGF positive cells/10(4)mu m(2), peribronchovascular edema, and angiogenesis], including remodeling (MMP-9, MMP-12, TIMP-1 and TGF-beta positive cells and volume fraction of collagen fibers I, collagen fibers III, collagen fibers V, decorin, lumican, actin, biglycan, fibronectin, and integrin), oxidative stress (iNOS positive cells and volume fraction of PGF2 alpha), and signaling pathways (FoxP3), as well as dendritic cells, NF-kB, ROCK-1, ROCK-2, STAT-1, and phosphor-STAT1-positive cells compared to OVA-LPS (p < 0.05). Conclusions In this model of LPS-induced asthma exacerbation, IL-17 inhibition represents a promising therapeutic strategy, indicating the potential of bronchial vascular control of Th2 and Th17 responses and the activation of the remodeling and oxidative stress pathways, associated with the control of signaling pathways.