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
310 resultados
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article 31 Citação(ões) na Scopus Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling(2011) BISELLI, P. J. C.; LOPES, F. D. T. Q. S.; MORIYA, H. T.; RIVERO, D. H. R. F.; TOLEDO, A. C.; SALDIVA, P. H. N.; MAUAD, T.; MARTINS, A.Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-beta 1 (TGF-beta 1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-beta 1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-beta 1.- Airway remodeling is reversed by aerobic training in a murine model of chronic asthma(2015) SILVA, R. A.; ALMEIDA, F. M.; OLIVO, C. R.; SARAIVA-ROMANHOLO, B. M.; MARTINS, M. A.; CARVALHO, C. R. F.The aim of this study was to investigate if the aerobic training (AT) reverses airway remodeling (AR) in an asthma model. BALB/c were divided into four groups: control (unsensitized and untrained); ovalbumin (OVA: sensitized and untrained); AT (unsensitized and trained) and OVA+AT. Allergic inflammation was induced with intraperitoneal and OVA inhalation. AT (low intensity; 5x/week; 60min/session) was performed at 7, 15, and 30 days. Leukocyte counting in the bronchoalveolar lavage fluid; the expression of IL-5, eotaxin, RANTES, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1); AR features (airway smooth muscle, epithelium thickness, collagen and elastic fibers, mucus production); and AR inducers (transforming growing factor-beta, osteopontin, vascular endothelial growth factor). OVA induced an increase in leukocyte airway migration and increased AR features (P<0.05). After 7 days, AT reversed the OVA-induced eosinophil and macrophage airway migration, the expression of IL-5, eotaxin, RANTES, ICAM-1, VCAM-1, and all AR inducers. However, total reversion of the AR features and inducers and airway inflammation occurred only after 15 days of AT compared with the OVA groups (P<0.05) and the effects were maintained until the 30th day. AT reverses AR after 15 days and this effect is preceded by the inhibition of leukocyte migration and occurs simultaneously with the reduction in the expression of inflammatory mediators and AR inducers.
- Exercise training is a determinant of weight-loss and improvement on asthma control, airway inflammation and psychosocial morbidity in obese asthmatics: A RCT(2015) FREITAS, Patricia D.; FERREIRA, Palmira G.; SILVA, Aline G.; CUKIER, Alberto; STELMACH, Rafael; CARVALHO-PINTO, Regina; SALGE, Joao M.; MANCINI, Marcio C.; MARTINS, Milton A.; CARVALHO, Celso R. F.
- Comparison of the Effects of Aerobic Conditioning Before and After Pulmonary Allergic Inflammation(2015) SILVA, Ronaldo Aparecido da; ALMEIDA, Francine Maria; OLIVO, Clarice Rosa; SARAIVA-ROMANHOLO, Beatriz Mangueira; PERINI, Adenir; MARTINS, Milton Arruda; CARVALHO, Celso Ricardo FernandesThe aim of this study is to compare the effects of aerobic conditioning (AC) before (ACBS) and after (ACAS) allergic sensitization. BALB/c mice were divided into two main groups: ACBS and ACAS. Each groups was divided into subgroups: control (nonsensitized/nontrained), AC (nonsensitized/trained), ovalbumin (OVA) (sensitized/nontrained), AC + OVA (trained/sensitized), and OVA + AC (sensitized/trained). Sensitization was induced using OVA and AC performed in treadmill (moderate intensity). We examined IgE and IgG(1) levels, eosinophil counting, expression of Th1 (interleukin (IL)-2, IFN-alpha) and Th2 cytokines (IL-4, IL-5, IL-13), IL-10, vascular endothelial growth factor (VEGF), and airway remodeling. IgE and IgG(1) were decreased only when exercise was performed before sensitization (ACBS); however, there was a decrease of eosinophils, Th2 cytokines, VEGF, and airway remodeling and increase in IL-10 in either ACBS or ACAS groups. Our results demonstrate that aerobic conditioning reduces Th2 response before and after sensitization by increasing IL-10 while the production of anaphylactic antibodies is reduced only when exercise is performed before sensitization.
conferenceObject IL-10 and IL-1ra mediates OVA-induced Th2 airway allergic response at short and long-term(2013) SILVA, Ronaldo Aparecido; ALMEIDA, Francine Maria; OLIVO, Clarice Rosa; SARAIVA, Beatriz Mangueira; PERINI, Adenir; MARTINS, Milton Arruda; CARVALHO, Celso Ricardo Fernandes- The tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure(2018) LOURENCO, Juliana D.; ITO, Juliana T.; CERVILHA, Daniela A. B.; SALES, Davi S.; RIANI, Alyne; SUEHIRO, Camila L.; GENARO, Isabella S.; DURAN, Adriana; PUZER, Luciano; MARTINS, Milton A.; SASAKI, Sergio D.; LOPES, Fernanda D. T. Q. S.Introduction. Smoking is the main risk factor for chronic obstructive pulmonary disease development and cigarette smoke (CS) exposure is considered an important approach to reproduce in rodents this human disease. We have previously shown that in an elastase induced model of emphysema, the administration of a protease inhibitor (rBmTI-A) prevented and attenuated tissue destruction in mice. Thus, in this study we aimed to verify the effects of rBmTI-A administration on the physiopathological mechanisms of CS induced emphysema. Methods. Mice (C57BL/6) were exposed to CS or room air for 12 weeks. In this period, 3 nasal instillations of rBmTI-A inhibitor or its vehicle were performed. After euthanasia, respiratory mechanics were evaluated and lungs removed for analysis of mean linear intercept, volume proportion of collagen and elastic fibers, density of polymorphonuclear cells, macrophages, and density of positive cells for MMP-12, MMP-9, TIMP-1 and gp91phox. Results. The rBmTI-A administration improved tissue elastance, decreased alveolar enlargement and collagen fibers accumulation to control levels and attenuated elastic fibers accumulation in animals exposed to CS. There was an increase of MMP-12, MMP-9 and macrophages in CS groups and the rBmTIA only decreased the number of MMP-12 positive cells. Also, we demonstrated an increase in gp91phox in CS treated group and in TIMP-1 levels in both rBmTI-A treated groups. Conclusion. In summary, the rBmTI-A administration attenuated emphysema development by an increase of gp91phox and TIMP-1, accompanied by a decrease in MMP-12 levels.
- Relationship among Medical Student Resilience, Educational Environment and Quality of Life(2015) TEMPSKI, Patricia; SANTOS, Itamar S.; MAYER, Fernanda B.; ENNS, Sylvia C.; PEROTTA, Bruno; PARO, Helena B. M. S.; GANNAM, Silmar; PELEIAS, Munique; GARCIA, Vera Lucia; BALDASSIN, Sergio; GUIMARAES, Katia B.; SILVA, Nilson R.; CRUZ, Emirene M. T. Navarro da; TOFOLI, Luis F.; SILVEIRA, Paulo S. P.; MARTINS, Milton A.Context Resilience is a capacity to face and overcome adversities, with personal transformation and growth. In medical education, it is critical to understand the determinants of a positive, developmental reaction in the face of stressful, emotionally demanding situations. We studied the association among resilience, quality of life (QoL) and educational environment perceptions in medical students. Methods We evaluated data from a random sample of 1,350 medical students from 22 Brazilian medical schools. Information from participants included the Wagnild and Young's resilience scale (RS-14), the Dundee Ready Educational Environment Measure (DREEM), the World Health Organization Quality of Life questionnaire - short form (WHOQOL-BREF), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Results Full multiple linear regression models were adjusted for sex, age, year of medical course, presence of a BDI score >= 14 and STAI state or anxiety scores >= 50. Compared to those with very high resilience levels, individuals with very low resilience had worse QoL, measured by overall (beta=-0.89; 95% confidence interval =-1.21 to -0.56) and medical-school related (beta=-0.85; 95% CI=-1.25 to -0.45) QoL scores, environment (beta=-6.48; 95% CI=-10.01 to -2.95), psychological (beta=-22.89; 95% CI=-25.70 to -20.07), social relationships (beta=-14.28; 95% CI=-19.07 to -9.49), and physical health (beta=-10.74; 95% CI=-14.07 to -7.42) WHOQOL-BREF domain scores. They also had a worse educational environment perception, measured by global DREEM score (beta=-31.42; 95% CI=-37.86 to -24.98), learning (beta=-7.32; 95% CI=-9.23 to -5.41), teachers (beta=-5.37; 95% CI=-7.16 to -3.58), academic self-perception (beta=-7.33; 95% CI=-8.53 to -6.12), atmosphere (beta=-8.29; 95% CI=-10.13 to -6.44) and social self-perception (beta=-3.12; 95% CI=-4.11 to -2.12) DREEM domain scores. We also observed a dose-response pattern across resilience level groups for most measurements. Conclusions Medical students with higher resilience levels had a better quality of life and a better perception of educational environment. Developing resilience may become an important strategy to minimize emotional distress and enhance medical training.
conferenceObject Reduction In Vacht Levels Induced Pulmonary Inflammation In Experimental Model Of Pulmonary Emphysema(2015) BANZATO, R.; PINHEIRO, N. M.; OLIVO, C.; RANCON, F.; LOPES, F.; CAPERUTO, L.; CAMARA, N.; MARTINS, M.; TIBERIO, I.; PRADO, M.; PRADO, V.; PRADO, C.conferenceObject Central Insulin Regulates Airways Reactivity by ERK1/2 Pathway in Cholinergic Neurons(2014) LEIRIA, Luiz; ARANTES-COSTA, Fernanda; MOURA, Rodrigo; DONATO JR., Jose; ANTUNES, Edson; VELLOSO, Licio A.; MARTINS, Milton Arruda; SAAD, Mario J. A.- Stress amplifies lung tissue mechanics, inflammation and oxidative stress induced by chronic inflammation(2012) REIS, Fabiana G.; MARQUES, Ricardo H.; STARLING, Claudia M.; ALMEIDA-REIS, Rafael; VIEIRA, Rodolfo P.; CABIDO, Claudia T.; SILVA, Luiz Fernando F.; LANCAS, Tatiana; DOLHNIKOFF, Marisa; MARTINS, Milton A.; LEICK-MALDONADO, Edna A.; PRADO, CarlaM.; TIBERIO, Iolanda F. L. C.Background: Mechanisms linking behavioral stress and inflammation are poorly understood, mainly in distal lung tissue. Objective: We have investigated whether the forced swim stress (FS) could modulate lung tissue mechanics, iNOS, cytokines, oxidative stress activation, eosinophilic recruitment, and remodeling in guinea pigs (GP) with chronic pulmonary inflammation. Methods: The GP were exposed to ovalbumin or saline aerosols (2x/wk/4wks, OVA, and SAL). Twenty-four hours after the 4th inhalation, the GP were submitted to the FS protocol (5x/wk/2wks, SAL-S, and OVA-S). Seventy-two hours after the 7th inhalation, lung strips were cut and tissue resistance (Rt) and elastance (Et) were obtained (at baseline and after OVA and Ach challenge). Strips were submitted to histopathological evaluation. Results: The adrenals' weight, the serum cortisol, and the catecholamines were measured. There was an increase in IL-2, IL-5, IL-13, IFN-gamma, iNOS, 8-iso-PGF2 alpha, and in %Rt and %Et after Ach challenge in the SAL-S group compared to the SAL one. The OVA-S group has had an increase in %Rt and %Et after the OVA challenge, in %Et after the Ach and in IL-4, 8-iso-PGF2 alpha, and actin compared to the OVA. Adrenal weight and cortisol serum were increased in stressed animals compared to nonstressed ones, and the catecholamines were unaltered. Conclusion & clinical relevance: Repeated stress has increased distal lung constriction, which was associated with an increase of actin, IL-4, and 8-iso-PGF2 alpha levels. Stress has also induced an activation of iNOS, cytokines, and oxidative stress pathways.