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
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- 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
- A possible association between fructose consumption and pulmonary emphysema (vol 9, 9344, 2019)(2020) SUEHIRO, Camila Liyoko; TOLEDO-ARRUDA, Alessandra Choqueta de; VIEIRA, Rodolfo de Paula; ALMEIDA, Francine Maria de; OLIVO, Clarice Rosa; MARTINS, Milton de Arruda; LIN, Chin Jia
- 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.
- Long-term endogenous acetylcholine deficiency potentiates pulmonary inflammation in a murine model of elastase-induced emphysema(2021) BANZATO, Rosana; PINHEIRO, Nathalia M.; OLIVO, Clarice R.; SANTANA, Fernanda R.; LOPES, Fernanda D. T. Q. S.; CAPERUTO, Luciana C.; CAMARA, Niels O.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; PRADO, Marco Antonio M.; PRADO, Vania F.; PRADO, Carla M.Acetylcholine (ACh), the neurotransmitter of the cholinergic system, regulates inflammation in several diseases including pulmonary diseases. ACh is also involved in a non-neuronal mechanism that modulates the innate immune response. Because inflammation and release of pro-inflammatory cytokines are involved in pulmonary emphysema, we hypothesized that vesicular acetylcholine transport protein (VAChT) deficiency, which leads to reduction in ACh release, can modulate lung inflammation in an experimental model of emphysema. Mice with genetical reduced expression of VAChT (VAChT KDHOM 70%) and wild-type mice (WT) received nasal instillation of 50 uL of porcine pancreatic elastase (PPE) or saline on day 0. Twenty-eight days after, animals were evaluated. Elastase instilled VAChT KDHOM mice presented an increase in macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid and MAC2-positive macrophages in lung tissue and peribronchovascular area that was comparable to that observed in WT mice. Conversely, elastase instilled VAChT KDHOM mice showed significantly larger number of NF-kappa B-positive cells and isoprostane staining in the peribronchovascular area when compared to elastase-instilled WT-mice. Moreover, elastase-instilled VAChT-deficient mice showed increased MCP-1 levels in the lungs. Other cytokines, extracellular matrix remodeling, alveolar enlargement, and lung function were not worse in elastase-instilled VAChT deficiency than in elastase-instilled WT-controls. These data suggest that decreased VAChT expression may contribute to the pathogenesis of emphysema, at least in part, through NF-kappa B activation, MCP-1, and oxidative stress pathways. This study highlights novel pathways involved in lung inflammation that may contribute to the development of chronic obstrutive lung disease (COPD) in cholinergic deficient individuals such as Alzheimer's disease patients.
- Effects of the serine protease inhibitor rBmTI-A in an experimental mouse model of chronic allergic pulmonary inflammation (vol 9, 12624, 2019)(2019) FLORENCIO, Ariana Correa; ALMEIDA, Robson S. de; ARANTES-COSTA, Fernanda M.; SARAIVA-ROMANHOLO, Beatriz M.; DURAN, Adriana F.; SASAKI, Sergio D.; MARTINS, Milton A.; LOPES, Fernanda D. T. Q. S.; TIBERIO, Iolanda F. L. C.; LEICK, Edna A.
- A possible association between fructose consumption and pulmonary emphysema(2019) SUEHIRO, Camila Liyoko; TOLEDO-ARRUDA, Alessandra Choqueta de; VIEIRA, Rodolfo de Paula; ALMEIDA, Francine Maria de; OLIVO, Clarice Rosa; MARTINS, Milton de Arruda; LIN, Chin JiaChronic Obstructive Pulmonary Disease (COPD) is a syndrome that comprises several distinct and overlapping phenotypes. In addition to persistent airflow limitation and respiratory symptoms, COPD is also characterized by chronic systemic inflammation. Epidemiological studies have shown that dietary fibers, fruits and vegetables intake protects against the COPD development, while fructose-loading is associated with increased risk of asthma and chronic bronchitis. Since dietary factors might affect susceptibility to COPD by modulating oxidative stress and inflammatory responses, we evaluated how fructose feeding might affect the smoking-induced emphysema in mice. We found that chronic fructose intake induced destruction and remodeling of lung parenchyma and impairment of respiratory mechanics, which are associated with distinctive cytokine profiles in bronchoalveolar lavage fluid, blood plasma and skeletal muscle. The combined effects of chronic fructose intake and cigarette smoking on destruction of lung parenchyma are more pronounced than the effects of either alone. Excessive intake of fructose might directly cause pulmonary emphysema in mice rather than just altering its natural history by facilitating the installation of a low-grade systemic inflammatory milieu.
- Clinical, functional and inflammatory evaluation in asthmatic patients after a simple short-term educational program: a randomized trial(2021) FELIX, Soraia Nogueira; AGONDI, Rosana Camara; AUN, Marcelo Vivolo; OLIVO, Clarice Rosa; ALMEIDA, Francine Maria de; AMORIM, Thais Santos; CEZARIO, Julia Caroline; GIAVINA-BIANCHI, Pedro; TIBERIO, Iolanda de Fatima Lopes Calvo; MARTINS, Milton de Arruda de; ROMANHOLO, Beatriz Mangueira SaraivaThis study aimed to evaluate the clinical evolution, functional parameters and inflammatory activity of asthma in patients who submitted to an educational intervention. 58 adult patients over 18 years of age with partly controlled and uncontrolled asthma were randomized into an intervention group (IG) (N = 32) and a control group (CG) (N = 26) and evaluated for 12 weeks. The Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Asthma Quality Life Questionnaire (AQLQ) and Beck Depression Inventory (BDI) questionnaires were applied. Spirometry, exhaled nitric oxide (NO), exhaled breath condensate (EBC) and induced sputum (IS), measurement of the peak flow and symptoms were performed. The IG patients received an educational activity for 30 min applied by a nurse. Statistical analysis: analysis of variance with repeated intragroup measures. IG presented a decreased number of eosinophils in IS and IL-17A in EBC, an increase in the percentage of FEV1 before and after bronchodilator and an improvement in quality of life compared to the CG. There was an improvement in depression levels and a decrease in IL-4 and IL-5 in the IS and in the EBC in both groups. Our results suggest that an educational intervention can bring benefits concerning the control of inflammation, lung function alterations, quality of life and levels of depression in asthmatic patients. Registration: ClinicalTrials.gov; NCT03655392.
- Effects of the serine protease inhibitor rBmTI-A in an experimental mouse model of chronic allergic pulmonary inflammation(2019) FLORENCIO, Adana Correa; ALMEIDA, Robson S. de; ARANTES-COSTA, Fernanda M.; SARAIVA-ROMANHOLO, Beatriz M.; DURAN, Adriana F.; SASAKI, Sergio D.; MARTINS, Milton A.; LOPES, Fernanda D. T. Q. S.; TIBERIO, Iolanda F. L. C.; LEICK, Edna A.To evaluate whether a recombinant serine protease inhibitor (rBmTI-A) modulates inflammation in an experimental model of chronic allergic lung inflammation. Balb/c mice were divided into four groups: SAL (saline), OVA (sensitized with ovalbumin), SAL + rBmTI-A (control treated with rBmTI-A) and OVA + rBmTI-A (sensitized with ovalbumin and treated with rBmTI-A). The animals received an intraperitoneal injection of saline or ovalbumin, according to the group. The groups received inhalation with saline or ovalbumin and were treated with rBmTI-A or saline by nasal instillation. After 29 days, we evaluated the respiratory mechanics; bronchoalveolar lavage fluid (BALF); cytokines; MMP-9, TIMP-1; eosinophils; collagen and elastic fibre expression in the airways; and the trypsin-like, MMP-1, and MMP-9 lung tissue proteolytic activity. Treatment with rBmTI-A reduced the trypsin-like proteolytic activity, the elastance and resistance maximum response, the polymorphonuclear cells, IL-5, IL-10, IL-13 and IL-17A in the BALF, the expression of IL-5, IL-13, IL-17, CD4+, MMP-9, TIM P-1, eosinophils, collagen and elastic fibres in the airways of the OVA + rBmTI-A group compared to the OVA group (p < 0.05). rBmTI-A attenuated bronchial hyperresponsiveness, inflammation and remodelling in this experimental model of chronic allergic pulmonary inflammation. This inhibitor may serve as a potential therapeutic tool for asthma treatment.
- The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association(2019) CERVILHA, Daniela A. B.; ITO, Juliana T.; LOURENCO, Juliana D.; OLIVO, Clarice R.; SARAIVA-ROMANHOLO, Beatriz M.; VOLPINI, Rildo A.; OLIVEIRA-JUNIOR, Manoel C.; MAUAD, Thais; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; VIEIRA, Rodolfo P.; LOPES, Fernanda D. T. Q. S.We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 +/- 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 mu l) or lipopolysaccharide (LPS) (1 mg/kg in 50 mu l of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4(+) and CD8(+) T cells, Treg cells, and IL-10(+) and IL-17(+) cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-gamma, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4(+) and CD8(+) T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17(+) cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5(+) cells corroborated the increased numbers of IL-17(+) and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL10(+) cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model.