BEATRIZ MANGUEIRA SARAIVA RAMANHOLO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
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- 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.
- 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 Bordetella Pertussis Whole-Cell Vaccine Inhibits Specific IgE, Inflammation and Airway Remodeling in a Murine Model of Asthma(2015) AUN, Marcelo Vivolo; ARANTES-COSTA, Fernanda; SARAIVA-ROMANHOLO, Beatriz Mangueira; ALMEIDA, Francine Maria; REGINA-BRUEGGERMANN, Thayse; MARTINS, Milton Arruda; KALIL, Jorge; GIAVINA-BIANCHI, Pedro- Collagenase mRNA Overexpression and Decreased Extracellular Matrix Components Are Early Events in the Pathogenesis of Emphysema(2015) ROBERTONI, Fabola S. Z.; OLIVO, Clarice R.; LOURENCO, Juliana D.; GONCALVES, Natalia G.; VELOSA, Ana Paula P.; LIN, Chin J.; FLO, Claudia M.; SARAIVA-ROMANHOLO, Beatriz M.; SASAKI, Sergio D.; MARTINS, Milton A.; TEODORO, Walcy R.; LOPES, Fernanda Degobbi T. Q. S.To describe the progression of parenchymal remodeling and metalloproteinases gene expression in earlier stages of emphysema, mice received porcine pancreatic elastase (PPE) instillation and Control groups received saline solution. After PPE instillation (1, 3, 6 hours, 3 and 21 days) we measured the mean linear intercept, the volume proportion of types I and III collagen, elastin, fibrillin and the MMP-1, -8, -12 and -13 gene expression. We observed an initial decrease in type I (at the 3rd day) and type III collagen (from the 6th hour until the 3rd day), in posterior time points in which we detected increased gene expression for MMP-8 and -13 in PPE groups. After 21 days, the type III collagen fibers increased and the type I collagen values returned to similar values compared to control groups. The MMP-12 gene expression was increased in earlier times (3 and 6 hours) to which we detected a reduced proportion of elastin (3 days) in PPE groups, reinforcing the already established importance of MMP-12 in the breakdown of ECM. Such findings will be useful to better elucidate the alterations in ECM components and the importance of not only metalloelastase but also collagenases in earlier emphysema stages, providing new clues to novel therapeutic targets.
conferenceObject Effect Of Proteinase Inhibitor Of Plant Origin Enterolobium Contortisiliquum Trypsin Inhibitor In An Experimental Model Of Chronic Allergic Pulmonary Inflammation(2015) RODRIGUES, A. P. D.; SANTOS, A. S. A. Dos; RIGHETTI, R. F.; ARANTES-COSTA, F. M.; SARAIVA-ROMANHOLO, B. M.; NOGUEIRA-FILHO, G. G.; BRITO, M. V. De; PRADO, C. M.; LEICK, E. A.; MARTINS, M. D. A.; OLIVA, M. V.; TIBERIO, I. C. L.- A randomized, controlled, crossover study in patients with mild and moderate asthma undergoing treatment with traditional Chinese acupuncture(2015) PAI, Hong Jin; AZEVEDO, Raymundo Soares; BRAGA, Alfesio Luis Ferreira; MARTINS, Lourdes Conceicao; SARAIVA-ROMANHOLO, Beatriz M.; MARTINS, Milton de Arruda; LIN, Chin AnOBJECTIVES: This study sought to verify the effects of acupuncture as an adjuvant treatment for the control of asthma. METHODS: This was a randomized, controlled, crossover trial conducted at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. A total of 74 patients withmild/moderate, persistent asthma were randomized into two therapeutic groups: Group A - 31 patients underwent 10 real weekly acupuncture sessions, followed by a 3-week washout period and 10 sham weekly acupuncture sessions; and Group B - 43 patients underwent 10 sham weekly acupuncture sessions, followed by a 3-week washout period and 10 real weekly acupuncture sessions. Patients used short-and long-acting beta-2 agonists and inhaled corticosteroids when necessary. Prior to treatment and after each period of 10 treatment sessions, the patients were evaluated for spirometry, induced sputum cell count, exhaled nitric oxide (NO) and with the Short Form 36 (SF-36) and Questionnaire on Quality of Life-Asthma (QQLA) questionnaires. Daily peak flow and symptom diaries were registered. The level of significance adopted was 5% (alpha=0.05). RESULTS: In Group B, after real acupuncture, there was a decrease in eosinophils (p=0.035) and neutrophils (p=0.047), an increase in macrophages (p=0.001) and an improvement in peak flow (p=0.01). After sham acupuncture treatment, patients experienced less coughing (p=0.037), wheezing (p=0.013) and dyspnea (p=0.014); similarly, after real acupuncture, patients reported less coughing (p=0.040), wheezing (p=0.012), dyspnea (p<0.001) and nocturnal awakening episodes (p=0.009). In Group A, there was less use of rescue medication (p=0.043). After the sham procedure, patients in Group A experienced less coughing (p=0.007), wheezing (p=0.037), dyspnea (p<0.001) and use of rescue medication (p<0.001) and after real acupuncture, these patients showed improvements in functional capacity (p=0.004), physical aspects (p=0.002), general health status (p<0.001) and vitality (p=0.019). Sham acupuncture also led to significant differences in symptoms, but these were not different from those seen with real acupuncture. Spirometry and exhaled NO levels did not show a difference between sham and real acupuncture treatment. In addition, no significant difference was demonstrated between treatments regarding the quality of life evaluation. CONCLUSION: Real and sham acupuncture have different effects and outcomes on asthma control. The crossover approach was not effective in this study because both interventions led to improvement of asthma symptoms, quality of life and inflammatory cell counts. Thus, sham acupuncture cannot serve as a placebo in trials with acupuncture as the main intervention for asthma.
- Aerobic training decreases bronchial hyperresponsiveness and systemic inflammation in patients with moderate or severe asthma: a randomised controlled trial(2015) FRANCA-PINTO, Andrezza; MENDES, Felipe A. R.; CARVALHO-PINTO, Regina Maria de; AGONDI, Rosana Camara; CUKIER, Alberto; STELMACH, Rafael; SARAIVA-ROMANHOLO, Beatriz M.; KALIL, Jorge; MARTINS, Milton A.; GIAVINA-BIANCHI, Pedro; CARVALHO, Celso R. F.Background The benefits of aerobic training for the main features of asthma, such as bronchial hyperresponsiveness (BHR) and inflammation, are poorly understood. We investigated the effects of aerobic training on BHR (primary outcome), serum inflammatory cytokines (secondary outcome), clinical control and asthma quality of life (Asthma Quality of Life Questionnaire (AQLQ)) (tertiary outcomes). Methods Fifty-eight patients were randomly assigned to either the control group (CG) or the aerobic training group (TG). Patients in the CG (educational programme+breathing exercises (sham)) and the TG (same as the CG+aerobic training) were followed for 3 months. BHR, serum cytokine, clinical control, AQLQ, induced sputum and fractional exhaled nitric oxide (FeNO) were evaluated before and after the intervention. Results After 12 weeks, 43 patients (21 CG/22 TG) completed the study and were analysed. The TG improved in BHR by 1 doubling dose (dd) (95% CI 0.3 to 1.7 dd), and they experienced reduced interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) and improved AQLQ and asthma exacerbation (p<0.05). No effects were seen for IL-5, IL-8, IL-10, sputum cellularity, FeNO or Asthma Control Questionnaire 7 (ACQ-7; p>0.05). A within-group difference was found in the ACQ-6 for patients with non-well-controlled asthma and in sputum eosinophil and FeNO in patients in the TG who had worse airway inflammation. Conclusions Aerobic training reduced BHR and serum proinflammatory cytokines and improved quality of life and asthma exacerbation in patients with moderate or severe asthma. These results suggest that adding exercise as an adjunct therapy to pharmacological treatment could improve the main features of asthma.
- Effects of acute hypochlorite exposure in OVA-sensitized and challenged mice(2015) GENARO, Isabella S. de; ALMEIDA, Francine M. de; HIZUME, Deborah; MORIYA, Henrique T.; CORDEIRO, Bruna N.; CRUZ, Joao Carlos G.; LOPES, Renan B.; VIEIRA, Rodolfo P.; SILVA, Ronaldo A.; MARTINS, Milton A.; ARANTES-COSTA, Fernanda M.; SARAIVA-ROMANHOLO, Beatriz M.
conferenceObject Effect Of Proteinase Inhibitor Of Plant Origin Crataeva Tapia Bark Lectin In An Experimental Model Of Chronic Allergic Pulmonary Inflammation(2015) SANTOS, A. S. A.; RODRIGUES, A. P. D.; ARANTES-COSTA, F. M.; SARAIVA-ROMANHOLO, B. M.; NOGUEIRA-FILHO, G. G.; BRITO, M. V.; RIGHETTI, R. F.; PRADO, C. M.; LEICK, E. A.; MARTINS, M. D. A.; OLIVA, M. V.; TIBERIO, I. C. L.- Aerobic training reverses airway inflammation by increasing the expression of anti-inflammatory cytokines by peribronchial cells but not by skeletal muscle(2015) SILVA, Ronaldo Aparecido; ALMEIDA, Francine Maria; OLIVO, Clarice Rosa; SARAIVA-ROMANHOLO, Beatriz Mangueira; PERINI, Adenir; MARTINS, Milton Arruda; CARVALHO, Celso Ricardo Fernandes