BEATRIZ MANGUEIRA SARAIVA RAMANHOLO

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina

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Autor: SARAIVA-ROMANHOLO, Beatriz M. ×

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  • conferenceObject
    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.
  • article 39 Citação(ões) na Scopus
    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.
  • article 14 Citação(ões) na Scopus
    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.
  • article 20 Citação(ões) na Scopus
    Respiratory rehabilitation: a physiotherapy approach to the control of asthma symptoms and anxiety
    (2012) LAURINO, Renata Andre; BARNABE, Viviane; SARAIVA-ROMANHOLO, Beatriz M.; STELMACH, Rafael; CUKIER, Alberto; NUNES, Maria do Patrocinio T.
    OBJECTIVES: The objectives of this study were to verify the degree of anxiety, respiratory distress, and health-related quality of life in a group of asthmatic patients who have experienced previous panic attacks. Additionally, we evaluated if a respiratory physiotherapy program (breathing retraining) improved both asthma and panic disorder symptoms, resulting in an improvement in the health-related quality of life of asthmatics. METHODS: Asthmatic individuals were assigned to a chest physiotherapy group that included a breathing retraining program held once a week for three months or a paired control group that included a Subtle Touch program. All patients were assessed using the Diagnostic and Statistical Manual of Mental Disorders IV, the Sheehan Anxiety Scale, the Quality of Life Questionnaire, and spirometry parameter measurements. RESULTS: Both groups had high marks for panic disorder and agoraphobia, which limited their quality of life. The Breathing Retraining Group program improved the clinical control of asthma, reduced panic symptoms and agoraphobia, decreased patient scores on the Sheehan Anxiety Scale, and improved their quality of life. Spirometry parameters were unchanged. CONCLUSION: Breathing retraining improves the clinical control of asthma and anxiety symptoms and the health-related quality of life in asthmatic patients.
  • article 42 Citação(ões) na Scopus
    Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury
    (2017) BITTENCOURT-MERNAK, Marcia Isabel; PINHEIRO, Nathalia M.; SANTANA, Fernanda P. R.; GUERREIRO, Marina P.; SARAIVA-ROMANHOLO, Beatriz M.; GRECCO, Simone S.; CAPERUTO, Luciana C.; FELIZARDO, Raphael J. F.; CAMARA, Niels O. S.; TIBERIO, Iolanda F. L. C.; MARTINS, Mlton A.; LAGO, Joao Henrique G.; PRADO, Carla M.
    Sakuranetin is the main isolate flavonoid from Baccharis retusa (Asteraceae) leaves and exhibits anti-inflammatory and antioxidative activities. Acute respiratory distress syndrome is an acute failure of the respiratory system for which effective treatment is urgently necessary. This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Animals were treated with intranasal sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours after ALI was induced, lung function, inflammation, macrophages population markers, collagen fiber deposition, the extent of oxidative stress, and the expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP- 9 (TIMP-1) and NF-kB were evaluated. The animals began to show lung alterations 6 h after LPS instillation, and these changes persisted until 24 h after LPS administration. Preventive and therapeutic treatment with sakuranetin reduced the neutrophils in the peripheral blood and in the bronchial alveolar lavage. Sakuranetin treatment also reduced macrophage populations, particularly that of M1-like macrophages. In addition, sakurnaetin treatment reduced keratinocyte-derived chemokines (IL-8 homolog) and NF-kB levels, collagen fiber formation, MMM-9 and TIMP-1-positive cells, and oxidative stress in lung tissues compared with LPS animals treated with vehicle. Finally, sakuranetin treatment also reduced total protein, and the levels of TNF-alpha and IL-1 beta in the lung. This study shows that sakuranetin prevented and reduced pulmonary inflammation induced by LPS. Because sakuranetin modulates oxidative stress, the NF-kB pathway, and lung function, it may constitute a novel therapeutic candidate to prevent and treat ALI.
  • conferenceObject
    Aerobic training decrease bronchial hyperresponsiveness and systemic inflammation in patients with moderate or severe asthma: A randomized controlled trial
    (2014) CARVALHO, Celso R. F.; FRANCA-PINTO, Andrezza; MENDES, Felipe A. R.; STELMACH, Rafael; CUKIER, Alberto; AGONDI, Rosana C.; MARTINS, Milton A.; SARAIVA-ROMANHOLO, Beatriz M.; KALIL, Jorge; GIAVINA-BIANCHI, Pedro
  • conferenceObject
    Histological analysis of compensatory lung growth effects in emphysematous rats after bilobectomy
    (2013) ALMEIDA, Francine Maria; SARAIVA-ROMANHOLO, Beatriz M.; PAULA, Rodolfo de; MORIYA, Henrique Takachi; LIGEIRO-DE-OLIVEIRA, Ana Paula; LOPES, Fernanda D. Q. S.; MAUAD, Thais; MARTINS, Milton de Arruda; PAZETTI, Rogerio
  • conferenceObject
    Inflammatory response to Streptococcus pneumoniae was attenuated by moderate aerobic exercise training
    (2020) CASTRO, Thamyres; LAIA, Roseane M.; MENDONCA, Luana D.; TRINDADE, Pietro Rocha; SOUZA, Jessica C.; SARAIVA-ROMANHOLO, Beatriz M.; OLIVEIRA, Maria Leonor S.; MIYAGI, Eliane N.; PRADO, Carla M.; TIBERIO, Iolanda F. C. L.; OLIVO, Clarice Rosa
  • article 6 Citação(ões) na Scopus
    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 An
    OBJECTIVES: 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.
  • conferenceObject
    High Intensity Interval Training control inflammation in mice exposed to Streptococus pneumoniae
    (2020) CASTRO, Thamyres B. P.; LAIA, Roseane M.; MENDONCA, Luana D.; TRINDADE, Pietro Rocha; SOUZA, Jessica C.; SARAIVA-ROMANHOLO, Beatriz M.; OLIVEIRA, Maria Leonor S.; MIYAGI, Eliane N.; PRADO, Carla M.; TIBERIO, Iolanda F. C. L.; OLIVO, Clarice Rosa