VERA LUIZA CAPELOZZI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
46 resultados
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conferenceObject Pathophysiological features of lung and skin in human SSc and collagen V/C57LB6 mouse model(2018) TEODORO, W. Paganelli Rosolia; VELOSA, A. P. Pereira; QUEIROZ, Z. A. de Jesus; SANTOS, L. Araujo dos; CATANOZI, S.; SANTOS FILHO, A. dos; BUENO, C.; VENDRAMINI, M. Borges Galhardo; FERNEZLIAN, S. de Moraes; EHER, E. Miristene; LOPES, F. Degobbi T. Q. S.; CAPELOZZI, V. L.- Biologic Impact of Mechanical Power at High and Low Tidal Volumes in Experimental Mild Acute Respiratory Distress Syndrome(2018) SANTOS, Raquel S.; MAIA, Ligia de A.; OLIVEIRA, Milena V.; SANTOS, Cintia L.; MORAES, Lillian; PINTO, Eliete F.; SAMARY, Cynthia dos S.; MACHADO, Joana A.; CARVALHO, Anna Carolinna; FERNANDES, Marcos Vinicius de S.; MARTINS, Vanessa; CAPELOZZI, Vera L.; MORALES, Marcelo M.; KOCH, Thea; ABREU, Marcelo Gama de; PELOSI, Paolo; SILVA, Pedro L.; ROCCO, Patricia R. M.Background: The authors hypothesized that low tidal volume (V-T) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of V-T and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS). Methods: Forty Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24h, 32 rats were randomly assigned to be mechanically ventilated (2 h) with a combination of different V-T (6 ml/kg and 11 ml/kg) and RR that resulted in low and high power. Power was calculated as energy (Delta P,(2)(L)/E,(L)) x RR (Delta P,(L) = transpulmonary driving pressure; E,(L) = lung elastance), and was three-fold higher in high than in low power groups. Eight rats were not mechanically ventilated and used for molecular biology analysis. Results: Diffuse alveolar damage score, which represents the severity of edema, atelectasis, and overdistension, was increased in high V-T compared to low V-T, in both low (low V-T: 11 [9 to 14], high V-T: 18 [15 to 20]) and high (low V-T: 19 [16 to 25], high V-T: 29 [27 to 30]) power groups. At high V-T, interleukin-6 and amphiregulin expressions were higher in high-power than in low-power groups. At high power, amphiregulin and club cell protein 16 expressions were higher in high V-T than in low V-T. Mechanical energy and power correlated well with diffuse alveolar damage score and interleukin-6, amphiregulin, and club cell protein 16 expression. Conclusions: In experimental mild ARDS, even at low V-T, high mechanical power promoted ventilator-induced lung injury. To minimize ventilator-induced lung injury, low V-T should be combined with low power.
- Butylated hydroxytoluene induces type-V collagen and overexpression of remodeling genes/proteins in experimental lung fibrosis(2018) MARTINS, Vanessa; TEODORO, Walcy Rosolia; VELOSA, Ana Paula Pereira; ANDRADE, Priscila; FARHAT, Cecilia; FABRO, Alexandre Todorovic; CAPELOZZI, Vera LuizaAnomalous histoarchitecture with increased levels of type-V collagen (Col V) in lungs of human idiopathic pulmonary fibrosis (IPF) and bleomycin (BLM) airway-centered interstitial fibrosis suggest that this collagen can be a possible trigger involved in the pathogenesis of these diseases. Butylated hydroxytoluene (BHT) injury model revealed a distal involvement of lung parenchyma with significant endothelial injury and fibrotic response, contrasting with the BLM airway-centered insult. We undertook this study to analyze whether BHT alters distal airway/alveolar epithelial cells (AECs) and extracellular matrix (ECM) signaling involved in the initiation and progression of pulmonary fibrosis in a different pathway concerning overexpression of Col V. Female mice C57BL/6 (n=6) were instilled intraperitoneally with 400mg/kg of BHT dissolved in 1 mL of corn oil and euthanized at day 14 or 21 after BHT administration. Morphometry, immunohistochemistry and transmission electron microscopy were performed to characterize microscopic and submicroscopic changes of AECs and endothelial cells through transforming growth factor beta (TGF-beta) basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) expression. Immunofluorescence and immunogold electron microscopy were performed to characterize Col V. Quantitative polymerase chain reaction (qPCR) was used to confirm differential levels of RNA messenger. BHT lungs showed marked fibrotic areas and hyperplastic AECs. The alveolar damage caused destruction of elastic fibers and a critical increase of Col V in ECM of distal lung parenchyma. Fibrogenesis-promoting markers TGF-beta, bFGF and VEGF were also overexpressed in situ, coinciding with up-regulation in remodeling enzymes, growth factors, cytokines, transduction and transcription genes. BHT alters distal lung parenchyma signaling involved in pulmonary fibrosis highlighted similarities to human IPF in a pathway involving Col V arising as a promissory model to identify effective therapeutic targets.
- Rapid On-Site Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspirations for the Diagnosis of Lung Cancer A Perspective From Members of the Pulmonary Pathology Society(2018) JAIN, Deepali; ALLEN, Timothy Craig; AISNER, Dara L.; BEASLEY, Mary Beth; CAGLE, Philip T.; CAPELOZZI, Vera Luiza; HARIRI, Lida P.; LANTUEJOUL, Sylvie; MILLER, Ross; MINO-KENUDSON, Mari; MONACO, Sara E.; MOREIRA, Andre; RAPARIA, Kirtee; REKHTMAN, Natasha; RODEN, Anja Christiane; ROY-CHOWDHURI, Sinchita; SANTOS, Gilda da Cunha; THUNNISSEN, Erik; TRONCONE, Giancarlo; VIVERO, MarinaContext.-Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer. Objective.-To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer. Data Sources.-An electronic literature search in PubMed and Google databases was performed using the following key words: cytology, lung cancer, on-site evaluation, rapid on-site evaluation, and ROSE EBUS-TBNA. Only articles published in English were included in this review. Conclusions.-Rapid on-site evaluation can ensure that the targeted lesion is being sampled and can enable appropriate specimen triage. If available, it should be used with EBUS-TBNA in the diagnosis of lung cancer because it can minimize repeat procedures for additional desired testing (ie, molecular studies). Some studies have shown that ROSE does not adversely affect the number of aspirations, total procedure time of EBUS-TBNA, or the rate of postprocedure complications; it is also helpful in providing a preliminary diagnosis that can reduce the number of additional invasive procedures, such as mediastinoscopy. As EBUS technology continues to evolve, our knowledge of the role of ROSE in EBUS-TBNA for the diagnosis of lung cancer will also continue to grow and evolve.
- Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats(2018) SAMARY, Cynthia S.; RAMOS, Alane B.; MAIA, Ligia A.; ROCHA, Nazareth N.; SANTOS, Cintia L.; MAGALHAES, Raquel F.; CLEVELARIO, Amanda L.; PIMENTEL-COELHO, Pedro M.; MENDEZ-OTERO, Rosalia; CRUZ, Fernanda F.; CAPELOZZI, Vera L.; FERREIRA, Tatiana P. T.; KOCH, Thea; ABREU, Marcelo Gama de; SANTOS, Claudia C. dos; PELOSI, Paolo; SILVA, Pedro L.; ROCCO, Patricia R. M.Background: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. Methods: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naive rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Results: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-alpha and IL-6) and in BALF (TNF-alpha). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naive rats only upregulated expression of TNF-alpha and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-alpha and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. Conclusions: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.
- Water-Related Mechanisms Proposed for Storing and Transmitting Homeopathic Information: Putative Links with Biological Responses(2018) GUEDES, Jose Roberto Pereira; BONAMIN, Leoni Villano; CAPELOZZI, Vera LuizaIntroduction There are two critical pillars of homeopathy that contrast with the dominant scientific approach: the similitude principle and the potentization of serial dilutions. Three main hypotheses about the mechanisms of action are in discussion: nanobubbles-related hormesis; vehicle-related electric resonance; and quantum nonlocality. Objectives The aim of this paper is to review and discuss some key points of such properties: the imprint of supramolecular structures based on the nanoparticle-allostatic, cross-adaptation-sensitization (NPCAS) model; the theory of non-molecular electromagnetic transfer of information, based on the coherent water domains model, and relying (like the NPCAS model) on the idea of local interactions; and the hypothesis of quantum entanglement, based on the concept of non-locality. Results and Discussion The nanoparticles hypothesis has been considered since 2010, after the demonstration of suspended metal nanoparticles even in very highly diluted remedies: their actual action on biological structures is still under scrutiny. The second hypothesis considers the idea of electric resonance mechanisms between living systems (including intracellular water) and homeopathic medicines: recent findings about potency-related physical properties corroborate it. Finally, quantum theory of 'non-local' phenomena inspires the idea of an 'entanglement' process among patient, practitioner and the remedy: that quantic phenomena could occur in supra-atomic structures remains speculative however. Conclusion Further studies are needed to ascertain whether and which of these hypotheses may be related to potential cellular effects of homeopathic preparations, such as organization of metabolic pathways or selective gene expression.
- Comprehensive analysis of immune, extracellular matrices and pathogens profile in lung granulomatosis of unexplained etiology(2018) SOUZA, Paola da Costa; DONDO, Patricia Suemi; SOUZA, Gabriela; LOPES, Deborah; MOSCARDI, Marcel; MARTINHO, Vinicius de Miranda; LOURENCO, Rodolfo Daniel de Mattos; PRIETO, Tabatha; BALANCIN, Marcelo Luiz; ASSATO, Aline Kawassaki; TEODORO, Walcy Rosolia; RODRIGUES, Silvia; LIMA, Mariana; CASTELLANO, Maria Vera; COLETTA, Ester; PARRA, Edwin Roger; CAPELOZZI, Vera LuizaThis study analyzed the type 1 and type 2 T helper (Th1/Th2) cytokines (including interleukins), immune cellular, matrix profile, and pathogens in granulomas with unexplained etiology compared to those with infectious and noninfectious etiology. Surgical lung biopsies from 108 patients were retrospectively reviewed. Histochemistry, immunohistochemistry, immunofluorescence, morphometry and polymerase chain reaction were used, respectively, to evaluate total collagen and elastin fibers, collagen I and III, immune cells, cytokines, matrix metalloproteinase-9, myofibroblasts, and multiple usual and unusual pathogens. No relevant polymerase chain reaction expression was found in unexplained granulomas. A significant difference was found between the absolute number of eosinophils, macrophages, and lymphocytes within granulomas compared to uninvolved lung tissue. Granulomas with unexplained etiology (UEG) presented increased number of eosinophils and high expression of interleukins (ILs) IL-4/IL-5 and transforming growth factor-beta. In sarcoidosis, CD4/CD8 cell number was significantly higher within and outside granulomas, respectively; the opposite was detected in hypersensitivity pneumonitis. Again, a significant difference was found between the high number of myofibroblasts and matrix metalloproteinase-9 in UEG, hypersensitivity pneumonitis, and sarcoidosis compared to granulomas of tuberculosis. Granulomas of paracoccidioisis exhibited increased type I collagen and elastic fibers. Th1 immune cellular profile was similar among granulomas with unexplained, infectious, and noninfectious etiology. In contrast, modulation of Th2 and matrix remodeling was associated with more fibroelastogenesis and scarring of lung tissue in UEG compared to infectious and noninfectious. We concluded that IL-4/IL-5 and transforming growth factor-beta might be used as surrogate markers of early fibrosis, reducing the need for genotyping, and promise therapeutic target in unexplained granulomas.
conferenceObject Pressure Support with Low Tidal Volume Minimizes Lung Injury Compared to Controlled Mechanical Ventilation in Experimental Mild Acute Respiratory Distress Syndrome(2018) SILVA, P. L.; PINTO, E. F.; SANTOS, R. S.; ANTUNES, M. A.; MAIA, L. A.; PADILHA, G. A.; MACHADO, J. A.; CARVALHO, A. C. F.; CAPELOZZI, V.; PELOSI, P.; ROCCO, P. R.- Collagen V oral administration decreases inflammation and remodeling of synovial membrane in experimental arthritis(2018) ATAYDE, Silvana Ramos; VELOSA, Ana Paula Pereira; CATANOZI, Sergio; BIANCO, Vanessa Del; ANDRADE, Priscila Cristina; RODRIGUES, Jose Eduardo de Castro M.; SANTOS FILHO, Antonio dos; ANTONANGELO, Leila; MELLO, Suzana Beatriz Verissimo de; CAPELOZZI, Vera Luiza; TEODORO, Walcy RosoliaBecause collagen type V (Col V) can be exposed in tissue injury, we hypothesized that oral administration of this collagen species modulates the inflammation and remodeling of experimental synovitis, avoiding joint destruction, and that the modulation may differ according to the temporal administration. Arthritis (IA, n = 20) was induced in Lewis rats by intraarticular (ia) injection of 500 mu g of methylated bovine serum albumin (mBSA) emulsified in complete Freund's adjuvant (CFA) (10 mu l) followed by an intraarticular booster of mBSA (50 mu g) in saline (50 mu l) administered at 7 and 14 days. The control group received saline (50 mu l, ia). After the first intraarticular injection, ten IA animals were supplemented via gavage with Col V (500 mu g/300 mu l) daily for 30 days (IA/Suppl). The control group received saline (50 mu L) and Col V supplement in the same way (Suppl). Col V oral administration in IA/Suppl led to 1) inhibited edema and severe inflammatory cell infiltration, 2) decreased collagen fiber content, 3) decreased collagen type I, 4) inhibited lymphocyte subpopulations and macrophages, 5) inhibited IL-1 beta, IL-10, IL-17 and TNF-alpha production and 6) increased expression of caspase-9 in the synovial tissue. In conclusion, Col V supplementation decreased synovial inflammation and the fibrotic response, possibly by increased the apoptosis of inflammatory cells.
conferenceObject COLLAGEN V/C57BL6 MOUSE MODEL: A NOVEL PRECLINICAL MODEL TO STUDY PATHOPHYSIOLOGY AND THERAPEUTIC APPROACHES IN SYSTEMIC SCLEROSIS(2018) TEODORO, W. R.; VELOSA, A. P. P.; QUEIROZ, Z. A. de J.; SANTOS, L. A. dos; CATANOZI, S.; SANTOS FILHO, A. dos; BUENO, C.; VENDRAMINI, M.; FERNEZLIAN, S. M.; EHER, E. M.; LOPES, F. D. T. Q. S.; SAMPAIO-BARROS, P. D.; CAPELOZZI, V. L.