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
23 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 23
- Variable Ventilation Improved Respiratory System mechanics and Ameliorated pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion(2017) SOLURI-MARTINS, Andre; MORAES, Lillian; SANTOS, Raquel S.; SANTOS, Cintia L.; HUHLE, Robert; CAPELOZZI, Vera L.; PELOSI, Paolo; SILVA, Pedro L.; ABREU, Marcelo Gama de; ROCCO, Patricia R. M.Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV (n = 6/group) [tidal volume (V-T) = 6 mL/kg, positive endexpiratory pressure (PEEP) = 2 cmH(2)O, fraction of inspired oxygen (FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated V-T values (n = 1200; mean V-T = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory systemmechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean +/- SD, VCV 3.6 +/- 1.3 cmH20/ml and 2.0 +/- 0.8 cmH(2)O/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.
- Molecular and Immune Biomarkers in Acute Respiratory Distress Syndrome A Perspective From Members of the Pulmonary Pathology Society(2017) CAPELOZZI, Vera Luiza; ALLEN, Timothy Craig; BEASLEY, Mary Beth; CAGLE, Philip T.; GUINEE, Don; HARIRI, Lida P.; HUSAIN, Aliya N.; JAIN, Deepali; LANTUEJOUL, Sylvie; LARSEN, Brandon T.; MILLER, Ross; MINO-KENUDSON, Mari; MEHRAD, Mitra; RAPARIA, Kirtee; RODEN, Anja; SCHNEIDER, Frank; SHOLL, Lynette M.; SMITH, Maxwell LawrenceAcute respiratory distress syndrome (ARDS) is a multifactorial syndrome with high morbidity and mortality rates, characterized by deficiency in gas exchange and lung mechanics that lead to hypoxemia, dyspnea, and respiratory failure. Histologically, ARDS is characterized by an acute, exudative phase, combining diffuse alveolar damage and noncardiogenic edema, followed by a later fibroproliferative phase. Despite an enhanced understanding of ARDS pathogenesis, the capacity to predict the development of ARDS and to risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the greatest risk of developing ARDS, to evaluate response to therapy, to predict outcome, and to improve clinical trials. The ARDS pathogenesis is presented in this article, as well as concepts and information on biomarkers that are currently used clinically or are available for laboratory use by academic and practicing pathologists and the developing and validating of new assays, focusing on the assays' major biologic roles in lung injury and/or repair and to ultimately suggest innovative, therapeutic approaches.
- Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension(2017) MENDONCA, Lucas de; FELIX, Nathane S.; BLANCO, Natalia G.; SILVA, Jaqueline S. Da; FERREIRA, Tatiana P.; ABREU, Soraia C.; CRUZ, Fernanda F.; ROCHA, Nazareth; SILVA, Patricia M.; MARTINS, Vanessa; CAPELOZZI, Vera L.; ZAPATA-SUDO, Gizele; ROCCO, Patricia R. M.; SILVA, Pedro L.Background: Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Methods: Twenty-eight Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, while a control group received saline (SAL) instead. On day 14, both groups were further randomized to receive 105 adipose-derived MSCs or SAL intravenously (n = 7/group). On day 28, right ventricular systolic pressure (RVSP) and the gene expression of mediators associated with apoptosis, inflammation, fibrosis, Smad-1 levels, cell proliferation, and endothelial-mesenchymal transition were determined. In addition, lung histology (smooth muscle cell proliferation and plexiform-like injuries), CD68(+) and CD163(+) macrophages, and plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were evaluated. Results: In the PAH group, adipose-derived MSCs, compared to SAL, reduced mean RVSP (29 +/- 1 vs 39 +/- 2 mmHg, p < 0.001), lung tissue collagen fiber content, smooth muscle cell proliferation, CD68(+) macrophages, interleukin-6 expression, and the antiapoptotic mediators Bcl-2 and survivin. Conversely, expression of the proapoptotic mediator procaspase-3 and plasma VEGF increased, with no changes in PDGF. In the pulmonary artery, MSCs dampened the endothelial-mesenchymal transition. Conclusion: In MCT-induced PAH, MSC therapy reduced lung vascular remodeling, thus improving hemodynamics. These beneficial effects were associated with increased levels of proapoptotic markers, mesenchymal-to-endothelial transition, reduced cell proliferation markers, and inflammation due to a shift away from the M1 phenotype.
conferenceObject Anti-VEGF and Anti-EGFR Reduce Malignant Pleural Effusion and Morbidity in an Experimental Adenocarcinoma Model(2017) TEIXEIRA, Lisete; ACENCIO, Milena; ALVARENGA, Vanessa; SILVA, Gabriela; BRITO, Zenaide; FERNEZLIAN, Sandra; PUKA, Juliana; MARTINS, Vanessa; CAPELOZZI, Vera- Bosutinib Therapy Ameliorates Lung Inflammation and Fibrosis in Experimental Silicosis(2017) CARNEIRO, Priscila J.; CLEVELARIO, Amanda L.; PADILHA, Gisele A.; SILVA, Johnatas D.; KITOKO, Jamil Z.; OLSEN, Priscilla C.; CAPELOZZI, Vera L.; ROCCO, Patricia R. M.; CRUZ, Fernanda F.Silicosis is an occupational lung disease for which no effective therapy exists. We hypothesized that bosutinib, a tyrosine kinase inhibitor, might ameliorate inflammatory responses, attenuate pulmonary fibrosis, and thus improve lung function in experimental silicosis. For this purpose, we investigated the potential efficacy of bosutinib in the treatment of experimental silicosis induced in C57BL/6 mice by intratracheal administration of silica particles. After 15 days, once disease was established, animals were randomly assigned to receive DMSO or bosutinib (1 mg/kg/dose in 0.1 mL 1% DMSO) by oral gavage, twice daily for 14 days. On day 30, lung mechanics and morphometry, total and differential cell count in alveolar septa and granuloma, levels of interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-4, transforming growth factor (TGF)-beta, and vascular endothelial growth factor in lung homogenate, M1 and M2 macrophages, total leukocytes, and T cells in BALF, lymph nodes, and thymus, and collagen fiber content in alveolar septa and granuloma were analyzed. In a separate in vitro experiment, RAW264.7 macrophages were exposed to silica particles in the presence or absence of bosutinib. After 24 h, gene expressions of arginase-1, IL-10, IL-12, inducible nitric oxide synthase (iNOS), metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, and caspase-3 were evaluated. In vivo, in silicotic animals, bosutinib, compared to DMSO, decreased: (1) fraction area of collapsed alveoli, (2) size and number of granulomas, and mononuclear cell granuloma infiltration; (3) IL-1 beta, TNF-alpha, IFN-gamma, and TGF-beta levels in lung homogenates, (4) collagen fiber content in lung parenchyma, and (5) viscoelastic pressure and static lung elastance. Bosutinib also reduced M1 cell counts while increasing M2 macrophage population in both lung parenchyma and granulomas. Total leukocyte, regulatory T, CD4(+), and CD8(+) cell counts in the lung-draining lymph nodes also decreased with bosutinib therapy without affecting thymus cellularity. In vitro, bosutinib led to a decrease in IL-12 and iNOS and increase in IL-10, arginase-1, MMP-9, and TIMP-1. In conclusion, in the current model of silicosis, bosutinib therapy yielded beneficial effects on lung inflammation and remodeling, therefore resulting in lung mechanics improvement. Bosutinib may hold promise for silicosis; however, further studies are required.
- Low-sodium diet induces atherogenesis regardless of lowering blood pressure in hypertensive hyperlipidemic mice(2017) FUSCO, Fernanda B.; GOMES, Diego J.; BISPO, Kely C. S.; TOLEDO, Veronica P.; BARBEIRO, Denise F.; CAPELOZZI, Vera L.; FURUKAWA, Luzia N. S.; VELOSA, Ana P. P.; TEODORO, Walcy R.; HEIMANN, Joel C.; QUINTAO, Eder C. R.; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; CATANOZI, SergioThis study investigated the influence of sodium restriction and antihypertensive drugs on atherogenesis utilizing hypertensive (H) low-density lipoprotein-receptor knockout mice treated or not with losartan (Los) or hydralazine (Hyd) and fed low-sodium (LS) or normal-sodium (NS) chow. Despite reducing the blood pressure (BP) of H-LS mice, the LS diet caused arterial lipid infiltration due to increased plasma total cholesterol (TC) and triglycerides (TG). Los and Hyd reduced the BP of H-LS mice, and Los effectively prevented arterial injury, likely by reducing plasma TG and nonesterified fatty acids. Aortic lipid infiltration was lower in Los-treated H-LS mice (H-LS+Los) than in normotensive (N)-LS and H-LS mice. Aortic angiotensin II type 1 (AT1) receptor content was greater in H-NS than H-LS mice and in H-LS+Hyd than H-LS+Los mice. Carboxymethyl-lysine (CML) and receptor for advanced glycation end products (RAGE) immunostaining was greater in H-LS than H-NS mice. CML and RAGE levels were lower in LS animals treated with antihypertensive drugs, and Hyd enhanced the AT1 receptor level. Hyd also increased the gene expression of F4/80 but not tumor necrosis factor-a, interleukin (IL)-1 beta, IL-6, IL-10, intercellular adhesion molecule-1 or cluster of differentiation 66. The novelty of the current study is that in a murine model of simultaneous hypertension and hyperlipidemia, the pleiotropic effect of chronic, severe sodium restriction elicited aortic damage even with reduced BP. These negative effects on the arterial wall were reduced by AT1 receptor antagonism, demonstrating the influence of angiotensin II in atherogenesis induced by a severely LS diet.
- Impact of Different Ventilation Strategies on Driving Pressure, Mechanical Power, and Biological Markers During Open Abdominal Surgery in Rats(2017) MAFIA, Ligia de A.; SAMARY, Cynthia S.; OLIVEIRA, Milena V.; SANTOS, Cintia L.; HUHLE, Robert; CAPELOZZI, Vera L.; MORALES, Marcelo M.; SCHULTZ, Marcus J.; ABREU, Marcelo G.; PELOSI, Paolo; SILVA, Pedro L.; ROCCO, Patricia Rieken MacedoBACKGROUND: Intraoperative mechanical ventilation may yield lung injury. To date, there is no consensus regarding the best ventilator strategy for abdominal surgery. We aimed to investigate the impact of the mechanical ventilation strategies used in 2 recent trials (Intraoperative Protective Ventilation [IMPROVE] trial and Protective Ventilation using High versus Low PEEP [PROVHILO] trial) on driving pressure (Delta P-RS), mechanical power, and lung damage in a model of open abdominal surgery. METHODS: Thirty-five Wistar rats were used, of which 28 were anesthetized, and a laparotomy was performed with standardized bowel manipulation. Postoperatively, animals (n = 7/group) were randomly assigned to 4 hours of ventilation with: (1) tidal volume (V-T) = 7 mL/kg and positive end-expiratory pressure (PEEP) =1 cm H2O without recruitment maneuvers (RMs) (low V-T/low PEEP/RM), mimicking the low-V-T/low-PEEP strategy of PROVHILO; (2) V-T = 7 mL/kg and PEEP = 3 cm H2O with RMs before laparotomy and hourly thereafter (low V-T/moderate PEEP/4 RM+), mimicking the protective ventilation strategy of IMPROVE; (3) V-T = 7 mL/kg and PEEP = 6 cm H2O with RMs only before laparotomy (low V-T/ high PEEP/1 RM+), mimicking the strategy used after intubation and before extubation in PROVHILO; or (4) V-T = 14 mL/kg and PEEP = 1 cm H2O without RMs (high V-T/low PEEP/RM), mimicking conventional ventilation used in IMPROVE. Seven rats were not tracheotomized, operated, or mechanically ventilated, and constituted the healthy nonoperated and nonventilated controls. RESULTS: Low V-T/moderate PEEP/4 RM+ and low V-T/high PEEP/1 RM+, compared to low V-T/ low PEEP/RM and high V-T/low PEEP/RM, resulted in lower APRs (7.1 +/- 0.8 and 10.2 +/- 2.1 cm H2O vs 13.9 0.9 and 16.9 0.8 cm H(2)0, respectively; P <.001) and less mechanical power (63 +/- 7 and 79 +/- 20 J/min vs 110 10 and 120 20 J/min, respectively; P =.007). Low V-T/high PEEP/1 RM+ was associated with less alveolar collapse than low V-T/low PEEP/ RM (P =.03). E-cadherin expression was higher in low V-T/moderate PEEP/4 RM+ than in low V-T/low PEEP/RM (P =.013) or high V-T/low PEEP/RM (P =.014). The extent of alveolar collapse, E-cadherin expression, and tumor necrosis factor-alpha correlated with Delta P-RS (r = 0.54 [P =.02], r = 0.48 [P =.05], and r = 0.59 [P =.09], respectively) and mechanical power (r = 0.57 [P =.02], r = 0.54 [P =.02], and r = 0.48 [P =.04], respectively). CONCLUSIONS: In this model of open abdominal surgery based on the mechanical ventilation strategies used in IMPROVE and PROVHILO trials, lower mechanical power and its surrogate. Delta P-RS were associated with reduced lung damage.
- Comprehensive Analysis of EMT Gene Signature in Primary and Metastatic Small Cell and Non-Small Cell Carcinomas of the Lung(2017) PRIETO, T.; SA, V. De; OLIVIERI, E.; SILVA, E. Da; REIS, R.; CARRARO, D.; CAPELOZZI, V.
conferenceObject Assessment of PDL1 and Immunoprofiling Using Multiplex Quantitative Immunofluorescence in Lung Cancer: Clinical Implications(2017) PRIETO, T.; FAHRAT, C.; TAKAGAKI, T.; RODRIGUEZ-CANALES, J.; WISTUBA, I.; CAPELOZZI, V.; CUENTAS, E. ParraconferenceObject Gene Signature of EMT in Neuroendocrine Lung Carcinoma: A Comparative Analysis with Adenocarcinoma and Squamous Cell Carcinoma(2017) PRIETO, Tabatha; SA, Vanessa De; OLIVIERI, Eloisa; SILVA, Eduardo Da; REIS, Rui; CARRARO, Dirce; CAPELOZZI, Vera
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