PAULO HILARIO NASCIMENTO SALDIVA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
57 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 57
- Inflammation and Remodeling in Infantile, Juvenile, and Adult Allergic Sensitized Mice(2011) CARNIELI, Denise S.; YOSHIOKA, Eliane; SILVA, Luiz Fernando F.; LANCAS, Tatiana; ARANTES, Fernanda M.; PERINI, Adenir; MARTINS, Milton A.; SALDIVA, Paulo Hilario N.; DOLHNIKOFF, Marisa; MAUAD, ThaisBackground: Airway structural changes occur early in childhood asthma, but it is unknown whether the development of airway alterations in children is similar to that of adults. We compared inflammation and remodeling parameters in allergic sensitized infantile, juvenile, and adult mice. Methods: Infantile mice (18D) were sensitized with three intraperitoneal injections (i.p.) of ovalbumin (OVA) at days 5 and 7 and challenged with OVA at days 14-16. The 18D1 group received an additional challenge at days 9-11. The juvenile mice (40D) received challenges at days 22-24 and 36-38. Adult mice (100D) were sensitized at days 60-62 and received three inhalations at days 77-79 and 96-98. Animals were submitted to whole body plethysmography. Airway eosinophils, CD3+ T-lymphocytes, IL-5+ cells, mucus content, collagen and reticular fibers density, and smooth muscle thickness were quantified. Results: All sensitized animals presented with airway hyperresponsiveness, without differences in eosinophil cell density The density of CD3+ T-cells was higher in the 100D and 1801 groups than in the 18D and 40D groups. Infantile sensitized groups demonstrated increased interleukin-5 expression in the airways. Infantile mice demonstrated more mucus in the bronchiolar epithelium than the 40D and 100D mice. The 18D animals demonstrated less collagen than the 18D1 group. Juvenile and adult mice had increased airway smooth muscle thickness when compared to age-matched controls, but no differences were observed in the infantile groups. Conclusion: We have shown that infantile mice develop inflammatory and structural alterations in the airways that are partially different from those developed in older animals. Pediatr Pulmonol. 2011;46:650-665. (C) 2011 Wiley-Liss, Inc.
- Lung ECM composition, its influence factors and transcriptomics in the lungs of severe COVID-19.(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Toledo Do; BRITO, Jose Mara De; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; MONTEIRO, Renata Aparecida De Almeida; DUARTE NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz Da; DOLHNIKOFF, Marisa; MAUAD, Thais
- Dynamics and Heterogeneity of the Lung Immunopathology in Severe COVID-19(2022) ERJEFALT, J.; COSTA, N. De Souza Xavier; JONSSON, J.; COZZOLINO, O.; DANTAS, K.; CLAUSSON, C.; SIDDHURAJ, P.; LINDO, C.; LOMBARDI, S. Ferreira Spina; MENDRONI JUNIOR, A.; ANTONANGELO, L.; FARIA, C. Silverio; DUARTE NETO, A. Nunes; MONTEIRO, R. De Almeida; PINHO, J. Rebello; GOMES-GOUVEA, M. Soares; PEREIRA, R. Verciano; MONTEIRO, J. Sirino; SETUBAL, J.; OLIVEIRA, E. Pierre De; THEODORO FILHO, J.; SANDEN, C.; ORENGO, J.; SLEEMAN, M.; SILVA, L. Ferraz Da; SALDIVA, P. Nascimento; DOLHNIKOFF, M.; MAUAD, T.
- Differences between postmortem computed tomography and conventional autopsy in a stabbing murder case(2014) ZERBINI, Talita; SILVA, Luiz Fernando Ferraz da; FERRO, Antonio Carlos Goncalves; KAY, Fernando Uliana; AMARO JUNIOR, Edson; PASQUALUCCI, Carlos Augusto Goncalves; SALDIVA, Paulo Hilario do NascimentoOBJECTIVE: The aim of the present work is to analyze the differences and similarities between the elements of a conventional autopsy and images obtained from postmortem computed tomography in a case of a homicide stab wound. METHOD: Comparison between the findings of different methods: autopsy and postmortem computed tomography. RESULTS: In some aspects, autopsy is still superior to imaging, especially in relation to external examination and the description of lesion vitality. However, the findings of gas embolism, pneumothorax and pulmonary emphysema and the relationship between the internal path of the instrument of aggression and the entry wound are better demonstrated by postmortem computed tomography. CONCLUSIONS: Although multislice computed tomography has greater accuracy than autopsy, we believe that the conventional autopsy method is fundamental for providing evidence in criminal investigations.
- Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model(2017) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; ALEMANY, Adair Aparecida dos Santos; BELOTTI, Luciano; ZATI, Douglas Hidalgo; CAVALCANTE, Marcela Frota; VERAS, Mariana Matera; RIBEIRO, Susan; KALLAS, Esper Georges; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOTT, Marisa; SILVA, Luiz Fernando Ferraz daBackground and objective Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35 - 46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) using nebulized lipopolysaccharide (LPS) in a non-invasive approach, focusing on its short and long-term effects. Methods Mice received nebulized LPS or vehicle only (control group). Blood, BALF and lung tissue were collected 24 hours (LPS 24h) or 5 weeks (LPS 5w) after the nebulized LPS-induced lung injury. Inflammatory cytokines were assessed in the blood serum, BALF and lung tissue. Stereological analyses and remodeling changes were assessed by histology and immunohistochemistry at the specified time points. Results The LPS 24h group showed increased pro-inflammatory cytokine levels, intense cell influx, increased total septal volume, septal thickening and decreased surface density of the alveolar septa. The LPS 5w group showed persistent lung inflammation, septal thickening, increased total lung volume, accentuated collagen deposition, especially of collagen type I, and decreased MMP-2 protein expression. Conclusion We present a feasible, reproducible and non-invasive nebulized-LPS animal model that allows the assessment of both the acute and late phases of acute lung injury. The presence of lung remodeling with collagen deposition after 5 weeks makes it useful to study the pathophysiology, complications, and possible therapeutic intervention studies that aim to understand and reduce pulmonary fibrosis in the late phases of ALI.
- Air pollution impairs recovery and tissue remodeling in a murine model of acute lung injury(2020) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; ALEMANY, Adair Aparecida dos Santos; BELOTTI, Luciano; SCHALCH, Alexandre Santos; CAVALCANTE, Marcela Frota; RIBEIRO, Susan; VERAS, Mariana Matera; KALLAS, Esper Georges; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; SILVA, Luiz Fernando Ferraz daEvidence regarding the impact of air pollution on acute respiratory distress syndrome (ARDS) is limited, and most studies focus on ARDS onset. Our study aimed to evaluate whether exposure to fine particulate matter interferes with lung recovery and remodeling in a murine model of acute lung injury. Forty-eight mice received nebulized LPS or the vehicle (controls). Blood, BALF, lungs and spleen were collected after 5 weeks of exposure to either PM2.5 (PM and LPS+PM group) or filtered air (control and LPS5w groups). Inflammatory cells and cytokines were assessed in the blood, BALF, lungs and spleen. Stereological analyses and remodeling assessments were performed by histology. The LPS+PM group showed increased BALF leukocytes, characterized by increased macrophages, increased IL-1 beta and IL-6 levels, anemia and thrombocytopenia. Moreover, we also observed septal thickening, decreased alveolar air space total volume and, septa surface density. Finally, regarding tissue remodeling, we observed elastosis of the lung parenchyma, and unlike in the LPS5w group, we did not observe fibrosis in the LPS+PM group. In conclusion, the delayed inflammation resolution due to subchronic exposure to PM2.5 could be influenced by low systemic and local lymphocyte counts, which lead to impaired lung injury recovery and tissue remodeling.
- Small airway remodeling in acute respiratory distress syndrome: a study in autopsy lung tissue(2011) MORALES, Maina M. B.; PIRES-NETO, Ruy C.; INFORSATO, Nicole; LANCAS, Tatiana; SILVA, Luiz F. F. da; SALDIVA, Paulo H. N.; MAUAD, Thais; CARVALHO, Carlos R. R.; AMATO, Marcelo B. P.; DOLHNIKOFF, MarisaIntroduction: Airway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients. Methods: We retrospectively studied autopsy lung tissue from subjects who died with ARDS and from control subjects who died of non pulmonary causes. Using image analysis, we quantified the extension of epithelial changes (normal, abnormal and denudated epithelium expressed as percentages of the total epithelium length), bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. The Student's t test or the Mann-Whitney test was used to compare data between the ARDS and control groups. Bonferroni adjustments were used for multiple tests. The association between morphological and clinical data was analyzed by Pearson rank test. Results: Thirty-one ARDS patients (A: PaO(2)/FiO(2) <= 200, 45 +/- 14 years, 16 males) and 11 controls (C:52 +/- 16 years, 7 males) were included in the study. ARDS airways showed a shorter extension of normal epithelium (A:32.9 +/- 27.2%, C:76.7 +/- 32.7%, P < 0.001), a larger extension of epithelium denudation (A:52.6 +/- 35.2%, C:21.8 +/- 32.1%, P < 0.01), increased airway inflammation (A:1(3), C:0(1), P = 0.03), higher airway wall thickness (A:138.7 +/- 54.3 mu m, C:86.4 +/- 33.3 mu m, P < 0.01), and higher airway content of collagen I, fibronectin, versican and matrix metalloproteinase-9 (MMP-9) compared to controls (P = 0.03). The extension of normal epithelium showed a positive correlation with PaO(2)/FiO(2) (r(2) = 0.34; P = 0.02) and a negative correlation with plateau pressure (r(2) = 0.27; P = 0.04). The extension of denuded epithelium showed a negative correlation with PaO(2)/FiO(2) (r(2) = 0.27; P = 0.04). Conclusions: Structural changes in small airways of patients with ARDS were characterized by epithelial denudation, inflammation and airway wall thickening with ECM remodeling. These changes are likely to contribute to functional airway changes in patients with ARDS.
- Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice(2013) CARVALHO, Ana Laura Nicoletti; ANNONI, Raquel; TORRES, Larissa Helena Lobo; DURAO, Ana Carolina Cardoso Santos; SHIMADA, Ana Lucia Borges; ALMEIDA, Francine Maria; HEBEDA, Cristina Bichels; LOPES, Fernanda Degobbi Tenorio Quirino Santos; DOLHNIKOFF, Marisa; MARTINS, Milton Arruda; SILVA, Luiz Fernando Ferraz; FARSKY, Sandra Helena Poliselli; SALDIVA, Paulo Hilario Nascimento; ULRICH, Cornelia M.; OWEN, Robert W.; MARCOURAKIS, Tania; TREVISAN, Maria Teresa Salles; MAUAD, ThaisAnacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle-(DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50 mu g of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250mg/kg of anacardic acids or vehicle (100 mu L of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs.
- Immune receptors and adhesion molecules in human pulmonary leptospirosis(2012) BERNARDI, Fabiola Del Carlo; CTENAS, Bruno; SILVA, Luiz Fernando Ferraz da; NICODEMO, Antonio Carlos; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; MAUAD, ThaisPulmonary involvement in leptospirosis has been increasingly reported in the last 20 years, being related to the severity and mortality of the disease. The pathogenesis of pulmonary hemorrhage in leptospirosis is not understood. Lung endothelial cells have been proposed as targets in the pathogenesis of lung involvement in leptospirosis through the activation of Toll-like receptor 2 or the complement system, which stimulates the release of cytokines that lead to the activation of adhesion molecules. The aim of this study was to investigate the involvement of immune pathways and of the intercellular and vascular cell adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule, respectively) in the lungs of patients with pulmonary involvement of leptospirosis. We studied the lungs of 18 patients who died of leptospirosis and compared them with 2 groups of controls: normal and noninfectious hemorrhagic lungs. Using immunohistochemistry and image analysis, we quantified the expression of the C3a anaphylatoxin receptor, intercellular adhesion molecule, vascular cell adhesion molecule, and Toll-like receptor 2 in small pulmonary vessels and in the alveolar septa. There was an increased expression of intercellular adhesion molecule (P <.03) and C3a anaphylatoxin receptor (P <.008) in alveolar septa in the leptospirosis group compared with the normal and hemorrhagic controls. In the vessels of the leptospirosis group, there was an increased expression of intercellular adhesion molecule (P=.004), vascular cell adhesion molecule (P=.030), and Toll-like receptor 2 (P=.042) compared with the normal group. Vascular cell adhesion molecule expression in vessels was higher in the leptospirosis group compared with the hemorrhagic group (P=.015). Our results indicate that immune receptors and adhesion molecules participate in the phenomena leading to pulmonary hemorrhage in leptospirosis.
- Main autopsyfindings of visceral involvement by fatal mpox in patients with AIDS: necrotising nodular pneumonia, nodular ulcerative colitis, and diffuse vasculopathy(2023) DUARTE-NETO, Amaro Nunes; GONCALVES, Ana Maria; ELIODORO, Raissa Heloisa de Araujo; MARTINS, Wilker Dias; CLARO, Ingra Morales; VALENCA, Ian Nunes; PAES, Vitor Ribeiro; TEIXEIRA, Ralcyon; SZTAJNBOK, Jaques; SILVA, Ivan Leonardo Avelino Franca e; LEITE, Luiz Antonio Ferreira; MALAQUE, Ceila Maria Sant'Ana; BORGES, Luciana Marques Sansao; GONZALEZ, Mario Peribanez; BARRA, Luiz Alberto Costa; PEREIRA JUNIOR, Luiz Carlos; MELLO, Claudia Figueiredo; QUEIROZ, Wladimir; ATOMYA, Angela Naomi; FERNEZLIAN, Sandra de Morais; ALVES, Venancio Avancini Ferreira; LEITE, Katia Ramos Moreira; FERREIRA, Cristiane Rubia; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; SILVA, Luiz Fernando Ferraz da; FARIA, Nuno R.; CORREA, Maria Cassia Jacinto Mendes; SABINO, Ester Cerdeira; SOTTO, Mirian Nacagami; DOLHNIKOFF, Marisa