MARISA DOLHNIKOFF
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
37 resultados
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- 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
- 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.
- 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.
- Exercise Performed Concomitantly with Particulate Matter Exposure Inhibits Lung Injury(2018) SILVA-RENNO, Adriano; BALDIVIA, Guilherme Crisitanini; OLIVEIRA-JUNIOR, Manoel C.; BRANDAO-RANGEL, Maysa Alves Rodrigues; EL-MAFARJEH, Elias; DOLHNIKOFF, Marisa; MAUAD, Thais; BRITTO, Jose Mara; SALDIVA, Paulo Hilario Nascimento; OLIVEIRA, Luis Vicente Franco; LIGEIRO-OLIVEIRA, Ana P.; GRAUDENZ, Gustavo Silveira; VIEIRA, Rodolfo PaulaAir pollution is a growing problem worldwide, inducing and exacerbating several diseases. Among the several components of air pollutants, particulate matter (PM), especially thick (10-2.5 mu m; PM 10) and thin (2.5 mu m; PM 2.5), are breathable particles that easily can be deposited within the lungs, resulting in pulmonary and systemic inflammation. Although physical activity is strongly recommended, its effects when practiced in polluted environments are questionable. Therefore, the present study evaluated the pulmonary and systemic response of concomitant treadmill training with PM 2.5 and PM 10 exposure. Treadmill training inhibited PM 2.5- and PM 10-induced accumulation of total leukocytes (p<0.001), neutrophils (p<0.001), macrophages (p<0.001) and lymphocytes (p<0.001) in bronchoalveolar lavage (BAL), as well as the BAL levels of IL-1beta (p<0.001), CXCL1/KC (p<0.001) and TNF-alpha (p<0.001), whereas it increased IL-10 levels (p<0.05). Similar effects were observed on accumulation of polymorphonuclear (p<0.01) and mononuclear (p<0.01) cells in the lung parenchyma and in the peribronchial space. Treadmill training also inhibited PM 2.5- and PM 10-induced systemic inflammation, as observed in the number of total leukocytes (p<0.001) and in the plasma levels of IL-1beta (p<0.001), CXCL1/KC (p<0.001) and TNF-alpha (p<0.001), whereas it increased IL-10 levels (p<0.001). Treadmill training inhibits lung and systemic inflammation induced by particulate matter.
- 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.
- Mechanical evaluation of the resistance and elastance of post-burn scars after topical treatment with tretinoin(2011) DEMATTE, Maria Fernanda; GEMPERLI, Rolf; SALLES, Alessandra Grassi; DOLHNIKOFF, Marisa; LANCAS, Tatiana; SALDIVA, Paulo Hilario Nascimento; FERREIRA, Marcus CastroOBJECTIVE: After burn injuries, scarred skin lacks elasticity, especially in hypertrophic scars. Topical treatment with tretinoin can improve the appearance and quality of the skin (i.e., texture, distensibility, color, and hydration). The objective of this prospective study was to examine the effects of treatment with 0.05% tretinoin for one year on the biomechanical behavior and histological changes undergone by facial skin with post-burn scarring. Setting: Tertiary, Institutional. METHOD: Fifteen female patients who had suffered partial thickness burns with more than two years of evolution were selected. Skin biopsies were obtained initially and after one year of treatment. The resistance and elastance of these skin biopsies were measured using a mechanical oscillation analysis system. The density of collagen fibers, elastic fibers, and versican were determined using immunohistochemical analysis. RESULTS: Tretinoin treatment significantly lowered skin resistance and elastance, which is a result that indicates higher distensibility of the skin. However, tretinoin treatment did not significantly affect the density of collagen fibers, elastic fibers, or versican. CONCLUSION: Topical tretinoin treatment alters the mechanical behavior of post-burn scarred skin by improving its distensibility and thus leads to improved quality of life for patients.
- 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
- Postmortem chest computed tomography in COVID-19: A minimally invasive autopsy method(2024) SAVOIA, Paulo; SAWAMURA, Marcio Valente Yamada; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; MARTIN, Maria da Graca Morais; DOLHNIKOFF, Marisa; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; LEITE, Claudia da Costa; SILVA, Luiz Fernando Ferraz da; CARDOSO, Ellison FernandoObjectives: Performing autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology and pathology to evaluate postmortem CT lung findings and their correlation with histopathology. Methods: Twenty-nine patients with fatal COVID-19 underwent postmortem chest CT, and multiple lung tissue samples were collected. The chest CT scans were analyzed and quantified according to lung involvement in five categories: normal, ground-glass opacities, crazy-paving, small consolidations, and large or lobar consolidations. The lung tissue samples were examined and quantified in three categories: normal lung, exudative diffuse alveolar damage (DAD), and fibroproliferative DAD. A linear index was used to estimate the global severity of involvement by CT and histopathological analysis. Results: There was a positive correlation between patient mean CT and histopathological severity score indexesPearson correlation coefficient (R) = 0.66 (p = 0.0078). When analyzing the mean lung involvement percentage of each finding, positive correlations were found between the normal lung percentage between postmortem CT and histopathology (R=0.65, p = 0.0082), as well as between ground -glass opacities in postmortem CT and normal lungs in histopathology (R=0.65, p = 0.0086), but negative correlations were observed between groundglass opacities extension and exudative diffuse alveolar damage in histological slides (R=-0.68, p = 0.005). Additionally, it was found is a trend toward a decrease in the percentage of normal lung tissue on the histological slides as the percentage of consolidations in postmortem CT scans increased (R =-0.51, p = 0.055). The analysis of the other correlations between the percentage of each finding did not show any significant correlation or correlation trends (p >= 0.10). Conclusions: A minimally invasive autopsy is valid. As the severity of involvement is increased in CT, more advanced disease is seen on histopathology. However, we cannot state that one specific radiological category represents a specific pathological correspondent. Ground -glass opacities, in the postmortem stage, must be interpreted with caution, as expiratory lungs may overestimate disease.
- Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19(2020) DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro Nunes; MONTEIRO, Renata Aparecida de Almeida; SILVA, Luiz Fernando Ferraz da; OLIVEIRA, Ellen Pierre de; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; NEGRI, Elnara Marcia