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
5 resultados
Resultados de Busca
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- 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.
- Airway and parenchyma immune cells in influenza A(H1N1) pdm09 viral and non-viral diffuse alveolar damage(2017) BUTTIGNOL, Monique; PIRES-NETO, Ruy Camargo; SILVA, Renata Calciolari Rossi e; ALBINO, Marina Ballarin; DOLHNIKOFF, Marisa; MAUAD, ThaisBackground: Diffuse alveolar damage (DAD), which is the histological surrogate for acute respiratory distress syndrome (ARDS), has a multifactorial aetiology. Therefore it is possible that the immunopathology differs among the various presentations of DAD. The aim of this study is to compare lung immunopathology of viral (influenza A(H1N1) pdm09) to non-viral, extrapulmonary aetiologies in autopsy cases with DAD. Methods: The lung tissue of 44 patients, was divided in the H1N1 group (n = 15) characterized by severe pulmonary injury due to influenza A(H1N1) pdm09 infection; the ARDS group (n = 13), characterized by patients with DAD due to non-pulmonary causes; and the Control group (n = 16), consisting of patients with non-pulmonary causes of death. Immunohistochemistry and image analysis were used to quantify, in the parenchyma and small airways, several immune cell markers. Results: Both DAD groups had higher expression of neutrophils and macrophages in parenchyma and small airways. However, there was a higher expression of CD4+ and CD8+ T lymphocytes, CD83+ dendritic cells, granzyme A+ and natural killer + cell density in the lung parenchyma of the H1N1 group (p < 0.05). In the small airways, there was a lower cell density of tryptase + mast cells and dendritic + cells and an increase of IL-17 in both DAD groups (p < 0.05). Conclusion: DAD due to viral A(H1N1) pdm09 is associated with a cytotoxic inflammatory phenotype, with partially divergent responses in the parenchyma relative to the small airways. In non-viral DAD, main immune cell alterations were found at the small airway level, reinforcing the role of the small airways in the pathogenesis of the exudative phase of DAD.
- Mast cell subtypes in adults and children with severe asthma(2017) ARAUJO-PAULINO, Bianca Bergamo de; ELLER, Miriam Cardoso Neves; VERGANI, Karina Pierantozzi; CARVALHO-PINTO, Regina Maria; STELMACH, Rafael; YOSHIZAKI, Kelly; GROTH, Espen Elias; RODRIGUES, Joaquim; DOLHNIKOFF, Marisa; MAUAD, Thais
- Recreational use of marijuana during pregnancy and negative gestational and fetal outcomes: An experimental study in mice(2017) BENEVENUTO, Sarah G.; DOMENICO, Marlise D.; MARTINS, Marco Antonio G.; COSTA, Natalia S.; SOUZA, Ana Rosa L. de; COSTA, Jose L.; TAVARES, Marina F. M.; DOLHNIKOFF, Marisa; VERAS, Mariana MateraThe prevalence of marijuana use among pregnant women is high. However, the effects on gestation and fetal development are not well known. Epidemiological and experimental studies present conflicting results because of the route of administration, dose, time of exposure, species used, and how Cannabis toxicity is tested (prepared extracts, specific components, or by pyrolysis). In this study, we experimentally investigated the effects of maternal inhalation of Cannabis sativa smoke representing as nearly as possible real world conditions of human marijuana use. Pregnant mice (n=20) were exposed (nose-only) daily for 5 min to marijuana smoke (0.2 g of Cannabis) from gestational day (GD) 5.5 to GD17.5 or filtered air. Food intake and maternal weight gain were recorded. Ultrasound biomicroscopy was performed on 10.5 and 16.5dpc. On GD18.5, half of the dams were euthanized for the evaluation of term fetus, placenta, and resorptions. Gestation length, parturition, and neonatal outcomes were evaluated in the other half. Five minutes of daily (low dose) exposure during pregnancy resulted in reduced birthweight, and litter size was not altered; however, the number of male pups per litter was higher. Besides, placental wet weight was increased and fetal to placental weight ratio was decreased in male fetuses, showing a sex-specific effect. At the end of gestation, females from the Cannabis group presented reduced maternal net body weight gain, despite a slight increase in their daily food intake compared to the control group. In conclusion, our results indicate that smoking marijuana during pregnancy even at low doses can be embryotoxic and fetotoxic.
- Histopathological Findings Associated With Gastroesophageal Reflux Disease and Aspiration After Lung Transplantation: Initial Brazilian Single-Center Experience(2017) CARRARO, R. M.; NASCIMENTO, E. C. T.; SZACHNOWICZ, S.; CAMARGO, P. C. L. B.; CAMPOS, S. V.; AFONSO JR., J. E.; SAMANO, M. N.; PEGO-FERNANDES, P. M.; DOLHNIKOFF, M.; TEIXEIRAA, R. H. O. B.; COSTA, A. N.Background. Gastro-esophageal reflux disease (GERD) and broncho-aspiration (BA) are known to increase the risk for chronic lung allograft dysfunction (CLAD). However, specific lung injury mechanisms are not clearly known. The objective of the study was to describe histopathological findings in surveillance lung transbronchial biopsies that can be correlated with episodes of BA in the lung allograft. Methods. This retrospective analysis of surveillance transbronchial biopsies was performed in lung transplant recipients, with available data of broncho-alveolar fluid (cultures and cytology), lung function parameters, and esophageal functional tests. Results. Were analyzed 11 patients, divided into 3 groups: (1) GERD group: 4 patients with GERD and CLAD diagnosis; (2) control group: 2 patients without GERD or CLAD; and (3) BA group: 5 patients with foreign material in lung biopsies. A histopathological pattern of neutrophilic bronchitis (NB) was present in 4 of 4 cases in the GERD group and in 1 of 5 cases in the BA group in 2 or more biopsy samples; culture samples were all negative; the 5 NB-positive patients developed CLAD and died (3/5) or needed re-transplantation (2/5). The other 3 patients in the BA group had GERD without NB or CLAD. Both patients in the control group had transient NB in biopsies with positive cultures but remained free of CLAD. Conclusions. Surveillance transbronchial biopsies may provide useful information other than the evaluation of acute cellular rejection and can help to identify high-risk patients for allograft dysfunction related to gastro-esophageal reflux.