RAQUEL ANNONI
Projetos de Pesquisa
Unidades Organizacionais
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
14 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 14
- Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma(2012) YICK, C. Y.; FERREIRA, D. S.; ANNONI, R.; THUSEN, J. H. von der; KUNST, P. W.; BEL, E. H.; LUTTER, R.; MAUAD, T.; STERK, P. J.Background: Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in ASM between asthma and controls. Second, we examined whether ECM expression is associated with bronchoconstriction and bronchodilation in vivo. Methods: Our cross-sectional study comprised 19 atopic mild asthma patients, 15 atopic and 12 nonatopic healthy subjects. Spirometry, methacholine responsiveness, deep-breath-induced bronchodilation (Delta R-rs) and bronchoscopy with endobronchial biopsies were performed. Positive staining of elastin, collagen I, III and IV, decorin, versican, fibronectin, laminin and tenascin in ASM was quantified as fractional area and mean density. Data were analysed using Pearson's or Spearman's correlation coefficient. Results: Extracellular matrix expression in ASM was not different between asthma and controls. In asthmatics, fractional area and mean density of collagen I and III were correlated with methacholine dose-response slope and DRrs, respectively (r = 0.71, P < 0.01; r = 0.60, P = 0.02). Furthermore, ASM collagen III and laminin in asthma were correlated with FEV1 reversibility (r = -0.65, P = 0.01; r = -0.54, P = 0.04). Conclusion: In asthma, ECM in ASM is related to the dynamics of airway function in the absence of differences in ECM expression between asthma and controls. This indicates that the ASM layer in its full composition is a major structural component in determining variable airways obstruction in asthma.
- Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice(2011) CARVALHO, Ana Laura Nicoletti; ANNONI, Raquel; SILVA, Paula Regina Pereira; BORELLI, Primavera; FOCK, Ricardo Ambrosio; TREVISAN, Maria Teresa Salles; MAUAD, ThaisAim of the study: Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models. Materials and methods: We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24 h after oral administration of 250 mg/kg AAs. Results: Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects. Conclusions: The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo.
- Impact of obesity on airway and lung parenchyma remodeling in experimental chronic allergic asthma(2011) SARAIVA, Simone A.; SILVA, Adriana L.; XISTO, Debora G.; ABREU, Soraia C.; SILVA, Johnatas D.; SILVA, Pedro L.; TEIXEIRA, Tatiana P. F.; PARRA, Edwin R.; CARVALHO, Ana Laura N.; ANNONI, Raquel; MAUAD, Thais; CAPELOZZI, Vera L.; SILVA, Patricia M. R.; MARTINS, Marco A.; ROCCO, Patricia R. M.The impact of obesity on the inflammatory process has been described in asthma, however little is known about the influence of diet-induced obesity on lung remodeling. For this purpose, 56 recently weaned A/J mice were randomly divided into 2 groups. In the C group, mice were fed a standard chow diet, while OB animals received isocaloric high-fat diet to reach 1.5 of the mean body weight of C. After 12 weeks, each group was further randomized to be sensitized and challenged with ovalbumin (OVA) or saline. Twenty-four hours after the last challenge, collagen fiber content in airways and lung parenchyma, the volume proportion of smooth muscle-specific actin in alveolar ducts and terminal bronchiole, and the number of eosinophils in bronchoalveolar lavage fluid were higher in OB-OVA than C-OVA. In conclusion, diet-induced obesity enhanced lung remodeling resulting in higher airway responsiveness in the present experimental chronic allergic asthma.
- Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma(2012) FERREIRA, D. S.; ANNONI, R.; SILVA, L. F. F.; BUTTIGNOL, M.; SANTOS, A. B. G.; MEDEIROS, M. C. R.; ANDRADE, L. N. S.; YICK, C. Y.; STERK, P. J.; SAMPAIO, J. L. M.; DOLHNIKOFF, M.; WENZEL, S. E.; MAUAD, T.Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics both large and small airways has not been investigated. Objective To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non-smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non-smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real-time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects. Results Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non-smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression. Conclusions and Clinical Relevance Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.
- 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.
- Extracellular matrix composition in COPD(2012) ANNONI, Raquel; LANCAS, Tatiana; TANIGAWA, Ryan Yukimatsu; MATSUSHITA, Marcus de Medeiros; FERNEZLIAN, Sandra de Morais; BRUNO, Andreina; SILVA, Luiz Fernando Ferraz da; ROUGHLEY, Peter J.; BATTAGLIA, Salvatore; DOLHNIKOFF, Marisa; HIEMSTRA, Pieter S.; STERK, Peter J.; RABE, Klaus F.; MAUAD, ThaisExtracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.
conferenceObject Elastic fibers and fibronectin expression in severe asthmatics(2013) FERREIRA, Diogenes; ANNONI, Raquel; CARVALHO-PINTO, Regina Maria; RABE, Klaus; CUKIER, Alberto; STELMACH, Rafael; DOLHNIKOFF, Marisa; MAUAD, ThaisconferenceObject Granzyme A Expression In Fatal Asthma(2013) SILVA, L. F.; SANTOS, F. E.; ANNONI, R.; NUSSBAUMER-OCHSNER, Y.; DOLHNIKOFF, M.; RABE, K. F.; MAUAD, T.; HIEMSTRA, P.- Regulatory T-Cell Distribution within Lung Compartments in COPD(2017) SALES, Davi S.; ITO, Juliana T.; ZANCHETTA, Ivy A.; ANNONI, Raquel; AUN, Marcelo V.; FERRAZ, Luiz Fernando S.; CERVILHA, Daniela A. B.; NEGRI, Elnara; MAUAD, Thais; MARTINS, Milton A.; LOPES, Fernanda D. T. Q. S.The importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF(+) cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17(+) cells only in small airways. A decrease in the density of Treg(+), TGF-beta(+) and IL-10(+) in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF(+) cells were also increased in COPD; however, changes in Treg inhibitory associated cytokineswere not observed in this compartment. Therefore, our results suggest that difference in Treg(+) cell distributions in lung compartments and the decrease in TGF-beta(+) and IL-10(+) cells in the airways may lead to the obstruction in smokers.
conferenceObject Versican, tenascin, periostin and IL-17A+cells in severe asthma(2014) MAUAD, Thais; FERREIRA, Diogenes S.; ANNONI, Raquel; OLIVEIRA, Bianca L.; KATAYAMA, Edgard H.; CARVALHO-PINTO, Regina M.; RABE, Klaus F.; CUKIER, Alberto; STELMACH, Rafael; DOLHNIKOFF, Marisa