ALESSANDRA CHOQUETA DE TOLEDO ARRUDA
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Nasal Mucociliary Clearance in Subjects With COPD After Smoking Cessation(2015) ITO, Juliana T.; RAMOS, Dionei; LIMA, Fabiano F.; RODRIGUES, Fernanda M. M.; GOMES, Paulo R.; MOREIRA, Graciane L.; MACCHIONE, Mariangela; TOLEDO, Alessandra C.; RAMOS, Ercy M. C.BACKGROUND: Exposure to cigarette smoke causes significant impairment in mucociliary clearance (MCC), which predisposes patients to secretion retention and recurrent airway infections that play a role in exacerbations of COPD. To determine whether smoking cessation may influence MCC and frequency of exacerbations, the following groups were evaluated: ex-smokers with COPD, smokers with COPD, current smokers with normal lung function, and nonsmokers with normal lung function. METHODS: Ninety-three subjects were divided into 4 groups: ex-smokers with COPD (n = 23, 62.4 +/- 8.0 y, 13 males), smokers with COPD (n = 17, 58.2 +/- 8.0 y, 6 males), current smokers (n = 27, 61.5 +/- 6.4 y, 17 males), and nonsmokers (n = 26, 60.8 +/- 11.3 y, 7 males). MCC was evaluated using the saccharin transit time (STT) test, and the frequency of exacerbations in the last year was assessed by questionnaire. The Kruskal-Wallis test followed by Dunn's test were used to compare STT among groups, and the Goodman test was used to compare the frequency of exacerbations. RESULTS: STT of smokers with COPD (16.5 [11-28] min; median [interquartile range 25-75%]) and current smokers (15.9 110-271 min) was longer compared with ex-smokers with COPD (9.7 [6-12] min) and nonsmokers (8 [6-16] min) (P < .001). There was no difference in STT values between smokers with COPD and current smokers, and these values in ex-smokers with COPD were similar to the control group (P > .05). The frequency of exacerbations was lower in ex-smokers with COPD compared with smokers with COPD. CONCLUSIONS: One year after smoking cessation, subjects with COPD had improved mucociliary clearance.
- Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated protein kinase activation, cytoskeleton instability, and cytotoxicity in human bronchial epithelial cells(2015) SERIANI, Robson; JUNQUEIRA, Mara S.; CARVALHO-SOUSA, Claudia E.; ARRUDA, Alessandra Ct.; MARTINEZ, Diana; ALENCAR, Adriano M.; GARIPPO, Ana L.; BRITO, Jose Mara; MARTINS, Milton A.; SALDIVA, Paulo H. N.; NEGRI, Elnara M.; MAUAD, Thais; MACCHIONE, MariangelaThis study assessed the effects of the diesel exhaust particles on ERR and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements. JNK and ERR were activated simultaneously by crude DEP with no alterations in viscoelasticity of the cells. Mitochondrial activity, however, revealed a decrease through the MIT assay. DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage), and also activated JNK. Our data suggest that the greater bioavailability of metals could be involved in JNK activation and, consequently, in the reduction of fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX reflect the toxic potential of diesel compounds. Considering the fact that the cells of the respiratory epithelium are the first line of defense between the body and the environment, our data contribute to a better understanding of the pathways leading to respiratory cell injury and provide evidence for the onset of or worsening of respiratory diseases caused by inorganic compounds present in DEP.
- Acute Mucociliary Clearance Response to Aerobic Exercise in Smokers(2015) RAMOS, Ercy M. C.; VANDERLEI, Luiz Carlos M.; ITO, Juliana T.; LIMA, Fabiano F.; RODRIGUES, Fernanda M. M.; MANZANO, Beatriz M.; FERNANDES, Romulo A.; CECILIO, Michel J.; TOLEDO-ARRUDA, Alessandra C.; RAMOS, DioneiBACKGROUND: Mucociliary clearance is the main defense mechanism of the respiratory system, and it is influenced by several stimuli, including aerobic exercise and cigarette smoking. We evaluated the acute response of mucociliary clearance to aerobic exercise in smokers and nonsmokers compared with that found after acute smoking and smoking combined with exercise. Also, we investigated whether there was a correlation between mucociliary clearance and the autonomic nervous system under these conditions. METHODS: Twenty-one smokers were evaluated for mucociliary clearance by saccharin transit time (STT), and the response of the autonomic nervous system was evaluated by heart rate variability after aerobic exercise, after exercise followed by smoking, after acute smoking, and after rest. For comparison, 17 nonsmokers were also assessed during exercise. Repeated-measures analysis of variance with the Tukey test or the Friedman test followed by the Dunn test was used to evaluate the STT, autonomic response, and other variables to exercise and/or smoking in smokers. A paired t test or Wilcoxon test was used to analyze responses to exercise in nonsmokers. Correlations were evaluated using Pearson or Spearman coefficients. RESULTS: The STT was reduced after exercise in both groups, with similar responses between them. Other stimuli also reduced the STT. The STT showed a negative correlation with sympathetic activity in smokers and a positive correlation with the parasympathetic system in nonsmokers. CONCLUSIONS: Although impaired in smokers, mucociliary clearance responded to the stimulus of exercise, as demonstrated by similar STTs compared with nonsmokers. This response was correlated with the autonomic nervous system in both groups. In smokers, mucociliary clearance also responded to the stimuli of smoking and exercise followed by smoking.
- Analysis of autonomic modulation after an acute session of resistance exercise at different intensities in chronic obstructive pulmonary disease patients(2015) NICOLINO, Juliana; RAMOS, Dionei; LEITE, Marceli Rocha; RODRIGUES, Fernanda Maria Machado; SILVA, Bruna Spolador de Alencar; TACAO, Guilherme Yassuyuki; TOLEDO, Alessandra Choqueta de; VANDERLEI, Luiz Carlos Marques; RAMOS, Ercy Mara CipuloPurpose: Physical exercises are employed as part of the treatment of patients with chronic obstructive pulmonary disease (COPD); however information regarding cardiac autonomic modulation after an acute session of resistance exercise (RE) is unknown. The aim of this study was to evaluate the cardiac autonomic modulation, via heart rate variability after an acute session of RE applied at different intensities in COPD patients. Patients and methods: Twelve COPD patients underwent an acute session of RE with an intensity of 600% and another of 9000 of the one repetition maximum test. For analysis of autonomic modulation, heart rate was recorded beat-by-beat for 20 minutes at rest and after the training session. Heart rate variability indexes were obtained in the time and frequency domains for the assessment of autonomic modulation. Results: Regardless of exercise intensity, RE acute sessions influenced the autonomic modulation the recovery period was compared with the baseline. An increase in standard deviation of normal to normal RR intervals was observed throughout recovery time after the RE, as compared to baseline in both protocols: 60% and 90% of the one repetition maximum test. The spectral component of low frequency index (ms) was higher throughout recovery when compared to baseline in both protocols. The same was also observed in the spectral component of high frequency index (ms) for the protocols of 60% and 90%. Conclusion: RE sessions impact on the autonomic modulation of COPD patients by promoting differences in the recovery period compared to baseline, regardless of the intensity of the exercise performed.
- Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice(2015) YOSHIZAKI, Kelly; BRITO, Jose Mara; MORIYA, Henrique T.; TOLEDO, Alessandra C.; FERZILAN, Sandra; OLIVEIRA, Ana Paula Ligeiro de; MACHADO, Isabel D.; FARSKY, Sandra H. P.; SILVA, Luiz F. F.; MARTINS, Milton A.; SALDIVA, Paulo H. N.; MAUAD, Thais; MACCHIONE, MariangelaBackground: Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified. Methods: We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 mu g/m(3)). Male BALB/c mice were divided into mice receiving a nasal instillation: saline (saline; n = 30) and 30 mu g/10 mu L of DEP (DEP; n = 30). Nasal instillations were performed five days a week, over a period of 90 days. Bronchoalveolar lavage (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13 and interferon-gamma (INF-gamma) were determined by ELISA-immunoassay. Assessment of respiratory mechanics was performed. The gene expression of Muc5ac in lung was evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2). Results: DEP decreased IFN-gamma levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p <= 0.001) and CD8+ T cells (p <= 0.001) increased in the parenchyma. Although IL-13 (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene expression was not altered in the lung of DEP-exposed animals. Although respiratory mechanics, elastic and collagen density were not modified, the mean linear intercept (Lm) was increased in the DEP-exposed animals (p <= 0.001), and the index D2 was statistically different (p = 0.038) from the control animals. Conclusion: Our data suggest that nasal instillation of low doses of DEP over a period of 90 days results in alveolar enlargement in the pulmonary parenchyma of healthy mice.
- Diesel Exhaust Particulates Affect Cell Signaling, Mucin Profiles, and Apoptosis in Trachea Explants of Balb/C Mice(2015) SERIANI, Robson; JUNQUEIRA, Mara de Souza; TOLEDO, Alessandra Choqueta de; MARTINS, Milton Arruda; SECKLER, Marcelo; ALENCAR, Adriano Mesquita; NEGRI, Elnara Marcia; SILVA, Luiz Fernando Ferraz; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; MACCHIONE, MariangelaParticulate matter from diesel exhaust (DEP) has toxic properties and can activate intracellular signaling pathways and induce metabolic changes. This study was conducted to evaluate the activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and to analyze the mucin profile (acid (AB(+)), neutral (PAS(+)), or mixed (AB/PAS(+)) mucus) and vacuolization (V) of tracheal explants after treatment with 50 or 100 mu g/mL DEP for 30 or 60 min. Western blot analyses showed small increases in ERK1/2 and JNK phosphorylation after 30 min of 100 mu g/mL DEP treatment compared with the control. An increase in JNK phosphorylation was observed after 60 min of treatment with 50 mu g/mL DEP compared with the control. We did not observe any change in the level of ERK1/2 phosphorylation after treatment with 50 mu g/mL DEP. Other groups of tracheas were subjected to histological sectioning and stained with periodic acid-Schiff (PAS) reagent and Alcian Blue (AB). The stained tissue sections were then subjected to morphometric analysis. The results obtained were compared using ANOVA. Treatment with 50 mu g/mL DEP for 30 min or 60 min showed a significant increase (p< 0.001) in the amount of acid mucus, a reduction in neutral mucus, a significant reduction in mixed mucus, and greater vacuolization. Our results suggest that compounds found in DEPs are able to activate acid mucus production and enhance vacuolization and cell signaling pathways, which can lead to airway diseases. (C) 2014 Wiley Periodicals, Inc.
- A flavanone from Baccharis retusa (Asteraceae) prevents elastase-induced emphysema in mice by regulating NF-kappa B, oxidative stress and metalloproteinases (vol 16, 79, 2015)(2015) TAGUCHI, Laura; PINHEIRO, Nathalia M.; OLIVO, Clarice R.; CHOQUETA-TOLEDO, Alessandra; GRECCO, Simone S.; LOPES, Fernanda D. T. Q. S.; CAPERUTO, Luciana C.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; CAMARA, Niels O.; LAGO, Joao Henrique G.; PRADO, Carla M.
- Organic and Inorganic Fractions of Diesel Exhaust Particles Produce Changes in Mucin Profile of Mouse Trachea Explants(2015) SERIANI, Robson; JUNQUEIRA, Mara S.; TOLEDO, Alessandra C.; CORREA, Aristides T.; SILVA, Luiz F. F.; MARTINS, Milton A.; SALDIVA, Paulo H. N.; MAUAD, Thais; MACCHIONE, MariangelaDiesel exhaust particles (DEP) contain organic and inorganic elements that produce damage to the respiratory epithelium. The aim of this study was to determine the mucus profile of tracheal explants exposed to either crude diesel exhaust particles (DEP) or DEP treated with nitric acid (DEP/NA), with hexane (DEP/HEX), or with methanol (DEP/MET) at concentrations of 50 and 100 mu g/ml for 30 and 60 min. Tracheal explants were subjected to morphometric analyses to study acidic (AB+), neutral (PAS+), and mixed (AB+/PAS+) mucus production and vacuolization (V). Incubation with 50 mu g/ml crude DEP resulted in a rise in acid mucus production, an increase in vacuolization at 30 min, and reduction in neutral mucus at 30 and 60 min. Tracheas exposed to DEP/MET at 50 mu g/ml for 30 or 60 min resulted in a significant decrease in neutral mucus production and an elevation in acid mucus production. DEP/HEX increased vacuolization at both 50 and 100 mu g/ml at 30 and 60 min of exposure. Treatment with 50 mu g/ml for 30 or 60 min significantly elevated mixed mucus levels. These results suggest that DEP appear to be more toxic when administered in combination with HEX or MET. DEP/MET modified the mucus profile of the epithelium, while DEP/HEX altered mucus extrusion, and these responses might be due to bioavailability of individual elements in DEP fractions.
- A flavanone from Baccharis retusa (Asteraceae) prevents elastase-induced emphysema in mice by regulating NF-kappa B, oxidative stress and metalloproteinases(2015) TAGUCHI, Laura; PINHEIRO, Nathalia M.; OLIVO, Clarice R.; CHOQUETA-TOLEDO, Alessandra; GRECCO, Simone S.; LOPES, Fernanda D. T. Q. S.; CAPERUTO, Luciana C.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; CAMARA, Niels O.; LAGO, Joao Henrique G.; PRADO, Carla M.Background: Pulmonary emphysema is characterized by irreversible airflow obstruction, inflammation, oxidative stress imbalance and lung remodeling, resulting in reduced lung function and a lower quality of life. Flavonoids are plant compounds with potential anti-inflammatory and antioxidant effects that have been used in folk medicine. Our aim was to determine whether treatment with sakuranetin, a flavonoid extracted from the aerial parts of Baccharis retusa, interferes with the development of lung emphysema. Methods: Intranasal saline or elastase was administered to mice; the animals were then treated with sakuranetin or vehicle 2 h later and again on days 7, 14 and 28. We evaluated lung function and the inflammatory profile in bronchoalveolar lavage fluid (BALF). The lungs were removed to evaluate alveolar enlargement, extracellular matrix fibers and the expression of MMP-9, MMP-12, TIMP-1, 8-iso-PGF-2 and p65-NF-kappa B in the fixed tissues as well as to evaluate cytokine levels and p65-NF-kappa B protein expression. Results: In the elastase-treated animals, sakuranetin treatment reduced the alveolar enlargement, collagen and elastic fiber deposition and the number of MMP-9- and MMP-12-positive cells but increased TIMP-1 expression. In addition, sakuranetin treatment decreased the inflammation and the levels of TNF-alpha, IL-1 beta and M-CSF in the BALF as well as the levels of NF-kappa B and 8-iso-PGF-2 alpha in the lungs of the elastase-treated animals. However, this treatment did not affect the changes in lung function. Conclusion: These data emphasize the importance of oxidative stress and metalloproteinase imbalance in the development of emphysema and suggest that sakuranetin is a potent candidate that should be further investigated as an emphysema treatment. This compound may be useful for counteracting lung remodeling and oxidative stress and thus attenuating the development of emphysema.
- Correlation between heart rate variability indexes and aerobic physiological variables in patients with COPD(2015) LEITE, Marceli R.; RAMOS, Ercy Mara C.; KALVA-FILHO, Carlos A.; RODRIGUES, Fernanda Maria M.; FREIRE, Ana Paula C. F.; TACAO, Guilherme Y.; TOLEDO, Alessandra C. de; CECILIO, Michel J.; VANDERLEI, Luiz Carlos M.; RAMOS, DioneiBackground and objectivePrevious studies have shown a relationship between the level of physical fitness and autonomic variables. However, these relationships have not been investigated in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to correlate the resting heart rate variability (HRV) indexes with aerobic physiological variables obtained at a maximal exercise test in patients with COPD. MethodsThirty-seven patients with COPD (63 (59-70) years; 46 (35.4-63.7) forced expiratory volume in 1 s (FEV1)%) underwent assessment of autonomic modulation at rest for 20min to determine the HRV indexes in time and frequency domains. Soon after that, the patients performed an incremental exercise test to determine the anaerobic threshold (GET), the peak oxygen uptake (VO2PEAK) and the velocity corresponding to VO2PEAK (vVO(2PEAK)). ResultsThe indexes that express parasympathetic component as RMSSD (11.4 [7.5-23.8], HF (ms(2)) (35 [17-195] and SD1 (8.1 [5.3-16.8]), correlated with GET (r=0.39; r=0.43; r=0.39 respectively). The indexes that represent the overall variability, SDNN (19.5 [13.9-28.8]), LF (ms(2)) (111 [38-229]), and SD2 (26.8 [18.6-35.4]) correlated with vVO(2PEAK) (r=0.37; r=0.38; r=0.37; r=0.44; r=0.43; r=0.46 respectively). Likewise, the indexes LF (ms(2)), LF (nu) (63.2 [46-77,9]), HF (nu) (36.8 [22.1-54]), and LF/HF (1.7 [0.9-3.5]) correlated with VO2PEAK (r=0.35; r=0.35; r=-0.35; r=0.40 respectively). ConclusionsThis study demonstrated that HRV indexes at rest may become a predictive tool for aerobic capacity in COPD patients after the development of more consistent methods. This study aimed to investigate whether the HRV indexes correlate with aerobic physiological variables obtained in cardiopulmonary exercise testing of patients with COPD. Such correlation would have important clinical implications as it would allow, prior to the realization of the maximal exercise testing, to infer the patient's aerobic capacity.