PAULO HILARIO NASCIMENTO SALDIVA

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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

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  • article 27 Citação(ões) na Scopus
    The effects of smoking and smoking cessation on nasal mucociliary clearance, mucus properties and inflammation
    (2016) UTIYAMA, Daniela Mitiyo Odagiri; YOSHIDA, Carolina Tieko; GOTO, Danielle Miyuki; CARVALHO, Tomas de Santana; SANTOS, Ubiratan de Paula; KOCZULLA, Andreas Rembert; SALDIVA, Paulo Hilario Nascimento; NAKAGAWA, Naomi Kondo
    OBJECTIVE: The aim of the present study was to assess nasal mucociliary clearance, mucus properties and inflammation in smokers and subjects enrolled in a Smoking Cessation Program (referred to as quitters). METHOD: A total of 33 subjects with a median (IQR) smoking history of 34 (20-58) pack years were examined for nasal mucociliary clearance using a saccharine transit test, mucus properties using contact angle and sneeze clearability tests, and quantification of inflammatory and epithelial cells, IL-6 and IL-8 concentrations in nasal lavage fluid. Twenty quitters (mean age: 51 years, 9 male) were assessed at baseline, 1 month, 3 months and 12 months after smoking cessation, and 13 smokers (mean age: 52 years, 6 male) were assessed at baseline and after 12 months. Clinicaltrials.gov: NCT02136550. RESULTS: Smokers and quitters showed similar demographic characteristics and morbidities. At baseline, all subjects showed impaired nasal mucociliary clearance (mean 17.6 min), although 63% and 85% of the quitters demonstrated significant nasal mucociliary clearance improvement at 1 month and 12 months, respectively. At 12 months, quitters also showed mucus sneeze clearability improvement (similar to 26%), an increased number of macrophages (2-fold) and no changes in mucus contact angle or cytokine concentrations. CONCLUSION: This study showed that smoking cessation induced early improvements in nasal mucociliary clearance independent of mucus properties and inflammation. Changes in mucus properties were observed after only 12 months of smoking cessation.
  • article 33 Citação(ões) na Scopus
    Impact of Exhaled Breath Acetone in the Prognosis of Patients with Heart Failure with Reduced Ejection Fraction (HFrEF). One Year of Clinical Follow-up
    (2016) MARCONDES-BRAGA, Fabiana G.; BATISTA, Guilherme L.; GUTZ, Ivano G. R.; SALDIVA, Paulo H. N.; MANGINI, Sandrigo; ISSA, Victor S.; AYUB-FERREIRA, Silvia M.; BOCCHI, Edimar A.; PEREIRA, Alexandre Costa; BACAL, Fernando
    Background The identification of new biomarkers of heart failure (HF) could help in its treatment. Previously, our group studied 89 patients with HF and showed that exhaled breath acetone (EBA) is a new noninvasive biomarker of HF diagnosis. However, there is no data about the relevance of EBA as a biomarker of prognosis. Objectives To evaluate whether EBA could give prognostic information in patients with heart failure with reduced ejection fraction (HFrEF). Methods After breath collection and analysis by gas chromatography-mass spectrometry and by spectrophotometry, the 89 patients referred before were followed by one year. Study physicians, blind to the results of cardiac biomarker testing, ascertained vital status of each study participant at 12 months. Results The composite endpoint death and heart transplantation (HT) were observed in 35 patients (39.3%): 29 patients (32.6%) died and 6 (6.7%) were submitted to HT within 12 months after study enrollment. High levels of EBA (>= 3.7 mu g/L, 50th percentile) were associated with a progressively worse prognosis in 12-month follow-up (log-rank = 11.06, p = 0.001). Concentrations of EBA above 3.7 mu g/L increased the risk of death or HT in 3.26 times (HR = 3.26, 95% CI = 1.56-6.80, p = 0.002) within 12 months. In a multivariable cox regression model, the independent predictors of all-cause mortality were systolic blood pressure, respiratory rate and EBA levels. Conclusions High EBA levels could be associated to poor prognosis in HFrEF patients.
  • article 18 Citação(ões) na Scopus
    Acute exposure to Buenos Aires air particles (UAP-BA) induces local and systemic inflammatory response in middle-aged mice: A time course study
    (2016) ORONA, Nadia S.; FERRARO, Sebastian A.; ASTORT, Francisco; MORALES, Celina; BRITES, Fernando; BOERO, Laura; TISCORNIA, Gisela; MAGLIONE, Guillermo A.; SALDIVA, Paulo H. N.; YAKISICH, Sebastian; TASAT, Deborah R.
    Exposure to air particulate matter (PM) is associated with increased cardiovascular morbimortality. However, PM doesn't affect equally to all people, being the old cohort the most susceptible and studied. We hypothesized that another specific life phase, the middle-aged subpopulation, may be negatively affected. Therefore, the aim of this study was to analyze in vivo the acute biological impact of two environmental particles, Urban Air Particles from Buenos Aires and Residual Oil Fly Ash, on the cardiorespiratory system of middle-aged mice, evaluating oxidative metabolism and inflammation. Both PM provoked a local and systemic inflammatory response, leading to a reduced alveolar area in the lung, an epicard inflammation in the heart, an increment of IL-6, and a reduction on PON 1 activity in serum of middle-aged animals. The positive correlation of local parameters with systemic markers of oxidative stress and inflammation could be responsible for associations of cardiovascular morbimortality in this subpopulation.
  • article 31 Citação(ões) na Scopus
    Associations of maternal personal exposure to air pollution on fetal weight and fetoplacental Doppler: A prospective cohort study
    (2016) CARVALHO, Mariana A.; BERNARDES, Lisandra S.; HETTFLEISCH, Karen; PASTRO, Luciana D. M.; VIEIRA, Sandra E.; SALDIVA, Silvia R. D. M.; SALDIVA, Paulo H. N.; FRANCISCO, Rossana P. V.
    We determined the influence of maternal air pollution exposure during each trimester of pregnancy on fetal and birth weight and fetoplacental hemodynamics. In total, 366 women with singleton pregnancies were prospectively followed in the city of Sao Paulo, Brazil. Nitrogen dioxide (NO2) and ozone (O-3) were measured during each trimester using passive personal samplers. We evaluated fetal weight and Doppler velocimetry data from the umbilical, middle cerebral, and uterine arteries in the 3rd trimester, and birth weight. Multivariate analysis was performed, controlling for known determinants of fetal weight. Exposure to higher levels of O-3 during the 2nd trimester was associated with higher umbilical artery pulsatility indices (PIs) [p = 0.013; beta = 0.017: standard error (SE) = 0.007]. Exposure to higher levels of O-3 during the 3rd trimester was associated with lower umbilical artery PIs (p = 0.011; beta = 0.021; SE = 0.008). Our results suggest that in the environment of Sao Paulo, 03 may affects placental vascular resistance.
  • article 23 Citação(ões) na Scopus
    Aerobic exercise in polluted urban environments: effects on airway defense mechanisms in young healthy amateur runners
    (2016) SA, Matheus Cavalcante de; NAKAGAWA, Naomi Kondo; ANDRE, Carmen Diva Saldiva de; CARVALHO-OLIVEIRA, Regiani; CARVALHO, Tamas de Santana; NICOLA, Marina Lazzari; ANDRE, Paulo Afonso de; SALDIVA, Paulo Hilario Nascimento; VAISBERG, Mauro
    In this study, the effects of aerobic exercise on the upper airways and their defense mechanisms were investigated in athletes. The athletes ran in two different environments: the downtown streets of the city of Sao Paulo (Street), more polluted, and an urban forest (Forest), less polluted. Thirty-eight young healthy athletes ran for 45 min d(-1) randomly during five consecutive days, with an interval of 48 h before changing environment. Clinical parameters and respiratory tract defense markers were evaluated before and after the first run on Mondays (1 d) and on Fridays (5 d). Street presented higher mean PM2.5 concentrations (65.1 +/- 39.1 mu gm(-3), p < 0.001) and lower temperature (22.0 degrees C, p = 0.010) than Forest (22.6 +/- 15.3 mu g m(-3) and 22.8 degrees C). After 1 d Street running, subjects showed an increment in heart rate (p < 0.001). At day 5, there was twice the number of athletes with impaired nasal mucociliary clearance (MCC) in the Street runners group when compared to the Forest runners group. Exhaled breath condensate pH values increased in the Forest group, with significant differences between groups in day 1 (p = 0.006) and day 5 (p < 0.001), despite the fact that both groups showed values within the normal range. After exposure to both environments, the number of cells in the nasal lavage fluid was reduced after exercise (p = 0.014), without alterations in cell type and IL-8 and IL-10 concentrations. Aerobic exercise can either maintain or acutely enhance MCC and it may help to regulate inflammatory responses in the airways. Here we show that exercise practice in polluted outdoor environment, over a 5 d period, impairs MCC. In contrast, athletes running in the less polluted environment (Forest) show higher exhaled breath condensate pH values when compared to those who exercised in a more polluted environment (Street).
  • article 22 Citação(ões) na Scopus
    Human bronchial epithelial cells exposed in vitro to diesel exhaust particles exhibit alterations in cell rheology and cytotoxicity associated with decrease in antioxidant defenses and imbalance in pro- and anti-apoptotic gene expression
    (2016) SERIANI, Robson; SOUZA, Claudia Emanuele Carvalho de; KREMPEL, Paloma Gava; FRIAS, Daniela Perroni; MATSUDA, Monique; CORREIA, Aristides Tadeu; FERREIRA, Marcia Zotti Justo; ALENCAR, Adriano Mesquita; NEGRI, Elnara Marcia; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; MACCHIONE, Mariangela
    Diesel exhaust particles (DEPs) from diesel engines produce adverse alterations in cells of the airways by activating intracellular signaling pathways and apoptotic gene overexpression, and also by influencing metabolism and cytoskeleton changes. This study used human bronchial epithelium cells (BEAS-2B) in culture and evaluates their exposure to DEPs (15ug/mL for 1 and 2 h) in order to determine changes to cell rheology (viscoelasticity) and gene expression of the enzymes involved in oxidative stress, apoptosis, and cytotoxicity. BEAS-2B cells exposed to DEPs were found to have a significant loss in stiffness, membrane stability, and mitochondrial activity. The genes involved in apoptosis [B cell lymphoma 2 (BCL-2 and caspase-3)] presented inversely proportional expressions (p=0.05, p=0.01, respectively), low expression of the genes involved in antioxidant responses [SOD1 (superoxide dismutase 1); SOD2 (superoxide dismutase 2), and GPx (glutathione peroxidase) (p=0.01)], along with an increase in cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) (p=0.01). These results suggest that alterations in cell rheology and cytotoxicity could be associated with oxidative stress and imbalance between pro-and antiapoptotic genes.
  • article 44 Citação(ões) na Scopus
    The influence of atmospheric particles on the elemental content of vegetables in urban gardens of Sao Paulo, Brazil
    (2016) AMATO-LOURENCO, Luis Fernando; MOREIRA, Tiana Carla Lopes; SOUZA, Vanessa Cristina de Oliveira; BARBOSA JR., Fernando; SAIKI, Mitiko; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais
    Although urban horticulture provides multiple benefits to society, the extent to which these vegetables are contaminated by the absorption of chemical elements derived from atmospheric deposition is unclear. This study was designed to evaluate the influence of air pollution on leafy vegetables in community gardens of Sao Paulo, Brazil. Vegetable seedlings of Brassica oleracea var. acephala (collard greens) and Spinacia oleracea (spinach) obtained in a non-polluted rural area and growing in vessels containing standard uncontaminated soil were exposed for three consecutive periods of 30, 60 and 90 days in 10 community gardens in Sao Paulo and in one control site. The concentrations of 17 chemical elements (traffic-related elements and those essential to plant biology) were quantified by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Tillandsia usneoides L. specimens were used as air plant biomonitors. The concentrations of As, Cd, Cr and Pb found in vegetables were compared to the recommended values for consumption. Principal Component Analysis (PCA) was used to cluster the elemental concentrations, and Generalized Linear Models (GLMs) were employed to evaluate the association of the factor scores from each PCA component with variables such as local weather, traffic burden and vertical barriers adjacent to the gardens. We found significant differences in the elemental concentrations of the vegetables in the different community gardens. These differences were related to the overall traffic burden, vertical obstacles and local weather. The Pb and Cd concentrations,in both vegetables exceeded the limit values for consumption after 60 days of exposure. A strong correlation was observed between the concentration of traffic-related elements in vegetables and in Tillandsia usneoides L An exposure response was observed between traffic burden and traffic-derived particles absorbed in the vegetables. Traffic-derived air pollution directly influences the absorption of chemical elements in leafy vegetables, and the levels of these elements may exceed the recommended values for consumption.
  • article 10 Citação(ões) na Scopus
    The genetics of human running: ACTN3 polymorphism as an evolutionary tool improving the energy economy during locomotion
    (2016) PASQUA, Leonardo A.; BUENO, Salomao; MATSUDA, Monique; MARQUEZINI, Monica V.; LIMA-SILVA, Adriano E.; SALDIVA, Paulo H. N.; BERTUZZI, Romulo
    Background: Covering long distances was an important trait to human evolution and continues to be highlighted for health and athletic status. This ability is benefitted by a low cost of locomotion (CoL), meaning that the individuals who are able to expend less energy would be able to cover longer distances. The CoL has been shown to be influenced by distinct and even 'opposite' factors, such as physiological and muscular characteristics, which are genetically inherited. In this way, DNA alterations could be important determinants of the characteristics associated with the CoL. A polymorphism in the ACTN3 gene (R577X) has been related to physical performance, associating the X allele with endurance and the R allele with strength/power abilities. Aim: To investigate the influence of ACTN3 genotypes on the CoL. Subjects and methods: One hundred and fifty healthy male individuals performed two constant speed tests (at 10 and 12 km/h) to determine the CoL. Results: Interestingly, the results showed that heterozygous individuals (RX genotype) presented significantly lower CoL compared to RR and XX individuals. Conclusions: It is argued that RX genotype might generate an intermediate strength-to-endurance phenotype, leading to a better phenotypic profile for energy economy during running and, consequently, for long-term locomotion.
  • article 0 Citação(ões) na Scopus
  • article 12 Citação(ões) na Scopus
    Influence of ACTN3 R577X polymorphism on ventilatory thresholds related to endurance performance
    (2016) PASQUA, Leonardo A.; BUENO, Salomao; ARTIOLI, Guilherme G.; LANCHA, Antonio H.; MATSUDA, Monique; MARQUEZINI, Monica V.; LIMA-SILVA, Adriano E.; SALDIVA, Paulo H. N.; BERTUZZI, Romulo
    The purpose of this study was to verify the association between ACTN3 polymorphism and physiological parameters related to endurance performance. A total of 150 healthy male volunteers performed a maximal incremental running test to determine the speeds corresponding to ventilatory threshold (VT) and respiratory compensation point (RCP). Participants were genotyped and divided into terciles based on the analysed variables. Genotype frequencies were compared through (2) test between lower and higher terciles, with the lowest or highest values of each analysed variable. ACTN3 XX genotype was over-represented in higher tercile for VT and RCP. Odds ratio also showed significantly higher chances of XX individuals to be in higher tercile compared to RR (7.3) and RR + RX (3.5) for VT and compared to RR genotype (8.1) and RR + RX (3.4) for RCP. Thus, XX individuals could attain the VT and RCP at higher speeds, suggesting that they are able to sustain higher running speeds in lower exercise intensity domains. It could result in higher lipid acids oxidation, saving muscle glycogen and delaying the fatigue during prolonged exercises, which could be the advantage mechanism of this genotype to endurance performance.