PAULO HILARIO NASCIMENTO SALDIVA
Projetos de Pesquisa
Unidades Organizacionais
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
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 31 Citação(ões) na Scopus Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling(2011) BISELLI, P. J. C.; LOPES, F. D. T. Q. S.; MORIYA, H. T.; RIVERO, D. H. R. F.; TOLEDO, A. C.; SALDIVA, P. H. N.; MAUAD, T.; MARTINS, A.Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-beta 1 (TGF-beta 1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-beta 1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-beta 1.- Ultrasonography on the non-living. Current approaches.(2023) THOMSEN, Thomas; BLAIVAS, Michael; SADIVA, Paulo; KRIPFGANS, Oliver D.; CHAN, Hsun-Liang; DONG, Yi; CHAMMAS, Maria Cristina; HOFFMANN, Beatrice; DIETRICH, Christoph F.The vast majority of clinicians associate diagnostic ultrasound with a tool that is designed for the living patient. However, it is of course possible to apply this imaging technology to evaluate the recently deceased patient for postmortem diagnosis, or even just examine postmortem tissue. We describe several cases in which ultrasound-enabled providers obtain answers in postmortem examinations and discuss potential future strategies and applications. In addition, we will also illustrate the use of sonography in minimally invasive post-mortem tissue sampling (MITS), an approach that can be used in post-mortem minimally invasive autopsies as well as for establishing ultrasound diagnostic parameters in new medical fields such as periodontal and dental implant specialties.
- Biomarkers of occupational exposure to air pollution, inflammation and oxidative damage in taxi drivers(2013) BRUCKER, Natalia; MORO, Angela M.; CHARAO, Mariele F.; DURGANTE, Juliano; FREITAS, Fernando; BAIERLE, Marilia; NASCIMENTO, Sabrina; GAUER, Bruna; BULCAO, Rachel P.; BUBOLS, Guilherme B.; FERRARI, Pedro D.; THIESEN, Flavia V.; GIODA, Adriana; DUARTE, Marta M. M. F.; CASTRO, Iran de; SALDIVA, Paulo H.; GARCIA, Solange C.Exposure to environmental pollutants has been recognised as a risk factor for cardiovascular events. 1-hydroxypyrene (1-OHP) is a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs) from traffic-related air pollution. Experimental studies indicate that PAH exposure could be associated with inflammation and atherogenesis. Thus, the purpose of this study was to evaluate whether the biomarker of PAH exposure is associated with biomarkers of inflammation and oxidative stress and if these effects modulate the risk of developing cardiovascular diseases in workers exposed to air pollution. This study included 60 subjects, comprising 39 taxi drivers and 21 non-occupationally exposed persons. Environmental PM25 and benzo[a]pyrene (BaP) levels, in addition to biomarkers of exposure and oxidative damage, were determined. Inflammatory cytokines (IL-beta, IL-6, IL-10, TNF-alpha, IFN-gamma and hs-CRP) and serum levels of oxidised LDL (ox-LDL), auto-antibodies (ox-LDL-Ab) and homocysteine (Hcy) were also evaluated. PM25 and BaP exhibited averages of 12.4 6.914 IT1-beta and 1.0 0.6 ng M-3, respectively. Urinary 1-OHP levels were increased in taxi drivers compared to the non-occupationally exposed subjects (p < 0.05) and were positively correlated with pro-inflammatory cytokines and negatively correlated with antioxidants. Furthermore, taxi drivers had elevated pro-inflammatory cytokines, biomarkers of oxidative damage, and ox-LDL, ox-LDL-Ab and Hcy levels, although antioxidant enzymes were decreased compared to the non-occupationally exposed subjects (p < 0.05). In summary, our findings indicate that taxi drivers showed major exposure to pollutants, such as PAHs, in relation to non-occupationally exposed subjects. This finding was associated with higher inflammatory biomarkers and Hcy, which represent important predictors for cardiovascular events. These data suggest a contribution of PAHs to cardiovascular diseases upon occupational exposure.
conferenceObject ELEVATED ROS LEVELS AND DNA FRAGMENTATION IN SPERM FROM CONVALESCENT MEN IN SARS-COV-2 INFECTION(2022) HALLAK, Jorge; BERNARDES, Felipe; TEIXEIRA, Thiago Afonso Carvalho Celestino; SALDIVA, Paulo Hilario Nascimento; KALLAS, Esper Georges; CALDINI, Elia Tamaso Espin Garcia; DUARTE NETO, Amaro Nunes; FAQUINETI, Heloisa; JESUS, Vinicius Luiz Menezes; GUTIERREZ, Raul Segundo Sanchez; DREVET, Joel R.- Wildfire-related PM2.5 and health economic loss of mortality in Brazil(2023) WU, Yao; LI, Shanshan; XU, Rongbin; CHEN, Gongbo; YUE, Xu; YU, Pei; YE, Tingting; WEN, Bo; COELHO, Micheline de Sousa Zanotti Stagliorio; SALDIVA, Paulo Hilario Nascimento; GUO, YumingBackground: Wildfire imposes a high mortality burden on Brazil. However, there is a limited assessment of the health economic losses attributable to wildfire-related fine particulate matter (PM2.5). Methods: We collected daily time-series data on all-cause, cardiovascular, and respiratory mortality from 510 immediate regions in Brazil during 2000-2016. The chemical transport model GEOS-Chem driven with Global Fire Emissions Database (GFED), in combination with ground monitored data and machine learning was used to estimate wildfire-related PM2.5 data at a resolution of 0.25 degrees x 0.25 degrees. A time-series design was applied in each immediate region to assess the association between economic losses due to mortality and wildfire-related PM2.5 and the estimates were pooled at the national level using a random-effect meta-analysis. We used a metaregression model to explore the modification effect of GDP and its sectors (agriculture, industry, and service) on economic losses.Results: During 2000-2016, a total of US$81.08 billion economic losses (US$5.07 billion per year) due to mortality were attributable to wildfire-related PM2.5 in Brazil, accounting for 0.68% of economic losses and equivalent to approximately 0.14% of Brazil's GDP. The attributable fraction (AF) of economic losses due to wildfire-related PM2.5 was positively associated with the proportion of GDP from agriculture, while negatively associated with the proportion of GDP from service.Conclusion: Substantial economic losses due to mortality were associated with wildfires, which could be influenced by the agriculture and services share of GDP per capita. Our estimates of the economic losses of mortality could be used to determine optimal levels of investment and resources to mitigate the adverse health impacts of wildfires.
- Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors(2023) CORRADI, Camila; VILAR, Juliana B.; BUZATTO, Vanessa C.; SOUZA, Tiago A. de; CASTRO, Ligia P.; MUNFORD, Veridiana; VECCHI, Rodrigo De; GALANTE, Pedro A. F.; ORPINELLI, Fernanda; MILLER, Thiago L. A.; BUZZO, Jose L.; SOTTO, Mirian N.; SALDIVA, Paulo; OLIVEIRA, Jocelanio W. de; CHAIBUB, Sulamita C. W.; SARASIN, Alain; MENCK, Carlos F. M.This manuscript describes the genetic alterations found in the skin tumors of XP-V patients deficient in translesion synthesis. The alterations include mutation signatures and retrotransposition insertions, which provide mechanistic information about DNA polymerase eta functions. Xeroderma pigmentosum variant (XP-V) is an autosomal recessive disease with an increased risk of developing cutaneous neoplasms in sunlight-exposed regions. These cells are deficient in the translesion synthesis (TLS) DNA polymerase eta, responsible for bypassing different types of DNA lesions. From the exome sequencing of 11 skin tumors of a genetic XP-V patients' cluster, classical mutational signatures related to sunlight exposure, such as C>T transitions targeted to pyrimidine dimers, were identified. However, basal cell carcinomas also showed distinct C>A mutation spectra reflecting a mutational signature possibly related to sunlight-induced oxidative stress. Moreover, four samples carry different mutational signatures, with C>A mutations associated with tobacco chewing or smoking usage. Thus, XP-V patients should be warned of the risk of these habits. Surprisingly, higher levels of retrotransposon somatic insertions were also detected when the tumors were compared with non-XP skin tumors, revealing other possible causes for XP-V tumors and novel functions for the TLS polymerase eta in suppressing retrotransposition. Finally, the expected high mutation burden found in most of these tumors renders these XP patients good candidates for checkpoint blockade immunotherapy.
- Effects of biomass burning on nasal mucociliary clearance and mucus properties after sugarcane harvesting(2011) GOTO, Danielle Miyuki; LANCA, Marina; OBUTI, Camila Akemi; BARBOSA, Cristiane Maria Galvao; SALDIVA, Paulo Hilario Nascimento; ZANETTA, Dirce Maria Trevisan; LORENZI-FILHO, Geraldo; SANTOS, Ubiratan de Paula; NAKAGAWA, Naomi KondoObjective: Biofuel from sugarcane is widely produced in developing countries and is a clean and renewable alternative source of energy. However, sugarcane harvesting is mostly performed after biomass burning. The aim of this study was to evaluate the effects of harvesting after biomass burning on nasal mucociliary clearance and the nasal mucus properties of farm workers. Methods: Twenty seven sugarcane workers (21-45 years old) were evaluated at the end of two successive time-periods: first at the end of a 6-month harvesting period (harvesting), and then at the end of a 3-month period without harvesting (non-harvesting). Nasal mucociliary clearance was evaluated by the saccharine transit test, and mucus properties were analyzed using in vitro mucus contact angle and mucus transportability by sneeze. Arterial blood pressure, heart rate, respiratory rate, pulse oximetry, body temperature, associated illness, and exhaled carbon monoxide were registered. Results: Data are presented as mean values (95% confidence interval). The multivariate model analysis adjusted for age, body-mass index, smoking status and years of working with this agricultural practice showed that harvesting yielded prolonged saccharine transit test in 7.83 min (1.88-13.78), increased mucus contact angle in 8.68 degrees (3.18-14.17) and decreased transportability by sneeze in 32.12 mm (-44.83 to -19.42) compared with the non-harvesting period. No significant differences were detected in any of the clinical parameter at either time-period. Conclusion: Sugarcane harvesting after biomass burning negatively affects the first barrier of the respiratory system in farm workers by impairing nasal mucociliary clearance and inducing abnormal mucus properties.
- 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 KondoOBJECTIVE: 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.
- Assessing socioeconomic bias of exposure to urban air pollution: an autopsy-based study in Sao Paulo, Brazil(2023) SINGER, Julio da Motta; ANDRE, Carmen Diva Saldiva de; ANDRE, Paulo Afonso de; ROCHA, Francisco Marcelo Monteiro; WAKED, Dunia; VAZ, Aline Macedo; GOIS, Gustavo Ferreira; ANDRADE, Maria de Fatima; VERAS, Mariana Matera; SALDIVA, Paulo Hilario Nascimento; BARROZO, Ligia VizeuBackground The characterisation of individual exposure to air pollution in urban scenarios is a challenge in environmental epidemiological studies. We investigated if the city's pollution monitoring stations over or underes-timate the exposure of individuals depending on their socioeconomic conditions and daily commuting times. Methods The amount of black carbon accumulated in the lungs of 604 deceased who underwent autopsy in Sao Paulo was considered as a proxy for PM10. The concentrations of PM10 in the residence of the deceased were estimated by interpolating an ordinary kriging model. These two-exposure metrics allowed us to construct an environmental exposure misclassification index ranging from -1 to 1. The association between the index and daily commuting, socioeconomic context index (GeoSES), and street density as predictors was assessed by means of a multilevel linear regression model. Findings With a decrease of 0.1 units in GeoSES, the index increases, on average, by 0.028 units and with an increase of 1 h in daily commuting, the index increases, on average, by 0.022 units indicating that individual exposure to air pollution is underestimated in the lower GeoSES and in people with many hours spent in daily commuting. Interpretation Reduction of health consequences of air pollution demands not only alternative fuel and more efficient mobility strategies, but also should include profound rethink of cities.
conferenceObject The Acute Effect Of Sugar Cane Burning Particles In A Mouse Model Of Allergic Asthma(2014) SILVA, T. G.; GOZZI, A.; FONSECA, V. M. B.; CARVALHO, A. P. F.; MILANI, T. M. S.; BORGES, M. C.; SALDIVA, P. H. N.; MAUAD, T.