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Air pollution is a public health concern that has been associated with adverse effects on the development and functions of the central nervous system (CNS). However, studies on the effects of exposure to pollutants on the CNS across the entire developmental period still remain scarce. In this study, we investigated the impacts of prenatal and/or postnatal exposure to fine particulate matter (PM 2.5 ) from São Paulo city, on the brain structure and behavior of juvenile male mice. BALB/c mice were exposed to PM 2.5 concentrated ambient particles (CAP) at a daily concentration of 600 μg/m³ during the gestational [gestational day (GD) 1.5-18.5] and the postnatal periods [postnatal day (PND) 22-90] to filtered air (FA) in both periods (FA/FA), to CAP only in the postnatal period (FA/CAP), to CAP only in the gestational period (CAP/FA), and to CAP in both periods (CAP/CAP). Behavioral tests were performed when animals were at PND 30 and PND 90. Glial activation, brain volume, cortical neuron number, serotonergic and GABAergic receptors, as well as oxidative stress, were measured. Mice at PND 90 presented greater behavioral changes in the form of greater locomotor activity in the FA-CAP and CAP-CAP groups. In general, these same groups explored objects longer and the CAP-FA group presented anxiolytic behavior. There was no difference in total brain volume among groups, but a lower corpus callosum (CC) volume was observed in the CAP-FA group. Also, the CAP-CAP group presented an increase in microglia in the cortex and an increased in astrocytes in the cortex, CC, and C1A and dentate gyrus of hippocampus regions. Gene expression analysis showed a decrease in BDNF in the hippocampus of CAP-CAP group. Treatment of immortalized glial cells with non-cytotoxic doses of ambient PM 2.5 increased micronuclei frequencies, indicating genomic instability. These findings highlight the potential for negative neurodevelopmental outcomes induced by exposure to moderate levels of PM 2.5 in Sao Paulo city., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The majority of epidemiological studies correlate the cardiorespiratory effects of air pollution exposure by considering the concentrations of pollutants measured from conventional monitoring networks. The conventional air quality monitoring methods are expensive, and their data are insufficient for providing good spatial resolution. We hypothesized that bioassays using plants could effectively determine pollutant gradients, thus helping to assess the risks associated with air pollution exposure. The study regions were determined from different prevalent respiratory death distributions in the Sao Paulo municipality. Samples of tree flower buds were collected from twelve sites in four regional districts. The genotoxic effects caused by air pollution were tested through a pollen abortion bioassay. Elements derived from vehicular traffic that accumulated in tree barks were determined using energy-dispersive X-ray fluorescence spectrometry (EDXRF). Mortality data were collected from the mortality information program of Sao Paulo City. Principal component analysis (PCA) was applied to the concentrations of elements accumulated in tree barks. Pearson correlation and exponential regression were performed considering the elements, pollen abortion rates and mortality data. PCA identified five factors, of which four represented elements related to vehicular traffic. The elements Al, S, Fe, Mn, Cu, and Zn showed a strong correlation with mortality rates (R 2 >0.87) and pollen abortion rates (R 2 >0.82). These results demonstrate that tree barks and pollen abortion rates allow for correlations between vehicular traffic emissions and associated outcomes such as genotoxic effects and mortality data., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Atherosclerosis is a chronic inflammatory disease responsible for the majority of cases of myocardial infarction and ischemic stroke. The electronegative low-density lipoprotein, a modified subfraction of native LDL, is pro-inflammatory and plays an important role in atherogenesis. To investigate the effects of a nanoformulation (scFv anti-LDL(-)-MCMN-Zn) containing a scFv reactive to LDL(-) on the inhibition of atherosclerosis, its toxicity was evaluated in vitro and in vivo and further it was also administered weekly to LDL receptor knockout mice. The scFv anti-LDL(-)-MCMN-Zn nanoformulation did not induce cell death in RAW 264.7 macrophages and HUVECs. The 5mg/kg dose of scFv anti-LDL(-)-MCMN-Zn did not cause any typical signs of toxicity and it was chosen for the evaluation of its atheroprotective effect in Ldlr(-/-) mice. This nanoformulation significantly decreased the atherosclerotic lesion area at the aortic sinus, compared with that in untreated mice. In addition, the Il1b mRNA expression and CD14 protein expression were downregulated in the atherosclerotic lesions at the aortic arch of Ldlr(-/-) mice treated with scFv anti-LDL(-)-MCMN-Zn. Thus, the scFv anti-LDL(-)-MCMN-Zn nanoformulation inhibited the progression of atherosclerotic lesions, indicating its potential use in a future therapeutic strategy for atherosclerosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The time-dependency of lung recovery after 3 intranasal instillations per week during four weeks of distilled water (C groups) or particles (15μg) from traffic (U groups) or biomass burning (B groups) was observed in BALB/c mice. Lung mechanics [static elastance (Est), viscoelastic component of elastance (ΔE), lung resistive (ΔP1) and viscoelastic/inhomogeneous (ΔP2) pressures] and histology were analyzed 1 (C1, U1, B1), 2 (C2, U2, B2), 7 (C7, U7, B7) or 14 days (C14, U14, B14) after the last instillation. Est, ΔE, ΔP1 and ΔP2 were higher in U1 and B1 than in C1, returning to control values at day 2, except for ΔP1 that normalized after 7 days. Alveolar collapse, bronchoconstriction index and alveolar lesion were larger in U1 and B1 than in C1, however collapse returned to baseline at 7 days, while the others normalized in 2 days. A 4-week exposure to U and B induced lung impairment that resolved 7 days after the last exposure., (Copyright © 2016 Elsevier B.V. All rights reserved.)

It is of great interest to evaluate if there is a relationship between possible sources and trace elements using biomonitoring techniques. In this study, tree bark samples of 171 trees were collected using a biomonitoring technique in the inner city of São Paulo. The trace elements (Al, Ba, Ca, Cl, Cu, Fe, K, Mg, Mn, Na, P, Rb, S, Sr and Zn) were determined by the energy dispersive X-ray fluorescence (EDXRF) spectrometry. The Principal Component Analysis (PCA) was applied to identify the plausible sources associated with tree bark measurements. The greatest source was vehicle-induced non-tailpipe emissions derived mainly from brakes and tires wear-out and road dust resuspension (characterized with Al, Ba, Cu, Fe, Mn and Zn), which was explained by 27.1% of the variance, followed by cement (14.8%), sea salt (11.6%) and biomass burning (10%), and fossil fuel combustion (9.8%). We also verified that the elements related to vehicular emission showed different concentrations at different sites of the same street, which might be helpful for a new street classification according to the emission source. The spatial distribution maps of element concentrations were obtained to evaluate the different levels of pollution in streets and avenues. Results indicated that biomonitoring techniques using tree bark can be applied to evaluate dispersion of air pollution and provide reliable data for the further epidemiological studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Tripoli is a microcrystalline siliceous rock used to polish metals and precious stones. Its inhalation has been associated with increased prevalence of breathing complaints and pneumoconiosis. However, its acute human exposure has not been so far studied. We aimed at evaluating the putative mechanical, morphological, biochemical and inflammatory lung damage in mice acutely exposed to Tripoli dust. BALB/c mice were randomly assigned to 2 groups: In control group (CTRL, n=6) animals received intratracheally (i.t.) 0.9% NaCl (50μl), while Tripoli group (TRIP, n=15) received 20mg of Tripoli powder diluted in 50μL of saline i.t. The experiments were done 15 days later. TRIP mice showed higher pulmonary mechanical impedance, polymorphonuclear cells, TNF-α, IL1-β and IL-6 than CTRL. TRIP presented granulomatous nodules containing collagenous fibers that occupied 35% of the lung tissue area. In conclusion, acute exposure to Tripoli dust triggered important lung damage in mice lungs that if found in human workers could trigger severe illness., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We compared the toxicity of subchronic exposure to equivalent masses of particles from sugar cane burning and traffic. BALB/c mice received 3 intranasal instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4) or particles (15μg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2, BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the last instillation. In all instances UP and BP groups presented worse pulmonary elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse bronchial and alveolar lesion scores than their controls; BP4 had greater bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4. In conclusion, biomass particles were more toxic than those from traffic after repeated exposures., (Copyright © 2013 Elsevier B.V. All rights reserved.)

BALB/c mice received saline (SAL groups) or ovalbumin (OVA groups) intraperitoneally (days 1, 3, 5, 7, 9, 11 and 13). After 27 days, a burst of intratracheal OVA or SAL (days 40, 43 and 46) was performed. Animals were then divided into four groups (N=8, each) and intranasally instilled with saline (SAL-SAL and OVA-SAL) or residual oil fly ash (SAL-ROFA and OVA-ROFA). 24h later, total, initial and difference resistances (Rtot, Rinit, Rdiff) and static elastance (Est) were measured. Lung responsiveness to methacholine was assessed as slope and sensitivity of Est, Rtot, Rinit, and Rdiff. Lung morphometry (collapsed and normal areas and bronchoconstriction index) and cellularity (polymorphonuclear, mononuclear and mast cells) were determined. OVA or ROFA similarly impaired lung mechanics and increased the amount of polymorphonuclear cells and collapsed areas. OVA-ROFA showed even higher hyperresponsiveness, bronchoconstriction and mast cell infiltration. Thus, we concluded that ROFA exposure may add an extra burden to hyperresponsive lungs., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We investigated the effects of salbutamol on the markers of epithelial function in a murine model of chronic allergic pulmonary inflammation by recording the ciliary beat frequency (CBF) and the transepithelial potential difference (PD) in vivo. Mice were sensitized and received four challenges of ovalbumin (OVA group) or 0.9% saline (control group). Forty-eight hours after the 4th inhalation, we observed eosinophilia in the bronchoalveolar lavage and epithelium remodeling with stored acid mucus in the OVA group (P < 0.001). No difference in the baseline CBF was noticed between the groups; however, the OVA group had a significantly lower baseline PD (P = 0.013). Salbutamol increased the CBF in all groups studied, and the dose response curve to salbutamol increased the PD in the OVA group from 10(-4)M to 10(-2)M. We suggest that salbutamol affects the CBF and the depth of the periciliary layer, which, in great part, determines the ability of the cilia to propel the mucus layer. This effect may have a positive impact on airway mucociliary transport in asthma and may have clinical implications., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Furosemide, a potent diuretic, affects ion and water movement across the respiratory epithelium. However, the effects of furosemide, as clinically used, on mucociliary clearance, a critical respiratory defense mechanism, are still lacking in humans. Fourteen young healthy subjects were assigned to three random interventions, spaced one-week apart: no intervention (control), oral furosemide (40mg), and furosemide+oral volume replacement (F+R). Nasal mucociliary clearance was assessed by saccharine test (STT), and mucus properties were in vitro evaluated by means of contact angle and transportability by sneeze. Urine output and osmolality were also evaluated. Urine output increased and reduced urine osmolality in furosemide and F+R compared to the control condition. STT remained stable in the control group. In contrast, STT increased significantly (40%) after furosemide and F+R. There were no changes in vitro mucus properties in all groups. In conclusion, furosemide prolongs STT in healthy young subjects. This effect is not prevented by fluid replacement, suggesting a direct effect of furosemide on the respiratory epithelium., (Copyright 2010 Elsevier B.V. All rights reserved.)

Effects of meteorological variables and air pollutants on child respiratory morbidity are investigated during two consecutive summers (December-March 1992/1993 and 1993/1994) at the Metropolitan Area of São Paulo (MASP), Brazil. The MASP, with almost 17 million inhabitants, is considered the most populous region in South America. Due to warmer temperatures, increased rainfall and consequent low levels of air pollutants during the summer compared to winter, less attention has been paid to epidemiological studies during this season, especially in tropical urban areas such as São Paulo. In the present work, principal component analysis (PCA) is applied to medical end environmental data to identify patterns relating child morbidity, meteorological variables and air pollutants during the summer. The following pollutant concentrations are examined: SO2, inhalable particulate matter (PM10), and O3. The meteorological variables investigated are air temperature, water vapor (water vapor density) and solar radiation. Although low correlation between respiratory morbidity and environmental variables are, in general, observed for the entire dataset, the PCA method indicates that child morbidity is positively associated with O3 for the 1992/1993 summer. This pattern is identified in the third principal component (PC3), which explains about 19% of the total variance of all data in this summer. However, the 1993/1994 summer shows a more complex association between both groups, suggesting stronger ties with meteorological variables. Marked changes in synoptic conditions from the end of January to end of March of the 1993/1994 summer seem to have played an important role in modulating respiratory morbidity. A detailed examination of meteorological conditions in that period indicates that prefrontal (postfrontal), hot (cold) and dry (wet) days favored the observed decrease (increase) of respiratory morbidity.

The study objectives were to compare in vitro transportability and physical properties of respiratory mucus, obtained invasively by direct collection (DC) right after endotracheal intubation and non-invasively by sputum induction with 3% hypertonic saline solution inhalation (SI) 24 h before the anesthesia. Twenty-two patients with no pulmonary disease scheduled for elective abdominal surgical procedures were studied. The parameters analyzed and the main results are as follows. (1) Transportability by cilia (MCT), SI was higher than DC (0.94+/-0.25 and 0.62+/-0.25; P<0.001). There was a significant correlation between the two methods and DC could be estimated by: DC=0.21+(0.44 SI) (r=0.44; P<0.001). (2) Transportability by cough (CC), SI was higher than DC (68.23+/-32.1 and 33.58+/-19.04 mm; P=0.002). (3) Contact angle (CA), SI was lower than DC (10+/-3 degrees and 22+/-14 degrees ; P=0.025). (4) Rheological properties (no significant difference obtained between SI and DC). These results indicated that SI changes mucus physical properties and transportability in non-expectorators.

Lipid emulsions provided with total parenteral nutrition (TPN) have been associated with mononuclear phagocytic system functional changes. The aim of the present investigation was to assess the influence of TPN with added lipid emulsions on macrophage (M phi) phagocytosis. Wistar rats (n = 70) with external jugular vein cannulation were randomized into seven groups. The rats received an oral diet or six different isocaloric (1.16 kcal/mL), isonitrogenous (1.5 g/mL), and isolipidic (30% non-protein calories) TPN regimens: (a) an oral diet with intravenous infusion of saline (OS); (b) non-lipid TPN (glucose); (c) TPN with 10% long chain triacylglycerol emulsions (LCT); (d) TPN with 90% LCT and 10% fish oil (FO) emulsion; (e) TPN with 50% LCT and 50% FO; (f) TPN with 10% lipid emulsion with 50% medium chain triacylglycerol (MCT) and 50% LCT; and (g) TPN with 45% MCT, 45% LCT, and 10% FO. After 96 h of TPN or saline infusion, colloidal carbon (Pelikan, Germany) was injected intravenously at 1.0 mL/kg body weight, and the rats were killed after 3 h. Liver, spleen, and lung were weighed and prepared by immunohistochemistry analyses with the HAM-56 anti-M phi antibody. Under light microscopy, the total M phi number (MT) and the colloidal carbon phagocytic M phi number (MP) were established, and the phagocytic index was calculated as MP/MT x 100. There were no statistical (P < 0.05) differences in liver, spleen, or lung weights among the seven groups in comparison with the OS group. Non-lipid TPN inhibited spleen and lung M phi phagocytosis when compared with the OS and lipid-TPN groups. Lipid TPN supplemented with fish oil emulsion increased total liver and lung M phi number and phagocytosis. These results indicate that TPN supplemented with fish oil increases M phi phagocytosis in rats.

This work was designed to develop a simple method based on the frog palate preparation to study the effects of hydrogen peroxide (H2O2) on ciliated epithelium. For this purpose, five sets (n = 10 per set) of frog palate preparations (Rana catesbeiana) were studied during 35 min after immersion in increasing concentrations of H2O2: 1, 8, 16, 32, and 64 microM. The effects of H2O2 on ciliated epithelium were assessed by measuring transepithelial potential difference (PD) and mucociliary transport (MT). Measurements were performed at 5-min intervals. In addition, the palates submitted to the 64 microM dose were immersed in Ringer's solution and followed by another 30 min to assess the possible recovery after maximal injury. Transepithelial potential difference (PD) was measured by means of agar-filled microelectrodes connected to the high input of a grounded electrometer. Mucociliary transport (MT) was determined by directly monitoring the movement of autologous mucus along the palate surface. Significant decrease in MT was observed in 16 microM and beyond and significant change in PD was observed in 32 microM and 64 microM. Palates submitted to 64 microM of H2O2 returned to their baseline levels of PD and MT within 30 min of recovery in Ringer's solution. In conclusion, the frog palate preparation was shown to be an efficient experimental tool to assess the deleterious effects of H2O2 on the ciliated epithelium.