Maria Lúcia Bueno Garcia

Eosinophilic inflammation and airway hyper‐responsiveness are profoundly inhibited by a helminth (Ascaris suum) extract in a murine model of asthma

Background The increase of atopic disorders in developed countries has been associated with the decline of infectious diseases, including helminthic infections. We have already demonstrated that adult worm extracts from Ascaris suum (ASC) suppress the IgE antibody production against unrelated antigens.

Air pollution and antibodies against modified lipoproteins are associated with atherosclerosis and vascular remodeling in hyperlipemic mice

We analyzed the impact of chronic exposure to urban air pollution on the development of atherosclerosis. Hyperlipemic mice (LDLR(-/-)) were submitted to a high fat diet and air pollution for four months. We measured the susceptibility of LDL to oxidative modifications (TBARS), the presence of anti-oxLDL and an apoB-derived peptide (apoB-D) in blood and the degree of atherosclerosis in the aortic arch. Air pollution increased the susceptibility of LDL to oxidation as well as anti-oxLDL and anti-apo-B levels. These levels were even higher than in mice submitted to a high fat diet and non-polluted air. The lipid content of the atherosclerotic plaques in the aorta was increased in groups with a high cholesterol diet independently of the air quality. However, the thickness of the arterial wall was greater in mice fed a high lipid diet with polluted air. Thus, we conclude that urban air pollution exacerbates the susceptibility of LDL to oxidation, atherogenesis and vascular remodeling in hyperlipemic mice and that an immune response accompanies this process.

The association between air pollution and blood pressure in traffic controllers in Santo André, São Paulo, Brazil☆

BACKGROUND Urban air pollutants are associated with cardiovascular events. Traffic controllers are at high risk for pollution exposure during outdoor work shifts. OBJECTIVE The purpose of this study was to evaluate the relationship between air pollution and systemic blood pressure in traffic controllers during their work shifts. METHODS This cross-sectional study enrolled 19 male traffic controllers from Santo André city (São Paulo, Brazil) who were 30-60 years old and exposed to ambient air during outdoor work shifts. Systolic and diastolic blood pressure readings were measured every 15 min by an Ambulatory Arterial Blood Pressure Monitoring device. Hourly measurements (lags of 0-5h) and the moving averages (2-5h) of particulate matter (PM(10)), ozone (O(3)) ambient concentrations and the acquired daily minimum temperature and humidity means from the São Paulo State Environmental Agency were correlated with both systolic and diastolic blood pressures. Statistical methods included descriptive analysis and linear mixed effect models adjusted for temperature, humidity, work periods and time of day. RESULTS Interquartile increases of PM(10) (33 μg/m(3)) and O(3) (49 μg/m(3)) levels were associated with increases in all arterial pressure parameters, ranging from 1.06 to 2.53 mmHg. PM(10) concentration was associated with early effects (lag 0), mainly on systolic blood pressure. However, O(3) was weakly associated most consistently with diastolic blood pressure and with late cumulative effects. CONCLUSIONS Santo André traffic controllers presented higher blood pressure readings while working their outdoor shifts during periods of exposure to ambient pollutant fluctuations. However, PM(10) and O(3) induced cardiovascular effects demonstrated different time courses and end-point behaviors and probably acted through different mechanisms.

Urban air pollution induces micronuclei in peripheral erythrocytes of mice in vivo.

In this study, we explored the role of chronic exposure to urban air pollution in causing DNA damage (micronuclei frequency in peripheral erythrocytes) in rodents in vivo. Mice (n=20) were exposed to the urban atmosphere of São Paulo for 120 days (February to June 1999) and compared to animals (n=20) maintained in the countryside (Atibaia) for the same period. Daily levels of inhalable particles (PM10), CO, NO(2), and SO(2), were available for São Paulo. Occasional measurements of CO and O(3) were made in Atibaia, showing negligible levels of pollution in the area. The frequency of micronuclei (repeated-measures ANOVA) increased with aging, the highest values obtained for the 90th day of experiment (P<0.001). The exposure to urban air pollution elicited a significant (P=0.016) increase of micronuclei frequency, with no significant interaction with time of study. Associations (Spearmans correlation) between pollution levels of the week that precede blood sampling and micronuclei counts were observed in São Paulo. The associations between micronuclei counts and air pollution were particularly strong for pollutants associated with automotive emissions, such as CO (P=0.037), NO(2) (P<0.001), and PM10 (P<0.001). Our results support the concept that urban levels of air pollution may cause somatic mutations.

Effects of formaldehyde on the frog's mucociliary epithelium as a surrogate to evaluate air pollution effects on the respiratory epithelium

The increasing use of alcohol as an alternative fuel to gasoline or diesel can increase emission of formaldehyde, an organic gas that is irritant to the mucous membranes. The respiratory system is the major target of air pollutants and its major defense mechanism depends on the continuous activity of the cilia and the resulting constant transportation of mucous secretion. The present study was designed to evaluate the effects of formaldehyde on the ciliated epithelium through a relative large dose range around the threshold limit value adopted by the Brazilian legislation, namely 1.6 ppm (1.25 to 5 ppm). For this purpose, the isolated frog palate preparation was used as the target of toxic injury. Four groups of frog palates were exposed to diluted Ringer solution (control, N = 8) and formaldehyde diluted in Ringer solution at three different concentrations (1.25, 2.5 and 5.0 ppm, N = 10 for each group). Mucociliary clearance and ciliary beat frequency decreased significantly in contact with formaldehyde at the concentrations of 2.5 and 5.0 ppm after 60 min of exposure (P<0.05). We conclude that relatively low concentrations of formaldehyde, which is even below the Brazilian threshold limit value, are sufficient to cause short-term mucociliary impairment.

The time course of vasoconstriction and endothelin receptor A expression in pulmonary arterioles of mice continuously exposed to ambient urban levels of air pollution

The present study aimed to verify the time course of the effects of environmental levels of urban air pollution toxicity on lung arterioles. BALB/c mice (n=56) were continuously exposed to selective chambers equipped with (filtered, F) or without (non-filtered, NF) filter devices for particles and toxic gases for 24h/day, over 14, 21, 30 or 45 days. After exposure, we evaluated the lumen-wall relationship (an estimator of arteriolar narrowing), endothelial nitric oxide synthase (eNOS) and endothelin type A receptor (ETAr) expression in the vascular wall and inflammatory influx of the peribronchiolar area. Concentrations of fine particulate matter (PM<or=2.5 microg/m(3)), nitrogen dioxide (NO(2)), black smoke (BS), humidity and temperature in both the environment and inside the chambers were measured daily. Filters cleared 100% of BS and 97% of PM inside the F chamber. The arteriole wall of the lungs of mice from NF chamber had an increased ETAr expression (p<or=0.042) concomitant to a decrease in the lumen/wall ratio (p=0.02) on the early days of exposure, compared to controls. They also presented a progressive increment of inflammatory influx in the peribronchiolar area during the study (p=0.04) and decrement of the eNOS expression on the 45th day of exposure in both vascular layers (p<or=0.03). We found that after 14 days of exposure, the ambient levels of air pollutants in Sao Paulo induced vasoconstriction that was associated with an increase in ETAr expression. These vascular results do not appear to be coupled to the progressive inflammatory influx in lung tissue, suggesting a down-regulation of vasoconstrictive mechanisms through an imbalance in the cytokines network. It is likely that these responses are protective measures that decrease tissue damage brought about by continuous exposure to air pollutants.

Effects of Chronic Exposure to Air Pollution from Sao Paulo City on Coronary of Swiss Mice, from Birth to Adulthood

To explore the hypothesis that air pollution promotes cardiovascular changes, Swiss mice were continuously exposed, since birth, in two open-top chambers (filtered and nonfiltered for airborne particles ≤ 0.3 μm) placed 20 m from a street with heavy traffic in downtown Sao Paulo, twenty-four hours per day for four months. Fine particle (PM2.5) concentration was determined gravimetrically; hearts were analyzed by morphometry. There was a reduction of the PM2.5 inside the filtered chamber (filtered = 8.61±0.79 μg/m3, nonfiltered = 18.05±1.25 μg/m3, p < .001). Coronary arteries showed no evidence of luminal narrowing in the exposed group but presented higher collagen content in the adventitia of LV large-sized and RV midsized vessels (p = .001) and elastic fibers in both tunicae adventitia and intima-media of almost all sized arterioles from both ventricles (p = .03 and p = .001, respectively). We concluded that chronic exposure to urban air since birth induces mild but significant vascular structural alterations in normal individuals, presented as coronary arteriolar fibrosis and elastosis. These results might contribute to altered vascular response and ischemic events in the adulthood.

A rat model of acute lung injury induced by cardiopulmonary bypass.

Impaired lung function is still a major complication after cardiac surgery with cardiopulmonary bypass. The purpose of the present study was to develop an experimental model of acute pulmonary injury induced by cardiopulmonary bypass in Wistar rats. Cardiopulmonary bypass was performed for 60 min using a non-pulsatile roller pump and a membrane oxygenator (n = 8 for cardiopulmonary bypass group and n = 7 for control rats). We measured tracheal pressure, airflow, and lung volume changes and obtained pulmonary resistance and dynamic elastance. After the cardiopulmonary bypass, lungs were submitted to a quick-freezing protocol and morphometric analysis was performed. There was a time-dependent increase in dynamic elastance, but not pulmonary resistance, only in the rats submitted to cardiopulmonary bypass (P = 0.005). Lungs from animals submitted to cardiopulmonary bypass showed significantly more alveolar hemorrhage (P = 0.025) and edema (P = 0.021), as well as perivascular edema (P = 0.003) when compared to control rats. In our experimental model, rats submitted to cardiopulmonary bypass developed acute pulmonary changes similar to the early phase of acute pulmonary distress syndrome. Cardiopulmonary bypass resulted in an increase in pulmonary elastance without changes in resistance. This experimental model is suitable for studies concerning the mechanisms of acute lung injury induced by cardiopulmonary bypass.

Lacrimal Cytokines Assessment in Subjects Exposed to Different Levels of Ambient Air Pollution in a Large Metropolitan Area

Background Air pollution is one of the most environmental health concerns in the world and has serious impact on human health, particularly in the mucous membranes of the respiratory tract and eyes. However, ocular hazardous effects to air pollutants are scarcely found in the literature. Design Panel study to evaluate the effect of different levels of ambient air pollution on lacrimal film cytokine levels of outdoor workers from a large metropolitan area. Methods Thirty healthy male workers, among them nineteen professionals who work on streets (taxi drivers and traffic controllers, high pollutants exposure, Group 1) and eleven workers of a Forest Institute (Group 2, lower pollutants exposure compared to group 1) were evaluated twice, 15 days apart. Exposure to ambient PM2.5 (particulate matter equal or smaller than 2.5 μm) was 24 hour individually collected and the collection of tears was performed to measure interleukins (IL) 2, 4, 5 and 10 and interferon gamma (IFN-γ) levels. Data from both groups were compared using Student’s t test or Mann- Whitney test for cytokines. Individual PM2.5 levels were categorized in tertiles (lower, middle and upper) and compared using one-way ANOVA. Relationship between PM2.5 and cytokine levels was evaluated using generalized estimating equations (GEE). Results PM2.5 levels in the three categories differed significantly (lower: ≤22 μg/m3; middle: 23–37.5 μg/m3; upper: >37.5 μg/m3; p<0.001). The subjects from the two groups were distributed unevenly in the lower category (Group 1 = 8%; Group 2 = 92%), the middle category (Group 1 = 89%; Group 2 = 11%) and the upper category (Group 1 = 100%). A significant relationship was found between IL-5 and IL-10 and PM2.5 levels of the group 1, with an average decrease of 1.65 pg/mL of IL-5 level and of 0.78 pg/mL of IL-10 level in tear samples for each increment of 50 μg/m3 of PM2.5 (p = 0.01 and p = 0.003, respectively). Conclusion High levels of PM2.5 exposure is associated with decrease of IL-5 and IL-10 levels suggesting a possible modulatory action of ambient air pollution on ocular surface immune response.

An approach to using heart rate monitoring to estimate the ventilation and load of air pollution exposure

BACKGROUND The effects of air pollution on health are associated with the amount of pollutants inhaled which depends on the environmental concentration and the inhaled air volume. It has not been clear whether statistical models of the relationship between heart rate and ventilation obtained using laboratory cardiopulmonary exercise test (CPET) can be applied to an external group to estimate ventilation. OBJECTIVES To develop and evaluate a model to estimate respiratory ventilation based on heart rate for inhaled load of pollutant assessment in field studies. METHODS Sixty non-smoking men; 43 public street workers (public street group) and 17 employees of the Forest Institute (park group) performed a maximum cardiopulmonary exercise test (CPET). Regression equation models were constructed with the heart rate and natural logarithmic of minute ventilation data obtained on CPET. Ten individuals were chosen randomly (public street group) and were used for external validation of the models (test group). All subjects also underwent heart rate register, and particulate matter (PM2.5) monitoring for a 24-hour period. RESULTS For the public street group, the median difference between estimated and observed data was 0.5 (CI 95% -0.2 to 1.4) l/min and for the park group was 0.2 (CI 95% -0.2 to 1.2) l/min. In the test group, estimated values were smaller than the ones observed in the CPET, with a median difference of -2.4 (CI 95% -4.2 to -1.8) l/min. The mixed model estimated values suggest that this model is suitable for situations in which heart rate is around 120-140bpm. CONCLUSION The mixed effect model is suitable for ventilation estimate, with good accuracy when applied to homogeneous groups, suggesting that, in this case, the model could be used in field studies to estimate ventilation. A small but significant difference in the median of external validation estimates was observed, suggesting that the applicability of the model to external groups needs further evaluation.