International study of temperature, heat and urban mortality: the `ISOTHURM` project

Background This study describes heat- and cold-related mortality in 12 urban populations in low- and middle-income countries, thereby extending knowledge of how diverse populations, in non-OECD countries, respond to temperature extremes. Methods The cities were: Delhi, Monterrey, Mexico City, Chiang Mai, Bangkok, Salvador, So Paulo, Santiago, Cape Town, Ljubljana, Bucharest and Sofia. For each city, daily mortality was examined in relation to ambient temperature using autoregressive Poisson models (2- to 5-year series) adjusted for season, relative humidity, air pollution, day of week and public holidays. Results Most cities showed a U-shaped temperature-mortality relationship, with clear evidence of increasing death rates at colder temperatures in all cities except Ljubljana, Salvador and Delhi and with increasing heat in all cities except Chiang Mai and Cape Town. Estimates of the temperature threshold below which cold-related mortality began to increase ranged from 15 degrees C to 29 degrees C; the threshold for heat-related deaths ranged from 16 degrees C to 31C. Heat thresholds were generally higher in cities with warmer climates, while cold thresholds were unrelated to climate. Conclusions Urban populations, in diverse geographic settings, experience increases in mortality due to both high and low temperatures. The effects of heat and cold vary depending on climate and non-climate factors such as the population disease profile and age structure. Although such populations will undergo some adaptation to increasing temperatures, many are likely to have substantial vulnerability to climate change. Additional research is needed to elucidate vulnerability within populations.

Vulnerability to heat-related mortality in Latin America: A case-crossover study in Sao Paulo, Brazil, Santiago, Chile and Mexico City, Mexico

Background Factors affecting vulnerability to heat-related mortality are not well understood. Identifying susceptible populations is of particular importance given anticipated rising temperatures from climatic change. Methods We investigated heat-related mortality for three Latin American cities (Mexico City, Mexico; Sao Paulo, Brazil; Santiago, Chile) using a case-crossover approach for 754 291 deaths from 1998 to 2002. We considered lagged exposures, confounding by air pollution, cause of death and susceptibilities by educational attainment, age and sex. Results Same and previous day apparent temperature were most strongly associated with mortality risk. Effect estimates remained positive though lowered after adjustment for ozone or PM(10). Susceptibility increased with age in all cities. The increase in mortality risk for those >= 65 comparing the 95th and 75th percentiles of same-day apparent temperature was 2.69% (95% CI: -2.06 to 7.88%) for Santiago, 6.51% (95% CI: 3.57-9.52%) for Sao Paulo and 3.22% (95% CI: 0.93-5.57%) for Mexico City. Patterns of vulnerability by education and sex differed across communities. Effect estimates were higher for women than men in Mexico City, and higher for men elsewhere, although results by sex were not appreciably different for any city. In Sao Paulo, those with less education were more susceptible, whereas no distinct patterns by education were observed in the other cities. Conclusions Elevated temperatures are associated with mortality risk in these Latin American cities, with the strongest associations in So Paulo, the hottest city. The elderly are an important population for targeted prevention measures, but vulnerability by sex and education differed by city.

Chronic exposure to fine particulate matter emitted by traffic affects reproductive and fetal outcomes in mice

Air pollution is an important environmental health risk factor that can result in many different gestational and reproductive negative outcomes. In this study, we have investigated the effects of two different times of exposure (before conception and during pregnancy) to urban ambient particulate matter on reproductive and pregnancy outcomes in mice. Using exposure chambers receiving filtered (F) and non-filtered (NF) air, we observed that exposed females exhibited changes in the length of estrus cycle and extended estrus and, therefore, a reduction in the number of cycles during the studied period (F2.6 +/- 0.22 and NF 1.2 +/- 0.29, p = 0.03). The mean number of antral follicles declined by 36% (p = 0.04) in NF mice (75 +/- 35.2) compared to F mice (118.6 +/- 18.4). our results further indicate a significant increase in time necessary for mating and decreased fertility and pregnancy indices (p = 0.003) in NF couples. Mean post-implantation loss rates were increased by 70% (p <= 0.005) in the NF2 group (exposed before and during pregnancy to NF air) compared to the F1 group (exposed before and during pregnancy to F air) and were influenced by both pre-gestational (p < 0.004) and gestational (p < 0.01) period exposure. Fetal weight was significantly higher in the F1 group when compared with the other groups (p < 0.001), at a 20% higher weight in the F1 group (0.86 +/- 0.18 g) than in the NF2 group (0.68 +/- 0.10g). Furthermore, fetal weight was influenced by both pre-gestational and gestational period exposure, and a significant interaction between these two factors was found (p < 0.001). This study demonstrated that exposure to ambient levels of urban traffic-generated particulate matter negatively affects different functions and stages of the reproductive process. Our results also reinforce the idea that maternal exposure to air pollution is linked to negative pregnancy outcomes, even if the exposure occurs only before conception. (C) 2009 Elsevier Inc. All rights reserved.

Association between micronuclei frequency in pollen mother cells of Tradescantia and mortality due to cancer and cardiovascular diseases: A preliminary study in Sao Jose dos Campos, Brazil

The present study was designed to explore the correlation between the frequency of micronuclei in Trad-MN, measured across 28 biomonitoring stations during the period comprised between 11 of May and 2 of October, 2006, and adjusted mortality rates due to cardiovascular, respiratory diseases and cancer in Sao Jose dos Campos, Brazil, an area with different sources of air pollution. For controlling purposes, mortality rate due to gastrointestinal diseases (an event less prone to be affected by air pollution) was also considered in the analysis. Spatial distribution of micronuclei frequency was determined using average interpolation. The association between health estimators and micronuclei frequency was determined by measures of Pearson`s correlation. Higher frequencies of micronuclei were detected in areas with high traffic and close to a petrochemical pole. Significant associations were detected between micronuclei frequency and adjusted mortality rate due to cardiovascular diseases (r = 0.841, p = 0.036) and cancer (r = 0.890, p = 0.018). The association between mortality due to chronic obstructive pulmonary diseases was positive but did not reach statistical significance (r = 0.640, p = 0.172), probably because of the small number of events. Gastrointestinal mortality did not exhibit significant association with micronuclei frequency. Because the small number of observations and the nature of an ecological study, the present findings must be considered with caution and considered as preliminary. Further studies, performed in different conditions of contamination and climate should be done before considering Trad-MN in the evaluation of human health risk imposed by air pollutants. (C) 2009 Elsevier Ltd. All rights reserved.

Comparative respiratory toxicity of particles produced by traffic and sugar cane burning

The impact of particle emissions by biomass burning is increasing throughout the world. We explored the toxicity of particulate matter produced by sugar cane burning and compared these effects with equivalent mass of traffic-derived particles. For this purpose, BALB/c mice received a single intranasal instillation of either distilled water (C) or total suspended particles (15 mu g) from an urban area (SP group) or biomass burning-derived particles (Bio group). Lung mechanical parameters (total, resistive and viscoelastic pressures, static elastance, and elastic component of viscoelasticity) and histology were analyzed 24h after instillation. Trace elements and polycyclic aromatic hydrocarbons (PAHs) metabolites of the two sources of particles were determined. All mechanical parameters increased similarly in both pollution groups compared with control, except airway resistive pressure, which increased only in Bio. Both exposed groups showed significantly higher fraction area of alveolar collapse, and influx of polymorphonuclear cells in lung parenchyma than C. The composition analysis of total suspended particles showed higher concentrations of PAHs and lower concentration of metals in traffic than in biomass burning-derived particles. In conclusion, we demonstrated that a single low dose of ambient particles, produced by traffic and sugar cane burning, induced significant alterations in pulmonary mechanics and lung histology in mice. Parenchymal changes were similar after exposure to both particle sources, whereas airway mechanics was more affected by biomass-derived particles. Our results indicate that biomass particles were at least as toxic as those produced by traffic. (C) 2008 Elsevier Inc. All rights reserved.

Chronic nasal instillation of residual-oil fly ash (ROFA) induces brain lipid peroxidation and behavioral changes in rats

Several epidemiological studies have linked particulate matter exposure to numerous adverse health effects on the respiratory, cardiovascular, and reproductive systems (Braga et al., 1999; Zanobetti et al., 2000; Anderson et al., 2001; Farhat et al., 2005). More recently, ambient levels of black carbon were associated to impaired cognitive function in children (Suglia et al., 2008), suggesting that the central nervous system (CNS) may be a target of air pollutants. The present study was conducted to (a) determine whether chronic residual oil fly ash (ROFA) exposure promotes behavioral changes and lipid peroxidation in rat brain areas, and (b) determine whether N-acetylcysteine (NAC), a general antioxidant, prevents these effects. Forty-five-day-old male Wistar rats were exposed or not to ROFA by intranasal instillation and were treated or not with NAC (150 mg/kg) ip for 30 days. One day later, rats were submitted to the open field test to evaluate the motor/exploratory activities and emotionality followed by decapitation. Striatum and cerebellum were dissected to determine lipid peroxidation by the accumulation of thiobarbituric acid-reactive substances (TBARS). ROFA instillation induced an increase in lipid peroxidation level in striatum (p = .033) and cerebellum (p = .030), as compared with the control group. NAC treatment blocked these changes. ROFA promoted a decrease in the frequency of peripheral walking (p = .006) and a decrease in exploration (p = .001), which were not blocked by N-acetylcysteine. The present study provides evidence that toxic particles, administered by the respiratory route, induce oxidative stress in structures of the central nervous system, as well as behavioral alterations. The administration of NAC reduces lipid peroxidation at the striatum and cerebellum levels, but does not influence behavioral disturbances.

Atmospheric pollutants monitoring by analysis of epiphytic lichens

The Canoparmelia texana epiphytic lichenized fungi was used to monitor atmospheric pollution in the Sao Paulo metropolitan region, SP, Brazil. The cluster analysis applied to the element concentration values confirmed the site groups of different levels of pollution due to industrial and vehicular emissions. In the distribution maps of element concentrations, higher concentrations of Ba and Mn were observed in the vicinity of industries and of a petrochemical complex. The highest concentration of Co found in lichens from the Sao Miguel Paulista site is due to the emissions from a metallurgical processing plant that produces this element. For Br and Zn, the highest concentrations could be associated both to vehicular and industrial emissions. Exploratory analyses revealed that the accumulation of toxic elements in C. texana may be of use in evaluating the human risk of cardiopulmonary mortality due to prolonged exposure to ambient levels of air pollution. (c) 2007 Elsevier Ltd. All rights reserved.

Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice

Air pollution is associated with morbidity and mortality induced by respiratory diseases. However, the mechanisms therein involved are not yet fully clarified. Thus, we tested the hypothesis that a single acute exposure to low doses of fine particulate matter (PM2.5) may induce functional and histological lung changes and unchain inflammatory and oxidative stress processes. PM2.5 was collected from the urban area of Sao Paulo city during 24 h and underwent analysis for elements and polycyclic aromatic hydrocarbon contents. Forty-six male BALB/c mice received intranasal instillation of 30 mu L of saline (CTRL) or PM2.5 at 5 or 15 mu g in 30 mu L of saline (P5 and P15, respectively). Twenty-four hours later, lung mechanics were determined. Lungs were then prepared for histological and biochemical analysis. P15 group showed significantly increased lung impedance and alveolar collapse, as well as lung tissue inflammation, oxidative stress and damage. P5 presented values between CTRL and P15: higher mechanical impedance and inflammation than CTRL, but lower inflammation and oxidative stress than P15. In conclusion, acute exposure to low doses of fine PM induced lung inflammation, oxidative stress and worsened lung impedance and histology in a dose-dependent pattern in mice.

Biological Effects and Dose-Response Assessment of Diesel Exhaust Particles on In Vitro Early Embryo Development in Mice

An increased risk of early pregnancy loss in women briefly exposed to high levels of ambient particulate matter during the preconceptional period was recently observed. The effects of this exposure on early embryo development are unknown. This study was designed to assess the dose-response and biological effects of diesel exhaust particles (DEP) on in vitro embryo development using the in vitro fertilization (IVF) mouse model. Zygotes obtained from superovulated mice after IVF were randomly cultured in different DEP concentrations (0, 0.2, 2, and 20 mu g/cm(2)) for 5 days and observed for their capacity to attach and develop on a fibronectin matrix until day 8. Main outcome measures included blastocyst rates 96 and 120 h after insemination, hatching discriminatory score, total cell count, proportion of cell allocation to inner cell mass (ICM) and trophectoderm (TE), ICM morphology, attachment rate and outgrowth area, apoptosis and necrosis rates, and Oct-4 and Cdx-2 expression. Multivariate analysis showed a negative dose-dependent effect on early embryo development and hatching process, blastocyst cell allocation, and ICM morphology. Although blastocyst attachment and outgrowth were not affected by DEP, a significant impairment of ICM integrity was observed in day 8 blastocysts. Cell death through apoptosis was significantly higher after DEP exposure. Oct-4 expression and the Oct-4/Cdx-2 ratio were significantly decreased in day 5 blastocysts irrespective of DEP concentration. Results suggest that DEP appear to play an important role in disrupting cell lineage segregation and ICM morphological integrity even at lower concentrations, compromising future growth and viability of the blastocyst.

Pulmonary function and histological impairment in mice after acute exposure to aluminum dust

Along the aluminum refining process, alumina (Al(2)O(3)) constitutes the main source of dust. Although aluminum refinery workers present respiratory symptoms with lung functional changes, no conclusive data about lung function impairment after alumina exposure has been so far reported. We examined the pulmonary alterations of exposure to material collected in an aluminum refinery in Brazil. BALB/c mice were exposed in a whole-body chamber for 1 h to either saline (CTRL, n = 11) or to a suspension (in saline) of 8 mg/m(3) of the dust (ALUM, n = 11) both delivered by an ultrasonic nebulizer. Twenty-four hours after exposure lung mechanics were measured by the end-inflation method. Lungs were prepared for histology. ALUM showed significantly higher static elastance (34.61 +/- 5.76 cmH(2)O/mL), elastic component of viscoelasticity (8.16 +/- 1.20 cmH(2)O/mL), pressure used to overcome the resistive component of viscoelasticity (1.62 +/- 0.24 cmH(2)O), and total resistive pressure (2.21 +/- 0.49 cmH(2)O) than CTRL (27.95 +/- 3.63 cmH(2)O/mL, 6.12 +/- 0.99 cmH(2)O/mL, 1.23 +/- 0.19 cmH(2)O, and 1.68 +/- 0.23 cmH(2)O, respectively). ALUM also presented significantly higher fraction area of alveolar collapse (69.7 +/- 1.2%) and influx of polymorphonuclear cells (27.5 +/- 1.1%) in lung parenchyma than CTRL (27.2 +/- 1.1% and 14.6 +/- 0.7%, respectively). The composition analysis of the particulate matter showed high concentrations of aluminum. For the first time it was demonstrated in an experimental model that an acute exposure to dust collected in an aluminum producing facility impaired lung mechanics that could be associated with inflammation.

Hippocampus lipid peroxidation induced by residual oil fly ash intranasal instillation versus habituation to the open field

Epidemiological studies have demonstrated the adverse effects of particulate matter (PM) inhalation on the respiratory and cardiovascular systems. It has been reported that air pollution may affect the central nervous system and decrease cognitive function. In rats, residual oil fly ash (ROFA) instillation causes decreased motor activity and increased lipid peroxidation in the striatum and the cerebellum. Our objective was to determine whether chronic instillation of particles induces changes in learning and memory in rats and whether oxidants in the hippocampus may contribute to these adverse effects. Forty-five-day-old male Wistar rats were exposed to ROFA by intranasal instillation and were treated with N-acetylcysteine (NAC) at 150 mg/kg i.p. for 30 days. Control groups were exposed to ROFA, NAC, or neither. On days 1, 8, and 30 of the protocol, rats were submitted to the open field test to evaluate habituation. After the last open field session, the rats were killed by decapitation. The hippocampus was used to determine lipid peroxidation (LP) by the thiobarbituric acid-reactive substances test. ROFA instillation induced an increase in LP in the hippocampus compared to all treatment groups (p = .012). NAC treatment blocked these changes. All of the treatment groups presented a decrease in the frequency of peripheral walking (p = .001), rearing (p = .001), and exploration (p = .001) over time. Our study demonstrates that exposure to particles for 30 days and/or NAC treatment do not modify habituation to an open field, a simple form of learning and memory in rats, and that oxidative damage induced by ROFA does not modulate these processes.

Effects of sidestream cigarette smoke exposure on baroreflex components in spontaneously hypertensive rats

We evaluated short-term effects of sidestream cigarette smoke (SSCS) exposure on baroreflex function in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) normotensive rats. Rats were exposed to SSCS during three weeks, 180min, five days per week, in a concentration of carbon monoxide (CO) between 100 and 300ppm. We observed that SSCS exposure increased tachycardic peak and heart rate range while it attenuated bradycardic reflex in WKY. In respect to SHR, SSCS also increased tachycardic peak. Taken together, our data suggests that three weeks of exposure to SSCS affects the sympathetic and parasympathetic component of the baroreflex in normotensive WKY while it tended to affect the sympathetic component in SHR.

In vitro fertilization, embryo development, and cell lineage segregation after pre- and/or postnatal exposure of female mice to ambient fine particulate matter

Objective: To evaluate effects of pre- and/or postnatal exposure to ambient fine particulate matter on fertilization, embryo development, and cell lineage segregation in preimplantation blastocysts using the IVF mouse model. Design: Animal model. Setting: Academic institution. Animal(S): Six-week-old, superovulated mice. Intervention(s): Pre- and postnatal exposure to filtered air (FA-FA), filtered-ambient air (FA-AA), or ambient air (AA-AA) in exposure chambers 24 hours a day for 9 weeks. Main Outcome Measure(S): Gestation length, litter size, sex ratio, ovarian response to superovulation, fertilization rate, embryo development, blastocyst and hatching rates, total cell count, and proportion of cell allocation to inner-cell mass (ICM) and trophectoderm (TE). Result(S): Gestation length, litter size and birth weight, live-birth index, and sex ratio were similar among exposure groups. Ovarian response was not affected by the exposure protocol. A multivariate effect for pre- and/or postnatal exposure to ambient fine particulate matter on IVF, embryo development, and blastocyst differential staining was found. Cell counts in ICM and ICM/TE ratios in blastocysts produced in the FA-FA protocol were significantly higher than in blastocysts produced in the FA-AA and AA-AA protocols. No difference in total cell count was observed among groups. Conclusion(S): Our study suggests that exposure to ambient fine particulate matter may negatively affect female reproductive health by disrupting the lineage specification at the blastocyst stage without interfering in early development of the mouse embryo. (Fertil Steril (R) 2009;92:1725-35. (C) 2009 by American Society for Reproductive Medicine.)

Correlation of fungi and endotoxin with PM2.5 and meteorological parameters in atmosphere of Sao Paulo, Brazil

Particulate matter, especially PM2.5, is associated with increased morbidity and mortality from respiratory diseases. Studies that focus on the chemical composition of the material are frequent in the literature, but those that characterize the biological fraction are rare. The objectives of this study were to characterize samples collected in Sao Paulo, Brazil on the quantity of fungi and endotoxins associated with PM2.5, correlating with the mass of particulate matter, chemical composition and meteorological parameters. We did that by Principal Component Analysis (PCA) and multiple linear regressions. The results have shown that fungi and endotoxins represent significant portion of PM2.5, reaching average concentrations of 772.23 spores mu g(-1) of PM2.5 (SD: 400.37) and 5.52 EU mg(-1) of PM2.5 (SD: 4.51 EU mg(-1)), respectively. Hyaline basidiospores, Cladosporium and total spore counts were correlated to factor Ba/Ca/Fe/Zn/K/Si of PM2.5 (p < 0.05). Genera Pen/Asp were correlated to the total mass of PM2.5 (p < 0.05) and colorless ascospores were correlated to humidity (p < 0.05). Endotoxin was positively correlated with the atmospheric temperature (p < 0.05). This study has shown that bioaerosol is present in considerable amounts in PM2.5 in the atmosphere of Sao Paulo, Brazil. Some fungi were correlated with soil particle resuspension and mass of particulate matter. Therefore, the relative contribution of bioaerosol in PM2.5 should be considered in future studies aimed at evaluating the clinical impact of exposure to air pollution. (C) 2010 Elsevier Ltd. All rights reserved.

Pre- and postnatal exposure to ambient levels of urban particulate matter (PM(2.5)) affects mice spermatogenesis

This work characterizes the effects of ambient levels of urban particulate matter (PM(2.5)) from the city of Sao Paulo on spermatogenesis using mice exposed during the embryo-fetal and/or postnatal phases of development. Parental generations (BALB/c mice) were exposed to air pollution in chambers with or without filtering PM(2.5) for 4 months. Animals were mated, and half of the 1-day-old offspring were moved between chambers, which yielded prenatal and postnatal groups. Remaining offspring comprised the non-exposed and pre+postnatal exposed groups. After 90 days, the animals were sacrificed for testis collection and weighing. Optical microscopy was used for the morphometric analyses of the cell counts, spermatogenic cycle, proliferation, and apoptosis. Prenatally exposed animals presented reduced body and testicular weight with an increased gonadosomatic index (GSI). Testicular volume also decreased, as well as the tubular diameter in testes of the same animals. Proliferation, apoptosis, and spermatogenic cycle analyses showed no significant differences among groups. However, the tubules at stage VII of pre- and postnatal animals presented a reduced number of elongated spermatids. Pre+postnatal group presented higher spermatid head retention at stages VIII-XII. These results show that ambient levels of PM(2.5) from Sao Paulo city affect spermatogenesis by damaging sperm production.