Environews
FOCUS | Dengue Reborn: Widespread Resurgence of a Resilient Vector
Dengue, once a relatively mild infection that was largely wiped out in the twentieth century, has reemerged in more locales than ever and increasingly in the more dangerous form of dengue hemorrhagic fever. What's behind the recent surge in this disease, and why is it showing up in areas so far from the tropics? This article (p. A382) looks at where dengue is spreading across the globe, the environmental factors that are helping it get there, and what needs to be done to once again curb the disease.
SPHERES OF INFLUENCE | Unnatural Disaster: Human Factors in the Mississippi Floods
Major flooding of the Mississippi River this past spring has underlined once more the constant threat posed to those living in floodplains, especially those areas created with the use of levees, wing dams, and other methods for altering a river's natural flow. A rising tide of research findings suggests these manipulations of the natural environment may actually be exacerbating the damage caused by the flooding that is an inescapable fact of life for any river. This article (p. A390) examines the state of the water control system along the Mississippi River and discusses ideas for future improvement.
Commentary
GENE EXPRESSION | Gene and Protein Expression, Mobile Phones
Several articles have been published on genome-wide and/or proteome-wide response after exposure to radiofrequency (RF) fields whose signal and intensities were similar to or typical of those of currently used mobile telephones. These studies were performed using powerful high-throughput screening techniques (HTSTs) of transcriptomics and/or proteomics, which allow for the simultaneous screening of the expression of thousands of genes or proteins. Vanderstraeten and Verchaeve (p. 1131) reviewed these HTST-based studies and compared the results, in light of the recent concept of microwave-assisted chemistry, with currently accepted concepts about the effects of RF fields on gene expression.
Research
SKIN | DEHP Exposure during Neonatal Periods Enhances Atopic Dermatitis
Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and is ubiquitous in developed countries. Maternal exposure to DEHP during fetal and/or neonatal periods has been reported to affect reproductive and developmental systems, but its effects on allergic diseases in offspring have not been determined. Yanagisawa et al. (p. 1136) found that maternal exposure to DEHP during neonatal periods can accelerate atopic dermatitis-like skin lesions related to mite allergen in male offspring, possibly via T helper 2–dominant responses, which can be responsible, at least in part, for the recent increase in atopic dermatitis.
DENTAL HEALTH | Fluoride Inhibits Protein Secretion
Exposure to excessive amounts of fluoride (F–) causes dental fluorosis in susceptible individuals, but the mechanism of F–-induced toxicity is unclear. Sharma et al. (p. 1142) investigated whether low-dose F– causes endoplasmic reticulum (ER) stress and activates the unfolded protein response in ameloblasts that are responsible for dental enamel formation. They also investigated whether F– interferes with the secretion of proteins from the ER. Results suggest that F– initiates an ER stress response in ameloblasts that interferes with protein synthesis and secretion. Consequently, ameloblast function during enamel development may be impaired, and this may culminate in dental fluorosis.
RISK ASSESSMENT | Temporal Model for Effects of Air Pollution on Health
To determine whether worldwide expenditures to improve air quality improve human health, Shin et al. (p. 1147) estimated the risk of death associated with outdoor air pollution over both space and time in 24 of Canada's largest cities for the 17-year period 1984–2000. Despite decreasing ambient concentrations, public health risks related to nitrogen dioxide appear to be increasing. Further study is needed to understand why the concentrations and adverse effects of NO2 show opposite time trends.
PHYTOCHEMICALS | Identification of Oridonin as a Novel Nrf2 Activator
Groundwater contaminated with arsenic imposes a big challenge to human health worldwide, and using natural compounds to subvert the detrimental effects of arsenic is an attractive strategy. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical regulator of the cellular antioxidant response and xenobiotic metabolism. Du et al. (p. 1154) identified oridonin as representing a novel class of Nrf2 activators and illustrated the mechanism by which the Nrf2 pathway is activated. The study demonstrated the feasibility of using natural compounds targeting Nrf2 as a therapeutic approach to protect humans from various environmental insults.
BONE AND CARTILAGE | Bone Mineral Density and PCB Exposure
Bone toxicity has been linked to organochlorine exposure following a few notable poisoning incidents, but results have been inconsistent in epidemiologic studies in populations with environmental organochlorine exposure. Hodgson et al. (p. 1162) investigated whether organochlorine exposure was associated with bone mineral density (BMD) in a population (60–81 years of age) living near the Baltic coast of Sweden, close to a river contaminated by polychlorinated biphenyls (PCBs). Long-term environmental organochlorine exposures experienced by this population sample in Sweden may have been sufficient to result in sex-specific changes in BMD.
CARDIOVASCULAR DISEASE | Right Heart Pressure Changes and Ambient Particles
Rich et al. (p. 1167) explored the association between acute changes in daily mean pulmonary artery (PA) and right ventricular (RV) pressures and concentrations of ambient fine particulate matter [PM ≤ 2.5 µm in aerodynamic diameter (PM2.5)]. Using data from the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure trial, they calculated daily mean pressures and studied the association between mean daily PA/RV pressures and mean ambient PM2.5 concentrations on the same day and previous 6 days. Each 11.62-µg/m3 increase in same-day mean PM2.5 concentration was associated with small but significant increases in estimated PA diastolic pressure. These pilot study findings suggest a potential mechanism for increased risk of HF associated with ambient PM.
RISK ASSESSMENT | Ambient Air Pollution and Daily Mortality
Wuhan, China, called an "oven" city because of its hot summers, has approximately 4.5 million permanent residents living in the 201-km2 core area of the city. To investigate whether high temperatures in Wuhan modified the mortality effects of air pollution, Qian et al. (p. 1172) used data from 2001–2004 in a generalized additive model to analyze pollution, mortality, and covariate data. The estimates of the interaction between high temperature and air pollution were obtained from the main effects and pollutant–temperature interaction models. Results showed synergistic effects between PM10 and high temperatures on daily nonaccidental, cardiovascular, and cardiopulmonary mortality in Wuhan.
RISK ASSESSMENT | Mortality Effects of Particulate Matter in Bangkok
Air pollution data in Bangkok, Thailand, indicate that levels of particulate matter ≤ 10 µm in aerodynamic diameter (PM10) are significantly higher than in most cities in North America and Western Europe, where its health effects are well documented. However, the pollution mix, seasonality, and demographics are different from those in developed Western countries. Using air pollution measures and temperature and relative humidity information, Vichit-Vadakan et al. (p. 1179) investigated the mortality risk from air pollution in Bangkok, Results suggest strong associations between several mortality outcomes and PM10. In many cases the effect estimates were higher than those typically reported in Western industrialized nations.
RISK ASSESSMENT | Modifiers of Health Effects of Air Pollution
The health effects of outdoor air pollution may be modified by various factors, but findings about these modifiers are inconsistent, and most previous studies were conducted in developed countries. Kan et al. (p. 1183) conducted a time-series analysis to examine the modifying effect of season, sex, age, and education on the association between outdoor air pollutants (particulate matter ≤ 10 µm in aerodynamic diameter, sulfur dioxide, nitrogen dioxide, and ozone) and daily mortality in Shanghai, China. Season, sex, age, and education may modify the health effects of outdoor air pollution in Shanghai. The findings provide new information about the effects of modifiers on the relationship between daily mortality and air pollution in developing countries and may have implications for local environmental and social policies.
Also see Science Selections, p. A394
RISK ASSESSMENT | Deprivation and Association with Air Pollution Mortality
Poverty is a major determinant of population health, but little is known about its role in modifying effects of air pollution. Wong et al. (p. 1189) studied 209 tertiary planning units (TPUs), the smallest units for town planning in the Special Administrative Region of Hong Kong. The socioeconomic status of each TPU was measured by a social deprivation index (SDI) based on data from the 2001 Population Census. A time-series analysis with Poisson regression was performed to examine the association between changes in daily concentrations of ambient air pollution and daily number of deaths in each SDI group for January 1996–December 2002. Results showed that neighborhood socioeconomic deprivation increases mortality risks associated with air pollution.
RISK ASSESSMENT | Public Health and Air Pollution Association
The deleterious effects of air pollution from fossil fuel combustion have been demonstrated in many Western nations, but fewer studies have been conducted in Asia. The Public Health and Air Pollution in Asia (PAPA) project assessed the effects of short-term exposure to air pollution on daily mortality in Bangkok, Thailand, and in Hong Kong, Shanghai, and Wuhan, China. Using Poisson regression models incorporating natural spline smoothing functions to adjust for seasonality and other time-varying covariates, Wong et al. (p. 1195) determined effect estimates for each city and then for the cities combined using a random-effects method. In individual cities, associations were detected between most of the pollutants (nitrogen dioxide, sulfur dioxide, particulate matter ≤ 10 µm in aerodynamic diameter, and ozone) and most health outcomes under study (i.e., all natural-cause, cardiovascular, and respiratory mortality).
GENE EXPRESSION | Bioactivities of Triclocarban, Its Analogs, and Triclosan
Concerns have been raised about the biologic and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. To assess these antimicrobials for their potential for adverse effects in vitro, Ahn et al. (p. 1203) assessed the activity of TCC, its analogs, and TCS in nuclear-receptor–responsive and calcium signaling bioassays. Carbanilides (including TCC) enhanced hormone-dependent induction of estrogen receptor– and androgen receptor–dependent gene expression but had little agonist activity, suggesting a new mechanism of action of endocrine-disrupting compounds. TCS, structurally similar to noncoplanar ortho-substituted polychlorinated biphenyls, exhibited weak aryl hydrocarbon receptor activity but interacted with ryanodine receptor type 1 and stimulated Ca2+ mobilization.
NANOTECHNOLOGY | SWCNT-Induced Molecular Changes in Mesothelial Cells
Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. However, preliminary investigations have suggested that SWCNTs could potentially be toxic, biopersistent, pathogenic , and able to translocate to subpleural areas. Pacurari et al. (p. 1211) used normal mesothelial cells and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT. Findings suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies.
CARDIOVASCULAR DISEASE | Asbestos and Atherosclerosis in ApoE–/– Mice
Associations between air pollution and morbidity/mortality from cardiovascular disease are recognized in epidemiologic and clinical studies, but the mechanisms by which inhaled fibers or particles mediate the exacerbation of atherosclerosis are unclear. To determine whether lung inflammation after inhalation of a well-characterized pathogenic particulate, chrysotile asbestos, is directly linked to exacerbation of atherosclerosis and the mechanisms involved, Fukagawa et al. (p. 1218) exposed apolipoprotein E–deficient (ApoE–/–) mice and ApoE–/– mice crossed with CD4–/– mice to ambient air, a reference sample of chrysotile asbestos, or fine titanium dioxide. Results show that the degree of lung inflammation and fibrosis does not correlate directly with cardiovascular effects of inhaled asbestos fibers and support a critical role of CD4+ T cells in linking fiber-induced pulmonary signaling to consequent activation of activator protein-1– and nuclear factor-κB–regulated genes in atherogenesis.
RESPIRATORY DISEASE | Urinary Cadmium and Pulmonary Function
High-level cadmium exposure causes emphysema in occupationally exposed workers, but little has been reported to date on the association between chronic environmental cadmium exposure and pulmonary function. To examine the association between pulmonary function and cadmium body burden in a subcohort of the Normative Aging Study, Lampe et al. (p. 1226) used mixed-effect models to predict pulmonary function based on individual 24-hr urinary cadmium output, adjusted for age, height, time elapsed from the baseline, and smoking status. Findings suggest that chronic cadmium exposure is associated with reduced pulmonary function, and cigarette smoking modifies this association. Because of the small sample size, the results should be interpreted with caution.
ENDOCRINE SYSTEM | Effects of PCB/Dioxins on Thyroid Hormone Receptor
The health of humans and various animals may be adversely affected by polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans, possibly through the thyroid hormone (TH) system. To examine the functional TH receptor (TR) domain responsible for the PCB-mediated suppression of TR action, Miyazaki et al. (p. 1231) used chimeric receptors generated from TR and the glucocorticoid receptor, transient transfection-based reporter gene assays, and electrophoretic mobility shift assays. Findings show that PCBs acted on the DNA-binding domain of TR.
CARDIOVASCULAR DISEASE | Omega-3 PUFA, Oxidative Stress, and PM2.5
The mechanisms of particulate matter (PM)-induced health effects are believed to involve inflammation and oxidative stress, and increased intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) appears to have anti-inflammatory effects. Romieu et al. (p. 1237) measured biomarkers of response to oxidative stimuli (copper/zinc) superoxide dismutase activity, lipoperoxidation products, and reduced glutathione and evaluated the impact of supplementation on plasma levels. Supplementation with n-3 PUFA appeared to modulate the adverse effects of PM ≤ 2.5 µm in aerodynamic diameter (PM2.5) particularly in the fish oil group. Supplementation with n-3 PUFA could modulate oxidative response to PM2.5 exposure.
Also see Science Selections, p. A394
ENDOCRINE SYSTEM | Esfenvalerate Delays Puberty
Synthetic pyrethroids, a widely used class of insecticides, are less acutely toxic to humans than to insects; however, in vitro studies have suggested that pyrethroids may be estrogenic. Pine et al. (p. 1243) assessed pubertal effects by orally administering 0.5, 1.0, and 5.0 mg/kg/day of the type II pyrethroid esfenvalerate (ESF) to female rats from postnatal day 22 until vaginal opening. ESF administration suppressed serum estradiol and delayed onset of puberty. Although the hypothalamus was able to respond to exogenous stimuli, absence of a normal afternoon rise in luteinizing hormone indicate a hypothalamic deficit in ESF-treated animals.
Environmental Medicine
NEUROBEHAVIORAL DISEASE | World Trade Center Rescue Worker Mental Health Morbidity
The World Trade Center (WTC) disaster exposed thousands of workers to hazardous environmental conditions and psychological trauma. To assess the health of these workers, the WTC Medical Monitoring and Treatment Program recruited a large cohort of WTC rescue, recovery, and cleanup workers. Stellman et al. (p. 1248) describe the mental health outcomes, social function impairment, and psychiatric comorbidity in the WTC worker cohort, as well as perceived symptomatology in workers' children.
Also see Science Selections, p. A395
Children's Health
EXPOSURE SCIENCE | EPHT of Childhood Asthma Using CHIS Data
Despite extensive evidence that air pollution impacts childhood asthma, state- and national-level tracking of asthma outcomes in relation to air pollution is limited. Wilhelm et al. (p. 1254) evaluated the feasibility of linking the 2001 California Health Interview Survey (CHIS), air monitoring, and traffic data; estimated associations between traffic density or outdoor air pollutant concentrations and childhood asthma morbidity; and evaluated the usefulness of such databases, linkages, and analyses to environmental public health tracking (EPHT). Results showed that the CHIS provides a useful framework for examining air pollution and childhood asthma morbidity in support of EPHT, especially since later surveys address some noted gaps.
GENE POLYMORPHISM | Iron Metabolism Genes Predict Children´s Blood Lead
To investigate the association between iron deficiency and lead absorption, Hopkins et al. (p. 1261) hypothesized that variants in iron metabolism genes would predict higher blood lead levels in young children. They examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children and found that iron metabolism gene variants modify lead metabolism, such that HFE variants were associated with increased blood lead levels in young children. The joint presence of variant alleles in the HFE and TF genes showed the greatest effect, suggesting a gene-by-gene-by-environment interaction.
Also see Science Selections, p. A395
FETAL DEVELOPMENT | Birth Defects and Disinfection By-Products in Australia
Water supplies in Perth, Western Australia, contain high levels of trihalomethanes (THMs), particularly the brominated forms. Geographic variability in these levels provided an opportunity to examine cross-city spatial relationships between THM exposure and rates of birth defects. Chisholm et al. (p. 1267) examined birth defect rates by exposure to THMs with a highly brominated fraction in metropolitan locations in Perth. Brominated forms constituted the significant fraction of THMs in all areas. Small but statistically significant increases in risks of birth defects were associated with residence in areas with high THMs.
RESPIRATORY DISEASE | Residential Traffic and Children's Respiratory Health
Living near traffic has been associated with asthma and other respiratory symptoms. However, most studies have been conducted in areas with high background levels of ambient air pollution, making it challenging to isolate an independent effect of traffic, and they have used surrogates of exposure. Few of these studies have measured traffic pollutants directly as part of the study. Kim et al. (p. 1274) conducted a cross-sectional study of current asthma and other respiratory symptoms in children living at varying distances from high-traffic roads in the San Francisco Bay Area of California. Results showed associations between current asthma and residential proximity to traffic. Children whose residences were within the highest quintiles of several different traffic metrics had approximately twice the adjusted odds of current asthma compared with children whose residences were within the lowest quintiles.