Differential gene expression associated with inflammation and blood pressure regulation induced by concentrated ambient particle exposure

Epidemiological studies have indicated that exposure to particle matter (PM) increased the risk of respiratory and cardiovascular morbidity and mortality. It is suggested that PM smaller than 2.5 μm in aerodynamic diameter (PM_2.5) may contribute to these responses. However, the molecular mechanism is still unknown. To elucidate the changes in molecular level, we investigated the gene expression profile of concentrated ambient particles (CAPs)-exposed rats. Aged F344 rats were exposed with CAPs (594 μg/m³) or clean air 4?h per day for 3 days, and lung and heart tissues were then excised for DNA microarray analysis. Expression profiles related to inflammation and blood pressure regulation revealed differential expression of 7 genes in the lung and that of 3 genes in the heart ventricle. According to the complement activation-associated genes, complement factor B (Bf), complement component 2 and 4a (C4a), and C1 inhibitor genes were up-regulated in CAPs-exposed rat lung. Bf and C4a genes were also up-regulated in the heart. These suggest the treated animal ready for production of these proteins when activation of complement cascade is required. Pro-inflammatory cytokine, interleukin-1β, was also up-regulated in CAPs-exposed rat lung. Gene related with blood pressure regulation (angiotensin I converting enzyme) was also up-regulated in CAPs-exposed rat lung. Negative regulator of blood pressure (neuropeptide Y) was down-regulated in CAPs-exposed rat heart. These results indicate that CAPs may affect respiratory and cardiovascular organs by activation of inflammatory responses and disintegration of blood pressure regulation in early stage of CAPs exposure.     

Sinus CT Scan Findings in Patients with Chronic Cough Following Sulfur Mustard Inhalation: A Case-Control Study

Sinusitis is one of the most common causes of chronic cough, which is the most common manifestation among patients exposed to sulfur mustard (SM). We conducted our study on exposed victims to SM with chronic cough for evaluation of probable sinus abnormality. In a case-control study, among referred patients for evaluation of persistent chronic cough, 39 patients with previous and 35 patients without previous history of exposure to SM underwent paranasal sinus computed tomography (CT) scans (Somatom CR CT scanner) in coronal planes. A well-designed standard pro forma was used for reporting sinus CT abnormalities. Data was analyzed with chi-square and Fisher exact test. Except one, all obtained CT scans findings showed some abnormalities. Mucosal abnormality was detected in 30 chemical-exposed cases (CEs) (76.9%), and 8 cases were categorized as severe types. In general, mucosal thickening in right (left) frontal, sphenoid, and maxillary sinus were observed in 12.8% (7.7), 5.1% (7.7), and 25.6% (30.8) of CEs, respectively; these proportions were 11.4% (11.4), 2.9% (2.9), and 45.6% (60) in non-chemical-exposed cases (NEs), respectively. Air fluid level in the right (left) frontal sinus was 10.3% (7.7) and in the right (left) maxillary sinus was 10.3% (15.4) in CEs; it was 2.9%(0) and 20%(20) in NEs for these locations, respectively. There were no statistically significant differences between findings of two groups (p > .05). Also, comparison of related data to osteomeatal complex obstruction, bulla ethmoidalis, haller cell, agger nasi, and pneumatized crista galli were not significant (p > .05). Thus; various types of sinus abnormalities were highly prevalent in both CEs and NEs with chronic chough and there was no specific pattern. Consequently, current approaches to chronic cough just based on conventional etiologies in this setting can lead to delay in diagnosis and mismanagement.     

The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells

Abstract

Introduction: The discovery of endothelial progenitor cells (EPCs) may help to explain observed cardiovascular effects associated with inhaled nickel nanoparticle exposures, such as increases in vascular inflammation, generation of reactive oxygen species, altered vasomotor tone and potentiated atherosclerosis in murine species.

Methods: Following an acute whole body inhalation exposure to 500?µg/m³ of nickel nanoparticles for 5?h, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells (CEPCs), circulating endothelial cells (CECs) and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the exposure.

Results and conclusions: Acute exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation (CEPCs). CECs were significantly elevated indicating that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. These results coincided with a decrease in the mRNA of receptors involved in EPC mobilization and homing. These data provide new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration (OSHA) permissible exposure limit may adversely affect EPCs and exacerbate cardiovascular disease states.     

Negligible respiratory irritation and inflammation potency of pigmentary TiO2 in mice

Abstract

Titanium dioxide (TiO₂) is manufactured in millions of tons yearly, and it is used widely as pigment in various applications. Until recently, TiO₂ was considered toxicologically harmless and without adverse health effects. In this study, respiratory irritation and inflammation potencies of commercially available pigmentary TiO₂ particles (<5?µm, rutile) were studied. Single head-only exposures (30?min) of male Crl:OF1 mice at mass concentrations 6, 11, 21, and 37?mg/m³, and repeated exposures (altogether 16?h, 1?h/day, 4 days/week for 4 weeks) of female BALB/c/Sca mice at mass concentration of 16?mg/m³ to pigmentary TiO₂ were conducted. Minor sensory irritation was observed during acute and repeated exposures seen as elongation of the break after the inhalation, which is typical in sensory irritation, and caused by closure of the glottis inhibiting airflow from the lungs after inspiration. No pulmonary irritation, airflow limitation, nasal or pulmonary inflammation was observed. In conclusion, the respiratory irritation and inflammation potencies of the studied pigmentary TiO₂ particles seemed to be low and thus can serve as an ideal control exposure agent in short-term studies in mice.     

Oxidative Stress in Smokers and Non-smokers

Oxidative stress plays an important role in the pathogenesis of some diseases such as lung cancer, chronic obstructive pulmonary disease, and atheroscleorosis. Smoking may enhance oxidative stress not only through the production of reactive oxygen radicals in smoke but also through weakening of the antioxidant defense systems. In this study, we investigated the effects of smoking on lipid peroxidation and paraoxonase activity in a healthy population. The study consisted of (n = 30) smokers and (n = 30) nonsmokers. The age of the population which is studied was 44.74 ± 10.59 yr. The levels of serum malondialdehyde (MDA) and paraoxonase (PON1) activities were measured by the modified Buege method and the Eckerson method, respectively. Student's t-test was used to analyze the data. The serum MDA levels were significantly higher (p < .05) and serum PON1 activities were significantly lower (p < .001) in smokers than in nonsmokers. Thus, increased levels of serum MDA and decreased PON1 activities may be important in determining the oxidant/antioxidant imbalance in smokers.     

The Health Relevance of Ambient Particulate Matter Characteristics: Coherence of Toxicological and Epidemiological Inferences

The aim of this article is to review progress toward integration of toxicological and epidemiological research results concerning the role of specific physicochemical properties, and associated sources, in the adverse impact of ambient particulate matter (PM) on public health. Contemporary knowledge about atmospheric aerosols indicates their complex and variable nature. This knowledge has influenced toxicological assessments, pointing to several possible properties of concern, including particle size and specific inorganic and organic chemical constituents. However, results from controlled exposure laboratory studies are difficult to relate to actual community health results because of ambiguities in simulated PM mixtures, inconsistent concentration measurements, and the wide range of different biological endpoints. The use of concentrated ambient particulates (CAPs) coupled with factor analysis has provided an improved understanding of biological effects from more realistic laboratory-based exposure studies. Epidemiological studies have provided information concerning sources of potentially toxic particles or components, adding insight into the significance of exposure to secondary particles, such as sulfate, compared with primary emissions, such as elemental and organic carbon from transportation sources. Recent epidemiological approaches incorporate experimental designs that take advantage of broadened speciation monitoring, multiple monitoring stations, source proximity designs, and emission intervention. However, there continue to be major gaps in knowledge about the relative toxicity of particles from various sources, and the relationship between toxicity and particle physicochemical properties. Advancing knowledge could be facilitated with cooperative toxicological and epidemiological study designs, with the support of findings from atmospheric chemistry.     

Endotracheal aerosolization of atropine sulfate protects against soman-induced acute respiratory toxicity in guinea pigs

The efficacy of endotracheal aerosolization of atropine sulfate for protection against soman (GD)-induced respiratory toxicity was investigated using microinstillation technique in guinea pigs. GD (841?mg/m³, 1.3 LCt₅₀ or 1121?mg/m³, 1.7 LCt₅₀) was aerosolized endotracheally to anesthetized male guinea pigs that were treated with atropine sulfate (5.0?mg/kg) 30 s postexposure by endotracheal microinstillation. Animals exposed to 841?mg/m³ and 1121?mg/m³GD resulted in 31 and 13% while treatment with atropine sulfate resulted in 100 and 50% survival, respectively. Cholinergic symptoms and increased body weight loss were reduced in atropine-treated animals compared to GD controls. Diminished pulse rate and blood O₂ saturation in GD-exposed animals returned to normal levels after atropine treatment. Increased cell death, total cell count and protein in the bronchoalveolar fluid (BALF) in GD-exposed animals returned to normal levels following atropine treatment. GD exposure increased glutathione and superoxide dismutase levels in BALF and that were reduced in animals treated with atropine. Respiratory parameters measured by whole-body barometric plethysmography revealed that treatment with atropine sulfate resulted in normalization of respiratory frequency, tidal volume, time of expiration, time of inspiration, end expiratory pause, pseudo lung resistance (Penh) and pause at 4 and 24?h post 841?mg/m³ GD exposure. Lung histopathology showed that atropine treatment reduced bronchial epithelial subepithelial inflammation and multifocal alveolar septal edema. These results suggest that endotracheal aerosolization of atropine sulfate protects against respiratory toxicity and lung injury induced by microinstillation inhalation exposure to lethal doses of GD.     

Long-term responses of canine lungs to acidic particles

Sixteen beagle dogs were housed in four large chambers under minimum restraint. They were exposed for 16 months to clean air and individual baseline data of markers were obtained. For 13 months, eight dogs were further exposed to clean air and eight dogs for 6?h/d to 1-μm MMAD (mass median aerodynamic diameter) acidic sulfate particles carrying 25?μmol H⁺ m^?3 into their lungs. To establish functional responses (lung function, cell and tissue integrity, redox balance, and non-specific respiratory defense capacity), each exposed animal served as its own control. To establish structural responses, the eight non-exposed animals served as controls. Acidic particles were produced by nebulization of aqueous sodium hydrogen sulfate at pH 1.5. Only subtle exposure-related changes of lung function and structure were detected. A significant increase in respiratory burst function of alveolar macrophages points to a marginal inflammatory response. This can be explained by the significant production of prostaglandin E₂, activating cyclooxygenase-dependent mechanisms in epithelia and thus inhibiting lung inflammation. The non-specific defense capacity was slightly affected, giving increased tracheal mucus velocity and reduced in vivo dissolution of moderately soluble test particles. Hypertrophy and hyperplasia of bronchial epithelia were not observed, but there was an increase in volume density of bronchial glands and a shift from neutral to acidic staining of epithelial secretory cells in distal airways. The acidic exposure had thus no pathophysiological consequences. It is therefore unlikely that long-term inhalation of acidic particles is associated with a health risk.     

Nanoparticles-containing spray can aerosol: characterization,exposure assessment,and generator design

This is the first report demonstrating that a commercially available household consumer product produces nanoparticles in a respirable range. This report describes a method developed to characterize nanoparticles that were produced under typical exposure conditions when using a consumer spray product. A well-controlled indoor environment was simulated for conducting spray applications approximating a human exposure scenario. Results indicated that, while aerosol droplets were large with a count median diameter of 22 µm during spraying, the final aerosol contained primarily solid TiO₂ particles with a diameter of 75?nm. This size reduction was due to the surface deposition of the droplets and the rapid evaporation of the aerosol propellant. In the breathing zone, the aerosol, containing primarily individual particles (>90%), had a mass concentration of 3.4?mg/m³, or 1.6?×?10⁵ particles/cm³, with a nanoparticle fraction limited to 170 µg/m³, or 1.2?×?10⁵ particles/cm³. The results were used to estimate the pulmonary dose in an average human (0.075 µg TiO₂ per m² alveolar epithelium per minute) and rat (0.03 µg TiO₂) and, consequently, this information was used to design an inhalation exposure system. The system consisted of a computer-controlled solenoid ‘‘finger’’ for generating constant concentrations of spray can aerosols inside a chamber. Test results demonstrated great similarity between the solenoid ‘‘finger’’-dispersed aerosol compared to human-generated aerosol. Future investigations will include an inhalation study to obtain information on dose–response relationships in rats and to use it to establish a No Effect Exposure Level for setting guidelines for this consumer product.     

Ambient Exposure to Criteria Air Pollutants and Risk of Death from Bladder Cancer in Taiwan

To investigate the relationship between air pollution and risk of death from bladder cancer, the authors conducted a matched case-control study using deaths that occurred in Taiwan from 1995 through 2005. Data on all eligible bladder cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of people who died from causes other than cancer or diseases associated with genitourinary problems. The controls were pair matched to the cases by sex, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Classification of exposure to municipality air pollution was based on the measured levels of nitrogen dioxide and sulfur dioxide. The results of the present study show that there is a significant positive association between the levels of air pollution and bladder cancer mortality. The adjusted odds ratios (95% confidence interval) were 1.37 (1.03–1.82) for the group with medium air pollution level and 1.98 (1.36–2.88) for the group with high air pollution level when compared to the group with the low air pollution level. Trend analyses showed statistically significant trend in risk of death from bladder cancer with increasing air pollution level. The findings of this study warrant further investigation of the role of air pollutants in the etiology of bladder cancer.