PM2.5 Extracts Induce INFγ-Independent Activation of CIITA, MHCII, and Increases Inflammation in Human Bronchial Epithelium.

The capacity of particulate matter (PM) to enhance and stimulate the expression of pro-inflammatory mediators has been previously demonstrated in non-antigen-presenting cells (human bronchial epithelia). Nonetheless, many proposed mechanisms for this are extrapolated from known canonical molecular pathways. This work evaluates a possible mechanism for inflammatory exacerbation after exposure to PM2.5 (from Puerto Rico) and CuSO4, using human bronchial epithelial cells (BEAS-2B) as a model. The induction of CIITA, MHCII genes, and various pro-inflammatory mediators was investigated. Among these, the phosphorylation of STAT1 Y701 was significantly induced after 4 h of PM2.5 exposure, concurrent with a slight increase in CIITA and HLA-DRα mRNA levels. INFγ mRNA levels remained low amidst exposure time, while IL-6 levels significantly increased at earlier times. IL-8 remained low, as expected from attenuation by IL-6 in the known INFγ-independent inflammation pathway. The effects of CuSO4 showed an increase in HLA-DRα expression after 8 h, an increase in STAT1 at 1 h, and RF1 at 8 h We hypothesize and show evidence that an inflammatory response due to PM2.5 extract exposure in human bronchial epithelia can be induced early via an alternate non-canonical pathway in the absence of INFγ.

Distribution of toxic metals and relative toxicity of airborne PM2.5 in Puerto Rico.

The exposure to airborne particulate matter (PM) and its constituents is an important factor to be considered when evaluating their potential health risk. Transition metals found in PM are known to contribute significantly to the exacerbation of respiratory ailments. Exposure to these constituents results in the induction of oxidative stress in the bronchial epithelium, thus promoting the secretion of inflammatory mediators. Therefore, it is important to know the contributions of PM2.5 constituents to further investigate their relationship with toxic responses and associated health risks. PM2.5 samples from three rural (Humacao, Guayama, and Guayanilla) and two urban (more populated) sites (Bayamón and Ponce) from Puerto Rico were analyzed for various inorganic constituents. A total of 59 trace elements were analyzed, of which eight were considered with the greatest toxic potential. The highest annual average concentration of PM2.5 was reported at the urban site of Ponce (5.82 ± 1.40 µg m-3), while Bayamón's average concentration was not as high (4.69 ± 1.30 µg m-3) compared to concentrations at the rural sites Humacao, Guayama, and Guayanilla (4.33 ± 1.20 µg m-3, 4.93 ± 1.50 µg m-3, and 4.88 ± 1.20 µg m-3 respectively. The concentration at the Ponce site exhibited the highest summer value (7.57 µg m-3) compared to that of all the rural sites (~ 6.40 µg m-3). The lowest summer PM2.5 values were obtained at the Humacao site with an average of 5.76 µg m-3. Average Cu and Zn concentrations were 3- and 2-fold higher at the urban sites (0.68 ng m-3 and 6.74 ng m-3 respectively) compared to the rural sites (0.17 ng m-3 and 4.11 ng m-3). Relative toxicity of inorganic PM extract indicates Bayamón (urban) and Guayama with similar low LC50 followed by Humacao, Guayanilla, and finally Ponce (urban) with the highest LC50. Of the eight potential toxic metals considered, only Fe was found to be higher at the rural sites. To our understanding, there are different sources of emission for these metals which potentially indicate main anthropogenic sources, together with the trade winds adding periodically volcanic and African Dust Storm particulates that affect Puerto Rico. These results are the first of their kind to be reported in Puerto Rico.

Rethinking the Dental Amalgam Dilemma: An Integrated Toxicological Approach.

Mercury (Hg) has been identified as one of the most toxic nonradioactive materials known to man. Although mercury is a naturally occurring element, anthropogenic mercury is now a major worldwide concern and is an international priority toxic pollutant. It also comprises one of the primary constituents of dental amalgam fillings. Even though dental mercury amalgams have been used for almost two centuries, its safety has never been tested or proven in the United States by any regulatory agency. There has been an ongoing debate regarding the safety of its use since 1845, and many studies conclude that its use exposes patients to troublesome toxicity. In this review, we present in an objective way the danger of dental amalgam to human health based on current knowledge. This dilemma is addressed in terms of an integrated toxicological approach by focusing on four mayor issues to show how these interrelate to create the whole picture: (1) the irrefutable constant release of mercury vapor from dental amalgams which is responsible for individual chronic exposure, (2) the evidence of organic mercury formation from dental amalgam in the oral cavity, (3) the effect of mercury exposure on gene regulation in human cells which supports the intrinsic genetic susceptibility to toxicant and, finally, (4) the availability of recent epidemiological data supporting the link of dental amalgams to diseases such as Alzheimer's and Parkinson.

Toxic Metals Depuration Profiles from a Population Adjacent to a Military Target Range (Vieques) and Main Island Puerto Rico.

Background: The island of Vieques (a municipality of Puerto Rico) was used as a military practice range by the US Navy for more than 60 years. Many studies have reported the presence of toxic metals in soil samples taken from Vieques. The bombing range is only 18 km upwind from the Vieques residential area and inhalable resuspended particles resulting from bombing are known to reach the populated area. The current study reports for the first time, the presence of toxic metals' depuration profiles obtained from Vieques and Main Island Puerto Rico human subjects. Objectives: This study was designed to evaluate the distribution of toxic metals in a random population exposed to contaminants originating from military activities and comparing it to a non-exposed random population from Main Island Puerto Rico. Methods: A total of 83 subjects studied; 32 were from Vieques and 51 were from Main Island Puerto Rico. A physician administrated chelation therapy to all subjects and collected urine samples during a 24-h period. A total of 20 trace elements associated with military activities were measured in urine by induced coupled plasma mass spectrometry (ICP-MS). The results were compared between both population samples. Results: Significant differences in the levels of eight trace elements associated with military practices were found between Vieques and Main Island Puerto Rico. Lead (Pb), aluminum (Al), uranium (U) (p < 0.001), arsenic (As), cadmium (Cd) (p = 0.02), and gadolinium (Gd) (p = 0.03) were significantly higher in Vieques while niobium (Nb) and platinum (Pt) levels (p < 0.006) were lower in the Vieques samples. Discussion: Higher concentrations of Pb, Al, As, Cd, Gd, and U were found in Vieques residents' urine samples compared to Main Island. Nonetheless, Pt and Ga were present in Main Island at higher concentrations than in Vieques. Although limited by its sample size, this report should set a basis for the importance of health assessment in these subjects exposed to military activities remnants throughout the years and further evaluation of their effects on the overall health of the population.