The aim of this epidemiologic study was to point out a relationship between the exposure to products of coal combustion, and complications in pregnancy where one third of causes of stillbirth are still unknown. In the town of Labin (Croatia) a coal-powered thermoelectric power plant is the single major air polluter. We compared the records of miscarriages, premature births and stillbirths in two periods: the control and the exposure period. Data on reproductive loss was based on the records of pregnant women visiting for regular monthly pregnancy checkups. At the time of the epidemiological prospective study, 260 women (n = 138 in the clean period and n = 122 in the dirty period) were considered representative. The data were processed using Chi square and correlation tests. The frequencies of miscarriages and stillbirths were significantly lower in the control than in the exposure period (p < 0.05). Methemoglobinemia and stillbirths recorded over the “exposure” period are significantly higher than in the “control” period (p = 0.0205). The level of methemoglobin in the bloodstream is an worthy biomarker, predictor and precursor of environmental toxics’ adverse effects on the mother and fetus, and can indirectly explain the unrecognized level of fetal methemoglobin. Methemoglobin and heme, having prooxidant properties, also cause the early and late endothelial dysfunction of vital organs. Despite our retrospective epidemiological study findings, we emphasize that the rate of reproductive loss represents a hypothetical risk, which needs to be confirmed with further fetal clinical and anatomopatholgical researches about the effects of methemoglobin catabolism products on the fetal CNS. Full article

In non-ideal scenarios involving partial or non-breastfeeding, cow’s milk-based dairy products are mainstream in infant feeding. Therefore, it is important to study the concentrations of potentially neurotoxic contaminants (Pb and Cd) and their respective counteracting elements (Ca and Zn) in infant dairy products. Fifty-five brands of infant formulas and milk sold in Brasilia, Brazil were analyzed. The dairy products came from areas in the central-west (26%), southeast (29%) and south of Brazil (36%) extending as far as Argentina (7%) and the Netherlands (2%). For toxic Pb and Cd, median concentrations in powdered samples were 0.109 mg/kg and 0.033 mg/kg, respectively; in fluid samples median Pb concentration was 0.084 mg/kg, but median Cd concentration was below the limit of detection and overall values were below reference safety levels. However, 62% of these samples presented higher Pb concentration values than those established by FAO/WHO. Although the inverse correlation between Cd and Zn (Spearman r = −0.116; P = 0.590) was not statistically significant, the positive correlation between Ca and Pb was (Spearman r = 0.619; P < 0.0001). Additionally, there was a significant correlation between Pb and Cd. Furthermore, the study also revealed that provision of the essential trace element Zn in infant formulas can provide adequate amounts of the recommended daily requirements. Infant formulas and milk sold for consumption by infants and children can be an efficient tool to monitor neurotoxic metal risk exposure among young children. Full article

Susceptibility to prostate or endometrial cancer is linked with obesity, a state of oestrogen excess. Oestrogen receptor (ER) splice variants may be responsible for the tissue-level of ER activity. Such micro-environmental regulation may modulate cancer initiation and/or progression mechanisms. Real-time reverse transcriptase (RT) polymerase chain reaction (PCR) was used to quantitatively assess the levels of four ER splice variants (ERαΔ3, ERαΔ5, ERβ2 and ERβ5), plus the full-length parent isoforms ERα and ERβ1, in high-risk [tumour-adjacent prostate (n = 10) or endometrial cancer (n = 9)] vs. low-risk [benign prostate (n = 12) or endometrium (n = 9)], as well as a comparison of UK (n = 12) vs. Indian (n = 15) benign prostate. All three tissue groups expressed the ER splice variants at similar levels, apart from ERαΔ5. This splice variant was markedly raised in all of the tumour-adjacent prostate samples compared to benign tissues. Immunofluorescence analysis for ERβ2 in prostate tissue demonstrated that such splice variants are present in comparable, if not greater, amounts as the parent full-length isoform. This small pilot study demonstrates the ubiquitous nature of ER splice variants in these tissue sites and suggests that ERαΔ5 may be involved in progression of prostate adenocarcinoma. Full article

Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products), considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC) studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS). These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and vulva; glandular epithelium of the prostate; and cytotrophoblast cells and syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA adduct accumulation in specific, vulnerable, cell types. This semi-quantative method for PAH-DNA adduct measurement could potentially see widespread use in molecular epidemiology studies. Full article

The immune response plays an important role in the pathophysiology of numerous diseases including asthma, autoimmunity and cancer. Application of biomarkers of immunotoxicity in epidemiology studies and human clinical trials can improve our understanding of the mechanisms that underlie the associations between environmental exposures and development of these immune-mediated diseases. Immunological biomarkers currently used in environmental health studies include detection of key components of innate and adaptive immunity (e.g., complement, immunoglobulin and cell subsets) as well as functional responses and activation of key immune cells. The use of high-throughput assays, including flow cytometry, Luminex, and Multi-spot cytokine detection methods can further provide quantitative analysis of immune effects. Due to the complexity and redundancy of the immune response, an integrated assessment of several components of the immune responses is needed. The rapidly expanding field of immunoinformatics will also aid in the synthesis of the vast amount of data being generated. This review discusses and provides examples of how the identification and development of immunological biomarkers for use in studies of environmental exposures and immune-mediated disorders can be achieved. Full article

Procedures for risk assessment of chemical mixtures, combined and cumulative exposures are under development, but the scientific database needs considerable expansion. In particular, there is a lack of knowledge on how to monitor effects of complex exposures, and there are few reviews on biomonitoring complex exposures. In this review we summarize articles in which biomonitoring techniques have been developed and used. Most examples describe techniques for biomonitoring effects which may detect early changes induced by many chemical stressors and which have the potential to accelerate data gathering. Some emphasis is put on endocrine disrupters acting via epigenetic mechanisms and on carcinogens. Solid evidence shows that these groups of chemicals can interact and even produce synergistic effects. They may act during sensitive time windows and biomonitoring their effects in epidemiological studies is a challenging task. Full article

The neurotoxic effects of fish-methylmercury (meHg) consumed regularly are considered hazardous to fetuses and newborn infants; as a result fish consumption advisories are an important asset to control meHg exposure in affluent societies. These concerns are now part of health promotion programs for Amazon subsistence villagers. While urban dwellers in affluent societies can choose an alternative nutritious diet, traditional and subsistence communities are caught up in controversial issues and lifestyle changes with unintended health consequences. Traditional fish-eating populations of industrialized and non-industrialized regions may be exposed to different neurotoxic substances: man-made pollutants and environmentally occurring meHg. Additionally, in non-industrialized countries, pregnant women and infants are still being immunized with thimerosal-containing vaccines (TCVs) which degrade to ethylmercury (etHg). Therefore, the complexity involving fish-meHg associated with wild-fish choices and Hg exposure derived from TCVs is difficult to disentangle and evaluate: are villagers able to distinguish exposure to differently hazardous chemical forms of Hg (inorganic, fish-meHg, and injected etHg)? Is it possible that instead of helping to prevent a plausible (unperceived) fish-meHg associated neurocognitive delay we may inadvertently arouse panic surrounding Hg exposure and disrupt subsistence fish-eating habits (necessary for survival) and life-saving vaccination programs (required by public health authorities)? These questions characterize the incompleteness of information related on the various chemical forms of Hg exposure and the need to convey messages that do not disrupt nutritional balance and disease prevention policies directed at Amazonian subsistence communities. Full article