Mercury

“A 52-year-old Caucasian woman was admitted to the hospital with high fever, sore throat, a rash over her entire body, itching, nausea, and extensive muscle pain. She had cervical, bilateral axillary and mediastinal lymphadenopathies. We learned that her son and husband had similar symptoms. After excluding infectious pathologies, autoimmune diseases and malignancy were investigated. Multiple organs of our patient were involved and her fever persisted at the fourth week of admission. A repeat medical history elicited that her son had brought mercury home from school and put it on the hot stove, and the family had been exposed to the fumes for a long period of time. Our patient’s serum and urine mercury levels were high. She was diagnosed with mercury poisoning and treated accordingly.”

“BACKGROUND:
Previously we have shown that acute exposure to thimerosal (Thi) can induce oxidative stress and DNA damage in a human conjunctival cell line. However, the long-term effect of Thi on Chang conjunctival cells is not clear. Therefore, the aim of this study was to further investigate the fate of the cells after acute exposure to Thi.

METHOD:
Cells were first exposed to various concentrations of Thi (0.00001 %???0.001 %) for 30 min, and then cells were assessed after a 24-h recovery period. Morphologic changes were observed under a light microscope and cell viability was evaluated. Cell apoptosis, cell cycle distribution and mitochondrial membrane potential (MMP) (rhodamine 123 assay) were detected by flow cytometry analysis. Poly (ADP-ribose) polymerase (PARP), activation of caspase-3 and microtubule-associated protein light chain 3 (LC-3) were examined by western blot analysis.

RESULTS:
DNA strand breaks were significantly increased in a dose-dependent manner with 30 min exposure to Thi, although no significant cell death was detected. However, after 24-h recovery, the ratio of apoptotic cells was significantly increased to 0.0005 % and 0.001 % in Thi treated groups (p?<?0.001 compared to the control group). Apoptosis was confirmed by the cleavage of PARP and caspase-3 activation. In addition, G2/M cell cycle arrest and decrease of MMP were recorded. Finally, the LC-3 results indicated the occurrence of autophagy in Thi-treated cells.

CONCLUSION:
Acute exposure to Thi can induce DNA damage, and eventually can lead to cell death, probably through the caspase-dependent apoptosis pathway, while autophagy might also be involved.”

“In order to reveal the time-depending mercury species uptake by human astrocytes, a novel approach for total mercury analysis is presented, which uses an accelerated sample introduction system combined on-line with an inductively coupled plasma mass spectrometer equipped with a collision/reaction cell. Human astrocyte samples were incubated with inorganic mercury (HgCl2), methylmercury chloride (MeHgCl), and thimerosal. After 1-h incubation with Hg(2+), cellular concentrations of 3 ?M were obtained, whereas for organic species, concentrations of 14-18 ?M could be found. After 24 h, a cellular accumulation factor of 0.3 was observed for the cells incubated with Hg(2+), whereas the organic species both showed values of about 5. Due to the obtained steady-state signals, reliable results with relative standard deviations of well below 5 % and limits of detection in the concentration range of 1 ng L(-1) were obtained using external calibration and species-unspecific isotope dilution analysis approaches. The results were further validated using atomic fluorescence spectrometry.”

“In this work, human whole blood and physiological simulation solutions were incubated with thimerosal to investigate its behaviour and binding partners in the blood stream. Inductively coupled plasma with optical emission spectrometry (ICP-OES) was used for total mercury determination in different blood fractions, while liquid chromatography (LC) coupled to electrospray ionisation time-of-flight (ESI-TOF) and inductively coupled plasma-mass spectrometry (ICP-MS) provided information on the individual mercury species in plasma surrogate samples. Analogous behaviour of methylmercury and ethylmercury species in human blood was shown and an ethylmercury-glutathione adduct was identified.”

“The Nrf family of transcription factors mediates adaptive responses to stress and longevity, but the identities of the crucial Nrf targets, and the tissues in which they function in multicellular organisms to promote survival, are not known. Here, we use whole transcriptome RNA sequencing to identify 810 genes whose expression is controlled by the SKN-1/Nrf2 negative regulator WDR-23 in the nervous system of Caenorhabditis elegans. Among the genes identified is the synaptic cell adhesion molecule nlg-1/neuroligin. We find that the synaptic abundance of NLG-1 protein increases following pharmacological treatments that generate oxidative stress or by the genetic activation of skn-1. Increasing nlg-1 dosage correlates with increased survival in response to oxidative stress, whereas genetic inactivation of nlg-1 reduces survival and impairs skn-1-mediated stress resistance. We identify a canonical SKN-1 binding site in the nlg-1 promoter that binds to SKN-1 in vitro and is necessary for SKN-1 and toxin-mediated increases in nlg-1 expression in vivo. Together, our results suggest that SKN-1 activation in the nervous system can confer protection to organisms in response to stress by directly regulating nlg-1/neuroligin expression.”

“The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co-genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl)ation contributes to organic Hg induced neurotoxicity.”

Methodology: A literature search was conducted on PubMed using the keywords dementia, dementia syndrome, Alzheimer disease, Alzheimer type dementia, exposure, neurotoxicity aluminium, mercury, pesticide. After reading all of the abstracts and ruling out irrelevant articles, only relevant articles in English or French were selected. We read more than 600 abstracts and based on these we selected and read 352 articles, 176 for each of the two authors. Finally, our bibliography includes 78 articles.
Results: The neurotoxicity data from animal experiments are old, and in the professional environment there is no evidence regarding the gradient of environmental toxicity. Synergistic, multiple-factor neurotoxicity is complex and difficult to document epidemiologically as it is due to a cumulative toxic continuum rather than a dose/effect relationship. Within this recognized multi-causal model of neurodegenerative diseases, particularly Alzheimer disease, chronic exposure to neurotoxic products has a real pathogenic effect on the central nervous system though certain aspects of this effect are not entirely proven.”

“Workplace conditions are directly reflected on the health of dental practitioners which in turn influences the quality of the medical services. Using a complementary approach our study aimed to determine the elemental composition, morphology and size distribution of non-microbial particles present in the air of a dental office, during various dental treatments, in order to identify and analyse potential risk factors for the human health. The samples were collected on carbon double adhesive tape – an original and very efficient particle collecting method. The aerosols produced during various treatments were analysed using the X–ray photoelectron spectroscopy (XPS), scanning electronic microscopy (SEM) and energy dispersive X-ray analysis (EDX). To the best of our knowledge, the present study is the first one to use the combination of these methods in studying dental aerosols. Using the highly sophisticated equipment allowed to augment the accuracy of our findings and helped to identify various types of elements, some of which were not reported in previous studies dealing with a similar problematic. Our results underline the aerosols potential of deeply penetrating into the respiratory system, even to the level of pulmonary alveoli, and thereby they represent serious health threats for the practitioners and patients.”

“Adverse reactions to dental materials occur and public interest in this topic has increased during recent decades.  Thus, improving the biocompatibility of dental materials is necessary and must be based on several strategies. First, a strategy for improving the administrative and technical conditions for material certification processes should be included, such as the development of in vitro tests with enhanced predictability of the generated data for use in the clinic. Second, research on material/tissue interactions must be enhanced and include mechanistic approaches, as this strategy leads to the development of new and more biocompatible materials. Research into patients and their individual exposure situation is a strategy directed at better defining risk groups. Finally, improvement of education will also lead to improved biocompatibility of dental materials.”