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About Arnhold F, Gührs KH, von Mikecz A.

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So far Arnhold F, Gührs KH, von Mikecz A. has created 1044 blog entries.

Amyloid domains in the cell nucleus controlled by nucleoskeletal protein lamin B1 reveal a new pathway of mercury neurotoxicity.

“Mercury (Hg) is a bioaccumulating trace metal that globally circulates the atmosphere and waters in its elemental, inorganic and organic chemical forms. While Hg represents a notorious neurotoxicant, the underlying cellular pathways are insufficiently understood. We identify amyloid protein aggregation in the cell nucleus as a novel pathway of Hg-bio-interactions. By mass spectrometry of purified protein aggregates, a subset of spliceosomal components and nucleoskeletal protein lamin B1 were detected as constituent parts of an Hg-induced nuclear aggregome network. The aggregome network was located by confocal imaging of amyloid-specific antibodies and dyes to amyloid cores within splicing-speckles that additionally recruit components of the ubiquitin-proteasome system. Hg significantly enhances global proteasomal activity in the nucleus, suggesting that formation of amyloid speckles plays a role in maintenance of protein homeostasis. RNAi knock down showed that lamin B1 for its part regulates amyloid speckle formation and thus likewise participates in nuclear protein homeostasis. As the Hg-induced cascade of interactions between the nucleoskeleton and protein homeostasis reduces neuronal signalling, amyloid fibrillation in the cell nucleus is introduced as a feature of Hg-neurotoxicity that opens new avenues of future research. Similar to protein aggregation events in the cytoplasm that are controlled by the cytoskeleton, amyloid fibrillation of nuclear proteins may be driven by the nucleoskeleton.”

By |2018-03-08T23:36:14+00:00January 1st, 2015|Mercury|

Low doses of mercuric chloride cause the main features of antinucleolar autoimmune process in female outbred CFW mice.

“The growth of the influence of anthropogenic factors aimed on the improvement of human life has its side effect, for example, living organisms receive increasing exposure to toxic mercuric compounds. Experimental data show that mercury (Hg) salts are able to induce systemic autoimmunity in rodents. This Hg-induced autoimmune process (HgIA) is characterized by T cell-dependent polyclonal activation of B lymphocytes, increased level of serum immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), production of antinucleolar autoantibodies (ANoA), and immune complex deposition in multiple organs. HgIA in mice is used as a model of human systemic autoimmune disorders. However, the dose of mercuric chloride (HgCl2) usually used in laboratory mice to induce HgIA is above the allowable limit for everyday levels of Hg exposure in humans. So, we decided to determine the lowest dose of HgCl2 that is able to trigger autoimmunity in outbred Carworth Farms Swiss Webster (CFW) mice not genetically prone to HgIA development. The lowest dose (50 µg/kg body weight (b.w.)/week) was chosen to match the World Health Organization provisional weekly tolerable intake of total Hg for humans. We also tested HgCl2 at 500 and 1500 µg/kg b.w./week (6.5- and 2-fold less than usually used for induction of HgIA in mice). We found that even the lowest dose of Hg resulted in a statistically significant increase in serum level of IgG1 after 8 weeks of treatment. HgCl2 in doses 500 and 1500 µg/kg b.w./week resulted in a significant increase in serum level of IgG1 after 4 weeks of treatment, followed by ANoA production. Sera of HgCl2-treated mice stained the regions in which the major autoantigen in HgIA, fibrillarin, was revealed. These results suggest that low doses of Hg are able to induce the main features of HgIA in genetically heterozygous mice, and that humans chronically exposed to low doses of Hg may be at risk of autoimmunity induction regardless of their genetic background.”

By |2018-03-08T23:25:20+00:00January 1st, 2015|Mercury|

A longitudinal cohort study of the relationship between Thimerosal-containing hepatitis B vaccination and specific delays in development in the United States: Assessment of attributable risk and lifetime care costs.

“Epidemiological evidence suggests a link between mercury (Hg) exposure from Thimerosal-containing vaccines and specific delays in development. A hypothesis-testing longitudinal cohort study (n=49,835) using medical records in the Vaccine Safety Datalink (VSD) was undertaken to evaluate the relationship between exposure to Hg from Thimerosal-containing hepatitis B vaccines (T-HBVs) administered at specific intervals in the first 6 months of life and specific delays in development [International Classification of Disease, 9th revision (ICD-9): 315.xx] among children born between 1991 and 1994 and continuously enrolled from birth for at least 5.81years. Infants receiving increased Hg doses from T-HBVs administered within the first month, the first 2months, and the first 6 months of life were significantly more likely to be diagnosed with specific delays in development than infants receiving no Hg doses from T-HBVs. During the decade in which T-HBVs were routinely recommended and administered to US infants (1991-2001), an estimated 0.5-1million additional US children were diagnosed with specific delays in development as a consequence of 25 μg or 37.5 μg organic Hg from T-HBVs administered within the first 6 months of life. The resulting lifetime costs to the United States may exceed $1 trillion.

 

Opinion on environmental risks and indirect health effects of mercury from dental amalgam.

“Most aspects of the mercury life cycle are addressed in the Community Strategy Concerning Mercury which key aim is to reduce mercury levels both in relation to human exposure and the environment. Pursuant to Action 6 of the Strategy, the use of dental amalgam should be evaluated with a view to considering whether additional regulatory measures are appropriate.”

FDA stands by its dental amalgam mistake.

“After another of its customary multi-year stalls on politically fraught issues, FDA in January substantially denied three five-year-old petitions seeking to rid American dentistry of mercury-based dental amalgams that have been scientifically linked to kidney damage and neurological disabilities and diseases like multiple sclerosis and Alzheimer’s.”

By |2018-04-17T20:27:37+00:00January 1st, 2015|Mercury|

Assess the amount of mercury in the urine of dentists in the Khorramabad city and their effective factors.

“Thirty experienced dentist with work experience is examined randomly, and a questionnaire containing questions about personal details such as age and experience, compliance or non-compliance personal hygiene, type of amalgam-consumption, conditioning and characteristics of work place of dentists was completed by them. From this people were collected the 60 urine samples during two phases and once a month. After sample preparation and digestion, by cold vapor atomic absorption system, mercury concentration in the samples was measured in terms of µg/L. To analyze the obtained data used SPSS and normalized tests, t two samples, t one sample, multivariate regression and one-way variance.”

By |2018-04-17T19:56:18+00:00January 1st, 2015|Mercury|

Combined exposure to lead, inorganic mercury and methylmercury shows deviation from additivity for cardiovascular toxicity in rats.

“Environmental exposure to metal mixtures in the human population is common. Mixture risk assessments are often challenging because of a lack of suitable data on the relevant mixture. A growing number of studies show an association between lead or mercury exposure and cardiovascular effects. We investigated the cardiovascular effects of single metal exposure or co-exposure to methylmercury [MeHg(I)], inorganic mercury [Hg(II)] and lead [Pb(II)]. Male Wistar rats received four different metal mixtures for 28 days through the drinking water. The ratios of the metals were based on reference and environmental exposure values. Blood and pulse pressure, cardiac output and electrical activity of the heart were selected as end-points. While exposure to only MeHg(I) increased the systolic blood pressure and decreased cardiac output, the effects were reversed with combined exposures (antagonism). In contrast to these effects, combined exposures negatively affected the electrical activity of the heart (synergism). Thus, it appears that estimates of blood total Hg levels need to be paired with estimates of what species of mercury dominate exposure as well as whether lead co-exposure is present to link total blood Hg levels to cardiovascular effects. Based on current human exposure data and our results, there may be an increased risk of cardiac events as a result of combined exposures to Hg(II), MeHg(I) and Pb(II). This increased risk needs to be clarified by analyzing lead and Hg exposure data in relation to cardiac electrical activity in epidemiological studies. “

By |2018-07-11T16:06:42+00:00January 1st, 2015|Mercury|

Elevated levels of antibodies against xenobiotics in a subgroup of healthy subjects.

“In spite of numerous research efforts, the exact etiology of autoimmune diseases remains largely unknown. Genetics and environmental factors, including xenobiotics, are believed to be involved in the induction of autoimmune disease. Some environmental chemicals, acting as haptens, can bind to a high-molecular-weight carrier protein such as human serum albumin (HSA), causing the immune system to misidentify self-tissue as an invader and launch an immune response against it, leading to autoimmunity. This study aimed to examine the percentage of blood samples from healthy donors in which chemical agents mounted immune challenges and produced antibodies against HSA-bound chemicals. The levels of specific antibodies against 12 different chemicals bound to HSA were measured by ELISA in serum from 400 blood donors. We found that 10% (IgG) and 17% (IgM) of tested individuals showed significant antibody elevation against aflatoxin-HSA adduct. The percentage of elevation against the other 11 chemicals ranged from 8% to 22% (IgG) and 13% to 18% (IgM). Performance of serial dilution and inhibition of the chemical-antibody reaction by specific antigens but not by non-specific antigens were indicative of the specificity of these antibodies. Although we lack information about chemical exposure in the tested individuals, detection of antibodies against various protein adducts may indicate chronic exposure to these chemical haptens in about 20% of the tested individuals. Currently the pathological significance of these antibodies in human blood is still unclear, and this protein adduct formation could be one of the mechanisms by which environmental chemicals induce autoimmune reactivity in a significant percentage of the population.”

By |2018-07-10T15:25:34+00:00January 1st, 2015|Mercury|

The statistical reporting quality of articles published in 2010 in five dental journals.

“METHODS: A total of 200 articles published in 2010 were analysed covering five dental journals: Journal of Dental Research, Caries Research, Community Dentistry and Oral Epidemiology, Journal of Dentistry and Acta Odontologica Scandinavica. Each paper underwent careful scrutiny for the use of statistical methods and reporting. A paper with at least one poor reporting item has been classified as ‘problems with reporting statistics’ and a paper without any poor reporting item as ‘acceptable’.

RESULTS:
The investigation showed that 18 (9%) papers were acceptable and 182 (91%) papers contained at least one poor reporting item.”

By |2018-07-09T21:57:09+00:00January 1st, 2015|Other|
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