Diagnosis and treatment of metal-induced side-effects

Environmental factors are recognized as a cause of the increasing frequency of allergic and autoimmune diseases. In addition to external pollutants, metal ions released from dental restorations or from other body implants might trigger inflammation in susceptible subjects. In humans, genes governing metal-induced inflammation and autoimmunity are not yet known. In clinical praxis, metal-sensitive patients will present various symptoms ranging from oral mucosal changes and skin disease to excessive fatigue and autoimmune diseases. Since genetic markers of genetic susceptibility in man are not known, one has to rely on the phenototypic markers. Such biomarkers might be certain detoxification enzymes but also the presence of metal-specific memory cells in the blood. With the increasing use of metal implants in medicine and dentistry, it is important to have a proper tool for the diagnosis of metal allergy in susceptible subjects. After nickel, gold is now the second most common sensitizer. In addition to patch test, an in vitro blood test, an optimized commercially available lymphocyte transformation test (MELISA) is discussed. Both tests were used for the diagnosis of metal allergy in a selected group of 15 patients who suffered from clinical metal sensitivity in addition to other health problems. The concordance of the two tests was good but MELISA detected more metal allergies than patch test. The removal of incompatible dental material (RID) resulted in long-term health improvement in the majority of patients. We postulate that in vivo, metal ions activate T-cells, initiating systemic inflammation, which, through cytokines, affects the brain and hypothalamus-pituitary-adrenal axis. We postulate that in vivo metal ions will activate T-cells starting systemic inflammation which, through cytokines affect the brain and hypothalamus-pituitary-adrenal (HPA) axis. The treatment and rehabilitation of metal sensitive patients is based on a firm understanding and recognition of individual susceptibility. RID has to be done done with extreme caution and according to standard working protocol. If performed properly, this treatment can result in decreased systemic inflammation and improved health in sensitized patients.     

Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease

BackgroundConnective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CTD often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD.MethodsThirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögren's syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA^® (Memory Lymphocyte Immuno Stimulation Assay).ResultsIn all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (P < 0.0001). The most frequent allergens were nickel, mercury, gold and palladium.ConclusionsPatients with SLE, RA and SS have an increased frequency of metal DTH. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in CTDs, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies.     

The immune profile of contact allergy patients

Nonspecific parameters of antibody-related and cellular immune responses were studied in a group of 30 patients treated for manifest contact allergy to metals (chromium, cobalt, nickel) or non-metals (epoxy resin, rubber) confirmed in each of them by specific patch test positivity. In addition, every patient was tested for the pattern of skin reactivity to the Immunoskintest (USOL, Prague) antigens administered intradermally. The group of 20 metal allergy patients had decreased suppressor index values, enhanced formation of immediate active rosettes and an elevation of serum IgM and IgA immunoglobulins. The remaining 10 patients reacted by a reduced ability of neutrophils to exert phagocytic action on HEMA particles and a decrease in levels of alpha-2-macroglobulins in serum. This may help select a series of suitable immune parameters to be used as prediction tests in the secondary prevention of cases of occupational contact dermatitis.     

Reaction to stainless steel wire following orthognathic surgery.

A patient is reported in whom, following orthognathic surgery, developed a bilateral burning sensation and pain along the masseteric muscles and preauricular region in the sight of the mandibular osteotomy where the lateral segment was tied to the medial segment using a single wire loop. This patient also had previous Kirschner wires used for a metatarsal osteotomy that needed to be removed because of similar symptoms. Removal of the mandibular wires resulted in elimination of the symptoms from the mandibular region as well. The patient's subsequent skin test proved a nickel allergy.     

Nickel induces apoptosis in human neutrophils

Nickel is an ubiquitous transition metal that is industrially applied in many forms, which inevitably leads to a high degree of occupational and environmental exposure. Over-exposure to nickel can produce a variety of adverse effects on human health, including allergy and lung and nasal cancers. In the present study, it is demonstrated, for the first time, that nickel [(Ni(II)] (as a nickel nitrate salt) at concentrations that may be attained in vivo, induces neutrophils’ apoptosis by the intrinsic pathway. The use of diphenyleneiodonium, a NADPH oxidase inhibitor, delayed Ni(II)-induced apoptosis, suggesting that NADPH oxidase-derived reactive oxygen species and subsequent signaling could contribute to this event. This is an important finding since increased apoptosis mediated by nickel may disrupt the physiological activities of neutrophils, with potential impact in its immunological and antimicrobial role.     

Trace metals in oral mucosa in relation to the lichen ruberplanus pathology. A preliminary study carried out by neutron activation analysis.

Lichen ruberplanus, contact allergy and hypersensitivity can be linked to oral exposure to metals released from metal alloys commonly used in dentistry. In this context neutron activation analysis was developed for the microdetermination of 36 elements in oral mucosa biopsies of two patients affected by lichen ruber planus and of five subjects as control group. In order to minimise metal contamination during sample collection, biopsies were taken by laser bistoury technique and then submitted to radiochemical neutron activation analysis (RNAA). Among the metals analysed, chromium showed obvious high concentration in gingival biopsies of the two pathological subjects compared to the corresponding tissues of control group. Cobalt and nickel were also determined in higher concentrations, but only in one of the oral mucosa of the two patients. The present findings way support the hypothesis concerning a potential link of lichen ruber planus condition with the exposure to Cr, Co and Ni as released into oral cavity from prosthodontic alloys.     

Trace metals in oral mucosa in relation to the lichen ruber planus pathology. A preliminary study carried out by neutron activation analysis

Lichen ruber planus, contact allergy and hypersensitivity can be linked to oral exposure to metals released from metal alloys commonly used in dentistry. In this context neutron activation analysis was developed for the microdetermination of 36 elements in oral mucosa biopsies of two patients affected by lichen ruber planus and of five subjects as control group.In order to minimise metal contamination during sample collection, biopsies were taken by laser bistoury technique and then submitted to radiochemical neutron activation analysis (RNAA).Among the metals analysed, chromium showed obvious high concentration in gingival biopsies of the two pathological subjects compared to the corresponding tissues of control group. Cobalt and nickel were also determined in higher concentrations, but only in one of the oral mucosa of the two patients.The present findings way support the hypothesis concerning a potential link of lichen ruber planus condition with the exposure to Cr, Co and Ni as released into oral cavity from prosthodontic alloys.     

Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study

BackgroundA cross-sectional study has reported that nickel allergy is associated with endometriosis. However, causal studies of this association are limited.ObjectiveThe objective of this study was to compare the prevalence of nickel allergy in women with and without endometriosis.MethodsWe used a National Health Insurance Service (NHIS) sample cohort dataset that included approximately 1 million individuals from South Korea; the data were obtained between January 01, 2002, and December 31, 2013. We selected the endometriosis group according to diagnosis code (N80.X), surgery codes, and drug codes during the years 2009~2013. The controls were randomly matched to the endometriosis patients at a ratio of 4:1 by age and socioeconomic status. Patients with nickel allergy were defined in the cohort dataset as those with a simultaneous diagnosis code (L23.0) and patch test code during 2002~2008.ResultsIn total, 4,985 women were selected from the NHIS cohort database and divided into an endometriosis group (997 women) and a control group (3,988 women). The number of patients with nickel allergy in the endometriosis group was eight (0.8%), and that in the control group was thirteen (0.3%). After adjustment for age and socioeconomic status, the rate of nickel allergy in was higher in the endometriosis group than in the control group [odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044].ConclusionsWe found that nickel allergy is a risk factor for endometriosis.     

Lead Exposure: A Contributing Cause of the Current Breast Cancer Epidemic in Nigerian Women

The paper discusses various approaches used to investigate biocompatibility by the analysis of metals release by the materials of which orthodontic appliances are made. Analysis of various biomarkers of exposure: saliva, serum, mucosa cells, or urine is used in in vivo tests. In this work, the techniques, results, and conclusions of original papers were compared by the implementation of the concept of a systematic review. The aim of the present work was to report the state-of-the-art in the research on methods used to assess exposure to trace metals from orthodontic appliances. The PubMed search identified 35 studies, among which nine met the selection criteria. The general conclusion in the studies was that metal ions were released mostly in the initial stage of the treatment. However, the majority of studies included 1–2 months long period and did not reflect long-term changes nor the impact of the complete treatment, the duration of which is several years, on the whole organism and the overall accumulation of metals from orthodontic appliances. In studies which evaluated nickel concentrations in blood and urine, long-term metal release was detected and significant differences were found. It leads to the conclusion that nickel ions are released from orthodontic appliances in measurable amounts to human organism.     

Investigation of Vetiver Grass Capability in Phytoremediation of Contaminated Soils with Heavy Metals (Pb,Cd, Mn,and Ni)

ABSTRACT

Soil contamination with heavy metals has become a worldwide concern. A sustainable technology to mitigate heavy metal contamination is extremely important. Phytoremediation is a cost-effective method, environmentally friendly, and esthetically pleasing. The aim of this study was to investigate the potential of Vetiver phytoremediation of soils contaminated with heavy metals. This research was conducted as a factorial design with four different heavy metals (lead, cadmium, manganese, and nickel) with three varying levels and also three replications for each treatment. Statistical analysis of data was performed using SPSS19 software and analysis of variance, Duncan and Pearson correlation tests. The results showed that, the highest uptake rate was related to lead metal with 282.45 mg/kg of dry soil and 83.4% uptake percentage. Then, the mean and percentage of adsorption for cadmium, nickel and manganese were 248.3 mg/kg (53.2%), 69.4 mg/kg (65.5%), and 63.29 mg/kg (61%), respectively. Lead was found to be the main component of uptake by Vetiver plant. It was found that the roots of the plant have absorbed more heavy metals than the shoots. And at the roots in total 1089.05 and on average 363.01 mg/kg and at the shoots 901.19 and on average 300.39 mg/kg, the metals used were adsorbed on three levels and four treatments. The results of analysis of variance, Duncan test and Pearson correlation showed that the effect of applied treatments on lead uptake in roots and shoots increased significantly (P ≤ 0.05) with increasing levels of treatments. The biological concentration factor was more than one, and the transfer factor was close to one. Therefore, it can be used as a phytostablization plant. The results showed that Vetiver can be considered as a refining plant due to its vegetative characteristics, cost-effectiveness and high adaptation to environmental conditions.     

Exposure to nickel, chromium, or cadmium causes distinct changes in the gene expression patterns of a rat liver derived cell line

Many heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays. We identified both common and unique biological responses to exposure to the three metals. Nickel, cadmium, chromium all induced oxidative stress with both similar and unique genes and pathways responding to this stress. Although all three metals are known to be genotoxic, evidence for DNA damage in our study only exists in response to chromium. Nickel induced a hypoxic response as well as inducing genes involved in chromatin structure, perhaps by replacing iron in key proteins. Cadmium distinctly perturbed genes related to endoplasmic reticulum stress and invoked the unfolded protein response leading to apoptosis. With these studies, we have completed the first gene expression comparative analysis of nickel, cadmium, and chromium in H4-II-E-C3 cells.     

In Vitro Penetration of Pig Skin by Heavy Metals in Soil

The potential health risk from exposure to heavy metal contaminated soil is often based on the quantity of metal that can be removed from soil by vigorous extraction procedures. This approach can overestimate risk since it ignores complex interactions between metals and soil that can result in a reduction in the amount of metal that desorbs from soil and is subsequently absorbed by the body. The aim of this research was to determine the relative contribution of the soil matrix and heavy metal sequestration in soil with time (“aging”) on the dermal penetration of arsenic, mercury, and nickel, respectively, as arsenic acid, mercuric chloride, and nickel chloride. In vitro flow-through diffusion cell studies were performed utilizing dermatomed male pig skin and radioactive compounds to measure total penetration (the sum of each metal in receptor fluid and skin). For arsenic and nickel, the soil matrix produced a 78–87% reduction in dermal penetration compared to 12–19% after aging. A greater effect was observed with aged mercury (52–56% decrease in dermal penetration) than in freshly spiked soil (40–43%). The results indicate that the potential health risk from dermal exposure to the metals can be significantly reduced by soil and aging.     

Effect of yeast extract on speciation and bioavailability of nickel and cobalt in anaerobic bioreactors

The speciation of metals plays an important role in their bioavailability. In the case of anaerobic reactors for the treatment of wastewaters, the ubiquitous presence of sulfide leads to extensive precipitation of metals like nickel and cobalt, which are essential for the metabolism of the anaerobic microorganisms that carry out the mineralization of the pollutants present in the wastewater. In practice, nickel, cobalt, and iron are added in excessive amounts to full-scale installations. This study is concerned with the complexation of nickel and cobalt with yeast extract and its effect on the biogas production by methanogenic biomass. Adsorptive stripping voltammetry (AdSV) was used to get information about the stability and complexing capacity of the metal-yeast extract complexes formed. Nickel and cobalt form relatively strong organic complexes with yeast extract. The bioavailability of these essential metals in anaerobic batch reactors was dramatically increased by the addition of yeast extract. This is due to the formation of dissolved bioavailable complexes, which favors the dissolution of metals from their sulfides. Trace doses of yeast extract may be effective in keeping additions of essential metals to anaerobic reactors at a minimum.     

Genetic and cellular mechanisms in chromium and nickel carcinogenesis considering epidemiologic findings

Genetic and environmental interactions determine cancer risks but some cancer incidence is primarily a result of inherited genetic deficits alone. Most cancers have an occupational, viral, nutritional, behavioral or iatrogenic etiology. Cancer can sometimes be controlled through broad public health interventions including industrial hygiene and engineering controls. Chromium and nickel are two human carcinogens associated with industrial exposures where public health measures apparently work. Carcinogenic mechanisms of these metals are examined by electron-spin-resonance-spectroscopy and somatic-mutation-and-recombination in Drosophila melanogaster in this report. Both metals primarily affect initiation processes in cancer development suggesting important theoretical approaches to prevention and followup.     

Metal ions in biological catalysis: from enzyme databases to general principles

We analysed the roles and distribution of metal ions in enzymatic catalysis using available public databases and our new resource Metal-MACiE (). In Metal-MACiE, a database of metal-based reaction mechanisms, 116 entries covering 21% of the metal-dependent enzymes and 70% of the types of enzyme-catalysed chemical transformations are annotated according to metal function. We used Metal-MACiE to assess the functions performed by metals in biological catalysis and the relative frequencies of different metals in different roles, which can be related to their individual chemical properties and availability in the environment. The overall picture emerging from the overview of Metal-MACiE is that redox-inert metal ions are used in enzymes to stabilize negative charges and to activate substrates by virtue of their Lewis acid properties, whereas redox-active metal ions can be used both as Lewis acids and as redox centres. Magnesium and zinc are by far the most common ions of the first type, while calcium is relatively less used. Magnesium, however, is most often bound to phosphate groups of substrates and interacts with the enzyme only transiently, whereas the other metals are stably bound to the enzyme. The most common metal of the second type is iron, which is prevalent in the catalysis of redox reactions, followed by manganese, cobalt, molybdenum, copper and nickel. The control of the reactivity of redox-active metal ions may involve their association with organic cofactors to form stable units. This occurs sometimes for iron and nickel, and quite often for cobalt and molybdenum. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Impact of fluorides on the removal of heavy metals from an electroplating effluent using a flocculent brewer’s yeast strain of Saccharomyces cerevisiae

Abstract

Besides several toxic heavy metals, electroplating effluents can have in solution different cations and anions, which may influence heavy metals removal by the biomass. Among them, fluorides are commonly used in the electroplating industries and thus can be found in the respective wastewaters. In the present work, the effect of the presence of fluorides in the efficiency of chromium(III), copper(II) and nickel(II) removal, from an effluent, by heat-inactivated cells of a brewing flocculent strain of Saccharomyces cerevisiae was evaluated. The presence of fluorides severely decreased (>60%) the removal of chromium(III) by yeast biomass. This effect impaired the effective treatment of the effluent according to the US Environmental Protection Agency and the Portuguese law; conversely, a higher removal of copper(II) and nickel(II) was observed. This behaviour can be understood by metal speciation. In the presence of fluorides, chromium(III) was mainly complexed, becoming unavailable for yeast accumulation; this effect decreased the efficiency of chromium(III) removal. Thus, in the presence of fluorides, less chromium(III) is associated with biomass and consequently more yeast binding sites remain available for the uptake of other metals present in solution. This fact explains the increase of copper(II) and nickel(II) removal in the presence of fluorides.     

Do metals inhibit acetylcholinesterase (AChE)? Implementation of assay conditions for the use of AChE activity as a biomarker of metal toxicity.

The enzymatic activity of acetylcholinesterase (AChE) has been shown to be altered by environmental contaminants such as metals. However, the available literature illustrates a background of contradictory results regarding these effects. Therefore, the main purpose of this study was to investigate the potential of five metal ions (nickel, copper, zinc, cadmium and mercury) to inhibit AChE activity in vitro. First, to accomplish this objective, the possible interference of metals as test toxicants in the Ellman's assay, which is widely used to assess AChE activity, was studied. The potential influence of two different reaction buffers (phosphate and Tris) was also determined. The results suggest that the selected metals react with the products of this photometric technique. It is impossible to ascertain the artefactual contribution of the interaction of the metals with the technique when measuring AChE inhibition. This constitutes a major obstacle in obtaining accurate data. The presence of phosphate ions also makes enzymatic inhibition difficult to analyse. Attending to this evidence, an assay using the substrate o-nitrophenyl acetate and Tris buffer was used to investigate the effects of metals on AChE activity. O-nitrophenyl acetate is also a substrate for esterases other than cholinesterases. It is therefore only possible to use it for the measurement of cholinesterase activity with purified enzymes or after a previous verification of the absence of other esterases in the sample tissue. Under these conditions, the results indicate that with the exception of nickel, all tested metals significantly inhibit AChE activity.     

Degradation of Alyssum murale biomass in soil

The Ni-hyperaccumulating plant Alyssum murale accumulates exceptionally high concentrations of nickel in its aboveground biomass. The reasons for hyperaccumulation remain unproven; however, it has been proposed that elemental alelopathy might be important. High-Ni leaves shed by the plant may create a "toxic zone" around the plant where germination or growth of competing plants is inhibited. The efficacy of this argument will partially depend upon the rate at which leaves degrade in soil and free metals are released, and the subsequent rate at which metals are bound to soil constituents. To test the degradation of biomass of hyperaccumulators, A. murale was grown on both high- and low-Ni soils to achieve high- (12.0 g Ni/kg) and low- (0.445 g Ni/kg) Ni biomass. Shredded leaf and stem biomass were added to a serpentine soil from Oregon that was originally used to grow high-Ni biomass and a low-Ni control soil from Maryland. Biomass Ni was readily soluble and extractable, suggesting near immediate release as biomass was added to soil Extractable nickel in soil amended with biomass declined rapidly over time due to Ni binding in soil These results suggest that Ni released from biomass of Ni hyperaccumulators may significantly affect their immediate niche only for short periods of time soon after leaf fall, but repeated application may create high Ni levels under and around hyperaccumulators.