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The influence of cobalt speciation on the toxicity of cobalt to methylotrophic methanogenesis in anaerobic granular sludge was investigated. The cobalt speciation was studied with three different media that contained varying concentrations of complexing ligands [carbonates, phosphates and ethylenediaminetetraacetic acid (EDTA)]. Three fractions (nominal added, dissolved and free) of cobalt were determined in the liquid media and were correlated with data from batch toxicity experiments. The average concentration of cobalt that was required for 50% inhibition of methanogenic activity (IC50) for free Co2+ in the three sets of measurements was 13 μmol/L with a standard deviation of 22% and a similarity of 72% between the data obtained in the three different media for the range of cobalt concentrations investigated. The standard deviation of the IC50 for the other two fractions was much higher, i.e. 85 and 144% for the added cobalt and dissolved cobalt, respectively, and the similarity was almost 0% for both fractions. Complexation (and precipitation) with EDTA, phosphates and carbonates was shown to decrease the toxicity of cobalt on methylotrophic methanogenesis. The free cobalt concentration is proposed to be the key parameter to correlate with cobalt toxicity. Thus, the toxicity of cobalt to granular sludge can be estimated based on the equilibrium-free cobalt concentration. [ABSTRACT FROM AUTHOR]

Background  The first series of cobalt cardiomyopathy was described in the 60s in relation to the abuse of a cobalt containing beer. Since then, millions of metal hip arthroplasties have been performed and a small number of cobalt cardiomyopathies related to metal prosthesis have been reported. Case summary  We report a case of a 48-year-old man who developed a severe non-dilated restrictive cardiomyopathy in the setting of a systemic metallosis following several hip arthroplasties. The diagnosis was suspected by exclusion of other more common causes for restrictive cardiomyopathies and confirmed by the levels of cobalt and chromium in the serum and the endomyocardial biopsy performance that showed metal deposits in myocardial tissue. Despite the removal of the metal prosthesis and a significant decrease in serum metal levels, he suffered cardiogenic shock (CS) and electric storm that required emergency mechanical circulatory support as a bridge to heart transplant. Discussion  Cobalt cardiomyopathy is a rare condition that has been observed in patients who develop cobalt toxicity after metal hip arthroplasty. The condition may improve after diagnosis and removal of the prosthesis or get worse and progress to end-stage heart failure or CS. The concern about the metal toxicity associated with metal hip prosthesis has increased in the last few years. Orthopaedic surgeons and cardiologists should be aware of this severe complication that is probably under diagnosed. [ABSTRACT FROM AUTHOR]

Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2αΔ/Δ) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2αΔ/Δ mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2αΔ/Δ and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung. [ABSTRACT FROM AUTHOR]

A 61-year-old previously healthy woman developed progressive hearing and visual loss over a period of 2-3 months prior to admission. Her medical/surgical history was remarkable for a left hip arthroplasty 11 years ago requiring revision approximately 6 months prior to admission. After dislocating the revised hip, she re-presented to her surgeon and underwent a closed reduction. Several weeks following the reduction, the patient began having polyuria and symptoms of hearing and vision loss along with numbness in her extremities and abdominal region. [ABSTRACT FROM AUTHOR]

Aims: This paper aims to quantify the growth and organic acid production of Aspergillus niger, Penicillium chrysogenum and Penicillium simplicissimum when these fungi are exposed to varying levels of lithium (Li) and cobalt (Co). The study also tests whether pre‐exposing the fungi to these metals enables the fungi to develop tolerance to Li or Co. Methods and Results: When cultures of A. niger, P. chrysogenum or P. simplicissimum were exposed to 250 mg l–1 of Li or Co, biomass production and excretion of organic acids were significantly inhibited after 5 days of growth compared to cultures grown in the absence of these metals. Pre‐exposing cultures of A. niger to 250 mg l–1 of Li or Co for 20 days significantly increased biomass production when the fungus was subsequently sub‐cultured into 250 or 500 mg l–1 of Li or Co. However, pre‐exposure of P. chrysogenum or P. simplicissimum to 250 mg l–1 of Li or Co for 20 days did not increase biomass production. Conclusions: Aspergillus niger, but not the Penicillium species, developed tolerance to Li and to Co during the 20‐day pre‐exposure period. Therefore, processes that utilize fungal bioleaching with A. niger to mobilize and recover valuable metals such as Li or Co should consider a pre‐exposure step for fungi to improve their tolerance to metal toxicity. Significance and Impact of the Study: Fungi may have the ability to extract valuable metals such as Li and Co from spent rechargeable batteries. However, the toxicity of the extracted metals can inhibit fungal growth and organic acid production. Pre‐exposure to metals may alleviate toxicity for some fungal species. This knowledge can be used to improve the design of bioleaching protocols, increasing the potential for fungal bioleaching to become an economical and environmentally friendly method of recovering Li and Co from spent batteries. [ABSTRACT FROM AUTHOR]

Nutritional immunity is a powerful strategy at the core of the battlefield between host survival and pathogen proliferation. A host can prevent pathogens from accessing biological metals such as Mg, Fe, Zn, Mn, Cu, Co or Ni, or actively intoxicate them with metal overload. While the importance of metal homeostasis for the enteric pathogen Salmonella enterica Typhimurium was demonstrated many decades ago, inconsistent results across various mouse models, diverse Salmonella genotypes, and differing infection routes challenge aspects of our understanding of this phenomenon. With expanding access to CRISPR-Cas9 for host genome manipulation, it is now pertinent to re-visit past results in the context of specific mouse models, identify gaps and incongruities in current knowledge landscape of Salmonella homeostasis, and recommend a straight path forward towards a more universal understanding of this historic host–microbe relationship. A comprehensive overview of the importance of metal uptake and resistance mechanisms during Salmonella infections. [ABSTRACT FROM AUTHOR]

Excess cobalt may lead to metallosis, characterized by sensorineural hearing loss, visual, and cognitive impairment, and peripheral neuropathy. In the present study, we sought to address the molecular mechanisms of cobalt-induced neurotoxicity, using Caenorhabditis elegans as an experimental model. Exposure to cobalt chloride for 2 h significantly decreased the survival rate and lifespan in nematodes. Cobalt chloride exposure led to increased oxidative stress and upregulation of glutathione S-transferase 4. Consistently, its upstream regulator skn-1 , a mammalian homolog of the nuclear factor erythroid 2-related factor 2, was activated. Among the mRNAs examined by quantitative real-time polymerase chain reactions, apoptotic activator egl-1 , proapoptotic gene ced-9 , autophagic (bec-1 and lgg-1), and mitochondrial fission regulator drp-1 were significantly upregulated upon cobalt exposure, concomitant with mitochondrial fragmentation, as determined by confocal microscopy. Moreover, drp-1 inhibition suppressed the cobalt chloride-induced reactive oxygen species generation, growth defects, and reduced mitochondrial fragmentation. Our novel findings suggest that the acute toxicity of cobalt is mediated by mitochondrial fragmentation and drp-1 upregulation. [ABSTRACT FROM AUTHOR]

Based on the wide use of cobalt substances in a range of important technologies, it has become important to predict the toxicological properties of new or lesser-studied substances as accurately as possible. We studied a group of 6 cobalt substances with inorganic ligands, which were tested for their bioaccessibility (surrogate measure of bioavailability) through in vitro bioelution in simulated gastric and intestinal fluids. Representatives of the group also underwent in vivo blood kinetics and mass balance tests, and both oral acute and repeated dose toxicity (RDT) testing. We were able to show a good correlation between high in vitro bioaccessibility with high in vivo bioavailability and subsequent high in vivo toxicity; consequently, low in vitro bioaccessibility correlated well with low in vivo bioavailability and low in vivo toxicity. In vitro bioelution in simulated gastric fluid was the most precise predictor of the difference in the oral RDT lowest observed adverse effect levels of 2 compounds representing the highly and poorly bioaccessible subset of substances. The 2 compounds cobalt dichloride hexahydrate and tricobalt tetraoxide differed by a factor of 440 in their in vitro bioaccessibility and by a factor of 310 in their RDT lowest observed adverse effect level. In summary, this set of studies shows that solubility, specifically in vitro bioelution in simulated gastric fluid, is a good, yet conservative, predictor of in vivo bioavailability and oral systemic toxicity of inorganic cobalt substances. Bioelution data are therefore an invaluable tool for grouping and read across of cobalt substances for hazard and risk assessment. [ABSTRACT FROM AUTHOR]

The use of electronic cigarettes (ECs) has been on the rise with increased number of battery explosions causing burns. This study is a retrospective review of patients who presented with burns caused by EC explosions.Here, we present a case series of eight patients sustaining burns from EC explosions, within a year, to elucidate the pattern of such burns and to provide a treatment guideline.All of them were males. Five patients had partial-thickness burns and three had full-thickness burns. TBSA ranged from 4 to 16% (burns to lower extremity [n = 7], hand [n =3], scrotum/penis [n =2], chest [n = 1]). None had inhalation injuries. Two patients (29%) required skin grafting. EC explosion is predominantly attributed to its lithium-ion battery. Several types of injuries can occur, including chemical and thermal burns, inhalation injuries, metal poisoning, etc. There are currently no specific guidelines on the management of burns due to lithium-ion battery exposure. Herein, we recommend the following: Initial assessment of injuries should accompany the Advanced Trauma Life Support guidelines; serum levels of lithium, cobalt, and manganese should be checked and elevated levels should be monitored; patients should be monitored for signs of metal toxicity; wound should be extensively debrided and irrigated to remove any residual materials; and litmus test should be performed to check for alkali pH prior to irrigation with water or other aqueous solutions. [ABSTRACT FROM AUTHOR]

In this study, the potential toxicity of α-Fe2O3-NPs was investigated using a unicellular eukaryote model, Saccharomyces cerevisiae (S. cerevisiae). The results showed that cell viability and proliferation were significantly decreased (p < 0.01) following exposure to 100–600 mg L−1 for 24 h. The IC50 and LC50 values were 352 and 541 mg L−1, respectively. Toxic effects were attributed to α-Fe2O3-NPs rather than iron ions released from the NPs. α-Fe2O3-NPs were accumulated in the vacuole and cytoplasm, and the maximum accumulation (3.95 mg g−1) was reached at 12 h. About 48.6% of cells underwent late apoptosis/necrosis at 600 mg L−1, and the mitochondrial transmembrane potential was significantly decreased (p < 0.01) at 50–600 mg L−1. Biomarkers of oxidative stress [reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] and the expression of apoptosis-related genes (Yca1, Nma111, Nuc1 and SOD) were significantly changed after exposure. These combined results indicated that α-Fe2O3-NPs were rapidly internalized in S. cerevisiae, and the accumulated NPs induced cell apoptosis mediated by mitochondrial impairment and oxidative stress. [ABSTRACT FROM AUTHOR]

Total hip arthroplasty ( THA) is a highly effective surgical treatment for severe joint involvement. However, due to the release of metal ions in the blood, the patients who undergo hip replacement with metal-on-metal ( MOM) bearings may develop signs of allergic skin disease. We report a case of a 60-year-old man who had received MOM hip resurfacing 5 years earlier for osteoarthritis. He presented with a 3-year history of diffuse dermatitis that did not respond to antihistamines and corticosteroids and also had elevated serum levels of chromium and cobalt. A patch test revealed chromium-sulfate hypersensitivity. A skin biopsy showed nonspecific perivascular lymphocytic infiltrate associated with histiocytes. A biopsy of an inguinal lymph node demonstrated large aggregates of Langerhans cells, suggesting type IV delayed-type hypersensitivity. The prosthesis was replaced using ceramic-on-ceramic bearings and the dermatitis resolved after 3 months. The lymph nodes decreased in volume and the serum chromium levels normalized within 24 months of revision surgery. The high levels of serum ions associated with the metal debris from MOM- THAs may induce sensitization and type IV hypersensitivity reactions. Replacing the prosthesis using alternative coupling surfaces is the only approach that has the capacity to resolve these symptoms. Physicians who are not familiar with this issue may misdiagnose systemic symptoms and provide inadequate treatment. [ABSTRACT FROM AUTHOR]

Metal-on-metal hip replacements are the subject of much current debate. There is some evidence that there may be a hypersensitivity reaction, specific to metalon- metal total hip replacements (THRs), which is associated with early failure of these prostheses. It has to date only been described in total replacements and not in metalon- metal hip resurfacing. We present the case of a 68-year-old man who underwent bilateral metal-on-metal hip resurfacing for osteoarthrosis. The patient presented 6 months after surgery with pain and lateral thigh swelling. Pre-operative ultrasound and MRI demonstrated findings similar to those described in early failing metal-onmetal THRs, as well as evidence of lymphoreticular spread of metal debris. The operative findings included extensive aseptic soft-tissue necrosis. Histology revealed necrosis and a dense perivascular lymphocytic infiltrate along with metal debris within sinus histiocytes. The surgical, radiological and histological findings are similar to softtissue reactions described in metal-on-metal THRs. [ABSTRACT FROM AUTHOR]

Fast-growing trees such as Salix viminalis L. and Populus tremula L. are well suited to phytoremediate heavy metal contaminated soils. However, information on tree performance, particularly leaf function, under conditions of heavy metal contamination is scarce. We used yearly coppiced saplings of S. viminalis and P. tremula growing in model ecosytems to test four hypotheses: (1) heavy metal contamination impairs photosynthesis by injuring leaf structure; (2) the effects of heavy metal contamination are enhanced by acidified rainwater and low soil pH; (3) heavy metal contamination increases dark respiration and, thus, repair processes; and (4) heavy metal contamination is tolerated and remediated better by S. viminalis than by P. tremula. We investigated heavy metal accumulation, tissue injury and gas exchange in leaves of plants subjected to controlled soil contamination with heavy metal dust. Additional treatments included acidic and calcareous natural forest subsoils in combination with irrigation with rainwater at pH 5.5 or 3.5. In both provenances of P. tremula that were studied, but not in S. viminalis, heavy metal treatment reduced photosynthesis and transpiration by varying amounts, except in the hot and dry summer of 2003, but had no effect on dark respiration. At light saturation, net CO2 uptake and water-use efficiency were reduced by heavy metal contamination, whereas the CO2 concentration in the leaf intercellular air space was increased. Rainwater pH and subsoil pH only slightly modified the effects of the heavy metal treatment on P. tremula. Gas exchange responses of P. tremula to heavy metals were attributed to leaf structural and ultrastructural changes resulting from hypersensitive- response-like processes and accelerated mesophyll cell senescence and necroses in the lower epidermis, especially along the transport pathways of heavy metals in the leaf lamina. Overall, the effects of heavy metals on P. tremula corroborated Hypothesis 1, but refuted Hypotheses 2 and 3, and were inconclusive for Hypothesis 4. Both P. tremula and S. viminalis showed appreciable potential for storing heavy metals in aging foliage. [ABSTRACT FROM AUTHOR]

Effects of 10 μM cadmium (supplied as Cd nitrate) on the utilization and allocation of iron (Fe) were investigated in poplar (Populus alba L.) plants grown in nutrient solution with Fe(III)-EDTA or Fe(III)-citrate as the Fe source. The effects of Cd were also compared with those of Fe deprivation. The accumulation of Fe in roots was 10-fold higher in plants grown with Fe-citrate than with Fe-EDTA. Cadmium decreased leaf chlorophyll concentrations and photosynthetic rates, and these decreases were more marked in plants grown with Fe-citrate than with Fe-EDTA. In both Fe treatments, addition of Cd caused large increases in root and shoot apoplasmic and non-apoplasmic Cd contents and increases in root Fe content; however, Cd decreased shoot Fe content, especially in plants grown with Fe-citrate. New leaves of plants grown with Fe-citrate had small cellular (non-apoplasmic) Fe pools, whereas these pools were large in new leaves of plants grown with Fe-EDTA. Non-apoplasmic Cd pools in new leaves were smaller in plants grown with Fe-citrate than with Fe-EDTA, indicating that inactivation of non-apoplasmic Cd pools is facilitated more by Fe-EDTA than by Fe-citrate. In the presence of Cd, Fe-EDTA was also superior to Fe-citrate in maintaining an adequate Fe supply to poplar shoots. Differences in plant responses to Fe-EDTA and Fe-citrate may reflect differences in long-distance transport of Fe rather than in acquisition of Fe by roots. [ABSTRACT FROM AUTHOR]

Workers are often simultaneously exposed to two or more chemicals, yet little is known about the toxicity of most chemical mixtures. The traditional assumption, in the absence of further information, has been that the chemical components of a mixture have mutually independent effects, and the toxic response to multiple chemicals is additive. The data presented here show that mixtures of NiCl2 and CoCl2 induce a synergistic (that is, greater than additive) toxic response in cell culture. Immortalized alveolar epithelial type II cells were incubated for 4 h with various concentrations of either NiCl2, CoCl2, or NiCl2 and CoCl2 together, and cell viability assessed 24 h later. The LD50 for NiCl2 was 5.7 mM. CoCl2, with an LD50 of 1.1 mM, was about five times more potent than NiCl2. Mixtures of NiCl2 and CoCl2 decreased cell viability synergistically. For example, a mixture of 750 mM NiCl2 and 750 mM CoCl2 reduced cell viability by more than three times the value predicted by the additive approach. We used concentration-response data from these studies in a mathematical model; this model describes the equivalent inhalation exposure to an aerosol composed of a mixture of chemicals with different toxicities and also accounts for synergistic responses to these chemicals. Our results along with previous studies using an animal model suggest that these synergisms should be taken into account when conducting future exposure assessments. [ABSTRACT FROM AUTHOR]

Of 270 patients successfully resuscitated from out-of-hospital cardiac arrest, 16% had no evidence of coronary heart disease. In these 43 patients, other forms of heart disease were found in 81% (35/43): cardiomyopathy in 18 patients, valvular disease in six, congenital heart disease in two, and primary arrhythmia in nine. Seven patients had evidence of only pulmonary disease and one had pancreatitis as his precipitating event. Nineteen of the 43 patients (44%) had serum potassium less than 3.6 m Eql-s in the initial blood sample after cardiac arrest. One- and two-year mortalities were 30% and 43%, respectively, for the group, which is similar to one year (20%) and two-year (35%) mortalities of the 227 resuscitated patients with coronary heart disease. Patients who survive a sudden death experience and who have no evidence of coronary artery disease are a unique but heterogeneous group who usually have identifiable cardiac or pulmonary disease. [ABSTRACT FROM PUBLISHER]

This article focuses on a case study of a woman suffering from osteo-arthritis of both knees. She had a total right knee replacement. An Attenborough prosthesis was inserted; this is of the metal-on-plastic type and the metal concerned is a cobalt and chromium alloy. Latter, her right knee became swollen, hot and painfull. Right knee was more swollen than left. Her skin was dry and she had a mild recurrence of the rash, with blotchy erythema and excoriations. It was found that metal sensitivity is linked with a reaction to an implant.

This paper aims to assess and compare currently available antidotes for cyanide poisoning. Such evaluation, however, is difficult. Thus, extrapolation from the results of animal studies has potential pitfalls, as significant inter-species differences in response may exist, and these experiments often involve administration of toxin and antidote almost simultaneously, rather than incorporating a more realistic time delay before initiation of treatment. Direct inference from human case reports is also problematic; either because of uncertainties over the exposure levels involved (and hence the likely outcome without treatment), or because of difficulties in identifying the specific contribution of a particular antidote within the overall treatment regimen. Certainly an effort to compare the relative efficacy of cyanide antidotes produces equivocal findings, with no single regimen clearly standing out. Indeed, factors such as the risks of antidote toxicity to various individuals and other practical issues, may be more important considerations. There is therefore no single treatment regimen which is best for all situations. Besides individual risk factors for antidote toxicity, the nature of the exposure and hence its likely severity, the evolving clinical features and the number of persons involved and their proximity to hospital facilities, all need to be considered. Clinically mild poisoning may be treated by rest, oxygen and amyl nitrite. Intravenous antidotes are indicated for moderate poisoning. Where the diagnosis is uncertain, sodium thiosulphate may be the first choice. With severe poisoning, an additional agent is required. Given the various risks with methaemoglobin formers or with unselective use of kelocyanor, hydroxocobalamin may be preferred from a purely risk-benefit perspective. However the former alternatives will likely remain important. [ABSTRACT FROM PUBLISHER]

Indwelling electrodes were implanted in rats one week before intraperitoneal injections of cardiotoxic doses of cobalt. Electrocardiograms were recorded from the rats at varying time intervals after dosing. The rats were subsequently killed and their hearts were examined histologically. The topography and histological characteristics of the cardiac lesion were established and were compared with alterations in the electrocardiogram. [ABSTRACT FROM PUBLISHER]

In the present study, we examined the effects of CoCl2 on multiple histone modifications at the global level. We found that in both human lung carcinoma A549 cells and human bronchial epithelial Beas-2B cells, exposure to CoCl2 (≥200 μM) for 24 h increased H3K4me3, H3K9me2, H3K9me3, H3K27me3, H3K36me3, uH2A and uH2B but decreased acetylation at histone H4 (AcH4). Further investigation demonstrated that in A549 cells, the increase in H3K4me3 and H3K27me3 by cobalt ions exposure was probably through enhancing histone methylation processes, as methionine-deficient medium blocked the induction of H3K4me3 and H3K27me3 by cobalt ions, whereas cobalt ions increased H3K9me3 and H3K36me3 by directly inhibiting JMJD2A demethylase activity in vitro, which was probably due to the competition of cobalt ions with iron for binding to the active site of JMJD2A. Furthermore, in vitro ubiquitination and deubiquitination assays revealed that the cobalt-induced histone H2A and H2B ubiquitination is the result of inhibition of deubiquitinating enzyme activity. Microarray data showed that exposed to 200 μM of CoCl2 for 24 h, A549 cells not only increased but also decreased expression of hundreds of genes involved in different cellular functions, including tumorigenesis. This study is the first to demonstrate that cobalt ions altered epigenetic homeostasis in cells. It also sheds light on the possible mechanisms involved in cobalt-induced alteration of histone modifications, which may lead to altered programs of gene expression and carcinogenesis since cobalt at higher concentrations is a known carcinogen. [ABSTRACT FROM AUTHOR]