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Uptake and toxicity of Ni-Co mixtures in Enchytraeus crypticus were determined after 4 d, 7 d, 10 d, and 14 d exposure. Generally, body concentrations of Ni and Co increased with increasing exposure concentrations. Ni body concentration was significantly reduced in the presence of Co, whereas Ni only marginally affected Co uptake. When expressed as free ion activities, individual toxicity of Ni and Co increased with time, with median lethal concentrations (LC50) decreasing from 78.3 μM and 511 μM at 4 d to 40.4 μM and 393 μM at 14 d, respectively. When expressed as body concentrations, LC50BodyNi remained constant with time whereas LC50BodyCo increased during the first 7 d but remained stable afterwards. As identified by the MIXTOX model, interactions between Ni and Co were mainly antagonistic when based on free ion activities, however, no interaction was observed when based on body concentrations. A process-based model, incorporating exposure time to analyze the mechanisms underlying the dynamic mixture toxicity confirmed the differences in toxicokinetics of the 2 metals. The author's findings suggest that body concentrations, which incorporate bioaccumulation processes, are time-independent and can act as a more constant indicator of metal toxicity. The observed antagonism was mainly caused by competition between Co and Ni for binding sites and subsequent inhibition of Ni uptake. This competitive interaction occurred at the uptake level (toxicokinetics), but not at the target level (toxicodynamics). Environ Toxicol Chem 2014;9999:1-10. © 2014 SETAC [ABSTRACT FROM AUTHOR]

Background: Prosthetic hip-associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal-on-metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described. Given that cobalt is predominantly albumin bound, it should theoretically be removed by TPE. Here we report a case of PHACT and our experience using TPE to lower plasma cobalt levels.Case Report: A 61-year-old woman developed deafness, blindness, ambulatory dysfunction, and endocrinopathies after MoM implant. Cobalt levels on admission were greater than 1500 µg/L. In an attempt to rapidly lower cobalt levels before MoM explant, hemodialysis and TPE were performed. Hemodialysis removed negligible amounts of cobalt. One session of TPE temporarily removed approximately two-thirds of measurable cobalt, but levels rebounded to pre-TPE values after 8 hours. It was only after MoM removal that cobalt levels plateaued below 300 µg/L and clinical symptoms improved.Discussion: TPE removed cobalt from a PHACT patient, but a durable decrease in cobalt was only achieved after MoM explant. These findings are comparable to reports where chelation was employed in PHACT patients before MoM explant. The observed rebound phenomenon is likely from rapid equilibration between the immense extravascular tissue source (the MoM) and the intravascular compartment.Conclusion: TPE may serve as adjunctive therapy for PHACT patients whose cobalt levels remain high after explant, especially in patients with renal failure, in whom chelation is contraindicated. [ABSTRACT FROM AUTHOR]

The article presents a case report of an 84-year-old woman with a orthopaedic history who experienced generalized pruritic eczematous rash. She had undergone a metal-on-metal (MoM) right total hip replacement for a fractured femur neck in May 2009. Skin biopsy of the rash revealed urticarial features with no overt histological evidence of a drug eruption. Diagnosis of the patient revealed systemic allergic dermatitis (SAD) caused by cobalt.

Metallosis with subsequent cardiac involvement is a possible long‐term complication of hip arthroplasty. We report the case of a young female referred to our centre for the suspicion of cardiac amyloidosis presenting with low electrocardiogram voltage, left ventricular hypertrophy, pericardial effusion, and global and longitudinal systolic impairment with apical sparing pattern. Her medical history was remarkable for arthroplasty in the context of congenital hip dysplasia. Two years prior to presentation, she underwent revision surgery for prosthesis malfunction, and tissue metallosis was initially documented. At the current presentation, cobalt metallosis was confirmed, as the circulating cobalt and chromium levels were severely elevated. The accurate diagnosis prompted the removal of the cobalt source with extensive tissue debridement and the use of chelating agents. Reversal of the cardiac abnormalities occurred as the circulating cobalt levels returned to normal. [ABSTRACT FROM AUTHOR]

Micronutrients play key roles in numerous metabolic processes in cyanobacteria. However, our understanding of whether the micronutrient cobalt influences the productivity of freshwater systems or the occurrence of cyanobacterial blooms is limited. This study aimed to quantify the concentration of Co necessary for optimal cyanobacterial growth by exposing Microcystis aeruginosa to a range of Co concentrations under culture conditions. Extended exposure to concentrations below ˜0.06 μg · L−1 resulted in notable inhibition of M. aeruginosa growth. A clear negative relationship was observed between Co concentration in solution and intracellular Fe quota of M. aeruginosa, possibly due to decreased transport of Fe at higher Co concentrations. Cyanocobalamin and any Co within the structure of cyanocobalamin appears to be non‐bioavailable to M. aeruginosa, instead they likely rely on the synthesis of a structural variant – pseudocobalamin, which may have implications for the wider algal community as the variants of cobalamin are not necessarily functionally exchangeable. To evaluate the likelihood of Co limitation of cyanobacterial growth under field conditions, a survey of 10 freshwater reservoirs in South‐Eastern Australia was conducted. Four of the ten sites had dissolved Co concentrations below the 0.06 μg · L−1 threshold value. All four of these sites rarely undergo cyanobacterial blooms, strengthening evidence of the potential for Co to limit growth, perhaps either alone or in combination with phosphorus. [ABSTRACT FROM AUTHOR]

Cobalt is well known for its ability to stimulate erythropoiesis via stabilization of hypoxia‐inducible factors. In sports, this can provide a competitive benefit to athletes, so the World Anti‐Doping Agency prohibits the use of cobalt in any form except its cobalamin vitamers. As of now, cobalt in biological fluids is detected by inductively coupled plasma mass spectrometry (ICP‐MS), a technique which has very limited availability in anti‐doping laboratories. Therefore, a quantitative method based on liquid chromatography–tandem mass spectrometry capable of measuring urinary cobalt in the form of its complex with 2‐(5‐chloro‐2‐pyridylazo)‐5‐diethylaminophenol (5‐Cl‐PADAP) has been developed and validated. A cobalt complex with deuterium‐labeled 5‐Cl‐PADAP was used as internal standard. The method was found linear over the concentration range of 5–500 ng/ml with a combined standard uncertainty less than 10% at 15, 200, and 450 ng/ml. Stability of cobalt ions in urine was investigated over the course of 2 months; the concentration of free Co2+ was observed to decline by approximately 50% but restored upon hydrolysis with hydrochloric acid. Unlike ICP‐MS, this method is practically unaffected by the presence of cyanocobalamin as the latter is resistant to acid hydrolysis. Notwithstanding the lack of formalized threshold concentration of cobalt in urine, it is highly desirable that more anti‐doping laboratories engage in testing for cobalt levels to better understand the prevalence of cobalt misuse in athletes. Given that cobalt salts are inexpensive and easily obtainable, the risk of such abuse should not be underestimated. [ABSTRACT FROM AUTHOR]

The replacement of a native hip joint by a metal‐on‐metal prosthesis may induce deleterious inflammatory side effects that are associated with the release of wear particles and metal ions. These events are referred to the adverse reaction to metal debris (ARMD) and the adverse local tissue reaction (ALTR). While wear particles seem involved in ARMD, the role of metal ions in ALTR and their impact on myoblasts, located in the prosthesis vicinity, has not been fully identified. To clarify this issue we investigated, using an in vitro culture system, the effect of cobalt and/or chromium ions (Co2+ and/or Cr3+) on human myoblast proliferation, cellular differentiation, and inflammatory marker expression. Freshly isolated human myoblasts were cultured in media supplemented with graded concentrations of Co2+ and/or Cr3+. Co2+ induced a concentration‐dependent decrease of both myoblast viability and myogenic differentiation while Cr3+ did not. Co2+ or Co2+/Cr3+ also induced the upregulation of ICAM‐1, whereas HLA‐DR expression was unaffected. Moreover, allogenic monocytes induced the synergistic increase of Co2+‐induced ICAM‐1 expression. We also found that Co2+ stabilized HIF‐1α and increased TLR4, tumor necrosis factor‐alpha (TNF‐α), and interleukin 1β (IL‐1β) expression in a dose and time‐dependent manner in human myoblasts. This study showed that Co2+, but not Cr3+, was toxic toward myoblasts and induced, in the surviving cells, expression of inflammatory markers such as ICAM‐1, TLR4, TNF‐α, and IL‐1β. This suggests that Co2+, most efficiently in the presence of monocytes, may be a key inducer of ALTR, which may, if severe and long‐lasting, eventually result in prosthesis loosening. [ABSTRACT FROM AUTHOR]

Enzyme mimics have been widely used as alternatives to natural enzymes, owing to their high stability and low cost. However, the activity and atom economy of enzyme mimics still need to be improved. Herein, we report the boosting effects of amino acids, peptides and proteins on the peroxidase‐like activity of Co2+. Among 20 amino acids, tryptophan (Trp) enhanced the activity of Co2+ approximately 8 times and was identified as the best stimulator. The study revealed the synergy of amino acids‐based species and HCO3− for efficient catalysis. Co2+ is proposed to bind simultaneously to HCO3− and Trp, and to form a ternary catalyst which facilitates the generation of reactive oxygen species. Based on the selective boosting by Trp, a simple and low‐cost Co2+ sensor with high sensitivity was developed, which showed a linear range of 10–300 μM and a limit of detection of 0.4 μM for Co2+. [ABSTRACT FROM AUTHOR]

Objective: To monitor cobalt concentrations in urine, red blood cells and plasma after chronic parenteral administration of cobalt chloride evaluate these results against the current International Federation of Horseracing Authorities thresholds for detecting cobalt misuse. Design: Eight mares were randomly assigned to four treatment groups, with two mares in each group: Group 1 – control group, Group 2 – 25 milligrams cobalt intravenously as CoCl2 weekly, Group 3 – 50 milligrams cobalt intravenously as CoCl2 weekly, and Group 4 – 25 milligrams cobalt intravenously mid‐week and at the end of the week. Urine and blood samples were collected before each weekly administration so that trough levels were assessed. In the group receiving two doses per week, urine and blood were collected prior to the dose given at the end of each week. Samples were initially collected at time zero then weekly for 10 weeks. Three further collections of urine and blood were made at days 81, 106 and 127. Methods: Urine creatinine measurements to assess horse hydration status were performed by the Jaffe reaction method. Cobalt determinations in plasma, blood and urine were by inductively coupled plasma—mass spectrometry. Haematocrit concentrations, used to calculate red cell cobalt levels, were performed using a microhematocrit centrifuge. Statistical analyses were conducted in Genstat (v17, VSNi). Results: Marked cobalt accumulation was evident with increasing cobalt concentrations for all sample matrices in specimens collected immediately prior to cobalt administration. Correlation between the sample matrices improved when urine cobalt concentration was adjusted for creatinine level. Red cell cobalt levels remained elevated for at least 12 weeks after cessation of administration, consistent with the lifespan of the red cell. There was no significant change in haematocrit concentrations for the duration of the study. Conclusion: The current urine cobalt threshold was only effective at detecting acute cobalt exposure while the plasma cobalt threshold was able to consistently identify chronic high‐level cobalt exposure and potential cobalt misuse. The threshold values legislated for urine cobalt do not correlate with those set for plasma. The acute nature of urinary cobalt excretion provides a relatively small window through which cobalt administration is detected. Plasma and red cell cobalt concentrations can provide a clearer picture of potential cobalt misuse. [ABSTRACT FROM AUTHOR]

The transition metal cobalt is categorized as an essential trace mineral. In addition, cobalt salts have been reported as constituents of dietary supplements administered orally at approximately 1 mg/day.[1] Ionic cobalt (Co SP 2+ sp ) acts as an efficient erythropoiesis stimulating agent due to its hypoxia-inducible factor-activating effects. Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the thoroughbred horse: Differentiating cobalt abuse from supplementation. [Extracted from the article]

Abstract: The geosphere and biosphere coevolved and influenced Earth's biological and mineralogical diversity. Changing redox conditions influenced the availability of different transition metals, which are essential components in the active sites of oxidoreductases, proteins that catalyze electron transfer reactions across the tree of life. Despite its relatively low abundance in the environment, cobalt (Co) is a unique metal in biology due to its importance to a wide range of organisms as the metal center of vitamin B12 (aka cobalamin, Cbl). Cbl is vital to multiple methyltransferase enzymes involved in energetically favorable metabolic pathways. It is unclear how Co availability is linked to mineral evolution and weathering processes. Here we examine important biological functions of Co, as well as chemical and geological factors that may have influenced the utilization of Co early in the evolution of life. Only 66 natural minerals are known to contain Co as an essential element. However, Co is incorporated as a minor element in abundant rock‐forming minerals, potentially representing a reliable source of Co as a trace element in marine systems due to weathering processes. We developed a mineral weathering model that indicates that dissolved Co was potentially more bioavailable in the Archean ocean under low S conditions than it is today. Mineral weathering, redox chemistry, Co complexation with nitrogen‐containing organics, and hydrothermal environments were crucial in the incorporation of Co in primitive metabolic pathways. These chemical and geological characteristics of Co can inform the biological utilization of other trace metals in early forms of life. [ABSTRACT FROM AUTHOR]

Background: Cobalt chloride (CoCl2) is administered to racehorses to enhance performance. The purpose of this study was to evaluate the clinical, cardiovascular, and endocrine effects of parenterally administered CoCl2. Objectives: To describe the effects of weekly intravenous doses of CoCl2 on Standardbred horses. Animals: Five, healthy Standardbred mares. Methods: Prospective, randomized, experimental dose‐escalation pilot. Five Standardbred mares were assigned to receive 1 of 5 doses of CoCl2 (4, 2, 1, 0.5, or 0.25 mg/kg) weekly IV for 5 weeks. Physical examination, blood pressure, cardiac output, and electrocardiography (ECG) were evaluated for 4 hours after administration of the first and fifth doses. Blood and urine samples were collected for evaluation of cobalt concentration, CBC and clinical chemistry, and hormone concentrations. Results: All mares displayed pawing, nostril flaring, muscle tremors, and straining after CoCl2 infusion. Mares receiving 4, 2, or 1 mg/kg doses developed tachycardia after dosing (HR 60–126 bpm). Ventricular tachycardia was noted for 10 minutes after administration of the 4 mg/kg dose. Increases in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) occurred after administration of all doses (4, 2, 1, 0.5, and 0.25 mg/kg). Profound hypertension was observed after the 4 mg/kg dose (SAP/DAP, MAP [mmHg] = 291–300/163–213, 218–279). Hemodynamics normalized by 1–2 hours after administration. ACTH and cortisol concentrations increased within 30 minutes of administration of all CoCl2 doses, and cardiac troponin I concentration increased after administration of the 4 and 2 mg/kg doses. Conclusions and Clinical Importance: The degree of hypertension and arrhythmia observed after IV CoCl2 administration raises animal welfare and human safety concerns. [ABSTRACT FROM AUTHOR]

Nanosilica (NSi) was functionalized by oxalic acid (NSi-Ox) and tartaric acid (NSi-Tar) using solvent-free microwave-assisted approach. The two surface-modified NSi sorbents were characterized by Fourier transform infrared, scanning electron microscopy, transmission electron microscopy, and thermal gravimetric analysis. NSi-Ox and NSi-Tar sorbents were examined for the removal of Co(II) from aqueous solutions by the batch adsorption technique. Removal of Co(II) was carried out at different controlling parameters such as pH, contact time, sorbent mass, and interfering ions. The maximum Co(II) uptake values were identified as 733.3 and 1026.7 μmol g−1 for NSi-Ox and NSi-Tar, respectively, and these were higher than the identified value by NSi sorbent (440 μmol g−1). This trend is mainly due to the surface functionalization with several active groups. The adsorption isotherms were evaluated using Langmuir and Freundlich models and the results were better fitted to the Langmuir model ( R2 = 0.983 and 0.989 for NSi-Ox and NSi-Tar, respectively). Kinetic studies were performed and the experimental data were found in good agreement with the pseudo-second-order model. The thermodynamic parameters were also determined. The potential applications of NSi sorbents for removal of Co(II) from drinking tap water and sea water samples were successfully achieved using microcolumn studies. [ABSTRACT FROM AUTHOR]

Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half-life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half-life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Unfair athletes seek ways to stimulate erythropoiesis, because the mass of haemoglobin is a critical factor in aerobic sports. Here, the potential misuse of cobalt deserves special attention. Cobalt ions (Co2+) stabilize the hypoxia-inducible transcription factors (HIFs) that increase the expression of the erythropoietin (Epo) gene. Co2+ is orally active, easy to obtain, and inexpensive. However, its intake can bear risks to health. To elaborate this issue, a review of the pertinent literature was retrieved by a search with the keywords 'anaemia', 'cobalt', 'cobalt chloride', 'erythropoiesis', 'erythropoietin', 'Epo', 'side-effects' and 'treatment', amongst others. In earlier years, cobalt chloride was administered at daily doses of 25 to 300 mg for use as an anti-anaemic agent. Co2+ therapy proved effective in stimulating erythropoiesis in both non-renal and renal anaemia, yet there were also serious medical adverse effects. The intake of inorganic cobalt can cause severe organ damage, concerning primarily the gastrointestinal tract, the thyroid, the heart and the sensory systems. These insights should keep athletes off taking Co2+ to stimulate erythropoiesis. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Metals are common enzymatic cofactors, and their acquisition must be assured under the various conditions encountered in the host. Although some strategies for acquisition of common metals such as iron and manganese have been elucidated, little is known about the conditions and mechanisms used to capture trace metals. Nickel is a transition metal required as a cofactor for several bacterial enzymes, including urease. Staphylococcus aureus does express a nickel ABC transporter, Nik, which functions in metal-replete medium and is necessary for nickel urease activity and urinary tract colonization. In this work, we identified a novel cobalt and nickel transporter, which we named Cnt (previously annotated Opp1), in the major opportunistic pathogen S. aureus. Metal transport activity was revealed by growing cells in a chemically defined medium devoid of metals. Zinc specifically inhibits Cnt-mediated nickel and cobalt uptake, on both functional and transcriptional levels. Mortality due to S. aureus cnt mutant in systemic infection and colonization of the bladder and kidneys in ascending urinary tract infection model were reduced compared to the parent strain. This study identifies a novel S. aureus trace metal transporter and its restricted conditions of activity, and establishes its role in infection. [ABSTRACT FROM AUTHOR]

The electrostatic nature of plant cell membrane (CM) plays significant roles in ionic interactions at the CM surface and hence in the biotic effects of metal ions. Increases in major cations (commonly Ca2+, Mg2+, H+, Na+, K+, etc.) in bulk-phase medium reduce the negativity of CM surface electrical potential (ψ0), but these slightly increase the driving force of a metal ion crossing CMs (surface-to-surface transmembrane potential difference, Em,surf). Toxicologists commonly attributes the interactions between heavy metals and common cations (e.g., H+, Ca2+, and Mg2+) to competitions for binding sites at a hypothetical CM surface ligand. The ψ0 effects are likely to be more important to metal toxicity and the alleviation of toxicity than site-specific competition. Models that do not consider ψ0, such as the biotic ligand model (BLM) and the free ion activity model (FIAM), as usually employed are likely to lead to false conclusions about competition for binding at CM surface ligands. In the present study a model incorporating ψ0 effects and site-specific competition effects was developed to evaluate metal (Cu2+, Co2+, and Ni2+) toxicities threshold (EA50, causing 50% inhibition) for higher plants. In addition, the mechanisms for the effects of common cations on toxicity of metals were also explored in terms of CM surface electrical potential. Environ. Toxicol. Chem. 2010;29:1503–1511. © 2010 SETAC [ABSTRACT FROM AUTHOR]

Background: Dyshidrotic eczema is a type of chronic intermittent dermatitis characterized by vesicles, dystrophic fingernail changes, and rarely bullae that affects the hands and feet. Many exogenous factors may trigger a flare including dermatophyte infections, contact irritants, and metal hypersensitivity. Although metal hypersensitivity does not play a role in all cases of dyshidrotic eczema, high oral ingestion of nickel and/or cobalt should be considered, regardless of patch test results. Objective: We updated and simplified existing published guidelines for low-cobalt diets. A recent review of the literature showed that dietary cobalt restriction, a safe yet burdensome treatment option for dyshidrosis, is referenced to dated sources. Methods: We have analysed current data for the cobalt content in common food items. Conclusion: We propose a revised, point-based diet that will eliminate much of the dietary cobalt (and nickel) and reduce dyshidrotic eczema flares. [ABSTRACT FROM AUTHOR]

Cobalt is widespread in the environment and excess dietary Co exposure can result in toxic effects in many organisms. However, whether the multi-biological toxicities caused by Co exposure can be transferred from parents to progeny has not been clarified. In the present study, we analyzed the multiple toxicities of Co to the nematode Caenorhabditis elegans and its progeny. Endpoints of life span, body size, vulva development, brood size, generation time, body bend, head thrash, and chemotaxis plasticity were used for toxicity testing. Our results indicate that Co induced multi-biological defects by affecting the life span, development, reproduction, behavior, and behavioral plasticity. Moreover, we found that most of these multi-biological defects could be transferred from parents to the filial generation (F1 and F2) progenies, and that this transmission could only be partially recovered. Certain specific phenotypes in the progeny exhibited even more severe defects than in the parents, such as chemotaxis plasticity. We classified the defects caused by Co exposure into four groups according to their transferable properties. Furthermore, the stress responses were investigated in embryos using a stable transgenic line, hsp16-2-gfp. Our data suggest that the multi-biological defects caused by Co exposure can be transferred from parents to progeny, and that Co toxicity might be accumulated in the eggs of nematodes. [ABSTRACT FROM AUTHOR]