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This document provides information on the topic of cobalt toxicity in patients with metal-on-metal (MoM) hip implants. Cobalt toxicity can lead to various symptoms and complications, including peripheral neuropathy, hearing loss, cardiomyopathy, and hypothyroidism. The diagnosis involves elevated cobalt levels, confirmed findings consistent with cobalt toxicity, and exclusion of other causes. Treatment options include symptomatic management, chelation therapy, and revision of the MoM hip implant. Early detection is important for better outcomes. [Extracted from the article]

Cobalt (Co2+) is a beneficial microelement for plants but toxic to metabolism in higher amounts. This study determined the influence of sublethal Co2+ level (0.5 mM) on the growth of maize (Zea mays L.) hybrids; Hycorn 11 plus (Co2+ sensitive) and P-1429 (Co2+ tolerant) and its alleviation with foliar spray of pre-optimized levels of stress protective chemicals (SPCs), i.e., salicylic acid (SA, 0.5 mM), thiourea (TU, 1.0 mM), and ascorbic acid (AsA, 0.5 mM) applied at seedling, vegetative, and late vegetative stages. Plants were harvested at early vegetative, late vegetative, and silking stages. Co2+ stress caused a decrease in shoot and root length, dry weight, leaf area, and culm diameter, reduced the activities of enzymatic antioxidants and concentrations of AsA and soluble phenolics more in root than shoot, but P-1429 was more tolerant of Co2+ than Hycorn 11 plus. SPCs spray alleviated oxidative damage by enhancing the antioxidant activity, AsA and soluble phenolics, sulfate-S and nitrate–N contents, which were significantly increased in roots than in shoots; P-1429 displayed better response than Hycorn 11 plus. Principal component analysis and correlation matrix revealed the profound roles of SPCs spray in improving Co2+ resistance in root leading to robust growth of hybrids. AsA was highly promising in reducing Co2+ toxicity while vegetative and silking stages were more sensitive. Results revealed that after translocation to root, the foliar-applied SPCs had individualistic modes of action in mitigating Co2+ toxicity on roots. In crux, the metabolism and phloem transport of the SPCs from shoot to root are plausible mechanism for Co2+ tolerance in maize hybrids. [ABSTRACT FROM AUTHOR]

Frequent discharge of cobalt in ionic form (Co2+) during industrial processes is contaminating agricultural soil through the addition of industrial effluent. Cobalt is beneficial element in trace amounts but its higher concentrations in soil severely damage the growth and development of plants. In this two-year study, the pre-selected sublethal level (0.5 mM) concentration of Co2+ was applied in soil to induce toxicity on two elite maize (Zea mays L.) hybrids ('Hycorn11plus' and 'P-1429'). To encounter the toxic effects of selected sub-lethal (0.5 mM) Co2+ level (applied using CoCl2·6H2O), pre-optimized levels of three stress protective chemicals (SPCs) i.e., ascorbic acid (0.5 mM), salicylic acid (0.5 mM) and thiourea (1.0 mM) were foliar sprayed. The Co2+ and SCPs treatments were applied 10 days after seedling emergence. After ten days of treatment application, the data were recorded for the growth, nutrients and leaf water status. The shoot and root dry weights and shoot-to-root (S/R) ratio were substantially reduced by the Co2+ stress. Co2+ intoxication also enhanced the leaf water loss (LWL) while relative water contents (RWC) were reduced in Co2+ stressed plants. The Co2+ treatment reduced the intake of nitrate-N, sulfate-S, phosphate-P, K+, Ca2+, Mg2+, Zn2+, and Fe2+ contents significantly both in the shoot and root. However, from the correlation matrix, it was noted that the foliar spray of SPCs effectively alleviated the Co2+damage by preventing the influx of Co2+ ions and enhanced the growth, water and nutrient contents except for LWL. From the reduced RWC and shoot and root nutrient contents, as well as increased LWL and Co2+ contents, it is evident that Co2+ interfered with either the function or structure of water and ion-transport systems located on the plasma lemma and tonoplast of root cells. AsA was more effective among the foliar applied SPCs due to its multiple metabolic roles in plants. The foliar spray of SPCs improved the root mass and tendency to absorb essential nutrients under Co2+toxicity indicating an intimate communication between shoot and root. The use of SPCs at the selected levels is a pragmatic strategy to counteract the Co2+ damage to maize in the marginally contaminated areas. [ABSTRACT FROM AUTHOR]

Dear Editor, We read with great interest the letter from Pelclova and Lach [[1]] on the efficacy of unithiol (2,3-dimercaptopropanesulfonate) and acetylcysteine in a patient with arthroplastic cobalt toxicity. Acetylcysteine increases cobalt urinary excretion and consistently maintains the serum cobalt concentration less than the threshold of 10 g/L, which we believe to be the goal in patients with metal-on-metal implants in order to minimise cobalt toxicity from the existing prosthesis [[3]]. The authors stated that chelation therapy, either with unithiol or acetylcysteine, is often clinically inefficient in patients with very elevated cobalt concentrations (greater than 100 g/L) as long as the damaged prosthesis remains I in situ i . [Extracted from the article]

Context:Post-arthroplasty metallosis, which refers to metallic corrosion and deposition of metallic debris in the periprosthetic soft tissues of the body, is an uncommon complication. Systemic cobalt toxicity post-arthroplasty is extremely rare. The few known fatal cases of cobalt toxicity appear to be a result of replacing shattered ceramic heads with metal-on-metal or metal-on-polyethylene implants. Friction between residual shards of ceramic and cobalt–chromium implants allows release of cobalt into the synovial fluid and bloodstream, resulting in elevated whole blood cobalt levels and potential toxicity. Case details:This is a single patient chart review of a 60-year-old woman with prior ceramic-on-ceramic right total hip arthroplasty complicated by fractured ceramic components and metallosis of the joint. She underwent synovectomy and revision to a metal-on-polyethylene articulation. Ten months post-revision, she presented to the emergency department (ED) with right hip pain, dyspnea, worsening hearing loss, metallic dysgeusia, and weight loss. Chest CTA revealed bilateral pulmonary emboli (PE), and echocardiogram revealed new cardiomyopathy with global left ventricular hypokinesis with an ejection fraction (EF) of 35–40% inconsistent with heart strain from PE. Whole blood cobalt level obtained two days into her admission was 424.3 mcg/L and 24-h urine cobalt level was 4830.5 mcg/L. Although the patient initially clinically improved with regard to her PE and was discharged to home on hospital day 5, she returned 10 days later with a right hip dislocation and underwent closed reduction of the hip. The patient subsequently decompensated, developing cardiogenic shock, and respiratory failure. She went into pulseless electrical activity (PEA) and expired. Autopsy revealed an extensive metallic effusion surrounding the right hip prosthesis that tested positive for cobalt (41,000 mcg/L). There was also cobalt in the heart muscle tissue (2.5 mcg/g). A whole blood cobalt level obtained two days before she expired was 641.6 mcg/L. Discussion:This is a case of fatal cobalt-induced cardiomyopathy in a patient whose ceramic components of a total hip arthroplasty fractured causing metallosis with worsening cobalt toxicity. We recommend that when a fractured device is revised with a prosthesis with cobalt–chromium components, whole blood and urine cobalt measurements should be obtained and periodically monitored to evaluate for rising concentrations. Providers should be aware of clinical signs and symptoms of cobalt toxicity in patients who have prostheses with cobalt–chromium components. If suspected, toxicology and orthopedics should be involved for possible chelation and removal of the prosthesis. [ABSTRACT FROM PUBLISHER]

Increased accumulation of heavy metal ions such as Cr6+ and Co2+ due to release from prostheses and metallic implants has been reported. These metal ions have been shown to affect both resting and activated lymphocytes. Natural remedies towards mitigating the cytotoxic effects of metal ions are clearly warranted. Polyphenolic compounds which are part of hydrolysable tannins from natural plant sources are considered effective in cheating heavy metal ions in a biological system. We have isolated and characterized a polyphenolic compound (ellagic acid) from Terminalia arjuna fruits that has been tested for its ability to attenuate the metal ion toxicity in primary human lymphocytes in culture. Cr6+ and Co2+ (100 μM) decreased lymphocyte viability and proliferation and increased apoptosis of resting as well as CD3 and/or CD28-stimulated lymphocytes. Metal ions markedly diminished the cytokine (interleukin-2 and interferon-γ) secretion from activated lymphocytes. Pretreatment with ellagic acid at 25, 50, and 100 μM concentrations effectively improved viability and proliferative responses of both resting and activated lymphocytes, while attenuating the apoptotic index. Ellagic acid also tended to normalize the cytokine secretion from the activated lymphocytes even in the presence of metal ions, suggesting broad effects on the adaptive immune system. [ABSTRACT FROM AUTHOR]

Introduction: Cobalt toxicity in patients with hip arthroplasty is a rare complication, but it should be considered in those patients who, after a ceramic fracture, were implanted with a metal-on-polyethylene prosthesis. The complete removal of ceramic particles during revision surgery can be complicated. If the bearing surface is replaced with a metal-on-polyethylene prosthesis, these residual ceramic particles may wear down the chrome-cobalt head, producing localised metallosis. This can trigger blood metal ion levels to rise, causing systemic toxicity. Visual and auditory alterations, cognitive deterioration, hypothyroidism, neuropathy, cardiomyopathy, anorexia, fatigue, diabetes, polycythemia, and respiratory and cutaneous symptoms are some of the clinical manifestations of prosthetic cobaltism. Case description: A young patient presented with multiorgan failure secondary to cobalt toxicity after a ceramic fracture and revision with a metal-on-polyethylene prosthesis; his serum cobalt and chromium levels were 652 μg/L and 270 μg/L, respectively. The patient needed a heart transplant after presenting with cobalt-induced cardiogenic shock. Conclusions: In a patient with a ceramic fracture who is subjected to revision surgery with a metal-on-polyethylene bearing, it is necessary to rule out the possibility of cobalt intoxication. Serum cobalt levels > 20 μg/L are inadmissible; in these cases, surgical treatment should be considered in the short term. A wide synovectomy and replacement of components should be performed with hard friction options, preferably with a ceramic-on-ceramic prosthesis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the sublethal Co toxicity on rainbow trout (Oncorhynchus mykiss). Trout were exposed to Co and selected parameters were evaluated at intervals of 1, 15 and 30 days. Fish exposed to higher levels of Co grew slower than fish exposed to lower levels of Co. Weight gain, specific growth rate (SGR) decreased linearly with the increase of cobalt in the water. The body condition factor (CF) of fish reared in water with low cobalt concentration decreased substantially but this decrease was not significant for fish exposed to higher cobalt concentration. The values of the feed conversion ratio (FCR) increased in fish exposed to higher levels of Co. Co significantly changed the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased at day 30, and in both cases this decrease was more remarkable at day 15 so that the level of AST and ALT reached the control value at day 30. The alkaline phosphatase (ALP) level also showed a remarkable 15-day decline. There was a significant increase in glucose (G) concentration in both Co-exposed groups on day 15. However, serum cholesterol (Chl) was significantly reduced on day 15 and increased on day 30; there were no significant differences in both exposed Co-groups. The triglyceride (TG) level also decreased substantially. There was no regular pattern of total protein (TP) in the serum, so that no significant differences were found in the level of TP between low and high-exposed fish. In summary, this study suggests that exposure of essential trace elements such as cobalt may change growth and biochemical parameters, and that measurement of these parameters may be used in toxicological studies to determine the general health status of fish. [ABSTRACT FROM AUTHOR]

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Safety concerns regarding cobalt-containing metal alloy hip prosthetics (Co-HP) have resulted in product recalls, a medical device alert, and issuance of guidance for clinicians. Recently, cases of suspected prosthetic hip-associated cobalt toxicity (PHACT) from Co-HP have been reported. Although little is known about suspected PHACT, these patients may be referred to medical toxicologists for evaluation and management recommendations. We searched MEDLINE, EMBASE, and unpublished abstracts from toxicology scientific meetings for references relevant to PHACT. Authors independently screened publications for inclusion criteria: publication in English, human study population, subject(s) are symptomatic (except for isolated hip pain), and cobalt values in any matrix (blood, serum, urine, CSF, synovial fluid) available for review. Data from 10 cases are reviewed. Patients with suspected PHACT had findings consistent with cobalt toxicity, including thyroid, cardiac, and neurologic dysfunction. Signs and symptoms appeared between 3 and 72 months after arthroplasty (median 19 months). Neurologic symptoms were most common. Ancillary testing varied considerably. All patients had elevated cobalt levels in one or more matrices. Enhanced elimination was attempted in 27 % of patients. At this time, the information currently available regarding patients with suspected PHACT is inadequate to guide clinical decision making. No consensus has been reached regarding the management of Co-HP patients with systemic symptoms. Indications for chelation have not been established and require further study. Improved case definitions, improved surveillance, and controlled studies are needed to elucidate the scope of this problem and guide future investigations. [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]

We conclude that treatment with either unithiol or acetylcysteine is inefficient in patients with very elevated serum cobalt concentrations, especially greater than 100 µg/L, as long as the damaged prosthesis remains I in situ i . Dear Editor, Previously [[1]] we reported a 56-year-old man with severe cobalt poisoning from a damaged metal-on-ceramic hip prosthesis. However, her serum cobalt concentration reached 221 µg/L in February 2022 on the day of the surgery, which subsequently decreased to 51 µg/L 11 days after surgery, 10 µg/L 2.5 months after surgery, and 3 µg/L 6 months after surgery, all without further treatment. [Extracted from the article]

This case illustrates the potential for systemic cobalt toxicity in non-metal-on-metal bearings and its potentially devastating consequences. We present a 71-year-old male with grinding sensations in his right hip following ceramic-on-ceramic total hip arthroplasty (THA). After diagnosing a fractured ceramic liner, the hip prosthesis was revised into a metal-on-polyethylene bearing. At one year postoperatively, X-rays and MARS-MRI showed a fixed reversed hybrid THA, with periarticular densities, flattening of the femoral head component, and a pattern of periarticular metal wear debris and pseudotumor formation. Before revision could take place, the patient was admitted with the clinical picture of systemic cobalt toxicity, supported by excessively high serum cobalt and chromium levels, and ultimately died. At autopsy dilated cardiomyopathy as cause of death was hypothesized. A third body wear reaction between ceramic remnants and the metal femoral head very likely led to excessive metal wear, which contributed systemic cobalt toxicity leading to neurotoxicity and heart failure. This case emphasizes that fractured ceramic-on-ceramic bearings should be revised to ceramic-on-ceramic or ceramic-on-polyethylene bearings, but not to metal-on-polyethylene bearings. We aim to increase awareness among orthopedic surgeons for clinical clues for systemic cobalt intoxication, even when there is no metal-on-metal bearing surface. [ABSTRACT FROM AUTHOR]

Metal toxicity from metal-on-metal hip replacements is now well documented and several large series have reported local reactions. Although less common, there are reports of similar reactions from failed ceramic liners. Systemic effects documented in literature have been grouped into cardiac, neuro-ocular and thyroid signs.~Introduction~Background~We report a case of a patient who had revision for fractured ceramic liner to metal on polyethylene. Third body effect of the ceramic particles led to wear through of the poly liner and the head directly articulating with metal shell. He developed cardiac and neurological features of cobalt toxicity in addition to extensive soft tissue destruction. Revision of the bearing surfaces and synovectomy led to clinical improvement and fall in metal ion levels.~Methods and Results~Results~We recommend 2-stage revision in such situations and close monitoring of all these patients.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]

Case: We present a case of systemic cobalt toxicity secondary to third-body wear of a cobalt-chromium (CoCr) femoral head following revision of a fractured ceramic bearing. Removal of the CoCr head was followed by resolution of much of the systemic symptoms. Conclusion: This case supports previous reports of cobalt toxicity secondary to catastrophic third-body wear of a CoCr femoral head following a fractured ceramic bearing. It also demonstrates the potential reversibility of many systemic sequelae associated with cobalt toxicity. To our knowledge, this case represents the highest documented blood cobalt level (45,840 nmol/L). [ABSTRACT FROM AUTHOR]

A fifty-two-year-old man underwent heart transplantation at our centre after four years of developing progressive heart failure symptoms due to cobalt toxicity-related cardiomyopathy. Between the ages of forty and forty-two, he underwent bilateral metal-on-metal hip arthroplasties for early onset osteoarthritis. Six years later, he developed increasing fatigue and pericardial effusions. Following a prolonged period of deterioration without a clear cause, the diagnosis of cobalt toxicity-related cardiomyopathy due to cobalt-chromium alloy hip prostheses was eventually made. He underwent bilateral revision hip arthroplasties and was listed for heart transplantation. Metal-on-metal joint replacement is a rare cause of iatrogenic cobalt toxicity. Anaesthetists may encounter patients with unexplained symptoms of heart failure, having a high index of suspicion presenting an opportunity for early diagnosis and intervention before end-stage disease develops. [ABSTRACT FROM AUTHOR]

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]

A 39-year-old female with elevated serum cobalt levels from her bilateral hip prostheses presented with a 3-week history of blurred vision in her left eye. Optical coherence tomography revealed patchy degeneration of the photoreceptor-retinal pigment epithelium (RPE) complex. The lesions were hypofluorescent on indocyanine green angiography. We postulate that this is a case of implant-related chorio-retinal cobalt toxicity. [ABSTRACT FROM AUTHOR]

Prosthetic hip-associated cobalt toxicity (PHACT) is gaining recognition due to the use of metal-on-metal total hip replacements. Identifying true toxicity from merely elevated cobalt levels can be extremely difficult due to the lack of available data. An extensive review of the medical literature was undertaken to characterize cobalt toxicity from prosthetic hips. As an objective approach to making the diagnosis of PHACT, we suggest the following criteria: (1) elevated serum or whole blood cobalt levels due to a prosthetic hip, (2) at least two test-confirmed findings consistent with cobalt toxicity, and (3) exclusion of other etiologies. Adhering to objective diagnostic data for PHACT is a realistic and prudent method by which to eliminate the subjectivity of vague or difficult to identify complaints. These diagnostic criteria are not meant to evaluate prosthetic hardware failure, but as a means to identify systemic cobalt toxicity. Finally, assessment of cobalt toxicity from prosthetic hips should be done in conjunction with a medical toxicologist. [ABSTRACT FROM AUTHOR]

Streptococcus suis is a zoonotic pathogen causing serious infections in swine and humans. Although metals are essential for life, excess amounts of metals are toxic to bacteria. Transcriptome-level data of the mechanisms for resistance to metal toxicity in S. suis are available for no metals other than zinc. Herein, we explored the transcriptome-level changes in S. suis in response to ferrous iron and cobalt toxicity by RNA sequencing. Many genes were differentially expressed in the presence of excess ferrous iron and cobalt. Most genes in response to cobalt toxicity showed the same expression trends as those in response to ferrous iron toxicity. qRT-PCR analysis of the selected genes confirmed the accuracy of RNA sequencing results. Bioinformatic analysis of the differentially expressed genes indicated that ferrous iron and cobalt have similar effects on the cellular processes of S. suis. Ferrous iron treatment resulted in down-regulation of several oxidative stress tolerance-related genes and up-regulation of the genes in an amino acid ABC transporter operon. Expression of several genes in the arginine deiminase system was down-regulated after ferrous iron and cobalt treatment. Collectively, our results suggested that S. suis alters the expression of multiple genes to respond to ferrous iron and cobalt toxicity. [ABSTRACT FROM AUTHOR]

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]

Systemic poisoning related to cobalt–chromium total hip arthroplasty can affect multiple organs. In the otolaryngologic area the most frequent symptoms are tinnitus and hearing loss. In this report, we describe 2 patients with cobalt-containing hip prostheses who presented with otologic symptoms. The first case describes a patient with an extremely high cobalt blood level, which we believe may be one of the highest reported to date, after replacing a broken ceramic-on-ceramic prosthesis with a metal-on-metal prosthesis. This patient suffered all known complications associated with cobalt poisoning and survived. The second case, a female patient with a left resurfacing metal-on-metal prothesis, presented with bilateral continuous high-pitched tinnitus that started 8 months after surgery. Orthopedic surgeons and otologists should be vigilant for cobalt-induced ototoxicity in patients with metal-on-metal total hip prostheses. [ABSTRACT FROM AUTHOR]

We report two Australian patients with possible cobalt toxicity related to metal-on-metal total hip replacements. Both patients were treated for osteoarthritis with a DePuy ASR (articular surface replacement) XL Acetabular Hip System prosthesis, which contains cobalt and chromium, and which has recently been recalled from the market. [ABSTRACT FROM AUTHOR]

This experiment was undertaken to study the toxic effects of cobalt chloride in rats. Sixty-five rats weighing 207 ± 7 g were used. Cobalt chloride was administrated orally in low and high doses for 90 d. The aim of study was to evaluate the effects of cobalt on blood (RBC, WBC, Hb, PLT and HCT) and to investigate the abilities of deferasirox (DFX) and desferrioxamine (DFO) as chelators in removing cobalt from the blood. Cobalt and iron concentrations were determined by flame atomic absorption spectrometer (FAAS). Results show that both of chelators are able to remove cobalt but DFX was more effective, whereas the combined therapy is more efficient. [ABSTRACT FROM AUTHOR]

Characteristics of fungal species tolerant to high levels of metals in natural environment can be amplified by isolation and selection of resistant mutants. Step-by-step culturing led to identification of highly stable Co-resistant (CoR) mutants of A. nidulans. Based on two distinct morphological features, Co-resistant mutants were categorized as CoRI and CoRII. The two mutants varied in their growth behavior and colony morphology that were reflected in supplemented as well as unsupplemented growth media over the generations. As compared to the CoRI, CoRII mutant exhibited sparse mycelia and conidiation but secreted higher amount of melanin. CoR mutants could tolerate up to 2.5mM Co in the medium, however, required a threshold concentration of 0.25mM Co for optimal growth and germination. Absence of Co in the medium caused a stressful situation for the CoR mutants and led to the secretion of a white extracellular precipitate found to be a glycoprotein. In response to interactions with Co-ions, CoR mutants produced oxalic acid and bioprecipitated Co as Co-oxalate providing scope for metal reclamation as well as oxalic acid extraction. The mutants could help to recover the insoluble Co-oxalate salt from aqueous solutions by entrapping it in their growing mycelial meshwork. [ABSTRACT FROM AUTHOR]

Tomato (Lycopersicon esculentum) cv. Pusa ruby was grown in refined sand with complete nutrition (control) and at 0.05, 0.1, 0.2, 0.4, and 0.5 mM of cobalt sulfate. Visible effects of excess cobalt (Co) manifested on tomato at 0.5 mM Co, after 3 days of metal supply to 40 day old plants. The symptoms of excess cobalt diffused chlorosis of young leaves from base and later necrotic spots appeared on chlorotic areas. The necrotic spots enlarged in size, coalesced and in due coarse most of the entire leaf turned necrotic and withered. With excess Co, there was loss of lamina and marginal scorching of affected leaves. The affected leaves were distorted and appeared hook like with rudimentary leaflets at the top. These effects were most severe at 0.5 mM and the intensity of symptoms gradually diminished with a decrease in Co supply from 0.5 to 0.05 mM. At the latter level of Co, no visible effects could be seen except for growth depression. Excess Co restricted the biomass, concentration of phosphorus (P), sulfur (S), and iron (Fe), chlorophyll a and b, DNA and RNA, reducing and non-reducing sugars, starch, total soluble proteins, protein and non-protein nitrogen, and increased phenol and Co concentrations. In excess Co treated tomato leaves, the activity of catalase decreased and peroxidase, ribonuclease, and acid phosphatase increased. The accumulation of Co was greatest in roots and old leaves and lowest in stem of tomato. [ABSTRACT FROM AUTHOR]

Heavy metal stress affects crop growth and yields as wheat (Triticum aestivum L.) growth and development are negatively affected under heavy metal stress. The study examined the effect of cobalt chloride (CoCl2) stress on wheat growth and development. To alleviate this problem, a pot experiment was done to analyze the role of sulfur-rich thiourea (STU) in accelerating the defense system of wheat plants against cobalt toxicity. The experimental treatments were, i) Heavy metal stress (a) control and (b) Cobalt stress (300 µM), ii) STU foliar applications; (a) control and (b) 500 µM single dose was applied after seven days of stress, and iii) Wheat varieties (a) FSD-2008 and (b) Zincol-2016. The results revealed that cobalt stress decreased chlorophyll a by 10%, chlorophyll b by 16%, and carotenoids by 5% while foliar application of STU increased these photosynthetic pigments by 16%, 15%, and 15% respectively under stress conditions as in contrast to control. In addition, cobalt stress enhances hydrogen peroxide production by 11% and malondialdehyde (MDA) by 10%. In comparison, STU applications at 500 µM reduced the production of these reactive oxygen species by 5% and by 20% by up-regulating the activities of antioxidants. Results have revealed that the activities of SOD improved by 29%, POD by 25%, and CAT by 28% under Cobalt stress. Furthermore, the foliar application of STU significantly increased the accumulation of osmoprotectants as TSS was increased by 23% and proline was increased by 24% under cobalt stress. Among wheat varieties, FSD-2008 showed better adaptation under Cobalt stress by showing enhanced photosynthetic pigments and antioxidant activities compared to Zincol-2016. In conclusion, the foliar-applied STU can alleviate the negative impacts of Cobalt stress by improving plant physiological attributes and upregulating the antioxidant defense system in wheat. [ABSTRACT FROM AUTHOR]

The effects of cobalt on the growth and nutrient balance of mung beans were investigated. Inhibition of seedling growth occurred at 5 μM Co and was associated with chlorosis of the younger leaves. Analysis of nutrient concentrations in root and leaf tissue of mung beans treated with 5 μM Co showed that none of the macronutrients and only two of the micronutrients, Mn and Fe, were significantly affected. The Mn concentration in roots was reduced by 55% and the Fe concentration in the leaves by 80%. Uptake of Fe into roots was not inhibited by Co but transport of Fe to the shoot was greatly reduced. It was shown that the effect of Co on growth was additive to that of Fe deficiency, which argues against Co-induced Fe deficiency as the primary cause of growth inhibition by Co. Rather, it was considered that the high concentrations of Co in the roots and leaves compared with essential micronutrient cations can disrupt a range of metabolic processes due to competitive interactions. Comparison of the toxic effects of Co with those of other toxic trace metals Cd, Cu, Ni and Hg showed that at an applied concentration of 5 μM, there were obvious differences in both the visual symptoms and in nutrient concentrations. The main difference between Co and the other metals was that only Co stimulated the uptake of S into the plant and its transport to the shoots, where the S concentration in the leaves was increased 2-fold. The common feature of all the trace metals examined was the strong inhibition of Fe transport to the shoot. A possible mechanism for the interaction of other trace metals with Fe transport is discussed. [ABSTRACT FROM AUTHOR]

The article discusses the cases of two osteoarthritic patients in Australia who were fitted with articular surface replacement (ASR) XL Acetbular Hip System prostheses that contains chromium and cobalt. It focuses on the revision surgeries performed on the patients despite the use of metal-on-metal bearings to reduce wear at the articulation interface. It explores the withdrawal of ASR implants because of the high failure rate and the increase of cobalt level in the body.

Background: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles. Methods: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mgkg per day, n=14) cobalt chloride hexahydrate (12 mg kg per day, n=14) or saline ( n=10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect. Results: During the study period, no significant increase in body weight was noted in the cobalttreated group (−4±1%), which was in contrast to the hydroxocobalamin-treated group (+21±2%) and the saline-treated group (22±2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90±16.30 vs 0.70±0.40 μmol μg in the control group, P<0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10±16.50 μmol μg, P<0.001 vs cobalt-treated group) and the myocardium (4.50±1.20 μmol μg, P<0.001 vs cobalt-treated group). Conclusion: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning. [ABSTRACT FROM AUTHOR]

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects--including peri-implant toxicity, aseptic loosening, and pseudotumor--as well as systemic toxic effects--including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint. [ABSTRACT FROM AUTHOR]

Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been reported to cause widespread systemic toxicity, but its effects on vision have been sparsely reported. The authors report the case of a patient who ingested cattle magnets, which remained in his stomach for an unknown duration of time. These magnets largely consist of cobalt that gradually leached into his blood stream, resulting in protean systemic manifestations, which included optic atrophy. [ABSTRACT FROM AUTHOR]

Background: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles.Methods: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect.Results: During the study period, no significant increase in body weight was noted in the cobalt-treated group (-4 +/- 1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and the saline-treated group (22 +/- 2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/- 16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P < 0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs cobalt-treated group).Conclusion: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning. [ABSTRACT FROM AUTHOR]

A man in his late 30s developed non-ischaemic cardiomyopathy due to systemic cobalt toxicity associated with accelerated bearing surface wear from metal-on- metal hip resurfacing implanted in the previous 6 years. Following revision arthroplasty, the patient regained baseline cardiac function. Cobalt-induced cardiomyopathy is a grave condition that deserves early consideration due to potentially irreversible morbidity. We present this case to increase awareness, facilitate early detection and emphasise the need for research into the diagnosis and management of at-risk patients. [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.

The article discusses the case of a patient with snake eyes sign in the magnetic resonance imaging (MRI) of the cervical spine. Topics discussed include the medical history of the patient, the diagnosis of lower motor neuron (LMN) syndrome of the upper limbs, and cobalt neurotoxicity which resulted from the release of cobalt from the patient's hip prosthesis.

Chemical overexposure is a growing environmental risk factor for many medical issues. Cobalt toxicity from environmental, industrial, and medical exposure has previously been linked to neurological impairment. Hence, the current study looked into the neuroprotective potential of curcumin, a natural polyphenol contained in the spice turmeric, against cobalt-induced neurotoxicity. Adult rats were randomly divided into six groups as follows: control, 40 mg/kg cobalt chloride (CoCl2) only, 240 mg/kg curcumin only, 120 mg/kg or 240 mg/kg curcumin, or 100 mg/kg vitamin C co-administered with CoCl2. The administration was via oral route daily for 4 weeks. After that, neurobehavioral tests were undertaken to evaluate short-term spatial memory. Biochemical investigation was performed to determine the hippocampal levels of status via measures of SOD, CAT, GST, and LPO. Furthermore, immunohistochemical assessment of the expression of GFAP and Nrf2 in the hippocampus was carried out. In the CoCl2 group, the results showed altered behavioral responses, a decrease in antioxidant activities, increased expression of GFAP and the number of activated astrocytes, and decreased immunoexpression of Nrf2. These effects were mitigated in the curcumin- and vitamin C–treated groups. These results collectively imply that curcumin enhances memory functions in rats exposed to cobalt possibly by attenuating oxidative responses, mitigating astrocytosis, and modulating Nrf2 signaling. [ABSTRACT FROM AUTHOR]

The use of wastewater in irrigation weakens the beneficial properties of the soil and leads to a threat to food safety standards. The present research was designed to explore the cobalt toxicity associated with the ingestion of wastewater irrigated wheat. Wheat plants of five different varieties were collected from 7 different sites of Punjab, Pakistan, which were irrigated with three different sources of water. The sampling was done in two cropping years. The cobalt values in water, soil and wheat samples (root, shoot, grain) ranged from 0.46 to 1.24 mg/l, 0.15 to 1.20, 0.29 to 1.30, 0.08 to 0.76 and 0.12 to 0.57 mg/kg, respectively. All the water samples showed high cobalt concentration than the maximum permissible value. However, all the soil and wheat plant samples were found within the maximum allowable range. The high cobalt concentration in irrigating water showed that the continuous usage of such type of water may lead to cobalt toxicity in living organisms with the passage of time and may results in severe health risks. [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]

Objective(s): Cobalt toxicity has become a health concern in recent years, due to overexposure resulting in neurological impairments. With a growing interest in the therapeutic roles of herbs, in toxicity research, it's worth looking into the curative effects of aqueous Prosopis africana seed extract, a plant rich in flavonoids on cobalt-induced neurotoxicity. Materials and Methods: We treated rats with CoCl2 or CoCl2 in combination with aqueous PA seed extract (PAE) orally for 14 days. Control rats received distilled water for the same period. Following treatments, behavioral experiments, analysis for oxidative stress, inflammation, and histological and immunohistochemical analysis were performed. Results: Results revealed that CoCl2 reduced the exploration time, recognition index in the novel object recognition test, percentage spontaneous alternation in the Y-maze tests, and reduced open arm entry and duration in elevated plus-maze. However, treatment with PAE improved these parameters to levels comparable with those of the control group. Furthermore, PAE therapy reduced CoCl2-induced surge in hydrogen peroxide, malondialdehyde, TNF-a and IL-1ß levels in brain homogenate, while also increasing superoxide dismutase and reduced reduced-glutathione activities. CoCl2 exposure resulted in obvious features of neurodegeneration like nuclear disintegration, nuclear shrinkage, and cytoplasmic vacuolations of the cells of the hippocampus and amygdala, with an increased expression of GFAP. The hippocampal and amygdala histology improved after PAE administration, while exacerbated GFAP expressions were attenuated. Conclusion: These findings imply that PAE may be anxiolytic and can help reduce cognitive impairments and hippocampal damage caused by CoCl2 neurotoxicity, via mechanisms that involve attenuation of oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Introduction: There have been concerns about prosthesis failure and the potential for systemic toxicity due to release of cobalt and chromium from metal-on-metal hip joint prostheses (MoM-HP). There is conflicting evidence on whether there is a correlation between higher cobalt and chromium concentrations and systemic toxicity. Methods: We undertook a retrospective review of consecutive patients with MoM-HP referred for outpatient review in toxicology clinics in London, UK, and in the USA recorded in the Toxicology Investigators Consortium (ToxIC) Registry from June 2011 to June 2015. Results: Thirty-one cases were identified; the median (IQR) serum cobalt concentration was 10.0 (3.8-32.8) mcg/L, and the median (IQR) serum chromium concentration was 6.9 (3.7-18.7) mcg/L. Twenty-three (74.2%) had symptoms, most commonly lethargy, hearing loss, and tinnitus. The odds ratios of symptomatic/asymptomatic patients for metal ion concentrations above/below 7 mcg/L were 1.87 (95% CI 0.37-9.57, p = 0.45) and 0.60 (95% CI 0.10-3.50, p = 0.57) for cobalt and chromium, respectively. Two (6.5%) patients with systemic cobalt toxicity had median (IQR) serum cobalt concentrations significantly higher than those without systemic features (630.4 [397.6-863.2] mcg/L versus 9.8 [2.9-16.4] mcg/L; p = 0.017). However, overall, there were no differences between cobalt ( p = 0.38) or chromium ( p = 0.92) concentrations between symptomatic and asymptomatic patients and no clinical features or investigation results correlated with cobalt or chromium concentration. Conclusion: Two (6.5%) of 31 individuals referred for assessment of MoM-HP were diagnosed with systemic cobalt toxicity. However, despite a high prevalence of reported symptoms, neither symptoms nor investigation results correlated with serum cobalt or chromium concentrations. [ABSTRACT FROM AUTHOR]

Purpose: Imaging studies of cobalt toxicity from cobalt-chromium alloy arthroprosthetics have focused on the local intra-articular and peri-articular presentation from failing joint replacements. Most studies investigating neurological findings have been small case series focused on the clinical findings of memory loss, diminished executive function, tremor, hearing and vision loss, depression, and emotional lability. This study utilizes software-based quantitative analysis of brain metabolism to assess the degree of hypometabolism and areas of susceptibility, determine if a pattern of involvement exists, and measure reversibility of findings after prosthetic revision to cobalt-free appliances. Methods: Over 48 months, 247 consecutive patients presenting to an orthopedic clinic with an arthroprosthetic joint containing any cobalt-chromium part were screened with whole blood and urine cobalt levels. A clinically validated inventory of 10 symptoms was obtained. Symptomatic patients with a blood cobalt level above 0.4 mcg/L or urine cobalt greater than 1 mcg/L underwent F-18 FDG PET brain imaging. Analysis was performed with FDA-approved quantitative brain analysis software with the pons as the reference region. Control group was the normal brain atlas within the software. Results: Of the 247 consecutively screened patients, 123 had blood and urine cobalt levels above the threshold. The 69 scanned patients had statistically significant regional hypometabolism and higher symptoms inventory. Fifty-seven patients were retained in the study. Distribution of hypometabolism was in descending order: temporal, frontal, Broca's areas, anterior cingulate, parietal, posterior cingulate, visual, sensorimotor, thalamic, and lastly caudate. Metal-on-metal (MoM) and metal-on-plastic (MoP) joint replacements produced similar patterns of hypometabolism. Of 15 patients with necessary revision surgery, 8 demonstrated improved metabolism when later re-scanned. Conclusion: All scanned patients had regions of significant hypometabolism. Neurological toxicity from elevated systemic cobalt levels following arthroprosthetic joint replacement has a pattern of regional susceptibility similar to heavy metals and solvents, differing from classical dementias and may occur at blood and urine cobalt levels as low as 0.4 mcg/L and 1 mcg/L, respectively. Presently accepted thresholds for cobalt exposure and monitoring may need revision. Quantitative F-18 FDG PET brain imaging may aid in the decision process for treatment options and timing of possible medical versus surgical intervention. [ABSTRACT FROM AUTHOR]

Introduction: An increase in blood serum metal ion levels is seen after implantation of all metal-on-metal (MoM) hip prosthesis. Systemic complaints contributed to raised cobalt ion concentrations in patients with MoM arthroplasty may lead to a variety of symptoms. The aim of this study is to investigate self-reported systemic complaints in association with cobalt ion concentrations in patients with any type of MoM hip prosthesis. Methods: A cohort study was conducted. Patients with both unilateral and bilateral, resurfacing and large head metal on metal total hip arthroplasties (LHMoM THA) were included. Cobalt ion concentrations were measured by inductively coupled plasma mass spectrometry. Based on the known cobalt toxicity symptoms of case-reports and toxicology reports a new non-validated questionnaire was developed. Analysis was performed on two groups; a low cobalt ion concentration group and a high cobalt ion concentration group. Results: A total of 62 patients were included with a mean age at surgery of 60.8 ± 9.3 years and a mean follow up of 6.3 ± 1.4 years. Mean cobalt ion concentrations were 104 ± 141 nmol/L (9-833). Based on the different thresholds (120-170 or 220 nmol/L) the low cobalt ion concentration group consisted of 44 (71%), 51 (82%) or 55 (89%) subjects respectively. In the 120 nmol/L and 170 nmol/L thresholds a significant difference in age was found. The composite score for OVS increased from 54% to 57%-68% with rising threshold value, a hint at the correlation between ion concentration and symptom prevalence Discussion: Ocular-vestibular symptoms were more common in high cobalt ion concentration groups for the three threshold levels tested and with increasing prevalence for higher threshold values. With regards to proactively inquired, self-reported symptoms the threshold where effects may be present could be lower than values currently applied in clinical follow-up [ABSTRACT FROM AUTHOR]