[Experimental study of the influence of phenozanic acid and its combination with valproic acid on the development of the epileptic system]. / Izuchenie vliyaniya fenozanovoi kisloty i ee kombinatsii s val'proevoi kislotoi na razvitie epilepticheskoi sistemy v eksperimente.

OBJECTIVE: To study the effect of phenosanic acid (PA) and its combination with valproic acid (VA) on the development of the Epi system. MATERIAL AND METHODS: A model of focal chronic epilepsy in rats was created by applying metallic cobalt to the surface of the sensorimotor area of the cortex. Long-term electrodes were implanted in the sensorimotor cortex of the left and right hemispheres, the hippocampus, and the hypothalamus. The effect of PA (80 mg/kg) and its combination with VA (200 mg/kg) on discharge activity was carried out on the 2nd day and at the stage of generalization of the Epi system - on the 6th day. The stability of the Epi system on day 10 was assessed by provoking the development of epileptic status (Epi status) in response to the administration of thiolactone homocysteine (HMC) at a dose of 5.5 mmol/kg. RESULTS: In rats treated with PA, low discharge activity is observed, which is confirmed by the absence of EEG and motor manifestations of status epilepticus caused by HMC. PA does not suppress paroxysmal activity at the stages of development of the Epi system. VA significantly suppresses paroxysmal activity, but does not affect the formation of new foci of Epi activity in subcortical structures and the contralateral cortex. The epi system of rats treated with VA is characterized by high discharge activity by the 10th day of the experiment and lability to provocation of epi status. The combination of drugs is more pronounced than PA, but less than VA, reduces the numerical characteristics of paroxysmal activity in the brain structures of rats. CONCLUSION: PA when administered alone, in combination with VA, causes a slowdown in the generalization of convulsive foci of Epi activity and prevents the formation of a stable Epi system. VA, having a pronounced anticonvulsant effect, does not weaken the development of the Epi system in the model of focal cobalt-induced epilepsy.

Cardiac function may be compromised in patients with elevated blood cobalt levels secondary to metal-on-metal hip implants.

Aims: Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods: A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results: Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion: This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties.

Hypoxaemia and risk of asphyxia during underground work in artisanal cobalt mines.

BACKGROUND: More than half the cobalt needed for vehicle electrification originates from the southern part of the Democratic Republic of the Congo (DRC), with a substantial part being extracted by artisanal miners. AIMS: To investigate oxygen saturation during underground work among cobalt artisanal miners. METHODS: In a field survey, we measured oxygen saturation (SpO2) and heart rate by pulse oximetry in 86 miners from two underground mines and 24 miners from a surface mine at four different time points: before descent into the mine (T1), at 50 minutes in the mine (T2), upon leaving the shaft (T3), and 10 minutes after having left the mine (T4). RESULTS: Miners working underground (-36 to -112 meters) were somewhat older (34.8 ±â€…6.7 years) than those working in the surface mine (32.0 ±â€…6.5 years), and they worked more hours daily (12.6 ±â€…1.2 hours) than controls (9.0 ±â€…0.0 hours). All participants had SpO2 >95% at T1 and T4. At T2, SpO2 dropped below 93% and 80% in 35% and 10% underground miners, respectively; SpO2 was still <93% at T3 in 13%. SpO2 remained stable among surface miners. Later, we showed that underground ambient oxygen levels decreased well below 21% in several pits. CONCLUSIONS: Pulse oximetry revealed relevant hypoxaemia during underground work in a substantial proportion of artisanal miners. Such hypoxaemia without evidence of underlying cardiovascular disease is indicative of low ambient oxygen, due to insufficient mine ventilation. This may cause deaths from asphyxia. The hazards of low ambient oxygen in artisanal mines must be prevented by appropriate technical measures ensuring the supply of sufficient fresh air.

Investigating the association between blood cobalt and gallstones: a cross-sectional study utilizing NHANES data.

Background: With the use of cobalt alloys in medical prosthetics, the risk of cobalt exposure has increased. The objective of this study was to investigate the correlation between blood cobalt levels and the occurrence of gallstones utilizing data from the National Health and Nutrition Examination Survey (NHANES). Methods: Data collected between 2017 and 2020 were analyzed, encompassing a total of 5,610 participants. Cobalt concentrations in whole blood specimens were directly measured using inductively coupled plasma mass spectrometry (ICP-MS). The presence of gallstones was ascertained through a standardized questionnaire. To assess the association between blood cobalt levels and the presence of gallstones, logistic regression analysis, restricted cubic spline analysis, and subgroup analysis were utilized. Results: The results of logistic regression analysis revealed a heightened risk of developing gallstones in the Quartiles 2 and Quartiles 4 groups based on blood cobalt levels when compared to the Quartiles 1 group (OR = 1.54, 95% CI: 1.15-2.07; OR = 1.35, 95% CI: 1.03-1.77). The restricted cubic spline analysis exhibited a positive linear correlation between blood cobalt levels and the occurrence of gallstones. Subgroup analyses further demonstrated a statistically significant correlation between the Quartiles 4 category of blood cobalt levels and an elevated risk of gallstones, particularly among individuals aged 60 years or older, females, those with a body mass index (BMI) equal to or exceeding 25, serum total cholesterol levels below 200 mg/dL, as well as individuals diagnosed with hypertension or diabetes. Conclusion: Our study findings indicate a notable association between elevated blood cobalt levels and an increased risk of gallstones. To establish a causal relationship between blood cobalt levels and the elevated risk of developing gallstones, further prospective cohort studies are warranted.

Is there still an indication for the Birmingham Hip Resurfacing in femoral head osteonecrosis?

PURPOSE: Osteonecrosis of the femoral head (ONFH) is a progressive hip disease. Hip resurfacing arthroplasty (HRA) is a preferred surgical procedure among hip arthroplasty performed in young patients. The aim of this study is to show the long-term clinical and radiological results of HRA procedures performed for patients suffering from ONFH. METHODS: Forty-five patients who underwent hip resurfacing with the diagnosis of femoral head osteonecrosis were included in the study. The Harris Hip Score (HHS) was used for clinical scoring of the patients. The blood chromium, cobalt, white blood cell (WBC) count, and CRP levels of patients were checked. Ultrasonography (USG) was performed for all patients at mid-term control checked for pseudo-tumours. For the radiological evaluation, acetabular inclination, stem shaft angle, prothesis-to-neck ratio, osteolysis zones, and heterotopic ossification were used. RESULTS: The mean age of the patients was 46.6 ± 9.3 years, and the mean follow-up period was 11.83 ± 2.9 years. The mean HHS was 90.3 ± 12.8 for final follow-up. The mean WBC value was 8.2 109/L, mean CRP value was 6.3 mg/L, mean chromium value was 4.9 µg/L, and mean cobalt value was 1.8 µg/L. Inclination changing 0.2°(p = 0.788), stem shaft angle changing 0.7°(p = 0.424), and neck-to-prosthesis ratio changing 0.01°(p = 0.075). No pseudo-tumours were detected in any patients in USG examination. CONCLUSION: HRA provides long-term implant survival and excellent clinical outcomes for end-stage ONFH patients with low complication rates.

The association of cobalturia with cobaltism symptoms a prospective blinded study of 229 post-arthroplasty patients.

INTRODUCTION: Cobalt is a mitochondrial toxin, clinical cobaltism manifests with constitutional, neurologic, and cardiovascular symptomatology. Cobalt's severe toxidrome is known through case reports from extreme wear or corrosion of cobalt-chromium arthroplasty components. However, the spectrum and epidemiology of orthopedic-implant cobaltism and its relationship to duration and degree of cobalt exposure are not well defined. METHODS: The relationship of urine-cobalt concentration and duration of exposure to cobalt-chromium joint implants and cobaltism symptomatology were prospectively studied in 229 patients. Subjects received a Cobaltism-Symptom-Inventory-Score (CSIS) based on a protocolized interview and examination followed by a spot urine-cobalt measurement. RESULTS: 129 (56%) subjects were cobalturic (urine-cobalt ≥1.0 ppb). 122 (53%) subjects had a CSIS of >2, this status significantly associates with cobalturia. Median [IQR] urine-cobalt in the subjects with a CSIS >2 was 4.1[1.1-17.0] ppb compared to 0.5[0.5-1.4] ppb in subjects with CSIS ≤ 2. Cobalturia has a sensitivity of 0.69, a specificity of 0.77, and a positive predictive value of 0.74 for a CSIS of >2. The product of years-exposed to a cobalt-chromium implant and urine-cobalt by quartiles significantly positively associates with the Cobaltism-Symptom-Inventory-Score. CONCLUSION: A urine-cobalt of ≥1 ppb likely indicates adverse systemic exposure to orthopedic-implant generated cobalt. Cobaltism severity as quantified by the CSIS significantly correlates with the product of spot urine-cobalt concentration and years-exposed to a cobalt-chromium orthopedic-implant indicating a dose-response relationship. Medical provider and public awareness of orthopedic-implant cobaltism is vital because tens-of-millions are at-risk and early cobaltism is reversible. Further use of cobalt-chromium orthopedic-implants should be questioned given cobaltism becomes clinically apparent at a spot urine-cobalt of 1 ppb or greater. Monitoring of patients with high-risk cobalt-chromium orthopedic-implants appears to be indicated.

Delayed Severe Gingivitis After Placement of Orthodontic Braces in an Atopic Teenager: A Case Report and Literature Review.

We report a case of a 15-year-old atopic patient presenting with delayed, severe ulcerative hypertrophic gingivitis after placement of orthodontic braces, which required removal of braces and restorative laser surgical procedures. Patch testing to multiple metals and chemicals showed weak positive reactions to steel bands and formaldehyde. The patient experienced urticarial, gingivitis, and other intraoral symptoms after patch testing and re-exposure to nickel-containing products. In contrast, nickel, cobalt, and cobalt-chromium (Co-Cr) bracket patch testing sites were negative. Nickel-caused contact dermatitis is Type IV delayed hypersensitivity reaction occurring at least 24 h after exposure. This reaction can result in intraoral blisters, ulcerations, eczematous and urticarial reactions of the face and more distant skin areas. This case illustrates the intraoral delayed response, symptom resolution after removing the braces, and brackets and local reactions upon subsequent nickel exposure, despite negative patch testing and lymphocyte stimulation test to nickel. This case further illustrates the difficulty associated with diagnosing nickel allergy.

Patch Testing With Cobalt in Adults: A North American Contact Dermatitis Group Experience, 2001-2018.

Background: Cobalt is a recognized cause of allergic contact dermatitis (ACD); however, detailed information on patient characteristics, sites, and sources is lacking. Objective: The aim of the study is to assess trends in patch test reactions to cobalt and associated patient characteristics, common sources, and body sites affected. Methods: The study used a retrospective analysis of adult patients who were patch tested to cobalt by the North American Contact Dermatitis Group between 2001 and 2018 (n = 41,730). Results: Overall, 2986 (7.2%) and 1362 (3.3%) had allergic or currently relevant patch test reaction to cobalt, respectively. Patients with versus without an allergic patch test reaction to cobalt were more likely to be female, employed, have a history of eczema or asthma, be Black, Hispanic, or Asian, and have occupational-related dermatitis. The most commonly identified sources of cobalt in allergic patients included jewelry, belts, and cement, concrete, and mortar. Affected body site(s) varied by cobalt source among patients with currently relevant reactions. Occupational relevance was found in 16.9% of patients with positive reactions. Conclusions: Positive patch test reactions to cobalt were common. The most common body sites were the hands, and affected site varied by the source of cobalt.

A Comparison of Clinical Outcomes After Total Knee Arthroplasty in Patients With Preoperative Nickel Allergy Receiving Cobalt Chromium or Nickel-Free Implant.

BACKGROUND: The role of metal hypersensitivity reactions in total knee arthroplasty (TKA) failure is debated. There is no consensus on whether use of a more expensive nickel-free implant is indicated for patients who have preoperative nickel allergy. The purpose of this study was to examine the outcome of patients who have preoperative nickel allergy receiving nickel-free or cobalt chromium (CoCr) implants. METHODS: This was a retrospective review of 17,798 patients who underwent 20,324 unilateral primary TKAs between 2016 and 2020. Presence of preoperative nickel allergy was determined (n = 282). Patients were divided into 2 cohorts: those receiving (1) nickel-free or (2) CoCr implants. Clinical outcome scores and revision rates were assessed. RESULTS: 243 received a nickel-free implant and 39 received a CoCr implant. There was no significant difference in revision rate between the cohorts. Survivorship free of revision was 94% in the CoCr implant cohort and 98% in the nickel-free implant cohort (P = .9). When comparing clinical outcome scores between cohorts, there was no difference in preoperative, 6-week or 1-year Knee Osteoarthritis Outcome Score Joint Replacement, Visual Analog Scale (VAS), Lower Extremity Activity Scale, Patient-Reported Outcomes Measurement Information System (PROMIS), and Veterans RAND 12-item scores between cohorts. CONCLUSION: In this retrospective cohort study, there was no difference in revision rates or clinical outcomes in patients who had a nickel allergy undergoing primary TKA with CoCr or nickel-free implants. Further studies are needed to determine if nickel allergy is an independent risk factor for worse TKA outcomes in general.

Copper modified cobalt-chromium particles for attenuating wear particle induced-inflammation and osteoclastogenesis.

The nature of aseptic prosthetic loosening mainly relates to the wear particles that induce inflammation and subsequent osteoclastogenesis. The ideal approach to impede wear particle-induced osteolysis should minimize inflammation and osteoclastogenesis. In this work, Co29Cr9W3Cu particles were used as a research model for the first time to explore the response of Co29Cr9W3Cu particles to inflammatory response and osteoclast activation in vitro and in vivo by using Co29Cr9W particles as the control group. In vitro studies showed that the Co29Cr9W3Cu particles could promote the generation of M2-phenotype macrophages and increase the expression level of anti-inflammatory factor IL-10, while inhibiting the formation of M1-phenotype macrophages and down-regulating the expression of inflammatory factors TNF-α, IL-6 and IL-1ß; More importantly, the Co29Cr9W3Cu particles reduced the expression of NF-κB and downstream osteoclast related-specific transcription marker genes, such as TRAP, NFATc1, and Cath-K; In vivo results indicated that the Co29Cr9W3Cu particles exposed to murine calvarial contributed to decreasing the amount of osteoclast and osteolysis area. These findings collectively demonstrated that Cu-bearing cobalt-chromium alloy may potentially delay the development of aseptic prosthetic loosening induced by wear particles, which is expected to provide evidence of Co29Cr9W3Cu alloy as an alternative material of joint implants with anti-wear associated osteolysis.

Characterization of ion release from a novel biomaterial, Molybdenum-47.5Rhenium, in physiologic environments.

BACKGROUND CONTEXT: Metals from spinal implants are released into surrounding tissues by various mechanisms. Metal ion release has been associated with clinical implant failure, osteolysis, and remote site accumulation with adverse events. Significant corrosion and associated metal ion release has been described with currently used spinal implant alloys. A novel metal alloy, Molybdenum-47.5Rhenium alloy (MoRe®), was approved for use in medical implants in 2019 by the FDA. PURPOSE: To evaluate the metal ion release profile of MoRe alloy after immersion in both a stable physiologic, as well as in an inflammatory environment. STUDY DESIGN: In vitro study. METHODS: The ion release profile of the MoRe alloy was comprehensively evaluated in-vitro after prolonged immersion in physiologic and inflammatory environments. Ion concentration analyses were then conducted using inductively coupled plasma-mass spectrometry (ICP-MS) methods. Comparative testing of titanium (Ti-6Al-4V) and cobalt chromium (Co-28Cr-6Mo) was also performed. RESULTS: Under baseline physiologic conditions, the MoRe alloy demonstrates very low molybdenum and rhenium ion release rates throughout the 30-day test period. During the first time interval (day 0-1), low levels of molybdenum and rhenium ions are detected (<0.3 µg/cm2 day) followed by a rapid reduction in the ion release rates to <0.05 µg/cm2 day during the second time interval (days 1-3) followed by a further reduction to very low steady-state rates <0.01 µg/cm2 day during the third time interval (days 3-7), which were maintained through 30 days. In the inflammatory condition (H2O2 solution), there was a transient increase in the release of molybdenum and rhenium ions, followed by a return to baseline ion release rates (days 2-4), with a further reduction to low steady-state rates of ∼0.01 µg/cm2 day (days 4-8). The measured molybdenum and rhenium ion release rates in both steady state (<0.01 µg/cm2 day), and inflammatory environments (0.01 µg/cm2 day) were far below the established FDA-permitted daily exposure (PDE) of 1,900 µg/cm2 day for molybdenum and 4,400 µg/cm2 day for rhenium. In contrast, titanium and cobalt chromium approached or exceeded their established PDE values in an inflammatory environment. CONCLUSIONS: The novel biomaterial MoRe demonstrated a lower metal ion release profile in both a physiologic and inflammatory environment and was well below the established PDE.  Comparative testing of the cobalt-chromium and titanium alloys found higher levels of ion release in the inflammatory environment that exceeded the PDE for cobalt and vanadium.

Cobalt nanoparticles cause allergic contact dermatitis in humans.

BACKGROUND: Cobalt (Co) causes allergic contact dermatitis (ACD) and the emerging use of Co nanoparticles (CoNPs) warrants gaining further insight into its potential to elicit ACD in sensitized individuals. OBJECTIVES: The aims of the study were to clarify to what extent CoNPs may elicit ACD responses in participants with Co contact allergy, and to evaluate whether the nanoparticles cause a distinct immune response compared with cobalt chloride (CoCl2) in the skin reactions. METHODS: Fourteen individuals with Co contact allergy were exposed to CoNPs, CoCl2, a Co-containing hard-metal disc (positive control), and an empty test chamber (negative control) by patch testing. Allergic responses were evaluated clinically by a dermatologist at Days 2, 4 and 7. At Day 2, patch-test chambers were removed, and remaining test-substance and skin-wipe samples were collected for inductive-coupled plasma mass spectrometry (ICP-MS) analysis. Additionally, skin biopsies were taken from patch-test reactions at Day 4 for quantitative real-time polymerase chain reaction analysis, histopathology and ICP-MS analysis of Co skin penetration. RESULTS: Patch testing with CoNPs elicited allergic reactions in Co-sensitized individuals. At all timepoints, clinical assessment revealed significantly lower frequencies of positive patch-test reactions to CoNPs compared with CoCl2 or to the positive control. CoNPs elicited comparable immune responses to CoCl2. Chemical analysis of Co residues in patch-test filters, and on skin, shows lower doses for CoNPs compared with CoCl2. CONCLUSIONS: CoNPs potently elicit immune responses in Co-sensitized individuals. Even though patch testing with CoNPs resulted in a lower skin dose than CoCl2, identical immunological profiles were present. Further research is needed to identify the potential harm of CoNPs to human health.

Contact allergy to metals in metalworkers: A systematic review and meta-analysis.

Occupational hand eczema is frequent in metalworkers. The contribution of metal allergies is poorly elucidated even though such exposures are common at the workplace. To estimate the prevalence of metal allergy to cobalt (Co), chromium (Cr) and nickel (Ni) in metalworkers and compare these to estimates from the European Surveillance System on Contact Allergies (ESSCA). Two authors independently searched PubMed for studies reporting on the prevalence of metal allergy in metalworkers. Proportion meta-analyses were performed to calculate the pooled proportions of metal allergy in metalworkers. In total, 29 studies (22 from Europe) were included yielding 5691 subjects for quantitative analysis. The pooled proportion (95% confidence interval) of Co, Cr and Ni in European metalworkers with dermatitis referred to patch test clinics was 8.2% (5.3%-11.7%), 8.0% (5.1%-11.4%), and 11.0% (7.3%-15.4%), respectively. The corresponding estimates for unselected metalworkers from workplace studies were 4.9% (2.4%-8.1%), 5.2% (1.0%-12.6%), and 7.6% (3.8%-12.6%), respectively. In comparison, the prevalence of metal allergy in 13 382 consecutive European males with dermatitis was 3.9% (3.6%-4.2%), 4.4% (4.1%-4.8%) and 6.7% (6.3%-7.0%) for Co, Cr and Ni, respectively. Data on sex, age, body piercings and atopic dermatitis in metalworkers with metal allergy was mostly lacking. Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA data, indicating a relationship to occupational exposures, however, confounders could not be accounted for.

Blood cobalt ion level in patients with different sizes of cobalt/chrome femoral head with the Accolade TMZF stem.

BACKGROUND: Corrosion of stem-cobalt/chromium (Co/Cr) head interface and subsequent systemic Co ion complication have been a clinical concern after total hip arthroplasty (THA). The aim of this study is to investigate correlation between type of femoral head and blood Co ion level. METHODS: One hundred four patients with THA using accolade TMZF and Co/Cr femoral head (32-mm; 55 cases, 36-mm; 20 cases, dual mobility system (DM) with 22.2 or 28-mm inner head; 29 cases) participated in this study, and blood Co ion concentration test was performed in patients a minimum of four years after THA. RESULTS: DM group was significantly older than 32-mm and 36-mm group (DM: 73.9 ± 4.6, 32-mm: 63.3 ± 8.5, 36-mm: 66.8 ± 10.5). The median (interquartile range) blood Co concentration of each group was 32-mm group 0.26 µg/L (0.69), 36-mm group; 0.21 µg/L (0.30); and DM group 0.21 µg/L (0.13). There was a significant difference of Co concentration between DM and 32-mm group (p = 0.023). Abnormal values of the blood Co concentration (> 1 µg/L) were observed in the 32-mm group; 12 cases (21.8%), 36-mm group; 2 cases (10.0%); and DM group; 0 case (0%) (p = 0.018). CONCLUSIONS: Co blood concentration differed among the different sizes of Co/Cr femoral head. THA using DM is a safe option with low risk of complication from cobalt ion if it is used for elderly patients.