Evaluating the serum levels of zinc, copper, magnesium, and 25-hydroxy vitamin D in children with idiopathic drug-resistant epilepsy; a cross-sectional study.

BACKGROUND: Drug-resistant epilepsy is defined as failure of seizure control in spite of using 2 or 3 proper antiepileptic drugs in appropriate time. Mineral elements play important roles in neuronal function; it is believed that mineral deficiency may lead to complications through seizure management. In the present study, serum levels of zinc (Zn), copper (Cu), magnesium (Mg), calcium (Ca), and 25-hydroxy vitamin D (Vit D) in drug-resistant-epilepsy (DRE) patients were evaluated and compared with the controlled patients. METHODS: In this cross-sectional study, epileptic patients were included and categorized into two groups of DRE and well-controlled patients. Patients' serum samples were analysed to evaluate Zn, Cu, Mg, Ca, and Vit D levels. The primary objective was comparison of serum levels of different trace elements between the groups. RESULTS: Sixty-four epileptic children including 33 DRE and 31 well-controlled children entered the study. The DRE children showed a significantly earlier onset of disease compared to the other group (p = 0.014). Comparing the frequency of developmental delay between the groups, the results showed this complication was significantly more frequent in the DRE group (p < 0.001). Concerning serum elements, the results showed a significantly higher concentration of Zn in the well-controlled group than the DRE group (p = 0.007). On the other hand, no significant differences were observed between the groups regarding the means of Vit D, Ca, Cu, and Mg levels (p > 0.05). CONCLUSION: The results of the present study delineated that drug-resistant epilepsy patients had earlier onset of disease and were at higher risk of neurodevelopmental delay compared with well-controlled-epilepsy patients. A significant lower serum levels of Zn were also observed in drug-resistant-epilepsy patients. This finding may suggest the role of zinc supplementation in help to better control of drug-resistant seizures, as well as, the importance of serum zinc monitoring in epileptic patients.

Association of whole blood copper, zinc, calcium, magnesium, and iron with non-alcoholic fatty liver disease in overweight and obese children. / å ¨è¡€é“œã€é”Œã€é’™ã€é•ã€é“ä¸Žè¶ é‡è‚¥èƒ–å„¿ç«¥éžé ’ç²¾æ€§è„‚è‚ªè‚ç— çš„å ³è”.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in overweight and obese children, and its etiology and pathogenesis remain unclear, lacking effective preventive and therapeutic measures. This study aims to explore the association between whole blood copper, zinc, calcium, magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years, providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. METHODS: A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys. Fasting blood samples were collected from the subjects, and various indicators such as blood glucose, blood lipid, and mineral elements were detected. All children were divided into an overweight group (n=400) and a NAFLD group (n=202). The NAFLD group was divided into 2 subgroups according to the ALT level: A non-alcoholic fatty liver (NAFL) group and a non-alcoholic steatohepatitis (NASH) group. Logistic regression analysis was used to analyze the association between minerals (copper, zinc, calcium, magnesium, and iron) and NAFLD, NAFL and NASH. RESULTS: A total of 602 subjects were included, of whom 73.6% were male, with a median age of 10 (9, 11) years, and a body mass index (BMI) of 24.9 (22.7, 27.4) kg/m2. The intergroup comparison results showed that compared with the overweight group, the NAFLD group had higher levels of age, BMI, diastolic blood pressure (DBP), systolic blood pressure (SBP), triglyceride (TG), low density lipoprotein (LDL), alanine transaminase (ALT) and aspartate aminotransferase (AST), and lower level of high density lipoprotein (HDL). The NAFL group had higher levels of age, BMI, DBP, SBP, ALT, and AST, and lower levels of HDL compared with the overweight group. The levels of age, BMI, DBP, SBP, TG, LDL, ALT, and AST of NASH were higher than those in the overweight group, while the level of HDL was lower than that in overweight group (all P<0.017). After adjusting for a variety of confounders, the OR of NAFLD for the highest quantile of iron was 1.79 (95% CI 1.07 to 3.00) compared to the lowest quantile, and no significant association was observed between copper, zinc, calcium, and magnesium, and NAFLD. The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21 (95% CI 1.26 to 3.88), while no significant association was observed between iron level and NASH. In addition, no significant associations were observed between copper, zinc, calcium, and magnesium levels and NAFL or NASH. CONCLUSIONS: High iron level increases the risk of NAFLD (more likely NAFL) in overweight and obese children, while copper, zinc, calcium, magnesium, and other elements are not associated with the risk of NAFLD in overweight and obese children.

Development and characterization of a non-enzymatic electrochemical biosensor for rapid determination of sorbent-based extracted trazodone and doxepin in complicated samples.

BACKGROUND: Given the importance of achieving optimal therapeutical concentration in patients treated with antidepressants, this study investigates a novel technique for the simultaneous determination of trazodone (TRZ) and doxepin (DOX) in human plasma and serum samples for the first time. RESULTS: To achieve simultaneous determination of two antidepressants, TRZ and DOX, a novel detection system was designed: a non-enzymatic voltammetric biosensor based on boron-reduced graphene oxide/manganese oxide nanoparticles (GCE/B-rGO/MnO NPs). The detection was accomplished after pre-concentration and extraction trace amounts of the analytes using the thin film-solid phase microextraction (TF-SPME) technique, which employed polyvinyl alcohol/polyvinyl acetate/copper oxide nanoparticles (PVA/PVAc/CuO NPs) electrospun nanofibers. The successful preparation of composite nanofibers and modified electrodes was confirmed using the evaluation of field emission-scanning electron microscopy (FE-SEM) and energy-dispersive X-ray spectroscopy (EDX). Also, the composite nanofibers were characterized with attenuated total reflectance-Fourier transform-infrared (ATR-FT-IR) and X-ray diffraction (XRD). In the solution of TRZ and DOX, under optimum experimental conditions, the linear dynamic ranges (LDRs) were 0.1-20.0 µmol L-1 and 0.5-27.0 µmol L-1, respectively. Also, the limit of detection (LOD) values of TRZ and DOX were 0.032 and 0.150 µmol L-1. SIGNIFICANCE: PVAc acts as a cross-linking agent for PVA, and their mixture is effective for sample preparation and pre-concentration of analytes in complex matrices. Also, adding CuO NPs to this polymeric mixture enhanced the adsorption efficiency. Taking advantage of the high surface area of MnO NPs and the high electrical conductivity of B-rGO, and considering the superiority of their simultaneous utilization, the constructed electrochemical biosensor is both cost-effective and rapid. It demonstrates excellent stability, repeatability, and sensitivity for the simultaneous determination of TRZ and DOX under optimal conditions. This biosensor, the first of its kind, is specifically designed for the simultaneous determination of TRZ and DOX in human plasma and serum samples, representing a significant advancement in biosensing technology.

Exploring the Regulatory Effect of LPJZ-658 on Copper Deficiency Combined with Sugar-Induced MASLD in Middle-Aged Mice Based on Multi-Omics Analysis.

Globally, metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), is one of the most common liver disorders and is strongly associated with copper deficiency. To explore the potential effects and mechanisms of Lactiplantibacillus plantarum LPJZ-658, copper deficiency combined with a high-sugar diet-induced MASLD mouse model was utilized in this study. We fed 40-week-old (middle-aged) male C57BL/6 mice a copper-deficient and high-sugar diet for 16 weeks (CuDS), with supplementary LPJZ-658 for the last 6 weeks (CuDS + LPJZ-658). In this study, we measured body weight, liver weight, and serum biochemical markers. Lipid accumulation, histology, lipidomics, and sphingolipid metabolism-related enzyme expression were investigated to analyze liver function. Untargeted metabolomics was used to analyze the serum and the composition and abundance of intestinal flora. In addition, the correlation between differential liver lipid profiles, serum metabolites, and gut flora at the genus level was measured. The results show that LPJZ-658 significantly improves abnormal liver function and hepatic steatosis. The lipidomics analyses and metabolic pathway analysis identified sphingolipid, retinol, and glycerophospholipid metabolism as the most relevant metabolic pathways that characterized liver lipid dysregulation in the CuDS group. Consistently, RT-qPCR analyses revealed that the enzymes catalyzing sphingolipid metabolism that were significantly upregulated in the CuDS group were downregulated by the LPJZ-658 treatment. In addition, the serum metabolomics results indicated that the linoleic acid, taurine and hypotaurine, and ascorbate and aldarate metabolism pathways were associated with CuDS-induced MASLD. Notably, we found that treatment with LPJZ-658 partially reversed the changes in the differential serum metabolites. Finally, LPJZ-658 effectively regulated intestinal flora abnormalities and was significantly correlated with differential hepatic lipid species and serum metabolites. In conclusion, we elucidated the function and potential mechanisms of LPJZ-658 in alleviating copper deficiency combined with sugar-induced middle-aged MASLD and hope this will provide possible treatment strategies for improving MASLD.

Trace Element Deficiency in Systemic Sclerosis-Too Much Effort for Some Traces?

Trace elements are essential for several physiological processes. To date, various data have suggested that inadequate levels of trace elements may be involved in the pathogenesis of different chronic diseases, including immune-mediated ones, or may develop during their course. Systemic sclerosis (SSc) is a complex autoimmune multisystemic disease, primarily characterized by microvascular dysregulation, the widespread activation of the immune system and tissue fibrosis. According to the latest reports regarding the pathogenesis of SSc, the main pathophysiological processes-inflammation, vasculopathy and fibrosis-may include various trace element derangements. The present literature review aims to update the available data regarding iron, zinc, copper and selenium status in SSc as well as to underline the possible implications of these trace elements in the complexity of the pathogenic process of the disease. We observe that the status of trace elements in SSc plays a crucial role in numerous pathogenic processes, emphasizing the necessity for proper monitoring and supplementation. The reported data are heterogenous and scarce, and future studies are needed in order to draw clearer conclusions about their complete spectrum.

Serum copper and obesity among healthy adults in the National Health and Nutrition Examination Survey.

BACKGROUND: Copper (Cu) homeostasis are important processes in the cause of metabolic diseases, but the association between Cu and obesity remains unclear. METHODS: Participants were drawn from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression assessed the associations of serum Cu concentrations (tertiles) with obesity and central obesity in individuals without comorbidities. Obesity was defined as a BMI ≥30.0 kg/m2, and central obesity was defined as a waist circumference ≥80 cm for women and ≥95 cm for men. RESULTS: This cross-sectional study included 1,665 adults without comorbidities, representing 24,744,034 people (mean age 35.1 years, 48.5% female). High serum Cu levels (tertile 3: ≥19.19 µmol/L) were associated with higher odds of obesity (adjusted odds ratio [OR]: 4.48, 95% CI[confidence interval]: 2.44-8.32) and central obesity (OR: 2.36, 95% CI: 1.19-4.66) compared to low serum Cu levels (tertile 1: ≤15.64 µmol/L). The dose-response curve showed a nonlinear association between Cu levels and obesity (P-nonlinear = 0.02) and a linear association with central obesity (P-nonlinear = 0.21). CONCLUSION: This study suggests that higher serum Cu levels are associated with increased odds of obesity in healthy American adults.

Selective and sensitive CQD-based sensing platform for Cu2+ detection in Wilson's disease.

Excessive Cu2+ intake can cause neurological disorders (e.g. Wilson's disease) and adversely affect the gastrointestinal, liver, and kidney organs. The presence of Cu2+ is strongly linked to the emergence and progression of Wilson's disease (WD), and accurately measuring the amount of copper is a crucial step in diagnosing WD at an early stage in a clinical setting. In this work, CQDs were fabricated through a facile technique as a novel fluorescence-based sensing platform for detecting Cu(II) in aqueous solutions, and in the serum samples of healthy and affected individuals by WD. The CQDs interact with Cu(II) ions to produce Turn-on and Turn-off states at nano-molar and micro-molar levels, respectively, with LODs of 0.001 µM and 1 µM. In fact, the Cu2+ ions can act like a bridge between two CQDs by which the charge and electron transfer between the CQDs may increase, possibly can have significant effects on the spectroscopic features of the CQDs. To the best of our knowledge, this is the first reported research that can detect Cu(II) at low levels using two different complexation states, with promising results in testing serum. The potential of the sensor to detect Cu(II) was tested on serum samples from healthy and affected individuals by WD, and compared to results obtained by ICP-OES. Astonishingly, the results showed an excellent correlation between the measured Cu(II) levels using the proposed technique and ICP-OES, indicating the high potential of the fluorimetric CQD-based probe for Cu(II) detection. The accuracy, sensitivity, selectivity, high precision, accuracy, and applicability of the probe toward Cu(II) ions make it a potential diagnostic tool for Wilson's disease in a clinical setting.

Association between serum copper and blood glucose: a mediation analysis of inflammation indicators in the NHANES (2011-2016).

Background: The rising prevalence of diabetes underscores the need for identifying effective prevention strategies. Recent research suggests environmental factors, particularly heavy metals like copper, significantly influence health outcomes, including diabetes, through mechanisms involving inflammation and oxidative stress. This study aims to explore how serum copper levels affect blood glucose, employing NHANES data from 2011 to 2016, to provide insights into environmental health's role in diabetes prevention and management. Methods: The study analyzed data from 2,318 NHANES participants across three cycles (2011-2016), focusing on those with available data on serum copper, inflammatory markers, and blood glucose levels. We utilized principal component analysis for selecting inflammatory markers, mediation analysis to examine direct and indirect effects, multiple linear regression for assessing relationships between markers and glucose levels, and weighted quantile sum regression for evaluating individual and collective marker effects, adjusting for demographic variables and serum copper. Results: Participants averaged 42.70 years of age, with a near-even split between genders. Average serum copper was 119.50 µg/dL, white blood cell count 6.82 × 109/L, and fasting blood glucose 107.10 mg/dL. Analyses identified significant mediation by inflammatory markers (especially white blood cells: 39.78%) in the copper-blood glucose relationship. Regression analyses highlighted a positive correlation between white blood cells (estimate: 1.077, 95% CI: 0.432 to 2.490, p = 0.013) and copper levels and a negative correlation for monocyte percentage (estimate: -1.573, 95% CI: 0.520 to -3.025, p = 0.003). Neutrophil percentage was notably influential in glucose levels. Sensitive analyses confirmed the study's findings. Conclusion: Serum copper levels significantly impact blood glucose through inflammatory marker mediation, highlighting the importance of considering environmental factors in diabetes management and prevention. These findings advocate for public health interventions and policies targeting environmental monitoring and heavy metal exposure reduction, emphasizing the potential of environmental health measures in combating diabetes incidence.

Effect of Enteral Zinc Supplementation on the Anthropometric Measurements of Preterm Infants at Discharge from the Neonatal Intensive Care Unit and Evaluation of Copper Deficiency.

Enteral zinc supplementation in preterm infants has been reported to improve short-term weight and height gain. This study aims to evaluate whether early enteral zinc supplementation in preterm infants admitted to the neonatal intensive care unit (NICU) affects their physical measurements at discharge, and to periodically test serum copper levels. Of the 221 patients admitted to the NICU, 102 were in the zinc group and 119 were in the no-zinc group. The zinc group was administered 3 mg/kg/day of zinc. Body weight, height, and head circumference at discharge (or on the expected delivery date) were evaluated, and the factors affecting these parameters were examined. Serum zinc and copper levels were also evaluated on admission and monthly thereafter. Multivariate analysis was performed and showed that the weeks of gestational age and small for gestational age (SGA) status affected the height and weight at discharge. SGA also affected the head circumference. Serum copper levels were within the reference range for all patients at 3 months of age. Enteral zinc supplementation of 3 mg/kg/day in preterm infants did not affect the weight, height, or head circumference at discharge, but was shown to be relatively safe.

Trace mineral concentrations in Canadian beef calves at weaning.

Objective: To describe the copper and selenium statuses of beef calves at weaning. Animal: Calves (n = 1998) were sampled from 106 Canadian cow-calf herds in the fall of 2021. Procedure: Serum samples from calves were tested for copper, selenium, and molybdenum concentrations. Results: Although the percentages of calves classified as selenium deficient (< 0.025 ppm) were relatively low (0.5% western Canada, 3% eastern Canada), 53% of calves from western Canada and 77% of calves from eastern Canada were classified as having less than adequate selenium concentrations (< 0.08 ppm). Copper deficiency (< 0.5 ppm) was common in calves from both western (17%) and eastern (14%) Canada. High molybdenum concentrations (> 0.10 ppm) were identified in 6% of calves from western Canada and 7% of calves from eastern Canada. Conclusion: Selenium concentrations were higher in calves from western Canada than from those in eastern Canada (P < 0.001). Copper and molybdenum concentrations were not significantly different between western and eastern Canada. Less-than-adequate serum copper was the most common deficiency identified in Canadian beef calves at weaning. Clinical relevance: Trace minerals are important for immune system function in calves at weaning. Selenium concentrations in calves at weaning were lower than in cows from the same herds collected at pregnancy testing 2 y earlier. Copper deficiency was also identified, though less frequently than for mature cows. Supplementation programs for calves should be customized based on testing and recognize both regional and age differences in risk.

Concentrations d'oligo-éléments minéraux chez les veaux de boucherie canadiens au sevrage. Objectif: Décrire les statuts en cuivre et en sélénium des veaux de boucherie au sevrage. Animal: Des veaux (n = 1998) ont été échantillonnés dans 106 troupeaux de type vache-veau canadiens à l'automne 2021. Procédure: Des échantillons de sérum de veaux ont été testés pour déterminer les concentrations de cuivre, de sélénium et de molybdène. Résultats: Même si les pourcentages de veaux classés comme déficients en sélénium (< 0,025 ppm) étaient relativement faibles (0,5 % dans l'ouest du Canada, 3 % dans l'est du Canada), 53 % des veaux de l'ouest du Canada et 77 % des veaux de l'est du Canada étaient classés comme ayant moins des concentrations de sélénium moins qu'adéquates (< 0,08 ppm). Une carence en cuivre (< 0,5 ppm) était courante chez les veaux de l'ouest (17 %) et de l'est (14 %) du Canada. Des concentrations élevées de molybdène (> 0,10 ppm) ont été identifiées chez 6 % des veaux de l'ouest du Canada et 7 % des veaux de l'est du Canada. Conclusion: Les concentrations de sélénium étaient plus élevées chez les veaux de l'ouest du Canada que chez ceux de l'est du Canada (P < 0,001). Les concentrations de cuivre et de molybdène n'étaient pas significativement différentes entre l'ouest et l'est du Canada. Un taux de cuivre sérique nettement insuffisamment était la carence la plus courante identifiée chez les veaux de boucherie canadiens au sevrage. Pertinence clinique: Les oligo-éléments sont importants pour le fonctionnement du système immunitaire des veaux au sevrage. Les concentrations de sélénium chez les veaux au sevrage étaient inférieures à celles des vaches des mêmes troupeaux collectées lors des tests de gestation deux ans plus tôt. Des carences en cuivre ont également été identifiées, quoique moins fréquemment que chez les vaches matures. Les programmes de supplémentation pour les veaux doivent être personnalisés en fonction des tests et reconnaître les différences de risque selon la région et l'âge.(Traduit par Dr Serge Messier).

Association of Diabetic Peripheral Neuropathy with Micronutrients.

INTRODUCTION: Diabetes mellitus (DM) is a common metabolic disorder that has been defined by hyperglycemia. Diabetic patients usually have high levels of oxidative stress. Mitochondrial dysfunction and inflammation of blood vessels are associated with a greater need for micronutrients in diabetic patients. These micronutrients may have an association with the complications in diabetics. The purpose of this study was to show the association of diabetic peripheral neuropathy (DPN) with levels of micronutrients such as copper (Cu), zinc (Zn), magnesium (Mg), and vitamin B12 (Vit B12). MATERIALS AND METHODS: This cross-sectional study was conducted in the Department of Medicine, Lala Lajpat Rai Memorial Medical College, Meerut. A total of 130 randomly selected cases of confirmed type-2 diabetic patients were included in this study. DPN cases were identified using the Michigan neuropathy screening instrument. Out of 130 diabetic patients, 28 patients were found to have diabetic neuropathy. The level of various micronutrients was assessed and correlated with the development of DPN. RESULTS: The association of DPN with Zn (p-value of 0.02) and Vit B12 (p-value of 0.008) was found to be significant, whereas Cu (p-value of 0.57) and Mg (p-value of 0.24) were found to be insignificant.

Maternal selenium deficiency during pregnancy in association with autism and ADHD traits in children: The Odense Child Cohort.

BACKGROUND: Selenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce. METHODS: 719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9+/-0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied. RESULTS: 155 of 719 (21.6 %) children had ASD traits and 59 of 719 (8.2 %) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 µg/L increment in selenium was 0.76 (95 % CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 µg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes. CONCLUSIONS: The results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial.

Concentrations of Bioelements (Zn, Cu, Fe, Cr, Mg, Mn) in Serum and Bone Tissue of Aging Men Undergoing Hip Arthroplasty: Implications for Erectile Dysfunction.

Background: Erectile dysfunction (ED) stands out as one of the most prevalent sexual disorders in men, with its incidence progressively escalating with age. As delineated by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction, the prevalence of ED among men under 40 years is estimated to be within the range of 1-10%. The aim of this study was to determine the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men with and without erectile dysfunction. Materials and methods: The retrospective cohort study included 152 men who underwent total hip arthroplasty for hip osteoarthritis at the Department of Orthopaedic Traumatology and Musculoskeletal Oncology at the Pomeranian Medical University in Szczecin. Certain exclusion criteria were applied to ensure the integrity of the study. These included individuals with diabetes, a history of cancer, alcohol abuse, liver or kidney failure, New York Heart Association (NYHA) class III or IV heart failure, and those taking medications that affect bone metabolism, such as mineral supplements, neuroleptics, chemotherapeutic agents, immunosuppressants, corticosteroids, or antidepressants. Patients with hypogonadism or infertility were excluded from the study. Results: The study showed an association between bioT concentrations and Cu concentrations in both patients with and without erectile dysfunction. A correlation between bioactive testosterone and Cr concentrations was also observed in both groups. Patients with erectile dysfunction showed a relationship between bioT concentration and Zn concentration, TT concentration and Mn concentration, FT concentration and Zn concentration, and E2 concentration and Cr concentration. An analysis of elemental concentrations in bone tissue showed an association between FT and Mg and Mn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between FT and Cu concentrations. A correlation was also observed between bioT concentrations and Mg, Mn, and Zn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between bioT and Cu concentrations. Conclusions: Studying the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men may be important in explaining the etiology of the problem. The study of the concentration of Zn and Cu in bone tissue and serum showed that these two elements, regardless of the place of accumulation, may be related to the concentration of androgens in men.

Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder.

BACKGROUND: It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. METHODS: 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. RESULTS: In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. CONCLUSIONS: Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

LLL 44-1 Micronutrients in clinical nutrition: Trace elements.

BACKGROUND: Trace elements are an essential component of metabolism and medical nutrition therapy, with key roles in metabolic pathways, antioxidation, and immunity, which the present course aims at summarizing. RESULTS: Medical nutrition therapy includes the provision of all essential trace elements. The clinical essential issues are summarized for Copper, Iron, Selenium, Zinc, Iodine, Chromium, Molybdenum, and Manganese: the optimal analytical techniques are presented. The delivery of all these elements occurs nearly automatically when the patient is fed with enteral nutrition, but always requires separate prescription in case of parenteral nutrition. Isolated deficiencies may occur, and some patients have increased requirements, therefore a regular monitoring is required. The clinicians should always consider the impact of inflammation on blood levels, mostly lowering them even in absence of deficiency. CONCLUSION: This text summarises the most relevant clinical manifestations of trace element depletion and deficiency, the difficulties in assessing status, and makes practical recommendations for provision for enteral and parenteral nutrition.

Relapse following withdrawal of D-penicillamine from combination (D-penicillamine + zinc) therapy in hepatic Wilson disease.

OBJECTIVES: Long-term D-penicillamine (D-pen) therapy in Wilson disease (WD) has numerous adverse effects which advocates its withdrawal, but with an inherent risk of relapse. This prospective observational study was conducted with the objective of evaluating incidence of relapse following withdrawal of D-pen from combination (D-pen + zinc) therapy in maintenance phase of previously symptomatic hepatic WD. METHODS: Hepatic WD patients <18 years of age and on combination therapy for >2 years with 6 months of biochemical remission were included. Biochemical remission was defined as achievement of (i) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times upper limit of normal (ULN), (ii) serum albumin >3.5 g/dL, international normalized ratio (INR) <1.5 and (iii) 24-h urinary copper excretion (UCE) <500 mcg/day, nonceruloplasmin-bound-copper (NCC) <15 mcg/dL. After D-pen withdrawal, monthly liver function test (LFT) and INR and 3 monthly UCE and NCC were done till 1 year or relapse (elevation of AST/ALT/both >2 times ULN or total bilirubin >2 mg/dL), whichever occurred earlier. RESULTS: Forty-five patients enrolled with median combination therapy duration of 36 months. Sixty percent of them had their index presentation as decompensated cirrhosis. Fourteen patients (31.8%) relapsed (cumulative incidence: 4 at 3 months, 11 at 6 months, and 14 at 12 months after D-pen discontinuation). All relapsers had index presentation as decompensated cirrhosis. On Cox-regression, ALT at D-pen withdrawal was an independent predictor of relapse (hazard ratio [HR]: 1.077, 95% confidence interval [CI]: 1.014-1.145, p = 0.017) with area under the receiver operating characteristic (AUROC) of 0.860. ALT ≥40 U/L predicted risk of relapse with 85.7% sensitivity, 70.9% specificity. CONCLUSION: Incidence of relapse after withdrawal of D-pen from combination therapy is 31.8% in hepatic WD. ALT ≥40 U/L, at the time of D-pen stoppage, predicts future relapse.

Association of Blood Copper With the Subclinical Carotid Atherosclerosis: An Observational Study.

BACKGROUND: Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains unclear. METHODS AND RESULTS: This observational study included consecutive participants from Xinqiao Hospital between May 2020 and August 2021. Blood metals were measured using inductively coupled plasma mass spectrometry and carotid atherosclerosis was assessed using ultrasound. Modified Poisson regression was performed to evaluate the associations of copper and other metals with subclinical carotid plaque presence. Blood metals were analyzed as categorical according to the quartiles. Multivariable models were adjusted for age, sex, body mass index, education, smoking, drinking, hypertension, diabetes, dyslipidemia, estimated glomerular filtration rate, and coronary artery disease history. Bayesian Kernel Machine Regression was conducted to evaluate the overall association of metal mixture with subclinical carotid plaque presence. One thousand five hundred eighty-five participants were finally enrolled in our study, and carotid plaque was found in 1091 subjects. After adjusting for potential confounders, metal-progressively-adjusted models showed that blood copper was positively associated with subclinical carotid plaque (relative risk according to comparing quartile 4 to quartile 1 was 1.124 [1.021-1.238], relative risk according to per interquartile increment was 1.039 [1.008-1.071]). Blood cadmium and lead were also significantly associated with subclinical carotid plaque. Bayesian Kernel Machine Regression analyses suggested a synergistic effect of copper-cadmium-lead mixture on subclinical carotid plaque presence. CONCLUSIONS: Our findings identify copper as a novel risk factor of subclinical carotid atherosclerosis and show the potential synergistic proatherogenic effect of copper, cadmium, and lead mixture.

Serum trace elements during treatment in pancreatic cancer patients and their associations with cancer prognosis.

BACKGROUND & AIMS: In this study, we assessed serum trace element concentrations in patients with pancreatic cancer and compared the results to those of healthy controls and patients with chronic pancreatitis. We evaluated the association between trace element concentrations during cancer treatment and the risk of cancer progression and mortality in pancreatic cancer patients. METHODS: A retrospective cohort study was conducted at a tertiary center in Korea. Serum trace element concentrations of cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) were measured at diagnosis using an inductively coupled plasma-mass spectrometry in 124 patients with pancreatic cancer, 50 patients with chronic pancreatitis, and 120 healthy controls. Trace elements were measured after a median of 282.5 (95% confidence interval [CI], 224.0-326.5) days from treatment initiation to assess changes in trace element concentrations during treatment. RESULTS: Serum Co concentrations were significantly higher in patients with chronic pancreatitis and pancreatic cancer compared to healthy controls, while serum Se concentrations were significantly lower. During treatment, serum concentrations of Cu, Se, and Zn significantly decreased in patients with pancreatic cancer. During the follow-up (median 152.5; 95% CI, 142.8-160.0 months), 85.5% of patients experienced progression or relapse, and 84.7% of patients died. Patients with decreased Se and Zn concentrations during treatment had a higher mortality (hazard ratio [HR], 2.10; 95% CI, 1.31-3.38; P = 0.0020 for Se; HR, 1.72; 95% CI, 1.06-2.79; P = 0.0269 for Zn) compared to those with unchanged or increased trace element concentrations during treatment. Patients with a greater reduction in Zn concentrations during treatment had a higher mortality than those with a smaller reduction (HR, 1.59; 95% CI, 1.01-2.52; P = 0.0483). Patients whose Zn status changed from normal to deficient during treatment had an increased mortality (HR, 1.76; 95% CI, 1.16-2.67, P = 0.0084). Patients with multiple (≥2) trace element deficiencies after treatment had poorer outcomes than those with no or single trace element deficiency. CONCLUSIONS: This study revealed that decreases in Se and Zn concentrations during cancer treatment were associated with adverse outcomes in terms of cancer progression and mortality in patients with pancreatic cancer. Further prospective investigations are recommended.

Serum concentrations of selenium, copper, and zinc in neonatal foals: Influence of failure of passive transfer and age-related changes.

Background: An adequate supply of trace elements is very important for equine neonates, as deficiencies can lead to health problems and even death. Objective: This study investigated serum concentrations of selenium (Se), copper (Cu), and zinc (Zn) in neonatal foals up to the 8th day of life. The influences of disease, age, and failure of passive transfer (FPT) on these concentrations were analyzed. Animals and procedure: Serum concentrations of Se, Cu, and Zn were determined from blood samples of 93 foals by means of inductively coupled plasma mass spectrometry. The foals were divided into 2 groups based on health status: clinically sick (n = 51) and clinically healthy (n = 42). The latter group was further divided into foals with FPT (n = 20) and those without (n = 22). Results: Mean serum concentrations for Se, Cu, and Zn were 60 ± 40 µg/L, 0.25 ± 0.22 mg/L, and 605 ± 285 µg/L, respectively. A significant influence of age on serum Cu concentration was observed (P < 0.0001). No differences were observed between any of the serum concentrations in clinically sick and clinically healthy foals on the 1st day of life. The FPT status was not associated with reduced serum concentrations of Se, Cu, or Zn. Conclusion and clinical relevance: It is not necessary to supplement trace elements in all foals with FPT.

Concentrations sériques de sélénium, de cuivre et de zinc chez les poulains nouveau-nés : influence de l'échec du transfert passif et des changements liés à l'âge. Contexte: Un apport suffisant en oligo-éléments est très important pour les nouveau-nés équins, car des carences peuvent entraîner des problèmes de santé, voire la mort. Objectif: Cette étude a examiné les concentrations sériques de sélénium (Se), de cuivre (Cu) et de zinc (Zn) chez les poulains nouveau-nés jusqu'au 8ème jour de vie. Les influences de maladies, de l'âge et de l'échec du transfert passif (FPT) sur ces concentrations ont été analysées. Animaux et procédure: Les concentrations sériques de Se, Cu et Zn ont été déterminées à partir d'échantillons de sang de 93 poulains au moyen d'une spectrométrie de masse à plasma à couplage inductif. Les poulains ont été divisés en 2 groupes en fonction de leur état de santé: cliniquement malades (n = 51) et cliniquement sains (n = 42). Ce dernier groupe a été divisé en poulains avec FPT (n = 20) et ceux sans (n = 22). Résultats: Les concentrations sériques moyennes de Se, Cu et Zn étaient respectivement de 60 ± 40 µg/L, 0,25 ± 0,22 mg/L et 605 ± 285 µg/L. Une influence significative de l'âge sur la concentration sérique de Cu a été observée (P < 0,0001). Aucune différence n'a été observée entre les concentrations sériques chez les poulains cliniquement malades et cliniquement sains au premier jour de leur vie. Le statut FPT n'était pas associé à une réduction des concentrations sériques de Se, Cu ou Zn. Conclusion et pertinence clinique: Il n'est pas nécessaire de supplémenter tous les poulains en oligo-éléments avec FPT.(Traduit par Dr Serge Messier).

The Effect of an Elevated Dietary Copper Level on the Vascular Contractility and Oxidative Stress in Middle-Aged Rats.

Copper (Cu), being an essential mineral, plays a crucial role in maintaining physiological homeostasis across multiple bodily systems, notably the cardiovascular system. However, an increased Cu level in the body may cause blood vessel dysfunction and oxidative stress, which is unfavorable for the cardiovascular system. Middle-aged (7-8 months old) male Wistar rats (n/group = 12) received a diet supplemented with 6.45 mg Cu/kg (100% of the recommended daily dietary quantity of copper) for 8 weeks (Group A). The experimental group received 12.9 mg Cu/kg of diet (200%-Group B). An ex vivo study revealed that supplementation with 200% Cu decreased the contraction of isolated aortic rings to noradrenaline (0.7-fold) through FP receptor modulation. Vasodilation to sodium nitroprusside (1.10-fold) and acetylcholine (1.13-fold) was potentiated due to the increased net effect of prostacyclin derived from cyclooxygenase-1. Nitric oxide (NO, 2.08-fold), superoxide anion (O2•-, 1.5-fold), and hydrogen peroxide (H2O2, 2.33-fold) measured in the aortic rings increased. Blood serum antioxidant status (TAS, 1.6-fold), Cu (1.2-fold), Zn (1.1-fold), and the Cu/Zn ratio (1.4-fold) increased. An increase in Cu (1.12-fold) and the Cu/Zn ratio (1.09-fold) was also seen in the rats' livers. Meanwhile, cyclooxygenase-1 (0.7-fold), cyclooxygenase-2 (0.4-fold) and glyceraldehyde 3-phosphate dehydrogenase (0.5-fold) decreased. Moreover, a negative correlation between Cu and Zn was found (r = -0.80) in rat serum. Supplementation with 200% Cu did not modify the isolated heart functioning. No significant difference was found in the body weight, fat/lean body ratio, and organ weight for either the heart or liver, spleen, kidney, and brain. Neither Fe nor Se, the Cu/Se ratio, the Se/Zn ratio (in serum and liver), heme oxygenase-1 (HO-1), endothelial nitric oxide synthase (eNOS), or intercellular adhesion molecule-1 (iCAM-1) (in serum) were modified. Supplementation with 200% of Cu potentiated pro-oxidant status and modified vascular contractility in middle-aged rats.