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Status of Serum Copper, Magnesium, and Total Antioxidant Capacity in Patients with Polycystic Ovary Syndrome.
Kanafchian, M, Esmaeilzadeh, S, Mahjoub, S, Rahsepar, M, Ghasemi, M
Biological trace element research. 2020;(1):111-117
Abstract
This study evaluates serum copper and magnesium and total antioxidant capacity levels in PCOS patients. In this regard, the probable association of copper and magnesium with total antioxidant capacity (TAC) was investigated. In total, 150 women (60 PCOS patients and 90 healthy subjects) participated in this case-control study. PCOS was diagnosed according to the Rotterdam criteria (2003). Serum Cu, Mg, Ca, TAC, insulin levels, and insulin resistance indices were determined. Insulin was measured using ELISA methods. Serum Cu and Mg levels were measured by an atomic absorption spectrophotometer and the Xylidyl Blue method respectively. The correlations between the parameters were analyzed using the Spearman correlation test. Serum Cu level was significantly higher while TAC was significantly lower in the PCOS patients than those in the controls (p = 0.019 and p = 0.002 respectively). No significant difference was detected between the two groups in terms of serum Mg and Ca levels and Ca/Mg ratio. In insulin-resistant PCOS subjects, there was a negative correlation between Mg levels and homeostatic model assessment for insulin resistance (r = - 0.449, p = 0.006) but a positive correlation between Mg levels and quantitative insulin sensitivity check index (r = 0.480, p = 0.003). A negative correlation also existed between Mg levels and TAC in non-insulin-resistant PCOS patients (r = - 0.407, p = 0.04). According to the results, copper and magnesium seem to contribute to oxidative stress and insulin resistance in PCOS patients. Therefore, to prevent long-term metabolic complications in PCOS women, it is recommended that these elements be routinely monitored. Also, significantly lower levels of serum TAC in PCOS patients than in normal women may suggest increased oxidative stress in such patients.
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2.
The Effect of Curcumin on Serum Copper and Zinc and Zn/Cu Ratio in Individuals with Metabolic Syndrome: A Double-Blind Clinical Trial.
Safarian, H, Parizadeh, SMR, Saberi-Karimain, M, Darroudi, S, Javandoost, A, Mohammadi, F, Moammeri, M, Ferns, GA, Ghayour-Mobarhan, M, Mohebati, M
Journal of dietary supplements. 2019;(6):625-634
Abstract
Metabolic syndrome is a complex disorder with high socioeconomic costs and a high global prevalence. The serum concentrations of some trace elements are higher in people with metabolic syndrome compared to normal individuals. Curcumin is derived from turmeric and has antioxidant and anti-inflammatory properties. Curcumin may therefore have a potential role in the management of cardiovascular risk. The aim of this study was to investigate the effects of curcumin on serum copper (Cu), zinc (Zn), and Zn/Cu ratio levels in patients with metabolic syndrome. A double-blind clinical trial was designed in which 120 individuals with metabolic syndrome were randomly assigned to one of three groups: curcumin 1gr/day, phospholipidated curcumin 1gr/day, or a placebo, each taken for 6 weeks. Serum copper and zinc were measured before and after intervention. At baseline, in addition to obtaining the anthropometric characteristics of participants, a fasting blood sample was taken from each participant, and the concentrations of serum Cu and Zn were measured by atomic absorption (Varian AA 240 FS model). Serum Zn concentrations rose significantly in the phospholipidated curcumin and curcumin groups, being significantly higher (p <.001) in the phospholipidated curcumin group than in the curcumin group (p <.05). Serum Zn concentration fell in the control group (p <.05). Changes in serum Zn level from baseline to the levels after six weeks' intervention were significantly different between the groups, but changes in serum Cu from between baseline until after intervention were not significantly different. The serum Zn/Cu level in phospholipidated curcumin and curcumin groups after intervention was higher than for the control group, but it was more significant in the group taking phospholipidated curcumin (p <.001). Curcumin and phospholipidated curcumin complex, given at a dose of 1 g per day for six weeks, were associated with an increase in serum zinc and consequently zinc-to-copper ratio.
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MEDNIK syndrome with a frame shift causing mutation in AP1S1 gene and literature review of the clinical features.
Incecik, F, Bisgin, A, Yılmaz, M
Metabolic brain disease. 2018;(6):2065-2068
Abstract
MEDNIK syndrome is an autosomal recessive rare disease as one of the most recently described copper metabolism disorder characterized by intellectual disability, ichthyosis, hearing loss, peripheral neuropathy, enteropathy and keratodermia. Here in, we reported a case presented with ichthyosis and intellectual disability with MEDNIK syndrome that confirmed by mutation analysis in a Turkish child. She was finally diagnosed with MEDNIK syndrome by clinical findings, which were confirmed by molecular genetic testing. Sequencing of AP1S1 gene showed a homozygous insertion c.364dupG (NM_001283.4), which is predicted to cause a frameshift of the reading frame (p.D122Gfs*18). To our knowledge, this is the first case of MEDNIK syndrome from Turkey. Diagnosis of MEDNIK syndrome is still challenging and we hope that this case will contribute to further understanding.
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4.
Core domain mutant Y220C of p53 protein has a key role in copper homeostasis in case of free fatty acids overload.
Arciello, M, Longo, A, Viscomi, C, Capo, C, Angeloni, A, Rossi, L, Balsano, C
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 2015;(6):1017-29
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is a pathology that includes a wide variety of clinical conditions ranging from simple steatosis to end-stage liver diseases. Despite the huge amount of researches, the molecular basis of NAFLD are still not fully understood. Recently, it was suggested a role for p53 in NAFLD pathogenesis. Among its targets there is Synthesis of Cytochrome c Oxidase 2 (SCO2), a copper chaperone, involved in both aerobic respiration and metal cellular excretion. Copper seems to play a role in NAFLD. It was demonstrated a low hepatic copper content in NAFLD patients, which correlates with metabolic syndrome parameters. Copper homeostasis deregulation, in fact, seems to be related to lipid metabolism alteration and insulin resistance. Here we provide evidence on the role of p53 in the modulation of copper homeostasis, in an experimental model of NAFLD. We used two different hepatoma cell lines, HepG2 and Huh 7.5.1, characterized by the presence of wt p53 and its Y220C mutant, respectively, treated with a free fatty acids (FFAs) solution. Interestingly, p53 activation correlated with the intracellular copper level maintenance. We demonstrated that, in hepatoma cell lines, core domain mutant Y220C of p53 affects the modulation of SCO2 and Copper transporter 1 (CTR1), influencing, in this way, intracellular copper homeostasis in presence of FFAs accumulation, and that the 220 residue of the protein is crucial for such control. The role of p53 we highlighted may have deep implications in clinical conditions where copper homeostasis is deregulated.
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Selenium, zinc, and copper plasma levels in patients with schizophrenia: relationship with metabolic risk factors.
Vidović, B, Dorđević, B, Milovanović, S, Škrivanj, S, Pavlović, Z, Stefanović, A, Kotur-Stevuljević, J
Biological trace element research. 2013;(1-3):22-8
Abstract
The aim of this study was to determine the plasma selenium (Se), copper (Cu), and zinc (Zn) levels and to evaluate their possible association with metabolic syndrome (MetS) components in patients with schizophrenia. The study group consisted of 60 patients with schizophrenia and 60 sex- and age-matched healthy controls. Anthropometric measurements, blood pressure, and biochemical analysis of fasting blood were performed in all subjects. Patients with schizophrenia had significantly higher plasma Cu concentrations compared with controls (0.97 ± 0.31 vs. 0.77 ± 0.32 mg/L, p = 0.001). The plasma Cu concentration showed a positive correlation with plasma glucose and diastolic blood pressure in the patient groups (r s = 0.263, p < 0.05 and r s = 0.272, p < 0.05, respectively). The plasma Se level correlated positive with MetS score (r s = 0.385, p < 0.01), waist circumference (r s = 0.344, p < 0.05), plasma glucose (r s = 0.319, p < 0.05), and triglyceride concentrations (r s = 0.462, p < 0.001) in patients with schizophrenia. Plasma Zn did not correlate with any of the MetS components. These results suggest that alterations in plasma Cu and Se levels in medicated patients with schizophrenia could be associated with metabolic risk factors.
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6.
Inborn errors of copper metabolism.
Kaler, SG
Handbook of clinical neurology. 2013;:1745-54
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Abstract
Two copper-transporting ATPases are essential for mammalian copper homeostasis: ATP7A, which mediates copper uptake in the gastrointestinal tract and copper delivery to the brain, and ATP7B, which mediates copper excretion by the liver into bile. Mutations in ATP7A may cause three distinct X-linked conditions in infants, children, or adolescents: Menkes disease, occipital horn syndrome (OHS), and a newly identified allelic variant restricted to motor neurons called X-linked distal hereditary motor neuropathy. These three disorders show variable neurological findings and ages of onset. Menkes disease presents in the first several months of life with failure to thrive, developmental delay, and seizures. OHS features more subtle developmental delays, dysautonomia, and connective tissue abnormalities beginning in early childhood. ATP7A-related distal motor neuropathy presents even later, often not until adolescence or early adulthood, and involves a neurological phenotype that resembles Charcot-Marie-Tooth disease, type 2. These disorders may be treatable through copper replacement or ATP7A gene therapy. In contrast, mutations in ATP7B cause a single known phenotype, Wilson disease, an autosomal recessive trait that results from copper overload rather than deficiency. Dysarthria, dystonia, tremor, gait abnormalities, and psychiatric problems may be presenting symptoms, at ages from 10 to 40 years. Excellent treatment options exist for Wilson disease, based on copper chelation. In the past 2 years (2012-2013), three new autosomal recessive copper metabolism conditions have been recognized: 1) Huppke-Brendel syndrome caused by mutations in an acetyl CoA transporter needed for acetylation of one or more copper proteins, 2) CCS deficiency caused by mutations in the copper chaperone to SODI, and 3) MEDNIK syndrome, which revealed that mutations in the σ1A subunit of adaptor protein complex 1 (AP-1) have detrimental effects on trafficking of ATP7A and ATP7B.
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Relationship between dietary magnesium, manganese, and copper and metabolic syndrome risk in Korean adults: the Korea National Health and Nutrition Examination Survey (2007-2008).
Choi, MK, Bae, YJ
Biological trace element research. 2013;(1-3):56-66
Abstract
Recent studies have reported correlations between mineral intake and metabolic syndrome (MS), but accurate relationships and consistency in the results are difficult to confirm. Accordingly, this study aims to assess the dietary intakes of magnesium (Mg), manganese (Mn), and copper (Cu) to determine their relationship with MS. Data from a total of 5,136 adults (2,084 men, 3,052 women) was collected from the 2007-2008 Korea National Health and Nutrition Examination Survey (KNHANES), and the intakes of Mg, Mn, and Cu of the MS patients were compared with those of healthy adults. The relationship between the intakes of these minerals and the MS risks was analyzed. Diagnosis of MS was evaluated by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) standards. Among all study subjects, 25.9 % (540 subjects) of the men and 24.5 % (748 subjects) of the women met diagnostic criteria for inclusion in the MS group. In the men, daily intakes of Mg and Cu in the MS group were significantly lower than those in control group, and in the women, daily intakes of energy, Mg, Mn, and Cu in the MS group were significantly lower than those of the control group. The women subjects with high blood pressure showed significantly lower intakes of Mg, Mn, and Cu than control subjects. In addition, in the women, the highest quartile of Mg and Cu was inversely associated with MS, but with adjustment were not maintained. However, in the postmenopausal women, MS was significant and inversely associated with the highest quartiles of Cu intake and the association remained significant after adjustments. Considering that MS incidence increases and dietary intake and nutrient density decrease with increasing age, and mineral intake is reduced accordingly, these results suggest that meal management with adequate mineral intake is advisable to control MS.
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8.
Copper deficiency myelopathy.
Jaiser, SR, Winston, GP
Journal of neurology. 2010;(6):869-81
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Abstract
Acquired copper deficiency has been recognised as a rare cause of anaemia and neutropenia for over half a century. Copper deficiency myelopathy (CDM) was only described within the last decade, and represents a treatable cause of non-compressive myelopathy which closely mimics subacute combined degeneration due to vitamin B12 deficiency. Here, 55 case reports from the literature are reviewed regarding their demographics, aetiology, haematological and biochemical parameters, spinal imaging, treatment and outcome. The pathophysiology of disorders of copper metabolism is discussed. CDM most frequently presented in the fifth and sixth decades and was more common in women (F:M = 3.6:1). Risk factors included previous upper gastrointestinal surgery, zinc overload and malabsorption syndromes, all of which impair copper absorption in the upper gastrointestinal tract. No aetiology was established in 20% of cases. High zinc levels were detected in some cases not considered to have primary zinc overload, and in this situation the contribution of zinc to the copper deficiency state remained unclear. Cytopenias were found in 78%, particularly anaemia, and a myelodysplastic syndrome may have been falsely diagnosed in the past. Spinal MRI was abnormal in 47% and usually showed high T2 signal in the posterior cervical and thoracic cord. In a clinically compatible case, CDM may be suggested by the presence of one or more risk factors and/or cytopenias. Low serum copper and caeruloplasmin levels confirmed the diagnosis and, in contrast to Wilson's disease, urinary copper levels were typically low. Treatment comprised copper supplementation and modification of any risk factors, and led to haematological normalisation and neurological improvement or stabilisation. Since any neurological recovery was partial and case numbers of CDM will continue to rise with the growing use of bariatric gastrointestinal surgery, clinical vigilance will remain the key to minimising neurological sequelae. Recommendations for treatment and prevention are made.