Serum Copper Concentrations Research Articles

Associations between serum mineral concentrations and mortality by renal function in the Ludwigshafen Risk and Cardiovascular Health Study

The association of serum concentrations of minerals and phosphate with overall and cardiovascular mortality based on renal function is poorly understood. 3307 patients (average age 62.7 ± 10.6 years) in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study were grouped by estimated glomerular filtration rate (eGFR) into three categories: < 60, 60–89, and ≥ 90 mL/min per 1.73 m2, per KDIGO 2022 guidelines and were analysed using Cox regression. Low serum sodium and iron concentrations were associated with poor renal function and increased overall mortality risk, whereas higher serum zinc concentrations were associated with reduced overall and cardiovascular mortality risk. Elevated serum copper concentrations were associated with increased mortality risk across all eGFR categories. Comparing low and normal eGFR, we observed a fourfold increase in all-cause mortality risk for eGFR < 60 mL/min per 1.73 m2 and a twofold increase for eGFR 60–89 mL/min per 1.73 m2, accompanied by changes in serum mineral concentrations. The optimal range of mineral and phosphate concentrations in serum was strongly related to renal function. To reduce mortality risk, it’s important to regularly monitor serum mineral and phosphate concentrations as well as renal function, especially in cardiovascular patients with compromised renal function.

Obesity Mediates the Association Between Serum Copper and Inflammation: A Cross-sectional and Mendelian Randomization Study.

Copper is an important biological trace element, but its overexposure can be harmful to the human body. Herein, we aimed to assess the association between serum copper levels and inflammation. A total of 5231 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016. Participants with higher serum copper levels had higher values of systemic inflammation indexes. The concentration of high-sensitive C-reactive protein (hs-CRP) increased with serum copper concentration (β = 2.8, p < 0.001). Participants with high and very high copper levels had higher ORs (odds ratios) of having inflammation (high: OR 2.92 (0.77-11.04), p = 0.074; very high: OR 8.66 (3.18-23.54), p = 0.011), which were further exacerbated in people with diabetes and males. Body mass index (BMI) and body fat percentage are two main mediators in the association between serum copper and hs-CRP, accounting for 12.62% and 19.72%, respectively. The random-effects inverse variance-weighted (IVW) analysis revealed that there was a genetic causal relationship between serum copper and obesity (OR 1.15, p = 0.014). Our results suggest that serum copper is positively associated with inflammation, which may be mainly mediated by obesity.

Prediction of fetal growth restriction in obese women

Objective. To develop a way of prediction of fetal growth restriction in the first trimester of pregnancy in obese women. Materials and methods. 85 obese pregnant women at 6–9 weeks of gestation took part in the study. Obesity was determined by body mass index, as squared height (m)-to-weight (kg) ratio, with a BMI 30 kg/m2. In the blood serum of all patients the level of total copper (Cuvol.) was determined by the colorimetric method, and ceruloplasmin (CP) by of V.S. Kamyshnikov`s method and the percentage of free copper (Cufree) was calculated. The free copper index was calculated using the formula: Cufree = (Cuvol. – (ceruloplasmin · 3)) / Cuvol. · 100, where Cufree is the percentage of free copper in the blood serum, %; Cuob. – content of total copper in blood serum, µmol/l; CP – content of ceruloplasmin in blood serum, mg/l; 3 – conversion factor. All pregnant women were divided into two groups depending on the percentage of free copper: group A – pregnant women with obesity and free copper content 25 % (n = 26); group B – obese pregnant women with a percentage of free copper 25 %, (n = 59). The control group consisted of 20 pregnant women with normal body weight. Results. Among the studied groups, in pregnant women with obesity statistically significant differences in the content of total copper (p = 0.013), and the percentage of free copper (p = 0.041) were revealed. In the group of pregnant women with a free copper content 25 % chronic placental insufficiency occurred 1.5 times more frequently and fetal growth restriction syndrome was 6.4 times more frequent than in the group of patients with a free copper content of 25 %. Conclusion. The free copper level, determined in the first trimester of pregnancy equal to 25% or more, can be considered as a predictor of fetal growth restriction in obese pregnant women.

Determination of Serum Copper Levels Effect on Learning Ability Among Apparently Healthy Schooling Adolescents Recruited from Sokoto, Nigeria

Copper is vital for human biological system especially for learning functions. The objective of this paper was to determine the effects of serum copper on learning ability among adolescents in Sokoto, Nigeria. Therewith, serum copper concentrations of the 230 recruited adolescents’ in-school from Sokoto, Nigeria were analyzed using the atomic absorption spectroscopy method, and reagents of analytical grade. The investigation of effect of copper concentration on learning potential was done in a quasi-experimental format. The findings (p&lt;0.05) of serum copper concentration revealed mean serum copper in healthy subjects was 211(91.74%); serum copper deficient subjects were 19(8.26%). The low copper concentration observed based on age shows, 13(5.6%) of 14-16 years; and 6(2.6%) of 16-18 years. Observation of copper level in relation to learning potential show a mean of 62.28 in normal participants, and 36.92 in low copper participants. There is need for utmost diverse nutritional intervention on zinc consumption. There are still some adolescents that have low copper level in the state, and it may affect their learning and entire learning. Thus, it is important to provide better nutrition through using disparate intervention methods to bail the situation.

Accurate non-ceruloplasmin bound copper: a new biomarker for the assessment and monitoring of Wilson disease patients using HPLC coupled to ICP-MS/MS.

Assessment of Wilson disease is complicated, with neither ceruloplasmin, nor serum or urine copper, being reliable. Two new indices, accurate non-ceruloplasmin copper (ANCC) and relative ANCC were developed and applied to a cohort of 71 patients, as part of a Wilson Disease Registry Study. Elemental copper-protein speciation was developed for holo-ceruloplasmin quantitation using strong anion exchange chromatography coupled to triple quadrupole inductively coupled plasma mass spectrometry. The serum proteins were separated using gradient elution and measured at m/z 63 (63Cu+) and 48 (32S16O+) using oxygen reaction mode and Cu-EDTA as calibration standard. The ANCC was calculated by subtraction of the ceruloplasmin bound copper from the total serum copper and the RelANCC was the percentage of total copper present as the ANCC. The accuracy of the holo-ceruloplasmin measurement was established using two certified reference materials, giving a mean recovery of 94.2 %. Regression analysis between the sum of the copper containing species and total copper concentration in the patient samples was acceptable (slope=0.964, intercept=0, r=0.987) and a difference plot, gave a mean difference for copper of 0.38 μmol/L. Intra-day precision for holo-ceruloplasmin at serum copper concentrations of 0.48 and 3.20 μmol/L were 5.2 and 5.6 % CVand the intermediate precision at concentrations of 0.80 and 5.99 μmol/L were 6.4 and 6.4 % CV, respectively. The limit of detection (LOD) and lower limit of quantification (LLOQ) for holo-ceruloplasmin were 0.08 and 0.27 μmol/L as copper, respectively. ANCC and Relative ANCC are important new diagnostic and monitoring biomarker indices for Wilson disease (WD).

Abnormalities in copper status associated with diminished ovarian reserve: A case-control and cross-sectional study.

This study aimed to illustrate the copper status of diminished ovarian reserve in Chinese women, especially the effects of copper, ceruloplasmin, non-ceruloplasmin-bound copper (NCC) and CuZn superoxide dismutase (SOD1). This case-control, cross-sectional investigation included women with diminished ovarian reserve (DOR group, n = 35) and matched normal ovarian reserve (NOR group, n = 35). The serum levels of copper, ceruloplasmin, NCC, SOD1, follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, and anti-Müllerian hormone were tested and analyzed. The serum copper concentrations (60.88%), NCC (54.75%) and SOD1 (54.75%) in the DOR group were significantly higher than those in the NOR group (all P < 0.001), and the concentrations of the three markers were higher in most subgroups (P < 0.001). The correlation analysis verified the correlation between copper status and impaired ovarian function. Additionally, linear regression analysis showed that NCC and SOD1 levels were negatively correlated with anti-Müllerian hormone (P < 0.05 or 0.001). Our exploration found significant increases in copper, NCC and SOD1 levels in DOR and suggests a possible link. Copper status is expected to serve as the predictive marker for DOR.

Serum Zinc and Copper Concentrations and Dyslipidemia as Risk Factors of Cardiovascular Disease in Adults: Data Mining Techniques.

This study aimed to examine the relationship between serum cholesterol levels and the ratio of zinc (Zn) and copper (Cu) in the blood serum and the incidence of cardiovascular disease (CVD). In Phase I of the study, 9704 individuals between the age of 35 and 65 years were recruited. Phase II of the cohort study comprised 7561 participants who completed the 10-year follow-up. The variables which were measured at the baseline of the study included gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP); biochemical parameters including serum Cu, Zn, copper-zinc ratio (Cu/Zn), zinc-copper ratio (Zn/Cu); fasted lipid profile consisting of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) as well as fasting serum glucose, and triglycerides-glucose (TyG) index. Decision tree (DT) and logical regression (LR) models were applied to examine the relationship between the aforementioned factors and CVD. CVD was diagnosed in 837 individuals (378 males and 459 females) out of 7561 participants. According to the LR models, SBP, TC, HDL, age, Zn/Cu, and TyG index for males and SBP, age, TyG index, HDL, TC, Cu/Zn, and Cu for females had the highest correlation with CVD (p-value ≤ 0.033). Based on the DT algorithm, 88% of males with SPB < 129.66 mmHg, younger age (age < 53 years), TyG index < 9.53, 173 ≤ TC < 187 mg/dL, and HDL ≥ 32 mg/dL had the lowest risk of CVD. Also, 98% of females with SBP < 128 mmHg, TyG index < 9.68, age < 44, TC < 222 mg/dL, and HDL ≥ 63.7 mg/dL had the lowest risk of CVD. It can be concluded that the Zn/Cu for men and Cu/Zn for women, along with dyslipidemia and SBP, could significantly predict the risk of CVD in this cohort from northeastern Iran.

Comprehensive insights into Menkes disease: Genetics, pathophysiology, animal models, diagnosis, and therapeutic strategies

Menkes disease (MD) is an inherited disorder affecting primarily the males which is X-linked recessive in inheritance pattern due to mutation in ATP7A gene that codes for copper transporter protein. This results in neurological complications and connective tissue lesions that make affected males succumb to death. MD can be classified as the classical and Occipital Horn Syndrome (OHS) varieties, though the severity and early presentation of the classical MD is more pronounced. Diagnostic assays include determination of serum copper and ceruloplasmin concentrations; neurochemical studies are also performed. The standard treatment usually entails the use of copper supplements with copper – Histidine being one of the most effective. Therefore, it is necessary to investigate the molecular pathophysiology of ATP7A disorder to come up with different therapies. Animal models such as zebrafish, fruit flies etc. are beneficial to know about MD pathology to get treatment. In summary, the early and accurate diagnosis of MD, followed by immediate treatment, plays a critical role in successful management of the disorder.

Brain and the whole-body bone imaging appearances in Menkes disease: a case report and literature review

BackgroundMenkes disease (MD) is a rare, inherited, multisystemic copper metabolism disorder. Classical Menkes disease is characterized by low serum copper and ceruloplasmin concentrations, leading to multiple abnormalities in the whole-body, especially in connective tissue and central nervous system. However, serum copper and ceruloplasmin levels are not reliable diagnostic biomarkers due to the low concentrations in healthy newborns either. The featured imaging manifestations play an important role in diagnosing Menkes disease. To our knowledge, there are few reports on the systemic imaging manifestations of Menkes disease.Case presentationA 4-month-old male patient presented with recurrent seizures. He had cognitive, intellectual, growth, gross motor, precision movement, and language developmental lags. The patient’s hemoglobin and serum ceruloplasmin level were low. On MRI, increased intracranial vascular tortuosity, cerebral and cerebellar atrophy, white matter changes, and basal ganglia abnormalities were observed. Plain radiograph revealed wormian bones, rib flaring, metaphyseal spurring, and periosteal reactions in the long bones of the limbs. A pathogenic variant in ATP7A gene was identified in the patient, so he was confirmed the diagnosis of Menkes disease. His symptoms did not improve despite symptomatic and supportive treatment during his hospitalization. Unfortunately, the infant died 3 months after leaving hospital.ConclusionA comprehensive and intuitive understanding of the disease’s imaging manifestations can help clinicians to identify the disease and avoid delays in care.

Serum copper assessment in patients with polycystic ovary syndrome and tubal infertility: A retrospective 5-year study.

The association between serum copper and polycystic ovary syndrome (PCOS) lacks definitive conclusions, and the intricate interactions with invitro fertilization (IVF) cycle characteristics in infertility remain insufficiently explored. This retrospective study included 560 patients with tubal infertility (no-PCOS) and 266 patients with PCOS undergoing IVF at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to December 2022. Patients' basic characteristics, hormonal and metabolic parameters, essential trace elements, and IVF cycle characteristics were measured and analyzed. The results revealed a significantly elevated serum copper level in the PCOS group compared to the control group [17.27 (15.54, 19.67) vs 15.4 (13.87, 17.35), μmol/L; p < .001]. Spearman correlation analyses revealed a significant positive correlation between serum copper concentration and body mass index (BMI), fasting glucose (FG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the no-PCOS group. Additionally, a notable negative correlation with high-density lipoprotein (HDL) was observed (r = -.184, p < .001). Within the PCOS group, serum copper concentration correlated significantly with BMI (r = .198, p = .004) and TG (r = .214, p = .002). The linear trend analysis indicated no significant relationship between serum copper concentration and ovarian response as well as preimplantation outcomes in both groups after adjusting for confounding factors. Our study provided evidence of elevated serum copper concentration in PCOS patients, closely associated with lipid metabolism but showing no correlation with IVF outcomes. These findings provide valuable real-world data, enriching our nuanced understanding of the role of copper in female fertility.

Fostering healthy aging through selective nutrition: A long-term comparison of two dietary patterns and their holistic impact on mineral status in middle-aged individuals—A randomized controlled intervention trial in Germany

Aging is associated with a decline in physiological functions and an increased risk of age-related diseases, emphasizing the importance of identifying dietary strategies for healthy aging. Minerals play a crucial role in maintaining optimal health during aging, making them relevant targets for investigation. Therefore, we aimed to analyze the effect of different dietary pattern on mineral status in the elderly. We included 502 individuals aged 50–80 years in a 36-month randomized controlled trial (RCT) (NutriAct study). This article focuses on the results within the two-year intervention period. NutriAct is not a mineral-modulating-targeted intervention study, rather examining nutrition in the context of healthy aging in general. However, mineral status might be affected in an incidental manner. Participants were assigned to either NutriAct dietary pattern (proportionate intake of total energy consumption (%E) of 35–45 %E carbohydrates, 35–40 %E fats, and 15–25 %E protein) or the German Nutrition Society (DGE) dietary pattern (proportionate intake of total energy consumption (%E) of 55 %E carbohydrates, 30 %E fats, and 15 %E protein), differing in the composition of macronutrients. Data from 368 participants regarding dietary intake (energy, calcium, magnesium, iron, and zinc) and serum mineral concentrations of calcium, magnesium, iron, copper, zinc, selenium, iodine, and manganese, free zinc, and selenoprotein P were analyzed at baseline, as well as after 12 and 24 months to gain comprehensive insight into the characteristics of the mineral status. Additionally, inflammatory status - sensitive to changes in mineral status - was assessed by measurement of C-reactive protein and interleukin-6. At baseline, inadequate dietary mineral intake and low serum concentrations of zinc and selenium were observed in both dietary patterns. Throughout two years, serum zinc concentrations decreased, while an increase of serum selenium, manganese and magnesium concentrations was observable, likely influenced by both dietary interventions. No significant changes were observed for serum calcium, iron, copper, or iodine concentrations. In conclusion, long-term dietary interventions can influence serum mineral concentrations in a middle-aged population. Our findings provide valuable insights into the associations between dietary habits, mineral status, and disease, contributing to dietary strategies for healthy aging.

The association between serum copper concentration and prevalence of diabetes among US adults with hypertension (NHANES 2011-2016).

The objective of this study was to examine the association between the serum copper concentration and the prevalence of diabetes among US adults with hypertension using the data from the National Health and Nutrition Examination Survey (NHANES). The study population was selected from adults aged over 20 years old in the three survey cycles of NHANES from 2011 to 2016. Logistic regression model analyses were applied to determine the independent risky effect of copper to the prevalence of diabetes. Also, a restricted cubic spline (RCS) model was performed to explore the potential nonlinear association between serum copper concentration and the prevalence of diabetes. A total of 1786 subjects (742 cases and 1044 controls) were included, and 924 were men (51.7%), and 742 (41.5%) were diabetic. Compared with non-diabetic individuals, the concentration of serum copper in diabetic patients with hypertension was higher. After adjusting for age, sex, race, education, marital status, body mass index (BMI), family poverty income ratio (PIR), smoking, alcohol drinking, physical activity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and hyperlipidemia, the highest quartile of serum copper concentration significantly increased the risk of diabetes as compared with the lowest quartile (OR: 1.38, 95% CI: 1.01-1.92, ptrend = 0.036). The results of RCS analysis showed significant non-linear relationship between serum copper concentration and prevalence of diabetes (p-non-linear = 0.010). This study finds that serum copper concentration are significantly associated with risk of diabetes in hypertensive patients, which suggests copper as an important risk factor of diabetes development.

Risk of Trace Element Imbalance in Cases of Occupational Allergic Diseases

Introduction: The relevance of the study is attributed to the lack of knowledge of the mechanisms of development and specifics of the clinical picture of occupational allergic diseases. Objective: To establish the levels of essential trace elements in biological substrates of patients with occupational allergies. Materials and methods: In 2014–2018, we analyzed zinc and copper levels in urine, blood serum, and lymphocytes of patients with occupational allergic skin and respiratory diseases by the atomic absorption method. Relative risk was calculated using a four-field contingency table. Results: In patients with work-related allergic contact dermatitis and bronchial asthma, zinc and copper concentrations in blood serum increased while urinary excretion of these elements decreased. Quantitative patterns of the concentrations of trace elements in body fluids of the patients with skin and respiratory allergies were unidirectional compared to the reference group. Relative risk values showed that lower levels of copper in urine and zinc in blood serum and lymphocytes, as well as higher serum copper indicated the risk of trace element imbalance in the body. Conclusion: The risk of trace element imbalance due to occupational allergic diseases is associated with impaired copper and zinc balance. Our findings prove that the levels of microelements are additional factors that aggravate the course of occupational allergic disorders.

Content of macro- and microelements in rats with experimental autoimmune thyroiditis and under the influence of lemna minor

The aim was to study the effect of aqueous extract and 30 % alcohol tincture of Lemna minor frond (AELM and TLM) on the content of macro- and microelements in rats with experimental autoimmune thyroiditis. Materials and methods. The effect of AELM and TLM was studied in a model of experimental autoimmune thyroiditis in rats, induced by immunization with human thyroid antigen. The serum levels of total thyroxine, total triiodothyronine, antibodies to thyroglobulin, antibodies to thyroperoxidase, and concentrations of macro- and microelements were studied. Results. The development of experimental autoimmune thyroiditis led to a decrease in the content of total thyroxine and antibodies to thyroperoxidase in the blood serum, an increase in the content of antibodies to thyroglobulin and a decrease in the concentrations of sodium, chlorine, potassium phosphorus, zinc, copper, iron and magnesium. It was found that the use of AELM and TLM against the background of autoimmune thyroiditis led to the restoration of T4 and elemental balance in rats, which was manifested in an increase in the content of sodium, chlorine, phosphorus, magnesium, zinc, iron, copper and calcium in the blood serum. It was also shown that TLM had a more powerful effect on the normalisation of the content of such elements as chlorine, potassium, copper and zinc. The obtained effect of AELM and TLM on the content of macro- and microelements in the blood serum of animals with experimental AIT can be explained by their positive effect on the functional activity of the thyroid gland. The studied extract and tincture may also affect other physiological and biochemical processes due to the content of macro- and microelements and other biologically active substances, which requires further research. Conclusions. Administration of AELM and TLM to rats with experimental AIT contributed to lowering the level of Anti-TG and restoring the thyroid and elemental status in the animals' blood serum. The obtained research data allow us to recommend AELM and TLM as a regulator of the elemental status of the body in case of changes in thyroid function

Determination of copper status by five biomarkers in serum of healthy women

BackgroundThe essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism. To this end, additional biomarkers besides serum copper and ceruloplasmin (CP) concentrations are required. ObjectivesThe aim of this study was to investigate the emerging copper biomarkers CP oxidase (CPO) activity, exchangeable copper (CuEXC) and labile copper in serum of healthy women and compare them with the conventional biomarkers total serum copper and CP. Method and main findingsThis observational study determined CPO activity, the non CP-bound copper species CuEXC and labile copper, total serum copper and CP in sera of 110 healthy women. Samples were collected at four time points over a period of 24 weeks. The concentrations of total serum copper and CP were within the reference ranges. The comparison of all five biomarkers provided insight into their relationship, the intra- and inter-individual variability as well as the age dependence. The correlation and Principal Component Analyses (PCA) indicated that CP, CPO activity and total copper correlated well, followed by CuEXC, while the labile copper pool was unrelated to the other parameters. ConclusionsThis study suggests that the non-CP-bound copper species represent copper pools that are differently regulated from total copper or CP-bound copper, making them interesting complementary biomarkers to enable a more complete assessment of body copper status with potential relevance for clinical application.

Effect of cuprum proteinate on blood parameters in broiler chickens

The data obtained during the scientific and economic experiment show that the replacement of copper sulfate with copper proteinate in broiler chickens, even in smaller doses, did not significantly affect hematological and biochemical blood parameters. Some increase in the total level of albumins and globulins, the activity of aspartate aminotransferase and alanine aminotransferase, and the content of calcium, phosphorus and copper in blood serum was noted. Introduction of cuprum proteinate to compound feed to broiler chickens of the third experimental group in doses of 13.9; 12.6 and 9.0 g/t (on average for 42 days – 12.5 g/t) contributed to a probable increase in total protein by 14.2 % (Р &lt; 0.05) on the 30th day of the experiment and by 12.3 % (Р &lt; 0.05) on the 42nd day of the experiment compared to the control group. At the same time, the level of albumins increased by 11.9 % (Р &lt; 0.05) and 15.8 % (Р &lt; 0.05), and globulins by 12.0 % (Р &lt; 0.05) and 10.7 %, respectively. This fact shows that reducing the dose of cuprum proteinate has a positive effect on protein synthesis, activation of albumin and globulin synthesis occurs, which reduces the load on the immune system of broiler chickens and has a positive effect on protein metabolism. On the 42nd day of the experiment, the calcium content in the blood of all groups increased, but in the experimental groups it was higher than the control indicator in the second group by 4.8 % and by 5.6 % in the third experimental group. Regarding the level of Phosphorus in the blood serum of experimental groups of broiler chickens, its amount increased to 1.85–1.96 mmol/l on the 42nd day. The content of cuprum in the blood of broiler chickens, which were fed cuprum proteinate as part of compound feed, was probably higher than the indicator of the control group. Chickens of the second experimental group, which were fed cuprum proteinate in quantities of 18.2; 16.8 and 12.0 g/t of compound feed exceeded their counterparts by 14.0–16.3 % (Р &lt; 0.05). Broiler chickens of the third experimental group, which were added to compound feed with cuprum proteinate in doses of 13.9, 12.6 and 30 g/t, prevailed on day 30 of the experiment by 18.8 % (Р &lt; 0.01), and on day 42 day by 18.9 % (Р &lt; 0.01). A higher level of Calcium and Phosphorus in the blood serum of experimental broiler chickens indicates an increase in the resistance of the bird to infections and better mineralization of bone tissue. Feeding of cuprum proteinate to broiler chickens makes it possible to reduce the dose of the trace element in compound feed, which reduces the burden on the bird's body and increases the biological availability of mineral compounds.

Copper Promotes LPS-Induced Inflammation via the NF-кB Pathway in Bovine Macrophages.

Inflammation is a complex physiological process that enables the clearance of pathogens and repairing damaged tissues. Elevated serum copper concentration has been reported in cases of inflammation, but the role of copper in inflammatory responses remains unclear. This study used bovine macrophages to establish lipopolysaccharide (LPS)-induced inflammation model. There were five groups in the study: a group treated with LPS (100ng/ml), a group treated with either copper chelator (tetrathiomolybdate, TTM) (20μmol) or CuSO4 (25μmol or 50μmol) after LPS stimulation, and a control group. Copper concentrations increased in macrophages after the LPS treatment. TTM decreased mRNA expression of pro-inflammatory factors (IL-1β, TNF-α, IL-6, iNOS, and COX-2), whereas copper supplement increased them. Compared to the control group, TLP4 and MyD88 protein levels were increased in the TTM and copper groups. However, TTM treatment decreased p-p65 and increased IкB-α while the copper supplement showed reversed results. In addition, the phagocytosis and migration of bovine macrophages decreased in the TTM treatment group while increased in the copper treatment groups. Results mentioned above indicated that copper could promote the LPS-induced inflammatory response in bovine macrophages, promote pro-inflammatory factors by activating the NF-кB pathway, and increase phagocytosis capacity and migration. Our study provides a possible targeted therapy for bovine inflammation.

Micronutrients intake and genetic variants associated with premature ovarian insufficiency; MASHAD cohort study

Background and aimpremature ovarian insufficiency (POI) is defined as the menopause before 40 years of age, and its prevalence is reported to be two-fold higher in Iranian women than the average for woman globally. POI is associated with several cardio/cerebrovascular complications as well as an increased overall mortality. Genetic factors, and serum levels of minerals and vitamin D, have been reported to be related to the prevalence of POI. We have investigated the association between some POI -related genotypes with the serum levels of some important micronutrients.MethodsOne hundred and seventeen women with POI and 183 controls without any renal, hepatic, and thyroid abnormalities were recruited as part of the MASHAD study. Demographic and anthropometric features were recorded and blood samples were collected and processed. DNA was extracted from the buffy coat of blood samples from all participants and 8 POI-related single nucleotide polymorphisms (SNPs) were determined using ASO-PCR or Tetra ARMS-PCR. Serum minerals and vitamin D concentrations were measured using routine methods.ResultsIn women with POI, serum copper, phosphate, and calcium were significantly different for those with rs244715, rs16991615, and rs4806660 genotypes, respectively. In our control population, significant differences were also found in serum copper concentrations between different genotypes of rs4806660, rs7246479, rs1046089, and rs2303369. After adjusting for all confounding factors, the women with POI carrying TC genotype (rs4806660) had a lower risk to have serum copper levels < 80 (µg/dL) than those carrying a TT genotype. Furthermore, women with POI carrying GG genotype (rs244715) had a 6-fold higher risk to have serum copper levels > 155 than those carrying AA genotype.ConclusionThe C and G alleles of the rs4806660 and rs244715 polymorphisms respectively are independently associated with serum copper in women with POI. Further studies are necessary to investigate the association of serum copper and other micronutrients in women and other POI -related polymorphisms.

Prediction of cardiovascular disease risk by serum zinc and copper concentrations and anthropometric measurements

IntroductionWe aimed to investigate the association between cardiovascular disease (CVD) and various anthropometric indices, as well as the serum levels of copper (Cu) and zinc (Zn), copper-zinc ratio (Cu/Zn ratio) and zinc-copper ratio (Zn/Cu ratio), in a large population sample from northeastern Iranian. Method9704 individuals aged 35 to 65 were enrolled in the first phase of the study. After a 10-year follow-up, 7560 participants were enrolled into the second phase. The variables used in this study included demographic characteristics, such as gender and age; biochemical parameters including: serum Zn, Cu, Cu/Zn ratio, and Zn/Cu ratio; anthropometric parameters including: waist circumference (WC), body mass index (BMI), and waist-to-hip ratio (WHR). The relationship between the aforementioned indices and CVD was examined using decision tree (DT) and logistic regression (LR) models. ResultsA total of 837 individuals were diagnosed with CVD among the 7560 participants. LR analysis showed that BMI, age, WH zinc-copper ratio (Zn/Cu ratio), and serum Zn/Cu ratio were significantly associated the development of CVD in men, and WHR, age, BMI, serum Cu, and Cu/Zn ratio in women. DT analysis showed that, age was the most important predictor of CVD in both genders. 71% of women, older than 49 years, with a WHR≥ 0.89, serum Cu< 75 (µg/dl), BMI≥ 22.93 (kg/m2), and serum Cu≥ 14 (µg/dl), had the highest risk of CVD. In men, among those who were ≥ 53 years, with a WHR≥ 0.98, serum Zn/Cu ratio< 1.69, and BMI≥ 22.30, had the highest risk of CVD. ConclusionAmong Iranian adult population, BMI, age, and WHR were one of the predictors of CVD for both genders. The Zn/Cu ratio was CVD predictor for men while Cu/Zn ratio was CVD predictor for women.

Trace elements and the inflammatory process development: predictive possibilities

Introduction. Late diagnosis of inflammatory pathologies leads to increased risks of chronicization of the process, generalization, development of complications, and reduced effectiveness of therapy. Routine methods of clinical laboratory diagnostics often have diagnostic value at the stage of already developed disease with pronounced clinical manifestations. Determination of blood serum trace elements may have prognostic value in the diagnosis of inflammatory diseases. The trace elements most extensively studied in the context of inflammation and immune defense are copper and zinc. The aim of the study. The aim of the study was to investigate the prognostic significance of determining copper and zinc concentrations in serum in the diagnosis of inflammation. Material and methods. Concentrations of CRP, ferritin, ceruloplasmin, leukocytes, neutrophils, fibrinogen, copper, and zinc were determined in 1153 examined people aged 18 to 86 years. Serum trace elements were determined by ICP-MS method, the rest of the parameters were measured by standard methods. ROC analysis was used to evaluate the prognostic significance of serum copper and zinc measurements. Positive predictive value and negative predictive value were also calculated for the laboratory tests. Results. It was shown that serum copper concentration in both men and women can be used as a predictor of abnormalities of CRP, ceruloplasmin, and fibrinogen. By abnormalities in serum copper concentration, it is possible to predict increased leukocytes in men and women; decreased leukocytes in men; and increased neutrophil levels in men and women. The prognostic significance of the laboratory test for serum zinc was found in relation to the detection of ferritin deficiency in women and ceruloplasmin deficiency in men and women. Conclusion. The results obtained in the study suggest the possible use of serum copper and zinc laboratory tests for prognostic purposes.