High Levels Of Copper Research Articles

The mechanism of copper homeostasis and its role in disease

AbstractCopper (Cuprum) is an essential trace metal indispensable for the function of numerous enzymatic molecules implicated in cellular metabolism. Emerging evidence has demonstrated the role of copper in angiogenesis and cellular signaling. Moreover, raised copper levels have been detected in hepatocellular carcinoma and other cancers. An inherited or acquired copper imbalance, including inadequately low or excessively high copper levels, as well as inappropriate copper distribution in the body, is implicated in a number of diseases. In addition, a recent groundbreaking study identified a copper‐induced type of programmed cell death named cuprotosis, the mechanism of which greatly deferred from that of other known cell death modes. The first part provides an overview of the regulation of copper homeostasis and discusses the underlying mechanisms of cuprotosis. In the second part, the authors focus on the functions of copper in liver diseases and other metabolic disorders, before discussing how this knowledge could contribute to the development of effective targets to treat such diseases.

Plasma zinc, copper and serum ceruloplasmin levels of autism spectrum disorder children in Bangladesh

Neural and cognitive processes require zinc and copper homeostasis and a normal zinc/copper ratio. Ceruloplasmin, an intrinsic antioxidant protein, maintains copper homeostasis, which might also influence autism spectrum disorder (ASD). ASD children are frequently reported with altered levels of these elements with wide geographical variations. This study evaluated any alteration in plasma zinc, copper, zinc/copper ratio and serum ceruloplasmin levels in Bangladeshi ASD children with respect to healthy controls. A cross-sectional study was conducted on 67 children aged 2 to 9 years of both sexes. Among them, 35 had ASD, while 32 were age, sex and body mass index (BMI) matched apparently healthy children. Plasma zinc and copper levels were estimated by the flame atomic absorption spectrophotometry method. Serum ceruloplasmin levels were estimated by the immunoturbidimetric method. Zinc and zinc/copper ratio in the 2–9 years old ASD children group were significantly lower (p=0.032 and p=0.002 respectively). On the other hand, copper (p=0.020) and ceruloplasmin (p = 0.045) levels were significantly higher than those of apparently healthy children. ASD was significantly associated with zinc deficiency (p=0.000) and copper toxicity (p=0.05). All children were again divided into 2–5 and 6–9 years age groups according to laboratory reference values for zinc and copper. Copper toxicity was significantly associated with ASD in the 2–5 years old age group (p=0.011), with a significant difference in plasma copper levels (p=0.009) and zinc/copper ratio (p=0.001) but not serum ceruloplasmin levels (p=0.110) compared to healthy controls. Serum ceruloplasmin was positively associated with plasma copper in ASD children of all age groups. This study shows that ASD in Bangladesh can be associated with low plasma zinc and high plasma copper and serum ceruloplasmin levels.

Effects of Diabetes on Elemental Levels and Nanostructure of Root Canal Dentin

IntroductionThis study evaluated the effects of diabetes mellitus (DM) on the nanostructure of root canal dentin using high-resolution transmission electron microscopy (HRTEM) and inductively coupled plasma mass spectrometry (ICP-MS). MethodsTwenty extracted human premolars from diabetic and nondiabetic patients (n = 10 in each group) were decoronated and sectioned horizontally into 40 2-mm-thick dentin discs, with each disc designated for a specific test. ICP-MS was used to determine the different elemental levels of copper, lithium, zinc, selenium, strontium, manganese, and magnesium in diabetic and nondiabetic specimens. HRTEM was used to analyze the shape and quantity of the apatite crystals in diabetic and nondiabetic dentin at the nanostructural level. Statistical analysis was performed using Kolmogorov-Smirnov and Student t test (P < .05). ResultsICP-MS revealed significant differences in trace element concentrations between the diabetic and nondiabetic specimens (P < .05), with lower levels of magnesium, zinc, strontium, lithium, manganese, and selenium (P < .05), and higher levels of copper in diabetic specimens (P < .05). HRTEM revealed that diabetic dentin exhibited a less compact structure with smaller crystallites and significantly more crystals in the 2500 nm2 area (P < .05). ConclusionDiabetic dentin exhibited smaller crystallites and altered elemental levels more than nondiabetic dentin, which could explain the higher root canal treatment failure rate in diabetic patients.

Copper-contaminated soil compromises thermal performance in the springtail Folsomia candida (Collembola)

The widespread agricultural and industrial emissions of copper-based chemicals have increased copper levels in soils worldwide. Copper contamination can cause a range of toxic effects on soil animals and influence thermal tolerance. However, toxic effects are commonly investigated using simple endpoints (e.g., mortality) and acute tests. Thus, how organisms respond to ecological realistic sub-lethal and chronic exposures across the entire thermal scope of an organism is not known. In this study, we investigated the effects of copper exposure on the thermal performance of a springtail (Folsomia candida), regarding its survival, individual growth, population growth, and the composition of membrane phospholipid fatty acids. Folsomia candida (Collembola) is a typical representative of soil arthropods and a model organism that has been widely used for ecotoxicological studies. In a full-factorial soil microcosm experiment, springtails were exposed to three levels of copper (ca. 17 (control), 436, and 1629 mg/kg dry soil) and ten temperatures from 0 to 30 °C. Results showed that three-week copper exposure at temperatures below 15 °C and above 26 °C negatively influenced the springtail survival. The body growth was significantly lower for the springtails in high-dose copper soils at temperatures above 24 °C. A high copper level reduced the number of juveniles by 50 %, thereby impairing population growth. Both temperature and copper exposure significantly impacted membrane properties. Our results indicated that high-dose copper exposure compromised the tolerance to suboptimal temperatures and decreased maximal performance, whereas medium copper exposure partially reduced the performance at suboptimal temperatures. Overall, copper contamination reduced the thermal tolerance of springtails at suboptimal temperatures, probably by interfering with membrane homeoviscous adaptation. Our results show that soil organisms living in copper-contaminated areas might be more sensitive to thermally stressful periods.

Long-term dietary exposure to copper in the population in Germany - Results from the BfR MEAL study.

The German Total Diet Study (BfR MEAL Study) measured copper in 356 foods. In 105 of these foods copper was determined separately for conventionally and organically pooled samples. Mammalian liver, nuts, oilseeds, cocoa powder and chia seeds contained the highest copper levels. Organically produced foods tended to have higher levels compared to conventionally produced foods. Children's copper exposure was between 0.04mg/kg body weight per day (mg/kg bw/day) and 0.07mg/kg bw/day (median). High exposure (95th percentile) ranged between 0.07mg/kg bw/day and 0.11mg/kg bw/day. Adult's exposure ranged between 0.02mg/kg bw/day (median) and 0.04mg/kg bw/day (95th percentile). Grains and grain-based products were main contributors for all age groups. Copper intake was about 10% higher in a scenario where consumers select the organically produced variants. Children's median and high exposure was above the acceptable daily intake (ADI) of 0.07mg/kg bw/day set by the European Food Safety Authority (EFSA). However, according to EFSA's evaluation this is not of concern due to higher requirement related to growth. For adults, frequent consumers of mammalian liver exceeded the ADI in median and 95th percentile. Intake of copper-containing dietary supplements may also lead to exceedance of the ADI in all age groups.

Unravelling copper effect on the production of varietal thiols during Colombard and Gros Manseng grape juices fermentation by Saccharomyces cerevisiae.

Nowadays the rapidly increasing organic vineyard management with the utilization of copper as sole fungal control pesticide against downy mildew raises once again the question of copper impact on varietal thiols in wine. For this purpose, Colombard and Gros Manseng grape juices were fermented under different copper levels (from 0.2 to 3.88 mg/l) to mimic the consequences in must of organic practices. The consumption of thiol precursors and the release of varietal thiols (both free and oxidized forms of 3-sulfanylhexanol and 3-sulfanylhexyl acetate) were monitored by LC-MS/MS. It was found that the highest copper level (3.6 and 3.88 mg/l for Colombard and Gros Manseng respectively) significantly increased yeast consumption of precursors (by 9.0 and 7.6% for Colombard and Gros Manseng respectively). For both grape varieties, free thiol content in wine significantly decreased (by 84 and 47% for Colombard and Gros Manseng respectively) with the increase of copper in the starting must as already described in the literature. However, the total thiol content produced throughout fermentation was constant regardless of copper conditions for the Colombard must, meaning that the effect of copper was only oxidative for this variety. Meanwhile, in Gros Manseng fermentation, the total thiol content increased along with copper content, resulting in an increase up to 90%; this suggests that copper may modify the regulation of the production pathways of varietal thiols, also underlining the key role of oxidation. These results complement our knowledge on copper effect during thiol-oriented fermentation and the importance of considering the total thiol production (reduced+oxidized) to better understand the effect of studied parameters and differenciate chemical from biological effects.

Linking Copper-Associated Signal Transduction Systems with Their Environment in Marine Bacteria.

Copper is an essential trace element for living cells. However, copper can be potentially toxic for bacterial cells when it is present in excess amounts due to its redox potential. Due to its biocidal properties, copper is prevalent in marine systems due to its use in antifouling paints and as an algaecide. Thus, marine bacteria must possess means of sensing and responding to both high copper levels and those in which it is present at only typical trace metal levels. Bacteria harbor diverse regulatory mechanisms that respond to intracellular and extracellular copper and maintain copper homeostasis in cells. This review presents an overview of the copper-associated signal transduction systems in marine bacteria, including the copper efflux systems, detoxification, and chaperone mechanisms. We performed a comparative genomics study of the copper-regulatory signal transduction system on marine bacteria to examine the influence of the environment on the presence, abundance, and diversity of copper-associated signal transduction systems across representative phyla. Comparative analyses were performed among species isolated from sources, including seawater, sediment, biofilm, and marine pathogens. Overall, we observed many putative homologs of copper-associated signal transduction systems from various copper systems across marine bacteria. While the distribution of the regulatory components is mainly influenced by phylogeny, our analyses identified several intriguing trends: (1) Bacteria isolated from sediment and biofilm displayed an increased number of homolog hits to copper-associated signal transduction systems than those from seawater. (2) A large variability exists for hits to the putative alternate σ factor CorE hits across marine bacteria. (3) Species isolated from seawater and marine pathogens harbored fewer CorE homologs than those isolated from the sediment and biofilm.

Health implications of pesticides application among cocoa farmers in Idanre local government area, Southwest Nigeria

Pesticides are routinely applied by cocoa farmers to enhance cocoa production, which is threatened by pest infestations and diseases. However, the undesired health implications of pesticide applications on the farmers are yet to be fully elucidated especially among cocoa farmers in Idanre despite being the hub of cocoa production in Southwestern Nigeria. This study assessed the extent of pesticide use by cocoa farmers in the study area and determined the effects of exposure on their health using haematological and biochemical parameters as indices. A cross-sectional survey comprising 150 cocoa farmers and 50 controls (artisans) was carried out using structured questionnaire. Blood samples were obtained from participants for the determination of copper and sulphate levels, haematological (haematocrit, red blood cell counts, white blood cell counts and platelet counts) and biochemical (creatinine, cholesterol, direct bilirubin and total bilirubin) parameters. The blood levels of copper and sulphate were significantly higher in the cocoa farmers than in the controls. However, there was no significant difference between the subjects and controls for most of the haematological and biochemical parameters except for the platelet counts and total bilirubin levels. The data from the study did not suggest any serious health effects due to pesticide exposure on the cocoa farmers despite the high blood levels of copper and sulphate, probably due to exposure to copper-based fungicides. However, the high serum bilirubin level among the subjects was an indication of possible liver damage. As such, cocoa farmers should be guided against indiscriminate use of pesticides on their farms.

Level of Manganese and Copper in Selected Vegetables Marketed in Kaduna Metropolis

Vegetables containing micronutrients such as manganese and copper are widely consumed due to their essential role in the human body. Human activities due to environmental pollution significantly contribute to high levels of manganese and copper in the human body, which can lead to toxic effects. The research is aimed at determining the level of manganese and copper in selected vegetables (Lactuca sativa, Telfairia occidentalis, Vernonia amygdalina, Spinacia olaracea and Adansonia digitata) marketed in Kaduna metropolis. The selected vegetables were processed and digested using a tri-acid mixture (HNO3:HClO4:H2SO4 = 5:1:1) and the Cu and Mn content of the digests obtained was determined by Atomic Absorption Spectrometry (AAS). The results obtained indicated that Spinacia olaracea had the highest (0.336 ± 0.001) level of Mn while Telfairia occidentalis had the least (0.018 ± 0.013). The highest (0.139 ± 0.0002) level of Cu was recorded in Vernonia amygdalina and the lowest level (0.068±0.005) was found in Lactuca sativa. All the concentrations recorded are within the official WHO permissible limit of 5mg/kg for manganese and 4mg/kg for copper in vegetable plant materials. Therefore, these values may suggest that the selected vegetables are safe for human consumption.

Grf10 regulates the response to copper, iron, and phosphate in Candida albicans.

The pathogenic yeast, Candida albicans, and other microbes must be able to handle drastic changes in nutrient availability within the human host. Copper, iron, and phosphate are essential micronutrients for microbes that are sequestered by the human host as nutritional immunity; yet high copper levels are employed by macrophages to induce toxic oxidative stress. Grf10 is a transcription factor important for regulating genes involved in morphogenesis (filamentation, chlamydospore formation) and metabolism (adenylate biosynthesis, 1-carbon metabolism). The grf10Δ mutant exhibited resistance to excess copper in a gene dosage-dependent manner but grew the same as the wild type in response to other metals (calcium, cobalt, iron, manganese, and zinc). Point mutations in the conserved residues D302 and E305, within a protein interaction region, conferred resistance to high copper and induced hyphal formation similar to strains with the null allele. The grf10Δ mutant misregulated genes involved with copper, iron, and phosphate uptake in YPD medium and mounted a normal transcriptional response to high copper. The mutant accumulated lower levels of magnesium and phosphorus, suggesting that copper resistance is linked to phosphate metabolism. Our results highlight new roles for Grf10 in copper and phosphate homeostasis in C. albicans and underscore the fundamental role of Grf10 in connecting these with cell survival.

Cisplatin reacts with the RING finger domain of RNF11 and interferes with the protein functions.

Protein reactions play important roles in the mechanism of action of cisplatin. In this work, we found that cisplatin is highly reactive to the RING finger domain of RNF11, a key protein involved in tumorigenesis and metastasis. The results show that cisplatin binds to RNF11 at the zinc coordination site and leads to zinc-ejection from the protein. The formation of S-Pt(II) coordination and Zn(II) ions release have been confirmed by UV-vis spectrometry using zinc dye and thiol agent, showing reducing the contents of thiol groups while forming S-Pt bonds and releasing zinc ions. ESI-MS measurement indicates that each RNF11 can bind up to three platinum atoms. Kinetical analysis shows a reasonable platination rate of RNF11 with t1/2 ∼ 3 h. CD, NMR and gel electrophoresis measurements indicate that the cisplatin reaction causes protein unfolding and oligomerization of RNF11. Pull-down assays confirms that the platination of RNF11 interferes with the protein interaction of RNF11 with UBE2N, a key step of the functionalization of RNF11. Furthermore, Cu(I) was found to promote the platination of RNF11, which could lead to increased protein reactivity to cisplatin in tumor cells with high copper level. These results indicate that the platination-induced zinc-release of RNF11 disrupts the protein structure and interferes with its functions.

Effect of high-copper diet on transference of bla CTX-M genes among Escherichia coli strains in rats' intestine.

Both ceftiofur (CTO) and high copper are widely utilized in animal production in China, and the occurrence of CTX-M-carrying Escherichia coli in food-producing animals is increasing. There are some specific associations between in-feed high-level copper and antibiotic resistance, but research in Gram-negative bacteria such as E. coli remains scarce. This study aimed to evaluate the effect of high-copper diet on the horizontal transfer of bla CTX-M-1 among E. coli. A total of 32 male SPF rats aged 21 days were randomly assigned to the following four groups: control (6 mg/kg in-feed copper, C-), high copper (240 mg/kg in-feed copper, H-), CTO (6 mg/kg in-feed copper with oral CTO administration, C+), and high copper plus CTO (240 mg/kg in-feed copper with oral CTO administration, H+). All rats were orally inoculated with an E. coli strain harboring a conjugative plasmid carrying bla CTX-M-1, and the C+ and H+ groups were given 10 mg/kg of body weight (BW) CTO hydrochloride at 26, 27, and 28 days, while the C- and H- groups were given salad oil at the same dose. Fecal samples collected at different time points were used for the enumeration of E. coli on Mac plates or for molecular analysis using PCR, pulsed-field gel electrophoresis (PFGE), S1-PFGE, and Southern-blot hybridization. The results showed that the number of the bla CTX-M-1 gene in the H- group was higher and that the loss speed of this gene was slower compared with the C- group. After administration of CTO, the counts of cefotaxime-resistant E. coli were significantly higher in the C+ group than that in the corresponding control group (C+ vs. C-; H+ vs. H-). In the in vitro test, the results showed that the transfer rates of the conjugation induced by the H- (12 mmol/L) group were significantly higher than that of low copper (2 mmol/L) group. The indigenous sensitive isolates, which were homologous to the bla CTX-M-positive isolates of rat feces, were found by PFGE. The further analysis of S1-PFGE and Southern-blot hybridization confirmed that the bla CTX-M-1 gene in new transconjugants was derived from the inoculated strain. Taken together, high-copper diet facilitates the horizontal transfer and maintenance of the resistant genes in the intestine of rats, although the effects of antibiotics on bacterial resistance appearance and maintenance are more obvious.

Personal air pollution exposure and metals in the nasal epithelial lining fluid of COPD patients

Sampling of the nasal epithelial lining fluid is a potential method to assess exposure to air pollution within the respiratory tract among high risk populations. We investigated associations of short- and long-term particulate matter exposure (PM) and pollution-related metals in the nasal fluid of people with chronic obstructive pulmonary disease (COPD). This study included 20 participants with moderate-to-severe COPD from a larger study who measured long-term personal exposure to PM2.5 using portable air monitors and short-term PM2.5 and black carbon (BC) using in-home samplers for the seven days preceding nasal fluid collection. Nasal fluid was sampled from both nares by nasosorption, and inductively coupled plasma mass spectrometry was used to determine the concentration of metals with major airborne sources. Correlations of selected elements (Fe, Ba, Ni, Pb, V, Zn, Cu) were determined within the nasal fluid. Associations between personal long-term PM2.5 and seven day home PM2.5 and BC exposure and nasal fluid metal concentrations were determined by linear regression. Within nasal fluid samples, concentrations of vanadium and nickel (r = 0.8) and lead and zinc (r = 0.7) were correlated. Seven day and long-term PM2.5 exposure were both associated with higher levels of copper, lead, and vanadium in the nasal fluid. BC exposure was associated with higher levels of nickel in the nasal fluid. Levels of certain metals in the nasal fluid may serve as biomarkers of air pollution exposure in the upper respiratory tract.

The Influence of Follicular Fluid Metals on Assisted Reproduction Outcome.

Infertility has become more common, with an increased exposure to toxic compounds including heavy metals (HM). Follicular fluid (FF) surrounds the developing oocyte in the ovary and can be analysed to assess metal content. The levels of twenty-two metals were measured in the FF of ninety-three females in a reproduction unit, and their influence on assisted reproduction technique (ART), were examined. The metals were determined by optical emission spectrophotometry. Low values of copper, zinc, aluminium, and calcium favour polycystic ovary syndrome. The relationships between the number of oocytes and metals: iron (rs=0.303; p=0.003) and calcium (rs=-0.276; p=0.007) are significant, as well as between the number of mature oocytes with iron (rs=0.319; p=0.002), calcium (rs=-0.307; p=0.003) and sodium (rs=-0.215; p=0.039) and are near to significance in the case of aluminium (rs=-0.198; p=0.057). In the group with a fertilisation rate ≤ 75%, 36% of the women presented calcium >176.62 mg/kg compared to the group with a fertilisation rate ≥ 75% where this percentage was only 10% (p=0.011). An excess of iron and calcium reduces the good quality embryo rate, and an excess of potassium impairs the blastocyst rate. If potassium is above 237.18 mg/kg and calcium is below 147.32 mg/kg, these conditions favour embryo implantation. Pregnancy is influenced by high potassium and low copper levels. Controlling exposure to toxic elements is recommended for all couples with reduced fertility or receiving an ART.

Ionomics-metabolome association analysis as a new approach to the impact of dietary copper levels in suckling piglets model

Ionomics-metabolomics association analysis is a novel method to elucidating the potential mechanisms underlying the effects of dietary copper on the overall health parameters of suckling piglets model. Few studies have elucidated the relationship between the changes of ionic and metabolic homeostasis responses to dietary copper level. The growth performance data was obtained from 180 suckling piglets which access to different copper levels: 6 (low copper diet, LC), 20 (control diet, CON), and 300 (high copper diet, HC) mg·kg−1 copper (based on diet, supplementation from CuSO4), and offered ad libitum from d 14 until weaning at 40 d of age. Dietary high level copper (300 mg·kg−1) increased the ADG and ADFI during d 14 to 28 of piglets. Six elements (Mg, Na, K, P, Cu, and Mn) concentrations significantly changes in hair among the three treatment diets. The significant increased concentrations of Na and K, and decreased concentration of Mg and Mn in 300 mg·kg−1 than 20 mg·kg−1 copper diet was observed. In current study, with the increase in copper level from 20 to 300 mg·kg−1 in diet, the correlation between hair Na, K and Cu, Mn, Zn vanish. Hair Na and K were positively correlated with serum total antioxidant capacity (T-AOC) and negatively correlated with tumor necrosis factor-α (TNF-α). The hair Cu was negatively correlated with serum malondialdehyde (MDA), total bile acid (TBA). The fecal Cu was positively correlated with serum growth hormone (GH). The results suggested that the average daily gain (ADG) in 6 mg·kg−1 copper diet and the average daily feed intake (ADFI) in 20 mg·kg−1 copper diet were decreased than 300 mg·kg−1 copper diet during d 14 to 28 and the ADG was decreased in 6 and 20 mg·kg−1 copper diets in d 29 to 40 of piglets. Dietary 20 mg·kg−1 copper maintain ion homeostasis due to increase the number of positive correlations between macroelements-microelements in hair and serum. Significantly changed Na, K, Mg, Mn and Cu concentrations in hair can reflect the adverse effects of dietary 300 mg·kg−1 copper of suckling piglets. We believe our results may benefit people to gain a better understanding of the ion interactions and metabolic homeostasis of heavy metal elements that are critical to human and animal health.

Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis.

Tuberculosis (TB) patients show dysregulated immunity, iron metabolism, and anemia. In this study, circulatory cytokines, trace metals, and iron-related proteins (hepcidin, ferroportin, transferrin, Dmt1, Nramp1, ferritin, ceruloplasmin, hemojuvelin, aconitase, and transferrin receptor) were monitored in case (active tuberculosis patients: ATB) and control (non-tuberculosis: NTB and healthy) study populations (n = 72, male: 100%, mean age, 42.94 years; range, 17-83 years). Using serum elemental and cytokine levels, a partial least square discriminate analysis model (PLS-DA) was built, which clustered ATB patients away from NTB and healthy controls. Based on the PLS-DA variable importance in projection (VIP) score and analysis of variance (ANOVA), 13 variables were selected as important biosignatures [IL-18, IL-10, IL-13, IFN-γ, TNF-α, IL-5, IL-12 (p70), IL-1β, copper, zinc, selenium, iron, and aluminum]. Interestingly, low iron and selenium levels and high copper and aluminum levels were observed in ATB subjects. Low circulatory levels of transferrin, ferroportin, and hemojuvelin with higher ferritin and ceruloplasmin levels observed in ATB subjects demonstrate an altered iron metabolism, which partially resolved upon 6 months of anti-TB therapy. The identified biosignature in TB patients demonstrated perturbed iron homeostasis with anemia of inflammation, which could be useful targets for the development of host-directed adjunct therapeutics.

Validity of Serum Zinc/Copper Ratio as a Potential Novel Biomarker in Childhood Epilepsy.

Alterations in zinc and copper homeostasis may contribute to seizure susceptibility, development, termination, and response to antiepileptic medications. The current study examined the profile of zinc, copper, and their ratio in childhood epilepsy and its pharmacological variants (pharmacoresistant and pharmacoresponsive). The study included 100 epileptic children (50 pharmacoresistant and 50 pharmacoresponsive) and 50 healthy, age- and gender-matched controls. History, clinical examination, and assays of serum zinc and copper were performed. Zinc/copper ratio was calculated. Serum zinc and the zinc/copper ratio were significantly lower in epileptic children than in controls (p < 0.001). Significantly lower zinc and zinc/copper ratio and higher copper levels were found in children treated with levetiracetam/sodium valproate/oxcarbazepine than those treated with levetiracetam alone or combined with sodium valproate (p < 0.05 for all). Epileptic children, particularly pharmacoresistant, exhibited significant negative correlations between the serum levels of zinc and copper (r = -0.279, p = 0.005, and r = -0.363 and p = 0.010, respectively). At cutoff value of zinc/copper ratio < 1.118 in diagnosing children with epilepsy, it gives a sensitivity of 64% and a specificity of 85% with the AUC = 0.8092. At cutoff value of zinc/copper ratio ≤ 0.7826 in distinguishing pharmacoresistant epilepsy, it produced 52% sensitivity, 64% specificity with AUC = 0.576 Conclusions: Low zinc and high copper levels were associated with childhood epilepsy especially those with pharmacoresistant type and treated with Oxcarbazepine. Zinc/copper ratio might be a potential biomarker in diagnosing childhood epilepsy and to some extent in predicting pharmacoresistant type.

Effects of Supplementation of Zinc, Manganese, or Copper and Different Phytase Levels in Serum and Bone Acid and Alkaline Phosphatases of Broiler Chicks

The knowledge of biological trace minerals and phytase requirements for modern broiler genotypes is not established and the pressure to reduce their usage in animal feeding due to environmental issues is increasing. Here, the alkaline phosphatase (ALP) and tartarate-resistant acid phosphatase (TRAP) of the tibia and serum of broilers fed with diets containing various levels of phytase and reduced levels of zinc, manganese, and copper was evaluated. The experiment was performed using 1,200 male Cobb broilers raised according to standard commercial husbandry techniques. Data were analyzed as a 4×3 factorial arrangement with four concentrations of zinc (0.34, 0.49, 0.64, and 0.79 ppm), manganese (0.18, 0.43, 0.68, and 0.93 ppm), or copper (0.09, 0.12, 0.15, and 0.18 ppm) and three concentrations of phytase (0, 500, and 1,000 FTU/kg) for age periods of 1-21 and 36-42 days. While the dietary supplementation with copper did not induce a significant effect in bone tissue biochemical markers, serum TRAP activity of 42-day old broilers increased with higher copper levels. Increasing dietary zinc levels linearly increased ALP activity in tibia growth, suggesting that zinc is essential for longitudinal bone growth. Phytase significantly promoted the increase of TRAP and ALP activities, suggesting that manganese increased growth plate activity, accelerated calcification, and remodeled the newly formed tissue into trabecular bone. Although not every enzymatic activity was affected by the treatments, the phytase use, along with trace minerals, improved the animal response to the rapid growth required nowadays and provided the nutrients for adequate bone metabolism.

Relationship between Occupational Exposure to Respirable Crystalline Silica and Serum Copper Level as an Indicator of Silicosis: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis study evaluates a relationship between occupational exposure to respirable crystalline silica and serum copper (Cu) levels as an indicator for early detection of silicosis. A systematic search was conducted, and the quality of results was evaluated in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The following databases were searched, including Web of Sciences, Scopus, and PubMed from inception until November 2021. The following keywords were selected for searching in the mentioned databases including, "copper" OR "serum copper" AND "silicosis". The mean (standard deviation [SD]) of Cu was extracted for both silicosis and non-silicosis subjects. The differences in mean effect size were pooled using the random-effect model. Heterogeneity and publication bias were evaluated using the I2 value and Begg's test and Egger's test, respectively. A total of 159 studies were initially found, among which eight studies were included in the meta-analysis. Random-effect meta-analysis of these eight studies showed that silicosis patients had higher copper levels than the non-silicosis group with a pooled standardized mean difference (SMD) of 3.02 (95% confidence interval: 0.25, 5.78); I2 = 99.3%, P value < 0.001. The subgroup analysis showed that the corresponding figures in those with mean age >40 years and <40 years were 5.79 (2.06, 9.52) and -0.43 (-4.57, 3.70), respectively. Moreover, no publication bias was found in the analyses. The results of the present study demonstrated that silica exposure may be associated with increasing serum Cu levels.

Evaluation of the Smoking Factor in the Blood of Workers in Diyala State Company and its Relationship to Heavy Metals (Lead, Nickel and Copper)

Environmental pollution of heavy metals is becoming an increasing problem and has become a major concern due to the adverse effects it causes worldwide. Heavy metals are naturally occurring elements that have a high atomic weight and a density at least five times greater than water. It’s a multiple industrial, domestic, agricultural, medical and technological applications have led to its widespread use in the environment; Raising concerns about their potential effects on human health and the environment. The aim of the current study is Evaluation the relationship between the smoking factor in the blood of workers in Diyala State Company and to the percentage of the heavy metals such as lead (Pb), nickel (Ni) and copper (Cu) . This study was conducted for the period from 1/10/2021 to 1/3/2022, Eighty two blood samples were collected (58 blood samples from workers working in the Diyala State Company affiliated to the Ministry of Industry and Minerals, while, 24 control samples were from control samples for employees who don’t working with industrial emissions).The workers were divided into three groups based on the location work inside the station, sector (A) represented painter workers, sector (B) characterized the workers specialized in the copper coil of the electrical transformer, while sector (C) represented the iron core section of the electrical transformer. Five ml. of venous blood was taken for each sample. The concentration of Pb, Ni and Cu in the blood samples were determined by using the Flameless Atomic Absorption Spectrometer (FLAAS). The results of the intensive study showed the presence of high levels of lead, nickel and copper in smokers and non-smokers workers within the profession compared to control samples during the service period, with significant differences (P < 0.05). The results showed increasing levels of lead, nickel and copper with the progression of the service life, and the elements (lead, nickel and copper) recorded the highest average during the service period of 21-34, The painting worker showed high level of Ni while, Cu level peaked in wires worker . Based on age periods, elements levels (Pb, Ni, and Cu) were increased with age period progression, where it is found the levels of Pb, Ni, and Cu scored highest mean within >50 age period, while the least mean value of Pb, and Cu at 3-40 years age period, and least mean value of Ni was at <30 age. Finally, the results discovered there is positive correlations among metals and worker’s age.