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1.  A comparison of serum selenium, zinc and copper level in visceral and cutaneous leishmaniasis 
Background:
Leishmaniasis is a widespread tropical infection, which has a high incidence rate in Iran. Visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) are two forms of this disease. In this study, we investigated if selenium (Se), zinc (Zn) and copper (Cu) levels differ in different forms of leishmaniasis.
Materials and Methods:
To determine if leishmaniasis has effects on trace elements status, they were determined by atomic absorption spectrometry (AAS) in patients (n = 155, 95 CL and 60 VL) and control group (n = 100).
Results:
Our findings indicate that there is a significant difference in the values of Se and Zn between control and patient groups (P < 0.0001 and P < 0.001, respectively). Se and Zn levels were 3.65 ± 0.88 and 67.24 ± 18.76 μg/dL in the leishmaniasis patients, and these values were observed to be statistically lower compared to the control groups (11.10 ± 2.37 and 119.61 ± 26.18 μg/dL, respectively). Meanwhile, no significant difference in status of Cu was found between the cases (110.55 ± 29.25 μg/dL) and healthy subjects (91.42 ± 27.54 μg/dL) (P > 0.05). When the patients were divided into two groups, there appeared to be a significant decrease (P < 0.001) in Se concentration for VL patients (2.57 ± 0.64 μg/dL) compared with CL patients (4.33 ± 1.06 μg/dL).
Conclusion:
Based on these results, serum Se and Zn levels could be a useful marker for the pathophysiology of leishmaniasis.
PMCID: PMC4115352  PMID: 25097609
Antioxidant trace elements; atomic absorption spectroscopy; cutaneous leishmaniasis; trace elements; visceral and cutaneous leishmaniasis
2.  Copper and Resveratrol Attenuates Serum Catalase, Glutathione Peroxidase, and Element Values in Rats with DMBA-Induced Mammary Carcinogenesis 
Biological Trace Element Research  2013;156(1-3):271-278.
In this paper, a hypothesis was assessed whether or not the intoxication with copper and supplementation with copper plus resveratrol would result in changes in the activities of catalase and glutathione peroxidase and moreover if the characteristic changes would appear in concentrations of copper, iron, calcium, magnesium, and zinc in the serum of rats with chemically induced carcinogenesis. Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet, were treated with copper (42.6 mg Cu/kg food as CuSO4·5H2O) or copper plus resveratrol (0.2 mg/kg body) via gavage for a period from 40 days until 20 weeks of age. In cancer groups, the rats were treated with a dose of 80 mg/body weight of 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) given in rapeseed oil at 50 and 80 days of age to induce mammary carcinogenesis. The control groups included the rats kept in the same conditions and fed with the same diet as the animals from the study groups, but not DMBA-treated. The activity of catalase significantly decreased in groups of rats with mammary carcinogenesis that were supplemented with copper (p < 0.05) or copper plus resveratrol (p < 0.001) in comparison with the control groups that received the same diets. In cancer groups of nonsupplemented rats, the increase of glutathione peroxidase activity was observed. The process of carcinogenesis and the applied supplementation significantly altered the concentrations of trace elements in serum, in particular as concerns iron and copper. The mean serum iron levels in rats with breast cancer were significantly lower than those in the control groups (p < 0.001). The mean serum copper levels significantly decreased in the groups of rats with mammary carcinogenesis that were supplemented with copper or copper plus resveratrol in comparison with the control groups that received the same diets (p < 0.001). The characteristic changes in iron content and the zinc/copper and zinc/iron ratios in blood may be used as one of the prognostic factors in breast cancer research.
doi:10.1007/s12011-013-9854-x
PMCID: PMC3844146  PMID: 24213724
Copper; Resveratrol; Serum mineral analysis; Catalase; Gluthatione peroxidase; Breast cancer
3.  Associations between Serum C-reactive Protein and Serum Zinc, Ferritin, and Copper in Guatemalan School Children 
Biological trace element research  2012;148(2):154-160.
Inflammation affects trace nutrient concentrations, but research on copper and particularly in children is limited. We assessed associations between serum C-reactive protein (CRP) and zinc, iron, copper, and other biomarkers (alkaline phosphatase, hemoglobin, and albumin), in 634 healthy 6- to 11-year-old Guatemalan schoolchildren. CRP was measured by a standardized, high-sensitive method. For significant associations with CRP, we stratified nutrient concentrations across categories of CRP and compared concentrations above and below several CRP cutoff points (0.5, 1, 3, 5, and 10 mg/L), and then adjusted values using correction factors (ratios of geometric means of the nutrients in the low and high groups). Prevalence of serum zinc (<65 μg/dL0, ferritin (<15 μg/L), and copper (<90 μg/dL) deficiency were 21%, 2.1%, and 23.8%, respectively. Median (25th and 75th percentiles) CRP was 0.56 (0.26 and 1.54) mg/L. CRP concentration was positively associated with ferritin and copper concentrations (r=0.23 and 0.29, respectively; P<0.0001) but not with zinc and other bio-markers (P>0.05). Regardless of CRP cutoffs, high (> cutoff) vs. low (≤ cutoff) CRP levels had higher ferritin and copper concentrations and lower prevalence of copper deficiency of <90 μg/dL (P<0.05). Adjustment for inflammation had the greatest influence on recalculated prevalence for the CRP 0.5 mg/L cutoff. The low ferritin prevalence hardly changed (from 2.1% to 2.5%) while the low copper prevalence changed appreciably (from 23.8% to 31.2%). In conclusion, CRP was positively associated with ferritin and copper but not with zinc concentrations. Adjustment for inflammation had little effect on low ferritin prevalence, low to begin with, and a large impact on low copper prevalence. High-sensitive CRP methods and the use of very low CRP cutoffs may be more accurate than traditional CRP methods in the adjustment of serum copper concentrations for inflammation in healthy school children.
doi:10.1007/s12011-012-9358-0
PMCID: PMC3734531  PMID: 22354676
Inflammation; C-reactive protein; School children; Ferritin; Zinc; Copper
4.  Studies on Association Between Copper Excess, Zinc Deficiency and TP53 Mutations in Esophageal Squamous Cell Carcinoma From Kashmir Valley, India-A High Risk Area 
Trace element deficiency or excess is implicated in the development or progression in some cancers. Here we report the elevated levels of copper and low level of zinc in the plasma of esophageal cancer patients in Kashmir India- a high incidence area. The average level of copper was significantly higher for patients than for controls (p<0.0001) with a mean concentration of 169 μg/dl and 149 μg/dl for patients and controls, respectively. In contrast, the average level of zinc in patients was significantly lower than in controls (p<0.0001) with a mean concentration of 86.8 μg/dl and 96.1 μg/dl for patients and controls, respectively. No significant difference in copper and zinc levels was observed for different age groups in controls or patients. For controls, the level of copper was not significantly different in males and females (median: 155 μg/dl for males and 144 μg/dl for females, p=0.10), but we observed a higher level of zinc in females (median: 90.5 μg/dl for males and 101 μg/dl for females, p=0.03). Copper or zinc concentrations were not significantly associated with gender, tumor site, green tea with salt (nun chai) consumption, smoking habits or snuff in cases. Patients with poorly differentiated tumors had a higher copper concentration than those with moderately or well-differentiated tumors (p<0.0001). No association was found between copper concentration and TP53 mutation status but patients with TP53 mutant tumor had lower zinc levels than those with no mutation. Our results point towards a role of the trace element imbalance in the esophageal tumorigenesis in high risk Kashmiri population exposed to a range of nitroso compounds or their precursors. Further prospective cohort studies are warranted to determine whether change in the plasma zinc and copper homeostasis may represent an independent risk factor for this malignancy as well as possible target for preventive intervention.
PMCID: PMC3068648  PMID: 21475450
Esophgeal squamous cell carcinoma; Trace elements; copper excess; Zinc deficiency; TP53 mutations; Kashmir
5.  Trace Element Status (Iron, Zinc, Copper, Chromium, Cobalt, and Nickel) in Iron-Deficiency Anaemia of Children under 3 Years 
Anemia  2014;2014:718089.
Aim. To determine trace element status and aetiologic factors for development of trace elements deficiencies in children with iron-deficiency anaemia (IDA) aged 0 to 3 years. Contingent and Methods. 30 patients of the University Hospital, Pleven, Bulgaria—I group; 48 patients of the Sumy Regional Child's Clinical Hospital, Sumy, Ukraine—II group; 25 healthy controls were investigated. Serum concentrations of iron, zinc, copper, chromium, cobalt, and nickel were determined spectrophotometrically and by atomic absorption spectrophotometry. Results. Because the obtained serum levels of zinc, copper, and chromium were near the lower reference limits, I group was divided into IA and IB. In IA group, serum concentrations were lower than the reference values for 47%, 57%, and 73% of patients, respectively. In IB group, these were within the reference values. In II group, results for zinc, cobalt, and nickel were significantly lower (P < 0.05), and results for copper were significantly higher in comparison to controls. Conclusion. Low serum concentrations of zinc, copper, cobalt, and nickel were mainly due to inadequate dietary intake, malabsorption, and micronutrient interactions in both studied groups. Increased serum copper in II group was probably due to metabolic changes resulting from adaptations in IDA. Data can be used for developing a diagnostic algorithm for IDA.
doi:10.1155/2014/718089
PMCID: PMC4003800  PMID: 24839556
6.  Analysis of Serum Zinc and Copper Concentrations in Hair Loss 
Annals of Dermatology  2013;25(4):405-409.
Background
It is well known that some trace elements such as zinc and copper play a significant role in many forms of hair loss. However, the effect of zinc and copper in the pathogenesis of hair loss is still unknown.
Objective
The purpose of this study is to evaluate the zinc and copper status in each of four types of hair loss.
Methods
A study was carried out with 30 health controls and 312 patients who were diagnosed with alopecia areata (AA), male pattern hair loss, female pattern hair loss and telogen effluvium (TE) (2008 to 2011; Hallym University Kangdong Sacred Heart Hospital). Zinc and copper serum concentrations were evaluated between controls and each of four types of hair loss patients.
Results
In all of the hair loss patients, the mean serum zinc was 84.33±22.88, significantly lower than the control group (97.94±21.05 µg/dl) (p=0.002), whereas the serum copper was 96.44±22.62, which was not significantly different (p=0.975). The analysis of each group showed that all groups of hair loss had statistically lower zinc concentration, but not copper concentrations. However, the ratio of the patients with serum zinc concentration lower than 70 µg/dl was significantly high in only the AA group (odds ratio, OR 4.02; confidence interval, CI 1.13 to 14.31) and the TE group (OR 1.12; CI 1.12 to 17.68).
Conclusion
The data led to the hypothesis of zinc metabolism disturbances playing a key role in hair loss, especially AA and TE, whereas the effect of copper on hair growth and shedding cycles still needs more study.
doi:10.5021/ad.2013.25.4.405
PMCID: PMC3870206  PMID: 24371385
Alopecia; Copper; Zinc
7.  Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study 
Background
The process of elimination of intracellular pathogens, such as Leishmania, requires a Th1 type immune response, whereas a dominant Th2 response leads to exacerbated disease. Experimental human zinc deficiency decreases Th1 but not Th2 immune response. We investigated if zinc and copper levels differ in different clinical forms of leishmaniasis, and if these trace metals might be involved in the immune response towards the parasite.
Methods
Blood was collected from 31 patients with either localized cutaneous (LCL), mucosal (ML) or visceral (VL) leishmaniasis, as well as from 25 controls from endemic and non-endemic areas. Anti-Leishmania humoral and cellular immune response were evaluated by quantifying specific plasma IgG, lymphoproliferation and cytokine production, respectively. Plasma levels of Cu and Zn were quantified by atomic absorption spectrophotometry.
Results
A significant decrease in plasma Zn was observed in all three patient groups (p < 0.01 for LCL and ML, p < 0.001 for VL), as compared to controls, but only VL (7/10) and ML (1/7) patients displayed overt Zn deficiency. Plasma Cu was increased in LCL and VL (p < 0.001) but not in ML, and was strongly correlated to anti-Leishmania IgG (Spearman r = 0.65, p = 0.0028). Cu/Zn ratios were highest in patients with deficient cellular (VL<LCL>ML) immune response. Ex vivo production of parasite-induced IFN-γ was negatively correlated to plasma Cu levels in LCL (r = -0.57, p = 0.01). In vitro, increased Cu levels inhibited IFN-γ production.
Conclusions
1. Zn deficiency in VL and ML indicate possible therapeutic administration of Zn in these severe forms of leishmaniasis. 2. Plasma Cu positively correlates to humoral immune response across patient groups. 3. Environmentally or genetically determined increases in Cu levels might augment susceptibility to infection with intracellular pathogens, by causing a decrease in IFN-γ production.
doi:10.1186/1471-2334-4-50
PMCID: PMC534101  PMID: 15546498
8.  Comparison of Zn, Cu, and Fe Content in Hair and Serum in Alopecia Areata Patients with Normal Group 
Background. Alopecia areata (AA) is an autoimmune condition, in which hair is lost from some areas of the body. Though its etiopathogenesis is not fully understood, there are claims that imbalance of trace elements may trigger the onset of AA, by distorting immune functions. In this study, we tried to investigate the relationship between AA and iron, zinc, and copper levels of serum and hair. Materials and Methods. Sixteen female patients with AA (14–40 years old) and 27 healthy female controls were enrolled in this study. Serum and hair level of iron, zinc, and copper were measured by flame emission spectroscopy. The resulting data was analyzed with SPSS15. Results. We did not detect a significant difference in the serum and hair level of iron, zinc, and copper between patients and controls. There was a significant correlation between serum and hair level of iron (r = 0.504,  P = 0.001), zinc (r = 0.684,  P = 0.0001), and copper (r = 0.759, P = 0.0001) in patients and controls. Discussion and Conclusion. According to this study, there was no statistically significant difference between trace elements among AA patients and controls. So the trace elements level in hair and serum may not be relevant to the immunologic dysfunction that exists in AA patients.
doi:10.1155/2014/784863
PMCID: PMC4160619  PMID: 25246935
9.  Serum antioxidant micromineral (Cu, Zn, Fe) status of drug dependent subjects: Influence of illicit drugs and lifestyle 
Background
Use of illicit drugs induces multiple nutrient deficiencies. Drug habit, sexual practice and socioeconomic factors influence the nutrient profile of drug dependent subjects. The literature on this issue is still insufficient. This study has tested the hypothesis that illicit drug use and lifestyle impair mineral status. To test this hypothesis, 253 men multiple drug users of age 18–45 years were recruited to investigate their serum copper, zinc and iron levels. Influence of illicit drugs and their lifestyle on the mineral levels was also examined. The study subjects were drug dependent who had shared needles and had sexual activity with multiple partners. Serum concentrations of the minerals were estimated by atomic absorption flame spectrometry.
Results
Results showed a significant increase in serum copper and zinc concentrations, and decrease in iron level in drug dependent subjects. The increase of copper level was found to be much higher than that of zinc. Period of drug abuse had made a significant positive influence on the copper and iron levels, but it was apparently reversed for zinc concentration. Multiple sexual partnerships had significant influence on zinc status. There also were significant relationships observed between body mass index (BMI) as well as certain socioeconomic factors, and mineral status of drug dependent subjects and non-drug dependent controls. A series of multiple linear regression analysis predicted mineral values for education, age and BMI. The group (drug dependent subject = 1, non-drug dependent control = 2) had a significant influence on these parameters. However, after controlling these factors, it was shown that illicit drug use significantly contributed to influence the serum mineral levels.
Conclusion
Illicit drug use impairs serum mineral value causing an increase in copper and zinc and a decrease in iron. Lifestyle and nutritional status of drug dependent subjects influence serum mineral concentrations.
doi:10.1186/1747-597X-2-12
PMCID: PMC1872021  PMID: 17417973
10.  Effect of Consuming Zinc-fortified Bread on Serum Zinc and Iron Status of Zinc-deficient Women: A Double Blind, Randomized Clinical Trial 
After iron deficiency, zinc deficiency is the major micronutrient deficiency in developing countries, and staple food fortification is an effective strategy to prevent and improve it among at-risk-populations. No action has been taken to reduce zinc deficiency via flour fortification so far in Iran, and little is known about the influence of zinc fortification of flour on serum zinc and the iron status, and also about the optimum and effective amount of zinc compound that is used in food fortification. The objective of this study is to evaluate the influence of consuming zinc-fortified breads on the zinc and iron status in the blood serum. In this study, three types of bread were prepared from non-fortified and fortified flours, with 50 and 100 ppm elemental zinc in the form of sulfate. Eighty zinc-deficient women aged 19 to 49 years were randomly assigned to three groups; The volunteers received, daily, (1) a non-fortified bread, (2) a high-zinc bread, and (3) a low-zinc bread for one month. Serum zinc and iron were measured by Atomic Absorption before and after the study. Results showed a significant increase in serum zinc and iron levels in all groups (p < 0.001) except in the control (p > 0.05). Absorption of zinc and iron in the group that consumed high-zinc bread was significantly greater than that in the group that received low-zinc bread (p < 0.01). It was concluded that fortification of flour with 50–100 ppm zinc was an effective way to achieve adequate zinc intake and absorption in zinc-deficient people. It also appeared that consuming zinc-fortified bread improved iron absorption.
PMCID: PMC3399305  PMID: 22826754
Bread fortification; Serum iron; Serum zinc; Zinc deficiency; Zinc sulfate
11.  Maternal Body Mass Index, Dietary Intake and Socioeconomic Status: Differential Effects on Breast Milk Zinc, Copper and Iron Content 
Health Promotion Perspectives  2011;1(2):140-146.
Background: As breast milk micronutrients content are essential for health and growth of the infants, this study was conducted to determine the breast milk zinc, copper and iron concen­trations and their possible correlations with maternal nutritional status, dietary intakes as well as socioeconomic status.
Methods: Breast milk samples and information on maternal anthropometric characteristics and dietary intake were collected from 90 Iranian lactating women with 3 different socioeco­nomic status who exclusively breastfed their infants. Concentrations of trace elements were analyzed using atomic absorption spectrophotometry. Nutritionist III program, Multiple Re­gression and ANOVA test were used for data analyses.
Results: The mean milk zinc, copper, and iron concentrations were 1.93 ± 0.71, 0.58 ± 0.32, and 0.81 ± 0.2 mg/l, respectively. In all three SES groups only zinc mean level was lower than the recommended range. A significant difference was observed in breast milk zinc, copper and iron concentration between high and low SES groups (Zn (P<0.001), Cu (P<0.001) and Fe (P<0.044)) and also moderate and low SES groups (Zn (P<0.03), Cu (P<0.001) and Fe (P<0.049)). After adjusting for maternal body mass index (BMI), socioeconomic status, mean dietary energy, zinc, copper, and iron intakes, there was a negative and significant association between maternal age and breast milk zinc (β=-0.28, P<0.034), copper (β=-0.18, P<0.048), and iron (β=-0.22, P<0.04) concentrations.
Conclusion: In low socioeconomic group with lower mean age, breast milk mineral levels were higher than others and there was no significant correlation between mineral levels and dietary intake. Hence it is supposed that maternal age may be better predictor of breast milk mineral levels.
doi:10.5681/hpp.2011.015
PMCID: PMC3963624  PMID: 24688910
Breast Milk; Zinc; Copper; Iron; Infants’ growth; Socioeconomic groups
12.  Serum level of vitamin D and trace elements in children with recurrent wheezing: a cross-sectional study 
BMC Pediatrics  2014;14(1):270.
Background
We aimed to show the relationship between recurrence of wheezing and serum levels of vitamin D, zinc, and copper in wheezy children compared with a healthy group.
Methods
In this cross sectional study, seventy-three children with wheezing and seventy-five controls were included without a follow-up period. The clinical characteristics of the children were assessed, the asthma predictive index and temporal pattern of wheeze were determined. The serum levels of vitamin D, zinc, and copper were measured. Pearson correlation analysis was used to evaluate the relationship between homogeneously distributed variables.
Results
Thirty-two of the seventy-three children (43.8%) had more than three wheezing attacks (recurrent wheezing). The Asthma Predictive Index index was positive in 26 patients (35.6%). When classified to temporal pattern of wheeze, fifty-three of the study group (72.6%) had episodic wheezing and the remainder (27.4%) was classified as multiple-trigger wheezing. We found no overall significant difference between the study and control group in terms of vitamin D and trace elements . The vitamin D and zinc levels were significantly lower and serum copper and copper/zinc ratio was significantly higher in patients with recurrent wheezing (p =0.03, p <0.01, p =0.013, p <0.01, respectively) positive Asthma Predictive Index and multiple-trigger temporal pattern of wheeze compared with patients with non- recurrent wheezing, negative Asthma Predictive Index and episodic temporal pattern of wheeze.
Conclusion
It may be postulated that for the determination of asthma risk in patients with recurrent wheezing, the serum level of vitamin D, copper and zinc can be used as a routine biomarker alongside the Asthma Predictive Index and temporal pattern of wheeze.
doi:10.1186/1471-2431-14-270
PMCID: PMC4286924  PMID: 25318349
13.  Wilson's disease: assessment of D-penicillamine treatment. 
Archives of Disease in Childhood  1985;60(7):652-655.
Serum copper and zinc concentrations and 24 hour urinary copper and zinc excretion were determined serially from the beginning of treatment with D-penicillamine in four children with Wilson's disease. The data show a progressive decrease in both serum copper and zinc concentrations in all. Urinary copper excretion gradually levelled off to approximately 50% of initial values, but zinc excretion increased. Urinary zinc:copper ratios therefore increased with the duration of treatment. Copper elimination was considered adequate as soon as challenge with a test dose of D-penicillamine did not result in an increase in copper excretion. Urinary zinc excretion was increased further by the test dose. Zinc depletion was suspected clinically in one patient on D-penicillamine maintenance treatment. Lowering the dose alleviated the symptoms, urinary zinc loss decreased from 64 to 34 mumol/24 hours, and copper excretion remained largely unchanged. Data obtained indicate that D-penicillamine alters the metabolism of both copper and zinc. The extent of this is not only dose dependent but is also related to the efficacy of copper elimination. Both copper and zinc concentrations must by monitored to assess the benefits of treatment and the risks of inducing manifest or subclinical zinc deficiency.
PMCID: PMC1777273  PMID: 4026361
14.  Serum Copper, Zinc and Copper/Zinc Ratio and their Relationship to Age and Growth Status in Yemeni Adolescent Girls 
Objectives:
As no previous study has evaluated copper and zinc status in adolescent Yemeni girls, the purpose of this study was to measure their serum levels of zinc and copper and to examine the relationship between the serum levels of these two trace minerals with age, and anthropometric parameters.
Methods:
The study was conducted in April 2007 in Alwehda district in the municipality of Sana’a, Yemen. One hundred and fourteen adolescent girls were selected using systematic stratified sampling from a representative school which was randomly selected. Anthropometric indices were measured and blood samples were collected for biochemical analysis.
Results:
The mean ±SD for copper, zinc, and copper/zinc ratio for the entire cohort were 17.47±3.31 μmol/L, 12.24±1.04 μmol/L, and 1.44±0.31, respectively. The prevalence of hypocuprimea was 4.4% and hypercuprimea was 2.6%. The levels of zinc were marginal in 96.5% of the girls and the prevalence of hypozincimea was 3.5%. The levels of copper were significantly higher (p = 0.007) and the levels of zinc were significantly lower (p = 0.003) in the 10–12 yrs girls than in other age groups. Height showed significant negative correlation with the levels of copper (p = 0.01) and significant positive correlation with the levels of zinc (p = 0.008).
Conclusion:
The results revealed that the Yemeni girls had marginal serum zinc levels, and 10–12 yrs girls had significantly lower zinc levels than other age groups. This provides a warning of consequent negative health effects since the physiological requirements for zinc are high in adolescence.
PMCID: PMC3074839  PMID: 21748074
Copper; Zinc; Copper/zinc ratio; Growth; Adolescent girls; Yemen
15.  The Relationship Between Serum Lipid Profile and Selected Trace Elements for Adult Men in Mosul City 
Oman Medical Journal  2012;27(4):300-303.
Objectives
To evaluate the correlations of the serum concentrations of copper, zinc, and manganese with lipid profile parameters of adult men in Mosul City, Iraq.
Methods
The study included 51 apparently healthy adult men as a control group aged 34-62 years (group 1), and 31 hyperlipidemic patients aged 37-60 years (group 2). Trace elements copper, zinc and manganese were determined using atomic absorption spectrometry. Concentrations of total cholesterol, triglyceride and high density lipoprotein cholesterol were determined using enzymatic method. Indirect serum concentration of low-density lipoprotein cholesterol were calculated via the Friedewald formula. Data were evaluated as mean and standard deviation by analysis of variance (ANOVA) and t-test.
Results
The results indicated that there is a significant lower level of serum zinc in hyperlipidemic patients compared with the control group, while copper and manganese showed no significant differences between the two groups. A significant negative correlation was found between serum zinc and total cholesterol, low-density lipoprotein cholesterol, triglyceride and low/high-density lipoprotein cholesterol ratio; while a significant positive correlation was found between serum zinc and high density lipoprotein cholesterol. In addition, a significant positive correlation between copper and triglyceride existed in the patient group, while the control group showed no such correlation.
Conclusion
Hyperlipidemia may possibly be related to a decrease in the level of serum zinc in hyperlipidemic adult men. The data also supports the concept that zinc supplementation might be useful in improving metabolic complications in subjects with hyperlipidemia.
doi:10.5001/omj.2012.74
PMCID: PMC3464753  PMID: 23071882
Lipid profile; Trace elements; Hyperlipidemic patient
16.  The Effect of Helicobacter pylori Eradication on the Levels of Essential Trace Elements 
BioMed Research International  2014;2014:513725.
Objective. This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. Patients and Methods. We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. Results. Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P = 0.06). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P < 0.05). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. Conclusion. H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327).
doi:10.1155/2014/513725
PMCID: PMC4274842  PMID: 25548772
17.  Maternal and Neonatal Serum Zinc Level and Its Relationship with Neural Tube Defects 
Neural tube defect (NTD) is a multi-factorial disorder in which nutritional, genetic and environmental factors are involved. Among the nutritional factors, low level of serum zinc has been reported from different parts of the world. This hospital-based case-control study was conducted with the objective of finding the relationship between serum zinc level in newborns and their mothers and NTDs in a Bangladeshi population. The study was conducted during August 2006–July 2007 at the Bangabandhu Sheikh Mujib Medical University (BSMMU) in Dhaka. In total, 32 mothers and their newborns with NTDs were included as cases and another 32 mothers with their normal babies were included as controls. Concentration of serum zinc was determined by pyro-coated graphite furnace atomic absorption spectrophotometer (GF-AAS). The mean age of the case and control mothers was 25.28 years and 24.34 years respectively. The mean gestational age of the case newborns was 36.59 weeks and that of the control newborns was 37.75 weeks. The mean serum zinc level of the case and control mothers was 610.2 μg/L and 883.0 μg/L respectively (p<0.01). The mean serum zinc level of the case and control newborns was 723 μg/L and 1,046 μg/L respectively (p<0.01). In both case and control groups, the serum zinc level of the newborns positively correlated with that of the mothers. The serum zinc levels of the mothers and newborns negatively correlated with NTDs. Mothers with serum zinc level lower than normal were 7.66 [95% confidence interval (CI) 2.5-23.28] times more likely to have NTDs compared to the normal zinc level of mothers. After adjusting for the zinc level of the newborns, parity, and age of the mothers, this risk reduced 1.61 times [confidence interval (CI) 95% 0.24-8.77]. On the other hand, the low serum zinc level of the newborns was 7.22 times more associated with NTDs compared to the newborns with the normal serum zinc level, which was statistically significant (p=0.001). After adjusting for other factors, such as maternal age and parity, newborns with the low serum zinc level was found to be 9.186 times more likely to be associated with NTDs compared to newborns with normal serum zinc level. Based on the findings, it may be concluded that the low serum zinc levels of newborns may be associated with NTDs. To confirm these findings, a further study with a larger sample-size is recommended. Moreover, a follow-up study with zinc supplementation to pregnant women and its impact on NTDs is also recommended.
PMCID: PMC2965325  PMID: 20824977
Atomic absorption spectrophotometer; Case-control studies; Neural tube defects; Serum zinc; Zinc deficiency; Bangladesh
18.  Zinc, ferritin, magnesium and copper in a group of Egyptian children with attention deficit hyperactivity disorder 
Background
Attention deficit hyperactivity disorder is a behavioral syndrome of childhood characterized by inattention, hyperactivity and impulsivity. There were many etiological theories showed dysfunction of some brain areas that are implicated in inhibition of responses and functions of the brain. Minerals like zinc, ferritin, magnesium and copper may play a role in the pathogenesis and therefore the treatment of this disorder.
Objective
This study aimed to measure levels of zinc, ferritin, magnesium and copper in children with attention deficit hyperactivity disorder and comparing them to normal.
Methods
This study included 58 children aged 5-15 years with attention deficit hyperactivity disorder attending Minia University Hospital from June 2008 to January 2010. They were classified into three sub-groups: sub-group I included 32 children with in-attentive type, sub-group II included 10 children with hyperactive type and sub-group III included 16 children with combined type according to the DSM-IV criteria of American Psychiatric Association, 2000. The control group included 25 apparently normal healthy children.
Results
Zinc, ferritin and magnesium levels were significantly lower in children with attention deficit hyperactivity disorder than controls (p value 0.04, 0.03 and 0.02 respectively), while copper levels were not significantly different (p value 0.9). Children with inattentive type had significant lower levels of zinc and ferritin than controls (p value 0.001 and 0.01 respectively) with no significant difference between them as regards magnesium and copper levels (p value 0.4 and 0.6 respectively). Children with hyperactive type had significant lower levels of zinc, ferritin and magnesium than controls (p value 0.01, 0.02 and 0.02 respectively) with no significant difference between them as regards copper levels (p value 0.9). Children with combined type had significant lower levels of zinc and magnesium than controls (p value 0.001 and 0.004 respectively) with no significant difference between them as regards ferritin and copper levels (p value 0.7 and 0.6 respectively).
Conclusions
Children with attention deficit hyperactivity disorder had lower levels of zinc, ferritin and magnesium than healthy children but had normal copper levels.
doi:10.1186/1824-7288-37-60
PMCID: PMC3268715  PMID: 22206662
Attention deficit; hyperactivity; zinc; ferritin; magnesium; copper
19.  Analysis of Serum and Urinal Copper and Zinc in Chinese Northeast Population with the Prediabetes or Diabetes with and without Complications 
This study investigated the association of copper and zinc levels in the serum or urine of patients living in northeast China, with either prediabetes or diabetes. From January 2010 to October 2011, patients with type 1 diabetes (T1D, n = 25), type 2 diabetes (T2D, n = 137), impaired fasting glucose (IFG, n = 12) or impaired glucose tolerance (IGT, n = 15), and age/gender matched controls (n = 50) were enrolled. In the T2D group, there were 24 patients with nephropathy, 34 with retinopathy, and 50 with peripheral neuropathy. Serum copper levels were significantly higher in IFG, IGT, and T2D groups. Serum zinc level was dramatically lower, and urinary zinc level was significantly higher in both T1D and T2D subjects compared with controls. The serum zinc/copper ratio was significantly lower in all the patients with IFG, ITG, T1D, and T2D. The serum copper level was positively associated with HbA1c in T2D subjects. Simvastatin treatment in T2D patients had no significant effect on serum and urinary copper and zinc. These results suggest the need for further studies of the potential impact of the imbalanced serum copper and zinc levels on metabolic syndrome, diabetes, and diabetic complications.
doi:10.1155/2013/635214
PMCID: PMC3794628  PMID: 24175012
20.  Zinc and copper levels in low birth weight deliveries in Medani Hospital, Sudan 
BMC Research Notes  2014;7:386.
Background
Low birth weight (LBW) is a worldwide health problem, especially in developing countries. We conducted a case–control study at Medani Hospital, Sudan. Cases were women who delivered a LBW (<2500 g) newborn and consecutive women who delivered a normal weight (>2500 g) newborn were controls. Questionnaires were used to collect clinical data. Zinc and copper levels were measured by an atomic absorption spectrophotometer.
Findings
The two groups (50 in each arm) were well matched in their basic characteristics. Median (25–75th interquartile range) maternal zinc (62.9 [36.3–96.8] vs. 96.2 [84.6–125.7] μg/dl; P <0.001) and copper (81.6 [23.7–167.5] vs. 139.8 [31.9–186.2] μg/dl; P = 0.04) levels were significantly lower in cases than in controls. Cord copper levels in cases were significantly lower than those in controls (108 [55.1–157.9] vs. 147.5 [84.5–185.2] μg/dl; P = 0.02). There were significant direct correlations between birth weight and maternal copper levels and maternal and cord zinc levels.
Conclusions
Maternal zinc and copper levels, as well as cord copper levels, are lower in LBW newborns than in those with normal weight.
doi:10.1186/1756-0500-7-386
PMCID: PMC4081538  PMID: 24958541
Zinc; Copper; Low birth weight; Sudan
21.  Serum iron, copper and zinc status in maternal and cord blood 
Pregnancy is associated with increased demand of all the nutrients like Iron, Copper, Zinc etc. and deficiency of any of these could affect pregnancy, delivery and out come of pregnancy. With this consideration, the study was conducted on 80 mothers and newborns and 20 age matched control women. Out of 80 mothers, 34 had Iron deficiency anemia and their Hb levels were below 9.0 gm/d1. Pregnant women had significantly lower Iron and Zinc levels while Copper and Total Iron Binding Capacity (TIBC) were significantly higher (P<0.001). Newborns had significantly elevated Iron and Zinc levels and low levels of Copper and TIBC as compared to their mothers irrespective of Iron deficiency anemia. Micronutrient status of newborn was found to be dependent on their mother's micronutrient status. Besides, results also suggest micronutrient interactions, which are reflected in Iron/Zinc, Iron/Copper and Zinc/Copper ratios. In view of this, there is need for proper, adequate and balanced micronutrient supplementation during pregnancy to affect a healthy outcome.
doi:10.1007/BF02894257
PMCID: PMC3454214  PMID: 23105456
Iron; Copper; Zinc; Pregnancy; Newborn; Iron Deficiency Anemia
22.  Analysis of Copper and Zinc Plasma Concentration and the Efficacy of Zinc Therapy in Individuals with Asperger’s Syndrome, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Autism 
Biomarker Insights  2011;6:127-133.
Aim
To assess plasma zinc and copper concentration in individuals with Asperger’s Syndrome, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) and autistic disorder, and to analyze the efficacy of zinc therapy on the normalization of zinc and copper levels and symptom severity in these disorders.
Subjects and methods
Plasma from 79 autistic individuals, 52 individuals with PDD-NOS, 21 individuals with Asperger’s Syndrome (all meeting DSM-IV diagnostic criteria), and 18 age and gender similar neurotypical controls, were tested for plasma zinc and copper using inductively-coupled plasma-mass spectrometry.
Results
Autistic and PDD-NOS individuals had significantly elevated plasma levels of copper. None of the groups (autism, Asperger’s or PDD-NOS) had significantly lower plasma zinc concentrations. Post zinc and B-6 therapy, individuals with autism and PDD-NOS had significantly lower levels of copper, but individuals with Asperger’s did not have significantly lower copper. Individuals with autism, PDD-NOS and Asperger’s all had significantly higher zinc levels. Severity of symptoms decreased in autistic individuals following zinc and B-6 therapy with respect to awareness, receptive language, focus and attention, hyperactivity, tip toeing, eye contact, sound sensitivity, tactile sensitivity and seizures. None of the measured symptoms worsened after therapy. None of the symptoms in the Asperger’s patients improved after therapy.
Discussion
These results suggest an association between copper and zinc plasma levels and individuals with autism, PDD-NOS and Asperger’s Syndrome. The data also indicates that copper levels normalize (decrease to levels of controls) in individuals with autism and PDD-NOS, but not in individuals with Asperger’s. These same Asperger’s patients do not improve with respect to symptoms after therapy, whereas many symptoms improved in the autism group. This may indicate an association between copper levels and symptom severity.
doi:10.4137/BMI.S7286
PMCID: PMC3235993  PMID: 22174567
autism; PDD-NOS; Asperger’s disorder; zinc; copper
23.  Zinc and Copper Status in Children with Beta-Thalassemia Major  
Iranian Journal of Pediatrics  2010;20(3):297-302.
Objective
There are some reports in which a condition of zinc deficiency and its associated outcomes with a change in concentration of serum copper among the thalassemic patients has been highlighted. The aim of this prospective study was to determine the serum zinc and copper levels in children with beta-thalassemia major.
Methods
In this cross sectional study all children under 12 years affected by beta thalassemia major (40 patients) were evaluated for serum zinc and copper levels in Qazvin thalassemia center (Qazvin, Iran) in 2007. Serum measurements for zinc and copper were performed by atomic absorption spectrophotometer.
Findings
The mean concentrations of serum zinc and copper levels were 67.35±20.38 and 152.42±24.17 µg/dl respectively. Twenty-six (65%) of thalassemic patients had zinc concentration under 70 µg/dl (hypozincemia). None of the thalassemic children had copper deficiency. No significant correlation between serum zinc level with age, weight, height, body mass index, duration of blood transfusion, desferrioxamine dose and ferritin level was observed in thalassemic patients (P=0.3).
Conclusion
This study revealed that hypozincemia is common in thalassemic patients, but in contrast, there is no copper deficiency. Further evaluation in this regard is recommended.
PMCID: PMC3446035  PMID: 23056720
Beta-thalassemia; Zinc; Copper; Children
24.  Quantitative analysis of serum levels of trace elements in patients with oral submucous fibrosis and oral squamous cell carcinoma: A randomized cross-sectional study 
Background and Objectives:
Metabolic disorders, oral precancerous conditions and oral cancer are accompanied by alterations in the concentration of one or more trace elements like copper, iron, zinc, magnesium etc., in some body fluids, especially blood serum or plasma, which can help not only in the early diagnosis and treatment but also in prognosis. The objective of the study is to evaluate the levels of circulating trace elements (copper, iron, magnesium, zinc and calcium) in serum of patients with Oral Submucous Fibrosis (OSF) and Oral Squamous Cell Carcinoma (OSCC), to analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression and their association with areca nut and betel quid chewing habits.
Materials and Method:
Serum levels of trace elements (copper, iron, magnesium, zinc and calcium) were estimated using electronic absorption colorimetric method. These levels were compared with controls and statistically evaluated using ANOVA and POST-HOC TUKEY tests.
Results:
The data analysis revealed that serum copper levels increased gradually from precancer to cancer, as the duration of betel quid chewing habit increased. However, serum iron, magnesium, zinc levels were decreased significantly in both the groups. Serum calcium levels were increased in the cancer group owing to bone resorption in the later stages of the disease, whereas it was close to normal in OSF patients. Among all the trace elements, the best predictor for occurrence of both the lesions was copper.
Conclusion:
The present study shows that the above trace elements may be associated with the pathogenesis and progression of OSF and OSCC. Betel quid and areca nut chewing habits are frequently associated with both disease states and may play a role in altering the serum levels of these trace elements. Concerted efforts would, therefore, help in early detection, management and monitoring the efficacy of treatment.
doi:10.4103/0973-029X.131902
PMCID: PMC4065448  PMID: 24959037
Arecanut; betel quid chewing habit; oral squamous cell carcinoma; oral submucous fibrosis; serum trace elements
25.  Salivary copper and zinc levels in oral pre-malignant and malignant lesions 
Recent technological advances have made saliva as a tool for diagnosis of many things; among them are hormone imbalances, liver function, immunodeficiency and even cancer.
Aim:
The present study was done to evaluate the levels of copper and zinc and copper/zinc ratio in saliva of premalignant and malignant lesions of oral cavity, because of the anatomical proximity of the saliva to both premalignant and malignant oral neoplasms.
Materials and Methods:
The levels of copper and zinc were estimated in the saliva of 5 patients with oral submucous fibrosis, 5 patients with oral leukoplakia, 5 patients with oral lichen planus and 10 patients with oral squamous cell carcinoma of oral cavity using inductively coupled mass spectrometry (ICP- MS). The values were compared with 6 normal age and sex matched control subjects.
Results:
There was significant difference of the mean salivary copper and zinc levels of premalignant and malignant lesions when compared to the normal controls. In oral cancer patients there was significant difference in the copper levels according the histodifferentiaton in squamous cell carcinoma. Within the premalignant group the copper levels were more in the oral sub mucous fibrosis when compared to the leukoplakia and lichen planus. Copper zinc ratio decreased in premalignant and malignant group when compared to the normal group.
Conclusions:
Saliva may be used as a potential diagnostic tool, which can be efficiently employed to evaluate the copper and zinc levels in pre malignant and malignant lesions of oral cavity. Key words: Copper, inductively couples mass spectrometry, leukoplakia, lichen planus, oral squamous cell carcinoma, oral submucous fibrosis, saliva, zinc
doi:10.4103/0973-029X.98452
PMCID: PMC3424931  PMID: 22923887
Copper; inductively coupled mass spectrometry; leukoplakia; lichen planus; oral squamous cell carcinoma; oral submucous fibrosis; saliva; zinc

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