Mean Serum Copper Concentrations Research Articles

COMPARATIVE COPPER PHARMACOKINETIC PROPERTIES OF A NOVEL LOW-DOSE NITINOL FRAME COPPER INTRAUTERINE DEVICE (IUD) AND THE COPPER T380A IUD: A RANDOMIZED CONTROLLED TRIAL

We compared the pharmacokinetics and bioavailability of serum copper in women receiving either a novel low-dose nitinol frame copper IUD or the copper T380A IUD through the first 57 days of use. Two sites participated in this parallel -single-blind study that randomized reproductive age women 1:1 to an investigational low-dose copper IUD (with 175 mm2 of exposed copper) or the approved copper T380A (Paragard, 380 mm2) IUD. Participants provided two baseline total serum copper samples at least 24 hours apart within 28 days prior to IUD placement followed by seven samples following randomization on days 1, 3, 8, 15, 22, 29, and 57. We used a noncompartmental mixed-effects linear analysis of variance (ANOVA) model with treatment as a fixed effect and subject as a random effect to calculate uncorrected PK parameters Cmax, Cmean, and AUC0-56 days. We compared relative bioavailability between the two groups by geometric mean ratios and 90% confidence intervals. We hypothesized that the relative bioavailability of total serum copper for the low-dose device would not exceed established normal (490 to 1840 ng/ml) or levels seen in users of the copper T380A. Of the 41 participants enrolled, 39 had successful IUD placements (20 in the low-dose group and 19 in the T380A group) with 36 of those subjects completing the treatment comparison phase of the study (19 low-dose and 17 T380A). Participants reported a mean age of 28.4 years. The baseline mean serum copper concentrations for the low-dose group were 1220 ng/ml standard deviation (SD) ± 285 ng/ml vs. 1250 ng/ml ± 276 ng/ml for the T380A group. Observed copper concentrations in both groups remained in the normal range; with the relative mean Cmax, Cmean, and AUC 0-56 days of 1210 ng/ml, 1070 ng/ml, and 59,700 for the low-dose IUD group vs. 1300, 1150, and 63,600 for the T380A group. Post IUD placement values for both the low-dose group and the copper T380A group were slightly lower than baseline values over the seven timepoints from 0-56 days. Respective baseline-corrected mean values for the low-dose group were 7.8 to 29.8 ng/ml and for the T380A group were 14.9 to 34.3 ng/ml lower than baseline. Relative bioavailability by geometric mean copper exposure for all parameters ranged from 0.93-0.94 (90% CI for all values 0.85-1.02) with all mean values for the low-dose IUD lower than the T380A. Serum copper concentrations for the two IUDs remained within the normal range and trended toward lower values for participants assigned to the low-dose copper IUD relative to the T380A. Neither IUD generated clinically meaningful changes in total serum copper concentrations during the first 56 days after IUD placement.

Laryngeal Neuropathy in Adult Goats With Copper Deficiency.

The aim of this study was to elucidate the cause of a neurological syndrome characterized by stridor in adult goats with clinical signs of copper deficiency. The main clinical signs consisted of apathy, emaciation, pale mucous membranes, mucous nasal discharge, dyspnea, severe achromotrichia, diffuse alopecia, torpor, ataxia, and stridor. When the goats were forced to move, the stridor increased. In a herd of 194 Toggenburg goats, 10 adult goats with clinical signs of copper deficiency were removed from the herd and divided into 2 groups: group 1, which consisted of 4 nannies and 1 buck with stridor, and group 2, which consisted of 4 nannies and 1 buck without stridor. Group 3, used as a control, consisted of 5 adult goats from another flock without any clinical signs of disease. The mean serum copper concentrations were 1.3 ± 0.3 μmol/L in group 1, 8.1 ± 1.1 μmol/L in group 2, and 11.3 ± 2.2 μmol/L in group 3. The mean serum iron concentrations were 42.3 ± 14.2 μmol/L in group 1, 39.1 ± 8.2 μmol/L in group 2, and 20.6 ± 6.1 μmol/L in group 3. The main histological lesions in goats from group 1 were axonal degeneration of the recurrent laryngeal nerves and atrophy of the muscles of vocal folds and of the dorsal cricoarytenoid and right and left cricothyroid muscles. Goats with ataxia had neuronal degeneration and necrosis of cerebellar Purkinje cells and of the cranial cervical ganglion. We concluded that the stridor was caused by axonal degeneration of the recurrent laryngeal nerves due to the severe copper deficiency.

Analysis of serum copper and iron levels in oral submucous fibrosis patients: A case–control study

Background: Oral submucous fibrosis (OSF) is a chronic debilitating disease and a potentially malignant disorder of the oral cavity. The pathogenesis of the disease is not well established. Trace elements such as copper and iron play an important role in the pathogenesis of OSF. Estimation of these elements in serum of the patients may be helpful in understanding the pathologic mechanism. Therefore, a study was carried out to analyze the level of serum copper and iron in the population of Central India. Materials and Methods: A case–control study was carried out on 35 patients with clinically diagnosed of OSF and 35 healthy controls. OSF patients were categorized by clinical staging. Serum copper and iron concentrations were measured by atomic absorption spectrophotometry. Results: Results of the study shows that the mean serum copper concentration was greater in study group (133.3 ± 19.2) compared to control group (113.9 ± 22.1) and the mean serum iron was lower in study group (116.0 ± 24.1) compared to control group (128.2 ± 23.4). The result obtained was statistically significant. The serum copper level increases as the clinical staging of OSF progresses, whereas serum iron level decreases as clinical staging progresses. Conclusion: There was an increase in copper level and decrease in iron level in study group compared to control group; this suggests that there is an increase in copper level with the advancement of clinical staging of OSF.

Maternal Serum Copper Concentration in Premature Rupture of Membrane: A Case-Control Study

Copper is an integrated parts of metal-protein required far varieties of oxide-reductive metabolic pathways in human. Copper deficiency is considered as risk factors in some pregnancies. Premature rupture of membrane is a pregnancy complication with major adverse effects and is believed maternal Copper deficiency can also be considered as interventional factors. This study was done to evaluate if there is a correlation between maternal serum Copper concentration and premature rupture of membrane in pregnancy. In this case-control study 60 pregnant women with Premature Rupture of Membrane (PROM) were selected as case group including term and pre term the control group consist of 60 pregnant women with normal delivery of term and pre term states. Both group were matched for maternal and pregnancy age. In case and control group the pregnancy at term and pre-term were grouped independently as well. In general the maternal mean serum Copper concentration were 192.4±78.2 and 201.08±82.06 in case and control groups, respectively but this differences statistically was not significant. Data in this study revealed that the absolute value of maternal serum Copper concentration of term or pre term in case groups was slightly lower than related controls. Drop in maternal Copper concentration in some disturbed pregnancies such as premature rupture of membrane is previously demonstrated and based on our data the absolute Copper serum concentration of women with premature rupture of membrane was also slightly lower compared to healthy pregnancy but it was not statistically significant. © Asian Network for Scientific Information.

Assessing chaperone for Zn, Cu-superoxide dismutase as an indicator of copper deficiency in malnourished children

It is not clear how frequent is copper deficiency in humans. Current copper markers are not sensitive enough to detect early copper deficiency and new markers are needed. CCS is a candidate to become a copper biomarker. ObjectiveMeasuring CCS mRNA relative expression in malnourished children and compare results (a) with those of the same children after nutritional recovery and (b) with well-nourished children. MethodOn admission to the protocol and after 15 day nutritional treatment, severely (G1=18) and moderately (G2=10) malnourished children were compared with well-nourished healthy controls (G3=15), measuring anthropometric indicators, blood biochemistry, Cu, Fe and Zn serum concentrations, ceruloplasmin, C Reactive protein and mRNA abundance of CCS, SOD and MT2 in peripheral mononuclear cells. ResultIn malnourished groups, mean serum copper concentration was below the cut-off on admission to hospital and increased after 15 days (t-test, p<0.01). On admission to protocol, CCS mRNA abundance in G1 and G2 was higher than in G3 (one way ANOVA, p<0.001). After 15 days, CCS expression decreased as expected (t-test, p<0.001). Initial SOD mRNA relative abundance was higher in study groups than controls and also between G1 and G2 (One way ANOVA, both p<0.01); after 15 days, G1 and G2 were not different (t-test, NS). MT2A abundance of transcripts did not follow a clear change pattern. ConclusionCCS mRNA abundance responded as expected, being higher in malnourished children than in controls; nutritional recovery in these latter resulted in decreasing expression of the chaperone, supporting the hypothesis that CCS may be a copper biomarker.

Serum trace mineral variations in Nili-Ravi buffaloes suffering with prepartum vaginal prolapse in two different agro-ecological zones of Punjab, Pakistan

The present study was conducted during 2005 and 2006 on 200 Nili-Ravi buffaloes kept in two agroecological zones (irrigated [zone 1] and rain-fed [zone-2]) of Punjab, Pakistan, with the objective to determine the level of trace minerals (Cu, Fe, Zn, Se) in serum of the buffaloes suffering from vaginal prolapse and to compare them with their healthy counterparts. In each zone 50 buffaloes suffering from prepartum vaginal prolapse during their seventh month of gestation were identified through survey. Vaginal prolapse-affected buffaloes belonging to zone 1 were identified as group VPB1 (N = 50), whereas buffaloes belonging to zone 2 were recognized as VPB2 (N = 50). The buffaloes of control group in zone 1 and zone 2 were identified as NCB1 and NCB2, respectively. The blood samples in all four groups of buffaloes were collected three times, i.e., first when these animals were in the eighth month of gestation, second during the eighth to ninth month of gestation, and finally when these animals were in the ninth or later month of gestation. The mean serum copper concentrations in buffaloes of group VPB1 were significantly lower (P < 0.05) in comparison with NCB1 and NCB2, whereas there were nonsignificant differences (P > 0.05) in copper concentrations between VPB1 and VPB2. There was a significant difference (P < 0.05) of iron concentration in VPB1 compared with NCB1 and NCB2. Similarly, VPB2 also had significantly lower (P < 0.05) iron concentrations compared with NCB1 and NCB2. Serum zinc concentrations were significantly lower (P < 0.05) in animals of the VPB1 group when compared with NCB1 and NCB2. Similarly, lower zinc concentrations were observed in VPB2 in comparison with NCB1 and NCB2. There was significantly lower (P < 0.05) zinc concentration in affected buffaloes (VPB1 and VPB2) from the ninth month of gestation to term when compared with those in the eighth to ninth mo of gestation, and with those not yet in the eighth month of gestation. Serum selenium concentration were significantly higher (P < 0.05) in control group buffaloes (NCB1 and NCB2) in comparison with vaginal prolapse-affected buffaloes (VPB1 and VPB2). During different stages of gestation, mean serum selenium concentrations varied nonsignificantly (P > 0.05) within each group of buffalo. Based on information obtained from this study, it was concluded that the low serum concentration of copper and selenium are linked to increased incidence of vaginal prolapse in buffaloes during the last trimester of gestation.

Copper Concentration in a Healthy Urban Adult Population of Southern Iran

Nutritional deficiencies are important and widespread problems in most developing countries. Preventing and correcting micronutrient deficiencies are important because of the multiple negative consequences of these deficiencies. This study was designed to determine the prevalence of copper deficiency in an adult population in Shiraz, southern Iran. We also determined the association between copper status and other factors such as age, sex, and body mass index (BMI). In this cross-sectional study, 416 adults residing in Shiraz were selected by two-stage sampling. Serum copper was measured by flame-atomic absorption spectrometry. The data were analyzed with SPSS software. Mean age in our sample was 39.33 ± 15.06 years, and mean BMI was 26.17 ± 4.81 kg/m(2). Mean serum copper concentration was 118.15 ± 54.33 μg/dL in the whole sample, 109.74 ± 56.22 μg/dL in men, and 122.15 ± 53.04 μg/dL in women. The overall prevalence of copper deficiency was 24%. The prevalence of copper deficiency differed significantly between men and women but not between different age groups. Serum copper concentration correlated significantly with BMI (p < 0.05). This study is the first to evaluate serum copper status in a healthy population in southern Iran. We show that the mean copper concentrations were higher than those reported for Iranian populations in northern cities and were also higher compared with studies in most other countries. We suggested more detailed studies to identify the etiological determinants of this nutritional deficiency in Iran and elsewhere.

Serum Copper Concentration in Adults with Acute, Uncomplicated Falciparum Malaria Infection

Serum copper concentration was measured in 80 adult patients (40 males and females each; age range: 18-40 yr) presenting with acute, uncomplicated falciparum malaria infection and a control group of 20 age-matched, healthy individuals. The mean serum copper concentration was 109.0 +/- 40.0 microg/dL in healthy individuals. Both male and female patients were found to have a significantly decreased serum copper concentration (p < 0.05). In the male patients, the mean serum copper concentration decreased by 33.95%, whereas it dropped by 38.53% in their female counterparts. A compromised enzymatic antioxidant defense capability, particularly superoxide dismutase (SOD) activity, has been reported in patients with falciparum malaria infection. Because SOD activity is dependent on copper, the ineffective SOD activity can be related to the decrease in the concentration of copper during the infection. Low serum copper can also contribute to the ineffective immune response of the host to the antigenic challenge of the falciparum parasite because copper is also important for normal immune function.

Serum Copper Levels among a Tribal Population in Jharkhand State, India: A Pilot Survey

Copper is an essential trace element that plays a pivotal role in cell physiology. Dietary intake of copper by a population of low-income groups in India has been found to be low, and hence the possibility of dietary copper deficiency exists. To determine serum copper levels among tribal populations in India, an area in which data are limited. The study was conducted among tribal populations 18 to 75 years of age residing in Sahibganj, Jharkhand. Two blocks in the district were selected (from a total of eight) for the detailed study. A semistructured pretested questionnaire was used to collect demographic and socioeconomic information about subjects. A total of 995 subjects were enrolled for the present study. Blood was drawn from the antecubital vein and collected in previously labeled polypropylene tubes. Serum copper was determined by the atomic absorption spectrophotometry method and serum samples with copper levels less than 80 microg/dL were considered to have low serum copper levels. The mean serum copper concentration of the study subjects was 91.18 +/- 35.48 microg/dL. Thirty-four percent of the study subjects had low serum copper levels (< 80 microg/dL). Nearly 35% of males and 34.4% of females had low serum copper levels. This study documented a high prevalence of low serum copper levels among the studied tribal population. Further multicenter studies with larger sample sizes are needed to assess the biological implications of copper deficiency among the tribal populations in India.

Non-Anemic Iron Depletion, Oral Iron Supplementation and Indices of Copper Status in College-Aged Females

Objectives: Indices of copper status, specifically serum copper and ceruloplasmin concentrations and erythrocyte superoxide dismutase activity, and iron status, including serum ferritin, transferrin receptors, hemoglobin and hematocrit, were studied in 27 college-aged females with adequate iron versus low iron stores.Methods: Serum copper and ceruloplasmin concentrations, erythrocyte superoxide dismutase activity, serum ferritin, transferrin receptors, hemoglobin and hematocrit were studied in 15 females with non-anemic iron depletion before and after five weeks of iron supplementation and in 12 healthy iron-adequate females aged 19 to 28 years.Results: Mean hemoglobin, hematocrit and ferritin concentrations of the control group (144 ± 11 g/L, 43 ± 3% and 38 ± 15 μg/L, respectively) were significantly higher than those of the iron depleted group prior to supplementation (134 ± 9 g/L, 39 ± 2% and 11 ± 6 μg/L, respectively). The serum transferrin receptor to serum ferritin ratio was significantly greater for the iron depleted group prior to supplementation (890 ± 753) versus the control group (151 ± 61). Mean serum copper and ceruloplasmin concentrations and erythrocyte superoxide dismutase activity of the iron-adequate control group (20.0 ± 5.7 μmol/L, 463 ± 142 mg/L and 527 ± 124 U/mL, respectively) were significantly higher than those of the iron depleted group (12.4 ± 3.8 μmol/L, 350 ± 108 mg/L and 353 ± 186 U/mL, respectively) prior to supplementation. Following iron supplementation, hematocrit and ferritin concentrations of the iron depleted group significantly increased to 42 ± 3% and 26 ± 8 μg/L, respectively. Mean serum transferrin receptor concentrations and the serum transferrin receptor to ferritin ratios significantly decreased in the iron depleted group following supplementation (6.1 ± 1.6 mg/L to 4.6 ± 1.5 mg/L and 890 ± 753 to 198 ± 114, respectively). Iron supplementation also significantly increased the mean serum copper concentration to 14.2 ± 5.4 μmol/L and, in subjects with serum ferritin concentrations ≤12 μg/L, the mean serum ceruloplasmin concentration.Conclusions: Non-anemic iron depletion characterized by low iron stores is associated with negative impacts on copper status. Iron supplements improved indices of iron status and serum copper and ceruloplasmin concentrations. Whether the diminished serum copper and ceruloplasmin concentrations and superoxide dismutase activity are associated with free radical damage to iron depleted cells requires further investigation.

Serum zinc and copper concentrations in Nigerian women with normal pregnancy

The impact of normal pregnancy on serum zinc and copper concentrations and on copper/zinc ratio has been determined in a cross-sectional study of eighty-four healthy pregnant Nigerian women. Fifty-seven healthy non-pregnant women served as controls. Serum zinc and copper levels were determined by atomic absorption spectroscopy. Mean serum copper concentration is significantly higher (P < 0.001) in the pregnant group than in controls [19.74(4.65) and 11.87(2.61) micromol/L respectively], while mean zinc level is significantly lower (P< 0.001) than in controls [4.40(1.34) and 5.54(1.04) micromol/L respectively. Copper/Zinc ratio is also significantly higher than (P<0.001) in the test subject [4.87(1.77) and 2.23(0.75) micromol/L respectively]. One-way analysis of variance shows that the mean serum zinc and copper concentrations and copper/zinc ratio differ significantly (P < 0.01, P < 0.05, and P < 0.05 respectively) between any two of the trimester groups. Furthermore, there is a significant positive correlation between gestational age and copper/zinc ratio (r- 0.201; P < 0.05), and a significant negative correlation between gestational age and serum zinc concentration (r = -0.274; P < 0.01). In normal pregnancy, a negative and positive linear relationship exists between gestational age and serum zinc level and copper/zinc ratio respectively. Serum copper does not show any significant trend throughout gestation, though pregnant subjects have higher mean serum copper level than controls.

Serum magnesium, copper, and zinc concentrations in acute myocardial infarction.

This study was carried out to assess the serum levels of magnesium, copper, and zinc after an acute episode of myocardial infarction. Determination of the metal concentrations were carried out on 41 patients with myocardial infarction and 41 healthy controls matched for age and sex. A slight decrease in the mean level of magnesium (P less than .05) was observed in patients (2.0 mg/dl) compared with the controls (2.1 mg/dl). The mean serum copper concentration was significantly higher (P less than .001) in patients (138 micrograms/dl) than in controls (98 micrograms/dl), while the mean serum zinc concentration was significantly lower (P less than .001) in patients (75 micrograms/dl) than in controls (100 micrograms/dl). The differences in serum copper and zinc levels between patients and controls were magnified considerably when the copper/zinc ratios were calculated for both groups (P less than .001). The mean copper/zinc value obtained for patients (1.91) was almost double that for the controls (1.02).

Serum copper and ceruloplasmin levels and urinary copper excretion in thermal injury

Conflicting reports regarding copper status in thermal injury patients have been published. We determined serial serum-copper and serum-ceruloplasmin levels and 24-h urinary excretion of copper in 23 patients with second- and third-degree thermal burns. Throughout hospitalization, mean serum-copper concentration was significantly depressed; lowest levels were found in patients with > 40% total body surface area burns. Serum ceruloplasmin was also depressed, an unexpected finding because this protein is a positive acute-phase reactant poststress. Mean urinary excretion of copper was elevated, reaching 2.5 times the upper limit of normal 2 wk postburn. Depressed serum-copper levels paralleled the serum-ceruloplasmin levels rather than the increased urinary-copper losses. Further studies are required to determine the mechanism(s) of this altered copper metabolism and whether physiological or biochemical evidence of copper deficiency accompanies the observed hypocupremia.

Atherosclerosis precursors in Finnish children and adolescents. XIII. Serum and hair copper and zinc concentrations.

The copper and zinc status of 3-18-year-old Finnish children was estimated by analysing 3,480 serum copper and zinc concentrations, 853 hair copper and 868 hair zinc concentrations. Both copper and zinc have been proposed to be connected with the pathogenesis of cardiovascular diseases. In addition, zinc is essential for normal growth and development. The mean serum copper concentration of 3-year-old children was 21.2 mumol/l and the concentration was significantly lower in older age groups. The average serum zinc concentration showed a narrow variation between 14.1 and 15.0 mumol/l in all age groups, nevertheless girls had significantly lower and boys higher values with increasing age. The distribution of hair copper concentration was skewed within the age groups; the median varied between 9.7 micrograms/g and 29.8 micrograms/g for 3-year-old urban girls and 18-year-old rural girls, respectively. Some rural girls had exceptionally high hair copper levels. Hair zinc concentrations increased with age. In the three youngest age groups (3, 6 and 9 years) the distribution was skewed and the levels low compared with results from the USA where a zinc concentration below 30 micrograms/g is found to be associated with the zinc deficiency syndrome.

Serum iron, copper, zinc, ferritin, and ceruloplasmin after intense heat exposure.

Twelve voluntary adult subjects twice took a 30-min sauna bath, at a temperature of 80 degrees C with a 30-min rest between each, every 12 h for 1 week. Measurements of serum iron, copper, zinc, ferritin and ceruloplasmin were performed before the experiment, after the first and second 30 min in the sauna and at the end of the week. The first two sauna baths did not significantly change the concentrations of the trace elements measured. After the week the mean serum copper concentration had decreased from 15.0 (SD 1.7) mumol x 1-1 to 13.5 (SD 2.0) mumol x 1-1 (p less than 0.02). The mean zinc concentration decreased from 13.8 (SD 2.4) mumol x 1-1 to 9.8 (SD 1.8) mumol x 1-1 (p less than 0.001) during the week of the experiment. At the beginning of the study period two subjects had zinc concentrations below the reference values and after the week nine subjects had zinc concentrations below the reference values. The concentration of serum ferritin decreased from 142.2 (SD 103) micrograms x 1-1 to 111.3 (SD 89) micrograms x 1-1 (p less than 0.02) whereas the values of ceruloplasmin remained unchanged. Our findings confirm the earlier suggestion that heavy exposure to heat can cause a loss of some trace elements, especially zinc.

Zinc and copper nutriture of women taking oral contraceptive agents

A cross-sectional and follow-up study of young women taking oral contraceptive agents revealed a marked increase in serum copper levels. This increase was significant after the taking of oral contraceptive agents for 3 months. No significant effect of oral contraceptive agents on serum zinc and hair levels or copper were observed. There was no correlation between duration of oral contraceptive agent therapy and zinc or copper concentrations in serum or hair. Serum and hair concentration of zinc or copper were also not significantly correlated.

Serum copper concentrations in sick and well preterm infants

In order to define the range of serum copper concentrations in preterm infants and to determine the effect of growth upon these values, serial serum copper concentrations were measured in 26 preterm infants over their first six weeks of life. Fourteen healthy, growing preterm infants (Group I) had mean serum copper concentrations below 32 microgram/dl throughout the study. Clinical and hematologic signs of copper deficiency which responded promptly to the oral administration of copper sulfate were noted in five of these 14 infants. Twelve ill preterm infants (Group II-A), who received parenteral nutrition without supplemental copper and had slow rates of growth, had mean serum copper concentrations above 50 micrograms/dl after the first week of life. Seven surviving from Group II-A (Group II-B) had a decrease in mean serum copper concentrations to values similar to those in Group I after two weeks of oral feedings and resumption of normal growth. Our findings suggest that preterm infants who have normal growth while receiving oral feedings are at significant risk for developing copper deficiency.

A simple automated micromethod for measuring serum copper

An automated micromethod for measuring copper concentration in 0.2 ml of serum employing formaldehyde-oxalyldihydrazide as chromogen and using an Auto-Analyzer (Technicon) is presented. The use of formaldehyde-oxalyldihydrazide resulted in a stable and noise-free baseline. The coefficient of variation of the micromethod was 2.4%. The recovery of copper added to samples was 102%. A good correlation between the serum values estimated by the described method and the manual method of Summers [1] ( r = 0.929; P < 0.001) was found when copper standards were prepared in 0.277 M glucose. The mean serum copper concentration found in 26 healthy adult males is 94.1 μg/dl (range: 80 to 120 μg/dl) and in 20 females is 109.8 μg/dl (range: 71 to 170 μg/dl), the difference being statistically significant ( P < 0.02).