A Systematic Review and Meta-Analysis of the Effects of Various Sources and Amounts of Copper on Nursery Piglets.

This study evaluated the impact of different dietary levels and sources of copper on the growth performance of nursery piglets through a combination of systematic review and meta-analysis. The database for this study was created using articles selected from major electronic databases. Data analysis involved forest plots and analysis of variance using mixed-effects models. The database included 63 articles published between 1990 and 2021, comprising 21,113 piglets in 946 treatments. Positive effects of supranutritional levels of copper from both inorganic and organic sources on the growth performance of nursery piglets were detected using Forest plots and analysis of variance (p < 0.001). Using mixed models, it was observed that piglet performance is influenced by body weight (p < 0.001), age (p < 0.001), and copper intake (p < 0.001). Both organic and inorganic sources of copper at supranutritional levels (>81 mg Cu/kg of diet) improved the performance of nursery piglets, but levels higher than 201 mg Cu/kg of diet did not further improve growth performance compared to 80-200 mg Cu/kg of diet. The feed conversion was worse in piglets fed with inorganic Cu sources (p < 0.001). In conclusion, dietary Cu supplementation influenced the weight gain and feed conversion rate in weaned piglets, particularly during the first few weeks post-weaning. Levels of 81 and 200 mg Cu/kg improved growth performance, but no further benefits were obtained for higher levels.

Abnormalities in Copper Status Associated with an Elevated Risk of Parkinson's Phenotype Development.

In the last 15 years, among the many reasons given for the development of idiopathic forms of Parkinson's disease (PD), copper imbalance has been identified as a factor, and PD is often referred to as a copper-mediated disorder. More than 640 papers have been devoted to the relationship between PD and copper status in the blood, which include the following markers: total copper concentration, enzymatic ceruloplasmin (Cp) concentration, Cp protein level, and non-ceruloplasmin copper level. Most studies measure only one of these markers. Therefore, the existence of a correlation between copper status and the development of PD is still debated. Based on data from the published literature, meta-analysis, and our own research, it is clear that there is a connection between the development of PD symptoms and the number of copper atoms, which are weakly associated with the ceruloplasmin molecule. In this work, the link between the risk of developing PD and various inborn errors related to copper metabolism, leading to decreased levels of oxidase ceruloplasmin in the circulation and cerebrospinal fluid, is discussed.

Determination of Copper at Extended Dose Levels of Copper (II)-acetylsalicylate and Pharmacokinetics Applications.

Rheumatoid arthritis has long been treated with acetylsalicylic acid, despite many side effects, including gastric ulcers. These side effects can be curtailed by preparing the metal complexes of8 acetylsalicylic acid, such as copper (II)-acetylsalicylate (CAS). Present study evaluates the pharmacokinetics parameters of CAS and the level of copper at extended dose levels using rabbit model. The concentrations of CAS and copper in plasma samples were determined by validated HPLC and atomic absorption spectroscopic (AAS) methods, respectively. Three doses, 1-3 mg Kg-1 were orally administered to six rabbits with two wash out periods. The blood samples were collected at different time intervals for 24 hours. The peak drug concentration (Cmax) for these doses at a time to peak drug concentration (tmax) 0.5 h was determined to be 0.38, 0.76 and 1.14 µg mL-1. The half-life of drug (t1/2) was 8.67, 8.73 and 8.81 h, which are perfect results for once a day dosing. The values of volume of distribution (Vd) and clearance (Cl) for CAS were 829, 833 and 837 L Kg-1 and 66.30, 66.74 and 66.95 L h-1, respectively. The AAS results showed that copper levels in rabbit blood plasma were increased with increasing the dosage of CAS, but still remains under the safer limit, which was twofold higher than the reported safe limit.

Establishment and Validation of Prognostic Nomograms Based on Serum Copper Level for Patients With Early-Stage Triple-Negative Breast Cancer.

Background: Altered copper levels have been observed in several cancers, but studies on the relationship between serum copper and early-stage triple-negative breast cancer (TNBC) remain scare. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions. Methods: We retrospectively analyzed clinicopathological information and baseline peripheric blood samples of patients diagnosed with early-stage TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center. The optimal cut-off point of serum copper level was determined using maximally selected log-rank statistics. Kaplan-Meier curves were used to estimate survival probabilities. Independent prognostic indicators associated with survival were identified using multivariate Cox regression analysis, and subsequently, prognostic nomograms were established to predict individualized disease-free survival (DFS) and overall survival (OS). The nomograms were validated in a separate cohort of 86 patients from the original randomized clinical trial SYSUCC-001 (SYSUCC-001 cohort). Results: 350 patients were eligible in this study, including 264 in the training cohort and 86 in the SYSUCC-001 cohort. An optimal cut-off value of 21.3 µmol/L of serum copper was determined to maximally divide patients into low- and high-copper groups. After a median follow-up of 87.1 months, patients with high copper levels had significantly worse DFS (p = 0.002) and OS (p < 0.001) than those with low copper levels in the training cohort. Multivariate Cox regression analysis revealed that serum copper level was an independent factor for DFS and OS. Further, prognostic models based on serum copper were established for individualized predictions. These models showed excellent discrimination [C-index for DFS: 0.689, 95% confidence interval (CI): 0.621-0.757; C-index for OS: 0.728, 95% CI: 0.654-0.802] and predictive calibration, and were validated in the SYSUCC-001 cohort. Conclusion: Serum copper level is a potential predictive biomarker for patients with early-stage TNBC. Predictive nomograms based on serum copper might be served as a practical tool for individualized prognostication.

Associations of the Dietary Iron, Copper, and Selenium Level With Metabolic Syndrome: A Meta-Analysis of Observational Studies.

BACKGROUND: Epidemiological studies have investigated the associations of dietary iron, copper, and selenium level with metabolic syndrome (MetS). However, their results are conflicting. This meta-analysis of observational study was, therefore, employed to investigate the associations above. METHODS: A comprehensive literature search was employed using PubMed, Web of Science, Embase, and Scopus database up to October 2021 (no restriction was set for the initiate time). The pooled relative risk (RR) of MetS for the highest vs. lowest dietary iron, copper, and selenium level was estimated, respectively. RESULTS: A total of 14 observational studies (55,131 participants) were identified as meeting the inclusion criteria. Specifically, 7 studies were related to the dietary iron level. The overall multivariable adjusted RR demonstrated that the dietary iron level was positively associated with MetS (RR = 1.27, 95% CI: 1.12-1.44; p < 0.001). With regard to the dietary copper level, 7 studies were included for meta-analysis. The overall multivariable adjusted RR showed that the dietary copper level was inversely associated with MetS (RR = 0.85, 95% CI: 0.78-0.93; p < 0.001). In addition, 4 studies were specified for the dietary selenium level. The overall multivariable adjusted RR indicated that the dietary selenium level was inversely associated with MetS (RR = 0.77, 95% CI: 0.63-0.95; p = 0.01) as well. CONCLUSION: Our results suggest that the dietary iron level is positively associated with MetS, whereas a negative association between the dietary copper and selenium level and MetS is obtained. Further large well-designed prospective cohort studies are warranted to elaborate on the issues examined in this study.

The copper content in the blood plasma of children with different types of short stature.

OBJECTIVE: The aim: to investigate the copper content in blood serum of children with different short stature types. PATIENTS AND METHODS: Materials and methods: In the first stage, a comprehensive survey of 258 school children aged 7-11 was carried out in Chernivtsi to assess the prevalence of short staturechildren of school-age. In the second stage, a comparative study of 42 children aged 3 to 15 years with different types of short stature was conducted. Research: anthropometry, determination of growth hormone, TSH, IGF-1, and copper level in blood plasma. RESULTS: Results: The largest growth rate in children with somatotropic insufficiency, the syndrome of a biologically inactive growth hormone ranged from 4.1 cm/year to 1.6 cm/year, the ones with a family constitutional low-growth - from 5.7 cm/year to 3.3 cm/year. In 57 cases, that makes 1% of children with short stature, the blood plasma level of copper made less and rated 0.89 ± 0.04 µg / ml, which is believed to be lower (pу0,001) the average copper in children of the control group - 1.07 ± 0.02 µg / ml. Indices of copper in blood plasma in children with somatotropic insufficiency were the lowest and averaged 0.75 ± 0.03 µg / l, p<0.05. CONCLUSION: Conclusions: The lack of copper in the blood plasma is observed in most children with short stature, which indicates the need for appropriate correction.

Association between serum copper levels and lung cancer risk: A meta-analysis.

OBJECTIVE: To evaluate the association between serum copper levels and lung cancer risk. METHODS: We searched the electronic PubMed, WanFang, CNKI, and SinoMed databases to identify studies including information on serum copper levels and lung cancer. Standard mean differences and corresponding 95% confidence intervals were calculated using Stata 12.0 software. We performed a meta-analysis on the identified studies overall and according to geographic location. We also evaluated heterogeneity among the studies and the occurrence of publication bias. RESULTS: Thirty-three articles including 3026 cases and 9439 controls were included in our study. The combined results showed that serum copper levels were higher in patients with lung cancer compared with controls without lung cancer, though the results showed high heterogeneity. In a subgroup analysis according to geographic location, significant associations between copper levels and lung cancer were found for both Asian and European populations. No publication bias was detected in this meta-analysis. CONCLUSIONS: High serum copper levels could increase the risk of lung cancer, suggesting that environmental copper exposure may be a risk factor for the development of lung cancer.

Association between serum copper levels and cervical cancer risk: a meta-analysis.

Whether serum copper levels were higher in patients with cervical cancer than that in controls was controversial. Hence, we conducted the present study to explore the relationship between serum copper levels and cervical cancer. We searched PubMed, WanFang, and China National Knowledge Internet (CNKI) for relevant studies before November 30, 2017. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to combine results across studies using the random-effect model. A total of 14 publications involving 747 patients with cervical cancer and 1014 controls were eligible through inclusion criteria. In comparison with controls, serum copper levels were significantly higher in patients with cervical cancer [summary SMD = 1.35; 95%CI: 0.10-2.59], with significant heterogeneity (I2 = 98.8%; P<0.001) was found. Significant association was also found among Asian populations [summary SMD = 1.39; 95%CI: 0.06-2.71]. The association was positive in subgroup analysis of population-based case-control studies (PBCC) [summary SMD = 1.64; 95%CI: 0.02-3.34], but not in hospital-based case-control studies (HBCC). Through a sensitivity analysis, we did not identify any single study to strongly influence the results of our serum copper levels and cervical cancer risk. No publication bias was found in our analysis. In conclusion, our study provided significant evidence of higher serum copper levels in patients with cervical cancer than in controls, suggesting that serum copper exposure was a risk factor on cervical cancer.

[The diagnostic value and limits of diagnostic parameters for Wilson's disease].

Wilson disease (WD) is a rare and treatable genetic disorder. This paper describes the new advances and author's long-term experiences in the diagnosis of WD. The characteristics in clinical and routine tests are: the age of presentation can be quite broad, the WD could not be excluded based on age only; the patients usually have mild digestive symptoms but obvious chronic liver disease signs; liver function tests may reveal normal or a mild elevation in bilirubin, ALT and AST, but quite abnormal in serum albumin and prothrombin time in most patients; Coombs-negative hemolytic anemia, normal or markedly subnormal serum alkaline phosphatase (typically < 40 IU/L) are useful for the diagnosis of fulminant WD. In china, Kayser-Fleischer rings are present in 72.2% of patients at the time of diagnosis, the positive rate is significantly higher in patients with a neurological presentation (93.4%) than patients presenting with liver disease (63.3%), however, they are usually absent in children under 6 years old, occasionly present in patients with chronic cholestatic liver disease. The mean serum ceruloplamin level in WD patients is 71.1 ± 48.7 mg/L, the level is < 200 mg/L in 98.9% of patients, < 100 mg/L in about three fourths patients, < 50 mg/L in about half patients, but it may be low in 50% of patients with severe end-stage liver disease of any etiology too, and even lower than 50 mg/L in patients with nephritic syndrome. Basal 24-hour urinary copper excretion may be≥100 g at presentation in 86.7% of patients with WD, but also in 22% of Patients with certain chronic liver diseases, the sensitivity of penicillamine challenge test is lower than basal urinary copper excretion, however, the specificity is significantly higher than former (97% versus 78%). Hepatic copper determination remains the gold standard for the diagnosis of WD. We have designed a standard method for hepatic copper determination. The most useful cut-off value is 209 g/g dry wt using our method, with the sensitivity of 99.4%, and specificity of 96.1%. However, long-standing hepatic failure and or obstruction can cause heptic copper elevations into the WD area. In recent years, direct complete DNA sequencing has become easy, rapid, less expensive and commercially available. Currently reported mutation detection rate is 90%, the specificity is almost 100%. The limitation to the method has been the ability to identify all the affected alleles in suspected individuals. If no mutation is identified, the diagnosis of WD could not be excluded. None of the laboratory parameters alone allows a definite diagnosis of WD. The WD diagnostic scoring system based on a composite of key parameters helps clinicians to gauge the degree of certainty of the diagnosis: WD scores greater than 4, the diagnosis of WD is highly likely; score 0 or 1, the diagnosis is unlikely. However, the WD diagnosis could not be excluded in suspected patients who do not perform genetic test and hepatic copper determination. Patients with chronic cholestatic liver disease may have scores more than 4.

A meta-analysis of copper level and risk of preeclampsia: evidence from 12 publications.

The association between copper level and risk of preeclampsia (PE) has produced inconsistent results. Thus, a meta-analysis was conducted to summarize the evidence from epidemiological studies for copper level and PE risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge up to April 2016. Standardized mean difference (SMD) was performed to combine the results. Random-effect model (REM) was used. Publication bias was estimated using Egger's regression asymmetry test. Twelve articles (10 case-control studies and 2 cross-sectional studies) involving 442 PE cases and 463 health controls were included in this meta-analysis. Our pooled results suggested that PE patients had a higher copper level compared with healthy pregnancy controls [summary SMD=0.69, 95% CI: 0.54-0.84, I(2)=96.7%; P<0.001]. The association was also significant in Asian population [SMD=0.73, 95% CI=0.57-0.90, I(2)=97.3%] and European populations [SMD=0.50, 95% CI=0.14-0.86, I(2)=58.9%]. After conducting the subgroup analysis and sensitive analysis, the results showed consistent significant association with the one based on all studies. No publication biases were found. Our analysis indicated that plasma or serum copper level in PE patients was significantly higher than that in healthy pregnancy women.

Effect of oral contraceptive progestins on serum copper concentration.

OBJECTIVES: Recent epidemiologic studies have shown an increased mortality from cardiovascular diseases in people with higher serum copper levels. Even though higher serum copper concentration in women using oral contraceptives is well known, there is still uncertainty about the influence of newer progestin compounds in oral contraceptives on serum copper concentration. This issue is of particular interest in the light of recent findings of an increased risk of venous thromboembolism in users of oral contraceptives containing newer progestins like desogestrel compared to users of other oral contraceptives. DESIGN: Cross-sectional epidemiologic study. Examinations included a detailed questionnaire on medical history and lifestyle factors, a seven day food record, and blood samples. SETTING: National health and nutrition survey among healthy people living in private homes in West Germany in 1987-1988. SUBJECTS: Nonpregnant and nonlactating women aged 18-44 y (n = 610). RESULTS: Overall, the use of oral contraceptives was positively associated with serum copper concentration in by bi- and multivariable linear regression models with log-transformed values of serum copper concentration as dependend variable and oral contraceptive preparations and potential confounding variables as independent variables. Serum copper concentration in women using oral contraceptives varied more strongly by different progestin compounds than by estrogen contents. The highest increase of serum copper was seen in women using oral contraceptives containing antiandrogen progestins (55%; 95% CI: 37-76%), followed by desogestrel (46%; 95% CI: 36-56%), norethisteron/lynestrenol (42%; 95% CI: 29-57%), and levonorgestrel (34%; 95% CI: 24-45%). CONCLUSION: While elevated serum copper concentration was found in users of all types of oral contraceptives, elevation was more pronounced among women taking oral contraceptives with antiandrogen effective progestins like antiandrogens or third generation oral contraceptives containing desogestrel. Further investigation is required to shed light on the possible role of high serum copper concentration in increasing cardiovascular or thrombotic risk of women using oral contraceptives.

PIP: High serum copper concentration--a well-known effect of oral contraceptive (OC) use--has been linked to increased mortality from cardiovascular disease. The influence of OCs containing newer progestins has not been investigated, however. This concern was addressed in a 1987-88 cross-sectional epidemiologic study of 610 nonpregnant, nonlactating West German women 18-44 years of age. 195 women (32.1%) were current OC users, but only 152 of these women were able to cite the name of the formulation they were taking. In 70% of cases, the OC contained less than 45 mcg of ethylestradiol (median dose, 32.4 mcg). The most common progestin components were desogestrel (41%) and levonorgestrel (30%). Mean serum copper concentration was higher among users of all types of OCs than among non-users, but this concentration varied more strongly according to the OC's progestin compound than its estrogen content. The greatest increase in serum copper (55% compared with non-users) was recorded in users of OCs containing anti-androgen progestins, followed by desogestrel (46%), norethisterone/lynestrenol (42%), and levonorgestrel (34%). The increase in serum copper was more pronounced in women taking OCs containing 45 mcg or less of ethylestradiol than in users of OCs with a high estrogen dose. In the regression models, the different progestin compounds alone explained 28% of the total variance in serum copper concentration. Further investigation of OC-induced increases in serum copper concentration and their impact on cardiovascular risk are warranted.

Serial copper and ceruloplasmin levels in African newborns with emphasis on the sick and stable preterm infant, and their antioxidant capacities.

Literature on serum copper (Cu) and its antioxidant protein (ceruloplasmin) in the African newborn is infrequent, and more reports are evident from developed or affluent societies. We, therefore, studied longitudinally our newborns to delineate their Cu and ceruloplasmin (CLP) status. All infants were born between July 1st, 1991 and June 30th, 1992 at the University of Maiduguri Teaching Hospital, Maiduguri, Nigeria. The preterm infants (PI) (gestational age < or = 36 weeks) were divided into 2 cohorts; A, sick and B, stable; commencing with n = 30 in each group. The groups were matched in respect to gender, gestational age, birthweight, Apgar scores and socioeconomic class. Cu levels were contemporaneously also determined in 30 (M:F, 17:13) stable full-term infants (appropriate-for-dates). Cu determination was made with atomic absorption spectrophotometry and CLP according to colorimetric P-phenylenediamine assay. Sick PI (cohort A) had significantly lower mean (SD) Cu and CLP levels at birth; 0.1 (0.2) micromol/ml and 0.5 (0.8) micromol/dl vs 0.6 (0.2) micromol/ml and 12.5 (1.2) micromol/dl in stable PI (cohort B), respectively; P < 0.05. Cu level was significantly increased by 4 weeks in cohort A; P < 0.001 (n = 25) and approached levels of the stable PI (0.7 (0.3) vs 0.8 (0.2) micromol/ml). Concerning CLP, however, catch-up of levels was delayed till 8 weeks, and a triphasic pattern of linear rise in Cu (both cohorts, but more prominent in A) and CLP (cohort A) was discernible by 24 weeks. The sick PI had mean (SD) serum CLP levels of 0.5 (0.8) micromol/dl, 5.9 (1.4), 15.2 (2.6), 17.3 (2.9), 21.2 (3.8), 25.1 (4.7) and 23.7 (3.8) micromol/dl at birth, 4, 8, 12, 20, and 24 weeks, respectively and were similar from 8 weeks in cohort B. Generally, CLP paralleled serum Cu levels. Cu levels in the full-term infant (FI) were higher at birth and became similar to PI's from 12 weeks, but were overtaken by levels in PI (both cohorts) at 24 weeks. The FI's Cu was significantly elevated by 8 weeks; mean (SD), 0.81 (0.16) micromol/ml vs 1.25 (0.19) micromol/ml; P < 0.01, paired t-test. Decreased growth rate, nonpitting pedal edema, exaggerated physiological anaemia and chronic lung disease were few morbidities noted in association with very low Cu and CLP levels (n = 15). Newborns with serum Cu and CLP>0.2 micromol/ml and >2.3 micromol/dl, respectively, did not have a poor outcome. It is tempting to suggest that absent serum CLP activity may portend a poor prognosis. Our findings (number albeit small) could be taken as a preliminary normative data for further comparisons.

PIP: Newborn infants were studied longitudinally to assess their serum copper (Cu) and ceruloplasmin (CLP) status. All infants were born between July 1, 1991, and June 30, 1992, at the University of Maiduguri Teaching Hospital, Maiduguri, Nigeria. Preterm infants (PI) of a maximum gestational age 36 weeks were divided into sick (A) and stable (B) cohorts, beginning with 30 in each of the 2 groups. The groups were matched with respect to gender, gestational age, birth weight, Apgar scores, and socioeconomic class. Cu levels were also determined in 30 stable, full-term infants. Sick PIs had significantly lower mean Cu and CLP levels at birth, while Cu level was significantly increased by 4 weeks in cohort A and approached levels of the stable PIs. With regard to CLP, catch-up of levels was delayed until 8 weeks, and a triphasic pattern of linear rise in Cu and CLP was discernible by 24 weeks. Sick PIs had mean serum CLP levels of 0.5 mcmol/dl, 5.9, 15.2, 17.3, 21.2, 25.1, and 23.7 mcmol/dl at birth, 4, 8, 12, 20, and 24 weeks, respectively, and were similar from 8 weeks in cohort B. Generally, CLP paralled serum Cu levels. Cu levels in the full-term infant (FI) were higher at birth and became similar to PIs from 12 weeks, but were overtaken by levels in PI at 24 weeks. FIs' Cu was significantly elevated by 8 weeks. Decreased growth rate, nonpitting pedal edema, exaggerated physiological anemia, and chronic lung disease were morbidities noted in association with very low Cu and CLP levels. Newborns with serum Cu and CLP higher than 0.2 mcmol/ml and 2.3 mcmol/dl, respectively, did not have a poor outcome.

Nitrites and L-citrulline levels in copper intrauterine device users.

The mechanism of copper in limiting intrauterine infections in intrauterine device (Cu IUD) users is poorly understood. Copper ions may enhance the release of reactive oxygen radicals, which in turn decrease the release of reactive nitrogen intermediates (RNI). RNI are known to have bactericidal effect. The present study compares the levels of RNI prior to Cu-T insertion and at different post-insertion intervals up to 12 weeks. The decrease in RNI was evident by one week and continued until 12 weeks. Therefore, the bactericidal effect of copper in IUD is via reactive oxygen intermediates. The superoxide anion inactivates this active intermediate nitric oxide. Therefore, excess of superoxide radical will markedly shorten the half-life of nitric oxide but will not prevent its conversion to nitrites and nitrates.

PIP: Copper ions may enhance the release of reactive oxygen radicals that decrease the release of reactive nitrogen intermediates (RNIs), known to have a bactericidal effect. The capability of the Copper-T IUD to generate RNIs was investigated in women seeking IUD insertion at a family planning clinic in Chandigarh, India. A significant decrease in nitric oxide levels was recorded from pre-insertion to 1 week post-insertion. Moreover, the values at 4 weeks' post-insertion were significantly lower than those at 1 week, and the 12 weeks' post-insertion level was lower than that recorded at 4 weeks. Uterine aspirate L-citrulline levels at 1 week post-insertion were significantly lower than pre-insertion levels; again, values at 4 and 12 weeks post-insertion were significantly less than those of the receding levels. There was no significant difference in levels of nitrites or serum L-citrulline before and after IUD insertion. Although the exact mechanism of the decrease in RNI levels at the local site after IUD insertion is unknown, it appears related to the sterile intrauterine milieu. At the peak of copper release, the inflammatory cells are activated to release reactive oxygen radicals. Copper potentiates the effect of superoxide dismutase, which influences the half-life of nitric oxide, but does not prevent its conversion to nitrites and nitrates.

The localization and concentration of copper in the fallopian tube in women with or without an intrauterine contraceptive device.

The localization and concentration of copper in cryostat sections of human fallopian tubes from women using an intrauterine contraceptive device (IUCD) and controls was determined by light microscopic- and atomic absorption spectrophotometric techniques. The copper was visually accumulated in the epithelium and the copper concentration in the tubal tissue was increased in the IUCD user group. We also measured the concentration of copper and ceruloplasmin in serum, but there was no statistical difference between the two groups studied. Our results indicate that the IUCD has effects beyond the uterine cavity. The accumulation of copper may be associated with earlier observations of the morphological changes and infiltration of inflammatory cells observed in the fallopian tube in IUCD users.

PIP: During laparoscopic sterilization at a hospital in Bergen, Norway, surgeons removed a 1 cm segment of the macroscopic isthmic portion of the fallopian tube from 40 healthy, nonpregnant women. They used light microscopic and atomic absorption spectrophometric techniques to localize and measure the concentration of copper in cryostat sections of the fallopian tubes of 20 women who had used a copper releasing IUD for more than six months and of 20 other women who used neither an IUD nor an hormonal contraceptive. Copper was visually present in the epithelium, but weakly so, in few of the biopsies from the non-IUD users. In IUD users, it accumulated throughout the epithelium and dwindled in the lamina propria. Its mean concentration in the fallopian tube was 58% higher in IUD users than non-IUD users (128.3 vs. 81.4 nmol/mg protein; p = 0.003). IUD use did not affect protein levels. The IUD affected neither the concentration of copper nor of the copper-transporting protein, ceruloplasmin, in serum. These findings suggest that the accumulation of copper in the fallopian tube in IUD users may effect morphological changes and infiltration of inflammatory cells in the fallopian tube.

Interactions between growth and nutrient status in school-age children of urban Bangladesh.

The relationship between biochemical, anthropometric, and sociodemographic indexes was investigated in 242 children aged 5-12 y from five schools in Dhaka City, Bangladesh. As height-for-age increased so too did the mean serum concentrations of hemoglobin, protein, vitamin A, and zinc; serum copper concentrations were highest in the shortest group. Serum copper concentrations were highest in those with the lowest serum vitamin A concentrations. By multiple regression analysis, family income, age, weight-for-age, hemoglobin, and serum copper were strongly related to serum vitamin A. For every unit change in serum vitamin A there was a 4.92 unit change in hemoglobin, when all the other factors were taken into account. This study shows that there is a complex interaction between concentrations of biochemical indexes of nutritional status and other anthropometric, biochemical, and sociodemographic variables.

PIP: Between February and March 1990, health workers interviewed and took anthropometric measurements and blood samples from 242 children 5-12 years old, attending 3 primary schools in affluent areas and 2 primary schools in poorer areas around a university campus in Dhaka, Bangladesh. Researchers wanted to study the interaction between anthropometric and biochemical measures of nutritional status in seemingly healthy school children. As the height-for-age increased, so did the mean serum levels of protein, hemoglobin, and vitamin A (p = 0.001 for protein and 0.01 for hemoglobin and vitamin A). The rising trends were strongest for hemoglobin and vitamin A. Children in the group with the highest serum vitamin A level ( 1.05 mcmol/L) had significantly higher hemoglobin levels than did those with lower vitamin A levels (adjusted, 138.9 g/L vs. 133.8 g/L for 0.7-1.07 mcmol/L and 132.8 g/L for 0.7 mcmol/L; p = 0.002). For every unit change in vitamin A, a 4.92 unit change in hemoglobin existed. Children who had the lowest serum vitamin A levels had the highest serum copper levels (22.8 mcmol/L vs. 22.3 mcmol/L middle vitamin A group and 19.8 mcmol/L highest vitamin A group; p = 0.05). Multiple regression analysis showed that family income, age, weight-for-age, and hemoglobin and serum copper levels were significantly associated with serum vitamin A levels. These findings reveal that short children who were light for their age had lower serum vitamin A and hemoglobin levels and higher serum copper levels than their taller and heavier counterparts. They demonstrate a complex interaction between serum levels of biochemical indexes of nutritional status and other anthropometric, biochemical, and sociodemographic variables.

Copper, zinc and superoxide dismutase activities in premature infants: a review.

PIP: Zinc and copper are quite abundant trace elements and important in many metabolic processes and enzyme systems. Preterm infants whose diet is deficient in copper and/or zinc may suffer anemia, anorexia, skin changes, diarrhea, growth retardation, impaired connective tissue formation, osteoporosis, and impaired cell mediated immunity as well as failure to thrive. The fetus stores 70% of its body reserve of copper and zinc in the last trimester, indicating that the premature infant has low reserves of cooper and zinc at delivery. They may not amass or develop body stores in the same was as does the fetus. Premature infants receiving pasteurized breast milk have a negative zinc balance for at least the first 60 days of life and a negative copper balance for the first 35 days of life. Parental nutrition without copper and zinc supplements result in deficiency conditions. Some oxidation-reduction reactions using oxygen may generate free radicals; with ventilators delivering oxygen directly into the alveoli, generated free radicals may pulmonary oxygen toxicity. This condition is called bronchopulmonary dysplasia (BPD). Preterm infants without hyaline membrane disease are more likely to support hyperopic increase of pulmonary superoxide dismutase (SOD) (a free radical scavenger) activities than those with hyaline membrane disease (e.g., plasma samples, 88.5% vs. 33%). This suggests that preterm infants with the condition do not have a plasma factor needed for pulmonary SOD response. A possible factor is ceruloplasmin. Copper and zinc are important components of both SOD and ceruloplasmin. More research is needed to examine serial levels of copper, zinc, SOD, and ceruloplasmin in newborns to determine whether postnatal levels are linked to associated morbidities. In the event of failure of vitamin E therapy, administration of bovine SOD to premature infants may prevent and reduce the severity of BPD. In developing countries, physicians should prevent BPD and other chronic problems of premature infants by administering antioxidants with copper and zinc.^ieng

Serum and endometrial copper, zinc, iron and cobalt with inert and copper-containing IUCDs.

Serum and endometrial copper (Cu), zinc (Zn), iron (Fe) and serum cobalt (Co) were measured in the mid-follicular and mid-luteal phases of the menstrual cycles in 30 Lippes loops users, 30 CuT-200 IUCD users and 24 matched controls by atomic absorption spectrophotometry. In the control group, there was no statistically significant difference in mean mid-luteal, compared to mid-follicular, levels of serum Cu, Zn, Fe and Co and endometrial Zn. Mid-luteal endometrium contained significantly higher mean Cu, and lower mean Fe levels. In Lippes loop users, compared to controls, the only statistically significant differences were lower mean mid-follicular serum Zn, lower mean endometrial Zn and Fe, and higher mean mid-luteal endometrial Fe. In CuT-200 users, compared to controls, there was significantly higher mean mid-follicular serum Zn and lower mean mid-luteal serum Co, higher mean mid-follicular endometrial Cu and lower mean mid-follicular endometrial Fe levels. Compared to Lippes loop, CuT-200 users had significantly higher mean mid-follicular serum Co and endometrial Cu and Zn, and lower mean mid-follicular endometrial Fe.

PIP: Serum and endometrial copper (Cu), zinc (Zn), iron (Fe) and serum cobalt (Co) were determined on menstrual cycle Day 6-9 or 9-22 in 30 women with Lippes loops, 30 with CuT-200 IUDs, and 24 controls. The women were clients of the family planning and gynecology clinic of Benha University Hospital, Egypt. Endometrial samples were obtained with a fine Sharmans currette. In controls, the only differences between the mid-follicular and mid-luteal phase were higher Cu and lower Fe levels in the endometrium in the luteal phase. Lippes loop users had lower follicular serum Zn, lower mean endometrial Zn and Fe, and higher mid-luteal endometrial Fe than controls. The CuT-200 IUD group had higher follicular serum Zn and lower luteal serum Co and higher follicular endometrial Cu and lower follicular endometrial Fe levels. The CuT-200 group also had higher follicular serum Co and endometrial Cu and Zn and lower follicular endometrial Fe than did the Lippes loop group.

Effect of family size and income on the biochemical indices of urban school children of Bangladesh.

The relationship between family size and income and the biochemical indices of 242 children (aged from 5 to 12 years) from five schools in Dhaka City, Bangladesh, was investigated. Socio-economic data were collected by questionnaire and blood samples were drawn by visiting each school on a prefixed date. Mean levels of all measures, except for serum zinc, fell within the normal range. Older boys, but not girls (10-12 years of age) had statistically significantly higher haemoglobin, serum protein and serum vitamin A levels compared with those of the younger boys (5-9 years of age). The children were divided into three family size groups (small, up to 4 members; medium, 5-7 members; and large, 8 or more) to investigate the effect of family size on the biochemical data. The children from smaller families showed significantly higher levels of haemoglobin and serum vitamin A compared with the children from large families. For serum protein, copper and zinc, there was no statistically significant difference between the children of different family size groups. To analyse the effect of family income, children were divided into three income groups (low, up to taka 2000; medium, taka 2001-4500; and high, 4501 or more). The children from the low family income group had significantly lower serum protein (7.5 g/100 ml) and haemoglobin (13.4 g/100 ml) levels compared with those of the children from the high family income group (for protein, 7.7 g/100 ml and haemoglobin, 14.1 g/100 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum copper levels in different stages of carcinoma cervix uteri.

PIP: Copper is a normal constituent of the diet and is present in all living matter. It is an important trace metal required for different metabolic processes. Detecting alterations in serum copper has an important role in the early detection and diagnosis of malignancy. Serum copper estimation was conducted on 95 women aged 32-60 using the P.P. Doxidase method. 62 women of varying age and parity had different stages of carcinoma cervix uteri and comprised the study group, while the control group was comprised of 33 non-pregnant women of different ages and parity. Approximately 40% of women in both groups were aged 41-45 years. In the control group, the mean serum copper level of reproductive age women was 118.3 ug% and 111.2 ug% among women of menopausal age. A linear progressive increase of serum copper levels was found in the study group with increasing stages of cervical malignancy. The mean values of stages I, II, III, and IV were 162.2 ug%, 190.64 ug%, 201.78 ug%, and 220.8 ug%, respectively.^ieng

Serum copper levels in users of multiload intra-uterine contraceptive devices.

The systemic absorption of copper incorporated into multiload intra-uterine contraceptive devices (IUDs), as indicated by serum copper levels in users of such devices, was assessed in a prospective longitudinal study. One hundred and ten healthy Nigerian women using either multiload copper 250 (MLCU 250) or multiload copper 375 (MLCU 375) IUDs participated in the study. Their serum copper levels were estimated serially during 12 months of continuous use of the devices. The mean (+/- s.e.m.) pre-insertion serum copper levels of our subjects using MLCU 250 (17.0 +/- 3 mumol/l) and MLCU 375 (16.7 +/- 0.5 mumol/l) were found to be lower than those reported in Americans (22.2 mumol/l) and in Germans (20.2 mumol/l), although similar to levels in Indians (17.0 mumol/l). There was no significant difference in the mean serum copper levels estimated before and after 1 month of continuous use of the device. Serial estimations of the serum copper levels in users showed that there was no alteration in these levels after a period of 12 months of continuous IUD use. We therefore conclude that the copper incorporated into multiload IUDs appears not to influence the concentration of serum copper of users.

PIP: The systemic absorption of copper incorporated into multiload IUDs as indicated by serum copper levels in users of such devices was assessed in a prospective, longitudinal study. 110 healthy Nigerian women using either a multiload copper 250 (MLCU 250) or the MLCU 375 participated in this study. Their serum copper levels were estimated serially during 12 months of continuous use. The mean (+or- s.e.m.) preinsertion serum copper levels in those subjects using the MLCU 250 were 17.0 +or- 3 mcmol/l and 16.7 +or- 0.5 mcmol/l in those using the MLCU 375. These levels were lower than those levels reported in Americans (22.2 mcmol/l) and in Germans (20.2 mcmol/l), although they were similar to those in Indians (17.0 mcmol/l). There was no significant difference in the mean serum copper levels estimated before and after 1 month of continuous use of the device. Serial estimations of the serum copper levels in users showed that there was no alteration in these levels after a period of 12 months of continuous IUD use. The authors conclude that the copper incorporated into multiload IUDs appears not to influence the concentration of serum copper in users. (author's modified)