Copper and Zinc in the Serum,Urine, and Hair of Patients with Wilson’s Disease Treated with Penicillamine and Zinc

The purpose of this study was to determine the different levels of copper and zinc in the serum, urine, and scalp hair of patients with Wilson’s disease receiving different, currently accepted methods of treatment to reduce the copper load (penicillamine—group 1, n = 8; zinc—group 2, n = 8; penicillamine+zinc—group 3, n = 8). Blood, urine, and hair samples were collected from the patients. All three treatments resulted in a significant decrease of the serum copper levels. Significantly increased levels of zinc in the serum were detected in the patients in groups 2 and 3 (19.1 and 18.8 μmol/l, respectively; p < 0.05). Copper excretion in the urine significantly increased during its administration to groups 1 and 3 (11.5 and 7.94 μmol/24 h respectively; p < 0.001) due to the effect of penicillamine. The administration of zinc as monotherapy (group 2) or in combination with penicillamine (group 3) led to an increase of its excretion (25.3 and 22.4 μmol/24 h, respectively; p < 0.01). Only an insignificant rise of the copper content in the hair was found in all three groups of patients. The content of zinc in the hair did not differ significantly in any of the groups in comparison with the control group.     

Serum α-tocopherol and selenium in belgian infants and children

Previous studies showed low selenium (Se) concentrations in Belgian children. Serum α-tocopherol, retinol, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, selenium (Se), and thiobarbituric acid-reactive substances were examined. In order to obtain further information on the Se status in Belgian children, Se, α-tocopherol, retinol, and lipid concentrations were examined and signs of peroxidative lipid damage were evaluated in a subgroup. The study was performed in 524 children (0–14 yr old) during vaccination campaigns. Three age groups were analyzed: 0–1, 1–4, and 4–14 yr. In 87 of them, where sufficient amounts of serum were available, analysis of thiobarbituric acid-reactive substances was done. Infants have high serum α-tocopherol concentrations: (23.2 μmol/L [median and interquartile range: 18.6–30.2]) and low Se concentrations (0.37 mol/L [0.27–0.47]). Se concentrations rise significantly during the first 4 yr (p < 0.0001) (Mann-Whitney U-test, tied p-values): 0.70 μmol/L (0.59–0.82); in the 4–14 yr olds, it was 0.75 μmol/L (0.67–0.86). These values remain low compared to results coming from other parts of the world. α-Tocopherol concentrations decrease significantly after infancy (p < 0.0001). The ratio α-tocopherol/total cholesterol is higher in infants. This is induced by the high vitamin E content of infant formulas. Signs of serum lipid peroxidation could not be detected by analysis of serum malondialdehyde concentrations. High α-tocopherol concentrations, as those observed in infant serum lipids, could be one of the protective mechanisms from the peroxidative lipid damages, sometimes observed in a low-Se status.     

Copper and dyes enhance laccase production in γ-proteobacterium JB

Laccase production in gamma-proteobacterium JB was enhanced 13-fold by adding 0.1 mM CuSO(4) 24 h after the onset of growth. Ethidium bromide (2.5 microM), Malachite Green, Phenol Red and Thymol Blue (10 microM each) enhanced laccase production 17-, 19-, 4- and 2-fold, respectively. Among the fourteen aromatic/organic compounds tried, p-aminobenzoic acid and an industrial effluent, from where the organism was isolated, showed 1.2- and 1.26-fold increases in production.     

Antigen-Bound and Free β-Amyloid Autoantibodies in Serum of Healthy Adults

Physiological β-amyloid autoantibodies (Aβ-autoantibodies) are currently investigated as potential diagnostic and therapeutic tools for Alzheimer's disease (AD). In previous studies, their determination in serum and cerebrospinal fluid (CSF) using indirect ELISA has provided controversial results, which may be due to the presence of preformed Aβ antigen-antibody immune complexes. Based on the epitope specificity of the Aβ-autoantibodies, recently elucidated in our laboratory, we developed (a) a sandwich ELISA for the determination of circulating Aβ-IgG immune complexes and (b) an indirect ELISA for the determination of free Aβ-autoantibodies. This methodology was applied to the analysis of serum samples from healthy individuals within the age range of 18 to 89 years. Neuropsychological examination of the participants in this study indicated non-pathological, age-related cognitive decline, revealed especially by tests of visual memory and executive function, as well as speed-related tasks. The ELISA serum determinations showed significantly higher levels of Aβ-IgG immune complexes compared to free Aβ-autoantibodies, while no correlation with age or cognitive performance of the participants was found.     

Serum ferritin and transferrin saturation levels in β⁰ and β(+) thalassemia patients

There have been few studies on the mutations that cause heterozygous beta-thalassemia and how they affect the iron profile. One hundred and thirty-eight individuals were analyzed, 90 thalasemic β? and 48 thalasemic β(+), identified by classical and molecular methods. Mutations in the hemochromatosis (HFE) gene, detected using PCR-RFLP, were found in 30.4% of these beta-thalassemic patients; heterozygosity for H63D (20.3%) was the most frequent. Ferritin levels and transferrin saturation were similar in beta-thalassemics with and without mutations in the HFE gene. Ferritin concentrations were significantly higher in men and in individuals over 40 years of age. Transferrin saturation also was significantly higher in men, but only in those without HFE gene mutations. There was no significant difference in the iron profile among the β? and β(+) thalassemics, with and without HFE gene mutations. The frequency of ferritin values above 200 ng/mL in women and 300 ng/mL in men was also similar in β? and β(+) thalassemics (P > 0.72). Our conclusion is that ferritin levels are variable in the beta-thalassemia, trait regardless of the type of beta-globin mutation. Furthermore, HFE gene polymorphisms do not change the iron profile in these individuals.     

Serum copper and zinc concentrations in healthy children aged 3–14 years in greece

Zinc (Zn) and copper (Cu) are essential trace elements in people, being required for functional activity of several enzyme systems. In this study, we determined Cu and Zn concentrations in the serum of 105 healthy children randomly selected, aged 3–14 yr, residing in a region of Greece (Thrace), and we investigated their association with children's gender, age, height, weight, and nutritional habits. The mean levels of Zn and Cu were 15.01±2.95 μmol/L and 26.18±5.47 μmol/L, respectively, with no significant difference between boys and girls. A significant positive correlation was found between age and Zn levels, and a negative one was found between age and Cu levels. Both Zn and Cu levels tended to increase with height, whereas Zn levels significantly decreased with increasing body mass indent (BMI). The consumption of meat, milk, and eggs were independent determinants for higher Zn levels, and the consumption of legumes and fruits were independent determinants for higher Cu levels. A significant negative correlation was found between Zn and Cu levels. In conclusion, our study, the first one evaluating the serum status of Cu and Zn in healthy Greek children, identified significant correlations of Zn and Cu levels with their age, height, BMI, and nutritional habits.     

Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson’s Disease

Background

The intestine is one of the first affected organs in Parkinson’s disease (PD). PD subjects show abnormal staining for Escherichia coli and α-synuclein in the colon.

Methods

We recruited 52 PD patients and 36 healthy cohabitants. We measured serum markers and quantified the numbers of 19 fecal bacterial groups/genera/species by quantitative RT-PCR of 16S or 23S rRNA. Although the six most predominant bacterial groups/genera/species covered on average 71.3% of total intestinal bacteria, our analysis was not comprehensive compared to metagenome analysis or 16S rRNA amplicon sequencing.

Results

In PD, the number of Lactobacillus was higher, while the sum of analyzed bacteria, Clostridium coccoides group, and Bacteroides fragilis group were lower than controls. Additionally, the sum of putative hydrogen-producing bacteria was lower in PD. A linear regression model to predict disease durations demonstrated that C. coccoides group and Lactobacillus gasseri subgroup had the largest negative and positive coefficients, respectively. As a linear regression model to predict stool frequencies showed that these bacteria were not associated with constipation, changes in these bacteria were unlikely to represent worsening of constipation in the course of progression of PD. In PD, the serum lipopolysaccharide (LPS)-binding protein levels were lower than controls, while the levels of serum diamine oxidase, a marker for intestinal mucosal integrity, remained unchanged in PD.

Conclusions

The permeability to LPS is likely to be increased without compromising the integrity of intestinal mucosa in PD. The increased intestinal permeability in PD may make the patients susceptible to intestinal dysbiosis. Conversely, intestinal dysbiosis may lead to the increased intestinal permeability. One or both of the two mechanisms may be operational in development and progression of PD.     

Serum aluminum levels in alzheimer’s disease and other senile dementias

The exact cause of Alzheimer’s disease and the part played in it by aluminum is still speculative. We have studied serum aluminum in 356 healthy people, and we have observed that serum aluminum concentration is increased in aging people in relation to age. We suggest that this could be associated with an enhanced gastric permeability or by an increase in metal accumulation proportional to age. We have measured serum aluminum levels in patients with probable Alzheimer’s disease, patients with other senile dementias, and agematched group. Patients with probable Alzheimer’s disease have statistically significant higher serum aluminum levels than patients with other types of senile dementias (alcoholic, vascular, multi-infart) and an age-matched control group. When we compare serum aluminum of patients with senile dementias from other causes with the agematched control group, we do not find significant differences.     

Alterations of Serum Zinc, Copper, Manganese, Iron, Calcium, and Magnesium Concentrations and the Complexity of Interelement Relations in Patients with Obsessive–Compulsive Disorder

The purpose of the present study was to evaluate the status of serum trace elements: zinc, copper, manganese, iron, calcium, and magnesium concentrations in obsessive-compulsive disorder patients. Forty-eight obsessive-compulsive disorder patients and 48 healthy volunteers were included in this study. Patients were recruited from Bangabandhu Sheikh Mujib Medical University by random sampling. Serum trace element concentrations were determined using flame atomic absorption spectroscopy (for zinc, copper, iron, calcium, and magnesium) as well as graphite furnace atomic absorption spectroscopy (for manganese). Data were analyzed using independent t test, Pearson's correlation analysis, regression analysis, and ANOVA. Statistical analysis of these data showed a definite pattern of variation among certain elements in patients with obsessive-compulsive disorder compared to controls. In patients' serum, zinc, iron, and magnesium concentrations decreased significantly (p<0.05) compared to the controls. Serum manganese and calcium concentrations were significantly higher (p<0.05) in patients compared to the controls. These data showed a definite imbalance in the interelement relations in obsessive-compulsive disorder patients compared to controls and therefore suggest a disturbance in the element homeostasis.     

Contribution to the Data on Copper Concentration in Blood and Urine in Patients with Wilson’s Disease and in Normal Subjects

Determination of copper in human tissues and body fluids may be crucial in the diagnosis of Wilson’s disease. In this study we evaluated urinary copper excretion and urine and blood concentration in 14 patients in whom Wilson’s disease was confirmed (group A) and in 21 subjects in whom the disease was only suspected (group B). The following values (mean ± SD) were found: 24-h urine (μg Cu/24 h), 152 ± 135 (A) and 31.8 ± 10.9 (B); urine (μg Cu/ml), 0.091 ± 0.087 (A) and 0.028 ± 0.011 (B); and blood (μg Cu/ml), 0.62 ± 0.25 (A) and 0.72 ± 0.09 (B). By comparison, urine copper concentration in the group of apparently healthy subjects was 0.035 ± 0.010 (n = 50), and blood copper concentration in autopsy cases of nonpoisoned people was 0.85 ± 0.19 (n = 73).     

Serum zinc and its relation to bone mineral density in β-thalassemic adolescents

Trace elements have been considered to play critical roles in bone metabolism. This study aims at determining the serum zinc profile and its association with bone mineral density (BMD) abnormalities in thalassemic patients. In 131 transfusion-dependent β-thalassemic patients, aged 10–20 yr, serum levels of zinc were measured by flame atomic absorption spectrophotometry (F-AAS). BMD values at the lumbar (L1–L4) and femoral neck were determined by dual X-ray absorptiometry (DXA). Dietary zinc intake and daily consumption of calcium were evaluated by a food-frequency questionnaire. Low serum zinc was found in 84.8% (in 44.7% severely low). Below −2 BMD Z-scores were observed in 68.7% and 17.6% of the patients at the lumbar and femoral regions, respectively. Female patients with severe zinc deficiency had lower lumbar BMD Z-scores in comparison to the other females (−3.26 vs −2.54). Serum zinc in females with femoral BMD Z-scores <−2 was significantly lower by 16.4 μg/dL than other females. Our study suggests that serum levels of zinc can be lowered in the thalassemic patients and partly affect the BMD.     

Evaluation of Mineral Concentrations in Maternal Serum Before and After Birth and in Newborn Cord Blood Postpartum—Preliminary Study

The mineral levels in maternal serum change during pregnancy and may be correlated with those of newborn cord blood. The aim of this study was to evaluate the concentrations of calcium (Ca), magnesium (Mg), zinc (Zn), iron (Fe), and copper (Cu) in maternal blood before and after delivery and in umbilical cord vein and artery serum. The study was carried out in 64 Caucasian pregnant women who delivered in a district hospital in Greater Poland region, aged 28.1 ± 5.4 years, with a mean gestational age of 39.2 ± 1.3 weeks. Blood samples were taken from women 2–8 h before delivery and immediately after childbirth. The umbilical cord artery and vein blood of newborns was obtained immediately after childbirth. The levels of minerals in serum were determined by flame atomic absorption spectrometry. A significant drop in the concentrations of Mg (17.71 ± 1.51 vs 17.07 ± 1.61 μg/ml; p < 0.007), Fe (1.08 ± 0.46 vs 0.82 ± 0.35 μg/ml; p < 0.0004), and Zn (0.63 ± 0.17 vs 0.46 ± 0.16; p < 0.0001) in maternal serum was found after delivery. Moreover, higher levels of Ca, Fe, and Zn and lower levels of Cu were observed in the umbilical vein (Ca: 102.80 ± 7.80 μg/ml; p < 0.0001, Fe: 1.96 ± 0.43 μg/ml; p < 0.0001, Zn: 0.65 ± 0.16 μg/ml; p < 0.0001, Cu: 0.36 ± 0.09 μg/ml; p < 0.0001) and in the umbilical artery cord blood (Ca: 98.07 ± 8.18 μg/ml; p < 0.0001, Fe: 1.63 ± 0.30 μg/ml; p < 0.0001, Zn: 0.65 ± 0.15 μg/ml; p < 0.0001, and Cu: 0.36 ± 0.10 μg/ml; p < 0.0001) compared to the maternal serum (Ca: 85.05 ± 10.76 μg/ml, Fe: 0.82 ± 0.35 μg/ml, Zn: 0.46 ± 0.16 μg/ml, and Cu: 1.90 ± 0.35 μg/ml). Fe levels in the cord artery serum negatively correlated with blood loss during delivery (R = ?0.48; p = 0.01), while the Ca concentration in the maternal serum after birth decreased with the age of the women (R = ?0.25; p = 0.03). In conclusion, it seems that the process of birth alters the mineral levels in pregnant women’s blood. Moreover, it was found that blood loss and the age of the mother are associated with mineral concentrations in the maternal serum and cord artery blood.     

Copper transport and Alzheimer’s disease

This brief review discusses copper transport in humans, with an emphasis on knowledge learned from one of the simplest model organisms, yeast. There is a further focus on copper transport in Alzheimer’s Disease (AD). Copper homeostasis is essential for the well-being of all organisms, from bacteria to yeast to humans: survival depends on maintaining the required supply of copper for the many enzymes, dependent on copper for activity, while ensuring that there is no excess free copper, which would cause toxicity. A virtual orchestra of proteins are required to achieve copper homeostasis. For copper uptake, Cu(II) is first reduced to Cu(I) via a membrane-bound reductase. The reduced copper can then be internalised by a copper transporter where it is transferred to copper chaperones for transport and specific delivery to various organelles. Of significance are internal copper transporters, ATP7A and ATP7B, notable for their role in disorders of copper deficiency and toxicity, Menkes and Wilson’s disease, respectively. Metallothioneins and Cu/Zn superoxide dismutase can protect against excess copper in cells. It is clear too, increasing age, environmental and lifestyle factors impact on brain copper. Studies on AD suggest an important role for copper in the brain, with some AD therapies focusing on mobilising copper in AD brains. The transport of copper into the brain is complex and involves numerous players, including amyloid precursor protein, Aβ peptide and cholesterol.     

Distribution of Copper, Iron, and Zinc in Biological Samples (Scalp Hair, Serum, Blood, and Urine) of Pakistani Viral Hepatitis (A–E) Patients and Controls

The aim of the present study was to compare the level of copper (Cu), iron (Fe) and zinc (Zn) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different viral hepatitis (A, B, C, D, and E; n?=?521) of both gender age ranged 31–45 years. For comparative study, 255 age-matched control subjects, of both genders residing in the same city were selected as referents. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in blood, sera, and scalp hair samples of hepatitis patients, while Zn level was found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p?<?0.05). These results are consistent with literature-reported data, confirming that the deficiency of zinc and hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.     

Identification and Characterization of GH Receptor and Serum GH-binding Protein in Chinese Sturgeon （Acipenser sinensis）

Growth hormone (GH) can stimulate bone and carti-lage cell proliferation and influence carbohydrate and lipidmetabolism. The binding of GH to its specific receptor(GHR) on the surface of target cells will induce dimeriza-tion of GHR, which allows the cytoplasmic region of GHRto interact and trigger downstream signaling and geneexpression [1,2]. GHR belongs to the cytokine receptor superfamily, andis expressed in many tissues such as the liver, muscle,adipose tissue, cartilage, and brain…     

Serum esterase genetics in rabbits. IV. The prealbumin and β-globulin systems

Discontinuous starch gel electrophoresis revealed a fourth allele of rabbit prealbumin serum esterase at locus Est-2. This allele is designated Est-2 ^f and appears to be silent. In addition to the prealbumin serum esterases, another serum esterase system was studied in rabbits. This system is localized in the β-globulin region. Genetic analysis indicated that one locus with two codominant alleles controls the variation in this region. Linkage of this system with Est-1 and Est-2 of the prealbumin serum esterases was demonstrated. Comparison of the arrangement of these esterase loci on linkage group VI with the esterase loci on chromosome 8 of the mouse gives additional support for the theory of evolutionary conservation of chromosomal segments coding for mammalian esterases.     

Serum prolidase enzyme activity and oxidative status in patients with Behçet's disease

Abstract

Objectives

To assess serum prolidase enzyme activity and oxidative stress in patients with Behçet's disease (BD).

Methods

The study population consisted of BD patients (n = 42) and healthy participants (n = 29). BD patients were classified as active (n = 18) or inactive (n = 24) according to disease activity. Serum prolidase enzyme activity, total antioxidant status (TAS), total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA) levels were measured.

Results

In BD patients with active disease, serum prolidase activity was significantly higher compared with the inactive and control participants. Serum prolidase activity was also significantly higher in all BD patients in comparison with controls. Serum prolidase activity was also positively correlated with OSI, C-reactive protein, and active BD. MDA, TOS, and OSI levels were all significantly higher in the BD group when compared with the healthy control participants. Serum TAS levels were significantly lower in BD patients in comparison with healthy controls.

Conclusion

High prolidase activity may indicate critical biological activities relevant to pathological events in BD, and this activity may be a biological indicator of disease. Further studies are needed to verify these findings.     

Serum COMP-C3b complexes in rheumatic diseases and relation to anti-TNF-α treatment

Introduction  

Cartilage oligomeric matrix protein (COMP) is found at elevated concentrations in sera of patients with joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). We recently showed that COMP activates complement via the alternative pathway and that COMP-C3b complexes are present in sera of RA patients, but not in healthy controls. We now set out to elaborate on the information provided by this marker in a variety of diseases and larger patient cohorts.