Speciation of Serum Copper and Zinc-Binding High- and Low-Molecular Mass Ligands in Dairy Cows Using HPLC-ICP-MS Technique.

The objective of the present study was assessment of the major copper and zinc species in dairy cow blood serum using a hybrid high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) technique. A total of seventeen 5-6-year-old female Simmental cows, cultivated in the Southern Ural region, were examined. Speciation of serum Cu and Zn was performed using chromatographic PerkinElmer Series 200 system equipped with Agilent Bio SEC-5 Column and docked with NexION 300D mass spectrometer. Analysis of serum 63Cu species revealed four major fractions containing 2.5% (A), 15.6% (B), 75.6% (C), and 11.9% (D) of total copper levels. The revealed fractions could be assigned to tetrameric and dimeric macroglobulin, ceruloplasmin, albumin, and low molecular mass (LMM) copper compounds, respectively. Minor fraction (E) containing <1% of total serum Cu levels may be represented by low-molecular mass Cu species. Speciation analysis also revealed four Zn fractions containing 6.3% (A), 16.9% (B), 71% (C), and 3% (D) of total Zn levels that may be attributed to zinc-bound tetrameric and dimeric macroglobulin, albumin, and Zn-amino acid compounds. Correlation analysis demonstrated that relative levels (%) of Zn-B (dimeric α2-macroglobulin), Zn-C (albumin), and Zn-D (LMM) fractions correlate inversely with Cu-A (monomeric α2-macroglobulin) (r = -0.600), Cu-D (albumin) (r = -0.696), and Cu-C (ceruloplasmin) (r = -0.652), respectively. The obtained data demonstrate the particular features of Zn and Cu transport in dairy cows that may be used for assessment of dietary status of trace elements.

Trace Element and Mineral Levels in Serum, Hair, and Urine of Obese Women in Relation to Body Composition, Blood Pressure, Lipid Profile, and Insulin Resistance.

The objective of this study was to evaluate serum, hair, and urinary trace element and mineral content in normal-weight and obese women in relation to metabolic risk factors. A total of 80 women aged 30-70 y.o. were enrolled in the obese group (n = 40) and normal-weight group (n = 40). Serum, hair, and urinary trace element and mineral levels were assessed using inductively coupled plasma spectrometry. Body fat percentage was evaluated using bioimpedance. Obese subjects were characterized by significantly higher body fat percentage, blood pressure, serum triglyceride concentration, and insulin resistance. Serum Ca, Fe, Mg, Se, V, Zn levels, hair Fe, Mg, V content, and urinary Se and V concentrations were found to be lower in obese subjects as compared to lean controls. In turn, serum Cu and urinary Fe levels in obese women were characterized by a significant increase. In multiple regression models serum Cu, Se, and Zn levels were significantly associated with BMI even after adjustment for blood biochemistry, body composition, and blood pressure. Serum trace element and mineral levels also significantly contributed to group discrimination. These findings allow to propose that obesity-associated disturbances in trace element and mineral status may at least partially contribute to metabolic risk in obese subjects.

Alteration of iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) tissue levels and speciation in rats with desferioxamine-induced iron deficiency.

The objective of the present study was to investigate the impact of iron deficiency and iron replenishment on serum iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn) speciation and tissue accumulation in a deferrioxamine-induced model of iron deficiency. A total of 26 male Wistar rats were divided into three groups: control; Fe-deficient; Fe-replenished (with iron (II) gluconate). Serum ferritin and transferrin levels were assessed using immunoturbudimetric method. Liver, spleen, and serum metal levels were assessed using ICP-MS. Speciation analysis was performed using a hyphenated HPLC-ICP-MS technique. Desferrioxamine injections resulted in a significant decrease in tissue iron content that was reversed by Fe supplementation. Iron speciation revealed a significant increase in serum transferrin-bound iron and reduced ferritin-bound Fe levels. Serum but not tissue Cu levels were characterized by a significant decrease in hypoferremic rats, whereas ceruloplasmin-bound fraction tended to increase. At the same time, Zn levels were found to be higher in liver, spleen, and serum of Fe-deficient rats with a predominant increase in low molecular weight fraction.Both iron-deficient and iron-replenished rats were characteirzed by increased transferrin-bound Mn levels and reduced low-molecular weight fraction. Hypothetically, these differences may be associated with impaired Fe metabolism under Fe-deficient conditions predisposing to impairment of essential metal handling. However, further studies aimed at assessment of the impact on Fe deficiency on metal metabolism are highly required.

Alterations in serum amino acid profiles in children with attention deficit/hyperactivity disorder.

The objective of the present study was to evaluate the circulating serum amino acid levels in children with attention deficit/hyperactivity disorder (ADHD). A total of 71 children with untreated ADHD and 31 neurotypical controls aged 7-14 years old were examined. Serum amino acid levels were evaluated using high-performance liquid chromatography (HPLC) with UV-detection. Laboratory quality control was performed with reference materials of human plasma amino acid levels. The obtained data demonstrated that children with ADHD were characterized by 29, 10 and 20% lower serum histidine (His), glutamine (Gln) and proline (Pro) levels compared with neurotypical children, respectively. In contrast, circulating aspartate (Asp), glutamate (Glu) and hydroxyproline (Hypro) levels exceeded the respective control values by 7, 7 and 42%. Correspondingly, the Gln-to-Glu and Pro-to-Hypro ratios were 28% and 49%, respectively, lower in ADHD cases compared with the controls. Total Gln/Glu levels were also significantly lower in ADHD patients. No significant group differences were observed between the groups in the other amino acids analyzed, including phenylalanine. Multiple linear regression analysis revealed significant associations between circulating serum Gln, lysine (Lys) (both negative) and Glu (positive) levels with total ADHD Rating Scale-IV scores. The observed alterations in Pro/Hypro and Gln/Glu levels and ratios are likely associated with the coexisting connective tissue pathology and alterations in glutamatergic neurotransmission in ADHD, respectively. Altered circulating levels of His, Lys and Asp may also be implicated in ADHD pathogenesis. However, further in vivo and in vitro studies are required in order to investigate the detailed mechanisms linking amino acid metabolism with ADHD pathogenesis.

Profiling of selenium and other trace elements in breads from rice and maize cultivated in a seleniferous area of Punjab (India).

The objective of the study was to assess selenium and other elements levels in Indian Roti bread from Se-rich maize and rice using inductively coupled plasma mass-spectrometry. Se levels in Roti bread from Se-rich maize and rice exceeded those in the control samples by a factor of more than 594 and 156, respectively. Using Se-enriched maize increased bread Co, Cr, Mn, Mo, and Zn content, whereas Fe and I levels were reduced. In Se-rich rice-based bread a decrease in Co, Cr, Cu, Fe, I, Mo, and Zn contents was observed. Daily consumption of Se-rich maize and rice bread (100 g) could account for 5.665% and 4.309% from recommended dietary allowance, also exceeding the upper tolerable levels by a factor of 7.8 and 5.9, respectively. Therefore, Roti bread from both Se-rich maize and rice may be considered as an additional source of selenium. At the same time, regular intake of Se-rich grains and its products including breads may cause adverse health effects even after a few days and should be regularly monitored in order to prevent Se overload and toxicity.

Selenium, Zinc, Chromium, and Vanadium Levels in Serum, Hair, and Urine Samples of Obese Adults Assessed by Inductively Coupled Plasma Mass Spectrometry.

The objective of this study was to investigate of selenium (Se), zinc (Zn), chromium (Cr), and vanadium (V) levels in blood serum, hair, and urine of adult obese patients. A total of 199 lean and 196 obese subjects were enrolled in the study. Serum, hair, and urinary metal and metalloid analysis were performed by inductively coupled plasma mass spectrometry at NexION 300D (PerkinElmer Inc., USA). The results established that obese subjects were characterized by 47% and 30% lower serum Cr and V levels compared with controls, respectively, whereas serum Se levels exceeded control values by 9%. In contrast, hair Cr, Se, and V content in obese subjects exceeded the control values by 51%, 21%, and 50%, respectively. In turn, hair Zn levels were found to be significantly lower by 11% compared with the lean control values. In urine, the levels of V and Zn were found to be 30% and 18% higher in obese patients. Prevalence of hypertension in obese subjects was associated with a trend for impaired Se and Zn levels. In a regression model adjusted for age, gender, hypertension, atherosclerosis, and glucose intolerance, serum Cr, V, and hair Zn were inversely associated with body mass index (BMI), whereas hair Se was considered as the positive predictor. Our data allow proposing that the observed alterations may at least partially contribute to metabolic disturbances in obesity. In turn, monitoring of Se exposure in a well-nourished adult population is required to reduce its potential contribution to obesity.

Relationship Between Elevated Hair Mercury Levels, Essential Element Status, and Metabolic Profile in Overweight and Obese Adults.

The objective of the present study was to evaluate hair essential and trace element levels and metabolic risk markers in overweight and obese subjects in relation to body mercury burden. According to 2 × 2 factorial design a total of 440 adults were distributed to four groups: (i) low-Hg normal-weight subjects (n = 114); (ii) high-Hg normal weight subjects (n = 113); (iii) low-Hg overweight (BMI > 25) subjects (n = 110); (iv) high-Hg overweight (BMI > 25) subjects (n = 110). Hg-exposed groups consisted of subjects characterized by frequent seafood consumption (> 4 times/week) subsequently evaluated by hair analysis (> 0.58 µg/g). Dietary-exposed subjects were characterized by a more than 3-fold higher hair Hg content irrespectively of body weight values. Both low-Hg and high-Hg overweight subjects were characterized by significantly higher ALT activity, as well as elevated serum glucose, LDL, and triglyceride levels as compared to the respective groups of normal weight subjects. High Hg body burden had a more significant effect on metabolic parameters in overweight and obese adults. Particularly, high-Hg overweight subjects were characterized by significantly higher serum creatinine and uric acid levels, as well as increased GGT and CK activity as compared to low-Hg overweight counterparts. In addition, hair Mg, Mn, and Sr content in high-Hg overweight subjects was significantly lower than that in low-Hg normal weight and overweight examinees. In turn, high Hg levels in overweight subjects were associated with significantly higher hair Se and Zn levels when compared to unexposed overweight adults. Generally, the obtained data demonstrate that increased hair Hg levels in overweight and obese subjects is associated with adverse metabolic profile. It is proposed that observed metabolic alterations may be at least partially mediated by Hg-associated disturbances in essential trace element and mineral metabolism.

Serum trace element and amino acid profile in children with cerebral palsy.

BACKGROUND: The existing data demonstrate that both trace elements and amino acids play a significant role in neurodevelopment and brain functioning. Certain studies have demonstrated alteration of micronutrient status in children with cerebral palsy, although multiple inconsistencies exist. THE OBJECTIVE: of the present study was to assess serum trace element and mineral, as well as amino acid levels in children with cerebral palsy. METHODS: 71 children with cerebral palsy (39 boys and 32 girls, 5.7 ±â€¯2.3 y.o.) and 84 healthy children (51 boys and 33 girls, 5.4 ±â€¯2.3 y.o.) were enrolled in the present study. Serum trace element and mineral levels were assessed using inductively-coupled plasma mass-spectrometry (ICP-MS). Amino acid profile was evaluated by means of high-pressure liquid chromatography (HPLC). RESULTS: Children with cerebral palsy are characterized by significantly lower Cu and Zn levels by 6% and 8%, whereas serum I concentration exceeded the control values by 7%. A tendency to increased serum Mn and Se levels was also observed in patients with cerebral palsy. Serum citrulline, leucine, tyrosine, and valine levels were 15 %, 23 %, 15 %, and 11 % lower than those in healthy controls. Nearly twofold lower levels of serum proline were accompanied by a 44 % elevation of hydroxyproline concentrations when compared to the control values. In multiple regression model serum I, Zn, and hydroxyproline levels were found to be independently associated with the presence of cerebral palsy. Correlation analysis demonstrated a significant correlation between Cu, Mn, Se, I, and Zn levels with hydroxyproline and citrulline concentrations. CONCLUSION: The observed alterations in trace element and amino acid metabolism may contribute to neurological deterioration in cerebral palsy. However, the cross-sectional design of the study does not allow to estimate the causal trilateral relationships between cerebral palsy, altered trace element, and amino acid metabolism.

Sulfhydryl groups as targets of mercury toxicity.

The present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. In vivo, Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg2+, CH3Hg+, C2H5Hg+, C6H5Hg+) protein. At the Cys34 residue, Hg2+ binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys196), thioredoxin reductase (TrxR) (Cys497) activity, as well as limiting GSH (GS-HgCH3) and Trx (Cys32, 35, 62, 65, 73) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload.

The role of glutathione redox imbalance in autism spectrum disorder: A review.

The role of glutathione in autism spectrum disorder (ASD) is emerging as a major topic, due to its role in the maintenance of the intracellular redox balance. Several studies have implicated glutathione redox imbalance as a leading factor in ASD, and both ASD and many other neurodevelopmental disorders involve low levels of reduced glutathione (GSH), high levels of oxidized glutathione (GSSG), and abnormalities in the expressions of glutathione-related enzymes in the blood or brain. Glutathione metabolism, through its impact on redox environment or redox-independent mechanisms, interferes with multiple mechanisms involved in ASD pathogenesis. Glutathione-mediated regulation of glutamate receptors [e.g., N-methyl-d-aspartate (NMDA) receptor], as well as the role of glutamate as a substrate for glutathione synthesis, may be involved in the regulation of glutamate excitotoxicity. However, the interaction between glutathione and glutamate in the pathogenesis of brain diseases may vary from synergism to antagonism. Modulation of glutathione is also associated with regulation of redox-sensitive transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) and downstream signaling (proinflammatory cytokines and inducible enzymes), thus providing a significant impact on neuroinflammation. Mitochondrial dysfunction, as well as neuronal apoptosis, may also provide a significant link between glutathione metabolism and ASD. Furthermore, it has been recently highlighted that glutathione can affect and modulate DNA methylation and epigenetics. Review analysis including research studies meeting the required criteria for analysis showed statistically significant differences between the plasma GSH and GSSG levels as well as GSH:GSSG ratio in autistic patients compared with healthy individuals (P = 0.0145, P = 0.0150 and P = 0.0202, respectively). Therefore, the existing data provide a strong background on the role of the glutathione system in ASD pathogenesis. Future research is necessary to investigate the role of glutathione redox signaling in ASD, which could potentially also lead to promising therapeutics.

Magnesium Status in Children with Attention-Deficit/Hyperactivity Disorder and/or Autism Spectrum Disorder.

OBJECTIVE: The objective of this study was to assess serum, hair, and urinary magnesium (Mg) levels in children with attention-deficit/ hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and both ASD and ADHD to reveal potential interactive effects. METHODS: A total of 148 boys aged 4-9 years old were enrolled in this study, including 44 children with ADHD, 40 pediatric patients with ASD, 32 patients with both ADHD and ASD, as well as 32 healthy neurotypical children. Hair, serum, and urinary Mg levels were assessed using inductively-coupled plasma mass spectrometry (ICP-MS). Laboratory quality control was performed using certified reference materials of human hair, plasma, and urine. RESULTS: No significant group difference in serum Mg levels was observed. Mg content in hair was found to be reduced in children with ADHD and ADHD+ASD compared to that in healthy controls by 11% and 15%, respectively. Urinary Mg levels in children with ADHD+ASD exceeded the control, ADHD, and ASD values by 51, 76, and 65%, respectively. Factorial analysis revealed significant contribution of ADHD to hair and urinary Mg levels. Multiple regression analysis demonstrated that hair and urinary Mg levels were considered as significant predictors of neurodevelopmental disorder complexity. CONCLUSION: We propose that impaired Mg status may provide a link between ADHD and ASD.

The impact of manganese on neurotransmitter systems.

BACKGROUND: Manganese (Mn) is a metal ubiquitously present in nature and essential for many living organisms. As a trace element, it is required in small amounts for the proper functioning of several important enzymes, and reports of Mn deficiency are indeed rare. METHODS: This mini-review will cover aspects of Mn toxicokinetics and its impact on brain neurotransmission, as well as its Janus-faced effects on humans and other animal's health. RESULTS: The estimated safe upper limit of intracellular Mn for physiological function is in anarrow range of 20-53 µM.Therefore, intake of higher levels of Mn and the outcomes, especially to the nervous system, have been well documented. CONCLUSION: The metal affects mostly the brain by accumulating in specific areas, altering cognitive functions and locomotion, thus severely impacting the health of the exposed organisms.

Hair trace element concentrations in autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD).

BACKGROUND: The existing data demonstrate that alteration of trace element and mineral status in children with neurodevelopmental disorders including ASD and ADHD. However, comparative analysis of the specific patterns of trace element and mineral metabolism in children with ASD and ADHD was not performed. Therefore, the primary objective of the present study was to assess hair trace element and mineral levels in boys with ADHD, ASD, as well as ADHD with ASD. METHODS: Boys with ADHD (n = 52), ASD (n = 53), both ADHD and ASD (n = 52), as well as neurotypical controls (n = 52) were examined. Hair analysis was performed using inductively-coupled plasma mass-spectrometry. RESULTS: The obtained data demonstrate that hair Co, Mg, Mn, and V levels were significantly reduced in children with ADHD and ASD, and especially in boys with ADHD + ASD. Hair Zn was found to be reduced by 20% (p = 0.009) only in children with ADHD + ASD as compared to healthy controls. Factor analysis demonstrated that ASD was associated with significant alteration of hair Co, Fe, Mg, Mn, and V levels, whereas impaired hair Mg, Mn, and Zn content was also significantly associated with ADHD. In regression models hair Zn and Mg were negatively associated with severity of neurodevelopmental disorders. The revealed similarity of trace element and mineral disturbances in ASD and ADHD may be indicative of certain similar pathogenetic features. CONCLUSION: The obtained data support the hypothesis that trace elements and minerals, namely Mg, Mn, and Zn, may play a significant role in development of both ADHD and ASD. Improvement of Mg, Mn, and Zn status in children with ASD and ADHD may be considered as a nutritional strategy for improvement of neurodevelopmental disturbances, although clinical trials and experimental studies are highly required to support this hypothesis.

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity.

Selenium (Se) homeostasis is tightly related to carbohydrate and lipid metabolism, but its possible roles in obesity development and in adipocyte metabolism are unclear. The objective of the present study is to review the current data on Se status in obesity and to discuss the interference between Se and selenoprotein metabolism in adipocyte physiology and obesity pathogenesis. The overview and meta-analysis of the studies on blood Se and selenoprotein P (SELENOP) levels, as well as glutathione peroxidase (GPX) activity in obese subjects, have yielded heterogenous and even conflicting results. Laboratory studies demonstrate that Se may modulate preadipocyte proliferation and adipogenic differentiation, and also interfere with insulin signaling, and regulate lipolysis. Knockout models have demonstrated that the selenoprotein machinery, including endoplasmic reticulum-resident selenoproteins together with GPXs and thioredoxin reductases (TXNRDs), are tightly related to adipocyte development and functioning. In conclusion, Se and selenoproteins appear to play an essential role in adipose tissue physiology, although human data are inconsistent. Taken together, these findings do not support the utility of Se supplementation to prevent or alleviate obesity in humans. Further human and laboratory studies are required to elucidate associations between Se metabolism and obesity.

Streptozotocin (STZ)-Induced Diabetes Affects Tissue Trace Element Content in Rats in a Dose-Dependent Manner.

The objective of the present study was investigation of tissue trace element distribution in a streptozotocin model of DM1 in rats. DM1 was modeled in 2-month-old male Wistar rats (n = 30) using intraperitoneal injection of 45 mg/kg b.w. (STZ1) and 55 mg/kg b.w. streptozotocin (STZ2), whereas control animals were injected with physiological saline. The rats were subjected to oral glucose tolerance test (OGTT) and HbA1c level assessment at day 14. At day 30, blood serum, liver, kidney, and heart samples were collected for tissue trace element assessment using inductively coupled plasma mass spectrometry (ICP-MS). STZ-treated rats were characterized by lack of significant weight gain and elevated HbA1c and blood glucose levels. ICP-MS analysis demonstrated a dose-dependent accumulation of Cu, Mn, Mo, and Se levels in the liver. Correspondingly, the dose-dependent increase in renal Cu, Mn, V, and Zn levels was significant, whereas the observed trend for kidney V and Mo accumulation was nearly significant. The patterns of trace element content in the myocardium of STZ-exposed rats were quite different from those observed for liver and kidney. Only cardiac Zn content was characterized by a significant decrease. Serum Co, Cr, Cu, Se, V, and Mo levels were characterized by a significant decrease in response to STZ-induced diabetes. Generally, the obtained data demonstrate that diabetes is associated with altered copper, manganese, molybdenum, chromium, and vanadium handling. In turn, only altered Zn status may provide a link to diabetic cardiotoxicity. However, the particular mechanisms of both impaired metal handling in STZ diabetes and their potential anti-diabetic activity require further investigation.

Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson's disease: A pilot study.

BACKGROUND: The objective of this pilot study was to assess iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) status (hair, serum, and urine) and speciation (serum) in Parkinson's disease (PD) patients. METHODS: A pilot study involving a total of 27 subjects (13 PD patients, 14 controls) was performed. Serum, urine, and hair metal content was assessed using ICP-MS. Speciation analysis of Cu, Zn, Fe, and Mn was performed using a hybrid HPLC-ICP-MS system. RESULTS: Group comparisons did not reveal any significant group difference in serum Cu, Zn, Fe, and Mn total metal level between PD patients and controls. Speciation analysis revealed a significant decrease in Cu/ceruloplasmin copper in association with elevation of low-molecular weight species (amino acids)-bound copper. It is proposed that in PD, binding of Cu(II) ions to ceruloplasmin is reduced and free copper ions coordinate with low molecular weight ligands. The level of Mn-albumin complexes in PD patients was more than 4-fold higher as compared to the respective value in the control group. The observed difference may be considered as a marker of redistribution between high and low molecular weight ligands. CONCLUSIONS: Metal speciation is significantly affected in serum of PD-patients. These findings are indicative of the potential role of metal metabolism and PD pathogenesis, although the exact mechanisms of such associations require further detailed studies.

Serum zinc, copper, zinc-to-copper ratio, and other essential elements and minerals in children with attention deficit/hyperactivity disorder (ADHD).

BACKGROUND: Essential trace elements and minerals play a significant role in neurodevelopment. Although certain studies demonstrated impaired essential trace element and mineral status in children with ADHD, the existing data are insufficient. The objective of the present study was to assess serum trace element and mineral levels in children with ADHD. METHODS: Serum trace element and mineral levels in 68 children with ADHD and 68 neurotypical controls were assessed using ICP-MS at NexION 300D (PerkinElmer Inc., USA) equipped with ESI SC-2 DX4 autosampler (Elemental Scientific Inc., USA). RESULTS: Serum Cr, Mg, and Zn levels in children with ADHD were 21 % (p = 0.010), 4 % (p = 0.005), and 7 % (p = 0. 001) lower as compared to the healthy controls, respectively. In turn, serum Cu/Zn values were 11 % higher than those in the control group. Age and gender had a significant impact on serum element levels in ADHD. Particularly, preschool children were characterized by significantly increased Cu (+8 %; p = 0.034), and Cu/Zn (+19 %; p < 0.001) values, whereas serum Zn (-9 %; p = 0.004) level was decreased. In primary school-aged children only 6 % (p = 0.007) lower Mg levels were observed. Both boys and girls with ADHD were characterized by 8 % (p = 0.016) lower serum Zn levels and 10 % (p = 0.049) higher Cu/Zn values when compared to neurotypical girls. Boys with ADHD also had significantly higher Cu/Zn, exceeding the respective control values by 12 % (p = 0.021), predominantly due to a 7 % (p = 0.035) decrease in serum Zn. Serum Mg levels were also found to be significantly lower than those in neurotypical children by 5 % (p = 0.007). In adjusted regression models serum Cr (ß=-0.234; p = 0.009) and Cu/Zn (ß = 0.245; p = 0.029) values were significantly associated with ADHD, respectively. Two-way ANOVA revealed a significant impact of ADHD on Cr, Mg, Zn, and Cu/Zn, whereas age was associated with Cu, I, Mg, Mo, and Cu/Zn, whereas gender accounted only for variability in serum Mn levels. Principal component analysis (PCA) also revealed significant contributions of Mg, Zn, and Cu/Zn values to ADHD variability. CONCLUSIONS: Hypothetically, the observed decrease of essential trace elements, namely Mg and Zn, and elevation of Cu/Zn may significantly contribute to the risk of ADHD or its severity and/or comorbidity.

A Search for Similar Patterns in Hair Trace Element and Mineral Content in Children with Down's Syndrome, Obesity, and Growth Delay.

The objective of the present study was to perform comparative analysis of hair trace element and mineral levels in children with Down's syndrome, growth delay, and obesity in order to reveal common and specific patterns. Hair Zn (14, 7, and 15%), Ca (38%, 24%, and 47%), and Mg (33%, 31%, and 49%) levels in children with Down's syndrome, obesity, and growth delay were lower than the respective control values. At the same time, patients with Down's syndrome and growth delay were characterized by 27% and 21%, as well as 24% and 20% lower hair Co as well as Cu content than healthy examinees. Certain alterations were found to be disease-specific. Particularly, in Down's syndrome children, hair Cr, Fe, and V levels were significantly lower, whereas hair P content exceeded the control values. Obese children were characterized by significantly increased hair Cr content. At the same time, hair Mn and Si levels in children with growth delay were lower as compared with the controls. In regression models, all three studied diseases were considered as negative predictors of hair Cu content. Down's syndrome and growth delay, but not obesity, were inversely associated with hair Co content. Both Down's syndrome and obesity were inversely associated with hair Zn content. Based on the revealed similarities in altered hair element, content it is proposed that deficiency of essential elements may predispose Down's syndrome patients to certain syndrome comorbidities including growth delay and obesity, although further detailed studies are required.

Zinc, copper, and oxysterol levels in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: The present study has the objective to assess the zinc (Zn), copper (Cu), and oxysterols plasma levels in type 1 (DM1) (n = 26) and type 2 (DM2) (n = 80) diabetes patients, as compared to healthy controls (n = 71), in order to testify whether metal levels may have a significant impact on the association between oxysterols and diabetes. METHODS: Plasma trace elements and plasma oxysterols were assessed using atomic absorption spectrometry and LC-MS/MS, respectively. Lifestyle, smoking status, alcohol intake, and drug usage, as well as microvascular complications, were also monitored and reported. RESULTS: The obtained data demonstrated that both DM1 and DM2 patients were characterized by significantly elevated HbA1c, FBG, TC, LDL-C, VLDL-C, and TG levels as compared to controls. Plasma Zn levels and Zn/Cu ratio in DM1 and DM2 patients were about 3- and 2-fold lower than controls. No significant differences in plasma Cu levels were reported. The 7-ketocholesterol (7-kchol) levels in DM1 and DM2 patients exceeded these values in healthy individuals by 2.5 and 5-fold, respectively. Similarly, cholestan-3ß, 5α, 6ß-triol (chol-triol) levels were more than 3- and 6-fold higher when compared to the respective values in non-diabetic controls. In regression models decreased plasma Zn and elevated oxysterol levels were significantly associated with HbA1c and fasting plasma glucose levels, after adjustment for anthropometric and clinical variables, as well as routine biochemical markers. CONCLUSIONS: Plasma Zn concentration is inversely associated with both 7-kchol and chol-triol levels. Assessment of Zn and oxysterol levels may be used both for risk assessment and as targets for the treatment of diabetes mellitus.

The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice.

The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2-3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.