Systemic Essential Metal and Metalloid Levels in Patients with Benign Breast Disease and Breast Cancer.

The objective of the present study is evaluation of serum and hair levels of essential metals and metalloids in women with benign breast disease and breast cancer in order to define similar and distinct patterns that may mediate the link between these pathologies. A total of 310 adult women aged 20-80 years old were enrolled in the present study. Of those, 103 patients had benign (fibrocystic) breast disease, 107 patients had breast cancer (stage II), and 100 women were healthy and with absence of breast pathology. Trace metal and metalloid levels in hair and serum were evaluated by inductively coupled argon plasma mass-spectrometry (ICP-MS). The data demonstrate that breast cancer patients were characterized by significantly higher hair Cr and V levels, as well as reduced Cu and Mn content as compared to both benign breast disease patients and controls. In contrast, serum Cu levels in women with breast cancer exceeded those in the controls and benign breast disease cases. Patients with both benign and malignant breast tumors were characterized by lower serum Mn levels as compared to the control values. Serum Cu/Zn and especially Cu/Mn were found to be significantly increased in cancer patients. Significantly reduced hair and serum Se levels were noted only in women with fibrocystic disease. Based on the analysis of two biosamples, it is proposed that malignant breast tumor development is associated with the reduction of systemic Mn and Zn levels, and a concomitant elevation of Cu concentrations.

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.

Serum levels of copper, iron, and manganese in women with pregnancy, miscarriage, and primary infertility.

BACKGROUND: Iron (Fe), copper (Cu), and manganese (Mn) play a significant role in female reproduction and fetal development. At the same time, high levels of metals may exert toxic effects. Correspondingly, both excess and deficiency of essential trace elements were shown to be associated with female infertility and adverse pregnancy outcome, although the existing data are rather contradictory. Therefore, the objective of the present study was to reveal the potential role of altered iron, copper, and manganese status in female reproductive health problems through assessment of serum metal levels in healthy non-pregnant and pregnant women, as well as patients with miscarriage and primary infertility. METHODS: A total of 150 healthy controls, 169 pregnant women (II trimester of pregnancy), 75 women with miscarriage, and 91 patients with primary infertility were enrolled. Serum metal levels were assessed using ICP-MS. RESULTS: Pregnant women are characterized by a significant increase in serum Cu an Mn levels by 40% (p < 0.001) and 16% (p = 0.043) as compared to the controls, respectively. Serum Cu levels in women with miscarriage and infertility were 30% and 35% lower than those in pregnant women (p < 0.001). No significant difference in serum iron levels were observed between the control and pregnant women. Women who had miscarriage were characterized by 13% (p = 0.042) higher serum Fe levels as compared to the pregnant ones. Multiple regression analysis demonstrated that serum copper levels was significantly associated both with pregnancy (ß = 0.436; p < 0.001) and reproductive health problems in women (ß = -0.272; p < 0.001). The latter was improved significant after adjustment for serum Fe and Mn levels, age, and BMI (ß = -0.431; p < 0.001). The model incorporating serum Cu, Fe, Mn, and anthropometric parameters accounted for 23% of variability in reproductive status (p < 0.001). CONCLUSIONS: It is proposed that the lack of pregnancy-associated increase in metal levels in miscarriage and infertility may be indicative of at least partial role of metal insufficiency in impaired pregnancy and reproductive function in general. However, detailed clinical studies as well as experimental investigations are required for assessment of the potential causes and mechanisms of the observed associations.

Hair concentration of essential trace elements in adult non-exposed Russian population.

Appropriate reference values of hair trace element content are required for correct interpretation of biomonitoring data. The primary objective of the current study was to estimate the reference values of selected essential trace elements in hair of adult Russian population. Involved in current investigation were 7256 occupationally non-exposed adults aged from 20 to 60 years and living in the European part of Russia. Occipital hair essential metal and metalloid (Co, Cr, Cu, Fe, Mn, Se, V, Zn) content was estimated using inductively coupled plasma mass spectrometry. The reference ranges were calculated in accordance with the International Union of Pure and Applied Chemistry (IUPAC) recommendations. Women were characterized by 55, 18, 58, and 7% higher values of hair Co, Cu, Mn, and Zn content as compared to the values observed in men. At the same time, hair Cr, Fe, Se, and V concentration in men significantly exceeded the respective female values by 65, 13, 20, and 56%. Consequently, the reference ranges of essential hair trace elements content should be separately calculated for both men and women. The obtained reference ranges for hair Co, Cr, Cu, Fe, Mn, Se, V, and Zn in men were 0.11-0.67, 0.007-0.045, 10.4-22.6, 11.1-40.5, 0.24-1.05, 0.089-0.480, 0.014-0.083, and 125.7-262.8 µg/g, respectively. The respective values estimated for women were 0.06-0.40, 0.011-0.085, 12.1-44.5, 8.9-25.6, 0.32-2.05, 0.094-0.504, 0.010-0.056, and 140.0-315.1 µg/g. The reference ranges for hair Co (0.07-0.50), Cr (0.009-0.073), Cu (11.8-29.2), Fe (9.6-31.5), Mn (0.29-1.76), Se (0.093-0.482), V (0.011-0.069), and Zn (134.7-301.9) content (µg/g) in the general cohort were also calculated.

Reference values of hair toxic trace elements content in occupationally non-exposed Russian population.

A total of 5908 occupationally non-exposed adults (4384 women and 1524 men) living in Moscow and Moscow region were involved in the current investigation. Hair Al, As, Be, Bi, Cd, Hg, Li, Ni, Pb, Sn, and Sr content was estimated by inductively-coupled plasma mass spectrometry using NexION 300D. Men are characterized by significantly higher hair Al, As, Cd, Hg, Li, and Pb content. At the same time, hair levels of Bi, Ni, Sn, and Sr were significantly higher in women. Consequently, the reference ranges were estimated for male, female, and general cohort as coverage intervals in accordance with IUPAC recommendations.