TY - JOUR AB - BACKGROUND: The validity of biomarkers to estimate exposure to selenium (Se) species and selenoproteins in the central nervous system (CNS) is not well studied. METHODS: Among 83 Italian participants with mild cognitive impairment, we estimated total Se and single Se species concentrations in paired serum and cerebrospinal fluid (CSF) samples using anion exchange chromatography-inductively coupled plasma-dynamic reaction cell-mass spectrometry. In each matrix (serum and CSF), we assessed associations between: 1) paired Se species and 2) total Se and Se species. RESULTS: The distribution of Se exposure was comparable to that generally found in European populations. We found few consistent patterns for most biomarkers, including total Se and some Se species. An exception was a positive association between the two matrices for selenoprotein-P-bound Se and the inorganic Se form selenate, and an unexpected inverse association for glutathione-peroxidase-bound Se. Total Se was positively associated with some Se species but inversely associated with other Se species in serum, while in CSF the positive association was stronger and more consistent across various Se species. CONCLUSIONS: Concentrations of total Se and single Se species in serum were not strongly correlated with their respective concentrations in CSF, the gold standard to estimate CNS exposure. Furthermore, total Se and selected Se species showed consistent positive correlations within CSF but not serum. Our results suggest that relying on serum Se concentrations to assess CNS exposure can introduce error in human studies. AU - Urbano, T.* AU - Filippini, T.* AU - Cardoso, B.R.* AU - Wise, L.A.* AU - Zamboni, G.* AU - Chiari, A.* AU - Vinceti, G.* AU - Tondelli, M.* AU - Marti, A.* AU - Malavolti, M.* AU - Vinceti, M.* AU - Michalke, B. C1 - 75645 C2 - 58218 CY - Hackerbrucke 6, 80335 Munich, Germany TI - Biomarkers of total selenium and selenium species in paired serum and cerebrospinal fluid samples. JO - J. Trace Elem. Med. Biol. VL - 92 PB - Elsevier Gmbh PY - 2025 SN - 0946-672X ER - TY - JOUR AU - Wessels, I. AU - Fischer, H.J.* C1 - 69850 C2 - 55282 CY - Hackerbrucke 6, 80335 Munich, Germany TI - ICTEM 2022 special issue: The versatile aspects of trace elements and metals The diverse world of trace element and metal research. JO - J. Trace Elem. Med. Biol. VL - 83 PB - Elsevier Gmbh PY - 2024 SN - 0946-672X ER - TY - JOUR AB - INTRODUCTION: Selenium (Se) is a trace element with different toxicological and nutritional properties according to its chemical forms. Among the wide range of selenium species, human serum albumin-bound selenium (Se-HSA) has still uncertain composition in terms of organic or inorganic selenium species. This study aimed at investigating the relation between Se-HSA levels with total selenium and the specific organic and inorganic selenium species. METHODS: We determined levels of total selenium and selenium species in serum of participants enrolled in two populations of the Emilia-Romagna region, in Northern Italy. Anion exchange chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry was used as quantification method. Correlations between Se-HSA and the other selenium compounds were analyzed using linear regression and restricted cubic spline regression models, adjusted for potential confounders. RESULTS: The first cohort comprised 50 participants (men/women: 26/24) with median (interquartile range, IQR) age 50 (55-62) years, while the second was composed of 104 participants (M/W: 50/54), median (IQR) age 48 (44-53) years. Median (IQR) levels of total selenium were 118.5 (109-136) µg/L and 116.5 (106-128) µg/L, respectively, while Se-HSA was 25.5 µg/L (16.2-51.5) and 1.1 (0.03-3.1) µg/L, respectively. In both populations, Se-HSA was positively associated with inorganic selenium species. Conversely, Se-HSA was inversely associated with organic selenium, especially with selenoprotein P-bound-Se (Se-SELENOP) and less strongly with selenomethionine-bound-Se (Se-Met), while the relation was null or even positive with other organic species. Evaluation of non-linear trends showed a substantially positive association with inorganic selenium, particularly selenite, until a concentration of 30 µg/L, above which a plateau was reached. The association with Se-SELENOP was inverse and strong until 100 µg/L, while it was almost null at higher levels. CONCLUSIONS: Our findings seem to indicate that Se-HSA incorporates more selenium when circulating levels of inorganic compounds are higher, thus supporting its mainly inorganic nature, particularly at high circulating levels of selenite. AU - Filippini, T.* AU - Urbano, T.* AU - Grill, P. AU - Malagoli, C.* AU - Ferrari, A.* AU - Marchesi, C.* AU - Natalini, N.* AU - Michalke, B. AU - Vinceti, M.* C1 - 68063 C2 - 54541 CY - Hackerbrucke 6, 80335 Munich, Germany TI - Human serum albumin-bound selenium (Se-HSA) in serum and its correlation with other selenium species. JO - J. Trace Elem. Med. Biol. VL - 79 PB - Elsevier Gmbh PY - 2023 SN - 0946-672X ER - TY - JOUR AB - PURPOSE: The therapeutic success of minimal invasive glaucoma surgery (MIGS) is challenging due to many factors including fibrotic or occlusive events. Recent clinical data show sudden peaks of intraocular pressure (IOP) in the postoperative care of glaucoma patients after suprachoroidal draining stents. Yet, the reasons for the IOP peaks are speculative. As a link between trace elements and fibrosis had been previously observed in systemic disorders, the present study aimed to investigate the impact of trace elements on the therapeutic success of the suprachoroidal draining stents in patients with open-angle glaucoma (OAG). MATERIAL AND METHODS: An analysis of a prospective single-center study was done: fifty-five eyes of patients with OAG (29 female, 26 male) underwent Cypass Micro-Stent implantation either as a stand-alone procedure or combined with cataract surgery. All patients underwent pre-operatively an ophthalmological examination which included slit lamp biomicroscopy and fundoscopy. IOP was measured by Goldmann applanation tonometry. Functional and morphometric data were assessed by Octopus G1-perimetry, which included measurement of retinal nerve fiber layer thickness (Spectralis OCT). Data of the patients' follow-ups were recorded during 18 months post-operatively. The therapeutic success of CyPass Micro-Stent was classified as 'success' (IOP reduction ≥20% compared to a pre-operative baseline without any medication), 'qualified success' (IOP reduction ≥20 % with same or lower additional eye medication), and 'failure' (IOP reduction ≤20 % or additional surgical treatment necessary). Aqueous humour was extracted once during surgery for analysis of the level of 14 trace elements: Copper (Cu), Cadmium (Cd), Cobalt (Co), Chromium (Cr), Iron (Fe), Lithium (Li), Magnesium (Mg), Manganese (Mn), Phosphorus (P), Lead (Pb), Titanium (Ti), Uranium (U), Vanadium (V), and Zinc (Zn). Analysis of the trace elements was done using an ELEMENT 2, ICP-sf-MS instrument (Thermo-Fisher Scientific, Bremen, Germany). Analysis of levels of trace elements was done across the patients' groups of the three subclasses of therapeutic success. Statistical investigations for substantial differences were conducted using the method of least squares to fit general linear models and mixed models. The last one for the repeated measurements of IOP. RESULTS: Levels of Mg were significantly lower one month postoperatively in the success group (LS-Mean 1.30 mg/L) compared to the qualified success group (LS-Mean 1.22 mg/L; p-value = 0.04). Fe was significantly increased in the failure group (LS-Mean 2.07 µg/L) compared to the qualified success group (LS-Mean 1.64 µg/L; p-value = 0.019) after 3 months of follow-up. Additionally, Fe levels were significantly lower in the success group (LS-Mean 1.47 µg/L) compared to the failure cohort (LS-Mean 2.07 µg/L; p-value = 0.009). After a period of 18 months, significantly higher levels of Mn were observed in the success group (LS-Mean 1.24 µg/L) than in the failure group (LS Mean 0.30 µg/L, p-value = 0.019). CONCLUSION: The present data might suggest that trace elements can influence therapeutic success of suprachoroidal draining devices postoperatively and thus offer first hints for potential novel therapeutic options. AU - Wörn, M.* AU - Lämmer, R.* AU - Lucio, M. AU - Michalke, B. AU - Rühl, E.* AU - Hohberger, B.* C1 - 67917 C2 - 54395 CY - Hackerbrucke 6, 80335 Munich, Germany TI - The influence of trace elements on the therapeutic success of suprachoroidal draining devices. JO - J. Trace Elem. Med. Biol. VL - 78 PB - Elsevier Gmbh PY - 2023 SN - 0946-672X ER - TY - JOUR AB - Background: Selective inhibitory effects of rhenium(I)-diselenoether (Re-diSe) were observed in cultured breast malignant cells. They were attributed to a decrease in Reactive Oxygen Species (ROS) production. A concomitant decrease in the production of Transforming Growth Factor-beta (TGFβ1), Insulin Growth Factor 1 (IGF1), and Vascular Endothelial Growth Factor A (VEGFA) by the malignant cells was also observed. Aim: The study aimed to investigate the anti-tumor effects of Re-diSe on mice bearing 4T1 breast tumors, an experimental model of triple-negative breast cancer, and correlate them with several biomarkers. Material and methods: 4T1 mammary breast cancer cells were orthotopically inoculated into syngenic BALB/c Jack mice. Different doses of Re-diSe (1, 10, and 60 mg/kg) were administered orally for 23 consecutive days to assess the efficacy and toxicity. The oxidative status was evaluated by assaying Advanced Oxidative Protein Products (AOPP), and by the dinitrophenylhydrazone (DNPH) test in plasma of healthy mice, non-treated tumor-bearing mice (controls), treated tumor-bearing mice, and tumors in all tumor-bearing mice. Tumor necrosis factor (TNFα), VEGFA, VEGFB, TGFβ1, Interferon, and selenoprotein P (selenoP) were selected as biomarkers. Results: Doses of 1 and 10 mg/kg did not affect the tumor weights. There was a significant increase in the tumor weights in mice treated with the maximum dose of 60 mg/kg, concomitantly with a significant decrease in AOPP, TNFα, and TGFβ1 in the tumors. SelenoP concentrations increased in the plasma but not in the tumors. Conclusion: We did not confirm the anti-tumor activity of the Re-diSe compound in this experiment. However, the transplantation of the tumor cells did not induce an expected pro-oxidative status without any increase of the oxidative biomarkers in the plasma of controls compared to healthy mice. This condition could be essential to evaluate the effect of an antioxidant drug. The choice of the experimental model will be primordial to assess the effects of the Re-diSe compound in further studies. AU - Collery, P.* AU - Lagadec, P.* AU - Krossa, I.* AU - Cohen, C.* AU - Antomarchi, J.* AU - Varlet, D.* AU - Lucio, M. AU - Guigonis, J.M.* AU - Scimeca, J.C.* AU - Schmid-Antomarchi, H.* AU - Schmid-Alliana, A.* C1 - 64122 C2 - 52086 TI - Relationship between the oxidative status and the tumor growth in transplanted triple-negative 4T1 breast tumor mice after oral administration of rhenium(I)-diselenoether. JO - J. Trace Elem. Med. Biol. VL - 71 PY - 2022 SN - 0946-672X ER - TY - JOUR AB - 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. AU - Ajsuvakova, O.P.* AU - Tinkov, A.A.* AU - Willkommen, D.* AU - Skalnaya, A.A.* AU - Danilov, A.B.* AU - Pilipovich, A.A.* AU - Aschner, M.* AU - Skalny, A.V.* AU - Michalke, B. AU - Skalnaya, M.G.* C1 - 57460 C2 - 47803 CY - Hackerbrucke 6, 80335 Munich, Germany TI - Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson's disease: A pilot study. JO - J. Trace Elem. Med. Biol. VL - 59 PB - Elsevier Gmbh PY - 2020 SN - 0946-672X ER - TY - JOUR AB - Background: Our survey has found eleven plants that have being consumed for traditional treatment of diabetes mellitus, particularly in Saudi Arabia and generally in many countries across the world. The literature reported about trace elements such as Cr and Mn positively affecting diabetes mellitus. The aim of this work is to determine the total, accessible element species, and protein-fraction contents of Cr and Mn in the edible parts of those plants. Methods: The total contents of Mn were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES), while the total contents of Cr was determined by ICP-sector field (sf)-mass spectrometry (MS) due to lower concentration. The protein-fraction contents were determined in accessible element species by size-exclusion chromatography (SEC)-ICP-MS. Results and discussion: The separation was successfully carried out to quantify Cr and Mn bound up to 11 protein fractions. The examined plants recorded wide ranges of total contents (Cr 44.7–1880.0 μg/kg and Mn 3.7–59.0 mg/kg) and accessible element species contents (Cr 0.93–29.40 μg/kg and Mn 0.82–35.85 mg/kg). Also wide ranges of percentages of accessible element species contents to total contents of Cr (0.65–4.21%) and Mn (5.43–68.42%) were obtained. The hazardous indices of both trace elements Cr and Mn for all examined plants consumed by both children and adults were all < 1, indicating no probability of health risk to occur. Moreover, Cr as carcinogen element reported no probability of cancer risk to occur from the consumption of all examined plants. Irrespective of plant species, Cr was quantified in all SEC fractions (mainly protein fractions), with the exception of 1.9-3.7 kDa, while Mn was quantified in all SEC fractions with the exception of 100–120 and 1.3-3.7 kDa. Nevertheless, the majority of accessible Cr species contents bound to the 10–14 and 0.05–0.40 kDa fractions, while that of Mn bound to 0.05–0.40 kDa fraction. To gather, the benefits of specific plant species in terms of accessible Cr and Mn species contents, in addition to accessible Zn species contents reported in our previous study, Haloxylon Salicornicum, Olea Europaea Momordica and Charantia are recommended to be consumed for traditionally controlling T2DM. AU - Ebrahim, A.M.* AU - Idris, A.M.* AU - Alnajjar, A.O.* AU - Michalke, B. C1 - 60058 C2 - 49199 CY - Hackerbrucke 6, 80335 Munich, Germany TI - Cr and Mn total, accessible species, and protein-fraction contents in plants used for traditional anti-diabetes treatment. JO - J. Trace Elem. Med. Biol. VL - 62 PB - Elsevier Gmbh PY - 2020 SN - 0946-672X ER - TY - JOUR AB - Background: The Nutrition Societies of Germany, Austria and Switzerland as the joint editors of the 'D-A-CH reference values for nutrient intake' have revised the reference values for zinc in July 2019.Methods: For infants aged 0 to under 4 months, an estimated value was set based on the zinc intake via breast feeding. For all other age groups, the reference values were calculated using the factorial method considering endogenous zinc losses via intestinal losses, urine, faeces, skin and sweat, semen in men and the additional zinc requirements to build up body weight in children and adolescents as well as in pregnant women. Due to the strong influence of phytate intake on zinc absorption, the recommendations for the intake of zinc for adults are derived depending on low (0.5 mmol/day, corresponding to 330 mg/day), moderate (1.0 mmol/day, corresponding to 660 mg/day) and high (1.5 mmol/day, corresponding to 990 mg/day) phytate intake. The reference values for lactating women take into account the zinc loss via breast milk.Results and conclusion: For adults, pregnant and lactating women, the recommended intake values for zinc range from 7 mg/day to 16 mg/day, depending on sex and dietary phytate intake. AU - Haase, H.* AU - Ellinger, S.* AU - Linseisen, J. AU - Neuhäuser-Berthold, M.* AU - Richter, M.* C1 - 59052 C2 - 48589 CY - Hackerbrucke 6, 80335 Munich, Germany TI - Revised D-A-CH-reference values for the intake of zinc. JO - J. Trace Elem. Med. Biol. VL - 61 PB - Elsevier Gmbh PY - 2020 SN - 0946-672X ER - TY - JOUR AB - Background: The aim of the study was to investigate if speciation analysis by liquid chromatography coupled to mass spectrometry could be used to detect organic and inorganic binding forms of selenium in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) and age-matched control subjects (AMC). Methods: PD patients and control subjects were enrolled from three different neurological departments. CSF samples were collected according to standardized biomarker protocols and subjected to inductively coupled plasma mass spectrometry (ICP-MS) for total selenium determination and ion exchange chromatography (IEC) hyphenated to ICP-MS for selenium speciation analysis. Results: 75 PD patients and 68 age-matched controls were enrolled for speciation analysis. 8 different species could be detected, but only selenoprotein P (SELENOP), human serum albumin-bound Se (Se-HSA), selenomethionine (Se-Met) and an unidentified Se-compound (U2) presented with more than 50% values above the limit of quantification, without showing significant differences between both groups (p > 0.05). The Se-HSA / Se-Met ratio yielded a significant difference between PD and AMC (p = 0.045). The inorganic species Se-IV and Se-VI were only detectable in a minor part of PD and AMC samples. A highly significant correlation between total selenium levels and SELENOP (PD p < 0.0001; AMC p < 0.0001) and Se-HSA (PD p < 0.0001; AMC p < 0.0001) could be demonstrated, respectively. Conclusions: Speciation analysis yielded new insight into selenium homeostasis in PD but cannot be used to establish a diagnostic biomarker. The small number of detectable values for Se-IV and Se-VI suggests an inferior role of these potentially neurotoxic binding forms in PD pathology in contrast to other neurodegenerative disorders. AU - Maass, F.* AU - Michalke, B. AU - Willkommen, D. AU - Schulte, C.* AU - Tönges, L.* AU - Boerger, M.* AU - Zerr, I.* AU - Bähr, M.* AU - Lingor, P.* C1 - 57008 C2 - 47466 TI - Selenium speciation analysis in the cerebrospinal fluid of patients with Parkinson's disease. JO - J. Trace Elem. Med. Biol. VL - 57 PY - 2020 SN - 0946-672X ER - TY - JOUR AU - Michalke, B. C1 - 57949 C2 - 48009 CY - Hackerbrucke 6, 80335 Munich, Germany TI - Editorial. JO - J. Trace Elem. Med. Biol. VL - 58 PB - Elsevier Gmbh PY - 2020 SN - 0946-672X ER - TY - JOUR AU - Michalke, B. C1 - 60169 C2 - 49822 TI - Editorial. JO - J. Trace Elem. Med. Biol. VL - 58 PY - 2020 SN - 0946-672X ER - TY - JOUR AB - PURPOSE: Glaucoma disease is known as multifactorial. Trace elements seemed to be linked via oxidative stress mediated changes to the complex glaucoma pathophysiology. Thus, it was the aim of this study to investigate serum levels of trace elements in primary open-angle glaucoma patients (POAG). PATIENTS AND METHODS: Peripheral venous blood samples were taken from a total of 40 subjects: 22 primary open-angle glaucoma patients (mean age 58.1 ± 13.9, female 8, male 14) and 18 controls (mean age 38.9 ± 11.6, 6 female 6, male 12). Serum samples of cadmium, cobalt, copper, iron, lead, manganese and zinc were analyzed by Inductively-Coupled-Plasma-Optical Emission Spectrometry (Cu, Fe, Zn) and Inductively-Coupled-Plasma-sectorfield-Mass-Spectrometry (Cd, Co, Mn, Pb, Se). Data were analyzed using ANCOVA and presented as log transformed LS-mean. RESULTS: Patients with POAG had significantly increased serum levels of iron (2.98 ± 0.03 μg/L vs 2.98 ± 0.03 μg/L) when compared to controls, and of cadmium (1.57 ± 0.05 ng/L vs. 1.40 ± 0.06 ng/L) considering the interaction between age and the class variable (control versus POAG). A gender effect was seen for cadmium, cobalt, copper, and iron in controls and POAG patients. Iron concentration was reduced in dependency of age for both genders in normals, however lesser in POAG patients. No difference was seen in serum levels of lead, manganese, and zinc between patients with POAG and controls. CONCLUSION: A significant elevation of serum cadmium and iron levels in POAG patients as well as an additional gender effect of cadmium, cobalt, copper, and iron in normals and POAG patients, may argue for a potential role of these trace elements in the pathogenesis of primary open-angle glaucoma. AU - Fick, A.* AU - Jünemann, A.* AU - Michalke, B. AU - Lucio, M. AU - Hohberger, B.* C1 - 55633 C2 - 46469 SP - 129-134 TI - Levels of serum trace elements in patients with primary open-angle glaucoma. JO - J. Trace Elem. Med. Biol. VL - 53 PY - 2019 SN - 0946-672X ER - TY - JOUR AB - Traceability of metal-glycinate-sulphate complexes (Metal-GLY) in feed requires specific analysis to differentiate complexes from inorganic forms. A previously described method focused on the quantification of Metal-GLY at one single concentration but not on the quantification of free metal ion forms. The objective of this work was to extend the method to quantify both Metal-GLY and free metal ion forms of various metals at low inclusion levels. A 50/50 w/w mix of corn flour and soybean meal was used as feed. Copper-glycinate(Cu-GLY), Manganeseglycinate (Mn-GLY) and Zinc-glycinate (Zn-GLY) complexes (provided by Pancosma SA) were used for in-feed inclusions. The feed metal background concentrations and species repartitions were assessed. Cu-GLY was spiked on feed at levels matching 5, 15 and 45 mg/kg, corresponding to metal concentrations of 1.2, 3.6 and 10.8 mg/kg. Mn-GLY and Zn-GLY were spiked at 15, 45 and 100 mg/kg, corresponding to 3.3, 9.9, 22 mg/kg Mn and 3.9, 11.7, 26mg/kg Zn, respectively. The water soluble fraction of un-supplemented feed contained 0.06 mg/kg Cu, 0.05 mg/kg Mn and 0.12 mg/kg Zn, with 69.5% of Cu, 33.2% of Mn and 24.3% of Zn being present under free metal ions but 30.4% of Cu being present under Cu-GLY, 66.82% of Mn and 75.7% of Zn being present under Mn-GLY and Zn-GLY, respectively. The supplemented feeds at the 3 tested doses, from the lowest to the highest inclusion levels, contained in total respectively: 1.1, 3.05 and 9.06 mg/kg Cu; 2.99, 8.9 and 18.2 mg/kg Mn; 3.72, 10.9 and 23.4 mg/kg Zn. The M-GLY species recovered by analysis within the different supplemented feeds ranged from 76.26 to 89.32% for Cu-GLY, form 94.5 to 98.51% for Mn-GLY and from 76.05 to 98.96% for ZnGLY. These results showed that CE-ICP-MS technique can be used to quantify low doses and to measure metalspecies repartition between Metal-GLY and free metal ions, when included in feeds. For the first time, this study highlighted that the raw materials used contain Metal-GLY compounds. This raises the question of the occurrence of these compounds within the different raw materials used in feed production that could dramatically affect the way to supplement minerals in animal feed. AU - Ionescu, C.* AU - Grill, P. AU - Witte, H. AU - Boigues, C.* AU - Blanchard, A.* AU - Löffler, B. AU - Michalke, B. C1 - 56959 C2 - 47451 CY - Hackerbrucke 6, 80335 Munich, Germany SP - 207-212 TI - Accurate quantification of metal-glycinates-sulphate complexes and free metals in feed by capillary electrophoresis inductively coupled plasma mass spectrometry. JO - J. Trace Elem. Med. Biol. VL - 56 PB - Elsevier Gmbh PY - 2019 SN - 0946-672X ER - TY - JOUR AB - Diabetes mellitus is a chronic metabolic disease caused by insulin deficiency (type I) or dysfunction (type II). Diabetes is a threatening public health concern. It is considered as one of the priority non-communicable diseases, due to its high and increasing incidence, the associated healthcare costs, and threatening medical complications. Two trace elements selenium (Se) and iodine (I) were intensively discussed in the context of diabetic pathology and, possibly, etiology. It seems there is a multilayer involvement of these essential nutrients in glucose tolerance, energy metabolism, insulin signaling and resistance, which are mainly related to the antioxidant selenoenzymes and the thyroid hormones. Other factors might be related to (auto)immunity, protection against endoplasmic reticulum stress, and leptin signaling. The aim of the current review is to evaluate the current understanding of the role of selenium and iodine in diabetes with a focus on the biochemical interplay between the elements, their possible role as biomarkers, and their chemical speciation. Possible impacts from novel analytical techniques related to trace element speciation and isotopic analysis are outlined. AU - Solovyev, N.* AU - Vanhaecke, F.* AU - Michalke, B. C1 - 56728 C2 - 47226 CY - Hackerbrucke 6, 80335 Munich, Germany SP - 69-80 TI - Selenium and iodine in diabetes mellitus with a focus on the interplay and speciation of the elements. JO - J. Trace Elem. Med. Biol. VL - 56 PB - Elsevier Gmbh PY - 2019 SN - 0946-672X ER - TY - JOUR AB - Several human studies imply that the trace element selenium and its species may influence the onset of neurological disease, including Alzheimer's dementia (AD). Nevertheless, the literature is conflicting, with reported associations between exposure and risk in opposite direction, possibly due to biases in exposure assessment. After conducting a cohort study that detected an excess AD risk associated with higher levels of inorganic-hexavalent selenium in subjects with mild cognitive impairment (MCI), we investigated the relation between selenium and AD using a case-control study design. We determined cerebrospinal fluid levels of selenium species in 56 MCI participants already included in the cohort study, considered as referents, and in 33 patients with established AD. AD risk was inversely correlated with inorganic selenium species and with the organic form bound to selenoprotein P. Selenium bound to other organo-selenium species was positively correlated with AD risk, suggesting compensatory selenoprotein upregulation following increased oxidative stress. The finding of an increased AD risk associated with inorganic-hexavalent selenium from the cohort study was not replicated. This case-control study yielded entirely different results than those generated by a cohort study with a partially overlapping participant population, suggesting that case-control design does not allow to reliably assess the role of selenium exposure in AD etiology. This inability appears to be due to exposure misclassification, falsely indicating an etiologic role of selenium deficiency likely due to reverse causation, and involving most selenium species. The case-control design may instead lend insights into the pathologic process underlying disease progression. AU - Vinceti, M.* AU - Michalke, B. AU - Malagoli, C.* AU - Eichmüller, M. AU - Filippini, T.* AU - Tondelli, M.* AU - Bargellini, A.* AU - Vinceti, G.* AU - Zamboni, G.* AU - Chiari, A.* C1 - 55710 C2 - 46465 SP - 154-162 TI - Selenium and selenium species in the etiology of Alzheimer's dementia: The potential for bias of the case-control study design. JO - J. Trace Elem. Med. Biol. VL - 53 PY - 2019 SN - 0946-672X ER - TY - JOUR AB - Purpose: Trace elements might play a role in the complex multifactorial pathogenesis of open-angle glaucoma. The aim of this study was to analyze concentrations of trace elements in aqueous humor samples of patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG). Patients and methods: Thirty-three aqueous humor samples were obtained from patients undergoing cataract surgery: 12 patients with POAG (age 65.3 +/- 10.50, female 8, male 4), 10 patients with PEXG (age 65.9 +/- 11.27, female 6, male 4) and 11 patients without glaucoma (age 69.5 +/- 13.70, female 7, male 4) serving as controls. Aqueous humor levels of cadmium, iron, manganese, cobalt, copper and zinc were measured by Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS). Results: From the statistical evaluation, we observed that patients with POAG had significantly higher aqueous humor levels of zinc (p = 0.006) compared to controls. Increased aqueous humor levels of zinc were also observed in patients with PEXG in relation to control (p = 0.0006). For iron we observed a significantly reduction in PEXG compared to control (p = 0.002) and a significant difference between POAG and PEXG (p = 0.0091). No significant differences were observed in aqueous humor levels of manganese, cobalt, copper, cadmium between glaucoma and control patients. No differences were seen for iron (POAG vs. controls). Analysis of trace element ratios was added. Conclusion: Significant differences in aqueous humor levels of zinc and iron between glaucoma and control patients support the hypothesis that these trace elements are involved in the pathogenesis of open-angle glaucoma. AU - Hohberger, B.* AU - Chaudhri, M.A.* AU - Michalke, B. AU - Lucio, M. AU - Nowomiejska, K.* AU - Schlötzer-Schrehardt, U.* AU - Grieb, P.* AU - Rejdak, R.* AU - Jünemann, A.G.M.* C1 - 52273 C2 - 44142 CY - Jena SP - 150-155 TI - Levels of aqueous humor trace elements in patients with open-angle glaucoma. JO - J. Trace Elem. Med. Biol. VL - 45 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2018 SN - 0946-672X ER - TY - JOUR AB - Purpose: Selenium supplementation was seen to be linked to glaucoma disease in a previous study (Lillico A. JE, Reid M et al. (2002) Selenium Supplementation and Risk of Glaucoma in the NPC trial University of Arizona, Tucson, AZ., Arizona Cancer Center). As aqueous humor levels of selenium seemed to be associated with primary open-angle glaucoma (POAG), the aim of this study was to analyze concentrations of selenium in aqueous humor samples of patients with POAG and pseudoexfoliation glaucoma (PEXG) in comparison to normal samples.Patients and Methods: Thirty-eight aqueous humor samples from patients undergoing cataract surgery were collected: Eleven patients with PEXG (age 65.8 +/- 10.69, female 6, male 5), 12 patients with POAG (age 65.3 +/- 10.50, female 7, male 5) and 15 patients without glaucoma (age 70.9 +/- 12.83, female 10, male 5, controls). Aqueous humor levels of selenium were measured by Flow-Injection-Inductively-Coupled-Plasma-DRC-Mass-Spectrometry (ICP-DRC-MS).Results: Maximum likelihood estimation of the least squares means (LS-means) and the relative 95% confidence limits of selenium aqueous humor levels were 6.90 +/- 1.03 mu g/L (control), 6.74 +/- 1.14 mu g/L (POAG) and 8.25 +/- 1.18 mu g/L (PEXG). The data were modeled using a generalized linear model (GLM) analysis, where selenium was set as dependent variable. The model was corrected for group differences in age and gender. The data show no differences among all the calculated differences between the least square means (LS means), taking in consideration the simultaneous 95% confidence limit and the multiple comparison tests with Tukey-Cramer adjustment. The evaluation of the model disclosed that POAG and PEXG patients had no significantly different aqueous humor selenium concentrations compared to controls and to each other. However, the quantile regression analysis of selenium aqueous humor levels showed differences in quantiles for open-angle glaucoma patients considering age and gender.Conclusion: As no significant difference in aqueous humor concentration of selenium was detected between open-angle glaucoma and controls, however, quantile analysis showed differences in quantiles levels for different age ranges in open-angle glaucoma patients, the trace element selenium seemed to be linked to glaucoma disease, yet not in a major role. AU - Jünemann, A.G.M.* AU - Michalke, B. AU - Lucio, M. AU - Chaudhri, A.* AU - Schlötzer-Schrehardt, U.* AU - Rejdak, R.* AU - Rękas, M.* AU - Hohberger, B.* C1 - 53700 C2 - 44969 CY - Office Jena, P O Box 100537, 07705 Jena, Germany SP - 67-72 TI - Aqueous humor selenium level and open-angle glaucoma. JO - J. Trace Elem. Med. Biol. VL - 50 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2018 SN - 0946-672X ER - TY - JOUR AB - Background: Aluminium is associated with disorders and is the commonly used vaccine adjuvant. Understanding the mechanisms of how Al is transported, metabolized or of its toxicity depends on the knowledge of Al-interactions with bioligands, i.e. Al-species. Al-speciation in serum is difficult because of low concentration and the risk of exogenous Al contamination. Furthermore, Al-measurements may be hampered according to various interferences. This study aims for developing quality controlled protocols for reliable Al- and Al-species determination and for investigating probable differences in Al (-speciation) after Al-containing subcutaneous immunotherapy (SIT).Methods: Sample donors were recruited either for the control group ("class-0", they never had been treated with SIT containing an Al-depot extract) or for the SIT-group ("class-1", they previously had been treated with SIT for insect venom allergy with an Al-depot extract). Blood was drawn for medical reasons and serum prepared. Additionally, some sample donors collected 24-h-urine. They had been informed (and they consented) about the scientific use of their samples. The study was approved by the ethic committee of the "Medical Association Westphalia-Lippe" and of the University of Munster, evaluating the study positively (No. 2013-667-f-S).We applied quality controlled sample preparation and interference-free Al detection by ICP sectorfield-mass spectrometry. Al-species were analysed using size-exclusion-chromatography-ICP-qMS.Findings: Al-concentrations or speciation in urine samples showed no differences between class-0 and class-1. Al-citrate was the main uric Al-species. In serum elevated Al-concentrations were found for both classes, with class-1 samples being significantly higher than class-0 (p = 0.041), but class-0 samples being approximately 10-fold too high compared to reference values from non-exposed persons. We identified gel-monovettes as contamination source. In contamination-free samples from HNO3-prewashed gel-free monovettes (n = 27) there was no difference in the serum Al concentration between the two patient groups (p = 0.669)Interpretation: Thorough cleaning of sample preparation ware and use of gel-free monovettes is decisive for an accurate Al analysis in serum. Without these steps, wrong analysis and wrong conclusions are likely. We conclude that gel-monovettes are unsuitable for blood sampling with subsequent Al-analysis. Whether Al in serum is elevated after SIT treatment containing an Al-depot extract, or not, remains inconclusive as the non-contaminated sample size was small. AU - Michalke, B. AU - Kramer, M.F.* AU - Brehler, R.* C1 - 53082 C2 - 44777 CY - Office Jena, P O Box 100537, 07705 Jena, Germany SP - 178-183 TI - Aluminium (Al) speciation in serum and urine after subcutaneous venom immunotherapy with Al as adjuvant. JO - J. Trace Elem. Med. Biol. VL - 49 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2018 SN - 0946-672X ER - TY - JOUR AB - Wilson disease (WD) is a rare genetic disorder of the copper metabolism leading to systemic copper accumulation, predominantly in the liver. The therapeutic approach in WD patients is the generation of a negative copper balance and the maintenance of copper homeostasis, currently by the use of copper chelators such as D-penicillamine (D-PA). However, in circumstances of delayed diagnosis, poor treatment compliance, or treatment failure, mortality is almost certain without hepatic transplantation. Moreover, even after years of D-PA treatment, high liver copper levels are present in WD patients.We have recently suggested the use of the bacterial peptide Methanobactin (MB), which has an outstanding binding affinity for copper, as potentially efficient and patient-friendly remedy against copper damage in WD. Here we substantiate these findings considerably, by demonstrating a significant removal of copper from liver samples of WD rats upon short, one week only, MB treatments. Using laser ablation-inductively coupled plasma mass spectrometry with a spatial resolution down to 4 pm, we demonstrate that only small copper hotspots remain in MB treated animal livers. We further demonstrate in WD rat liver, seven weeks after the stopped MB treatment, a lower liver copper concentration as compared to untreated control animals. Thus, MB highly efficiently depletes liver copper overload with a sustained therapeutic effect. AU - Müller, J.C.* AU - Lichtmannegger, J. AU - Zischka, H. AU - Sperling, M.* AU - Karst, U.* C1 - 53651 C2 - 44933 CY - Office Jena, P O Box 100537, 07705 Jena, Germany SP - 119-127 TI - High spatial resolution LA-ICP-MS demonstrates massive liver copper depletion in Wilson disease rats upon Methanobactin treatment. JO - J. Trace Elem. Med. Biol. VL - 49 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2018 SN - 0946-672X ER - TY - JOUR AB - Population-based and interventional studies have shown that elevated zinc levels can reduce the progression to advanced age-related macular degeneration. The objective of this study was to assess whether elevated extra cellular zinc has a direct effect on retinal pigment epithelial cells (RPE), by examining the phenotype and molecular characteristics of increased extracellular zinc on human primary RPE cells. Monolayers of human foetal primary RPE cells were grown on culture inserts and maintained in medium supplemented with increasing total concentrations of zinc (0, 75, 100, 125 and 150 mu M) for up to 4 weeks. Changes in cell viability and differentiation as well as expression and secretion of proteins were investigated. RPE cells developed a confluent monolayer with cobblestone morphology and transepithelial resistance (TER) > 200 Omega*cm(2) within 4 weeks. There was a zinc concentration-dependent increase in TER and pigmentation, with the largest effects being achieved by the addition of 125 mu M zinc to the culture medium, corresponding to 3.4 nM available (free) zinc levels. The cells responded to addition of zinc by significantly increasing the expression of Retinoid Isomerohydrolase (RPE65) gene; cell pigmentation; Premelanosome Protein (PMEL17) immunoreactivity; and secretion of proteins including Apolipoprotein E (APOE), Complement Factor H (CFH), and High-Temperature Requirement A Serine Peptidase 1 (HTRA1) without an effect on cell viability. This study shows that elevated extracellular zinc levels have a significant and direct effect on differentiation and function of the RPE cells in culture, which may explain, at least in part, the positive effects seen in clinical settings. The results also highlight that determining and controlling of available, as opposed to total added, zinc will be essential to be able to compare results obtained in different laboratories. AU - Pao, P.-J.* AU - Emri, E.* AU - Abdirahman, S.B.* AU - Soorma, T.* AU - Zeng, H.H.* AU - Hauck, S.M. AU - Thompson, R.B.* AU - Lengyel, I.* C1 - 53225 C2 - 44482 CY - Office Jena, P O Box 100537, 07705 Jena, Germany SP - 184-191 TI - The effects of zinc supplementation on primary human retinal pigment epithelium. JO - J. Trace Elem. Med. Biol. VL - 49 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2018 SN - 0946-672X ER - TY - JOUR AB - Intensive rice-wheat cultivation cycle in Northern belt of India in general and in the State of Punjab in particular results in large volumes of straw and other post-harvest residue annually. The agricultural area, bordering the districts of Nawanshahr and Hoshiarpur, is popularly known as the seleniferous belt of India. The agri-residues, generated in seleniferous region of this state, are observed to contain significantly high concentration of selenium (Se). The present study was aimed to evaluate the Se uptake by different mushroom species: Pleurotus sajorcaju, Pleurotus ostreatus, Pleurotus citrinopileatus, Agaricus bisporus, and Volvariella volvacea, cultivated on Se-rich wheat and paddy straw from the seleniferous region. Wheat (Pleurotus species and A. bisporus) and paddy straw (V. volvacea) was inoculated with the mycelium spawn and left for 7-20 days, depending on the species, to grow. Control mushrooms were grown analogously using the agricultural residues from non-seleniferous area of the State of Punjab. All fruiting bodies were collected and analyzed in triplicate. Se was quantified using inductively coupled plasma sector field mass spectrometry. The Se accumulation was high in all species under study, being the highest in A. bisporus (1396 mu g/g vs. 46.8 mu g/g in controls - dry weight) and V. volvacea (231 mu g/g vs. 3.77 mu g/g - dry weight). The observed biological efficiency and total yield for all mushroom species showed good and unaltered productivity in Se-rich conditions, if compared to the controls. The Se-rich mushrooms can be prospective Se-supplements sourcing and biofortified foods, providing readily bioavailable and accessible Se for the diets deficient of this biologically essential element. AU - Solovyev, N.* AU - Prakash, N.T.* AU - Bhatia, P.* AU - Prakash, R.* AU - Drobyshev, E.* AU - Michalke, B. C1 - 54114 C2 - 45352 CY - Office Jena, P O Box 100537, 07705 Jena, Germany SP - 362-366 TI - Selenium-rich mushrooms cultivation on a wheat straw substrate from seleniferous area in Punjab, India. JO - J. Trace Elem. Med. Biol. VL - 50 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2018 SN - 0946-672X ER - TY - JOUR AB - Major and trace elements may play a role in the diagnosis of diseases. In this study, we investigated the concentration of 26 major and trace elements in the serum by inductively coup led plasma (ICP) - optical emission spectrometry (OES) and ICP-sector field-mass spectrometry (sf-MS). We analyzed the serum from a discovery cohort of 6 bladder cancer (BCa) patients and 12 healthy controls as well as from a validation cohort of 21 BCa patients, 29 non-tumor bladder patients (with acute and chronic inflammation) and 18 healthy controls. Patients were recruited after written consent was obtained at one medical center. Serum was prepared from peripheral blood prior to surgical treatment. Differences in the levels of major and trace elements were determined by at nonparametric Mann-Whitney test and Kruskal-Wallis statistics. In the discovery cohort, we measured significantly increased levels of calcium, mercury, potassium, lithium, nickel, phosphorus and strontium and a significantly decreased level of sodium in BCa patients compared with healthy controls. These findings were reassessed in our validation cohort. We measured significantly increased levels of boron, calcium, cadmium, copper, chromium, lead, lithium, potassium, magnesium, nickel, sulfur, strontium, titan, vanadium and zinc and significantly decreased levels of iron and molybdenum. When we studied the concordance for the discovery and validation cohorts, concentrations of five elements were detected as significantly increased in BCa patients compared with healthy controls: calcium, lithium, potassium, nickel, and strontium. Interestingly, the levels of three elements (calcium, potassium and strontium) were also significantly increased in non-tumor bladder patients compared with healthy controls. But no element was significantly altered between non-tumor bladder patients and BCa patients. In summary, we suggest that determination of the elements calcium, lithium, nickel and strontium in the serum could be a new and promising tool for the early diagnosis of BCa. AU - Wach, S.* AU - Weigelt, K.* AU - Michalke, B. AU - Lieb, V.* AU - Stoehr, R.* AU - Keck, B.* AU - Hartmann, A.* AU - Wullich, B.* AU - Taubert, H.* AU - Chaudhri, A.* C1 - 52716 C2 - 44218 CY - Jena SP - 150-155 TI - Diagnostic potential of major and trace elements in the serum of bladder cancer patients. JO - J. Trace Elem. Med. Biol. VL - 46 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2018 SN - 0946-672X ER - TY - JOUR AB - Background: Parkinson's disease is affecting about 1% of the population above 65 years. Improvements in medicine support prolonged lifetime which increases the total concentration of humans affected by the disease. It is suggested that occupational and environmental exposure to metals like iron (Fe), manganese (Mn), copper (Cu) and zinc (Zn) can influence the risk for Parkinson's disease. These metals play a key role as cofactors in many enzymes and proteins.Methods: In this case-control study, we investigated the Mn-, Fe-, Cu- and Zn-species in cerebrospinal fluid (CSF) by size-exclusion chromatography hyphenated to inductively coupled plasma mass spectrometry (SEC-ICP-MS) and the total concentration of these metals by inductively coupled plasma sector field mass spectrometry (ICP-sf-MS).Results: The investigation of total metal concentration and speciation provided only minor changes, but it produced strong significance for a number of ratios. The analysis revealed a strong change in the ratio between total concentration of Fe and the amino acid-fraction of Cu. This could be observed when analyzing both the respective element concentrations of the fraction (which also depends on individual variation of the total element concentration) as well as when being expressed as percentage of total concentration (normalization) which more clearly shows changes of distribution pattern independent of individual variation of total element concentrations.Conclusion: Speciation analysis, therefore, is a powerful technique to investigate changes in a case-control study where ratios of different species play an important role. AU - Willkommen, D. AU - Lucio, M. AU - Schmitt-Kopplin, P. AU - Gazzaz, M.* AU - Schroeter, M.L.* AU - Sigaroudi, A.* AU - Michalke, B. C1 - 53045 C2 - 44761 CY - Office Jena, P O Box 100537, 07705 Jena, Germany SP - 164-170 TI - Species fractionation in a case-control study concerning Parkinson's disease: Cu-amino acids discriminate CSF of PD from controls. JO - J. Trace Elem. Med. Biol. VL - 49 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2018 SN - 0946-672X ER - TY - JOUR AB - At present, the copper chelator D-penicillamine (DPA) is the first-line therapy of Wilson's disease (WD), which is characterized by an excessive copper overload. Lifelong DPA treatments aim to reduce the amount of detrimental excess copper retention in the liver and other organs. Although DPA shows beneficial effect in many patients, it may cause severe adverse effects. Despite several years of copper chelation therapy, discontinuation of DPA therapy can be linked to a rapidly progressing liver failure, indicating a high residual liver copper load. In order to investigate the spatial distribution of remaining copper and additional elements, such as zinc and iron, in rat and human liver samples after DPA treatment, a high resolution (spotsize of 10 μm) laser ablation-inductively coupled plasma-mass spectrometry (LA‐ICP‐MS) imaging method was applied. Untreated LPP‐/− rats, an established animal model for WD, appeared with a high overall copper concentration and a copper distribution of hotspots distributed over the liver tissue. In contrast, a low (>2-fold decreased) overall copper concentration was detected in liver of DPA treated animals. Importantly, however, copper distribution was highly inhomogeneous with lowest concentrations in direct proximity to blood vessels, as observed using novel zonal analysis. A human liver needle biopsy of a DPA treated WD patient substantiated the finding of an inhomogeneous copper deposition upon chelation therapy. In contrast, comparatively homogenous distributions of zinc and iron were observed. Our study indicates that a high resolution LA‐ICP‐MS analysis of liver samples is excellently suited to follow efficacy of chelator therapy in WD patients. AU - Hachmöller, O.* AU - Zibert, A.* AU - Zischka, H. AU - Sperling, M.* AU - Groba, S.R.* AU - Grünewald, I.* AU - Wardelmann, E.* AU - Schmidt, H.H.J.* AU - Hartmut, H.J.* AU - Karst, U.* C1 - 51299 C2 - 43099 CY - Jena SP - 26-31 TI - Spatial investigation of the elemental distribution in Wilson's disease liver after D-penicillamine treatment by LA-ICP-MS. JO - J. Trace Elem. Med. Biol. VL - 44 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2017 SN - 0946-672X ER - TY - JOUR AB - The influence of rhodanine and haematoxylin and eosin (HE) staining on the copper distribution and concentration in liver needle biopsy samples originating from patients with Wilson's disease (WD), a rare autosomal recessive inherited disorder of the copper metabolism, is investigated. In contemporary diagnostic of WD, rhodanine staining is used for histopathology, since rhodanine and copper are forming a red to orange-red complex, which can be recognized in the liver tissue using a microscope. In this paper, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method is applied for the analysis of eight different WD liver samples. Apart from a spatially resolved elemental detection as qualitative information, this LA-ICP-MS method offers also quantitative information by external calibration with matrix-matched gelatine standards. The sample set of this work included an unstained and a rhodanine stained section of each WD liver sample. While unstained sections of WD liver samples showed very distinct structures of the copper distribution with high copper concentrations, rhodanine stained sections revealed a blurred copper distribution with significant decreased concentrations in a range from 20 to more than 90%. This implies a copper removal from the liver tissue by complexation during the rhodanine staining. In contrast to this, a further HE stained sample of one WD liver sample did not show a significant decrease in the copper concentration and influence on the copper distribution in comparison to the unstained section. Therefore, HE staining can be combined with the analysis by means of LA-ICP-MS in two successive steps from one thin section of a biopsy specimen. This allows further information to be gained on the elemental distribution by LA-ICP-MS additional to results obtained by histological staining. AU - Hachmöller, O.* AU - Aichler, M. AU - Schwamborn, K.* AU - Lutz, L.* AU - Werner, M.* AU - Sperling, M.* AU - Walch, A.K. AU - Karst, U.* C1 - 51460 C2 - 43505 CY - Jena SP - 71-75 TI - Investigating the influence of standard staining procedures on the copper distribution and concentration in Wilson's disease liver samples by laser ablation-inductively coupled plasma-mass spectrometry. JO - J. Trace Elem. Med. Biol. VL - 44 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2017 SN - 0946-672X ER - TY - JOUR AB - Boron exposure is of interest and concern from an occupational point of view. Usual daily boron intake is related to boron blood plasma concentration <1 mg/L and to <3 mg/L in urine, but after exposure urine concentrations are quickly elevated. Reliable boron biomonitoring, typically in urine, thus is mandatory for occupational health control institutions. This paper reports on the development of a simple, fast and reliable boron determination procedure based on inductively coupled plasma – optical emission spectrometry (ICP-OES). Major aims for this method were simplicity in sample preparation, low risk for artifacts and interferences, high precision and accuracy, possibly low costs, including lower costs for element selective detection, short total analysis time and suitability for occupational health laboratories. Precision data (serial or day-to-day) from urine and doped urine were very good: <1.5 or <2%. Accuracy was calculated from analysis of a certified reference material (ERM-CD 281), as 99% or according to recoveries of doped concentrations ranging from 102 to 109% recovery. For cross-checking ICP-OES determinations, samples were analyzed also by quadrupole ICP-qMS and by sectorfield ICP-sf-MS at low and medium resolution. Both systems confirmed ICP-OES measurements when using 11B for quantification. Determinations based on 10B however showed some bias, except with ICP-sf-MS at medium resolution. The observed elevated signals are discussed with respect to the known Ne++ interference (as an impurity in Ar), which is not separated in low resolving quadrupole ICP-MS systems or ICP-sf-MS at low resolution. AU - Michalke, B. C1 - 50126 C2 - 42212 CY - Jena SP - 24-29 TI - Biomonitoring of boron: Development and characterization of a simple, reliable and quality controlled biomonitoring method. JO - J. Trace Elem. Med. Biol. VL - 40 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2017 SN - 0946-672X ER - TY - JOUR AB - Exposure to neurotoxic chemicals such as pesticides, selenium, and heavy metals have been suggested to play a role in the etiology of amyotrophic lateral sclerosis (ALS). We assessed exposure to lead, cadmium, and mercury in 38 ALS patients (16 men and 22 females) and 38 hospital-admitted controls by using their cerebrospinal fluid (CSF) content as biomarker. We determined CSF heavy metal levels with inductively coupled plasma sector field mass spectrometry, according to a methodology specifically developed for this biological matrix. ALS patients had higher median values for Pb (155 vs. 132. ng/L) but lower levels for Cd (36 vs. 72. ng/L) and Hg (196 vs. 217. ng/L). In the highest tertile of exposure, ALS odds ratio was 1.39 (95% CI 0.48-4.25) for Pb, 0.29 (0.08-1.04) for Cd and 3.03 (0.52-17.55) for Hg; however, no dose-response relation emerged. Results were substantially confirmed after conducting various sensitivity analyses, and after stratification for age and sex. Though interpretation of these results is limited by the statistical imprecision of the estimates, and by the possibility that CSF heavy metal content may not reflect long-term antecedent exposure, they do not lend support to a role of the heavy metals cadmium, lead and mercury in ALS etiology. AU - Vinceti, M.* AU - Filippini, T.* AU - Mandrioli, J.* AU - Violi, F.* AU - Bargellini, A.* AU - Weuve, J.* AU - Fini, N.* AU - Grill, P. AU - Michalke, B. C1 - 50331 C2 - 42188 CY - Jena SP - 121-125 TI - Lead, cadmium and mercury in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: A case-control study. JO - J. Trace Elem. Med. Biol. VL - 43 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2017 SN - 0946-672X ER - TY - JOUR AB - A laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method is developed and applied for the analysis of paraffin-embedded liver needle biopsy specimens of patients with Wilson's disease (WD), a rare autosomal recessive disorder of the copper metabolism causing various hepatic, neurological and psychiatric symptoms due to a copper accumulation in the liver and the central nervous system. The sample set includes two WD liver samples and one negative control sample. The imaging analysis was performed with a spatial resolution of 10 μm. Besides copper, iron was monitored because an elevated iron concentration in the liver is known for WD. In addition to this, both elements were quantified using an external calibration based on matrix-matched gelatine standards. The presented method offers low limits of detection of 1 and 5 μg/g for copper and iron, respectively. The high detection power and good spatial resolution allow the analysis of small needle biopsy specimen using this method. The two analyzed WD samples can be well differentiated from the control sample due to their inhomogeneous copper distribution and high copper concentrations of up to 1200μg/g. Interestingly, the WD samples show an inverse correlation of regions with elevated copper concentrations and regions with high iron concentrations. AU - Hachmöller, O.* AU - Aichler, M. AU - Schwamborn, K.* AU - Lutz, L.* AU - Werner, M.* AU - Sperling, M.* AU - Walch, A.K. AU - Karst, U.* C1 - 48263 C2 - 41005 CY - Jena SP - 97-102 TI - Element bioimaging of liver needle biopsy specimens from patients with Wilson's disease by laser ablation-inductively coupled plasma-mass spectrometry. JO - J. Trace Elem. Med. Biol. VL - 35 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2016 SN - 0946-672X ER - TY - JOUR AB - This study was performed to characterise selenium (Se) and Se species in cerebrospinal fluid (CSF) of sheep and its relation to the respective Se concentrations in serum. Paired samples from 10 adult sheep were used for the study. Five sheep were fed a diet with a marginal Se concentration of <0.05mg Se/kg diet dry weight (dw, Se(-)), and five animals were fed the same diet supplemented with sodium selenite revealing a concentration of 0.2mg Se/kg diet dw (Se(+)). The feeding strategy was conducted for two years; The results on metabolic effects were published previously. At the end of the feeding period, paired samples of serum and CSF were collected and analysed using ion exchange chromatography inductively coupled plasma-dynamic reaction cell-mass spectrometry (IEC-ICP-DRC-MS) technique for total Se concentration and concentrations of Se species. Albumin concentrations were analysed additionally. The feeding strategy caused significant differences (p<0.01) in serum Se concentrations with 33.1±5.11μg Se/l in the Se(-) group and 96.5±18.3μg Se/l in the Se(+) group, respectively. The corresponding total Se concentrations in CSF were 4.38±1.02μg Se/l and 6.13±1.64μg Se/l in the Se(-) and the Se(+) group, respectively, missing statistical significance (p=0.077). IEC-ICP-DRC-MS technique was able to differentiate the Se species selenoprotein P-bound Se (SePP), selenomethionine, glutathione peroxidase-bound Se (Se-GPx), selenocystine, thioredoxin reductase-bound Se, ovine serum albumin-bound Se (Se-OSA), SeIV and SeVI in ovine serum and CSF. Quantitatively, SePP is the main selenoprotein in ovine serum followed by Se-GPx. The CSF/blood ratio of albumin (QAlbumin) reflected a physiological function of the blood-CSF barrier in all sheep. QSe-species were higher than QAlbumin both feeding groups, supporting the hypothesis of local production of Se species in the brain. Significant positive regression lines for CSF vs. serum were found for albumin and Se-OSA only, suggesting a role of albumin to convey Se across the blood-CSF barrier. The ovine model, together with the IEC-ICP-DRC-MS technique to characterise the Se species, might be a worthwhile model for further studies as repeated sample collection as well as modification of the nutritional status is feasible and effective. AU - Humann-Ziehank, E.* AU - Ganter, M.* AU - Michalke, B. C1 - 47542 C2 - 40650 SP - 14-20 TI - Selenium speciation in paired serum and cerebrospinal fluid samples of sheep. JO - J. Trace Elem. Med. Biol. VL - 33 PY - 2016 SN - 0946-672X ER - TY - JOUR AB - Neurodegenerative diseases get a growing relevance for societies. But yet the complex multi-factorial mechanisms of these diseases are not fully understood, although it is well accepted that metal ions may play a crucial role. Manganese (Mn) is a transition metal which has essential biochemical functions but from occupational exposure scenarios it appeared that Mn can cause severe neurological damage. This "two-faces"-nature of manganese initiated us to start a project on Mn-speciation, since different element species are known to exhibit different impacts on health. A summary about the step-wise developments and findings from our working group was presented during the annual conference of the German trace element society in 2015. This paper summarizes now the contribution to this conference. It is intended to provide a complete picture of the so far evolved puzzle from our studies regarding manganese, manganese speciation and metabolomics as well as Mn-related mechanisms of neural damage. Doing so, the results of the single studies are now summarized in a connected way and thus their interrelationships are demonstrated. In short terms, we found that Mn-exposure leads to an increase of low molecular weight Mn compounds, above all Mn-citrate complex, which gets even enriched across neural barriers (NB). At a Mn serum concentration between 1.5 and 1.9μg/L a carrier switch from Mn-transferrin to Mn-citrate was observed. We concluded that the Mn-citrate complex is that important Mn-carrier to NB which can be found also beyond NB in human cerebrospinal fluid (CSF) or brain of exposed rats. In brain of Mn-exposed rats manganese leads to a decreased iron (Fe) concentration, to a shift from Fe(III) to Fe(II) after long term exposure and thus to a shift toward oxidative stress. This was additionally supported by an increase of markers for oxidative stress, inflammation or lipid peroxidation at increased Mn concentration in brain extracts. Furthermore, glutamate and acetylcholineesterase were elevated and many metabolite concentrations were significantly changed. AU - Michalke, B. C1 - 48185 C2 - 41081 CY - Jena SP - 50-61 TI - Review about the manganese speciation project related to neurodegeneration: An analytical chemistry approach to increase the knowledge about manganese related parkinsonian symptoms. JO - J. Trace Elem. Med. Biol. VL - 37 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2016 SN - 0946-672X ER - TY - JOUR AB - Manganese (Mn) is an essential nutrient that can be toxic in excess concentrations, especially during early development stages. The mechanisms of Mn toxicity is still unclear, and little information is available regarding the role of Mn speciation and fractionation in toxicology. We aimed to investigate the toxic effects of several chemical forms of Mn in embryos of Danio rerio exposed during different development stages, between 2 and 122h post fertilization. We found a stage-specific increase of lethality associated with hatching and removal of the chorion. Mn(II), ([Mn(H2O)6](2+)) appeared to be the most toxic species to embryos exposed for 48h, and Mn(II) citrate was most toxic to embryos exposed for 72 and/or 120h. Manganese toxicity was associated with calcium disruption, manganese speciation and metal fractionation, including bioaccumulation in tissue, granule fractions, organelles and denaturated proteins. AU - Hernández, R.B.* AU - Nishita, M.I.* AU - Espósito, B.P.* AU - Scholz, S.* AU - Michalke, B. C1 - 46628 C2 - 37652 SP - 209-217 TI - The role of chemical speciation, chemical fractionation and calcium disruption in manganese-induced developmental toxicity in zebrafish (Danio rerio) embryos. JO - J. Trace Elem. Med. Biol. VL - 32 PY - 2015 SN - 0946-672X ER - TY - JOUR AB - After high-dose-short-term exposure (usually from occupational exposure) and even more under low-dose long term exposure (mainly environmental) manganese (Mn) biomonitoring is still problematic since these exposure scenarios are not necessarily reflected by a significant increase of total Mn in blood or serum. Usually, Mn concentrations of exposed and unexposed persons overlap and individual differentiation is often not possible. In this paper Mn speciation on a large sample size (n=180) was used in order to be able to differentiate between highly Mn-exposed or low or unexposed individuals at low total Mn concentration in serum (Mn(S)). The whole sample set consisted of three subsets from Munich, Emilia Romagna region in Italy and from Sweden. It turned out that also at low total Mn(S) concentrations a change in major Mn carriers in serum takes place from Mn-transferrin (Mn-Tf(S)) towards Mn-citrate (Mn-Cit(S)) with high statistical significance (p<0.000002). This carrier switch from Mn-Tf(S) to Mn-Cit(S) was observed between Mn(S) concentrations of 1.5μg/L to ca. 1.7μg/L. Parallel to this carrier change, for sample donors from Munich where serum and cerebrospinal fluid were available, the concentration of Mn beyond neural barriers - analysed as Mn in cerebrospinal fluid (Mn(C)) - positively correlates to Mn-Cit(S) when Mn(S) concentration was above 1.7μg/L. The correlation between Mn-Cit(S) and Mn(C) reflects the facilitated Mn transport through neural barrier by means of Mn-citrate. Regional differences in switch points from Mn-Tf(S) to Mn-Cit(S) were observed for the three sample subsets. It is currently unknown whether these differences are due to differences in location, occupation, health status or other aspects. Based on our results, Mn-Cit(S) determination was considered as a potential means for estimating the Mn load in brain and CSF, i.e., it could be used as a biomarker for Mn beyond neural barrier. For a simpler Mn-Cit(S) determination than size exclusion chromatography inductively coupled plasma mass spectrometry (SEC-ICP-MS), ultrafiltration (UF) of serum samples was tested for suitability, the latter possibly being a preferred choice for routine occupational medicine laboratories. Our results revealed that UF could be an alternative if methodical prerequisites and limitations are carefully considered. These prerequisites were determined to be a thorough cleaning procedure at a minimum Mn(S) concentration >1.5μg/L, as at lower concentrations a wide scattering of the measured concentrations in comparison to the standardized SEC-ICP-MS results were observed. AU - Michalke, B. AU - Aslanoglou, L. AU - Ochsenkühn-Petropoulou, M.* AU - Bergström, B.* AU - Berthele, A.* AU - Vinceti, M.* AU - Lucio, M. AU - Lidén, G.* C1 - 46629 C2 - 37651 SP - 145-154 TI - An approach for manganese biomonitoring using a manganese carrier switch in serum from transferrin to citrate at slightly elevated manganese concentration. JO - J. Trace Elem. Med. Biol. VL - 32 PY - 2015 SN - 0946-672X ER - TY - JOUR AB - Observational studies addressing the relation between selenium and human health, particularly cancer risk, yielded inconsistent results, while most recent randomized trials showed a fairly consistent pattern suggesting null or adverse effects of the metalloid. One of the most plausible explanations for such inconsistencies is inadequate exposure assessment in observational studies, commonly carried out by measuring total Se content without taking into account the specific exposure to the individual chemical forms of the metalloid, whose toxic and nutritional properties may vary greatly. Data on the distribution of these species in human blood and their correlation with overall selenium levels are very limited. The concentrations of organic and inorganic selenium species were analyzed in serum of fifty subjects sampled from the general population of the municipality of Modena, northern Italy, aged from 35 to 70 years. Samples were collected during a 30-month period, and determinations of selenium species were carried out using high pressure liquid chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry. The majority of selenium was found to be present as organic species, but the inorganic forms showed higher levels than expected. These species showed limited correlations with age, sex and body mass index, while the organic forms increased in subjects consuming selenium-containing dietary supplements and decreased in smokers. The length of the sample storage period strongly influenced the distribution of selenium compounds, with a clear tendency towards higher inorganic and lower organic selenium levels over time. In multivariate analysis adjusting for potential confounders, total serum selenium correlated with human serum albumin-bound selenium and, in males, with two organic species of the metalloid (selenocysteine and glutathione peroxidase-bound selenium), while little association existed with the other organic forms and the inorganic ones. These findings highlight the potential for exposure misclassification of observational epidemiologic investigations based on overall selenium content in blood and possibly other tissues, and the critical role of the storage conditions for speciation analysis. AU - Vinceti, M.* AU - Grill, P.* AU - Malagoli, C.* AU - Filippini, T.* AU - Storani, S.* AU - Malavolti, M.* AU - Michalke, B. C1 - 44050 C2 - 36728 CY - Jena SP - 1-10 TI - Selenium speciation in human serum and its implications for epidemiologic research: A cross-sectional study. JO - J. Trace Elem. Med. Biol. VL - 31 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2015 SN - 0946-672X ER - TY - JOUR AB - Manganese (Mn) is known to be a neurotoxic agent for nearly 175 years now. A lot of research has therefore been carried out over the last century. From preliminary describing only symptoms of Mn-(over)exposed workers, research was preceded to more detail on toxic mechanisms of Mn. Unraveling those neurotoxic mechanisms implicated a number of studies, which were summarized partly in several reviews (e.g. Yokel RA. Neuromol Med 2009;11(4):297-310; Aschner M, et al. Toxicology Appl Pharmacol 2007;221(2):131-47; Michalke B, et al. J Environ Monit 2007;9(7):650). Since our recent review on Mn-speciation in 2007 (Michalke B, et al. J Environ Monit 2007;9(7):650), Mn-research was considerably pushed forward and several new research articles were published. The very recent years though, Mn toxicity investigating science is spreading into different fields with very detailed and complex study designs. Especially the mechanisms of Mn-induced neuronal injury on cellular and molecular level was investigated in more detail, discussing neurotransmitter and enzyme interactions, mechanisms of action on DNA level and even inclusion of genetic influences. Depicting the particular Mn-species was also a big issue to determine which molecule is transporting Mn at the cell membranes and which one is responsible for the injury of neuronal tissue. Other special foci on epidemiologic studies were becoming more and more important: These foci were directed toward environmental influences of Mn on especially Parkinson disease prevalence and the ability to carry out follow-up studies about Mn-life-span exposure. All these very far-reaching research applications may finally lead to a suitable future human Mn-biomonitoring for being able to prevent or at least detect the early onset of manganism at the right time. AU - Michalke, B. AU - Fernsebner, K. C1 - 28242 C2 - 33026 CY - Jena SP - 106-116 TI - New insights into manganese toxicity and speciation. JO - J. Trace Elem. Med. Biol. VL - 28 IS - 2 PB - Elsevier - Urban & Fischer PY - 2014 SN - 0946-672X ER - TY - JOUR AB - An appropriate and controlled supply of thyroid hormones is vital for proper body function. In turn, an appropriate synthesis of T3 and T4 in the thyroid gland is dependent on a sufficient and balanced iodide concentration in blood serum. Due to widespread iodine deficiency or some cases of iodine over exposure, iodide biomonitoring in serum is important and it is that biomonitoring approach being closest to the bioavailable I- supply for the thyroid gland. Therefore, this paper describes a biomonitoring method for iodide determination in serum based on ion chromatography-inductively coupled plasma mass spectrometry (IC-ICP-MS). Since in literature only very few data are available on iodide in serum but many in urine the method is also extended to I- monitoring in urine. The method was additionally designed to have short analysis time (8 min) for increased sample throughput, good precision in serial measurement (serum: 4.86%; urine: 1.4%), and day-to-day determination (serum: 5.7%; urine: 2.28%), high accuracy (serum: 105%; urine: 101%) and good recovery (serum: 102%; urine: 99%) even in matrix-rich samples at low I- concentration. Also, investigations were performed to elucidate whether internal standardization during chromatography, sample preparation for protein-matrix removal or matrix-matched calibration are advantageous for analytical performance. Finally, limits of detection (3σ) of 0.12 μg/L or 0.05 μg/L (serum or urine) and limit of quantification (10σ) of 0.39 μg/L or 0.17 μg/L (serum or urine) were achieved. AU - Michalke, B. AU - Witte, H. C1 - 31560 C2 - 34645 CY - Jena SP - 63-68 TI - Characterization of a rapid and reliable method for iodide biomonitoring in serum and urine based on ion chromatography-ICP-mass spectrometry. JO - J. Trace Elem. Med. Biol. VL - 29 PB - Elsevier Gmbh, Urban & Fischer Verlag PY - 2014 SN - 0946-672X ER - TY - JOUR AB - Copper is an essential redox-active metal ion which in excess becomes toxic due to the formation of reactive oxygen species. In Wilson disease the elevated copper level in liver leads to chronic oxidative stress and subsequent hepatitis. This study was designed to evaluate the copper chelating efficiency of the bacterial methanobactin (MB) in a rat model for Wilson disease. Methanobactin is a small peptide produced by the methanotrophic bacterium Methylosinus trichosporium OB3b and has an extremely high affinity for copper. Methanobactin treatment of the rats was started at high liver copper and serum aspartate aminotransferase (AST) levels. Two dosing schedules with either 6 or 13 intraperitoneal doses of 200mg methanobactin per kg body weight were applied. Methanobactin treatment led to a return of serum AST values to basal levels and a normalization of liver histopathology. Concomitantly, copper levels declined to 45% and 24% of untreated animals after 6 and 13 doses, respectively. Intravenous application of methanobactin led to a prompt release of copper from liver into bile and the copper was shown to be associated with methanobactin. In vitro experiments with liver cytosol high in copper metallothionein demonstrated that methanobactin removes copper from metallothionein confirming the potent copper chelating activity of methanobactin. AU - Summer, K.H. AU - Lichtmannegger, J. AU - Bandow, N.* AU - Choi, D.W.* AU - DiSpirito, A.A.* AU - Michalke, B. C1 - 5964 C2 - 28448 CY - Stuttgart SP - 36-41 TI - The biogenic methanobactin is an effective chelator for copper in a rat model for Wilson disease. JO - J. Trace Elem. Med. Biol. VL - 25 IS - 1 PB - Gustav Fischer PY - 2011 SN - 0946-672X ER - TY - JOUR AB - The aim of this study was to evaluate the relationship between cerium content in human breast milk and blood plasma or serum. Blood samples and breast milk at various stages of lactation, from 5 days to 51 weeks post partum, were donated by 42 healthy breast-feeding mothers from Munich, Germany and by 26 lactating Spanish mothers from Madrid at 4 weeks post partum. Inductively coupled plasma mass spectrometry was applied for the determination of cerium in the biological samples. Cerium concentration in the digested milk samples from Munich showed low values and the arithmetic mean values ranged between the quantification limit of 5 ng/L up to 65 ng/L. The median value amounted to 13 ng/L. The cerium concentrations in the Spanish breast milk samples amounted to similar low values. The data were about a factor of eight lower than values found in a former study of samples from an eastern German province. All cerium concentrations in the German plasma samples, except for two, were at the quantification limit of 10 ng/L. Interestingly, the serum samples of the Spanish mothers showed cerium values ranging between 21.6 and 70.3 ng/L; these higher data could be explained by an enhanced intake of cerium by humans in Madrid. This could be caused by increased cerium concentrations in particulate matter due to a higher traffic volume in Madrid compared to Munich. The results obtained in this study contribute to setting reference baseline values of cerium in human breast milk and blood plasma/serum and indicate a varying cerium amount depending on the cerium environmental pollution. Possibly, the cerium content in plasma/serum could be an indicator for environmental cerium, which is not valid for breast milk. AU - Höllriegl, V. AU - González-Estecha, M.* AU - Trasobares, E.M.* AU - Giussani, A. AU - Oeh, U. AU - Herraiz, M.A.* AU - Michalke, B. C1 - 545 C2 - 27233 SP - 193-199 TI - Measurement of cerium in human breast milk and blood samples. JO - J. Trace Elem. Med. Biol. VL - 24 IS - 3 PB - Elsevier PY - 2010 SN - 0946-672X ER - TY - JOUR AB - This article reviews approaches on platinum speciation with respect to Pt drugs in anti-cancer therapies. The paper starts with the introduction of available platinum-based drugs and describes their assumed principle of action. It is now generally accepted that these Pt complexes exhibit their therapeutic action by coordination to DNA which leads to bending of the DNA structure and to an inhibition of the DNA polymerase progression. But dose-limiting side effects, including nephrotoxicity as well as resistance to some of these Pt compounds, are still a major problem. Platinum speciation moved increasingly into the focus of interest when it became clear that (1) the active drugs were the hydrolyzation products rather than the originally administered ones and (2) that the parallel formation of inactive Pt-protein complexes, which additionally reduce the efficacy of Pt anti-tumor agents, compete with the formation of the cytotoxic Pt-DNA lesions. Speciation analysis methods were employed based on chromatography or capillary electrophoresis respectively, each coupled to inductively coupled plasma (ICP)-mass spectrometry (MS) or electrospray ionization (ESI)-MS. The paper describes these Pt-speciation investigations, which started with exploring hydrolyzation kinetics in aqueous solutions. These experiments were followed by the speciation investigations in model solutions containing proteins or other sulphur-containing ligands, which could also be responsible for deactivation of the Pt agent in vivo. The experiments improved the understanding of the metabolite form, by which the metal complex enters the tumor cells, and whether and how this metabolized complex is already inactivated at this time. As an example, reaction kinetics of cisplatin (cis-[diamminedichloroplatinum(II)]) with albumin, transferrin, myoglobin, ubiquitin, and metallothionein were investigated and reaction products were speciated. Finally, Pt-speciation in serum of medicated cancer patients was conducted by several research groups, which are outlined in the Section "Investigations in serum". The section "Investigations in urine of cancer treated patients" deals with speciation experiments on the Pt-metabolites excreted by the organism. By these means an assessment of the in vivo metabolism of Pt-drugs may be possible. Finally, the development of new anti-cancer metallodrugs needs the respective analytical techniques reported in the last section of the paper. AU - Michalke, B. C1 - 43 C2 - 27147 SP - 69-77 TI - Platinum speciation used for elucidating activation or inhibition of Pt-containing anti-cancer drugs. JO - J. Trace Elem. Med. Biol. VL - 24 IS - 2 PB - Elsevier PY - 2010 SN - 0946-672X ER - TY - JOUR AU - Michalke, B. AU - Skalny, A.* AU - Köhrle, J.* C1 - 5687 C2 - 28005 SP - 221-222 TI - Report on the 4th International FESTEM Symposium on 'Recent advances in trace element research: From experiments to nutritional and clinical applications in humans' (Saint Petersburg, Russia, June 09-12th, 2010). JO - J. Trace Elem. Med. Biol. VL - 24 IS - 4 PB - Elsevier PY - 2010 SN - 0946-672X ER - TY - JOUR AB - The well-known beneficial health effects of Se have demanded the development of rapid and accurate methods for its analysis. A flow injection (FI) method with inductively coupled plasma mass spectrometry (ICP-MS) as a selenium-selective detector was optimized. Flow injection was carried out using a Knauer 1100 smartline inert series liquid chromatograph coupled with a Perkin Elmer DRC II ICP-mass spectrometer. For sample injection a Perkin Elmer electronic valve equipped with a 25microL sample loop was employed. Before measurement, standards or samples were administered with 1microg/L rhodium as internal standard for correction of changes in detector response according to changes in sample electrolyte concentration. The method characterization parameters are: LOD (3sigma criterion): 26ng/L, LOQ (10sigma criterion): 86ng/L, linearity: 0.05->10microg/L, r(2)=0.9999, serial or day-to-day precision at 2microg/L: 4.48% or 5.6%. Accuracy was determined by (a) recovery experiments (CSF spiked with 2microg/L Se); (b) comparison of FI-ICP-MS measurement with graphite furnace atomic absorption (GFAAS) measurements of 1:10 diluted serum samples; (c) Se determination in urine and serum control materials. Recovery (a) was 101.4%, measurement comparison with GFAAS (b) showed 98.8% (5 serum samples, 1:10 diluted in the range of 0.5-1.3microg/L, compared to GFAAS determination, which was set to 100%), and accuracy was 96.8% or 105.6% for the serum or urine control material. Analysis time per sample was short and typically below 2min for the complete measurement, including sample introduction, sample-line purge and quadruplicate Se determination. This method was used to determine Se in cerebrospinal fluid (CSF) and plasma (here parallel to GFAAS) in 35 paired serum and CSF samples. Se determination gave values in the range of 42-130microg/L for serum and 1.63-6.66microg/L for CSF. The median for Se in 35 individual CSF samples was 3.28microg/L, the mean (+/-SD) was 3.67 (1.35)microg/L, whilst for individual serum samples the median was 81microg/L and the mean (+/-SD) was 85 (26)microg/L. When relating the paired Se concentrations of CSF samples to respective serum samples it turned out that Se-CSF (behind blood brain barrier (BBB)) is independent on Se-serum concentration (before BBB). AU - Michalke, B. AU - Grill, P. AU - Berthele, A.* C1 - 928 C2 - 26647 CY - Jena SP - 243-250 TI - A method for low volume and low Se concentration samples and application to paired cerebrospinal fluid and serum samples. JO - J. Trace Elem. Med. Biol. VL - 23 IS - 4 PB - Elsevier PY - 2009 SN - 0946-672X ER - TY - JOUR AB - Manganese (Mn) at high concentrations can have adverse effects on health, mainly because of its toxicity to the central nervous system. Health impacts of Mn are known mostly from occupational health studies, but the exact mechanisms how Mn, being bound to transferrin (TF) in the blood, enters the brain--are unknown. Mn speciation at the neural barriers can help to obtain more information about the pathways and carriers. This paper summarizes investigations on the size distribution of Mn carriers (e.g. proteins, peptides, carbonic acids) in serum before the neural barriers and in cerebrospinal fluid (CSF) behind them as a first characterization step of the Mn carriers being involved in moving Mn across the neural barriers. Further identification of Mn-species in CSF was successfully achieved by CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-mass spectrometry (MS). Serum samples showed Mn mean concentrations of 1.7+/-0.8 microg L(-1). The size distribution of Mn-carriers showed a main peak in the TF/albumin size fitting to the known physiological ligands. However, also an increasing Mn peak at 700 Da with increasing total Mn concentration was seen. Samples of CSF showed Mn mean concentrations of 2.6 microg L(-1)=48 nM. In CSF Mn was found to be mostly bound to low-molecular-mass (LMM)-Mn carriers in the range of 640-680 Da. This is similar to the LMM compound in serum and to Mn-citrate complexes suggested to be present in body fluids. Citrate concentration was 573 microM, thus being in huge excess compared to Mn. CSF was further analyzed by CZE-ICP-DRC-MS. Several Mn-species were monitored and mostly identified. The most abundant Mn-species was Mn-citrate at a concentration of around 0.7 microg Mn L(-1). AU - Michalke, B. AU - Berthele, A.* AU - Mistriotis, P.* AU - Ochsenkühn-Petropoulou, M.* AU - Halbach, S. C1 - 4128 C2 - 25059 SP - 4-9 TI - Manganese species from human serum, cerebrospinal fluid analyzed by size exclusion chromatography-, capillary electrophoresis coupled to inductively coupled plasma mass spectrometry. JO - J. Trace Elem. Med. Biol. VL - 21 IS - SUPPL. 1 PB - Elsevier PY - 2007 SN - 0946-672X ER - TY - JOUR AU - Stocker, A. AU - Schramel, P. AU - Kettrup, A. AU - Bengsch, E. C1 - 3607 C2 - 23032 SP - 183-189 TI - Trace and mineral elements in royal jelly and homeostatic effects. JO - J. Trace Elem. Med. Biol. VL - 19 PY - 2005 SN - 0946-672X ER -