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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. [ABSTRACT FROM AUTHOR]

The aim of this systematic review, meta-analysis and meta-regression was to examine the relationship between type 2 diabetes mellitus (T2DM) and concentration of zinc in whole blood, as well as dietary zinc intake. Searches were performed using Ovid MEDLINE, Embase (Ovid) and The Cochrane Library (CENTRAL). Observational studies conducted on diabetic and healthy adults, with data on dietary zinc intake and/or concentration of zinc in whole blood, were selected. The search strategy yielded 11,150 publications and the manual search 6, of which 11 were included in the meta-analyses. Mean difference (MD) and 95% confidence interval (CI), were calculated using the generic inverse-variance method with random-effects models. Heterogeneity was assessed by the Cochran Q-statistic and quantified by the I 2 statistic. Meta-regressions and stratified analysis were used to examine whether any covariate had influence on the results. The pooled MD for the dietary zinc intake meta-analysis was −0.40 (95% CI: −1.59 to 0.79; I 2  = 61.0%). Differences between diabetic and non-diabetic subjects became significant in the presence of complications associated with diabetes (MD = −2.26; 95% CI: −3.49 to −1.02; I 2  = 11.9%). Meta-regression showed that for each year since the diagnosis of diabetes the concentration of zinc in whole blood decreased in diabetic patients regarding healthy controls [MD (concentration of zinc in blood) = 732.61 + (−77.88303) × (duration of diabetes in years)], which is not generally explained by a lower intake of zinc. [ABSTRACT FROM AUTHOR]

Cadmium is a known carcinogen that has been implicated in prostate cancer, but how it affects prostate carcinogenesis in humans remains unclear. Evidence from basic science suggests that cadmium can bind to the androgen receptor causing endocrine disruption. The androgen receptor is required for normal prostate development and is the key driver of prostate cancer progression. In this study, we examined the association between cadmium content and androgen receptor protein expression in prostate cancer tissue of African American (N = 22) and European American (N = 30) men. Although neither overall tumor cadmium content (log transformed) nor androgen receptor protein expression level differed by race, we observed a race-cadmium interaction with regard to androgen receptor expression ( P  = 0.003) even after accounting for age at prostatectomy, smoking history, and Gleason score. African American men had a significant positive correlation between tumor tissue cadmium content and androgen receptor expression (Pearson correlation = 0.52, P  = 0.013), while European Americans showed a non-significant negative correlation between the two (Pearson correlation = −0.19, P  = 0.31). These results were unchanged after further accounting for tissue zinc content or dietary zinc or selenium intake. African American cases with high-cadmium content (>median) in tumor tissue had more than double the androgen receptor expression (0.021 vs. 0.008, P  = 0.014) of African American men with low-cadmium level. No difference in androgen receptor expression was observed in European Americans by cadmium level (high 0.015 vs. low 0.011, P  = 0.30). Larger studies are needed to confirm these results and if upheld, determine the biologic mechanism by which cadmium increases androgen receptor protein expression in a race-dependent manner. Our results suggest that cadmium may play a role in race disparities observed in prostate cancer. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate, by five different administration protocols, the impact of the dosage, the time passed after the last injection and the frequency of injections, on accumulation and distribution of Gd-containing species in the body tissues of healthy mice upon repeated injections of Gadolinium Based Contrast Agents (GBCAs). Gadodiamide and Gadoteridol have been compared. The amount of Gd retained in several tissues/organs (cerebrum, cerebellum, spleen, liver, kidneys, eyes, skin, bone and muscle) has been assessed by ICP-MS upon administration of the GBCAs i) at three weeks or three months after the last administration, ii) when one, three or twelve doses of GBCA were administered and iii) when administrations were made every two weeks. Gd was found in all tissues after the administration of Gadodiamide. Conversely, in the case of Gadoteridol, Gd was detected only in spleen, kidneys, liver and bone. The amounts of Gd found in spleen, liver and kidneys markedly decrease upon increasing the time that has passed after the last administration, whereas, in the case of Gadodiamide, the decrease of Gd found in bone, cerebrum and cerebellum appears to occur at a much slower rate. Overall, areas of long term deposition appear to be bone and spleen for both GBCAs. In conclusion, our findings demonstrate that intravenous multiple administrations of GBCAs is associated with extensive multiorgan retention which is reduced but not eliminated by the use of the macrocyclic Gadoteridol as well as by adopting reduced and/or less frequent dosing. [ABSTRACT FROM AUTHOR]

Alongside the Brazil nut’s role as an excellent source of vitamins, oil, fatty acids, lipids and nutrients, it is also recognized as a rich source of selenium. The pathway along which selenium and sulfur are metabolized in plants is theorized to be the same as that used for tellurium. Total tellurium content and its bioaccessibility are then evaluated by ICP-MS. Interferences and sample preparation are evaluated for the accurate determination of tellurium, and the accuracy determined through analysis of the certified reference material 1643e. A concentration of 4.02 ± 0.391 ng g −1 is obtained as an average concentration through external and internal calibrations. Through this reliable result, tellurium bioaccessibility in Brazil nuts is obtained via an in vitro validated unified bioaccessibility method. Values of 32% and 30% of total tellurium are available in the gastric and gastrointestinal fractions, respectively. [ABSTRACT FROM AUTHOR]

The metabolic alterations associated with obesity include mineral dysregulation. Essential trace elements are nutrients with a relevant function in a large number of cellular processes and multiple roles in the correct functioning of metabolic enzymes. Paraoxonase-1 (PON1) is an antioxidant and anti-inflammatory enzyme that is compromised in obesity. In the present study, the potential alterations in trace elements in morbidly obese women were assessed in relation to serum PON1 activity and concentration, as well as to other obesity-related comorbidities such as diabetes mellitus and fatty liver. We recruited 41 morbidly obese women and 51 control individuals. The serum concentrations of 30 elements, PON1 paraoxonase and lactonase activities, and PON1 concentration were measured. We observed significant alterations in the levels of As, Ba, Cu, Ca, Fe, Mg, Na, Se, Sr, and Zn in obese women; some of them (As, Ca, Cr, Cu, Mg, and Se) being significantly correlated with serum PON1 values. The most relevant changes were observed in the concentrations of As, Sr and Mg, the last of which was also significantly associated with diabetes mellitus. The current results raise the possibility that increased ingestion and/or storage of a number of trace elements may be factors predisposing to obesity-related comorbidities and metabolic alterations. [ABSTRACT FROM AUTHOR]

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 coupled 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 a 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. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common type of primary tumor of the central nervous system with a poor prognosis, needing the development of new therapeutic drugs. Few studies focused on sodium selenite (SS) effects in cancer cells cultured as multicellular tumor spheroids (MCTS or 3D) closer to in vivo tumor. We investigated SS anticancer effects in three human GBM cell lines cultured in 3D: LN229, U87 (O(6)-methyguanine-DNA-methyltransferase (MGMT) negative) and T98G (MGMT positive). SS absorption was evaluated and the cytotoxicity of SS and temozolomide (TMZ), the standard drug used against GBM, were compared. SS impacts on proliferation, cell death, and invasiveness were evaluated as well as epigenetic modifications by focusing on histone deacetylase (HDAC) activity and dimethyl-histone-3-lysine-9 methylation (H3K9m2), after 24 h to 72 h SS exposition. SS was absorbed by spheroids and was more cytotoxic than TMZ (i.e., for LN229, the IC50 was 38 fold-more elevated for TMZ than SS, at 72 h). SS induced a cell cycle arrest in the S phase and apoptosis via caspase-3. SS decreased carbonic anhydrase-9 (CA9) expression, invasion on a Matrigel matrix and modulated E- and N-Cadherin transcript expressions. SS decreased HDAC activity and modulated H3K9m2 levels. 3D model provides a relevant strategy to screen new drugs and SS is a promising drug against GBM that should now be tested in GBM animal models. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus is a condition that predisposes a higher risk for the development of osteoporosis. The objective of this study was to investigate the influence of boron supplementation on bone microstructure and strength in control and non-obese diabetic mice for 30 days. The animals were supplemented with 40 μg/0,5 ml of boron solution and controls received 0,5 ml of distilled water daily. We evaluated the biochemical parameters: total calcium, phosphorus, magnesium and boron; bone analysis: bone computed microtomography, and biomechanical assay with a three point test on the femur. This study consisted of 28 animals divided into four groups: Group water control - Ctrl (n = 10), Group boron control - Ctrl±B (n = 8), Group diabetic water - Diab (n = 5) and Group diabetic boron - Diab±B (n = 5). The results showed that cortical bone volume and the trabecular bone volume fraction were higher for Diab±B and Ctrl±B compared to the Diab and Ctrl groups (p ≤ 0,05). The trabecular specific bone surface was greater for the Diab±B group, and the trabecular thickness and structure model index had the worst values for the Diab group. The boron serum concentrations were higher for the Diab±B group compared to non-supplemented groups. The magnesium concentration was lower for Diab and Diab±B compared with controls. The biomechanical test on the femur revealed maintenance of parameters of the bone strength in animals Diab±B compared to the Diab group and controls. The results suggest that boron supplementation improves parameters related to bone strength and microstructure of cortical and trabecular bone in diabetic animals and the controls that were supplemented. [ABSTRACT FROM AUTHOR]

Neuropathic pain affects 1–10% of the general population and is caused by a lesion or disease of the somatosensory nervous system. Spinal cord stimulation (SCS), a method where implanted electrodes stimulate the spinal cord, has been successfully used to treat drug-resistant neuropathic pain, but the mechanism of action is largely unknown. Studies show that SCS changes the protein levels in CSF (cerebrospinal fluid) of pain patients. Several neurological conditions have been shown to alter the elemental composition of CSF. Therefore changes in the levels of ions and trace elements in the CSF may correspond to SCS use. This study used ICP-MS (Inductively coupled plasma mass spectrometry) and ICP-AES (Inductively coupled plasma atomic emission spectroscopy) to quantify 10 elements in CSF from chronic neuropathic pain patients using SCS. The element concentrations in CSF from patients with SCS treatment on/off, were measured. No effect on the element concentrations in CSF from treatment with SCS could be detected. Also, the elemental concentrations in pooled CSF from patients without chronic neuropathic pain was determined and compared to the patients using SCS. The concentration of the elements Ca, Sr, Na, K, P, Mg and Ti were, significantly higher in patients compared to the CSF-control. [ABSTRACT FROM AUTHOR]

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 1.9 μg/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. [ABSTRACT FROM AUTHOR]

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 (3 σ ) of 0.12 μg/L or 0.05 μg/L (serum or urine) and limit of quantification (10 σ ) of 0.39 μg/L or 0.17 μg/L (serum or urine) were achieved. [ABSTRACT FROM AUTHOR]