Background The association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain. Methods Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single metals and cardiovascular incidence. We used a Probit extension of Bayesian Kernel Machine Regression (BKMR-P) to handle metal mixtures in a survival setting. Results In single-metal models, the hazard ratios [confidence intervals (CIs)] of cardiovascular incidence, comparing the 80th to the 20th percentiles of metal distributions, were 1.35 (1.06, 1.72) for Cu, 1.43 (1.07, 1.90) for Zn, 1.51 (1.13, 2.03) for Sb, 1.46 (1.13, 1.88) for Cd, 1.64 (1.05, 2.58) for Cr and 1.31 (1.01, 1.71) for V. BKMR-P analysis was confirmatory of these findings, supporting that Cu, Zn, Sb, Cd, Cr and V are related to cardiovascular incidence in the presence of the other metals. Cd and Sb showed the highest posterior inclusion probabilities. Conclusions Urine Cu, Zn, Sb, Cd, Cr and V were independently associated with increased cardiovascular risk at levels relevant for the general population of Spain. Urine metals in the mixture were also jointly associated with cardiovascular incidence, with Cd and Sb being the most important components of the mixture.

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24Lung cancer is one of the ten most common causes of death worldwide, so that the search for 25 early diagnosis biomarkers is a very challenging task. Bronchoalveolar lavage fluid (BALF) provides 26 information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and 27 no previous metabolomic studies have been performed with BALF samples from patients with lung 28 cancer. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. 29In this way, two complementary metabolomics techniques based on direct infusion high resolution mass 30 spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been 31 applied to compare statistically differences between lung cancer (LC) and control (C) BALF samples, 32 using partial least square discriminant analysis (PLS-DA) in order to find and identify potential 33 biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic 34 pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this 35 disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the 36 receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential 37 sensitive and specific biomarkers for lung cancer diagnosis and prognosis.

Background: The apolipoprotein E (APOE) gene exists in three isoforms in humans: APOE2, APOE3 and APOE4. APOE4 causes structural and functional alterations in normal brains, and is the strongest genetic risk factor of the sporadic form of Alzheimer's disease (LOAD). Research on APOE4 has mainly focused on the neuronal damage caused by defective cholesterol transport and exacerbated amyloid-β and Tau pathology. The impact of APOE4 on non-neuronal cell functions has been overlooked. Astrocytes, the main producers of ApoE in the healthy brain, are building blocks of neural circuits, and Ca 2+ signaling is the basis of their excitability. Because APOE4 modifies membrane-lipid composition, and lipids regulate Ca 2+ channels, we determined whether APOE4 dysregulates Ca 2+ signaling in astrocytes. Methods: Ca 2+ signals were recorded in astrocytes in hippocampal slices from APOE3 and APOE4 gene targeted replacement male and female mice using Ca 2+ imaging. Mechanistic analyses were performed in immortalized astrocytes. Ca 2+ fluxes were examined with pharmacological tools and Ca 2+ probes. APOE3 and APOE4 expression was manipulated with GFP-APOE vectors and APOE siRNA. Lipidomics of lysosomal and whole-membranes were also performed.

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Environmental metabolomics is an emerging field referred to the application of metabolomics to characterize the interactions of living organisms with their environment. In this sense, the importance of monitoring the effects of toxic metals on living organisms has increased as a consequence of natural changes and anthropogenic activities that have led to an increase of toxic metal levels in terrestrial and aquatic ecosystems. For this purpose, the use of metabolomics based on MS to study metal toxicity is gaining importance in recent years. Environmental metabolomics can be used to: discover the mode of action (MOA) of toxic metals through controlled laboratory experiments; evaluate toxicity (biological adverse response to a substance), that may be useful in risk assessment; and develop new biomarkers (based in metabolome shifts discovered through controlled laboratory experiments) that may be applied in environmental biomonitoring (environmental realistic scenario). In this review, it is discussed how metabolomics based on MS can be applied to study metal toxicity, considering the most important hallmarks related to metabolomic experiments.

The potential of coupling anion‐exchange high‐performance liquid chromatography, hydride generation and atomic fluorescence spectrometry (HPLC–HG–AFS) for arsenic speciation is considered. The effects of hydrochloric acid and sodium tetrahydroborate concentrations on signal‐to‐background ratio, as well as argon and hydrogen flow rates, were investigated. Detection limits for arsenite, dimethylarsinic acid (DMA), monomethylarsonic acid (MMA) and arsenate were 0.17, 0.45, 0.30 and 0.38 μg l−1, respectively, using a 20‐μl loop. Linearity ranges were 0.1–500 ng for As(III) and MMA (as arsenic), and 0.1–800 ng for DMA and As(V) (as arsenic). Arsenobetaine (AsB) was also determined by introducing an on‐line photo‐oxidation step after the chromatographic separation. In this case the limits of detection and linear ranges for the different species studied were similar to the values obtained previously for As(V). The technique was tested with a human urine reference material and a volunteer's sample. © 1998 John Wiley & Sons, Ltd.