RESUMO
RATIONALE: An evaluation of bipolar disorder (BD) and schizophrenia (SCZ) was carried out, from a metallomics point of view, using native conditions, attempting to preserve the interaction between metals and biomolecules. METHOD: For this task, blood serum samples from healthy individuals and patients were compared. In addition, the profiles of metal ions and metalloids involved in the pathologies were quantified, and a comparison was carried out of the protein profile in serum samples of healthy individuals and diseased patients. RESULTS: After optimization and accuracy evaluation of the method, different concentrations of Li, Mg, Mn and Zn were observed in the samples of BD patients and high levels of copper for SCZ patients, indicating an imbalance in the homeostasis of important micronutrients. The treatment, especially with lithium, may be related to competition between metallic ions. BD-related metallobiomolecules were detected, preserving the binding between metal ions and biomolecules, with four fractions detected in the ultraviolet range (280 nm). Four fractions were collected by high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICP-MS) and the proteins were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The Ig lambda chain V-IV region Hil, immunoglobulin heavy constant gama 1 (IGHG1) and beta-2-glycoprotein 1 (or ApoH) was identified in SCZ samples, suggesting its relationship with mood disorders. Surprisingly, Protein IGKV2D-28 was identified only in BD samples, opening up new possibilities for studies regarding the role of this protein in BD. CONCLUSIONS: This approach brings new perspectives to the comprehension of mood disorders, highlighting the importance of metallomics science in disease development. This strategy showed an innovative potential for evaluating mood disorders at the proteomic level, making it possible to identify proteins related to mood disorders and BD.
Assuntos
Transtorno Bipolar/sangue , Análise Química do Sangue/métodos , Metais/sangue , Esquizofrenia/sangue , Oligoelementos/sangue , Adulto , Transtorno Bipolar/tratamento farmacológico , Análise Química do Sangue/instrumentação , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/química , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Masculino , Manganês/sangue , Espectrometria de Massas/métodos , Micro-Ondas , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Zinco/sangueRESUMO
Experiments in saturated soil columns were performed to investigate the transport and retention of 25 nm and 75 nm silver nanoparticles stabilized with polyvinylpyrrolidone (PVP-AgNPs) in two Brazilian soils (sandy and sandy-clay). The normalized concentration of the PVP-AgNPs was obtained through a flow injection analysis method based on the surface plasmon ressonance effect of the metallic nanoparticles. The use of the ultraviolet-visible spectroscopy (UV-Vis) allows a rapid and low-cost analysis. The obtained breakthrough curves (BCs) were modeled with a deterministic model of solute transport in steady conditions of water flow and considering two regions of non-physical equilibrium; this model allowed the determination of the hydrodynamic parameters. It was found that the process occurs in condition of non-equilibrium, with a low mass transfer for larger NP, and that the process is predominantly advective and affected by the pore size of the soil packed in the columns. The BCs for PVP-AgNPs obtained by UV-Vis spectroscopy were compared with the BCs obtained by ICP-MS and with BCs of the bromide anion, confirming that the nanoparticles have a low retention and few modifications when transported through the soil column. These PVP-AgNPs are highly mobile and can be transported through the studied tropical soils, representing a potential environmental problem, due to the possibility of these materials reaching groundwater. On the contrary, the conservative behavior of PVP-AgNPs in the studied tropical soils, indicates its potential use as tracers, substituting the bromide anion which has been demonstrated to be not a good tracer in the same conditions.
Assuntos
Nanopartículas Metálicas/química , Povidona/química , Prata/química , Solo/normas , Silicatos de Alumínio , Brasil , Argila , Meio Ambiente , Água Subterrânea/química , HidrodinâmicaRESUMO
The efficiency of three different depletion methods to remove the most abundant proteins, enriching those human serum proteins with low abundance is checked to make more efficient the search and discovery of biomarkers. These methods utilize magnetic nanoparticles (MNPs), chemical reagents (sequential application of dithiothreitol and acetonitrile, DTT/ACN), and commercial apparatus based on immunoaffinity (ProteoMiner, PM). The comparison between methods shows significant removal of abundant protein, remaining in the supernatant at concentrations of 4.6±0.2, 3.6±0.1, and 3.3±0.2µgµL-1 (n=3) for MNPs, DTT/ACN and PM respectively, from a total protein content of 54µgµL-1. Using GeLC-MS/MS analysis, MNPs depletion shows good efficiency in removing high molecular weight proteins (>80kDa). Due to the synergic effect between the reagents DTT and ACN, DTT/ACN-based depletion offers good performance in the depletion of thiol-rich proteins, such as albumin and transferrin (DTT action), as well as of high molecular weight proteins (ACN action). Furthermore, PM equalization confirms its efficiency in concentrating low-abundant proteins, decreasing the dynamic range of protein levels in human serum. Direct comparison between the treatments reveals 72 proteins identified when using MNP depletion (43 of them exclusively by this method), but only 20 proteins using DTT/ACN (seven exclusively by this method). Additionally, after PM treatment 30 proteins were identified, seven exclusively by this method. Thus, MNPs and DTT/ACN depletion can be simple, quick, cheap, and robust alternatives for immunochemistry-based protein depletion, providing a potential strategy in the search for disease biomarkers.