Magnetic carbon nanotubes modified with proteins and hydrophilic monomers: Cytocompatibility, in-vitro toxicity assays and permeation across biological interfaces.

Carbon nanotubes are promising materials for biomedical applications like delivery systems and tissue scaffolds. In this paper, magnetic carbon nanotubes (M-CNTs) covered with bovine serum albumin (M-CNTs-BSA) or functionalized with hydrophilic monomers (M-CNTs-HL) were synthesized, characterized, and evaluated concerning their interaction with Caco-2 cells. There is no comparison between these two types of functionalization, and this study aimed to verify their influence on the material's interaction with the cells. Different concentrations of the nanotubes were applied to investigate cytotoxicity, cell metabolism, oxidative stress, apoptosis, and capability to cross biomimetic barriers. The materials showed cytocompatibility up to 100 µg mL-1 and a hemolysis rate below 2 %. Nanotubes' suspensions were allowed to permeate Caco-2 monolayers for up to 8 h under the effect of the magnetic field. Magnetic nanoparticles associated with the nanotubes allowed estimation of permeation through the monolayers, with values ranging from 0.50 to 7.19 and 0.27 to 9.30 × 10-3 µg (equivalent to 0.43 to 6.22 and 0.23 to 9.54 × 10-2 % of the initially estimated mass of magnetic nanoparticles) for cells exposed and non-exposed to the magnets, respectively. Together, these results support that the developed materials are promising for applications in biomedical and biotechnological fields.

Modern anthropogenic drought in Central Brazil unprecedented during last 700 years.

A better understanding of the relative roles of internal climate variability and external contributions, from both natural (solar, volcanic) and anthropogenic greenhouse gas forcing, is important to better project future hydrologic changes. Changes in the evaporative demand play a central role in this context, particularly in tropical areas characterized by high precipitation seasonality, such as the tropical savannah and semi-desertic biomes. Here we present a set of geochemical proxies in speleothems from a well-ventilated cave located in central-eastern Brazil which shows that the evaporative demand is no longer being met by precipitation, leading to a hydrological deficit. A marked change in the hydrologic balance in central-eastern Brazil, caused by a severe warming trend, can be identified, starting in the 1970s. Our findings show that the current aridity has no analog over the last 720 years. A detection and attribution study indicates that this trend is mostly driven by anthropogenic forcing and cannot be explained by natural factors alone. These results reinforce the premise of a severe long-term drought in the subtropics of eastern South America that will likely be further exacerbated in the future given its apparent connection to increased greenhouse gas emissions.

One-point calibration and matrix-matching concept for quantification of potentially toxic elements in wood by LA-ICP-MS.

The aim of this work is to evaluate two quantitative methods, based on the external calibration applied in laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis, known as (i) analytical curve and (ii) one-point calibration, using the concept of matrix matching to quantify three potentially toxic elements (PTEs) in wood samples. These can biologically register changes in the abiotic environment and be applied to monitoring climate change or environmental toxicity. In this case, standard sample preparation was evaluated to prepare the standard pellets using Pinus taeda species as a matrix-matching concept. Six pellets of P. taeda, with different Pb, Cd, and Ba concentrations, were prepared to build the analytical curve and one-point calibration strategies. The LA-ICP-MS parameters were optimised for 206Pb, 208Pb, 112Cd, 114Cd, 137Ba, and 138Ba isotope analysis in wood samples. The two calibration strategies provided 74-110% analytical recovery from certified reference materials and similar results to those obtained by ICP-MS through the acid digestion of environmental wood samples from São Paulo City (Brazil). This demonstrated the applicability of the one-point calibration strategy in quantifying PTEs in wood samples, which could be used with environmental analyses. Differences observed between the Ba isotope results obtained via LA-ICP-MS and ICP-MS quantification were related to sampling by LA-ICP-MS and the ICP-MS sample introduction, as well as to laser matrix and transport effects because of the difference between the wood species evaluated.

The role of silver nanoparticles effects in the homeostasis of metals in soybean cultivation through qualitative and quantitative laser ablation bioimaging.

BACKGROUND: Nanoparticles (NPs) are currently found in the world in the form of natural colloids and volcanic ash, as well as in anthropogenic sources, such as nanofertilizers; however, in the literature, there is still a lack of toxicological evidence, risk assessment, and regulations about the use and environmental impact of NPs in the agroindustrial system. Therefore, the aim of this work was to evaluate alterations caused by the presence of AgNPs during the development of soybean plants. METHODS: The BRS232 non-transgenic (NT) soybean plant and 8473RR (TRR) and INTACTA RR2 PRO (TIntacta) transgenic soybean plants were irrigated for 18 days under controlled conditions with deionized water (control), AgNPs, and AgNO3. The isotopes 107Ag+, 55Mn+, 57Fe+, 63Cu+, and 64Zn+ were mapped in leaves, using 13C+ as an internal standard (IS), and carried out using a laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) technique with a Nd:YAG (213 nm) laser source in the imagagin mode using the LA-iMageS software and also Mathlab. RESULTS: Leaf images showed a low Ag translocation, indicated by the basal signal of this ion. Additionally, the presence of Ag in the ionic form and as NPs altered the homeostasis of 112Cd+, 64Zn+, 55Mn+, 63Cu+, and 57Fe+ in different ways. Quantitative image analysis was performed for Cu. CONCLUSION: The behavior of TRR and TIntacta plants was different in the presence of ionic silver or AgNPs, confirming that the metabolism of these two plants, despite both being transgenic, are different. Through the images, it was observed that the response of plants was different in the face of the same stress conditions during their development.

There Is Plenty of Room in Plant Science: Nanobiotechnology as an Emerging Area Applied to Somatic Embryogenesis.

Somatic embryogenesis is an essential technology for high productivity in plant culture, and with the advent of nanotechnology, the synergism between these areas could be the answer to developing concepts involving Agriculture 4.0. This perspective permeates both areas, presenting the opportunities and challenges for the consolidation of ideas involving the application of nanoparticles to micropropagation processes (callus induction, preservation, growing, and modification, among others) and also to the production of byproducts (such as biosynthesis of nanoparticles and production of secondary metabolites). Nanotoxicological aspects are also emphasized as well as up-to-date instrumentation involved in these studies.

A feasible strategy based on high ultrasound frequency and mass spectrometry for discriminating individuals diagnosed with bipolar disorder and schizophrenia through ionomic profile.

RATIONALE: A viable and accurate method based on high-power ultrasound-assisted microextraction and inductively coupled plasma mass spectrometry was developed to determine metals in human serum from patients with bipolar disorder and schizophrenia. METHODS: A simple and rapid sample preparation method using a cup-horn sonoreactor was developed. The acid concentration of HNO3 (10, 20, and 40% v/v) and HCl (1, 5, 15, and 30% v/v) of the extraction solution, the sonication time (1, 3, 6, and 10 min), and the sonication amplitude (20, 40, 60, and 80%) were evaluated. Cd, Cu, Fe, Li, Pb, and Zn were determined in serum samples from patients with bipolar disorder and schizophrenia, and from healthy controls. Quantitative metal recoveries using the proposed method were compared under the same conditions using an ultrasonic bath, magnetic stirring, and microwave-assisted digestion. RESULTS: Optimum extraction conditions were obtained using HNO3 (40% v/v) + HCl (30% v/v) as the extraction solution with 3 min sonication time and 60% sonication amplitude. Significant differences were observed among the methods compared. On application of the sample preparation method based on high-power ultrasound-assisted microextraction coupled with inductively coupled plasma mass spectrometry, Pb and Cd in all the studied samples were below the limit of detection of our method. Compared with healthy controls, the concentration of Cu, Li, Fe, and Zn was found to be significantly higher for the bipolar disorder group, while these metals and Li were found at a lower level for the group diagnosed with schizophrenia. CONCLUSIONS: Principal component analysis showed a significant separation for the groups studied based on their ionomic profiles after the application of high-power ultrasound-assisted microextraction as a sample preparation strategy.

Spatial-temporal variability of metal pollution across an industrial district, evidencing the environmental inequality in São Paulo.

Although air pollution decreased in some cities that shifted from an industrial to a service-based economy, and vehicular emission regulation became more restrictive, it is still a major risk factor for mortality worldwide. In central São Paulo, Brazil, air quality monitoring stations and tree-ring analyses revealed a decreasing trend in the concentrations of particulate matter and metals. Such trends, however, may not be observed in industrial districts located in the urban periphery, where the usual mobile sources may be combined with local stationary sources. To evaluate environmental pollution in an industrial district in southeastern São Paulo, we assessed its spatial variability, by measuring magnetic properties and concentrations of Al, Ba, Ca, Cl, Cu, Fe, K, Mg, Mn, P, S, Sr, Zn in the bark of 62 trees, and its temporal trends, by measuring Cd, Cu, Ni, Pb, V, Zn in tree rings of three trees. Source apportionment analysis based on tree barks revealed two clusters with high concentrations of metals, one related to vehicular and industrial emissions (Al, Ba, Cu, Fe, Zn) in the east side of the industrial cluster, and the other related to soil resuspension (Cu, Zn, Mn) in its west side. These patterns are also supported by the magnetic properties of bark associated with iron oxides and titanium-iron alloy concentrations. Dendrochemical analyses revealed that only the concentrations of Pb consistently decreased over the last four decades. The concentrations of Cd, Cu, Ni, V, and Zn did not significantly decrease over time, in contrast with their negative trends previously reported in central São Paulo. This combined biomonitoring approach revealed spatial clusters of metal concentration in the vicinity of this industrial cluster and showed that the local population has not benefited from the decreasing polluting metal concentrations in the last decades.

Metallomics-based platforms for comparing the human blood serum profiles between bipolar disorder and schizophrenia patients.

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.

Dissolved arsenic in the upper Paraguay River basin and Pantanal wetlands.

Although high levels of dissolved arsenic were detected in surface and ground waters of Nhecolândia, a sub-region of the vast Pantanal wetlands in Brazil, the possible sources have not been clearly identified and the potential release from the wetland to the draining rivers has not been investigated. In this study we measured the dissolved As content in all the rivers and small streams that supply the southern Pantanal region, as well as in the two main rivers draining the wetland, i.e., the Cuiaba and Paraguay rivers and tributaries. In addition, Arsenic in surface waters, perched water-table, soils and sediments from 3 experimental sites located in the heart of Nhecolândia were compared. On the one hand, the results show the absence of As contamination in rivers that supply the Pantanal floodplain, as well as a lack of significant release from the floodplain to the main drains. The As contents in the rivers are <2 µg L-1, with variations that depend on the lithology and on the geomorphology at the collection point (uplands or floodplain). On the other hand, they confirm the regional extension of As contamination in Nhecolândia's alkaline waters with some values above 3 mg L-1. Arsenic is mainly in the arsenate form, and increases with the evaporation process estimated from sodium ion concentrations. The pH of soil solution and surface water increases rapidly during evapo-concentration up to values above 9 or 10, preventing adsorption processes on oxides and clay minerals and promoting the retention of dissolved arsenic in solution. Solutions from organic soil horizons show higher As contents in relation to Na, attributed to the formation of ternary complex As-(Fe/Al)-OM. In this alkaline pH range, despite high levels of dissolved As, soil horizons and lake sediments in contact with these waters show As values that correspond to uncontaminated environments.

Optimization of a Methodology for Quantification and Removal of Zinc Gives Insights Into the Effect of This Metal on the Stability and Function of the Zinc-Binding Co-chaperone Ydj1.

Ydj1, a class B J-protein (Hsp40) in yeast, has two zinc finger domains in each monomer and belongs to an important co-chaperone family that plays crucial roles in cells, such as recognizing and binding partially folded proteins and assisting the Hsp70 chaperone family in protein folding. Yeast cells with ydj1 deletion were less efficient at coping with zinc stress than wild-type cells, and site-directed mutagenesis studies that impair or delete the zinc finger region have confirmed the importance of this region to the function of Ydj1; however, little is known about whether the presence of zinc is critical for the function of the protein. To gain insights into the effect of zinc on the structure and function of Ydj1 without having to modify its primary structure, a method was developed and optimized to quantify and remove the zinc from the protein. Recombinant Ydj1 was produced and purified, and its zinc content was determined by ICP-MS. The result showed that two zinc atoms were bound per monomer of protein, a good indicator that all sites were saturated. To optimize the removal of the bound zinc, variations on chelating agent (EDTA, EGTA, 1,10-phenanthroline), chelator concentration, reaction time, pH, and temperature were tested. These procedures had no effect on the overall secondary structure of the protein, since no significant changes in the circular dichroism spectrum were observed. The most significant removal (91 ± 2%, n = 3) of zinc was achieved using 1,10-phenanthroline (1 × 10-3 mol L-1) at 37°C with a pH 8.5 for 24 h. Zinc removal affected the stability of the protein, as observed by a thermal-induced unfolding assay showing that the temperature at the middle of the transition (Tm) decreased from 63 ± 1°C to 60 ± 1°C after Zn extraction. In addition, the effect on the ability of Ydj1 to protect a model protein (luciferase) against aggregation was completely abolished after the Zn removal procedure. The main conclusion is that zinc plays an important role in the stability and activity of Ydj1. Additionally, the results highlight the medical importance of chaperones, as altered zinc homeostasis is implicated in many diseases, such as neurodegenerative disorders.

Sample Preparation Focusing on Plant Omics.

Because of strong impact of omics in many fields, and the complexity of the samples when focusing on areas such as genomics, (metallo)proteomics, metabolomics, among others, it is easy to rationalize the great importance that sample preparation has for achieving reliable results, mainly considering plant science. Then, this chapter points out applications of the sample preparation focusing on such areas, and a diversity of strategies, techniques, and procedures is highlighted and commented.

Minimalist strategies applied to analysis of forensic samples using elemental and molecular analytical techniques - A review.

Forensic science is an emerging field driven by a number of factors, and the development of different methods of analyses, instruments, and techniques is of great help to experts in the field. Sampling and sample preparation in forensic cases are of utmost importance, and therefore, the methods for processing (or not) the samples are critical for acquiring accurate results. Some alternatives for attaining the minimalist concept, i.e. little or no sample treatment, are discussed in this review. For elemental analysis, analytical techniques, such as X-ray spectrometry, laser-ablation mass spectrometry, laser-induced breakdown spectrometry, inductively coupled plasma mass spectrometry and optical emission spectrometry, and Mössbauer spectrometry are overviewed. Molecular analysis, such as Raman spectroscopy, and ambient ionization mass spectrometry are discussed. Some representative examples are presented that involve in situ analysis, counterfeit bank notes and documents, post-mortem and bone analyses, and forensic analysis of drugs, glass, fingerprints, biological fluids and explosives.

Quantifying proteins at microgram levels integrating gel electrophoresis and smartphone technology.

A combination between gel electrophoresis and smartphone technology is applied for quantifying proteins in a serum sample. Electrophoresis not only allows one to separate different proteins but also to build-up a calibration curve for those proteins. To expand its applicability, a smartphone allows one to capture a gel image, through its camera. Additionally, the treatment of the data extracted through each protein band is performed using a freely available program (PhotoMetrix), which is downloaded to one's own smartphone. Through this approach, the quantification of proteins such as albumin, immunoglobulin, and carbonic anhydrase is performed in a serum sample by acquiring images using 32 × 32 pixels for each image in the region of the protein bands. An LOQ from 1.9 to 2.4 µg and r2 > 0.980 may be obtained. Comparing results through the analyses of the gels using Image Master 2D Platinum 6.0 software reflects good agreement (95% confidence level) between the results. SIGNIFICANCE STATEMENT: In many biological studies involving structural analysis or biophysical and biochemical characterization after purification process, or even in assays of protein:protein interaction, the estimation of protein quantity and protein purity is a fundamental step. However, even although many methodologies are proposed in the literature for quantifying proteins, they present some limitations, once are frequently expensive and require solution sample. In addition, they usually do not quantify the specific active concentration, but the total amount. Thus, it is necessary to develop an easy, fast and low-cost method that allows to quantify and to evaluate protein purity of reactional system, for example, a protein:protein interaction. In this way, we presented a simple strategy based on the integration of Smartphone technology and gel electrophoresis, where SDS-PAGE provides multiple information regarding the quality of the protein, such as the presence of degradation products, as well as if there was interaction reaction between proteins. Then, the smartphone detects the proteins in the SDS-PAGE gel, allowing to evaluate purity degree and the quantity, at microgram level, of the protein. We believe that the combination of these features may help to increase the productivity and accuracy of gel electrophoresis analysis, and the results obtained through a smartphone, easily achieved in our pockets.

Chemical Speciation and Metallomics.

Chemical speciation approaches is an inherent part of metallomics, once metals/metalloids and organic structures need to be currently evaluated for attaining metallomics studies. Then, this chapter focuses on the applications of the chemical speciation applied to the human health risk, food and human diet, drugs, forensic, nanoscience, and geological metallomics, also pointing out the advances in such area. Some aspects regarding sample preparation is commented along this chapter, and some strategies for maintaining the integrity of the metallomics information are also emphasized.

The enigma of aluminum deposition in bone tissue from a patient with chronic kidney disease: a case report.

About four decades ago, the relationship between dialysis-dementia and aluminum (Al) began to be established. The restriction of drugs containing Al and improvements on water quality used for dialysis resulted in the clinical disappearance of Al intoxication. However, high prevalence of Al deposition in bone tissue from Brazilian dialysis patients is still being detected. Through the case report of a patient on hemodialysis (HD) for one year, presenting significant Al deposition in bone tissue, we speculated if this problem is not being underestimated. We used extensive investigation to identify potential sources of Al exposure with a careful review of medication history and water quality controls. Al concentration was measured by different methods, including mass spectrometry, in poly-electrolyte concentrate solutions and solution for peritoneal dialysis, in an attempt to elucidate the possible sources of contamination. The objective of this case report is to alert the medical community about a potential high prevalence of Al deposition in bone tissue and to discuss the possible sources of contamination in patients with chronic kidney disease (CKD).

The enigma of aluminum deposition in bone tissue from a patient with chronic kidney disease: a case report / O enigma da deposição de alumínio no tecido ósseo de um paciente com doença renal crônica: relato de caso

ABSTRACT About four decades ago, the relationship between dialysis-dementia and aluminum (Al) began to be established. The restriction of drugs containing Al and improvements on water quality used for dialysis resulted in the clinical disappearance of Al intoxication. However, high prevalence of Al deposition in bone tissue from Brazilian dialysis patients is still being detected. Through the case report of a patient on hemodialysis (HD) for one year, presenting significant Al deposition in bone tissue, we speculated if this problem is not being underestimated. We used extensive investigation to identify potential sources of Al exposure with a careful review of medication history and water quality controls. Al concentration was measured by different methods, including mass spectrometry, in poly-electrolyte concentrate solutions and solution for peritoneal dialysis, in an attempt to elucidate the possible sources of contamination. The objective of this case report is to alert the medical community about a potential high prevalence of Al deposition in bone tissue and to discuss the possible sources of contamination in patients with chronic kidney disease (CKD).

RESUMO Cerca de quatro décadas atrás, a relação entre demência relacionada à diálise e alumínio (Al) começou a ser estabelecida. A restrição de medicamentos contendo Al e melhorias na qualidade da água utilizada na diálise resultaram no desaparecimento clínico da intoxicação por Al. Contudo, no Brasil continua a ser identificada uma elevada prevalência de deposição de Al no tecido ósseo de pacientes em diálise. O presente relato de caso de um paciente em hemodiálise (HD) há um ano com deposição significativa de Al no tecido ósseo nos leva a especular se esse problema não tem sido subestimado. Realizamos uma ampla investigação para identificar possíveis fontes de exposição ao Al, com uma revisão cuidadosa do histórico de medicação e dos controles de qualidade da água. A concentração de Al foi medida por diferentes métodos, incluindo espectrometria de massa, nos concentrados polieletrolíticos para hemodiálise e soluções de diálise peritoneal, na tentativa de elucidar as possíveis fontes de contaminação. O objetivo do presente relato de caso é alertar a comunidade médica sobre uma possível elevada prevalência de deposição de Al no tecido ósseo e discutir as possíveis fontes de contaminação nos pacientes com doença renal crônica (DRC).

Evaluation of changes in the macro and micronutrients homeostasis of transgenic and non-transgenic soybean plants after cultivation with silver nanoparticles through ionomic approaches.

An ionomic approach is conducted for evaluating the silver distribution, in different soybean plant compartments, as well as its influence on the homeostasis of some macro (P and S) and micro (Cu, Fe, Mn and Zn) nutrients. Silver is added to transgenic and non-transgenic soybean plants as nanoparticles or silver nitrate for comparative purposes. The transgenic plants translocate a higher amount of silver (100 and 65% for silver nanoparticles and silver nitrate expositions, respectively) than non-transgenic, and considering the treatments, the cultivation with silver nanoparticles results in a higher translocation rate (100 and 21% for transgenic and non-transgenic plants, respectively). In addition, significant differences are found (p < 0.05) considering those macro and micronutrients in all plant compartments, mainly in the roots of those treated plants, indicating not only that both silver forms evaluated interfere in the plant metabolism, but also their toxicities.

Mobility of polivinylpyrrolidone coated silver nanoparticles in tropical soils.

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.

Elemental fingerprinting of schizophrenia patient blood plasma before and after treatment with antipsychotics.

Antipsychotics are the main line of treatment for schizophrenia, a disorder that affects about 1% of the worldwide population. Considering the poor performance of antipsychotics on patients, this work aimed at detecting alterations in the elemental profile resulting from the use of this type of medication using an elemental fingerprinting strategy. We evaluated 56 plasma samples from schizophrenia patients by inductively coupled plasma mass spectrometry (ICP-MS) before (t0) and after 6 weeks (t6) of treatment. The level of response of the patients (good vs. poor responders) and the medications taken were considered. Zinc, aluminum, phosphorus, and iron levels were found to be increased, whereas sodium, potassium, calcium, and magnesium levels decreased after treatment. Aluminum presented a higher level in poor responders at t0 when compared to good responders. At t6, iron showed an increased level when compared to t0 for good responders; however, its level remained constant in poor responders. The results of this exploratory study provide clues for further investigations on the role of metal ions in the treatment of schizophrenia.

Simplifying the human serum proteome for discriminating patients with bipolar disorder of other psychiatry conditions.

PURPOSE: An exploratory analysis using proteomic strategies in blood serum of patients with bipolar disorder (BD), and with other psychiatric conditions such as Schizophrenia (SCZ), can provide a better understanding of this disorder, as well as their discrimination based on their proteomic profile. METHODS: The proteomic profile of blood serum samples obtained from patients with BD using lithium or other drugs (N=14), healthy controls, including non-family (HCNF; N=3) and family (HCF; N=9), patients with schizophrenia (SCZ; N=23), and patients using lithium for other psychiatric conditions (OD; N=4) were compared. Four methods for simplifying the serum samples proteome were evaluated for both removing the most abundant proteins and for enriching those of lower-abundance: protein depletion with acetonitrile (ACN), dithiothreitol (DTT), sequential depletion using DTT and ACN, and protein equalization using commercial ProteoMiner® kit (PM). For proteomic evaluation, 2-D DIGE and nanoLC-MS/MS analysis were employed. RESULTS: PM method was the best strategy for removing proteins of high abundance. Through 2-D DIGE gel image comparison, 37 protein spots were found differentially abundant (p<0.05, Student's t-test), which exhibited ≥2.0-fold change of the average value of normalized spot intensities in the serum of SCZ, BD and OD patients compared to subject controls (HCF and HCNF). From these spots detected, 13 different proteins were identified: ApoA1, ApoE, ApoC3, ApoA4, Samp, SerpinA1, TTR, IgK, Alb, VTN, TR, C4A and C4B. CONCLUSIONS: Proteomic analysis allowed the discrimination of patients with BD from patients with other mental disorders, such as SCZ. The findings in this exploratory study may also contribute for better understanding the pathophysiology of these disorders and finding potential serum biomarkers for these conditions.