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1.
J Chromatogr A ; 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30509618

RESUMO

A capillary electrophoresis with diode array and tandem mass spectrometry detection (CE-UV-MS/MS) method has been developed for the targeted assessment of cardiovascular biomarkers candidates, trimethylamine-N-Oxide (TMAO) and l-carnitine, and creatinine in human urine samples. The dual detection was applied due to the high concentration of creatinine (monitored by UV detection at 200 nm) in relation to TMAO and l-carnitine (quantified by selected reaction monitoring (SRM) mass spectrometry), in human urine. All instrumental parameters, sheath liquid (SHL) and background electrolyte (BGE) compositions were optimized with a pool of urine provided by adult healthy volunteers and evaluated by signal-to-noise ratio (SNR) and peak shape of TMAO. The compositions for the optimized BGE was formic acid at concentration of 0.10 mol L-1, and for SHL was 70:30 MeOH:H2O containing 0.05% (v/v) formic acid, delivered at a flow rate of 5 µL min-1. Limits of detection for TMAO, l-carnitine and creatinine were 0.76, 0.54 and 303 µmol L-1, respectively. Limits of quantification were 2.5, 1.8 and 1000 µmol L-1, respectively. Linearity was evaluated by ANOVA and presented R2 from 0.993 to 0.997. Precision and accuracy were evaluated at three concentration levels. Coefficients of variation (CV) from 1 to 21% were obtained for the intra-day precision evaluation and from 2 to 16% for the inter-day precision evaluation. The recovery ranged from 75 to 116%. Quantitation of TMAO and l-carnitine in infarcted patients urine in comparison to healthy individuals indicated a 2.2 fold increase of TMAO and a 7.0 fold increase of l-carnitine. These results showed the potential applicability of the proposed method for the evaluation of TMAO and l-carnitine in urine within a panel of candidate metabolites in targeted metabolomics studies of cardiovascular diseases among other conditions.

2.
Trials ; 18(1): 601, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29258572

RESUMO

BACKGROUND: Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling. METHODS/DESIGN: BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months. The trial will also evaluate the improvement in the immune/inflammatory responses mediated by B and T lymphocytes. Omics field (metabolomics and proteomics) will help to understand these responses by molecular events. DISCUSSION: BATTLE-AMI is aimed to (1) evaluate the role of subsets of lymphocytes on microcirculation improvement and (2) show how the choice of statin/antiplatelet therapy may affect cardiac remodeling after acute myocardial infarction with ST elevation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02428374 . Registered on 28 September 2014.


Assuntos
Anti-Inflamatórios/administração & dosagem , Linfócitos B/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Mediadores da Inflamação/sangue , Inibidores da Agregação de Plaquetas/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Terapia Trombolítica , Adenosina/administração & dosagem , Adenosina/análogos & derivados , Anti-Inflamatórios/efeitos adversos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores/sangue , Brasil , Protocolos Clínicos , Clopidogrel , Angiografia Coronária , Quimioterapia Combinada , ELISPOT , Ezetimiba/administração & dosagem , Feminino , Citometria de Fluxo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imagem por Ressonância Magnética , Masculino , Metabolômica , Inibidores da Agregação de Plaquetas/efeitos adversos , Proteômica , Projetos de Pesquisa , Rosuvastatina Cálcica/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , Sinvastatina/administração & dosagem , Volume Sistólico/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Terapia Trombolítica/efeitos adversos , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
3.
Psychiatry Res ; 258: 268-273, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28918859

RESUMO

The present study aimed at investigating possible alterations in the serum lipid profile of euthymic patients with bipolar disorder type I (BD) compared to healthy controls (HC). Thirty-five individuals from both genders were recruited, with 14 diagnosed and treated as BD patients (BD group) and 21 healthy subjects (HC group). Clinical assessment was based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Young Mania Rating Scale (YMRS), and 17-items of Hamilton Depression Rating Scale (HDRS-17) data, which were used to confirm diagnosis, to verify psychiatric comorbidities, and to estimate the severity of manic and depressive symptoms. Ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) was applied to analyze the lipids extracted from all serum samples from both studied groups. In this pioneer and exploratory study, we observed different serum lipid profiles for BD and HC groups, especially regarding glycerophospholipid, glycerolipid, and sphingolipid distribution. Multivariate statistical analyses indicated that 121 lipids were significantly different between BD and HC. Phosphatidylinositols were identified as the most altered lipids in BD patient sera. The results of this preliminary study reinforce the role of lipid abnormalities in BD and offer additional methodological possibilities for investigation in the field.


Assuntos
Transtorno Bipolar/sangue , Lipídeos/sangue , Espectrometria de Massas , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Comorbidade , Depressão/sangue , Depressão/diagnóstico , Depressão/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositóis/sangue
4.
Adv Exp Med Biol ; 965: 3-17, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28132174

RESUMO

Nowadays, there is a growing interest in deeply understanding biological mechanisms not only at the molecular level (biological components) but also the effects of an ongoing biological process in the organism as a whole (biological functionality), as established by the concept of systems biology. Within this context, metabolomics is one of the most powerful bioanalytical strategies that allow obtaining a picture of the metabolites of an organism in the course of a biological process, being considered as a phenotyping tool. Briefly, metabolomics approach consists in identifying and determining the set of metabolites (or specific metabolites) in biological samples (tissues, cells, fluids, or organisms) under normal conditions in comparison with altered states promoted by disease, drug treatment, dietary intervention, or environmental modulation. The aim of this chapter is to review the fundamentals and definitions used in the metabolomics field, as well as to emphasize its importance in systems biology and clinical studies.


Assuntos
Metabolômica , Biologia de Sistemas , Humanos
5.
Adv Exp Med Biol ; 965: 77-98, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28132177

RESUMO

Amongst all omics sciences, there is no doubt that metabolomics is undergoing the most important growth in the last decade. The advances in analytical techniques and data analysis tools are the main factors that make possible the development and establishment of metabolomics as a significant research field in systems biology. As metabolomic analysis demands high sensitivity for detecting metabolites present in low concentrations in biological samples, high-resolution power for identifying the metabolites and wide dynamic range to detect metabolites with variable concentrations in complex matrices, mass spectrometry is being the most extensively used analytical technique for fulfilling these requirements. Mass spectrometry alone can be used in a metabolomic analysis; however, some issues such as ion suppression may difficultate the quantification/identification of metabolites with lower concentrations or some metabolite classes that do not ionise as well as others. The best choice is coupling separation techniques, such as gas or liquid chromatography, to mass spectrometry, in order to improve the sensitivity and resolution power of the analysis, besides obtaining extra information (retention time) that facilitates the identification of the metabolites, especially when considering untargeted metabolomic strategies. In this chapter, the main aspects of mass spectrometry (MS), liquid chromatography (LC) and gas chromatography (GC) are discussed, and recent clinical applications of LC-MS and GC-MS are also presented.


Assuntos
Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Humanos
6.
Trials ; 18(1): 601-601, 2017.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-36830

RESUMO

BACKGROUND: Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling. METHODS/DESIGN: BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months...(AU)


Assuntos
Infarto do Miocárdio , Linfócitos B , Espectroscopia de Ressonância Magnética , Metabolômica , Proteômica
7.
Electrophoresis ; 36(18): 2336-2347, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26095472

RESUMO

This review article compiles in a critical manner literature publications regarding seven neglected diseases (ND) prioritized in Brazil (Chagas disease, dengue, leishmaniasis, leprosy, malaria, schistosomiasis, and tuberculosis) under the perspective of metabolomics. Both strategies, targeted and untargeted metabolomics, were considered in the compilation. The majority of studies focused on biomarker discovery for diagnostic purposes, and on the search of novel or alternative therapies against the ND under consideration, although temporal progression of the infection at metabolic level was also addressed. Tuberculosis, followed by schistosomiasis, malaria and leishmaniasis are the diseases that received larger attention in terms of number of publications. Dengue and leprosy were the least studied and Chagas disease received intermediate attention. NMR and HPLC-MS technologies continue to predominate among the analytical platforms of choice in the metabolomic studies of ND. A plethora of metabolites were identified in the compiled studies, with expressive predominancy of amino acids, organic acids, carbohydrates, nucleosides, lipids, fatty acids, and derivatives.

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