Publications by authors named "Igor Gustavo Carvalho Oliveira"

Background: High circulating concentrations of homocysteine (Hcy), a sulfur-containing amino acid, and homocysteic acid (HCA), an Hcy oxidized derivative, are an independent risk factor for developing Alzheimer's disease (AD), a neurodegenerative disorder that causes progressive cognitive decline. Therefore, these two endogenous compounds might be potential AD biomarkers. Nevertheless, few studies have attempted to quantify Hcy and HCA in the cerebrospinal fluid (CSF), the best validated fluid for evaluating neurodegenerative disorders.

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Despite the widespread use of L-3,4-dihydroxyphenylalanine (L-DOPA) as the gold standard for dopamine (DA) replacement in Parkinson's Disease (PD), its prolonged administration frequently leads to L-DOPA-induced dyskinesia (LID), a significant therapeutic challenge. Modulating the endocannabinoid system has emerged as a promising approach for managing LID. This study explored whether cannabidiol (CBD), a non-psychoactive compound of Cannabis sativa, and PECS-101, a fluorinated derivative of CBD, could mitigate the onset and progression of LID.

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Cannabidiol (CBD) and Δ-tetrahydrocannabinol (THC), the main components of Cannabis sativa plants, can interact with specific cell receptors known as cannabinoid receptors (CBs). The endogenous compounds anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are CB agonists, and, alongside enzymes, they constitute the endocannabinoid system (ECS) and take part in neuromodulation. Several LC-MS/MS methods have been developed to quantify these compounds in biological matrixes, but a fast and simple method that can determine these analytes in plasma samples simultaneously is not available.

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In this study, we present a novel combination of carbon nanotubes (CNT), widely used as a sorbent material in solid-phase extraction-based methodologies, with polybenzimidazole (PBI), recently introduced as a universal binder for physical immobilization of sorbent particles. This combination was used to prepare CNT-PBI coated solid-phase microextraction (SPME) devices (fibers, arrows, and blades) suitable for both thermal and solvent desorption. The resulting CNT-PBI SPME devices presented excellent mechanical resistance and high thermal stability, capable of enduring multiple thermal desorption cycles without compromising extraction efficiency.

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To evaluate the endocannabinoid system in an animal model of Parkinson's disease, in-tube solid-phase microextraction (in-tube SPME) was directly coupled to a tandem mass spectrometry (MS/MS) system for determination of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat brain samples. In-tube SPME-which consisted of a microtube of restricted access material (RAM) with a hydrophilic diol external surface and a hydrophobic octyl inner surface-efficiently excluded (up to 95%) macromolecules from the biological samples and selectively pre-concentrated the analytes. In-tube SPME parameters, such as sample volume, mobile phases, flow rate, and pre-concentration time, were evaluated to improve the extraction efficiency and throughput performance.

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A simple and reliable method was developed and validated to determine the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat brain samples by micro salting-out assisted liquid-liquid extraction combined with ultra-high performance liquid chromatography tandem mass spectrometry (SALLLE/UHPLC-MS/MS). The SALLE parameters (brain homogenate volume, salting-out agent, salt concentration, salt solution volume, organic solvent, organic solvent volume, and centrifugation temperature) were optimized to improve sensitivity and selectivity of the method. The SALLE/UHPLC-MS/MS method presented linear ranges from 2.

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