ESS - FAR - Artigos
URI permanente para esta coleção:
Navegar
Entradas recentes
- Flow-through 3D-printed device for automatic microsampling and handling of dried urine spotsPublication . Fernandes, Sara R.; Cunha, Diana R.; Guidetti, Federica; Barreiros, Luísa; Miró, Manuel; Segundo, Marcela A.; Barreiros, Luisa; Fernandes, Sara3D printing has revolutionized analytical chemistry by allowing the development of miniaturized and high- precision devices. In bioanalysis, sample collection and pre-treatment can be facilitated using 3D printing combined with flow analysis and mass spectrometry. Hence, a customized 3D-printed device was designed for sampling, clean-up, and target retrieval using filter paper as a sample collection material and sorbent. This device was integrated into a flow network for fully automatic extraction and applied to detect three anticoagulants in human urine. Different printing materials, designs and other factors related to fused deposition modeling 3D printing such as the infill percentage were evaluated to achieve the configuration that allowed the implementation of sampling and separation procedures in the same device. After establishing the final design of the device, several parameters such as the eluent composition and the hydrodynamic conditions were studied to enhance the recovery of the target analytes, namely apixaban, rivaroxaban, and warfarin. The processed samples were analyzed by UHPLC-MS/MS in positive ionization mode using a BEH C18 column. The method demonstrated good linearity (r2 >0.998) for quantification of the target analytes at concentrations ranging from 0.20 to 20 μg L 1 for apixaban and warfarin, and from 0.50 to 20 μg L 1 for rivaroxaban. LOD and LOQ values of 0.06–0.2 μg L 1 and 0.1–0.5 μg L 1, respectively, for undiluted urine were obtained. The method was found to be accurate (97.0–102 %) and precise (CV ≤6.0 %). This new approach, according to the scores obtained by applying the AGREEprep (0.70), AGREE (0.65) and BAGI (70) metrics, can be described as environmentally friendly, practical and suitable for bioanalytical purposes.
- Understanding the influence of transfusion and blood loss on tranexamic acid concentration in scoliosis surgery with blood lossPublication . Sá, Paula Alexandra; Barreiros, Luísa; Segundo, Marcela A.; Cruz, Eugénia; Langenecker, Sibylle; Barreiros, LuisaTranexamic acid (TXA) stabilizes clot formation by inhibiting fibrin degradation and improves postoperative outcomes. However, rare adverse events (e.g., thrombosis, seizures) warrant dose–risk evaluation. This study examines how perioperative blood loss and transfusion practices affect TXA concentrations during paediatric scoliosis surgery. Forty-three patients undergoing scoliosis surgery with TXA were retrospectively analysed. The study assessed the impact of packed red blood cell (PRBC) transfusion on plasma TXA levels and whether maintaining concentrations ≥10 μg/ mL correlated with intraoperative blood loss. TXA levels were measured using UHPLC–MS/MS. Results: Median TXA concentration 30 min after the loading dose was 37.8 μg/mL (IQR: 31.4–39.6 μg/mL), decreasing to 10.6 μg/mL (IQR: 9.7–13.5 μg/mL) after transfusion. At surgery end, the mean concentration was 12.9 ± 2.5 μg/mL. Thirty-one patients maintained TXA levels ≥10 μg/mL, associated with 80% inhibition of tissue plasminogen activator. Of six patients below this threshold, five had received transfusions. A significant correlation was found between higher intraoperative blood loss and lower TXA levels, consistent with a dilutional effect. In contrast, among patients with TXA ≥ 10 μg/mL, correlation with blood loss was weak (Spearman's ρ = 0.11, p = 0.54). Findings suggest homologous PRBC transfusion reduces plasma TXA through volume expansion. Sustaining TXA concentrations >10 μg/mL is essential for antifibrinolytic efficacy and haemostatic outcomes. The dilutional impact of PRBC transfusion underscores the need for intraoperative dose adjustment. Optimizing TXA dosing requires understanding pharmacokinetics and patient variability.
- Targeted mass spectrometry method for the determination of multiple gut-microbiota metabolites in human plasmaPublication . Fernandes, Sara R.; Barreiros, Luísa; Azorín, Cristian; Silva, Eduarda M.P.; Segundo, Marcela A.; Barreiros, LuisaThe gut microbiota profoundly impacts human health by producing metabolites that can act as biomarkers for disease diagnosis and therapy. However, accurately measuring these metabolites in biomatrices is challenging due to their low concentrations, high molecular diversity, and interference from matrix components, demanding advanced and precise analytical methodologies. Hence, an ultra-high-performance liquid chromatography method coupled to triple quadrupole-tandem mass spectrometry detection, combined with a chemical derivatization procedure, was developed and validated to quantify seven gut metabolites, namely acetic acid, propionic acid, butyric acid, p-cresol sulfate, 3-indoxyl sulfate, indole-3-acetic acid, and L-tryptophan, in human plasma. Samples were prepared by protein precipitation with acetonitrile and subsequently derivatized using 3-nitrophenylhydrazine. Chromatographic separation was achieved using a BEH C18 column, with elution performed at a f low rate of 0.2mLmin 1 and in gradient mode using formic acid-water (1:1000, v/v) and formic acid- acetonitrile (1:1000, v/v) as mobile phase components. The mass spectrometer was operated in negative ionization mode and data was acquired in selected reaction monitoring. Good linearity was achieved (r 2 >0.997) for all the target gut metabolites in the evaluated concentration ranges, with low LLOQ values (0.4–8 M). The method proved to be accurate (87.0–114 %) and precise (CV ≤ 13.5 %), achieving a score of 65 in the Blue Applicability Grade Index (BAGI) metric, which confirmed its practicality. The developed method was ultimately employed to the analysis of plasma samples from children and adults involved in clinical studies, demonstrating its usefulness in medical research.
- Untargeted metabolomics HRMS data processing using regions of interest and multivariate curve resolution approaches to unveil health-to-disease transitionPublication . Barreiros, Luísa; Maia, Benedita Sampaio; Alencastre, Inês Soares; Tauler, Româ; Segundo, Marcela A.; Barreiros, LuisaEarly diagnosis has the potential to prevent or minimize the progression of diseases. The discovery of biomarkers that permit to pinpoint the health-to-disease transition is thus of crucial importance to improve diagnostic eff iciency and treatment. Over the last years, untargeted metabolomic analysis of biomatrices has become a valuable tool to identify biomarkers of health status. However, it is still a recent research field with many challenges to address, namely the implementation of data treatment strategies that allow to deal efficiently with the highly complex data sets generated, without losing accuracy or relevant information. This work pursued the application of the chemometrics method Regions of Interest-Multivariate Curve Resolution (ROIMCR) to the MS- based metabolomic profiling of plasma samples aiming at the identification of chronic kidney disease (CKD) biomarkers. ROIMCR successfully resolved the plasma profiles of three groups of individuals: healthy controls, intermediate stage (pre-dialysis) and end-stage (in dialysis) CKD patients. Positive (MS1+) and negative (MS1 ) data were processed simultaneously without requiring previous time alignment, resulting in time-effective analysis with increased metabolite coverage and identification. Multivariate analysis (PCA, PLS-DA, ASCA) revealed that samples were clustered according to health status and permitted to determine the most influential metabolites in differentiating groups. Metabolites identification evidenced recognized biomarkers of CKD, validating the proposed approach, and potential new indicators of disease onset and progression. A new analytical workflow involving instrumental analysis by UHPLC-HRMS and data treatment by chemometrics method ROIMCR, followed by multivariate analysis, is available for plasma metabolomic profiling. This platform can be easily adapted to other biomatrices and diseases, and applied to profile the same individual along time, fostering the development of personalized medicine.
- Enantiomeric biodistribution, metabolic profile, and toxicity of 3-chloromethcathinone in Wistar rats following acute exposurePublication . Langa, Ivan; Rocha-Pereira, Carolina; Silva, Paula; Milhazes, Nuno; Silva, Diana Dias da; Domingues, Susana; Resende, Albina Dolores; Barbosa, Joana; Faria, Juliana; Tiritan, Maria Elizabeth; Ribeiro, Cláudiaynthetic cathinones are a class of new psychoactive substances (NPS) with 3-chloromethcathinone (3-CMC) accounting for over 46% of NPS-related seizures in 2023. Sold as a racemate, 3-CMC exhibits enantioselective metabolism and pharmacological effects, making enantioselectivity a critical factor in evaluating its toxicokinetics and toxicodynamics. This study aimed to evaluate the enantiomeric biodistribution, metabolic profile, and toxicity of 3-CMC racemate in Wistar rats following acute exposure. For this purpose, a gas chromatography–mass spectrometry (GC–MS) method was validated for quantifying 3-CMC in biological matrices and for characterizing its biodistribution in vivo. Rats were intraperitoneally administered with saline (control) or 3-CMC (10 or 20 mg kg−1, b.w.). Animals were sacrificed 24 h after administration, and plasma, urine, and tissues were collected for biodistribution, biochemical, and histopathological analyses. 3-CMC was exclusively detected in the urine, along with three additional pairs of enantiomeric metabolites. Both 3-CMC and its metabolites exhibit enantiomeric fractions (EF) different from 0.5, indicating enantiomeric enrichment. Administration of 3-CMC significantly decreased plasma levels of creatine kinase-MB, alkaline phosphatase, and aspartate aminotransferase, along with increased levels of glucose and urea. In the urine, decreased levels of albumin were observed. Oxidative stress and energy biomarkers were altered in the brain, lungs, and kidneys. Histopathological analysis revealed morphological alterations in the brain, liver, and lungs at both doses, and in the kidneys at the highest dose. However, no significant alterations were observed in the other tissues. Taken together, our findings suggest enantioselective metabolism and indicate that, although rapidly eliminated by the kidneys, 3-CMC still causes significant toxicity in target organs, such as the brain, liver, lungs, and kidneys. This highlights the high toxicity of the drug or its metabolites, even over short-term exposure.
- Cost analysis of Multidose Drug Dispensing (MDD) system implementation in a community pharmacy in PortugalPublication . Reis, Ana; Jesus, Ângelo; Martín, Maria Luisa; Jesus, ÂngeloCommunity pharmacies are increasingly delivering structured services to support chronic disease management, such as Multidose Drug Dispensing (MDD). This strategy can improve adherence and safety, but evidence of its economic feasibility in Portuguese pharmacies remains limited. To estimate the cost of implementing and operating an MDD system in a community pharmacy, informing reimbursement models and policy. A micro-costing approach assessed fixed and variable expenses for serving polymedicated elderly patients. Costs were calculated in euros (2024/2025) and expressed per working day based on 253 annual preparation days. First-year costs totaled €70,985.68, including €8184.00 for setup, €21,579.00 for supplies, and €41,222.68 for staff salaries. The daily operating cost was €280.58, with labour representing the major expense. A break-even analysis indicated sustainability with around 700 users at €10/month. Although requiring significant initial investment, MDD can become financially viable through scaling, workflow efficiency, and supportive reimbursement strategies.
- Adverse reactions mediated by 99mTc-tetrofosmin: Literature review and analysis of post-marketing reportsPublication . Martins, Sara; Costa, Sara Poças; Sousa, Mariana; Moreira, Fernando; Martín-Suaréz, A.; Jesus, Ângelo; Jesus, Ângelo; Moreira, Fernando99mTc-tetrofosmin is a diagnostic radiopharmaceutical used to evaluate cardiac pathologies. Despite the lower incidence of reactions compared to other drugs, radiopharmaceuticals can still cause adverse reactions. For this reason, pharmacovigilance plays a crucial role in detecting, understanding, evaluating and preventing them. This study aims to review the available literature,on the safety of99mTc-tetrofosmin, and to analyze spontaneous adverse drug reaction reports from the European EudraVigilance database. A literature review was conducted according to PRISMA methodology. An analysis of spontaneous notifications was carried out in EudraVigilance, until 2022. The review identified a selection of 7 articles. The most reported adverse reactions were skin irritation, strange taste in the mouth and nausea. Regarding the EudraVigilance analysis, 220 notifications were identified, accounting for 477 adverse reactions. The majority belong to males (51%), between 18-64 years (45%). Health professionals were the main reporters (84%). The most prevalent System Organ Class was “general disorders and administration site conditions” (21%) and the most reported adverse reaction was pruritus (10%). Approximately 67% of reactions were considered serious, with 6 fatal cases recorded. The results demonstrated that adverse reactions associated with99mTc-tetrofosmin do occur and should not be minimized. Over a period of 17 years, only 220 notifications were recorded, which may highlight potential challenges in pharmacovigilance for radiopharmaceuticals. Therefore, raising awareness about the importance of reporting adverse reactions is crucial.
- Adverse reactions by radiopharmaceuticals: Retrospective analysis of the Portuguese National Pharmacovigilance SystemPublication . Martins, Sara; Jesus, Ângelo; Andrade, Ricardo; Rocha, Mariana; Martín-Suarez, Ana; Jesus, ÂngeloRadiopharmaceuticals are essential in the field of nuclear medicine, but like any other medicinal product, radiopharmaceuticals can potentially cause adverse reactions in patients. To describe the adverse reactions to radiopharmaceuticals reported to the Portuguese National Pharmacovigilance System (SNF). Methods: We performed a retrospective, observational study by examining individual case safety reports (ICSRs) provided by the SNF related to all radiopharmaceuticals commercially available in Portugal from 2010 to 2023. The SNF received a total of 84 ICSRs. These reports resulted in a total of 224 adverse drug reactions (ADR), which involved a total of 15 different radiopharmaceuticals. The mean age of patients was 61.9 years old. Twenty-one different system organ classes (SOCs) were identified, with the most prevalent situations being “Gastrointestinal Disorders” (18.3%; n = 41) followed by “General disorders and administration site conditions” (16.5%; n = 37), “Skin and subcutaneous tissue disorders” (11.2%; n = 25) and “Blood and lymphatic system disorders” (10.3%; n = 23). Fifty-seven reports (67.85%) showed at least 1 serious ADR. Most notified radiopharmaceuticals were, respectively, radium—223 (n = 36, 41.4%), lutetium-177 oxotreotide (n = 12, 13.8%) and iodide—131 (n = 9, 10.3%). Although the number of notifications is limited, these findings provide valuable insights into the types and frequencies of adverse reactions associated with radiopharmaceuticals used in Portugal between 2010 and 2023. The data highlight the importance of continued pharmacovigilance efforts to monitor the safety of these specialized medical products and inform clinical decision-making.
- Health effects of ergonomics and personal protective equipment on chemotherapy professionalsPublication . Reis, Ana; Silva, Vítor; Joaquim, João José; Valadares, Luís; Matos, Cristiano; Valeiro, Carolina; Mateos-Campos, Ramona; Moreira, Fernando; Moreira, FernandoChemotherapy drugs are vital for treating cancer, but the professionals who prepare and administer them may be exposed to small amounts that can harm their health over time. To stay protected, they use personal protective equipment like gloves, gowns, and masks, and must also work under ergonomic conditions that prevent strain from repetitive tasks and awkward postures. This review examined recent studies to see how these protective measures are applied and what risks remain. We found that use of protective equipment is often inconsistent and ergonomic challenges are common, especially for nurses and pharmacy technicians. These findings show the importance of better training, safer workplace design, and stronger institutional support. Improving protective practices and ergonomics can help protect healthcare workers, enhance their wellbeing, and ensure safer patient care.
- Multidimensional evaluation of Lisdexamfetamine: Pharmacology, therapeutic use, toxicity and forensic implicationsPublication . Silva-Carvalho, Mariana; Barbosa, Daniel José; Silva, Diana Dias da; Oliveira, Ricardo Jorge Dinis; Dias da Silva, Diana CristinaLisdexamfetamine (LDX), a prodrug of d-amphetamine, is widely used in the pharmacological treatment of neuropsychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder (BED). Chemically, it consists of the amino acid lysine linked to d-amphetamine. Its enzymatic conversion to d-amphetamine sets the stage for a prolonged and controlled release, influencing its clinical profile and differentiating it from other stimulant medications. As a central nervous system stimulant, LDX primarily acts by increasing the release of neurotransmitters, particularly dopamine and noradrenaline, in the brain. Clinically, this enhanced availability of neurotransmitters is believed to contribute to improvements in attention, focus and impulse control in individuals with ADHD. The side effects of LDX include insomnia, decreased appetite, weight loss and xerostomia. This work reviews the pharmacological mechanisms, clinical applications and forensic considerations associated with its use. It is expected that clinicians, researchers and policymakers have a comprehensive understanding of the pharmacological and toxicological aspects of LDX.