ESS - FAR - Comunicações em eventos científicos
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- Enantiomeric biodistribution and toxicity of 3-chloromethcathinone (3-CMC) in Wistar rats after acute exposure – preliminary dataPublication . Langa, Ivan; Rocha-Pereira, Carolina; Milhazes, Nuno; Silva, Diana Dias da; Domingues, Susana; Silva, Paula; Barbosa, Joana; Faria, Juliana; Tiritan, Maria Elizabeth; Ribeiro, Cláudia; Dias da Silva, Diana CristinaThere has been a surge in global attention to New Psychoactive Substances (NPS) [1]. Synthetic cathinones stand out as a widely consumed NPS class. Notably, 3-chloromethcathinone (3-CMC) accounted for over 34% of NPS seizures in 2021 [2], which underscores concerns regarding its consumption and health effects. Of note, 3-CMC is chiral and mostly sold as a racemate. As human me-tabolism and pharmacological effects can be enantioselective [3], determination of the impact of enanti-oselectivity in toxicokinetics/toxicodynamics is essential for the assessment of 3-CMC effects. This work aimed to evaluate in vivothe enantioselective biodistribution and toxicity of racemic 3-CMC, after an acute exposure to 3-CMC. Ten-week-old male Wistar rats were administered intraperitoneally with saline or 3-CMC (10 or 20 mg/kg; n=6). Twenty-four hours after, animals were deeply anesthetized and nine organs (brain, liver, kidneys, lungs, heart, spleen, gut, muscle, adipose tis-sue), blood and urine were collected. For evaluation of the enantiomeric biodistribution, a previous in houseestablished indirect method by gas chromatography [3], was adapted and validated. Some biochem-ical analysis was performed using an analyser, whereas TBARS, ATP, glutathione and total protein were determined by spectrophotometry. Organs were also processed for histological analysis. After 24 h, 3-CMC was not found in most organs. Both enantiomers were detected in urine with one dominant enantiomer, suggesting enantioselectivity in metabolism. The histopathological results showed possible central chromatolysis in the brain (20 mg/kg), liver inflammation, renal lesions, lungs’ haemoptysis, and alveolar haemorrhage, in most 3-CMC-exposed animals. No differences were observed inthe heart. Our findings show rapid 3-CMC renal elimination, with enantio selectivity in metabolism. Alt-hough biochemical evaluations are ongoing, the results are expected to give further insights on the 3-CMC toxicity and histological abnormalities found in the brain, kidneys, liver and lungs.
- The effect of synthetic cannabinoid ADB-FUBI-NACA on primary neuronal cultures ß-galacto-sidase activity: preliminary findingsPublication . Roque-Bravo, Rita; Carmo, Helena; Silva, João Pedro; Carvalho, Félix; Silva, Diana Dias da; Dias da Silva, Diana CristinaADB-FUBINACA (ADB-FUB) is a synthetic cannabinoid (SC) that has gained popularity among users as a new psychoactive substance. This stems from SC's pharmacological similarity to the active principle of cannabis, D9-tetrahydrocannabinol (THC). However, unlike THC, SCs demonstrate full agonism of cannabinoid receptors 1 and 2 [1]. Recent scientific developments have shown that can-nabis use may aggravate ageing-related parameters [2,3]. Moreover, a study using human fibroblasts re-vealed that 1 μM THC (2h-longexposure, for 15 days) can increase ß-galactosidase activity [3], which serves as a first-line marker for cellular senescence. This study was designed to investigate whether these biologically-relevant concentrations could accelerate neuronal ageing. PHC were isolated from Wistar rat day 18-19 embryos and cultured for up to 21 days-in-vitro (DIV). Exposure to 1 pM, 1 nM and 1 μM ADB-FUB (concentrations previously shown to be non-cytotoxic to PHC) started either on DIV3 or DIV7 and was maintained up to 21 DIV. At that final timepoint, ß-galactosidase activity was evaluated. DMSO at 0.02% was employed as solvent control. Under these experi-mental conditions, PHC exposed to 1 nM and 1 μM ADB-FUB in the DIV3-21 protocol had lower ß-galactosidase activity when compared to control conditions (p<0.05, 1 nM; p<0.001, 1 μM). No statisti-cally significant results were registered for PHC under the DIV7-21 exposure protocol. These findings are, to the best of our knowledge, the first evidence of a potential “anti-ageing” effect of ADB-FUB. Evaluation of other senescence-related endpoints will follow. Moreover, experiments using another in vitroneuronal model (human neuroblastoma cell line SH-SY5Y) are underway to compare the effects of the same drug in different models and further substantiate conclusions on ADB-FUB’s effect.
- Chemical differences between alternative and traditional tobacco productsPublication . Monteiro, Vânia; Freitas, Inês; Silva, Diana Dias da; Pinho, Paula Guedes de; Pinto, Joana; Dias da Silva, Diana CristinaElectronic cigarettes (E-cigs) and heated tobacco products (HTPs) have gained popularity as alternatives to traditional tobacco products (TTPs), claiming to reduce harm. The carcinogenic proper-ties of chemicals in the smoke of TTPs are widely recognized. However, there is still an incomplete understanding of the different chemicals in E-cigs and HTPs and their toxicity to human cells [1]. Thus, this study aimed at characterizing and comparing the chemical composition of three different brands of E-cigs, HTPs and TTPs. We selected the three top-selling brands of E-cigs, HTPs, and TTPs in Portugal, and each brand (n=9) was analyzed in triplicate. Volatile compounds present in all brands were extracted by headspace solid-phase microextraction (HS-SPME) and solvent extraction (di-chloromethane). The volatile compounds in the headspace and solvent extracts were analysed by gas chromatography-mass spectrometry (GC-MS). Compound annotation was performed by comparing the mass spectrum of each chromatographic peak in the sample with a mass spectral library and standards, where available. A total of 53 compounds were detected in E-cigs, 44 in HTPs and 41 in TTPs by HS-SPME. Solvent extraction revealed 43 compounds in E-cigs, 35 in HTPs and 22 in TTPs. Only 7 compounds were common to E-cigs, HTPs, and TTPs. Overall, the chemical classes included alcohols, aldehydes, ketones, esters, pyridines and others.The composition of HTPs and TTPs was similar (20 compounds in common), particularly in the classes of ketones, alcohols, terpenoids, and pyridines. In contrast, E-cigs contain a larger number of compounds than HTPs and TTPs, including several alcohols, esters, pyranones, and lactones. The volatile composition of HTPs and TPPs showed less variation be-tween different brands, whereas E-cig brands showed greater variability in their composition. HTPs have a volatile chemical composition similar tothat of TTPs in their original form, so their health effects will depend on the impact of the different types of combustion. E-cigs show a distinct chemical profile across all brands, with chemical classes that are potentially relevant for toxicological studies.
- Efficacy and safety of Tocilizumab in the treatment of Rheumatoid Arthritis: An umbrella reviewPublication . Silva, David; Moreira, Fernando; Santos, Marlene; Moreira, FernandoTocilizumab (TCZ) is a humanized immunoglobulin G1 monoclonal antibody that targets and inhibits the interleukin-6 (IL-6) receptor. As a selective inhibitor of this cytokine, TCZ offers a targeted approach in managing inflammatory conditions. Given its specificity and potential therapeutic benefits, this article aims to provide a comprehensive summary of the efficacy and safety of TCZ in the treatment of RA.
- Exploring the role of oral antidiabetic medications as adjuncts in depression treatmentPublication . Santos, Marlene; Santos, Angela; Jesus, Ângelo; Jesus, ÂngeloDepression is a complex and multifaceted disorder with a poorly defined etiology and numerous risk factors. Despite the availability of several antidepressant classes, many treatments have limitations that compromise their effectiveness and impact patients’ quality of life.
- Pharmacological approaches in Amyotrophic Lateral Sclerosis: A systematic review of clinical trials on efficacy, survival, and safety profilesPublication . Tomé, Pedro; Moreira, Fernando; Santos, Marlene; Moreira, Fernando; Santos, MarleneAmyotrophic lateral sclerosis is a progressive neurodegenerative disease that results in the deterioration of neuromuscular connections, with no effective treatment currently available.
- Development and validation of an analytical method to assess the importance of using gauze dressings in luer-lock connection systems during the preparation of cytotoxic drugsPublication . Silva, Clara; Carmo, Helena; Oliveira, Vânia; Carvalho, Daniel; Moreira, Fernando; Moreira, FernandoHealthcare professionals face occupational hazardous when handling cytotoxic drugs used for cancer treatment. The International Society of Oncology Pharmacy Practice (ISOPP) standards are the guidelines recommended by the European Parliament for safety procedures but, unlike others (e.g. Occupational Safety and Health Administration (OSHA)), fail to mention the need to use dressings at luer-lock connections to contain cytotoxic leaks. This study aims to develop and validate an analytical method capable of identifying and quantifying cyclophosphamide (CP) and 5-fluorouracil (5-FU) in gauze dressings. Methods: Gauze dressings (20x10 cm) containing varying concentrations of CP and 5-FU were placed in 15 mL falcons containing acetonitrile:methanol:water (19:13:68). After stirring, the samples were passed through a 0.22 µm filter. The extracted samples were then analyzed using HPLC-DAD, equipped with a C18 column (Hypersil Gold ™ 150mm x 4.6mm and 5µm particle size). The mobile phases employed were acetonitrile:methanol:water (19:13:68) (CP) and 0.5% acetic acid in water (5-FU) and detection was set at 205 nm (CP) and 260 nm (5-FU). The mean of five calibration curves generated for each drug were calculated, each exhibiting R² > 0.997, thus confirming the linearity for both drugs. Regarding sensitivity, LOD of 0.006 µg/cm2 for 5-FU and 0.11 µg/cm2 for CP and LOQs of 0.02 µg/cm2 for 5-FU and 0.32 µg/cm2 for CP, were obtained. Accuracy fell within the range of 93%-110% and precision was set between 91% and 99%. At room temperature, gauze dressings deliberately contaminated exhibited superior stability for 5-FU compared to CP. The method has been successfully validated and, once suitability is confirmed, it will be applicable for the evaluation of the importance of using gauze dressing when handling cytotoxic drugs, by testing contaminations occurring during reallife routine handling of these cytotoxic drugs.
- Sources of bias when assessing seasonal Influenza vaccine performance: a narrative reviewPublication . Martins, André Miguel; Juan, Luis Félix Valero; Santos, Marlene; Martins, João PauloThe best way to prevent influenza infection is through vaccination. Evaluating vaccine performance is essentially done through two types of study: clinical trials and the test negative design, an observational study derived from the case control. While in clinical trials the sources of bias are perfectly identified and there are specific tools for assessing them, in test negative design we find very varied sources of bias and a lot of scattered information without there being a validated tool for assessing the risk of bias. The aim of this narrative review is to identify the most important sources of bias in both types of study and to contribute to the development of a risk assessment tool for test negative design studies, given their major importance in evaluating the performance of the seasonal influenza vaccine.
- Segurança e eficácia do uso de inibidores da PARP no tratamento do cancro do ovário e mama metastizadoPublication . Jesus, Ângelo; Pinto, Rafaela; Jesus, ÂngeloO cancro da mama é um dos cancros mais comuns na mulher. O cancro do ovário, embora tenha uma taxa de incidência relativamente baixa, quando é detetado está geralmente numa fase muito avançada, o que resulta num mau prognóstico e, consequentemente, numa elevada taxa de mortalidade. Estes cancros têm uma forte componente genética de onde resulta uma perda da proteína funcional através da linha germinal ou mutação somática, levando a uma maior dependência de mecanismos de reparação de DNA mais propensos a erros, promovendo a carcinogénese. Os PARPies são uma classe de agentes de supressão da atividade das enzimas PARP. Objetivo: Analisar a segurança e eficácia dos inibidores PARP no tratamento do cancro do ovário e mama metastático, possuindo como medidas as reações adversas major a PFS.
- Development and implementation of a gravimetric control method for chemotherapeutic preparationsPublication . Fonseca, Débora; Ré, Susana; Cruz, José Pedro; Oliveira, Ana Isabel; Moreira, Fernando; Moreira, Fernando; Oliveira, Ana IsabelThe complexity of antineoplastic preparation increases the risk of errors, thus demanding robust safety systems. Common methods to prevent errors committed during aseptic preparation include double visual verification and gravimetric control (GC), in which the mass of each preparation is determined to ensure product accuracy. The aim of this work is to develop a GC that routinely, quickly, and simply enables quality control of antineoplastic preparations in the Centro Hospitalar de Baixo Vouga (CHBV) hospital unit.