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- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseasesPublication . Rojo, Ana I.; Buttari, Brigitta; Cadenas, Susana; Carlos, Ana Rita; Cuadrado, Antonio; Falcão, Ana Sofia; López, Manuela G.; Georgiev, Milen I.; Grochot-Przeczek, Anna; Gumeni, Sentiljana; Jimenez-Villegas, José; Horbanczuk, Jarosław Olav; Konu, Ozlen; Lastres-Becker, Isabel; Levonen, Anna-Liisa; Maksimova, Viktorija; Michaeloudes, Charalambos; Mihaylova, Liliya V.; Mickael, Michel Edwar; Milisav, Irina; Miova, Biljana; Rada, Patricia; Santos, Marlene; Seabra, Miguel C.; Strac, Dubravka Svob; Tenreiro, Sandra; Trougakos, Ioannis P.; Dinkova-Kostova, Albena T.Non-communicable chronic diseases (NCDs) are most commonly characterized by agerelated loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.
- Ten-year analgesic utilization patterns and economic implications in PortugalPublication . Duarte, Nuno; Martins, João Paulo; García-Pedraza, Jose-Ángel; Santos, MarleneThis study evaluated the 10-year consumption and economic patterns of classical analgesics, adjuvants and opioids in Portugal (2012-2022), and conducted a comparative analysis between Portugal, Spain and Denmark to explore the consumption patterns among these countries for 2022. Data on sales and national health service (NHS) costs were obtained from the Portuguese National Authority of Medicines and Health Products. Sales data were converted to defined daily dose (DDD) per 1000 inhabitants per day according to the Anatomical Therapeutic Chemical (ATC) classification/DDD methodology, while comparisons between Spain and Denmark were evaluated with the chi-square test, when appropriate. The findings reveal that classical analgesics use in Portugal remained stable during the period 2012-2022, with ibuprofen being the most consumed. Adjuvants, specifically gabapentinoids, experienced an 84% increase in use, primarily attributed to pregabalin. Weak opioids, led by tramadol, witnessed a 117% rise in use, while strong opioid use, led by tapentadol, increased by 618%. Portugal presented the lowest overall opioid consumption when compared to Denmark and Spain in 2022. Economic trends indicated a heightened NHS expenditure on analgesics, primarily driven by increased opioid use. Notwithstanding, there was no significant burden on relative expenditure over the 10-year period. Portugal presented a major increase in both weak and strong opioid prescriptions, aligning with the trends for Spain and Denmark. The development and approval of generic medicines and vigilant market monitoring are imperative strategies for managing the escalated costs resulting from heightened consumption, particularly concerning opioids.
- Microcarrier-based fluorescent yeast estrogen screen assay for fast determination of endocrine disrupting compoundsPublication . Gregório, Bruno J.R.; Ramos, Inês I.; Marques, Sara S.; Barreiros, Luísa; Magalhães, Luís M.; Schneider, Rudolf J.; Segundo, Marcela A.The presence of endocrine-disrupting compounds (EDCs) in water poses a significant threat to human and animal health, as recognized by regulatory agencies throughout the world. The Yeast Estrogen Screen (YES) assay is an excellent method to evaluate the presence of these compounds in water due to its simplicity and capacity to assess the bioaccessible forms/fractions of these compounds. In the presence of a compound with estrogenic activity, Saccharomyces cerevisiae cells, containing a lacZ reporter gene encoding the enzyme β-galactosidase, are induced, the enzyme is synthesised, and released to the extracellular medium. In this work, a YES-based approach encompassing the use of a lacZ reporter gene modified strain of S. cerevisiae, microcarriers as solid support, and a fluorescent substrate, fluorescein di-β-d-galactopyranoside, is proposed, allowing for the assessment of EDCs’ presence after only 2 h of incubation. The proposed method provided an EC50 of 0.17 ± 0.03 nM and an LLOQ of 0.03 nM, expressed as 17β-estradiol. The assessment of different EDCs provided EC50 values between 0.16 and 1.2 × 103 nM. After application to wastewaters, similar results were obtained for EDCs screening, much faster, compared to the conventional 45 h spectrophotometric procedure using a commercial kit, showing potential for onsite high-throughput screening of environmental contamination.
- Interações medicamentosas potenciais: uma análise exploratória em farmácia comunitáriaPublication . Fernandes, Daniela; Jesus, ÂngeloInterações medicamentosas (IMs) podem ser descritas como a influência farmacológica de um fármaco sobre outro, quando administrados em combinação. Com o avanço da tecnologia farmacêutica, aumentam os fármacos disponíveis, aumentando também as possibilidades da ocorrência de interações entre medicamentos, já que a administração simultânea de dois ou mais medicamentos para um mesmo paciente se tornou uma prática comum. Analisar e classificar as interações medicamentosas potenciais (IMPs) do tipo fármaco-fármaco em prescrições de utentes com dislipidémia e/ou diabetes mellitus; determinar quais as IMPs mais prevalentes; determinar quais os fármacos mais associados a IMs; identificar todas as IMPs major, minor e moderadas na amostra. Este estudo avaliou informação recolhida a partir de 101 prescrições de utentes com dislipidémia e/ou diabetes no distrito do Porto e Braga. Posteriormente, as informações relativas a cada um dos grupos da amostra foram analisadas com recurso à base de dados IBM Micromedex Complete Drug Interactions. Finalmente, foi feito o tratamento estatístico descritivo dos dados. Resultados: Em 101 prescrições, existem 116 potenciais interações medicamentosas no total, 32 Major e 84 Moderadas. Existem IMPs em 50 (ou 49,5%) das prescrições e em 24 das prescrições, (ou 23,8%) existe potencial para IMP major. Perante estes resultados, urge encontrar soluções que se foquem nas potenciais reações adversas ao medicamento (RAMs) provocados por IMs, de modo a aumentar a segurança dos utentes e da própria comunidade e melhorar a saúde pública.
- Testes rápidos para o rastreio de infeções por VIH em farmácia comunitária - estudo exploratórioPublication . Gomes, Micael; Jesus, ÂngeloA inclusão de testes rápidos de rastreio de VIH em farmácias comunitárias pode melhorar a deteção de infeções não diagnosticadas. As farmácias são parceiras valiosas nos esforços de promoção da saúde e podem ser um recurso de saúde acessível para a sua inclusão. No entanto, foram levantadas preocupações sobre a prontidão das farmácias comunitárias para fornecer este serviço, assim como a disponibilidade e preparação dos profissionais de farmácia. Neste estudo exploratório, foi aplicado um questionário aos profissionais de farmácia comunitária que exercem funções no concelho de Braga (N=64). Noventa e cinco por cento das farmácias estavam fisicamente prontas para prestar este serviço. Os profissionais de farmácia estavam cientes dos diferentes tipos de testes disponíveis e mais de 50% estavam dispostos a ter um papel central no processo para o rastreio do VIH. A maioria dos inquiridos considera que este tipo de teste proporciona “maior controlo da doença” (27,3%), “resultados rápidos” (25,6%) e “acessibilidade” (25%). No entanto, 95% dos profissionais inquiridos consideram que deve ser exigida formação prévia obrigatória, nomeadamente sobre “como lidar com resultados positivos”, mas também sobre os fundamentos das opções de infeção, transmissão e tratamento do VIH. Este estudo exploratório mostra que as farmácias estão fisicamente preparadas para fornecer os testes rápidos e que a maioria dos profissionais estão dispostos a participar. No entanto, um foco na formação obrigatória e um código geral de conduta devem ser definidos, a fim de fornecer um serviço de qualidade.
- Pharmacovigilance of radiopharmaceuticals: Challenges and opportunitiesPublication . Martins, Sara; Jesus, Ângelo; Martín-Suárez, AnaRadiopharmaceuticals are unique in that they contain radioactive isotopes which emit radiation for diagnostic or therapeutic purposes.1 They are also used in very small dosages when compared to conventional drugs and the frequency of administrating radiopharmaceuticals in an individual during is lifetime is also very low. Nevertheless due to their specific nature, radiopharmaceuticals require careful monitoring and surveillance to detect and manage any potential adverse effects or safety concerns.2 Pharmacists, radiations technologists, physicians and other hospital staff play a crucial role in ensuring the safe handling, administration, and monitoring of these specialized drugs. Their joint involvement in pharmacovigilance is essential for maintaining patient safety and optimizing the use of radiopharmaceuticals.
- Polypharmacy and drug interactions in older patients with cancer receiving chemotherapy: associated factorsPublication . Ferraz Oliveira, Rita; Oliveira, Ana Isabel; Cruz, Agostinho; Ribeiro, Oscar; Afreixo, Vera; Pimentel, FranciscoPolypharmacy in older adults with cancer receiving chemotherapy leads to increased risks of drug interactions, translating in potential hazardous health outcomes. This study aims to assess the prevalence of polypharmacy, drug–drug interactions (DDIs), and severe-drug interactions (SDIs) in older patients with cancer. Antineoplastic agents (ANAs) involvement and possible risk contexts (comorbidities with cardiac risk, and high-risk medications) were also analysed. ents (ANAs); it was conducted in three hospitals from the north of Portugal. Data collection was obtained using self-reports and medical records. DDIs were identifed and classifed using Micromedex® software. Descriptive and association analyze statistics were performed. Statistical hypothesis tests with p value less than 0.05 were considered signifcant. All statistical procedures and analysis were performed with R version 4.1.3. We enrolled 552 patients. Polypharmacy prevalence was 88.40%; 76.45% and 56.16% of the patients presented with DDIs and SDIs, respectively. SDIs with ANAs were found in 21.20% of the patients. High-risk medications were associated with a higher risk of polypharmacy, DDIs, and SDIs. Polypharmacy and DDIs were higher in patients with hypertension or diabetes. SDIs were higher in patients with diabetes. Polypharmacy, potential DDIs and SDIs were highly prevalent in older adults with cancer. A careful review of the medication administered is necessary to decrease it. These fndings warrant further research to optimize medication in this population and decrease problems related to medication, which may lead to emergency room visits and hospitalisations, compromising patient safety and/or ongoing treatments.
- Assessing the differences of two vineyards soils’ by NIR spectroscopy and chemometricsPublication . Machado, Sandia; Barreiros, Luísa; Graça, António R.; Madeira, Manuel; Páscoa, Ricardo N. M. J.; Segundo, Marcela A.; Lopes, João A.Soil properties influence greatly the status of vine plants which consequently influences the quality of wine. Therefore, in the context of viticulture management, it is extremely important to assess the physical and chemical parameters of vineyards soils. In this study, the soils of two vineyards were analysed by near-infrared (NIR) spectroscopy and established analytical reference procedures. The main objective of this study was to verify if NIR spectroscopy is a potential tool to discriminate the soils of both vineyards as well as to quantify differences of soil’s parameters. For that, a total of eight sampling spots were selected at each vineyard taking into consideration the soil type and sampled at different depths. The data analysis was performed using analysis of variance (ANOVA), principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) and partial least squares (PLS) regression. The ANOVA results revealed that 12 out of the 18 parameters analysed through the reference procedures can be considered statistically different (p < 0.05). Regarding PCA, the obtained results revealed a clear separation between the scores of both vineyards either considering NIR spectra or the chemical parameters. The PLS-DA model was able to obtain 100 % of correct predictions for the discrimination of both vineyards. PLS regression analysis using NIR spectra revealed R2 P and RER values higher than 0.85 and 10, respectively, for 8 (pH (H2O), N, Ca2+, Mg2+, SB, CEC, ECEC and GSB) of the 18 chemical parameters evaluated. Concluding, these results demonstrate that it is possible to discriminate the soils of the different vineyards through NIR spectroscopy as well as to quantify several chemical parameters through soils NIR spectra in a rapid, accurate, cost-effective, simple and environmentally friendly way when compared to the reference procedures.
- Total analysis system for the determination of uremic toxins in human plasma based on bead injection solid phase extraction hyphenated to mass spectrometryPublication . Fernandes, Sara; Barreiros, Luísa; Sampaio-Maia, Benedita; Miró, Manuel; Segundo, Marcela A.Indoxyl sulfate (INDS) and p-cresol sulfate (pCS) are two of the most relevant uremic toxins that are recognized to have an essential role in chronic kidney disease (CKD) progression and associated cardiovascular risk. Thus, it is crucial to accurately assess their circulating levels in the body. Aiming at establishing an analytical strategy for quantification of INDS and pCS in human plasma, an automatic on-line micro-solid-phase extraction (μSPE) procedure hyphenated to tandem mass spectrometry (MS/MS) detection without previous chromatographic separation was herein developed. The bead injection (BI) concept was used to implement the μSPE procedure in the lab-on-valve (LOV) format. After studying the extraction conditions, the anion-exchange OASIS WAX sorbent beads (10 mg) and 99% ACN–H2O (15:85, v/v)–1% (v/v) NH4OH were chosen as sorbent and eluent, respectively, as they provided the highest analyte recoveries. Subsequently, the μSPE-BI-LOV system was hyphenated on-line to a MS/MS detector and the full analytical cycle, comprising sample preparation and analytes detection, was completed in <20 min. The developed μSPE-BI-LOV-MS methodology presented good linearity (r2 > 0.999) for quantification of the target analytes at concentrations ranging from 18 to 360 μg mL−1 in plasma. LOQ values were 2 μg mL−1 for INDS and 7 μg mL−1 for pCS in plasma. Human plasma samples from healthy subjects and individuals with CKD were successfully analyzed using the developed approach. The proposed automatic methodology can be described as an eco-friendly strategy, with a favorable score of 0.64 after greenness evaluation using the AGREE metric.
- Avaliação da prevalência de Trichomonas vaginalis pelos métodos direto e culturalPublication . Alves, Maria José; Cruz, Agostinho; Balteiro, Jorge; Ferraz Oliveira, Rita; Cunha, AgostinhoA tricomoniose é a doença sexualmente transmitida não víral de maior prevalência nos seres humanos. Apresenta grande variabilidade de manifestações clínicas, desde a ausência de sintomas a um elevado risco de inflamação pélvica e ínfertilidade. Sinais clínicos e sintomas não são nem sensíveis nem específicos o suficiente para serem usados isoladamente no diagnóstico da tricomoniose, como tal o diagnóstico laboratorial é fundamental na detecção desta parasitose. A baixa sensibilidade dos métodos usados no diagnóstico laboratorial desta infecção subestima a sua prevalência. Consistiram em detenninar a prevalência de Trichomonas vaginalis em mulheres recorrendo ao exame directo e cultural com intuito de verificar as respectivas sensibilidades. Foi propósito demonstrar a importância da utilização sequencial destas duas metodologias no diagnóstico da tricomofíiose. As colheitas dos exsudados vaginais foram efectuadas em 288 mulheres que frequentavam a consulta de planeamento familiar dos Centro de Saúde 1, Centro de Saúde 2 e Hospital Distrital de Chaves, recorrendo a duas metodologias de diagnóstico (método Directo/Cultural). Das 288 mulheres investigadas a infecção por T. vaginalis foi detectada em 11 (3, 8%) recorrendo conjuntamente às duas metodologias. A infecção foi diagnosticada pelo método directo em 4 das 11 mulheres, no entanto o método cultural (Meio TYM) detectou os 11 casos positivos. Apesar de continuar a ser o mais utilizado no diagnóstico da tricomoniose o método directo apresentou uma sensibilidade de apenas 36,3%. Pela comparação de sensibilidades é visível a elevada precisão do método cultural relativamente ao directo. A associação destas duas metodologias poderá ser uma mais valia no diagnóstico da tricomoniose.