Loading...
63 results
Search Results
Now showing 1 - 10 of 63
- Bdnf-NRF2 crosstalk in depression disorderPublication . Santos, Marlene; Caldevilla, Renato; Morais, Stephanie; Carvalho, Serafim; Medeiros, Rui; Barroso, Maria FátimaThe World Health Organization estimates that major depressive disorder (MDD) affects over 264 million individuals globally, posing a significant public health challenge. Treatment-resistant depression (TRD) represents a severe form of MDD with poor treatment outcomes. Genetic variations are known to impact MDD treatment responses, yet genome-wide association studies have struggled to identify consistent marker alleles. Previous research has linked the Brain Derived Neurotrophic Factor (BDNF) genetic polymorphism with TRD. BDNF is essential for neuronal survival and neuroplasticity, processes influenced by antidepressant treatment, and regulated by transcription factors like Nuclear factor erythroid 2-related factor 2 (NRF2). NRF2 regulates antioxidant and anti-inflammatory responses and plays a crucial role in depression pathogenesis. NRF2 knockout mice exhibit reduced BDNF levels and depression-like behaviors, indicating that NRF2activation enhances BDNF expression and antidepressant efficacy. The BDNF rs6265 (Val66Met) polymorphism is associated with variations in antidepressant response rates. Research suggests that the interaction between BDNF and NRF2 pathways could enhance antidepressant effectiveness. NRF2 activation, such as through the compound sulforaphane, has demonstrated rapid antidepressant effects by increasing BDNF expression. Lower levels of NRF2 and BDNF are observed in stress-induced depression models, and ketamine treatment influences NRF2-related genes. Simultaneously, there is a growing need for efficient genotyping methods, and genosensors offer a promising solution. This presentation will address the interplay between BDNF and NRF2 in depression, explore its relationship in antidepressant response, and present a putative genosensor for BDNF rs6265 (Val66Met) polymorphism identification, improving antidepressant treatment outcome.
- FOXO3-REST Axis: a therapeutic target for medulloblastoma?Publication . Monteiro, Ricardo; Baiula, Mónica; Santos, Marlene; Spampinato, SantiMedulloblastoma has poor outcome due also to adverse events caused by the treatment [1]. An improved anti-tumor strategy is needed to enhance patient survival rate. REST is a transcription factor overexpressed in medulloblastoma cells and it’s associated with the formation of this brain tumor and the low survival rate, suggesting an oncogenic role [2][3].
- Construction and optimization of an electrochemical genosensor for the detection of BDNF gene Val66Met polymorphismPublication . Caldevilla, Renato; Santos, Marlene; Barroso, M. FátimaMajor depression disorder (MDD) is the most prevalent psychiatric condition worldwide. Currently, antidepressants constitute the main pharmacological treatment for this condition. Despite the growing arsenal of antidepressant medications, almost half of MDD patients have insufficient remission rates during their treatments. A growing body of scientific evidence points to genetic factors as having a crucial role in patients’ response to antidepressant treatments. One of these genetic components is the BDNF gene, that codes for the BDNF neurotrophin, an important player in neuroplasticity and neurogenesis.
- Electrochemical chemically based sensors and emerging enzymatic biosensors for antidepressant drug detection: a reviewPublication . Caldevilla, Renato; Morais, Stephanie L.; Cruz, Agostinho; Delerue-Matos, Cristina; Moreira, Fernando; Pacheco, João G.; Santos, Marlene; Barroso, Maria FátimaMajor depressive disorder is a widespread condition with antidepressants as the main pharmacological treatment. However, some patients experience concerning adverse reactions or have an inadequate response to treatment. Analytical chromatographic techniques, among other techniques, are valuable tools for investigating medication complications, including those associated with antidepressants. Nevertheless, there is a growing need to address the limitations associated with these techniques. In recent years, electrochemical (bio)sensors have garnered significant attention due to their lower cost, portability, and precision. Electrochemical (bio)sensors can be used for various applications related to depression, such as monitoring the levels of antidepressants in biological and in environmental samples. They can provide accurate and rapid results, which could facilitate personalized treatment and improve patient outcomes. This state-of-the-art literature review aims to explore the latest advancements in the electrochemical detection of antidepressants. The review focuses on two types of electrochemical sensors: Chemically modified sensors and enzyme-based biosensors. The referred papers are carefully categorized according to their respective sensor type. The review examines the differences between the two sensing methods, highlights their unique features and limitations, and provides an in-depth analysis of each sensor.
- Seasonal influenza vaccine effectiveness in persons aged 15–64 years: a systematic review and meta-analysisPublication . Martins, João Paulo; Santos, Marlene; Martins, André; Felgueiras, Miguel; Santos, RuiInfluenza is a respiratory disease caused by the influenza virus, which is highly transmissible in humans. This paper presents a systematic review and meta-analysis of randomized controlled trials (RCTs) and test-negative designs (TNDs) to assess the vaccine effectiveness (VE) of seasonal influenza vaccines (SIVs) in humans aged 15 to 64 years. An electronic search to identify all relevant studies was performed. The outcome measure of interest was VE on laboratory-confirmed influenza (any strain). Quality assessment was performed using the Cochrane risk-of-bias tool for RCTs and the ROBINS-I tool for TNDs. The search identified a total of 2993 records, but only 123 studies from 73 papers were included in the meta-analysis. Of these studies, 9 were RCTs and 116 were TNDs. The pooled VE was 48% (95% CI: 42–54) for RCTs, 55.4% (95% CI: 43.2–64.9) when there was a match between the vaccine and most prevalent circulating strains and 39.3% (95% CI: 23.5–51.9) otherwise. The TNDs’ adjusted VE was equal to 39.9% (95% CI: 31–48), 45.1 (95% CI: 38.7–50.8) when there was a match and 35.1 (95% CI: 29.0–40.7) otherwise. The match between strains included in the vaccine and strains in circulation is the most important factor in the VE. It increases by more than 25% when there is a match with the most prevalent circulating strains. The laboratorial method for confirmation of influenza is a possible source of bias when estimating VE.
- Análise do consumo de antidepressivos e seus encargos em Portugal ContinentalPublication . Nogueira, Joana; Santos, MarleneA OMS define a depressão como uma perturbação mental comum, caraterizada por tristeza, perda de interesse ou prazer, sentimento de culpa ou baixa autoestima, perturbações de sono ou de apetite, sensação de cansaço e falta de concentração. É uma doença multifatorial, condicionada por fatores biológicos, genéticos e psicossociais. De acordo com a Organização Mundial de Saúde (OMS), estima-se que a sua prevalência aumente, atingindo o 2º lugar nas causas das doenças degenerativas e suicídio.
- ABCB1 C1236T, G2677TA and C3435T genetic polymorphisms and antidepressant response phenotypes: results from a portuguese major depressive disorder cohortPublication . Santos, Marlene; Lima, Luís; Carvalho, Serafim; Brandão, Andreia; Barroso, Fátima; Cruz, Agostinho; Medeiros, RuiP-glycoprotein (P-GP) is a transporter molecule expressed on the apical surface of capillary endothelial cells of the Blood–Brain Barrier (BBB), whose activity heavily influences drug distribution, including antidepressants. This transporter is encoded by ABCB1 gene, and genetic variations within ABCB1 gene have been proposed to affect drug efflux and have been previously associated with depression. In this context, we aimed to evaluate the role of C1236T, G2677TA and C3435T ABCB1 genetic polymorphisms in antidepressant treatment phenotypes from a cohort of patients harboring Major Depressive Disorder. Patients enrolled in the study consisted of 80 individuals with Major Depressive Disorder, who took part in a 27-month follow-up study at HML, Portugal. To investigate the correlation between ABCB1 polymorphisms and antidepressant response phenotypes, DNA was extracted from peripheral blood, and C1236T, C3435T and G2677TA polymorphisms were genotyped with TaqMan® SNP Genotyping Assays. Despite the fact that the evaluated polymorphisms (C1236T, C3435T and G2677TA) were not associated with treatment resistant depression, or relapse, we observed that patients carrying TT genotype of the C3435T polymorphism remit earlier than the ones carrying CC or CT genotypes (10.2 weeks vs. 14.9 and 21.3, respectively, p = 0.028, Log-rank test). Since we found an association with C3435T and time to remission, and not to the absence of remission, we suggest that this polymorphism could have an impact on antidepressant drug distribution, and thus influence on the time to remission will occur, without influencing the risk of remission itself.
- Avaliação do efeito anti-inflamatório do antidepressivo fluvoxamina – revisão sistemáticaPublication . Ramalho, Ana; Cruz, Agostinho; Santos, MarleneA fluvoxamina é um inibidor seletivo da recaptação de serotonina utilizado principalmente no tratamento da depressão e ansiedade. Evidências da literatura apontaram para que o tratamento com fluvoxamina em doentes infetados com SARS-CoV-2, melhore os sintomas da COVID-19. Assim, torna-se relevante explorar o mecanismo anti-inflamatório da fluvoxamina. O objetivo deste trabalho centrou-se em rever as evidências científicas de estudos in vitro e in vivo, centrados na compreensão do efeito anti-inflamatório da fluvoxamina. Este trabalho consistiu numa revisão sistemática conduzida na base de dados Pubmed, e incluiu estudos que avaliassem o efeito ou moléculas inflamatórias, e que abordassem a fluvoxamina. As evidências sugerem que a fluvoxamina reduz significativamente a produção das interleucinas IL-6, IL-1, NO, IFN-γ, COX-2, TNF-α e o cortisol, e aumenta a produção de IL-4, IL-10, TGF-β e melatonina. Foi ainda verificado que fluvoxamina é um agonista do recetor sigma-1, através do qual controla a inflamação. Em conclusão, os dados sugerem que a fluvoxamina é dotada de propriedades anti-inflamatórias por múltiplos mecanismos de ação. Será importante realizar-se estudos adicionais que explorem a atividade anti-inflamatória da fluvoxamina, avaliando mediadores inflamatórios, designadamente, a COX-2, LOX e TNF-α.
- Impact of the first wave of the COVID-19 outbreak on mental health and psychiatric drug use among portuguese pharmacy professionalsPublication . Carvalho, A.R.; Cruz, Agostinho; Santos, MarleneThe COVID-19 outbreak was considered a pandemic by the World Health Organization on March 11, 2020 [1]. This outbreak has raised public health problems, bringing with it several implications both on physical and psychological level, in particular for health professionals on the front line of the pandemic, for the greater risk of infection [2,3]. In this sense, it is pertinent to evaluate how the COVID-19 outbreak had implications on the mental health and in the consumption of psychotropic drugs in Portugal, and among pharmacy professionals.
- Design of an electrochemical genosensor for the BDNF gene polymorphism sequence detection using an enzymatic labelled DNA probePublication . Caldevilla, Renato; Morais, Stephanie; Carvalho, Serafim; Medeiros, Rui; Delerue-Matos, Cristina; Cruz, Agostinho; Santos, Marlene; Barroso, M. FátimaThe BDNF gene is associated with high degrees of variability in antidepressant treatments. The Val66Met polymorphism is widely known as a source of this variability, warranting growing interest in genotyping patients that undergo antidepressant treatment to better suit their needs. This paper reports on an electrochemical genosensing platform, based on gold electrodes, capable of detecting this polymorphism, through the use of synthetic enzymatic labelled DNA-probes for 2 different BDNF alleles. The sensor showed promising results, and its applicability to real samples is currently being tested.