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- Livro de atas do IX Colóquio de FarmáciaPublication . Cruz, Agostinho; Cunha, Agostinho; Oliveira, Ana Isabel; Jesus, Ângelo; Pinho, Cláudia; Santos, Marlene; Correia, Patrícia Carla dos Santos; Ferraz Oliveira, RitaLivro de Atas do “IX Colóquio de Farmácia”: “Envelhecimento e Saúde” da “9 th Pharmacy Academic Conference Proceedings” em Abril de 2013.
- FAS -670A>G genetic polymorphism Is associated with treatment resistant depressionPublication . Santos, Marlene; Carvalho, Serafim; Lima, Luís; Mota-Pereira, Jorge; Pimentel, Paulo; Maia, Dulce; Correia, Diana; Gomes, Sofia; Cruz, Agostinho; Medeiros, RuiHippocampal neurogenesis has been suggested as a downstream event of antidepressants (AD) mechanism of action and might explain the lag time between AD administration and the therapeutic effect. Despite the widespread use of AD in the context of Major Depressive Disorder (MDD) there are no reliable biomarkers of treatment response phenotypes, and a significant proportion of patients display Treatment Resistant Depression (TRD). Fas/FasL system is one of the best-known death-receptor mediated cell signaling systems and is recognized to regulate cell proliferation and tumor cell growth. Recently this pathway has been described to be involved in neurogenesis and neuroplasticity. Since FAS -670A>G and FASL -844T>C functional polymorphisms never been evaluated in the context of depression and antidepressant therapy, we genotyped FAS -670A>G and FASL -844T>C in a subset of 80 MDD patients to evaluate their role in antidepressant treatment response phenotypes. We found that the presence of FAS -670G allele was associated with antidepressant bad prognosis (relapse or TRD: OR=6.200; 95% CI: [1.875–20.499]; p=0.001), and we observed that patients carrying this allele have a higher risk to develop TRD (OR=10.895; 95% CI: [1.362–87.135]; p=0.008). Moreover, multivariate analysis adjusted to potentials confounders showed that patients carrying G allele have higher risk of early relapse (HR=3.827; 95% CI: [1.072–13.659]; p=0.039). FAS mRNA levels were down-regulated among G carriers, whose genotypes were more common in TRD patients. No association was found between FASL-844T>C genetic polymorphism and any treatment phenotypes. Small sample size. Patients used antidepressants with different mechanisms of action. To the best of our knowledge this is the first study to evaluate the role of FAS functional polymorphism in the outcome of antidepressant therapy. This preliminary report associates FAS -670A>G genetic polymorphism with Treatment Resistant Depression and with time to relapse. The current results may possibly be given to the recent recognized role of Fas in neurogenesis and/or neuroplasticity.
- O conceito da qualidade nos produtos à base de Ginkgo biloba comercializados em PortugalPublication . Pinho, Cláudia; Correia, Patrícia; Cunha, Agostinho; Jesus, Ângelo; Oliveira, Ana Isabel; Ferraz Oliveira, Rita; Santos, Marlene; Cruz, AgostinhoO extracto de Ginkgo biloba é o produto fitoterápico mais vendido na Europa. Em Portugal e muitos países, a maioria dos produtos à base de plantas são comercializados como suplementos alimentares, não estando garantidos, parâmetros de qualidade, segurança e eficácia. Realizouse um estudo, com recolha de informações, tendo por base uma amostra de 50 produtos à base de ginkgo. Da análise, verificou-se que 94% podiam ser encontrados à venda na internet, e desse total, 89% possuíam informação on-line quanto à composição. Apenas 40% referem a utilização do extracto padronizado de ginkgo e muitos recomendam doses superiores às referidas como terapêuticas.
- 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.
- Influence of common ABCB1 genetic polymorphisms in the risk of Major Depressive Desorder and ntidepressant treatment phenotypesPublication . Santos, Marlene; Carvalho, Serafim; Lima, Luís; Nogueira, Augusto; Assis, Joana; Mota-Pereira, Jorge; Pimentel, Paulo; Maia, Dulce; Correia, Diana; Gomes, Sofia; Cruz, Agostinho; Medeiros, RuiMajor depressive Disorder (MDD) is a highly prevalent disorder, which has been associated with na abnormal response of hypothalamus-pituitary-adrenal (HPA) axis.
- 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.
- The role of IL18-607C > A and IL18-137G > C promoter polymorphisms in antidepressant treatment phenotypes: A preliminary reportPublication . Santos, Marlene; Carvalho, Serafim; Lima, Luís; Mota-Pereira, Jorge; Pimentel, Paulo; Maia, Dulce; Correia, Diana; Gomes, Sofia; Cruz, Agostinho; Medeiros, RuiRecent studies suggest that immune activation and cytokines, such as IL-18, are involved in depression. IL-18 is expressed in brain and is increased in patients with moderate to severe depression. In this study we aim to evaluate the role of IL18-607C > A and IL18-137G > C promoter polymorphisms in antidepressant treatment phenotypes, specifically relapse and treatment resistant depression (TRD). We genotyped the referred polymorphisms in a subset of 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. Patients carrying IL18-607 CA or AA genotypes were significantly more prone to relapse after AD treatment and present a significantly lower time to relapse than patients carrying CC genotype. Similarly, patients carrying IL18-137 GC or CC genotypes have a significantly higher risk of relapse and display relapse significantly earlier than the ones carrying GG genotype. Due to the low number of IL18-607 CC and IL18-137 GG in the relapse subgroup (n = 3 and n = 5, respectively), results were validated by bootstrapping analysis, and remained significant. No association was found between the evaluated genetic polymorphisms and TRD. IL18 peripheral mRNA levels were upregulated in IL18-607 CA or AA carriers. This preliminary report indicates that IL18-607C > A and IL18-137G > C genetic polymorphisms seem to influence depression relapse after antidepressant treatment in our subset of depressed patients, and may possibly contribute to the disregulated IL-18 levels found in patients with depression.
- 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.