Enantioselective HPLC-UV method for determination of eslicarbazepine acetate (BIA 2-093) and its metabolites in human plasma

Eslicarbazepine acetate (BIA 2-093) is a novel central nervous system drug undergoing clinical phase III trials for epilepsy and phase II trials for bipolar disorder. A simple and reliable chiral reversed-phase HPLC-UV method was developed and validated for the simultaneous determination of eslicarbazepine acetate, oxcarbazepine, S-licarbazepine and R-licarbazepine in human plasma. The analytes and internal standard were extracted from plasma by a solid-phase extraction using Waters Oasis® HLB cartridges. Chromatographic separation was achieved by isocratic elution with water–methanol (88:12, v/v), at a flow rate of 0.7 mL/min, on a LichroCART 250-4 ChiraDex (β-cyclodextrin, 5 μm) column at 30°C. All compounds were detected at 225 nm. Calibration curves were linear over the range 0.4–8 μg/mL for eslicarbazepine acetate and oxcarbazepine, and 0.4 – 80 μg/ mL for each licarbazepine enantiomer. The overall intra- and interday precision and accuracy did not exceed 15%. Mean relative recoveries varied from 94.00 to 102.23% and the limit of quantification of the assay was 0.4 μg/mL for all compounds. This method seems to be a useful tool for clinical research and therapeutic drug monitoring of eslicarbazepine acetate and its metabolites S-licarbazepine, R-licarbazepine and oxcarbazepine

Os novos shâmanes: um contributo para o estudo da narratividade na poesia portuguesa mais recente

Universidade da Madeir

Genome Characterization and Spaciotemporal Dispersal Analysis of Bagaza Virus Detected in Portugal, 2021

Funding Information: This work received financial support from the Global Health and Tropical Medicine Center (which is funded through Fundação para a Ciência e a Tecnologia (FCT) contract UID/Multi/04413/2013). This research was also funded by FCT, Project UIDB/00276/2020 and LA/P/0059/2020-AL4AnimalS, and by the Interdisciplinary Research Center on Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon (Portugal). Finally, this research was also partially funded by the Interdisciplinary Research Center on Animal Health (Project CIISA-INOV 4/2021), Faculty of Veterinary Medicine, University of Lisbon (CIISA, FMV-UL) (Portugal). Publisher Copyright: © 2023 by the authors.In September 2021, Bagaza virus (BAGV), a member of the Ntaya group from the Flavivirus genus, was detected for the first time in Portugal, in the heart and the brain of a red-legged partridge found dead in a hunting ground in Serpa (Alentejo region; southern Portugal). Here we report the genomic characterization of the full-length sequence of the BAGV detected (BAGV/PT/2021), including phylogenetic reconstructions and spaciotemporal analyses. Phylogenies inferred from nucleotide sequence alignments, complemented with the analysis of amino acid alignments, indicated that the BAGV strain from Portugal is closely related to BAGV strains previously detected in Spain, suggesting a common ancestor that seems to have arrived in the Iberia Peninsula in the late 1990s to early 2000s. In addition, our findings support previous observations that BAGV and Israel turkey meningoencephalitis virus (ITV) belong to the same viral species.publishersversionpublishe

Effect of a single intra-articular high molecular weight hyaluronan in a naturally occurring canine osteoarthritis model : a randomized controlled trial

Research Areas: OrthopedicsBackground Osteoarthritis (OA) is a complex joint disease and chronic pain source, affecting a patient's quality of life and posing a financial burden. As the dog is considered a nearly ideal species for translation research of human OA and the most used model for research, exploring spontaneous dog OA under the One Health/One Medicine concept can improve both humans and dogs' health and well-being. Methods In a clinical treatment experiment, forty (N=40) joints were selected and randomly assigned to a control group (CG), which received 0.9% NaCl or a treatment (HG), which received Hylan G-F 20. Evaluations were performed on treatment day (T0), 8, 15, 30, 90, and 180 days post-treatment. They consisted of four different Clinical Metrology Instruments (CMI), evaluation of weight distribution, joint range of motion, thigh girth, radiographic and digital thermography imaging, synovial fluid interleukin-1 (IL-1), and C-reactive protein concentrations. Results were compared with repeated measures ANOVA, with a Huynh-Feldt correction, Paired samples T-test, or Wilcoxon signed-ranks test, with pResults Patients had a mean age of 6.5 +/- 2.4 years and a bodyweight of 26.6 +/- 5.2kg, and joints graded as mild (n=28, 70%), moderate (n=6, 15%), and severe OA (n=6, 15%). No differences were found between groups at T0. Symmetry index and deviation showed significant improvements in HG from 30 days (p<0.01) up to 180 days (p=0.01). Several CMI scores, particularly pain scores, improved from 90 to 180 days. Radiographic signs progressed in both groups. In both groups, increasing body weight and age corresponded to worse clinical presentation. IA hyaluronan administration produced increased lameness in six cases, which resolved spontaneously. Conclusions This study characterizes the response to treatment with Hylan G-F 20, which can produce significant functional and pain level improvements in patients with OA, even those with factors related to worse response to treatment.info:eu-repo/semantics/publishedVersio

Altered iron metabolism is part of the choroid plexus response to peripheral inflammation.

Iron is essential for normal cellular homeostasis but in excess promotes free radical formation and is detrimental. Therefore, iron metabolism is tightly regulated. Here, we show that mechanisms regulating systemic iron metabolism may also control iron release into the brain at the blood-choroid plexus-cerebrospinal fluid (CSF) barrier. Intraperitoneal administration of lipopolysaccharide (LPS) in mice triggers a transient transcription of the gene encoding for hepcidin, a key regulator of iron homeostasis, in the choroid plexus, which correlated with increased detection of pro-hepcidin in the CSF. Similarly, the expression of several other iron-related genes is influenced in the choroid plexus by the inflammatory stimulus. Using primary cultures of rat choroid plexus epithelial cells, we show that this response is triggered not only directly by LPS but also by molecules whose expression increases in the blood in response to inflammation, such as IL-6. Intracellular conveyors of these signaling molecules include signal transducer and activator of transcription 3, which becomes phosphorylated, and SMAD family member 4, whose mRNA levels increase soon after LPS administration. This novel role for the choroid plexus-CSF barrier in regulating iron metabolism may be particularly relevant to restrict iron availability for microorganism growth, and in neurodegenerative diseases in which an inflammatory underlying component has been reported.This work was supported by Grant POCTI/SAU-NEU/56618/2004 from Fundacao para a Ciencia e Tecnologia (Portugal) and a grant from The Dana Foundation (USA). F. M. is the recipient of postdoctoral fellowship, and A. M. F. is the recipient of a Ph. D., fellowship from Fundacao para a Ciencia e Tecnologia (Portugal)

Impacts of the shift from distressed pavements to low noise pavements in motorways – a case study in Portugal

Road traffic noise is a relevant environmental problem, resulting essentially from the contact mechanisms between tyre and pavement surface. According to the current legislation, noise management actions must primarily intervene at the source. BRISA is employing efforts to determine pavement influence as a parameter of source noise reduction in order to address the well-being of the population surrounding highways and simultaneously comply with European directives regarding Environmental Noise evaluation and management. This Project evaluates the environmental noise effects of replacing a wearing course of Porous and Bituminous Asphalt at end-of-life for a course of SMA12, using two different methodologies for tyre-road noise measurement: the Statistical Pass-By method and the Close Proximity method

Environmental determinants of health: NOVA National School of Public Health research to tackle ongoing threats and challenges

The environment in which we live represents a major determinant of our health and well-being. The complex human-animal-ecosystem interface imposes an increasing risk to public health with population health influenced by the interaction of multiple environmental determinants. Recognizing how the environment influences human health and disease allows us to identify the most relevant risk factors and the most suitable measures to mitigate environmental factors that adversely affect human health and ecological systems. Climate change represents a major threat to human health, and it is nowadays undermining every dimension of global health monitored, increasing the fragility of the global systems, and increasing the vulnerability of populations, with a special emphasis on the already most vulnerable. The world is now facing frequent extreme weather events such as heatwaves, floods, droughts, and hurricanes. Rising temperatures and changes in precipitation patterns also affect the seasonality and geographic range of many infectious diseases, particularly those transmitted by vectors. Predictably, air quality will be negatively impacted, leading to an increase in the burden of noncommunicable diseases. Biological and chemical contaminants in food are also impacted by climate change, modifying their virulence, occurrence, and distribution patterns, which may increase the risk of human exposure to foodborne hazards. Agricultural productivity and clean water availability may decrease, resulting in malnutrition, foodborne illnesses, and waterborne diseases, endangering food security and safety. The transition to more sustainable and healthier diets constitutes a significant challenge for human populations already under the pressure of climate change-associated events but is considered one of the solutions to tackle this global threat.info:eu-repo/semantics/publishedVersio

In vitro biological activity and phenolic profile of selected portuguese monofloral honeys

Portuguese monofloral honeys from carob tree, chestnut, bell heather, eucalyptus, incense, orange, and strawberry tree, were evaluated in vitro for antimicrobial, antioxidant, wound healing, and cell viability effect, compared to manuka honey 850+. Antimicrobial activity was determined against Gram+-and Gram- bacteria and yeast. Antioxidants, wound healing, and cell viability effects were studied in the Human Keratinocyte (HaCaT) cell line. Chestnut, bell heather, eucalyptus, manuka and strawberry tree honeys were most effective against S. aureus with a minimum inhibitory concentration (MIC) of 12.5%-25.0% (w/v), and greater ability to decrease reactive oxygen species (ROS) production (> 75%), than manuka honey (68%). Incense and orange honeys exhibited high wound healing rates, 89% and 86%, respectively, higher than manuka honey, 53%. Honeys showed cell viability > 76%. Bell heather and strawberry tree honeys exhibited the highest total phenolic content, 38 and 137 mg/100 g honey respectively, being more effective against the microorganisms tested and showing greater antioxidant activity. Opposite, incense, and orange honeys with lower phenolic amounts, 11 and 15 mg/100g honey, respectively, achieved higher wound healing ability. Flavonoid aglycones were the most abundant flavonoids in all honeys. This knowledge can be further explored in formulations that take the best out of each honey type composition and biological activity capacity.To FCT for AMM PhD grant SFRH/BD/117013/2016, JM CEECINST/00145/2018, LMG CEECIND/03143/2017, SIF for the institutional scientific employment program-contract. Partially funded by FCT/MCTES under CESAM UIDP/50017/2020 + UIDB/50017/2020 + LA/P/ 0094/2020, CIMO UID/AGR/00690/2020, MED UIDB/05183/2020, iMed.ULisboa UID/DTP/04138/2019 and UIDB/04138/2020, FEDER and PT2020 PACompete 2020.info:eu-repo/semantics/publishedVersio

a preliminary report

© European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES: Since the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pressure to minimise its impact on public health has led to the implementation of different therapeutic strategies, the efficacy of which for the treatment of coronavirus disease 2019 (COVID-19) was unknown at the time. Remdesivir (REM) was granted its first conditional marketing authorisation in the EU in June 2020. The European Medicines Agency (EMA) and local health authorities all across the EU have since strongly recommended the implementation of pharmacovigilance activities aimed at further evaluating the safety of this new drug. The objective of this study was to evaluate adverse drug reactions (ADRs) attributed to either REM or hydroxychloroquine (HCQ) in patients hospitalised for COVID-19 in Centro Hospitalar de Lisboa Ocidental, a Portuguese hospital centre based in Lisbon. We present the preliminary results reporting plausible adverse effects of either HCQ or REM. METHODS: An observational cohort study was carried out between 16 March and 15 August 2020. Participants were divided into two cohorts: those prescribed an HCQ regimen, and those prescribed REM. Suspected ADRs were identified using an active monitoring model and reported to the Portuguese Pharmacovigilance System through its online notification tool. The ADR cumulative incidence was compared between the two cohorts. RESULTS: The study included 149 patients, of whom 101 were treated with HCQ and the remaining 48 with REM. The baseline characteristics were similar between the two cohorts. A total of 102 ADRs were identified during the study period, with a greater incidence in the HCQ cohort compared with the REM cohort (47.5% vs 12.5%; p<0.001). Causality was assessed in 81 ADRs, all of which were considered possible. CONCLUSIONS: Real-world data are crucial to further establish the safety profile for REM. HCQ is no longer recommended for the treatment of COVID-19.publishersversionpublishe

Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients

Funding Information: We thank Cláudia Andrade for technical support and Juliana Gonçalves for testing samples for SARS-CoV-2 exposure. We are extremely grateful to all the participants of the study and to the whole rheumatology department at Hospital Egas Moniz that made this study possible. This work was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/MEC-REU/29520/2017, by iNOVA4Health UID/Multi/04462 and by Portuguese Society for Rheumatology (SPR) grants to H.S. H.S. is supported by FCT through IF/01722/2013 and CEECIND/01049/2020, DAS and RCT were supported by FCT through PD/BD/137409/2018 and UID/Multi/04462, respectively. Publisher Copyright: © 2021, The Author(s).CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.publishersversionpublishe