160 research outputs found

    The role of ionic vs. non-ionic excipients in APIs-based eutectic systems

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    Aiming to contribute to drug pre-formulation, new eutectic mixtures were developed. Thymol, coumarin, or quaternary ammonium chlorides as excipients, were combined with the active pharmaceutical ingredients (APIs) acetylsalicylic acid, acetaminophen, ibuprofen, ketoprofen, or lidocaine. Their solid-liquid equilibrium (SLE) binary phase diagrams were measured to study eventual phase separation between the compounds, preventing manufacturing problems, and to study the molecular interactions between the APIs and ionic or non-ionic excipients. The Conductor-like Screening Model for Real Solvents (COSMO-RS) capability to predict the SLE of mixtures containing non-ionic excipients was further evaluated. COSMO-RS gives a good quantitative description of the experimental SLE being a tool with great potential in the screening of eutectic systems containing APIs and non-ionic excipients. While thymol presents strong interactions with the APIs, and consequently negative deviations to thermodynamic ideality, systems containing coumarin follow a quasi-ideal behavior. Regarding the ionic excipients, both choline chloride and the tetraalkylammonium chlorides are unable to establish relevant interactions with the APIs, and no significant negative deviations to ideality are observed. The liquefaction of the APIs here studied is favored by using non-ionic excipients, such as thymol, due to the strong interactions it can establish with the APIs.This work was developed within the scope of the project CICECO Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, and CIMO-Mountain Research Center, UIDB/00690/2020, both financed by national funds through the Portuguese Foundation for Science and Technology/MCTES. L.P.S. acknowledges FCT for her PhD grant (SFRH/BD/135976/2018).info:eu-repo/semantics/publishedVersio

    Antimicrobial resistance three ways: healthcare crisis, major concepts, and the relevance of biofilms

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    Worldwide, infections are resuming their role as highly effective killing diseases, as current treatments are failing to respond to the growing problem that is antimicrobial resistance (AMR). The social and economical burden of AMR seems ever rising, with health- and research-related organizations rushing to collaborate on a worldwide scale to find effective solutions. Resistant bacteria are spreading even in first-world nations, being found not only in healthcare-related settings, but also in food and in the environment. In this mini-review, the impact of AMR in healthcare systems and the major bacteria behind it are highlighted. Ecological aspects of AMR evolution and the complexity of its molecular mechanisms are explained. Major concepts, such as intrinsic, acquired, and adaptive resistance, as well as tolerance and heteroresistance, are also clarified. More importantly, the problematic of biofilms and their role in AMR, namely its main resistance and tolerance mechanisms, is elucidated. Finally, some of the most promising anti-biofilm strategies being investigated are reviewed. Much is still to be done regarding the study of AMR and the discovery of new anti-biofilm strategies. Gladly, considerable research on this topic is generated every day and increasingly concerted actions are being engaged globally to try and tackle this problem.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge COMPETE2020 and FCT for the project POCI-01-0145-FEDER-029841, and FCT for the PhD Grants of Andreia Magalhães [grant number SFRH/BD/132165/2017] and Tânia Grainha [grant number SFRH/BD/136544/2018].info:eu-repo/semantics/publishedVersio

    Development of a new chitosan hydrogel for wound dressing

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    Wound healing is a complex process involving an integrated response by many different cell types and growth factors in order to achieve rapid restoration of skin architecture and function. The present study evaluated the applicability of a chitosan hydrogel (CH) as a wound dressing. Scanning electron microscopy analysis was used to characterize CH morphology. Fibroblast cells isolated from rat skin were used to assess the cytotoxicity of the hydrogel. CH was able to promote cell adhesion and proliferation. Cell viability studies showed that the hydrogel and its degradation by-products are noncytotoxic. The evaluation of the applicability of CH in the treatment of dermal burns in Wistar rats was performed by induction of full-thickness transcutaneous dermal wounds. Wound healing was monitored through macroscopic and histological analysis. From macroscopic analysis, the wound beds of the animals treated with CH were considerably smaller than those of the controls. Histological analysis revealed lack of a reactive or a granulomatous inflammatory reaction in skin lesions with CH and the absence of pathological abnormalities in the organs obtained by necropsy, which supported the local and systemic histocompatibility of the biomaterial. The present results suggest that this biomaterial may aid the re-establishment of skin architecture

    A psicologia como neurociência cognitiva : implicações para a compreensão dos processos básicos e suas aplicações

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    O presente artigo procura ilustrar o modo como os desenvolvimentos das neurociências cognitivas poderão ajudar a compreender alguns dos processos psicológicos básicos e, simultaneamente, ser traduzidos para importantes domínios da psicologia aplicada, particularmente no domínio clínico. Exemplificaremos a partir de algumas linhas de investigação programática em curso nas diferentes subsecções do Laboratório de Neuropsicofisiologia da Escola de Psicologia da Universidade do Minho. As potencialidades metodológicas proporcionadas pela neurofisiologia, neuroimagiologia, neuromodelação, psicofisiologia, neurobioquímica e neurogenética serão exemplificadas nas suas aplicações à linguagem (e suas implicações para a compreensão da esquizofrenia), funcionamento sócio-cognitivo (e implicações para a compreensão das perturbações do neurodesenvolvimento), funcionamento executivo (com implicações para a compreensão das perturbações do espectro obsessivo), empatia (e implicações para a compreensão da psicoterapia), mecanismos de stress (com implicações para a compreensão das perturbações de ansiedade), e, finalmente, comportamento animal (com implicações para o conhecimento dos sistemas sensoriais e perceptuais).(undefined

    Is prnt a pseudogene? identification of ram prt in testis and ejaculated spermatozoa

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    A hallmark of prion diseases or transmissible spongiform encephalopaties is the conversion of the cellular prion protein (PrPC), expressed by the prion gene (prnp), into an abnormally folded isoform (PrPSc) with amyloid-like features that causes scrapie in sheep among other diseases. prnp together with prnd (which encodes a prion-like protein designated as Doppel), and prnt (that encodes the prion protein testis specific - Prt) with sprn (shadow of prion protein gene, that encodes Shadoo or Sho) genes, constitute the "prion gene complex". Whereas a role for prnd in the proper functioning of male reproductive system has been confirmed, the function of prnt, a recently discovered prion family gene, comprises a conundrum leading to the assumption that ruminant prnt is a pseudogene with no protein expression. The main objective of the present study was to identify Prt localization in the ram reproductive system and simultaneously to elucidate if ovine prnt gene is transcribed into protein-coding RNA. Moreover, as Prt is a prnp-related protein, the amyloid propensity was also tested for ovine and caprine Prt. Recombinant Prt was used to immunize BALB/c mice, and the anti-Prt polyclonal antibody (APPA) immune response was evaluated by ELISA and Western Blot. When tested by indirect immunofluorescence, APPA showed high avidity to the ram sperm head apical ridge subdomain, before and after induced capacitation, but did not show the same behavior against goat spermatozoa, suggesting high antibody specificity against ovine-Prt. Prt was also found in the testis when assayed by immunohistochemistry during ram spermatogenesis, where spermatogonia, spermatocytes, spermatids and spermatozoa, stained positive. These observations strongly suggest ovine prnt to be a translated protein-coding gene, pointing to a role for Prt protein in the ram reproductive physiology. Besides, caprine Prt appears to exhibit a higher amyloid propensity than ovine Prt, mostly associated with its phenylalanine residue.publishersversionpublishe

    Glycemic index and glycemic response of corn starch porridge with addition of oats, flaxseed or soluble fiber isolated

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    Indexación: ScopusIntroduction: Fibers are commonly known to contribute in the improvement of glycemic and lipid profile, exerting a beneficial effect on health, but its effect on the glycemic index of food is still controversial. Objective: To evaluate the effect of adding high-fiber foods (oats and flaxseed) and a supplement of soluble fiber isolated on the glycemic index (GI) and glycemic response of a porridge of corn starch. Methodology: The study was of crossover, where six healthy subjects ingested preparations based on a maize porridge added to different foods rich in fiber, the GI of the preparations was calculated according to the methodology of FAO. Results: The preparation of linseed added resulting in a lesser glycemic response times 45-90 min and with the addition of oat preparation showed the best results at times 60 and 90 minutes. The mean area under the curve of the glycemic response and GI of the preparations did not differ. Conclusion: Oatmeal linseed seem foods with beneficial properties reduce the glycemic response to food.http://revista.nutricion.org/revista.asp?id=4

    Inhibition of ovine in vitro fertilization by anti-Prt antibody: hypothetical model for Prt/ZP interaction

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    BACKGROUND: The impact of prion proteins in the rules that dictate biological reproduction is still poorly understood. Likewise, the role of prnt gene, encoding the prion-like protein testis specific (Prt), in ram reproductive physiology remains largely unknown. In this study, we assessed the effect of Prt in ovine fertilization by using an anti-Prt antibody (APPA) in fertilization medium incubated with spermatozoa and oocytes. Moreover, a computational model was constructed to infer how the results obtained could be related to a hypothetical role for Prt in sperm-zona pellucida (ZP) binding. METHODS: Mature ovine oocytes were transferred to fertilization medium alone (control) or supplemented with APPA, or pre-immune serum (CSerum). Oocytes were inseminated with ovine spermatozoa and after 18 h, presumptive zygotes (n = 142) were fixed to evaluate fertilization rates or transferred (n = 374) for embryo culture until D6-7. Predicted ovine Prt tertiary structure was compared with data obtained by circular dichroism spectroscopy (CD) and a protein-protein computational docking model was estimated for a hypothetical Prt/ZP interaction. RESULTS: The fertilizing rate was lower (P = 0.006) in APPA group (46.0+/−6.79%) when compared to control (78.5+/−7.47%) and CSerum (64.5+/−6.65%) groups. In addition, the cleavage rate was higher (P < 0.0001) in control (44.1+/−4.15%) than in APPA group (19.7+/−4.22%). Prt CD spectroscopy showed a 22% alpha-helical structure in 30% (m/v) aqueous trifluoroethanol (TFE) and 17% alpha in 0.6% (m/v) TFE. The predominant alpha-helical secondary structure detected correlates with the predicted three dimensional structure for ovine Prt, which was subsequently used to test Prt/ZP docking. Computational analyses predicted a favorable Prt-binding activity towards ZP domains. CONCLUSIONS: Our data indicates that the presence of APPA reduces the number of fertilized oocytes and of cleaved embryos. Moreover, the CD analysis data reinforces the predicted ovine Prt trend towards an alpha-helical structure. Predicted protein-protein docking suggests a possible interaction between Prt and ZP, thus supporting an important role for Prt in ovine fertilization

    Spatial extremes of wildfire sizes: Bayesian hieralquical models for extremes

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    In Portugal, due to the combination of climatological and ecological factors, large wildfires are a constant threat and due to their economic impact, a big policy issue. In order to organize efficient fire fighting capacity and resource management, correct quantification of the risk of large wildfires are needed. In this paper, we quantify the regional risk of large wildfire sizes, by fitting a Generalized Pareto distribution to excesses over a suitably chosen high threshold. Spatio-temporal variations are introduced into the model through model parameters with suitably chosen link functions. The inference on these models are carried using Bayesian Hierarchical Models and Markov chain Monte Carlo methods
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