Historical origin and antiepileptic drug development

INTRODUCTION: New antiepileptic drugs are needed because many epileptic patients do not achieve complete control with current antiepileptic drugs. METHODS: We reviewed the historical origin of antiepileptic drugs, the different phases of the medical treatment related to monotherapy or polytheraphy, and the experimental models applied to develop new medications nowadays. RESULTS: Experimental models have been used for many years in order to detect some rational mechanisms of action. The results are interesting but limited. Some drugs fail the scrutiny and still they may be clinically effective. On the other hand, some drugs have good experimental profile but are extremely toxic in humans. CONCLUSION: Despite mild advance in the understanding of antiepileptic drug mechanism of action and experimental models of epilepsy, the development of antiepileptic drugs is mostly empirically oriented.INTRODUÇÃO: Há necessidade de novas medicações antiepilépticas, uma vez que um contingente importante dos pacientes com epilepsia não obtém controle satisfatório de suas crises epilépticas com o arsenal terapêutico disponível. Existe preocupação com o desenvolvimento racional de novas drogas antiepilépticas para preencher esta lacuna. MATERIAL E MÉTODOS: Revisão da literatura sobre o desenvolvimento e o surgimento das drogas antiepilépticas, assim como as diferentes fases históricas com relação ao uso de uma (monoterapia) versus o uso de mais do que uma medicação simultaneamente (politerapia). RESULTADOS: Modelos experimentais de epilepsia foram utilizados na predição da eficácia das drogas antiepilépticas. Os resultados obtidos têm limitações, isto é, drogas que não evidenciaram atividade nestes modelos experimentais mostraram-se úteis na prática clínica. Por outro lado, drogas que atuaram nestes modelos não se mostraram clinicamente adequadas por toxicidade excessiva no homem. CONCLUSÃO: A despeito do melhor conhecimento científico do mecanismo de ação das drogas antiepilépticas o desenvolvimento de novas drogas ainda tem sido fundamentalmente empírico.182

Comorbidades associadas às epilepsias e cefaleias

Comorbidities are often associated with chronic neurological diseases, such as headache and epilepsy. OBJECTIVES: To identify comorbidities associated with epilepsy and headaches, and to determine possible drug interactions. METHODS: A standardized questionnaire with information about type of epilepsy/headache, medical history, and medication was administered to 80 adult subjects (40 with epilepsy and 40 with chronic headache). RESULTS: Patients with epilepsy had an average of two comorbidities and those with headache of three. For both groups, hypertension was the most prevalent. On average, patients with epilepsy were taking two antiepileptic medications and those with headache were taking only one prophylactic medication. Regarding concomitant medications, patients with epilepsy were in use, on average, of one drug and patients with headache of two. CONCLUSIONS: Patients with chronic neurological diseases, such as epilepsy and headaches, have a high number of comorbidities and they use many medications. This may contribute to poor adherence and interactions between different medications.As comorbidades geralmente estão associadas a doenças neurológicas crônicas, tais como cefaleia e epilepsia. OBJETIVOS: Identificar comorbidades associadas à epilepsia e cefaleia e determinar as possíveis interações de drogas. MÉTODOS: Questionário padronizado com informações sobre o tipo de epilepsia/cefaleia, os antecedentes médicos e as medicações foi aplicado a 80 indivíduos adultos (40 com epilepsia e 40 com cefaleia crônica). RESULTADOS: Pacientes com epilepsia e cefaleia apresentaram uma média de duas e três comorbidades, respectivamente, sendo, para ambos, hipertensão arterial sistêmica a mais prevalente. Em média, os pacientes com epilepsia estavam em uso de duas medicações antiepilépticas; aqueles com cefaleia, uma medicação profilática. Em relação às medicações concomitantes, os pacientes com epilepsia estavam em uso, em média, de uma droga e os pacientes com cefaleia de duas. CONCLUSÕES: Pacientes com doenças neurológicas crônicas, como epilepsia e cefaleia, apresentam elevado número de comorbidades e utilizam grande número de medicações. Isso pode contribuir para diminuir a aderência ao tratamento e facilitar interações entre diversas medicações.27427

Understanding pseudo-albinism in sole (Solea senegalensis): a transcriptomics and metagenomics approach

Pseudo-albinism is a pigmentation disorder observed in flatfish aquaculture with a complex, multi-factor aetiology. We tested the hypothesis that pigmentation abnormalities are an overt signal of more generalised modifications in tissue structure and function, using as a model the Senegalese sole and two important innate immune barriers, the skin and intestine, and their microbiomes. Stereological analyses in pseudo-albino sole revealed a significantly increased mucous cell number in skin (P < 0.001) and a significantly thicker muscle layer and lamina propria in gut (P < 0.001). RNA-seq transcriptome analysis of the skin and gut identified 573 differentially expressed transcripts (DETs, FDR < 0.05) between pseudo-albino and pigmented soles (one pool/tissue from 4 individuals/phenotype). DETs were mainly linked to pigment production, skin structure and regeneration and smooth muscle contraction. The microbiome (16 S rRNA analysis) was highly diverse in pigmented and pseudo-albino skin but in gut had low complexity and diverged between the two pigmentation phenotypes. Quantitative PCR revealed significantly lower loads of Mycoplasma (P < 0.05) and Vibrio bacteria (P < 0.01) in pseudo-albino compared to the control. The study revealed that pseudo-albinism in addition to pigmentation changes was associated with generalised changes in the skin and gut structure and a modification in the gut microbiome.Agência financiadora H2020 European Funds MSCA-RISE project 691102 Portuguese national funds from FCT - Foundation for Science and Technology UID/Multi/04326/2019 Portuguese national funds from the operational programme CRESC Algarve 2020 EMBRC. PT ALG-01-0145-FEDER-022121 Portuguese national funds from the operational programme COMPETE 2020 EMBRC. PT ALG-01-0145-FEDER-022121 European Union (EU) 654008 Fundacao para a Ciencia e a Tecnologia (FCT) SFRH/BPD/84033/2012 Portuguese Institute for Employment and Vocational Training 0068/ET/18info:eu-repo/semantics/publishedVersio

O concheiro de Salamansa (Ilha de São Vicente, arquipélago de Cabo Verde) : nota preliminar

Cardoso, João Luís [et al.] - O concheiro de Salamansa (Ilha de São Vicente, arquipélago de Cabo Verde) : nota preliminar. "Portugalia" [Em linha]. ISSN 0871-4290. Nova Série, vol. 23 (2002), p. 221-23

Escherichia coli expression and purification of four antimicrobial peptides fused to a family 3 carbohydrate-binding module (CBM) from Clostridium thermocellum

Antimicrobial peptides (AMPs) are molecules that act in a wide range of physiological defensive mechanisms developed to counteract bacteria, fungi, parasites and viruses. Several hundreds of AMPs have been identified and characterized. These molecules are presently gaining increasing importance, as a consequence of their remarkable resistance to microorganism adaptation. Carbohydrate-binding modules (CBMs) are non-catalytic domains that anchor glycoside hydrolases into complex carbohydrates. Clostridium thermocellum produces a multi-enzyme complex of cellulases and hemicellulases, termed the cellulosome, which is organized by the scaffoldin protein CipA. Binding of the cellulosome to the plant cell wall results from the action of CipA family 3 CBM (CBM3), which presents a high affinity for crystalline cellulose. Here CipA family 3 CBM was fused to four different AMPs using recombinant DNA technology and the fusion recombinant proteins were expressed at high levels in Escherichia coli cells. CBM3 does not present antibacterial activity and does not bind to the bacterial surface. However, the four recombinant proteins retained the ability to bind cellulose, suggesting that CBM3 is a good candidate polypeptide to direct the binding of AMPs into cellulosic supports. A comprehensive characterization of the antimicrobial activity of the recombinant fusion proteins is currently under evaluation.Instituto de Tecnologia Química e Biológica,Fundação para a Ciência e a Tecnologia (FCT

Antioxidant potential of the bio-based fucose-rich polysaccharide fucopol supports its use in oxidative stress-inducing systems

UIDP/04378/2020 UIDB/04378/2020 SFRH/BD/144258/2019Reactive oxygen species (ROS) are dangerous sources of macromolecular damage. While most derive from mitochondrial oxidative phosphorylation, their production can be triggered by ex-ogenous stresses, surpassing the extinction capacity of intrinsic antioxidant defense systems of cells. Here, we report the antioxidant activity of FucoPol, a fucose-rich polyanionic polysaccharide produced by Enterobacter A47, containing ca. 17 wt% of negatively charged residues in its struc-ture. Ferric reducing antioxidant power (FRAP) assays coupled to Hill binding kinetics fitting have shown FucoPol can neutralize ferricyanide and Fe3+-TPTZ species at an EC50 of 896 and 602 µg/mL, respectively, with positive binding cooperativity (2.52 ≤ H ≤ 4.85). This reducing power is greater than most polysaccharides reported. Moreover, an optimal 0.25% w/v FucoPol concentration shown previously to be cryo-and photoprotective was also demonstrated to protect Vero cells against H2O2-induced acute exposure not only by attenuating metabolic viability decay, but also by accentuating post-stress proliferation capacity, whilst preserving cell morphology. These results on antioxidant activity provide evidence for the biopolymer’s ability to prevent positive feedback cascades of the radical-producing Fenton reaction. Ultimately, FucoPol provides a biotechnological alternative for implementation in cryopreservation, food supplementation, and photoprotective sunscreen formula design, as all fields benefit from an antioxidant functionality.publishersversionpublishe

Viden i Verden

I marts 2017 tog vi til Cuba med 17 kandidatstuderende fra ’Turisme’ på Aalborg Universitet. Forløbet var en del af ’Creative Learning Camp’, som var en integreret del af 8. semester på kandidatuddannelsen. I forløbet blev de studerende stillet over for en opgave sat af en amerikansk NGO om bæredygtig turisme i Viñales, Cu-ba, som de skulle løse, og som de skulle levere til organisationen efter deres feltarbejde. Vi diskuterer i denne artikel, hvordan det at tage de studerende ud af undervisningslokalet til en for dem ukendt kontekst kan gøre deres læring anderledes og relevant for et senere arbejdsliv, da de skulle løse en opgave ’fra det virkelige liv’ kombineret med det at skulle begå sig i en helt ny kontekst. Vi er inspireret af Kolbs læringscirkel (2014), og vi diskuterer både peer learning og læring i grupper inden for denne teoretiske ramme. Vores antagelse er, at læringsprocesserne styrkes inden for PBL, hvis man inddrager en erfaringsbaseret og eksperimenterende læring i en virkelighedsnær kontekst. Vi betragter i denne sammenhæng de studerende som både medforskere og konsulenter

[treatment Of Epilepsy: Consensus Of The Brazilian Specialists].

Epilepsy is a frequent condition in the world. Recently a study in Brazil showed prevalence of 18/1000 inhabitants in São José do Rio Preto, São Paulo State. In the last decade, new therapeutic options were discovered or developed. The main therapeutic decision method is based on randomized clinical trials. This method represents the higher level of evidence. However, even these studies have limitations and in some cases the treatment of choice remains controversial. In these instances, the epilepsy experts' opinions become helpful. In 2001 a similar study had been conducted in USA. The aim of this study is to create guidelines for epilepsy treatment based on the opinion of the Brazilian experts. These guidelines can be used to create manuals and strategies for the treatment of some epileptic syndromes according to Brazilian experts. As compared to the North-American guidelines our study better reflects the resources available in our country.611045-7