Canabinóides : estrutura química, efeitos farmacológicos e utilização terapêutica

Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas MonizNos últimos anos a Canábis L. Sativa tem sido o foco da atenção da comunidade científica em todo o mundo, devido às potenciais aplicações de um dos seus principais componentes – os canabinóides. De facto, os efeitos terapêuticos demonstrados com a sua utilização no tratamento de diversas patologias têm suscitado um interesse crescente por parte de muitos investigadores. A sua interação com o sistema endocanabinóide tem revelado evidências do envolvimento dos canabinóides em diversos processos fisiológicos como a dor, náuseas, vómitos, esclerose múltipla entre outros. Embora a sua utilização seja controversa, existe um número crescente de estudos que comprovam que os canabinóides podem ser utilizados como terapêutica inicial para diversas patologias. No entanto, é ainda necessária mais investigação para fundamentar a sua aplicação terapêutica. Assim, ao longo deste trabalho, apresentou-se uma visão das diferentes formas como os canabinóides podem ser utilizados para o tratamento de diversas doenças.In recent years Cannabis L. Sativa has been the focus of attention of the scientific community around the world due to the potential applications of one of its main components - cannabinoids. In fact, the therapeutic effects shown by its use in the treatment of various pathologies have raised increasing interest from many researchers. Their interaction with the endocanabinoid system has revealed evidence of the involvement of cannabinoids in several physiological processes such as pain, nausea, vomiting, multiple sclerosis among others. Although their use is controversial, there are an increasing number of studies that prove that cannabinoids can be used as initial therapy for several pathologies. However, further research is still needed to substantiate their therapeutic application. Thus, throughout this work, a vision of the different ways cannabinoids can be used for the treatment of several diseases has been presented

Identification of a non-canonical Ebox motif as a regulatory element in the proximal promoter region of the apolipoprotein E gene

We have used the yeast one-hybrid system to identify transcription factors with binding capability to specific sequences in proximal regions of the apolipoprotein E gene (APOE ) promoter. The sequence between k113 and k80 nt, which contains regulatory elements in various cell types, was used as a bait to screen a human brain cDNA library. Four cDNA clones that encoded portions of the human upstream-stimulatory-factor (USF) transcription factor were isolated. Electrophoretic-mobility-shift assays (' EMSAs ') using nuclear extracts from various human cell lines as well as from rat brain and liver revealed the formation of two DNA-protein complexes within the sequence CACCT-CGTGAC (region k101\k91 of the APOE promoter) that show similarity to the E-box element. The retarded complexes contained USF1, as deduced from competition and supershift assays. Functional experiments using different APOE promoterluciferase reporter constructs transiently transfected into U87

Resgate da via aérea dificil, um caso clínico de emergência pré-hospitalar

Apresentamos o caso clínico de uma doente de 45 anos, obesa (IMC 35kg/m2), hipertensa e diabética que sofreu paragem cardiorrespiratória, provavelmente secundária a episódio de enfarte agudo do miocárdio,com necessidade de manobras de suporte avançado de vida. Apresentava via aérea difícil, pelo pescoço curto, grosso e com baixa mobilidade, distância entre incisivos de cerca de 3cm e distância tiro-mentoniana inferior a 6 cm. Durante as manobras de ressucitação foi tentada intubação orotraqueal, sem sucesso. Após 1 tentativa falhada foi rapidamente colocada máscara laríngea com adequada ventilação e oxigenação da doente e recuperação da circulação espontânea e posterior transporte para o hospital para intervenção coronária bem-sucedida. A máscara laríngea pode ser utilizada na emergência pré-hospitalar nos doentes com via aérea difícil após tentativa de intubação orotraqueal de forma a garantir adequada ventilação e oxigenação do doente crítico.info:eu-repo/semantics/publishedVersio

Educação ambiental e ensino da Física e da Química no 3º ciclo do Ensino Básico: o programa Eco-Escolas

Dissertação de mestrado, Ensino das Ciencias no 3º Ciclo do Ensino Básico e no Ensino Secundário, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014Este relatório descreve a atividade profissional desenvolvida pela autora durante os treze anos dedicados ao ensino da Física e da Química no 3º ciclo do ensino básico. São exploradas as vertentes profissional e formativa deste percurso, numa perspetiva reflexiva e de valorização profissional e pessoal. No contexto do processo de ensino-aprendizagem são descritas as estratégias implementadas, os instrumentos pedagógicos utilizados, as modalidades de avaliação e as experiências pedagógicas vivenciadas. São apresentados exemplos ilustrativos concretos e a revisão da literatura sobre as temáticas que deu suporte às abordagens escolhidas. São descritas também as ações de formação frequentadas, analisando-as e destacando a sua relevância na aquisição de saberes e competências pedagógicas e o seu contributo para a criação de ações pedagógicas e cívicas diversificadas que promoveram o sucesso na disciplina e a formação de jovens civicamente ativos e responsáveis, capazes de um pleno exercício da cidadania democrática. Os desafios que as questões ambientais nos colocam requerem alterações profundas na nossa visão, levando ao reconhecimento da necessidade de uma atuação direta dos cidadãos, questão central na promoção da sustentabilidade. Daí a importância da educação ambiental, a qual, atualmente, é defendida como um tema transversal a ser trabalhado por todas as disciplinas do currículo. Desta forma, pretende-se apresentar estratégias de educação ambiental que foram incluídas nas aulas de Física e Química, associando a transmissão de conteúdos e a educação ambiental, através da dinamização de programas que permitiram relacionar a ciência com a tecnologia, sociedade e ambiente, vertentes primordiais da literacia científica, potenciando o conhecimento em ação e a educação para a cidadania. O programa Eco-Escolas é uma importante ferramenta ao serviço da educação ambiental que permite envolver os alunos de forma responsável, participada e democrática, na melhoria da qualidade ambiental da escola e na implementação da Agenda 21 Local. Ao longo deste trabalho serão apresentados exemplos de situações em que, através da resposta a questões e desafios lançados pelo programa Eco-Escolas, os alunos adquiriram conceitos de Física e de Química, aplicando-os num contexto real, apoiados por diferentes parcerias estabelecidas no âmbito deste program

Association of Multiple Myeloma and Giant Cell Arteritis – A Case Report

Autoimmune diseases (AID) have been associated with a variety of lymphoproliferative disorders. Multiple myeloma (MM), one of the most common haematologic malignancies characterized by clonal proliferation of bone marrow plasma cells, has been associated with a range of autoimmune disorders. In this report, we described a case study of a patient admitted to our Internal Medicine Department for a bone marrow biopsy and myelogram due to a monoclonal peak observed by his general practitioner. However, at admission he presented typical giant cell arteritis (GCA) complaints, suggesting the coexistence of both diseases. The possible pathogenesis, as found in the literature, explaining the association will be discussed

Derivation of Cerebellar Neurons from Human Pluripotent Stem Cells

Here we provide a protocol for differentiation of human embryonic stem cells (hESC) into cerebellar neurons using a novel defined culture method. This protocol is based on the application of inductive signaling factors involved in the early patterning of the cerebellar region of the neural tube, followed by the application of factors responsible for cerebellar neuron specification. Human pluripotent stem cells are induced to form spherical embryonic-like structures called embryoid bodies (EBs) and neuroepithelial tube-like rosettes using defined chemical conditions. In the presence of FGF, Wnt, and RA signaling factors the rosettes were specified to OTX2-expressing cells. Further specification of derived cells involves application of BMP factors involved in early development of granule cell progenitors, followed by mitogens and neurotrophins. It typically takes 5 weeks to generate the functional cerebellar granule neurons. This protocol is feeder-free, applies human recombinant factors, and produces high yield of desired neurons

The role of Zic genes in inner ear development in the mouse: Exploring mutant mouse phenotypes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109293/1/dvdy24186.pd

Wnt Signaling Promotes Neuronal Differentiation from Mesenchymal Stem Cells Through Activation of Tlx3

Wnt/β-catenin signaling promotes neural differentiation by activation of the neuron-specific transcription factors, Neurogenin1 ( Ngn1 ), NeuroD , and Brn3a , in the nervous system. As neurons in cranial sensory ganglia and dorsal root ganglia transiently express Ngn1, NeuroD , and Brn3a during embryonic development, we hypothesized that Wnt proteins could instructively promote a sensory neuronal fate from mesenchymal stem cells (MSCs) directed to differentiate into neurons. Consistent with our hypothesis, Wnt1 induced expression of sensory neuron markers including Ngn1, NeuroD , and Brn3a , as well as glutamatergic markers in neurally induced MSCs in vitro and promoted engraftment of transplanted MSCs in the inner ear bearing selective loss of sensory neurons in vivo. Given the consensus function of T-cell leukemia 3 ( Tlx3 ), as a glutamatergic selector gene, we postulated that the effects of canonical Wnt signaling on sensory neuron and glutamatergic marker gene expression in MSCs may be mediated by Tlx3 . We first confirmed that Wnt1 indeed upregulates Tlx3 expression, which can be suppressed by canonical Wnt inhibitors. Next, our chromatin immunoprecipitation assays revealed that T-cell factor 3/4, Wnt-activated DNA binding proteins, interact with a regulatory region of Tlx3 in MSCs after neural induction. Furthermore, we demonstrated that forced expression of Tlx3 in MSCs induced sensory and glutamatergic neuron markers after neural induction. Together, these results identify Tlx3 as a novel target for canonical Wnt signaling that confers somatic stem cells with a sensory neuron phenotype upon neural induction. S TEM C ELLS 2011;29:836–846Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83767/1/624_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/83767/2/STEM_624_sm_suppinfoFigs.pd

Sexual Phenotype Differences in zic2 mRNA Abundance in the Preoptic Area of a Protogynous Teleost, Thalassoma bifasciatum

The highly conserved members of the zic family of zinc-finger transcription factors are primarily known for their roles in embryonic signaling pathways and regulation of cellular proliferation and differentiation. This study describes sexual phenotype differences in abundances of zic2 mRNA in the preoptic area of the hypothalamus, a region strongly implicated in sexual behavior and function, in an adult teleost, Thalassoma bifasciatum. The bluehead wrasse (Thalassoma bifasciatum) is a valuable model for studying neuroendocrine processes because it displays two discrete male phenotypes, initial phase (IP) males and territorial, terminal phase (TP) males, and undergoes socially-controlled protogynous sex change. Previously generated microarray-based comparisons suggested that zic2 was upregulated in the brains of terminal phase males relative to initial phase males. To further explore this difference, we cloned a 727 bp sequence for neural zic2 from field-collected animals. Riboprobe-based in situ hybridization was employed to localize zic2 signal in adult bluehead brains and assess the relative abundance of brain zic2 mRNA across sexual phenotypes. We found zic2 mRNA expression was extremely abundant in the granular cells of the cerebellum and widespread in other brain regions including in the thalamus, hypothalamus, habenula, torus semicircularis, torus longitudinalis, medial longitudinal fascicle and telencephalic areas. Quantitative autoradiography and phosphorimaging showed zic2 mRNA hybridization signal in the preoptic area of the hypothalamus was significantly higher in terminal phase males relative to both initial phase males and females, and silver grain analysis confirmed this relationship between phenotypes. No significant difference in abundance was found in zic2 signal across phenotypes in the habenula, a brain region not implicated in the control of sexual behavior, or cerebellum

Stem cell treatment of degenerative eye disease

Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment