574 resultados para Fármaco neuroprotetores


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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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Enquadramento – A hipotermia terapêutica consiste na redução controlada da temperatura central dos doentes com objetivos terapêuticos pré-definidos, assumindo-se actualmente como uma mais-valia no tratamento clínico de vítimas com TCE. Objetivos – Avaliar a eficácia da HT intra-hospitalar na redução da morbilidade e mortalidade do adulto vítima de TCE. Métodos – Foi realizada uma revisão sistemática da literatura sobre a eficácia da HT intrahospitalar na redução da morbilidade e mortalidade do adulto vítima de TCE. Efetuou-se uma pesquisa na PUBMED, The Cochrane Library, Scielo e Google Académico de estudos publicados entre 1 de janeiro de 2012 a 31 de agosto de 2014. Partindo dos critérios de inclusão previamente definidos, os estudos selecionados foram posteriormente avaliados. Dois revisores avaliaram a qualidade dos estudos a incluir, utilizando a grelha para a avaliação crítica de um estudo de Ascenção et al. (2008). Resultados – Quatro artigos preencheram os critérios de inclusão, tendo-se constituído como corpus amostral. Como metasíntese e seleção da análise dos artigos, inferiu-se que os potenciais benefícios neuroprotetores da hipotermia terapêutica, sem efeitos colaterais negativos, deve ser implementada como parte do quotidiano de tratamento e controlo das vítimas de TCE e não como terapia de resgate. Contudo, a validação das implicações práticas da HT carece de mais estudos, cuja indução seja fator neuroprotetor, independentemente do valor da PIC, individualizando a duração da indução da hipotermia. Conclusão – Os benefícios da HT em adultos vítimas de TCE são ainda alvo de debate, requerendo a realização de mais metanálises e ensaios clínicos, visando a atualização das suas recomendações. Palavras-chave – Hipotermia terapêutica; traumatismo crânio-encefálico; eficácia

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Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

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Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

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Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

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Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

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Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

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Bipolar disorder is a chronic psychopathology that reaches from 1 to 4% of the world population. This mood disorder is characterized by cyclical mood changes, in which an individual alternates between states of depression and mania. Mania is described in the literature as an abnormal state of exacerbation of humor, in which the subject presents an expansive, euphoric behavior, but with increased irritability, psychomotor agitation and a feeling of invincibility, which will contribute to risks exposure. The treatment of this psychopathology is complex and it is not effective in all cases, and it evokes many side effects. In this respect, the system of Nociceptin/Orphanin FQ (N/OFQ) can be studied as a possible therapeutic target for the treatment of bipolar disorder, due to its modulatory role on monoaminergic systems and on mood. This study aims to investigate the effect of NOP receptor ligands in an animal model of mania induced by methylphenidate. To this aim, locomotor activity was assessed in an open field, in mice treated with methylphenidate (10 mg/kg, sc, 15 min). Valproate (300 mg / kg, ip, 30 min), standard treatment of mania, prevented methylphenidate-induced hyperlocomotion. The acute treatment with the antagonist of NOP receptor UFP-101 (1-10 nmol, icv, 5 min) per se did not affect the spontaneous locomotion of mice, but it was able of attenuating hyperlocomotion induced by methylphenidate. The acute treatment with N/OFQ (1 and 0.1 nmol, icv, 5 min) did not alter the distance moved, but when tested at a dose of 1 ηmol, N/OFQ slightly reduced methylphenidate-induced hiperlocomotion. In conclusion, the administration of UFP-101 and N/OFQ produced antimanic-like actions. Furthermore, these data suggest that the system of N/OFQ performs a complex modulation of voluntary movement, and consequently on dopaminergic neurotransmission.

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Spondias tuberosa Arruda (Anacardiaceae) is a fruitful tree popularly known as umbuzeiro, tapereba or umbu. It is a native and endemic species from Brazil, widespread in Brazilian Northeast. The species is important in folk medicine of the semi-arid Northeast, where it is mainly used to treat various inflammatory conditions, digestive problems as well as viral and bacterial infections. However, despite the common use in folk medicine, there are scarce pharmacological and phytochemicals studies that afford scientific evidence to its popular use. Therefore, this study aimed to characterize the chemical markers in S. tuberosa leaves extract, obtained by maceration ethanol:water (70:30, [v/v]), and evaluate its anti-inflammatory potential in vivo. The phytochemical profile in TLC analysis suggested the occurence of the flavonoids rutin and isoquercitrin. HPLC analysis enabled us to confirm the presence of flavonoids and also, were detected the phenolic acids, chlorogenic acid and caffeic acid. In addition was developed and validated a HPLC method to evaluate the content of the identified compounds in S. tuberosa leaves extract according to RDC 899/2003 of ANVISA and ICH Guidelines 2005. In order to evaluate the anti-inflammatory potential of S. tuberosa leaves extract, the peritonitis and paw edema models induced by carrageenan were used, administration i.p. in mice. The results highlighted the anti-inflammatory property in vivo at 125, 250 and 500 mg/kg since a decrease in leukocyte influx to the site of inflammation, diameter of the edema and the level of myeloperoxidase were observed when compared to the drug control dexamethasone (2 mg/kg, i.p. route). Taken together, the results pointed out S. tuberosa as a potential species for developing phytotherapic derivatives in according to its popular use. With regard to the characterization markers, chlorogenic acid, caffeic acid, rutin and isoquercitrin were identified and quantified in Spondias tuberosa leaves extract so they could be used in quality control analyses of the raw material and extracts of this species.

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Triamcinolone is a relevant anti-inflammatory costicosteroid drug, used mainly by injectable suspensions due its poor water solubility. The association of triamcinolone with cyclodextrins and co-solvents (triethanolamine TEA and N-methylpirrolidone NMP) was held to solubilize the drug and explain the involved interactions. Phase-solubility diagrams showed that triamcinolone was solubilized forming incredible stable complexes with cyclodextrins, in which bests results were observed applying randomyl-methylated-beta-cyclodextrin (RMβCD) (161 fold on increased solubility). The co-solvents TEA and NMP also enhanced drug solubility 1.4 and 6.7 fold, respectively. The association of both co-solvents with CDs seems decreased complexation stability, but enables higher amount of uncomplexed drug. Experimental magnetic resonance 2D-ROESY and theoretical molecular modeling studies demonstrated TRI-CDs interactions and elucidated the structure of formed complex, which occurred due to the inclusion of ring A of TRI on CDs cavity. Physicochemical aspects of solid binary and ternary complexes prepared by spray drying were assessed by using FTIR, X-ray diffraction and SEM photographs. Dissolution studies showed that binary and ternary associations presented higher dissolution efficacy in detrimental to pure drug system. In addition, the ternary complex containing TEA and RMβCD allowed drug dissolution faster than binary complex with RMβCD. Therefore, given the higher solubility and drug dissolution rate, binary and ternary complexes are new raw materials with great potential for pharmaceuticals containing triamcinolone.