Identificação de alvos na terapia anti-cancerígena utilizando técnicas de modelação molecular

Miguel Fernandes

Novos vectores baseados em dendrímeros com aplicações em terapia antisense

A terapia genética tem se revelado uma ferramenta potente na Medicina, na tentativa de revolucionar o tratamento de várias doenças hereditárias e adquiridas. A introdução de genes em células pretende a expressão estável e prolongada de proteínas com efeitos terapêuticos. O silenciamento de genes, através da terapia genética que faz uso de oligonucleótidos antisense, pequenos RNA de interferência (siRNA) ou ribozimas, visa o decréscimo ou anulação do funcionamento de um gene cuja expressão amplificada, por algum motivo, leva ao desenvolvimento de umapatologia. A internalização de material genético nas células, usualmente, carece de métodos e/ou sistemas de entrega (vectores). Estes podem pertencer a duas categorias, designadamente, métodos virais e métodos não-virais. O primeiro é considerado o mais eficiente, apresentando porém, sérias desvantagens como o risco de carcinogénese. A solução é a utilização de métodos não virais,que podem ser físicos ou químicos. O objectivo principal desta dissertação foi a utilização de dendrímeros para o silenciamento do gene da proteína fluorescente optimizada (EGFP) em células HeLa, previamente modificadas para expressarem esta proteína. Dendrímeros poli(amidoamina) geração 5 (PAMAM G5) modificados com 4 ou 8 moléculas de ácidos gordos de diferentes comprimentos foram complexados com oligonucleótidos antisense. A vantagem que estes apresentam em relação aos dendrímeros nativos é que são capazes de interagir com os lípidos da membrana celular, esperando-se, por isso, uma melhor eficiência de transfecção e efeitos antisense. Isto foi efectivamente verificado, sendo que o nível de silenciamento do gene da EGFP obtido, está directamente relacionado com o aumento da razão NP, o número e o comprimento das cadeias hidrofóbicas. O silencimento de genes tem sofrido grandes avanços, havendo actualmente uma série de ensaios clínicos para a sua utilização no tratamento de doenças como cancros de origem hereditária ou viral, prevendo-se que venha para ficar, juntamente com o silenciamento mediado por siRNA.

Fenômeno vivido por familiares de pacientes internados em unidade de terapia intensiva

COMASSETTO, Isabel, ENDERS, Bertha Cruz. Fenômeno vivido por familiares de pacientes internados em Unidade de Terapia Intensiva. Revista Gaúcha de Enfermagem., Porto Alegre(RS), v.30,n., p.46-53. Mar. 2009. Disponivel em: < http://www.seer.ufrgs.br/index.php/RevistaGauchadeEnfermagem/search/results>.

Prevenção de úlceras por pressão segundo a perspectiva do enfermeiro intensivista

Analisar a atuação dos enfermeiros de unidade de terapia intensiva na prevenção da úlcera por pressão. Método: trata-se de estudo descritivo desenvolvido com 13 enfermeiros da unidade de terapia intensiva do Hospital Universitário Onofre Lopes (HUOL), em Natal-RN. Foi aplicado um questionário, submetido à análise de conteúdo temática. O estudo foi aprovado pelo Comitê de Ética da Universidade Federal do Rio Grande do Norte (UFRN), sob o CAAE n. 0240.0.051.000-10. Resultados: os enfermeiros reportaram a realização da mudança de decúbito, a avaliação de risco, a discussão com os colegas sobre as medidas adotadas, a higiene e hidratação da pele do paciente através de uso de ácidos graxos essenciais e hidratante corporal, o cuidado com a disposição dos lençóis, de forma a evitar dobras, a utilização de colchão de ar e a aplicação de placas de hidrocoloide nas proeminências ósseas. Conclusão: a prática da prevenção das úlceras por pressão aplicada pelos enfermeiros da unidade de terapia intensiva ocorre sem padronização dos cuidados

Desenvolvimento de nanosistemas farmacêuticos para terapia gênica

Gene therapy is one of the major challenges of the post-genomic research and it is based on the transfer of genetic material into a cell, tissue or organ in order to cure or improve the patient s clinical status. In general, gene therapy consists in the insertion of functional genes aiming substitute, complement or inhibit defective genes. The achievement of a foreigner DNA expression into a population of cells requires its transfer to the target. Therefore, a key issue is to create systems, vectors, able to transfer and protect the DNA until it reaches the target. The disadvantages related to the use of viral vectors have encouraged efforts to develop emulsions as non-viral vectors. In fact, they are easy to produce, present suitable stability and enable transfection. The aim of this work was to evaluate two different non-viral vectors, cationic liposomes and nanoemulsions, and the possibility of their use in gene therapy. For the two systems, cationic lipids and helper lipids were used. Nanoemulsions were prepared using sonication method and were composed of Captex® 355; Tween® 80; Spam® 80; cationic lipid, Stearylamine (SA) or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) and water (Milli-Q®). These systems were characterized by average droplet size, Polidispersion Index (PI) and Zeta Potential. The stability of the systems; as well as the DNA compaction capacity; their cytotoxicity and the cytotoxicity of the isolated components; and their transfection capacity; were also evaluated. Liposomes were made by hydration film method and were composed of DOTAP; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), containing or not Rhodaminephosphatidylethanolamine (PE- Rhodamine) and the conjugate Hyaluronic Acid DOPE (HA-DOPE). These systems were also characterized as nanoemulsions. Stability of the systems and the influence of time, size of plasmid and presence or absence of endotoxin in the formation of lipoplexes were also analyzed. Besides, the ophthalmic biodistribution of PE-Rhodamine containing liposomes was studied after intravitreal injection. The obtained results show that these systems are promising non-viral vector for further utilization in gene therapy and that this field seems to be very important in the clinical practice in this century. However, from the possibility to the practice, there is still a long way

Terapia ocupacional em ação interdisciplinar: jogos educativo-nutricionais na prevenção da obesidade infantil

The inter-subjectivity is the answer in the search for the solution of complex problems, which concerns interfaces of knowledge, respecting their borders. This paradigm is essential in the author's work. So, the search on screen is based on this perspective, by using inter-subject groups of work conduced by professionals of Computer Science, Social Communication, Architecture and Urbanism, Pedagogy, Psicopegagogy, Nutritional Science, Endocrinology, Occupational Therapy and Nursing, it was also part of this group an 8 year old child, daughter of one of the professional who took part of the group. This thesis aims to present the course of investigation developed, analyzing the action of inter-subject Occupational Therapy and Nutrition on the promotion of learning nutritional concepts through educative-nutritional games in order to prevent child's obesity in an educative context. The research was analytic, interventionist and almost experimental. It took place in a public school in Fortaleza, Ceará, Brazil, between August and December 2004. It was selected a sample non-probabilistic, by convenience, of 200 children, born from 1994 to 1996. It was selected almost nonprobabilistically, by convenience, 200 children born between 1994 and 1996. To analyze the results it was used a triangulation, associated by quantitative and qualitative approaches. The basis collect happened through games specially manufactured to these research- video-games, board games, memory games, puzzles, scramble, searching words and iterative basics. There were semi-structured interviews, direct and structured observations and focus in-groups. It was noticed the efficiency of educativenutritional games in the learning process, which lead to a changing of attitude towards the eating choices. These games gave similar results in relation to the compared variations preferences, experience and attitudes, theses attitudes were observed through the game; and the categories to compare the possibility of learning by playing, the fantasy in the learning process, learning concepts of nutritional education and the need of help in the learning process (mediation). It was proved that educativenutritional games could be used to teach nutritional concepts, in an inter-subjective action of Occupational Therapy and Nutrition in schools. The simultaneous application of these games lead to the optimization of child s learning process. It should be emphasized the need of studies about the adaptation of tools used in a child s Nutritional Education, with the help of inter-subjective action. Because just one subject, in a fractionated way can give an answer to complex problems and help to a change of the reality with effectiveness and resolution

Significados e percepções de puérperas sobre as síndromes hipertensivas da gravidez e parto prematuro

Hypertensive syndromes in pregnancy (HSP) are configured as one of the major complications in the pregnancy and postpartum period and can lead premature newborn and subsequent hospitalization of the newborn to the Neonatal Intensive Care Unit (NICU). This study aimed to analyze the perceptions, meanings and feelings of mothers on the hypertensive syndromes in pregnancy and premature obstetric labor. The research was qualitative and has a theoretical methodological the Social Representations Theory(SRT) in the approach to the Central Nucleus Theory. The study included 70 women, mean age 29 years, predominantly school to high school, most of them married or in consensual union, primiparous and prevalence of cesarean delivery occurred between 32 and 37 weeks of pregnancy.The data were collected from may to december 2008 in the Maternity School Januário Cicco in Natal , and obtained through the following instruments for data collection: questionnaire including questions about socio-demographic status; the Free Words Association Test (FWAT) and and verbalized mental image construction used three stimuli: such as pregnancy with high blood pressure, preterm birth and NICU, and interview with the following guiding question: what it meant for you to have a pregnancy with high blood pressure and consequently the birth of a premature baby? Data analysis was performed using multi-method obtained from the data processing by EVOC (Ensemble Programmes Permettant L 'Analyze des Évocations) and ALCESTE (Analyse Lexicale par Contexte d'un Ensemble de Segment de Texte) and thematic analysis in categories. The results will be presented in four thematic units under the following representative universes: HSP, prematurity as a result of HSP, NICU and the social representations of mothers on the hypertensive disorder of pregnancy sequenced premature birth and hospitalization of the child in the NICU. The results obtained by multimethod analyses showed similar constructions and point to death as the central nucleus and negative aspects, coping strategies, need of care, knowledge about the disease, fragility and meanings of the NICU as peripheral elements. It is considered that the perceptions, meanings and feelings of puerperal women in relation to HSPs and to premature delivery are a negative social representation, with representational elements that may have influenced the adverse effects on the disease and its consequences. We suggest action on the peripheral elements of this representation, with adequate orientation, early diagnosis, effective conduct, receptive attitude on the part of the team, health promotion measures and effective public policies, in order to improve the care provided to puerperal women, making them feel welcome and minimizing their suffering