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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
61

Riscos de eventos adversos gastrintestinais nos projetos de pesquisa de fármacos envolvendo seres humanos

Marodin, Gabriela January 2008 (has links)
A avaliação do risco é um processo sistemático pelo qual a possibilidade de dano, a exposição e o próprio risco são identificados e quantificados. A consideração, de que a participação em um estudo é de risco, fundamenta-se no princípio da precaução, que é a garantia da existência de medidas de proteção contra riscos potenciais. De acordo com a gravidade dos eventos adversos, e de sua probabilidade de ocorrência, determina-se se o risco previsto é negligenciável, tolerável ou intolerável. Portanto, a caracterização do risco representa um importante elo entre os dados científicos obtidos nos diferentes estudos e as tomadas de decisões, ao monitoramento e à comunicação do risco. O objetivo deste estudo é avaliar os riscos previstos de eventos adversos gastrintestinais em projetos de pesquisa em seres humanos na área farmacológica, realizados no Hospital de Clínicas de Porto Alegre (HCPA), através da análise do Termo de Consentimento Livre e Esclarecido (TCLE), do manual do pesquisador e do projeto. Realizou-se um estudo transversal, com unidade de observação nos eventos adversos (EAs) gastrintestinais, através do levantamento de risco de projetos de pesquisa farmacológica, com patrocínio privado, submetidos e aprovados pelo Comitê de Ética em Pesquisa (CEP) do HCPA, no ano de 2004. De 58 projetos analisados, identificou-se 9734 referências de riscos de EAs gerais, sendo que 1463 (15,0%) eram gastrintestinais. Destas, 181 (12,4%) aparecem somente no TCLE, desprovida de embasamento teórico; já 1047 (71,6%) estão descritas nos documentos não disponibilizados ao participante, informação não compartilhada, tendo embasamento teórico; e apenas 235 referências de riscos, que representam 16,0% dos riscos gastrintestinais totais, como informação compartilhada e documentada, para o participante e pesquisador, com embasamento teórico. Essas 1463 referências de riscos de EAs gastrintestinais foram padronizadas, fazendo-se uso do Código Internacional de Doenças, décima revisão (CID 10), obtendo-se 170 tipos diferentes de riscos. Os riscos com maior repetição de referência nos projetos foram: náusea e vômitos 14,1%; alteração do hábito intestinal 6,5%; aumento dos níveis de transaminases e da desidrogenase lática 5,7%; outras dores abdominais e as não especificadas 4,9%. Quanto à gravidade, dos 170 tipos de riscos, obteve-se 65 (38,2%) graves, 52 (30,6%) moderados, 30 (17,6%) leves e 23 (13,5%) múltipla classificação. Todos os documentos relativos ao projeto de pesquisa deveriam conter a descrição e quantificação dos riscos importantes, seja pela alta gravidade ou freqüência associada. No TCLE, parte dos riscos estavam descritos, porém desprovidos de uma quantificação e caracterização adequadas. O manual apresentava as informações sobre os riscos, mas de forma dispersa ao longo do documento, levando a uma dificuldade de utilização desses dados nas intervenções propostas. Nos projetos analisados, observa-se a falta de homogeneidade e padronização para se expressar adequadamente os riscos já ocorridos em estudos prévios. Isso demonstra a importância da leitura atenta de toda documentação encaminhada para avaliação pelo CEP, visando a proteção ativa dos sujeitos da pesquisa. / Risk evaluation is a systematic process whereby damage possibility, exposure and the risk itself are identified and quantified. The consideration that the participation in a study is risky is founded on the precaution principle, i.e., the warranty of existing protection measures against potential risks. According to the severity of the adverse events and of its occurrence probability, one determines if the foreseen risk is negligible, tolerable or intolerable. Therefore, risk characterization represents an important link between the scientific data obtained from the different studies and the decision-makings, to monitoring and to risk communication. The objective of this study is evaluating the foreseen risks of gastrointestinal adverse events (AEs) in research projects with human beings in the pharmacological field carried out at Hospital de Clínicas de Porto Alegre – HCPA by means of the Informed Consent Form – ICF, of the researcher brochure and of the Research Protocol. A transversal study was carried out with an observation unit in the gastrointestinal AEs, through the survey of risk of projects of clinical trial with private sponsorship submitted to and approved by the Research Ethics Committee – REC of the HCPA in 2004. Out of 58 analyzed protocols were identified 9734 risk references of general AEs, being 1463 (15.0%) gastrointestinal. Out of these, 181 (12.4%) appear on the ICF only, deprived of theoretical basis; while 1047 (71.6%) are described in documents non available for the participant, non-shared information, with theoretical basis; only 235 risk references that represent 16.0% of the total gastrointestinal risk, as shared and documented information for the participant and the researcher, having theoretical basis. These 1463 risk references of gastrointestinal AEs were standardized by making use of the International Code of Diseases – 10th Revision –, and 170 different risk types were obtained. The risks with more reference repetition in the protocols were: nausea and vomit 14.1%; alteration of intestinal habit 6.5%; increase of the levels of transaminases and of lactic dehydrogenase 5.7%; abdominal pain 4.9%. As to the severity, out of the 170 risk types, 65 (38.2%) are severe, 52 (30.6%) moderate, 30 (17.6%) soft and 23 (13.5%) of multiple classification. All of the documents regarding the research protocol should contain the description and quantification of the important risks either due to high severity or to frequency. In the ICF, some of the risks were described however deprived of an adequate quantification and characterization. The brochure presented the information about the risks, however in a disperse way over the document leading to a difficult utilization of these data in the proposed interventions. In the analyzed protocols was observed lack of homogeneity and standardization to adequately express the risks that had already occured in previous studies. This observation demonstrates the importance of careful reading of all of the documentation addressed for evaluation by the REC aiming at the active protection of the research subjects.
62

Efeitos da imunossupressão sobre a depuração mucociliar de ratos: comparação entre dois esquemas de terapia tríplice / Effects of immunosuppression on mucociliary clearance of rats: comparison between two triple therapy regimens

Maristela Prado e Silva 05 April 2016 (has links)
INTRODUÇÃO: O transplante de pulmão é parte fundamental no tratamento das doenças terminais do pulmão, constituindo uma modalidade terapêutica eficaz para pacientes com doença pulmonar incapacitante, progressiva e em estágio final. No entanto, as drogas imunossupressoras usadas para evitar a rejeição do enxerto podem causar efeitos colaterais em diversos tecidos. O sistema mucociliar, presente nas vias aéreas, é um dos principais mecanismos de defesa do trato respiratório e pode ser alterado por ação das drogas imunossupressoras. Desta forma, o objetivo deste estudo foi avaliar o sistema mucociliar traqueobrônquico de ratos submetidos a dois esquemas de terapia tríplice imunossupressora. MÉTODOS: Foram utilizados 90 ratos machos Wistar distribuídos em 3 grupos conforme o tratamento: controle (C) = solução salina; terapia 1 (TI) = tacrolimus + micofenolato de mofetil + prednisona; terapia 2 (TII) = ciclosporina + azatioprina + prednisona. Após o período de tratamento (7, 15 ou 30 dias), os animais foram sacrificados e realizadas as seguintes medidas: transportabilidade do muco (TM), frequência de batimento ciliar (FBC), quantificação de muco neutro e ácido, velocidade de transporte mucociliar (VTMC), e contagem total e diferencial de células no lavado broncoalveolar (LBA). RESULTADOS: A TM não foi afetada pelas terapias em nenhum dos tempos estudados. Ambas as terapias causaram significativa redução da FBC dos animais tratados por 7 e 15 dias. A produção de muco neutro foi menor nos animais tratados com a TI por 7, 15 e 30 dias. Porém, com a TII, essa redução ocorreu apenas aos 7 dias. Por outro lado, a quantidade de muco ácido foi significativamente maior em todos os animais tratados com as duas terapias. Todos os animais tratados com as terapias imunossupressoras apresentaram redução da VTMC nos três tempos. Houve aumento do número total de células e de macrófagos e neutrófilos no grupo TI em 7 dias. CONCLUSÕES: Ambas as terapias imunossupressoras foram prejudiciais ao transporte mucociliar das vias aéreas de ratos, tanto pela redução da FBC e da VTMC, quanto pela maior produção de muco ácido e menor produção de muco neutro. A TI foi mais prejudicial ao sistema mucociliar em comparação à TII / INTRODUCTION: Lung transplantation is an essential part in the treatment of terminal lung diseases, providing an effective therapeutic modality for patients with disabling, progressive and final stage lung disease. However, the immunosuppressant drugs used to prevent graft rejection may cause side effects in several tissues. The mucociliary system, present in the airways, is a major defense mechanism of the respiratory tract and can be changed by action of immunosuppressive drugs. Thus, the aim of this study was to evaluate the tracheobronchial mucociliary system of rats submitted to two triple immunosuppressive therapy regimens. METHODS: We used 90 male Wistar rats divided into 3 groups according to treatment: control (C) = saline solution; therapy 1 (TI) = tacrolimus + mycophenolate mofetil + prednisone therapy; therapy 2 (TII) = cyclosporine + azathioprine + prednisone. After the period of treatment (7, 15, or 30 days), the animals were sacrificed and the following measures taken: mucus transportability (MT), ciliary beating frequency (CBF), quantification of neutral and acid mucus, mucociliary transport velocity (MCTV), and total and differential counting of cells in bronchoalveolar lavage (BAL). RESULTS: MT was not affected by treatments in any of the periods studied. Both therapies have caused significant reduction of CBF of animals treated for 7 and 15 days. The neutral mucus production was lower in animals treated with TI for 7, 15 and 30 days. But with TII, this reduction occurred only at 7 days. Moreover, the amount of acid mucus was significantly higher in all animals treated with both therapies. All animals treated with immunosuppressive therapies had reduced MCTV at the three times. There was an increase of total cells and macrophages and neutrophils in the TI group in 7 days. CONCLUSIONS: Both immunosuppressive therapies were harmful to the mucociliary clearance of the airways of rats, either by reducing the CBF and MCTV, as by the increased production of acid mucus and decreased production of neutral mucus. TI was more harmful to the mucociliary system in comparison to TII
63

Contribution à l'étude de la limitation de l'aptitude aérobie en hypoxie

Faoro, Vitalie 07 May 2008 (has links)
On sait depuis longtemps que l’exposition à l’altitude est associée à une réduction de l’aptitude aérobie. Différentes hypothèses ont été posées pour expliquer cette limitation à l’effort en hypoxie (une limitation ventilatoire ou diaphragmatique, une altération de la diffusion pulmonaire et une disconcordance entre de la perfusion et la diffusion tissulaire, etc.) mais généralement, la limitation de l’effort aérobie en hypoxie est attribuée à une diminution du transport sanguin de l’O2 (TO2) parc convection vers les muscles. Le TO2 dépend du débit cardiaque (Q) et du contenu artériel en O2 (CaO2). <p>Le CaO2 est diminué en altitude à cause d’une diminution de la pression partielle inspirée en O2. Cependant, le chémoréflexe hypoxique tente de contrebalancer cet effet en élevant la ventilation et en diminuant la pression alvéolaire en CO2 afin de maintenir la pression alvéolaire en O2 constante. De plus, avec l’acclimatation, le rein produit de l’érythropoïétine permettant au taux d’hémoglobine d’augmenter. Ces deux principales adaptations à l’altitude ramènent le CaO2 à sa valeur de base du niveau de la mer en 2 à 3 semaines passées à 5000 m d’altitude mais sans amélioration de l’aptitude à l’effort aérobie.<p>L’exposition à l’altitude est aussi associée à une diminution du Q maximal. Les mécanismes à l’origine de cette limitation du Q maximal restent, à l’heure actuelle, incompris. Les principales explications évoquées sont, une diminution de la réserve chronotrope, une diminution de la commande nerveuse centrale vers le cœur ou une diminution de la demande périphérique. Récemment, des études sur des sujets sains en hypoxie suggérèrent qu’au moins une partie de la limitation du Q maximal à l’effort est liée à une élévation de la postcharge ventriculaire droite suite à l’hypertension pulmonaire induite par l’hypoxie. C’est cette hypothèse que nous avons voulu vérifier dans une première étude.<p>Nous avons étudié l’effet d’une inhibition de l’hypertension pulmonaire d’altitude par le sildénafil, un inhibiteur de la phosphodiestrérase-5, chez des sujets sains, en normoxie, en hypoxie aiguë et en hypoxie chronique. Les résultats de cette étude ont confirmé l’effet vasodilatateur pulmonaire du sildénafil et une augmentation de la VO2max en hypoxie aiguë. Cependant, la prise de ce dernier était couplée à une amélioration de l’oxygénation, si bien que l’élévation de la performance aérobie observée en hypoxie aiguë sous sildénafil ne pouvait être entièrement attribuée à une réduction de l’hypertension pulmonaire. <p>Nous conclurent que cette amélioration de la performance était probablement d’avantage liée à une amélioration de l'oxygénation qu’à un effet vasodilatateur pulmonaire.<p>Les résultats équivoques obtenus lors de cette première étude nous ont incité à tester les effets d’une amélioration de l’oxygénation sur la performance aérobie en haute altitude. Pour ce faire, quinze sujets sains ont été testés au niveau de la mer et après acclimatation à 4700 m d’altitude soit sous placebo, soit sous acétazolamide, un inhibiteur de l’anhydrase carbonique augmentant l’oxygénation par stimulation ventilatoire en réponse à une acidose métabolique. La prise d’acétazolamide n’eut aucun effet sur l’hémodynamique pulmonaire et sur la VO2max et la charge maximale. Nous avons toutefois observé qu’une amélioration de l’oxygénation durant l’effort retarde l’apparition du seuil ventilatoire améliorant ainsi la phase aérobie de l’effort. Cette étude confirme donc qu’une élévation du CaO2 permet une amélioration de l’aptitude aérobie. <p>Finalement, la dernière étude a pour but d’étudier les effets isolés d’une vasodilatation pulmonaire sur la performance aérobie en altitude. Les résultats d’une étude préliminaire montrent que l’inhibition de la vasoconstriction hypoxique par un agent pharmacologique antagoniste des récepteurs de l’endothéline ETA et ETB, le bosentan, permet une élévation de l’aptitude aérobie en hypoxie aiguë, sans effets sur l’oxygénation, confirmant ainsi notre hypothèse initiale qu’une postcharge ventriculaire droite augmentée en hypoxie peut contribuer à une limitation de l’aptitude à l’effort aérobie en hypoxie. <p><p>Conclusions :<p>L’ensemble de nos résultats suggère que l’aptitude aérobie en altitude est déterminée par le transport d’O2 qui peut être augmenté par manipulation pharmaceutique du débit ventriculaire droit maximal après inhibition de la vasoconstriction pulmonaire hypoxique (bosentan), amélioration de l’oxémie (acétazolamide) ou des deux (sildénafil).<p> / Agrégation de l'enseignement supérieur en kinésithérapie et réadaptation / info:eu-repo/semantics/nonPublished
64

The effect of zilpaterol hydrochloride on feedlot performance and carcass characteristics in weaner steers

Mantiziba, Chipo Winnie 12 January 2015 (has links)
An experiment was conducted using forty-one Bonsmara steers (age ± 7 months) to determine the effect of zilpaterol hydrochloride (ZH) on the growth performance and carcass characteristics. The trial was structured using a completely randomized design with two treatments, control and ZH group. The steers were fed ZH for 28 consecutive days at the end of the finishing period and ZH was withdrawn from the diet 2 days prior to slaughter of the animals. The steers were placed in individual pens and weighed fortnightly throughout the 4 months trial. Zilpaterol hydrochloride (ZH) was included in the diet at a rate of 8.3 mg/kg of DM. Feeding of ZH increased (P< 0.05) body weight (BW) gain and ADG (1.102 vs. 1.444) and tended to increase (P = 0.067) feed efficiency (F:G) during the last month of the finishing period. There were no significant differences (P> 0.05) in daily dry matter intakes (DMI). For the control group, high treatment weight gains were significantly associated with high initial weight (r = 0.424, P = 0.049) and also high pre-treatment body weight (r = 0.678, P= 0.001). Treatment weight gain increased as the initial and pre-treatment weight gain increased in the control group. For the steers that were fed ZH, there was no significant correlation between the treatment body weight gain with initial weight (r = 0.097, P = 0.694) and also pre- treatment live weight (r = 0.393, P = 0.096). Supplementation of ZH significantly increased (P < 0.0001) the dressing percentage (56.4% vs. 58.4%) and had no significant (P>0.05) effect on the carcass weight. The outcome of the study suggest that supplementation of ZH in the diet during the last month of the finishing period enhances growth performance and shows the repartitioning capacity of the feed additive as a beta- agonist. / Agriculture and  Animal Health / M. Sc. (Agriculture (Animal Science)
65

The effect of zilpaterol hydrochloride on feedlot performance and carcass characteristics in weaner steers

Mantiziba, Chipo Winnie 12 January 2015 (has links)
An experiment was conducted using forty-one Bonsmara steers (age ± 7 months) to determine the effect of zilpaterol hydrochloride (ZH) on the growth performance and carcass characteristics. The trial was structured using a completely randomized design with two treatments, control and ZH group. The steers were fed ZH for 28 consecutive days at the end of the finishing period and ZH was withdrawn from the diet 2 days prior to slaughter of the animals. The steers were placed in individual pens and weighed fortnightly throughout the 4 months trial. Zilpaterol hydrochloride (ZH) was included in the diet at a rate of 8.3 mg/kg of DM. Feeding of ZH increased (P< 0.05) body weight (BW) gain and ADG (1.102 vs. 1.444) and tended to increase (P = 0.067) feed efficiency (F:G) during the last month of the finishing period. There were no significant differences (P> 0.05) in daily dry matter intakes (DMI). For the control group, high treatment weight gains were significantly associated with high initial weight (r = 0.424, P = 0.049) and also high pre-treatment body weight (r = 0.678, P= 0.001). Treatment weight gain increased as the initial and pre-treatment weight gain increased in the control group. For the steers that were fed ZH, there was no significant correlation between the treatment body weight gain with initial weight (r = 0.097, P = 0.694) and also pre- treatment live weight (r = 0.393, P = 0.096). Supplementation of ZH significantly increased (P < 0.0001) the dressing percentage (56.4% vs. 58.4%) and had no significant (P>0.05) effect on the carcass weight. The outcome of the study suggest that supplementation of ZH in the diet during the last month of the finishing period enhances growth performance and shows the repartitioning capacity of the feed additive as a beta- agonist. / Agriculture and  Animal Health / M. Sc. (Agriculture (Animal Science)
66

Contribution à l'étude de l'aptitude aérobie dans la décompensation cardiaque / Contribution to determination of exercise capacity in heart failure.

Deboeck, Gaël 26 March 2009 (has links)
La décompensation cardiaque se manifeste par une symptomatologie de dyspnée et de fatigue, et par une diminution de l’aptitude aérobie. La décompensation cardiaque peut être globale ou gauche (DCG), ou droite comme dans le cas de l’hypertension artérielle pulmonaire (HTAP). Les mesures fonctionnelles de repos (fonction ventriculaire gauche ou pression artérielle pulmonaire moyenne) sont peu corrélées à l’aptitude aérobie, qui est cependant un élément important de la mise au point et du suivi clinique des patients atteints de DCG ou d’HTAP. <p>\ / Doctorat en Sciences de la motricité / info:eu-repo/semantics/nonPublished
67

Modelování elektromagnetického pole ve tkáni / Elektromagnetic field mapping in tissue

Port, Martin January 2013 (has links)
This thesis is an introduction to the modeling of electromagnetic fields in the tissue and is focused on the knowledge of electromagnetic field theory. Maxwell's equations and their solutions are described the spread of plane waves in the environment. It also discusses the exposure limit values of specific absorbed power and hygienic limits based on the standards in force in the Czech Republic on health protection against nonionizing radiation in accordance with Government Regulation No. 106/2010 Coll. It also deals with the software interface in COMSOL Multiphysics 4.2 for solving physical modeling and simulation. There is mention of the RF module, which is used for modeling. Work mentions in detail about the menu of the program and the most important part - the Model Builder.
68

Games,gestures and learning in Basotho children's play songs

Ntsihlele, Flora Mpho 31 December 2003 (has links)
Colonialism in Africa had an impact on the indigenous peoples of Africa and this is shown in some of their games. The purpose of this study is to gain deeper insight into Basotho children's games and to demonstrate that the Western ideas of music and games are not necessarily the same as Basotho folk children's conceptions. The literature on Basotho children's games is reviewed though not much has been contributed by early and present Basotho writers who have generally approached it from the angle of literature without transcribing the songs. The Sesotho word for games (lipapali) embraces entertainment but a further investigation of it shows that aspects of learning of which the children were aware in some cases and in others they were not aware, are present. These are supported by musical examples and texts. The definition of play versus games is treated (with regard to infants and children) and these two concepts are still receiving constant attention and investigation by scholars and researchers as the words are synonymous and can be misleading. Infants' play is unorganised and spontaneous while games are organised structures. Furthermore, play and games are important in child development education. In this study, they are given attention in order to lay the foundation for the understanding and interpretation of games used in both cultures. It is a misconception that African children's games are accompanied with music in the Western sense. Hence, the word `music' in Sesotho children's games takes on a different connotation from those in the West. Music' in Sesotho children's games embraces not only tunes that are sung, but game verses chanted in a rhythmic manner as opposed to spoken verse. Yet, mino (music) exists in Sesotho and is equivalent to the Western idea. These chanted rhythms and games are analysed against the backdrop of specific cultural dimensions for children depending on the function of the game played. The results of this study indicated that though the idea of music in children's games is not the same, games are an educational in character building and learning. Recommendations are made for educationists and music educators. / ART HIST, VIS ARTS & MUSIC / DLITT ET PHIL (MUSICOLOGY)
69

Games,gestures and learning in Basotho children's play songs

Ntsihlele, Flora Mpho 31 December 2003 (has links)
Colonialism in Africa had an impact on the indigenous peoples of Africa and this is shown in some of their games. The purpose of this study is to gain deeper insight into Basotho children's games and to demonstrate that the Western ideas of music and games are not necessarily the same as Basotho folk children's conceptions. The literature on Basotho children's games is reviewed though not much has been contributed by early and present Basotho writers who have generally approached it from the angle of literature without transcribing the songs. The Sesotho word for games (lipapali) embraces entertainment but a further investigation of it shows that aspects of learning of which the children were aware in some cases and in others they were not aware, are present. These are supported by musical examples and texts. The definition of play versus games is treated (with regard to infants and children) and these two concepts are still receiving constant attention and investigation by scholars and researchers as the words are synonymous and can be misleading. Infants' play is unorganised and spontaneous while games are organised structures. Furthermore, play and games are important in child development education. In this study, they are given attention in order to lay the foundation for the understanding and interpretation of games used in both cultures. It is a misconception that African children's games are accompanied with music in the Western sense. Hence, the word `music' in Sesotho children's games takes on a different connotation from those in the West. Music' in Sesotho children's games embraces not only tunes that are sung, but game verses chanted in a rhythmic manner as opposed to spoken verse. Yet, mino (music) exists in Sesotho and is equivalent to the Western idea. These chanted rhythms and games are analysed against the backdrop of specific cultural dimensions for children depending on the function of the game played. The results of this study indicated that though the idea of music in children's games is not the same, games are an educational in character building and learning. Recommendations are made for educationists and music educators. / ART HIST, VIS ARTS and MUSIC / DLITT ET PHIL (MUSICOLOGY)

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