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Kirk, Robert George William. "Reliable animals, responsible scientists : constructing standard laboratory animals in Britain c.1919-1976." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445731/.
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This thesis explores the attempt to construct a national supply of standard laboratory- animals in Britain between 1919 and 1976. The demand for a national supply of standard laboratory-animals is located in the formation during the interwar period of the discipline of biological standardization. In contrast to other disciplines within the sciences biological standardization placed great emphasis upon the routine replication of experimental results. In consequence the field of biological standardization problematized the laboratory-animal and sought its standardization in order to construct it as a reliable diagnostic tool. In 1947 the Medical Research Council responded to pressure from an unprecedented coalition of scientific societies and established the Laboratory Animals Bureau tasked with regulating the British laboratory-animal production toward producing standard laboratory-animals. The work of the Laboratory Animal Bureau is analysed but the main focus of the thesis is upon the relationship between the practices of standardization and the promotion of the welfare of laboratory-animals. Particularly after the close of the Second World War the project to standardize laboratory-animals became increasingly associated with the promotion of their welfare. The relationship between the two was made explicit through the work of the Universities Federation for Animal Welfare in collaboration with the Laboratory Animals Bureau. In order to understand the relationship between standardization and welfare Michel Foucault's concept of biopower is employed. It is subsequently argued that the analytics of biopower need not be restricted to human life but equally encompasses non-human life. Through the Foucaultian perspective of biopower it is argued that standardization and welfare are two poles of the same biopolitical process.
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Lainetti, Elizabeth Brigagão de Faria. "Proposta conceitual de uma instalação para manuseio de mini porcos (minipigs) utilizados em pesquisas científicas." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-22022019-143417/.
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Para a realização de pesquisas científicas biológicas universais e reprodutivas, é fundamental a produção e o fornecimento de animais de laboratório de alta qualidade. Contudo, a qualidade e a saúde desses animais dependem, em grande parte, das instalações disponíveis para a sua produção e alojamento, de forma a garantir a qualidade sanitária e o seu bem-estar, respeitando os princípios éticos que regem a atividade. Nas instalações destinadas a criação, manutenção e experimentação com animais de laboratório são adotadas diretrizes, tanto nacionais como internacionais, para garantir a biossegurança e o bem-estar animal. Além disso, as instalações devem preencher outros requisitos, tais como: a funcionalidade dos ambientes, que devem possibilitar o manejo adequado e eficiente dos animais, facilitando a execução das atividades rotineiras; a climatização ambiental; a instalação de barreiras sanitárias para limitar e impedir o acesso de agentes indesejáveis; o respeito a princípios ergonômicos, para proporcionar um ambiente seguro e o bem-estar dos operadores; a biossegurança, para prevenir, minimizar ou eliminar riscos à saúde do homem e dos animais, a preservação do meio ambiente e a qualidade dos resultados. Dessa forma, o projeto das instalações é de importância vital para que os requisitos mencionados sejam atingidos, com a obtenção de animais sadios, com o mínimo de estresse, proporcionando o bem-estar e reduzindo variações que podem afetar os resultados de pesquisa. Neste documento, é apresentada uma introdução com a importância do suíno na medicina e na experimentação animal, além de alguns parâmetros importantes adotados na construção de instalações destinadas à criação e alojamento desta espécie. Finalmente, é apresentado um projeto conceitual de uma instalação, que reunirá características que representem o estado-da-arte sobre o assunto, para que o espaço destinado ao alojamento dos animais atenda, da melhor maneira, as recomendações sobre aspectos inerentes dos animais de laboratório, com relação à saúde, à alimentação, controle da transmissão de doenças, á adequação das instalações às exigências e às normas internacionais que visam o bem-estar animal. O projeto da instalação reunirá características únicas e inéditas, para que seja possível realizar pesquisas científicas avançadas, contribuindo para o crescimento da ciência nacional, bem como para o desenvolvimento inovador no âmbito da CNEN.In order to carry out outstanding universal and reproductive biological scientific research, the production and supply of high quality laboratory animals are of fundamental importance. However, the quality and health of these animals depends on a large extent on the facilities available for their production and housing in order to ensure the sanitary quality and their well-being, respecting the ethical principles governing the activity. National and international guidelines for facilities for breeding, maintenance and testing of laboratory animals are aimed, among other things, biosafety and animal welfare. In addition, facilities must meet other requirements, such as: the functionality of the environments, which should allow the proper and efficient management of the animals, facilitating the execution of routine activities; environmental air conditioning; the installation of sanitary barriers to limit and prevent access of undesirable agents; respect for ergonomic principles, to provide a safe environment and the well-being of operators; biosafety, to prevent, minimize or eliminate risks to the health of man and animals, the preservation of the environment and the quality of results. In this way, the design of the facilities is of vital importance in order to achieve the mentioned requirements, obtaining healthy animals with minimum stress, providing well-being and reducing variations that can affect the results of research. This paper presents an introduction to the importance of pig in medicine and animal experimentation, as well as some important parameters adopted in the construction of facilities for breeding and housing of this specie. Finally, a conceptual design of an installation is presented, which will bring up characteristics that represent the state of the art on the subject, so that the space destined to the housing of the animals meets, in the best way, the recommendations on inherent aspects of laboratory animals, with regard to health, food, control transmission of diseases, adaptation of facilities to international requirements and standards for animal welfare. The facilities project will bring also unique and unprecedented features, so that it is possible to carry out scientific cutting-edge research, contributing to the further development of national science, as well as innovative research within CNEN.
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Moreira, Virgínia Barreto [UNESP]. "Eficiência reprodutiva e comportamento parental de camundongos isogênicos e heterogênicos produzidos em ambiente modificado." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/126631.
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000841528.pdf: 469659 bytes, checksum: 2dd38d332ff2b50df196e07151da31a3 (MD5)O objetivo deste estudo foi avaliar a preferência e efeito do fornecimento de materiais de nidificação sobre o desempenho reprodutivo de camundongos isogênicos da linhagem BALB/c e da linhagem heterogênica Swiss em sistema de acasalamento intensivo monogâmico. Primeiro foi realizado um estudo para avaliar a preferência dos camundongos pelo material oferecido para nidificação. Utilizou-se um sistema composto de quatro gaiolas, com livre acesso a água e ração, interligados por tubos de PVC que permitiam que os animais se locomovessem entre todas as gaiolas. Quatro tipos de materiais foram oferecidos para a construção do ninho: algodão, gaze, rolinho de papelão, e touca de polipropileno descartável. Cada um dos quatro materiais foi oferecido simultaneamente em uma das quatro gaiolas que compunham o sistema. Foram usados 10 sistemas iguais e cada um abrigou um casal da linhagem BALB/c, desde os 28 dias de idade até o terceiro ciclo reprodutivo. Os mais encontrados na confecção do ninho, em ordem decrescente, foram a touca, rolinho, algodão e gaze (P< 0,0083). Com base nestes resultados foram selecionados dois tipos de materiais para fornecimento aos animais no experimento 2. Embora o rolinho tenha sido o segundo material mais utilizado optou-se pelo algodão devido a inviabilidade de fornecimento do item durante todo o período de duração do experimento 2. O segundo experimento avaliou a eficiência reprodutiva em cinco ciclos reprodutivos do nascimento até o desmame. Usou-se 60 casais de irmãos completos da linhagem BALB/c (isogênica) e 60 casais formados por acasalamentos aleatórios da linhagem Swiss (heterogênica) de padrão sanitário controlado, criados e mantidos em ambiente padronizado. Eles foram distribuídos, num delineamento inteiramente casualizado, em arranjo fatorial 2x2 (duas linhagens em alojamento com ou sem material para nidificação). Como forma de ...
The objective of this study was to evaluate the preference and effect of nesting materials provision on performance of inbred mice of the BALB/c strain and of heterogenic Swiss in intensive monogamous mating system. Firstly, a study was conducted to evaluate the preference of mice for the material offered for nesting. A system composed of four cages was used, with free access to water and food, connected by PVC tubing, which allowed animal displacement among all cages. Four types of materials were available for construction of the nest: cotton, gauze, cardboard rolls, and disposable polypropylene cap. Each of the four materials was offered simultaneously in one of four cages that formed the system. Ten identical system were used and each one housed a BALB/c couple, from 28 days of age up to the third reproductive cycle. The most commonly found materials in nest making were cap, roll, cotton and gauze (P <0.0083). Based on these results, two types of materials were selected to be offered to the animals in experiment 2. Although the roll was the second most used material, we chose cotton due to unfeasibility supplying of the item throughout the duration of the second experiment. The second experiment evaluated the reproductive efficiency in five reproductive cycles from birth to weaning. Sixty BALB / c full siblings pairs (inbred) and 60 pairs formed by random mating of Swiss strain (outbred), bred and maintained in a standardized environment were used. They were distributed in a completely randomized design in a 2x2 factorial arrangement (two strains in housing with or without nesting material). As a way of cage enrichment, polypropylene disposable cap cut into 8 pieces of approximately 1 cm each and one piece of cotton about 3 g were used after being previously packaged and autoclaved . The following characteristics were evaluated: age at first parturition, litter intervals, pre-weaning mortality and ...
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Draper, Adrian. "Gene & environmental interactions in sensitization to laboratory animals and other epidemiological aspects of laboratory animal allergy in the United Kingdom." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.519616.
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Moreira, Virgínia Barreto 1974. "Eficiência reprodutiva e comportamento parental de camundongos isogênicos e heterogênicos produzidos em ambiente modificado /." Botucatu, 2015. http://hdl.handle.net/11449/126631.
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Orientador: Ana Silvia Alves Meira Tavares MouraBanca: Simone Fernandes
Banca: Valderez Bastos Valero-Lapckick
Banca: Denose Rangel da Silva Sartori
Banca: Luiz Edivaldo Pezzato
Resumo: O objetivo deste estudo foi avaliar a preferência e efeito do fornecimento de materiais de nidificação sobre o desempenho reprodutivo de camundongos isogênicos da linhagem BALB/c e da linhagem heterogênica Swiss em sistema de acasalamento intensivo monogâmico. Primeiro foi realizado um estudo para avaliar a preferência dos camundongos pelo material oferecido para nidificação. Utilizou-se um sistema composto de quatro gaiolas, com livre acesso a água e ração, interligados por tubos de PVC que permitiam que os animais se locomovessem entre todas as gaiolas. Quatro tipos de materiais foram oferecidos para a construção do ninho: algodão, gaze, rolinho de papelão, e touca de polipropileno descartável. Cada um dos quatro materiais foi oferecido simultaneamente em uma das quatro gaiolas que compunham o sistema. Foram usados 10 sistemas iguais e cada um abrigou um casal da linhagem BALB/c, desde os 28 dias de idade até o terceiro ciclo reprodutivo. Os mais encontrados na confecção do ninho, em ordem decrescente, foram a touca, rolinho, algodão e gaze (P< 0,0083). Com base nestes resultados foram selecionados dois tipos de materiais para fornecimento aos animais no experimento 2. Embora o rolinho tenha sido o segundo material mais utilizado optou-se pelo algodão devido a inviabilidade de fornecimento do item durante todo o período de duração do experimento 2. O segundo experimento avaliou a eficiência reprodutiva em cinco ciclos reprodutivos do nascimento até o desmame. Usou-se 60 casais de irmãos completos da linhagem BALB/c (isogênica) e 60 casais formados por acasalamentos aleatórios da linhagem Swiss (heterogênica) de padrão sanitário controlado, criados e mantidos em ambiente padronizado. Eles foram distribuídos, num delineamento inteiramente casualizado, em arranjo fatorial 2x2 (duas linhagens em alojamento com ou sem material para nidificação). Como forma de ...
Abstract: The objective of this study was to evaluate the preference and effect of nesting materials provision on performance of inbred mice of the BALB/c strain and of heterogenic Swiss in intensive monogamous mating system. Firstly, a study was conducted to evaluate the preference of mice for the material offered for nesting. A system composed of four cages was used, with free access to water and food, connected by PVC tubing, which allowed animal displacement among all cages. Four types of materials were available for construction of the nest: cotton, gauze, cardboard rolls, and disposable polypropylene cap. Each of the four materials was offered simultaneously in one of four cages that formed the system. Ten identical system were used and each one housed a BALB/c couple, from 28 days of age up to the third reproductive cycle. The most commonly found materials in nest making were cap, roll, cotton and gauze (P <0.0083). Based on these results, two types of materials were selected to be offered to the animals in experiment 2. Although the roll was the second most used material, we chose cotton due to unfeasibility supplying of the item throughout the duration of the second experiment. The second experiment evaluated the reproductive efficiency in five reproductive cycles from birth to weaning. Sixty BALB / c full siblings pairs (inbred) and 60 pairs formed by random mating of Swiss strain (outbred), bred and maintained in a standardized environment were used. They were distributed in a completely randomized design in a 2x2 factorial arrangement (two strains in housing with or without nesting material). As a way of cage enrichment, polypropylene disposable cap cut into 8 pieces of approximately 1 cm each and one piece of cotton about 3 g were used after being previously packaged and autoclaved . The following characteristics were evaluated: age at first parturition, litter intervals, pre-weaning mortality and ...
Doutor
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Delpire, Veronique Charline. "Ethical schemes for the use of transgenic laboratory animals." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324118.
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Burt, John Michael. "Birdsong communication and perception : field and laboratory studies /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/9129.
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Agarwal, Rajat. "A model for minimizing cost for housing laboratory mice." [Gainesville, Fla.] : University of Florida, 2003. http://purl.fcla.edu/fcla/etd/UFE0001241.
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Carrillo, Martha. "Studies on protective immunity to toxocara canis in laboratory animals /." The Ohio State University, 1989. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487671108307319.
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Ali, Cairo F. "Animal rights and animal research." The Ohio State University, 1987. http://rave.ohiolink.edu/etdc/view?acc_num=osu1371556393.
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Augustsson, Hanna. "Ethoexperimental studies of behaviour in wild and laboratory mice : risk assessment, emotional reactivity and animal welfare /." Uppsala : Dept. of Large Animal Clinical Sciences, Swedish Univ. of Agricultural Sciences, 2004. http://epsilon.slu.se/v174.pdf.
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Neuenschwander, Stefan. "Structural and functional genomics in farm animals : a laboratory view point /." Zürich : ETH, Eidgenössische Technische Hochschule Zürich, Departement der Agrar- und Lebensmittelwissenschaften, Institut für Nutztierwissenschaften, Gruppe Züchtungsbiologie, 2001. http://e-collection.ethbib.ethz.ch/show?type=habil&nr=15.
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Hamaguchi, Satoshi. "Laboratory animals developed and established in Japan : The Ninth Medaka Symposium." Laboratory of Freshwater Fish Stocks Bioscience Center Nagoya University, 1996. http://hdl.handle.net/2237/13816.
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Wang, Jian Ping. "Health effects of chronic arsenic toxicity in humans and laboratory animals /." St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16894.pdf.
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Spangenberg, Elin. "Housing laboratory dogs and rats : implications of physical and social activity /." Uppsala : Dept. of Clinical Sciences, Swedish University of Agricultural Sciences, 2007. http://epsilon.slu.se/2007103.pdf.
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Ramos, Romero Sara. "Influencia de la ingesta de cacao en la respuesta inflamatoria aguda y crónica inducida en rata." Doctoral thesis, Universitat de Barcelona, 2011. http://hdl.handle.net/10803/669225.
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La respuesta inflamatoria es una reacción fisiológica ante una agresión con el fin de recuperar la homeostasis del organismo. Sin embargo, esta respuesta puede llegar a mermar la calidad de vida de las personas que la padecen de forma crónica, como es el caso de la artritis reumatoide. En este contexto resulta interesante hallar productos no farmacológicos que ayuden a paliar las consecuencias de la respuesta inflamatoria o que actúen como coadyuvantes de terapias antiinflamatorias. El cacao es un alimento que proporciona una cantidad relativamente elevada de flavonoides, compuestos polifenólicos con reconocida actividad antioxidante, antiproliferativa, protectora de los sistemas cardiovascular y nervioso e inmunomoduladora.
La hipótesis de partida de este estudio ha sido que la actividad inmunomoduladora de los flavonoides del cacao puede mantenerse tras su metabolismo y llegar a modular la respuesta inflamatoria in vivo. En base a esta hipótesis, el objetivo general de esta tesis ha sido establecer el efecto de la ingesta de cacao sobre la respuesta inflamatoria experimental.
Para alcanzar este objetivo, el diseño experimental ha contemplado la inducción de diferentes modelos experimentales de inflamación local aguda (inducidos por carragenina, histamina, serotonina, bradicinina y prostaglandina E2) y también de inflamación crónica sistémica (artritis adyuvante y artritis inducida por colágeno). En todos los casos, la ingesta de cacao se ha realizado de forma previa y durante el desarrollo del proceso inflamatorio. Para establecer el efecto del cacao sobre la respuesta inflamatoria in vivo, se han evaluado variables clínicas (como el edema articular) e inmunológicas (respuesta en anticuerpos, subpoblaciones linfocitarias, secreción de citocinas, etc.). Asimismo, se ha estudiado la capacidad antioxidante que confiere la ingesta de flavonoides de cacao.
Los resultados de este estudio han puesto de manifiesto que la dieta rica en cacao es capaz de reducir el edema articular inducido por carragenina. Este efecto puede atribuirse, al menos parcialmente, a la acción reguladora del cacao sobre el mediador inflamatorio bradicinina y sobre el potencial inflamatorio y prooxidante de los macrófagos. Por otra parte, la ingesta de cacao antes y durante el desarrollo de artritis adyuvante o inducida por colágeno, si bien no modifica la evolución clínica del edema articular, ejerce un efecto beneficioso ya que modula la producción de mediadores proinflamatorios (como TNF-¿), la respuesta humoral, la proporción de células efectoras de la respuesta inflamatoria crónica (linfocitos Th, Tc, Treg y NK) y el estrés oxidativo asociado a esta patología (ROS y NO).
En resumen, la acción beneficiosa de la ingesta de cacao sobre la respuesta inflamatoria, conjuntamente a sus propiedades antioxidantes, confieren al cacao potencial como coadyuvante en el tratamiento antiinflamatorio y en procesos autoinmunes.
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Colom, Codina Helena. "Estudio farmacocinético de la cianamida en la rata, en el perro y en voluntarios sanos." Doctoral thesis, Universitat de Barcelona, 1994. http://hdl.handle.net/10803/672887.
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La cianamida es un inhibidor de la ALDH que se utiliza en el tratamiento aversivo del alcoholismo crónico. Los objetivos del trabajo realizado son:
1) Estudio farmacocinético de la cianamida a dosis terapéuticas en la rata (2 Mg/Kg IV,PO), en el perro (1, 2, 4 Mg/Kg IV, y 4 Mg/Kg PO) y en voluntarios sanos (0,03, 0.1, 0.3, 0.6 y 1 Mg/Kg perfusión IV y 4 Mg/Kg PO).
2) Estudio de la actividad de la ALDH en sangre de voluntarios sanos tras dosis orales de 0.3, 1.0 y 1.5 Mg/Kg de cianamida.
3)Intentar establecer correlaciones entre niveles plasmáticos de cianamida y actividad de la ALDH en sangre tras dosis orales de 0.3, 1.0 y 1.5 Mg/Kg haciendo uso de modelos cinético-dinámicos.
La cianamida ha presentado una fugaz permanencia en las tres especies ensayadas a juzgar por los valores de T1/2, CLP, y MRT obtenidos. La velocidad de absorción es rápida, alcanzándose las concentraciones plasmáticas máximas después de 5, 35 y de 14 a 26 minutos en rata, perro y hombre respectivamente. La biodisponibilidad absoluta es incompleta en las tres especies siendo atribuible a un efecto de primer paso importante. La cianamida presenta un comportamiento cinético dosis-dependiente tras su administración oral al hombre, que se explica asumiendo un efecto de primer paso saturable junto con el paso del fármaco a circulación sistémica según un proceso de primer orden. La duración de la inhibición de la ALDH hemática fue de 12 a 48 horas (0.3 Mg/Kg )y de 36 a 144 (1.0 y 1.5 Mg/Kg), confirmando en un modelo "in vivo" el carácter reversible de la inhibición de la ALDH hemática.
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Torres, Cano Alejo. "WT1 in heart and gonad development: a crucial gene for cell plasticity and differentiation." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/673447.
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Wt1 is a complex gene that encodes a protein whose best described function is to act as a transcription factor. Wt1 plays a crucial role in several organ developments, including kidneys, liver, heart or gonads. Moreover, Wt1 is implicated in the etiology of a set of syndromes and diseases ranging from cancer to disorders of sex development (DSD). Additionally, Wt1 has been described to play a role in adult homeostasis. In this thesis, I focused on Wt1 role in development, specifically in gonad and heart morphogenesis. For this purpose, I used two previously described Cre mouse models to generate two different Wt1KOs.
The heart is the first organ being formed and it is primarily composed of three layers: the endocardium, the myocardium and the epicardium. The epicardium is a mesothelial layer of cells covering the vertebrate heart surface. Epicardial cells give rise to epicardial derived cells (EPDCs), progenitors of crucial cell types in heart development like vascular smooth muscle cells and cardiac fibroblasts. Moreover, the epicardium contributes to heart morphogenesis by secreting paracrine factors. After myocardial infarction, the epicardium embryonic genetic signature is reactivated. Thus, understanding the mechanisms behind epicardial development constitutes a topic of general interest.
The epicardial genetic program has been previously characterized and the Wt1 role in the regulation of this program has been established. One of the pathways modulated during epicardium development is the BMP4 pathway. The results of this thesis demonstrate that WT1 directly regulates Bmp4 expression. Additionally, exposed results demonstrate how the BMP4 pathway is crucial for epicardial cell maturation, through the regulation of cell morphology, from a cuboidal to a squamous cell shape, epicardial proliferation, and transcriptomic changes. Finally, the data shown in this work indicated that changes and mechanisms described for epicardium may be a phenomenon extrapolated to other mesotheliums like the lung mesothelium.
To better study Wt1 role in the development of other organs, we have characterized the recombination activity of a Wt1Cre mouse model using two different reporter mouse models, the R26RmTmG and the R26RtdRFP. Results demonstrated that Wt1Cre is efficiently activated in hearts and gonads but not in other organs generated from the genital ridge, like the kidney or the adrenal gland. Taking advantage of this, the Wt1Cre mouse model was used to generate a new Wt1KO: the Wt1Cre; Wt1Loxp/GFP. Wt1Cre; Wt1Loxp/GFP mice show a partial embryonic lethality, potentially caused by defects in heart development, but some of them reach adulthood, becoming an ideal model to investigate Wt1 role from embryonic to adult stages. Therefore, we decided to study Wt1role in gonad development in Wt1Cre; Wt1Loxp/GFP mice.
Sex development is a complex and coordinated process that starts with the differentiation of the bipotential gonads. WT1 mutations or haploinsufficiency have been reported in different syndromes and conditions linked to DSD. The study of WT1 role in embryonic development and the impact on adult sex development has been hampered by the complete gonadal agenesis or embryonic lethality presented by other Wt1KO mouse models.
The results presented demonstrate a sharp reduction in Wt1 levels in Wt1Cre; Wt1Loxp/GFP gonads since the bipotential stage. This causes, in the adult, the formation of small, atrophic gonads, a hermaphroditism of the genital tract and external ambiguous genitalia. Besides, the data reported in this thesis demonstrates that Wt1Cre; Wt1Loxp/GFP mice present an impaired gonad embryonic development due to the lack of differentiation of the main cell lineages responsible for gonad development and function: supportive cells, steroidogenic cells and primordial germ cells (PGCs).
Finally, the observed sub-lethality in Wt1Cre; Wt1Loxp/GFP mice is explained by the observation of a severe heart developmental impairment in a portion of Wt1Cre; Wt1Loxp/GFP embryos, whereas others show no apparent heart defects at embryonic stages. Equally, an histological study performed on Wt1Cre; Wt1Loxp/GFP mice also described changes in the spleen and brown adipose tissue.
In summary, our results indicate the importance of morphological changes epicardial cells undergo during development, a process regulated by Wt1 modulation of the BMP4 pathway. In addition, the generation and characterization of the Wt1Cre; Wt1Loxp/GFP mouse renders an informative and useful tool to study Wt1 role beyond embryonic stages and provide a more accurate frame for the understanding of results previously obtained when using the Wt1Cre mouse model.
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LAINETTI, ELIZABETH B. de F. "Analise critica para adequacao fisica e implantacao de novos procedimentos na divisao de animais de laboratorios do IPEN." reponame:Repositório Institucional do IPEN, 2009. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9442.
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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
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Ogden, Jacqueline Jean. "A comparative evaluation of naturalistic habitats for captive lowland gorillas (Gorilla gorilla gorilla)." Diss., Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/29173.
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McKinley, Jean. "Training in a laboratory environment : methods, effectiveness and welfare implications for two species of primate." Thesis, University of Stirling, 2004. http://hdl.handle.net/1893/23412.
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The use of Positive Reinforcement Training (PRT) for co-operation during routine husbandry and laboratory procedures is widely advocated as a means of promoting the welfare of nonhuman primates. However, while research originating in US zoos provide qualitative descriptions of how PRT may be used in the training of a wide variety of species, quantitative data and evidence to support the view that PRT reduces stress predominately comes from laboratory studies of primates whose training may have used other methods. Despite official guidelines, training is rarely carried out in the UK and the educational and wider organisational structures concerning training, present in the US are largely absent. The techniques used in the UK were assessed through detailed observations recorded when four stump-tailed macaques were trained to co-operate during venipuncture. Data recorded during training sessions showed that although food rewards were given, their delivery was slow and inconsistent. A certain amount of coercion was used which violates a principle of PRT which states that co-operation should be voluntary. The macaques showed increasing resistance to the process and a mild but detrimental effect on the subsequent behaviour of the study animals. When training resumed 18 months later there were considerable improvements in the techniques used. The macaques showed a greater willingness to participate and there were no significant changes in their behaviour when training days were compared to those when training did not take place. The behaviour of the macaques during venipuncture was judged to be arising from engineered compliance rather than voluntary co-operation. However, it was concluded that the technique observed, if carried out correctly, was a reasonable compromise between forced restraint and voluntary co-operation given the paucity of evidence showing the effectiveness of PRT for invasive procedures. However, it was also concluded that the use of coercion should be recognised and provide a focus for future refinement. The effectiveness and welfare implications ofPRT was assessed through the training of common marmosets to target and allow in-homecage weighing and to provide urine samples. It was found that the trained animals perfonned reliably and that time invested in training could be recouped through faster data collection. Following a period of training or increased positive contact with humans, observations of marmoset behaviour showed a decrease in stress related behaviours and an increase in allogrooming supporting the view that improved relations with humans had a beneficial effect. Following exposure to a mild stressor, trained marmosets showed no elevation in levels of urinary cortisol or stress related behaviours. Untrained animals showed increased levels of locomoting and selfscratching following exposure to the same stressor. It was concluded that PRT successfully reduced the stress associated with the presence of, and manipulation by, humans. Final recommendations were that training can promote the welfare of nonhuman primates and should be used in UK laboratories to a greater extent than is currently the case. However, the lack of educational opportunities for animal trainers in the UK needs to be addressed. It was also recommended that in light of the growing evidence showing the benefits that can arise from training and good relations with humans, the zero-handling policy practiced in many UK zoos should be reassessed.
22
CIFANI, Carlo. "Development and pharmacological characterization of models of binge eating in laboratory animals." Doctoral thesis, Università degli Studi di Camerino, 2007. http://hdl.handle.net/11581/404151.
Full textAbstract:
Introduction and aim of the studies: Binge eating disorder (BED) is a more
recently defined syndrome that features recurrent episodes of overeating,
without inappropriate compensatory behaviors.
The development of an animal model is an important step for understanding
the aetiology of BED, and for developing effective treatments. Most
importantly, the utility of an animal model lies in its face validity or
embodiment of the characteristics prevalent in clinical populations. During my
studies I worked to reproduce two animal models of binge eating described in
literature: 1) Key synergistic role of past caloric restriction and stress;
2) Contrast-induced cycling: consummatory and emotional dependence on
preferred food. A model of intermittent excessive behavior.
and to develop two new animal models of binge eating with the
pharmacological characterization: 3) Exposure to environmental-food
associated cues elicited compulsive behavioural response to actively obtain
food rewards in female rats; 4) Exposure to food related cues induced
overeating in female rats exposed to cyclic dieting
5) I studied also the susceptibility of congenic DA.WOKW rats to develop
binge eating as possible model to elucidate the genetics of binge eating
disorder.
Results: 1) We were able to obtain binge eating by combining repeated
caloric restrictions and electric foot-shock stress only in msP rats with
maternal separation. This animal study might support the clinical hypothesis
that severe stress during childhood leads to vulnerability to abnormal eating
behavior in response to stress in later life in humans.
2) The present study failed to replicate the work by Cottone and co-workers.
In particular we have not been able to detect significant difference in body
weight gain between control and High-Palatable food exposed rats. To
investigate the reasons of these discrepancies would require a detailed
analysis of several variables. We decided, therefore, to develop an
alternative model to use for drug test purposes.
3) This model used was developed exploiting food cues-induced overeating
under operant self-administration condition. Prior presentation of cues
predictive of food reward engage the animal into a food-seeking state
resulting in overfeeding occurring at beginning of the food delivery session.
This increase of responding over baseline condition may reflect an increased
“craving” for food resulting in loss of control reaction to food cues.
Rimonabant and Sibutramine reduced food intake in both cue-preexposed
and nonpreexposed rats suggesting a general inhibition of appetitive
behaviour following drug administrationof these drugs.
Fluoxetine and Topiramate, on the other hand, more potently affected food
self-administration in cue preexposed rats. This effect is indicative of a more
selective action of these compound in the regulation of food-seeking
behaviour rather than in the control of satiety mechanisms.
4) In this model electric foot-shock of Hagan’s model was substituted with a
different stress, related to lack of control over environmental circustances
induced by allowing rats to see and to smell the palatable food but
preventing them from access to it for 15 min. We obtained a clear binge
eating response in rats that was confirmed for all the experiments.
In this model the treatment with fluoxetine (3 mg/Kg) is able to reduce HP
food intake in the group of R + P and not in NR + NP showing a specific effect
in reducing the loss of control in overeating after the pre-exposure to HP food
with a history of restriction.
5) DA.WOKW 16, DA.WOKW 5a, and DA.WOKW 3a, did not develop binge
eating while DA, WOKW and DA.WOKW 3b developed binge eating. It will be
necessary more studies to well correlate these genetics results and
behavioural studies.
Conclusion: The development of this animal model of binge eating should
prove useful in identifying and assessing further critical enviromental triggers
and specific physiological changes that precipitate and maintain the behavior
and eventually, in guiding better prevention and treatment strategies for binge
eating disorders.
23
CIFANI, Carlo. "Development an pharmacological characterization of models of binge eating in laboratory animals." Doctoral thesis, Università degli Studi di Camerino, 2008. http://hdl.handle.net/11581/404145.
Full textAbstract:
Introduction and aim of the studies: Binge eating disorder (BED) is a more
recently defined syndrome that features recurrent episodes of overeating,
without inappropriate compensatory behaviors.
The development of an animal model is an important step for understanding
the aetiology of BED, and for developing effective treatments. Most
importantly, the utility of an animal model lies in its face validity or
embodiment of the characteristics prevalent in clinical populations. During my
studies I worked to reproduce two animal models of binge eating described in
literature: 1) Key synergistic role of past caloric restriction and stress;
2) Contrast-induced cycling: consummatory and emotional dependence on
preferred food. A model of intermittent excessive behavior.
and to develop two new animal models of binge eating with the
pharmacological characterization: 3) Exposure to environmental-food
associated cues elicited compulsive behavioural response to actively obtain
food rewards in female rats; 4) Exposure to food related cues induced
overeating in female rats exposed to cyclic dieting
5) I studied also the susceptibility of congenic DA.WOKW rats to develop
binge eating as possible model to elucidate the genetics of binge eating
disorder.
Results: 1) We were able to obtain binge eating by combining repeated
caloric restrictions and electric foot-shock stress only in msP rats with
maternal separation. This animal study might support the clinical hypothesis
that severe stress during childhood leads to vulnerability to abnormal eating
behavior in response to stress in later life in humans.
2) The present study failed to replicate the work by Cottone and co-workers.
In particular we have not been able to detect significant difference in body
weight gain between control and High-Palatable food exposed rats. To
investigate the reasons of these discrepancies would require a detailed
analysis of several variables. We decided, therefore, to develop an
alternative model to use for drug test purposes.
3) This model used was developed exploiting food cues-induced overeating
under operant self-administration condition. Prior presentation of cues
predictive of food reward engage the animal into a food-seeking state
resulting in overfeeding occurring at beginning of the food delivery session.
This increase of responding over baseline condition may reflect an increased
“craving” for food resulting in loss of control reaction to food cues.
Rimonabant and Sibutramine reduced food intake in both cue-preexposed
and nonpreexposed rats suggesting a general inhibition of appetitive
behaviour following drug administrationof these drugs.
Fluoxetine and Topiramate, on the other hand, more potently affected food
self-administration in cue preexposed rats. This effect is indicative of a more
selective action of these compound in the regulation of food-seeking
behaviour rather than in the control of satiety mechanisms.
4) In this model electric foot-shock of Hagan’s model was substituted with a
different stress, related to lack of control over environmental circustances
induced by allowing rats to see and to smell the palatable food but
preventing them from access to it for 15 min. We obtained a clear binge
eating response in rats that was confirmed for all the experiments.
In this model the treatment with fluoxetine (3 mg/Kg) is able to reduce HP
food intake in the group of R + P and not in NR + NP showing a specific effect
in reducing the loss of control in overeating after the pre-exposure to HP food
with a history of restriction.
5) DA.WOKW 16, DA.WOKW 5a, and DA.WOKW 3a, did not develop binge
eating while DA, WOKW and DA.WOKW 3b developed binge eating. It will be
necessary more studies to well correlate these genetics results and
behavioural studies.
Conclusion: The development of this animal model of binge eating should
prove useful in identifying and assessing further critical enviromental triggers
and specific physiological changes that precipitate and maintain the behavior
and eventually, in guiding better prevention and treatment strategies for binge
eating disorders.
24
Gunn, Deborah. "Evaluation on welfare in the husbandry of laboratory rabbits." Thesis, University of Birmingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391022.
Full text
25
DeClue, Amy E. "Ketamine immunomodulation during endotoxemia." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/6276.
Full textAbstract:
Thesis (M.S.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "August 2007" Includes bibliographical references.
26
Ríos, Kristjánsson Juan Gabriel. "The Effect of intermittent hypobaric hypoxia and exercise on the recovery of induced skeletal muscle damage in trained laboratory rats: performance evaluation, plasma markers and M. Soleus differential gene expression = El efecto de hipoxia hipobárica intermitente y ejercicio de la recuperación del daño muscular esquelético inducido en ratas de laboratorio entrenadas: evaluación de rendimiento, marcadores plasmáticos y expresión génica diferencial del M. Soleus." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/402579.
Full textAbstract:
One of the key players in the regenerating injured skeletal muscle fibers are their surrounding satellite cells (specific stem cells), arranged between the basal lamina and the sarcolemma, in relatively few numbers per fiber. The satellite cells, which are myogenic precursor cells are activated during injury to fuse and mature into the injured fiber. Some studies have demonstrated that exercise and hypoxia facilitate the activation and migration into the blood circulation, moving more stem cells to an injured or activated area which in turn aids the repairing of the injury. The aim of this thesis was to study the regeneration profile over fourteen days after an eccentric-exercise induction of skeletal muscle damage in treadmill-trained laboratory rat, submitting them to series of daily (4 h) intermittent hypobaric hypoxia (with the simulated altitude of 4000 m) with or without the combination of light exercise as part of their rehabilitation. The rats could potentially react differently to the exercise training prior and post the induction of muscle damage, and furthermore, be differently susceptible to the injury-induction protocol, influenced by their training. This premise led to the formation of the rat AEY performance score, throughout the study, as a complementary tool for the data acquired during the injury regeneration. The regeneration was profiled four times over the recovery fourteen days from the injury induction via the concentration of myoglobin and creatine kinase (CK-MM) plasma markers and differential gene expression analysis in m. soleus, which is generally considered to be one of the most susceptible muscle to eccentric-exercise injury when running downhill. The plasma marker results indicate that the effect of the injury-induction protocol was very short lived, as after the significantly different peak concentrations for the control (passive recovery) and they hypoxia groups (sessions of intermittent hypoxia during recovery) 1 day post injury, had dropped down to basal level again 3 days post injury. However, the hypoxia+exercise group (sessions of intermittent hypoxia followed by light exercise during recovery) had a distinct profile with its slowly rising peak 3 days post injury and then dropping down again. Still, this profile was only significant for the CK-MM measurements, whilst myoglobin did not show any significant change following injury. It is clear that the hypoxia-exercise conditions cause different physiological reactions to the injury. However, the level of the injury would need to be greater in order to obtain a more significant pattern and to be able to interpret if the pattern is reflecting potentially beneficial effects or not. The differential gene expression analysis also indicates that the injury induction needed to have been greater to achieve differential expression. The hypoxia and hypoxia+exercise profiles are not parallel to each other, still the data also suggest that the hypoxia sessions could have been more effective. Therefore, it is difficult to give a general conclusion to which hypoxia or hypoxia+exercise facilitate the injury regeneration to a higher degree. The certain fact is that there are ethical and humane factors that need to be respected, but limit the margin of how the injury-induction can be carried out in the way it was done in this study.Uno de los actores clave en la regeneración de fibras musculares esqueléticas dañadas son las células satélite circundantes (células madre específicas), dispuestos entre la lámina basal y el sarcolema, en relativamente pocos números por fibra. Las células satélite, que son células precursoras miogénicas se activan durante lesión para fusionar y madurar en la fibra heridos. Algunos estudios han demostrado que el ejercicio y la hipoxia facilitan la activación y la migración en la circulación sanguínea, moviéndose más células a un área lesionada o activados que a su vez ayuda a la reparación de la lesión del tallo. El objetivo de esta tesis fue estudiar el perfil de regeneración más de catorce días después de una inducción excéntrico ejercicio de daño muscular esquelético en ratas de laboratorio caminadora entrenados, sometiéndolos a la serie de diario (4 h) la hipoxia hipobárica intermitente (con la altitud simulada de 4000 m), con o sin la combinación de ejercicio ligero, como parte de su rehabilitación. Las ratas podrían potencialmente reaccionan de manera diferente a la práctica de ejercicio, previa y la inducción de daño muscular, y además, ser diferente susceptible al protocolo de inducción de lesiones, influenciado por su formación. Esta premisa conducía a la creación de la puntuación de rendimiento AEY de las ratas a lo largo del estudio, como una herramienta complementaria para los datos adquiridos durante la regeneración de la lesión. La regeneración se perfila cuatro veces en los catorce días de recuperación de la inducción de lesiones a través de la concentración de mioglobina y la creatina quinasa (CK-MM) marcadores de plasma y análisis de la expresión diferencial de genes en m. sóleo, que generalmente se considera ser uno de el músculo más susceptibles a las lesiones excéntrica-ejercicio cuando se ejecuta cuesta abajo. Los resultados de los marcadores de plasma indican que el efecto del protocolo de la lesión de la inducción fue muy corta duración, ya que después de las muy diferentes concentraciones máximas para el control (recuperación pasiva) y la hipoxia grupos (sesiones de hipoxia intermitente durante la recuperación) después de la lesión de 1 día, había caído hasta el nivel basal de nuevo 3 días después de la lesión. Sin embargo, el grupo de hipoxia + ejercicio (sesiones de hipoxia intermitente seguido de ejercicio ligero durante la recuperación) tenía un perfil distinto con su pico lento aumento de 3 días después de la lesión y luego de descender de nuevo. Sin embargo, este perfil sólo fue significativa para las mediciones de CK-MM, mientras que la mioglobina no mostró ningún cambio significativo después de una lesión. Es evidente que las condiciones de hipoxia de ejercicio causan diferentes reacciones fisiológicas a la lesión. Sin embargo, el nivel de la lesión tendría que ser mayor con el fin de obtener un patrón más significativa y para ser capaz de interpretar si el patrón está reflejando efectos potencialmente beneficiosos o no. El análisis de la expresión diferencial de genes también indica que la inducción de lesiones necesario haber sido mayor para lograr la expresión diferencial. Los perfiles de la hipoxia y la hipoxia + ejercicio no son paralelas entre sí, siendo los datos también sugieren que las sesiones de hipoxia podría haber sido más eficaz. Por lo tanto, es difícil dar una conclusión general a la que la hipoxia o hipoxia + ejercicio facilitan la regeneración lesión a un grado superior. El hecho cierto es que hay factores éticos y humanos que necesitan ser respetado, pero limitan el margen de cómo la lesión de la inducción puede llevarse a cabo en la forma en que se llevó a cabo en este estudio.
27
Bueno, Aline [UNESP]. "Repercussões de diferentes intensidades glicêmicas no início do desenvolvimento embrionário de ratas." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/99239.
Full textAbstract:
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In vitro studies suggest that maternal hyperglycemia insult impairs the early embryogenesis in the preimplantation period. In this paper, we show that streptozotocin given at birth day of life or in adulthood of rats caused hyperglycemic state. Regardless of hyperglycemic intensities (mild or severe diabetes), the embryos of these dams presented development retardation and decreased development competence. Apoptosis was detected using terminal dUTP nick end labeling (TUNEL) assays, and the morulas from mild and severe diabetic rats have a higher incidence of apoptotic cells than control embryos. Tumor necrosis factor-alpha, a cytokine whose synthesis is up-regulated in the diabetic uterus, did not alter the incidence of TUNEL-positive nuclei. The glycemic intensity is related with the increased in the apoptosis indexes in morulas. On the other hand, dams with hyperglycemia, regardless of the glycemic intensity and of the tumor necrosis factor-alpha level presented preimplantation embryos with development retardation and increase of non-viable preimplantation embryos, suggesting that the presence of the hyperglycemia leads to a decreased competence development of preimplantation embryos
28
Lombard, Chereé. "Animal welfare and the law : towards legal regulation of the welfare of laboratory animals in South Africa / Chereé Lombard." Thesis, North-West University, 2012. http://hdl.handle.net/10394/8718.
Full textAbstract:
The current legal framework pertaining to animals does not sufficiently address the welfare of animals. The Animal Protection Act 71 of 1962 does not specifically regulate the welfare of animals contained in research laboratories. Animals utilized for experimental research purposes endure tremendous “unnecessary suffering” due to legislative inaptitude. Experimental animals suffer inherent abuses associated with experimental research because of the methods, procedures and processes relevant to the experiments. The most controversial method of experimental research is vivisection. The method of vivisection is not only invasive but also causes “unnecessary suffering” to animals. The non-inherent abuses animals suffer during confinement in a laboratory solely relates to uncontrolled and unregulated conduct of staff.
Continuing the application of the current legislative framework may also be detrimental to the health and well-being of humans. Animals are specifically utilized as objects of science in research laboratories. The data obtained from research experiments conducted on animals are for the benefit of humankind rather than the animals. Scientific research concluded that not only are invasive methods of research conducted on live animals generally regarded as useless but extrapolating data from animals to humans can also be misleading, unnecessary and dangerous. False results and questionable methodologies are some of the other problems that seem to require urgent attention. Ethically, neither human nor animal should be utilized at the expense of the other and therefore it would be reasonable to recommend that legislative reform takes place.
The human perception of animals in terms of the relationship we have with them is the reason why legislative inaptitude in terms of animal welfare exists. The current approach followed is the philosophy of Utilitarianism. Utilitarians believe that neither humans nor animals have rights but interests. Utilitarianism focuses on the permissibility of an act (the use of animals) by weighing the benefits of such an act to the costs suffered because of such act. If the benefits outweigh the costs suffered, the act is permissible. The application of Utilitarianism seems to be the crux of our legislative inaptitude. The human perception and view of animals must therefore be re-directed to develop a sufficient legal framework in terms of animal welfare. A solution offered is to apply an alternative interpretation to the concept of “dignity” (capabilities approach) and progressive realisation. In terms of this solution a species capabilities in terms of its value, capabilities and worth are considered. Inherent to its value, capabilities and worth, is its “dignity”. Once the alternative interpretation of “dignity” is acknowledged, the progressive realisation of its interests can be achieved.Thesis (LLM)--North-West University, Potchefstroom Campus, 2013
29
Stoodley, Marcus A. "Pathophysiology of Syringomyelia /." Title page, contents and abstract only, 1996. http://web4.library.adelaide.edu.au/theses/09PH/09phs882.pdf.
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30
Orrego, Lagarón Naiara. "Estudios de absorción y disposición de naringenina y quercetina. Estudios preclínicos." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/396654.
Full textAbstract:
En los últimos años se ha visto un creciente interés en el estudio de los compuestos bioactivos que se encuentran en frutas y hortalizas debido a la relación “Dieta mediterránea vs. Salud”, con el fin de conocer cuáles de ellos son los responsables de dicha relación. La presente tesis doctoral se enmarca en este contexto y en concreto en el estudio de una de las hortalizas más consumidas en Europa, el tomate.
El tomate es conocido por contener grandes cantidades de polifenoles entre ellos destacan dos flavonoides, naringenina y quercetina. Ambos son conocidos como posibles responsables de su efecto beneficioso sobre la salud. Sin embargo, ambos compuestos tienen una baja biodisponibilidad oral, lo que acarrea ciertas dudas acerca de su implicación real en estos efectos, ya que ambos factores están correlacionados. La biodisponibilidad oral depende básicamente de la permeabilidad del compuesto en el lugar de absorción, del efecto metabólico que sufre a nivel intestinal y hepático, y de la influencia de la microflora intestinal.
Hasta la fecha no se conocen estudios que engloben el estudio de la biodisponibilidad de la naringenina a lo largo de todo el tracto gastrointestinal, que informen acerca de los factores que afectan a su permeabilidad intestinal y/o metabolismo incluyendo la influencia de la microbiota. Es por ello que la presente tesis doctoral tiene como objetivos mejorar los datos que se tiene sobre la permeabilidad de la naringenina, estudiando la misma a todos los niveles gastrointestinales: estómago, intestino delgado y colon en un modelo de perfusión intestinal in situ en ratón, así como conocer como se ve afectada por el metabolismo intestinal y hepático. Además se estudian otros factores, como el efecto que la microbiota del colon tiene respecto a su permeabilidad y metabolismo o el efecto sobre los mismos de su coadministración con quercetina.
Los resultados muestran una mayor permeabilidad de la naringenina a nivel del intestino delgado, seguido del colon y estómago, respectivamente. Respecto a los metabolitos, se observó como a nivel de lumen intestinal el número de metabolitos era mayor al de plasma y bilis, demostrando por tanto, mayor importancia del metabolismo intestinal sobre el hepático para la naringenina. El tratamiento con Rifaximina (un antibiótico que actúa a nivel intestinal), provocó un descenso en la permeabilidad de la naringenina, demostrando el efecto que la microbiota intestinal tiene en la permeabilidad de dicho compuesto. El tratamiento antibiótico también produjo cambios en el perfil metabólico de la naringenina. El uso de una técnica complementaria como es el LTQ-Orbitrap junto con el HPLC-MS/MS, resultó ser muy útil en la mejora del perfil metabólico de la naringenina a nivel del estómago y el colon, gracias al uso de ambas técnicas se pudo identificar un mayor número de metabolitos en las muestras de lumen de los estudios de estómago y colon.
Respecto al efecto de la coadministración de naringenina con quercetina, se observó como la permeabilidad de la misma disminuía respecto a los datos de administración sola. Los mismos resultados se obtuvieron para la quercetina, siendo menor el coeficiente de permeabilidad cuando se administraba junto a la naringenina que sola. El metabolismo también se vio afectado por la coadministración observándose un incremento en el número de metabolitos en las muestras perfusión, bilis y plasma. Estos resultados demuestran como la coadministración
favorece el ciclo enterohepático y por tanto, el tiempo de residencia de los compuestos y de sus metabolitos en el cuerpo.Since it is known the correlation “Mediterranean diet vs. Health”, a lot of studies have been carried out in order to known which are the compounds responsible of this relation and how they acted. The current thesis was framed within this context and focused on one of the most consumed vegetables in Europe: the tomato. Tomato holds a high amount of polyphenols, such as the flavonoids naringenin and quercetin. Although both have been identified as possible responsible of the tomato´s healthy effect, their low oral bioavailability raises many questions about how they really participate on them. Oral bioavailability depends basically on the permeability of the compound in the absorption side, on the intestinal and hepatic metabolism and on the influence of the microflora. The studies carried out within this thesis improve the knowledge about the permeability of naringenin along the entire gastrointestinal tract, using an intestinal in situ perfusion model in mice, as well as its intestinal and hepatic metabolism. Other factors studied were the effect of the colon microbiota and the effect of the coadministration with quercetin on the permeability and the metabolism. The results showed that the highest permeability level of naringenin was on small intestine followed by colon and stomach, respectively. Metabolism data highlighted the importance of the intestinal metabolism beyond the hepatic one; the use of Rifaximine in colon perfusion assays proved the importance of the microbiota on the permeability and metabolism of the compound and the use of a complementary technique (LTQ-Orbitrap) on the analysis of the lumen samples, together with the HPLC-MS/MS provided an improvement on the metabolic profile of naringenin in colon and stomach studies. On the other hand, the coadministration of naringenin and quercetin showed lower permeability coefficients compared to those obtained in their alone administration. Regarding to their metabolism, the coadministration showed an increased on the number of metabolites in perfusion samples, bile and plasma, proving that the coadministration favors the enterohepatic cycle, and therefore the residence time of the compounds and their metabolites in the body.
31
Bueno, Aline. "Repercussões de diferentes intensidades glicêmicas no início do desenvolvimento embrionário de ratas /." Botucatu : [s.n.], 2012. http://hdl.handle.net/11449/99239.
Full textAbstract:
Orientador: Débora Cristina DamascenoCoorientador: Yuri Karen Sinzato
Banca: Maria José Sparça Salles
Banca: Felipe Perecin
Resumo: Não disponível
Abstract: In vitro studies suggest that maternal hyperglycemia insult impairs the early embryogenesis in the preimplantation period. In this paper, we show that streptozotocin given at birth day of life or in adulthood of rats caused hyperglycemic state. Regardless of hyperglycemic intensities (mild or severe diabetes), the embryos of these dams presented development retardation and decreased development competence. Apoptosis was detected using terminal dUTP nick end labeling (TUNEL) assays, and the morulas from mild and severe diabetic rats have a higher incidence of apoptotic cells than control embryos. Tumor necrosis factor-alpha, a cytokine whose synthesis is up-regulated in the diabetic uterus, did not alter the incidence of TUNEL-positive nuclei. The glycemic intensity is related with the increased in the apoptosis indexes in morulas. On the other hand, dams with hyperglycemia, regardless of the glycemic intensity and of the tumor necrosis factor-alpha level presented preimplantation embryos with development retardation and increase of non-viable preimplantation embryos, suggesting that the presence of the hyperglycemia leads to a decreased competence development of preimplantation embryos
Mestre
32
Connolly, Ashley Rex. "Cytokine gene expression in a rat model of polyarthritis /." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phc75238.pdf.
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El-Beyrouthi, Nayla. "RNA interference and somatic cell nuclear transfer to generate an apolipoprotein E deficient pig : a new model of atherosclerosis." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116103.
Full textAbstract:
Atherosclerosis is a complex disease which develops silently over decades and can lead to acute myocardial infarction or stroke, the main cause of death worldwide. Apoliporotein E (apo E) is a glycoprotein known for its major role in lipid metabolism and its pro-atherogenic effects. Swine make a unique and viable research model as it shares most of the anatomic and physiologic characteristics with humans, notably for the the cardiovascular system. In addition, it is the only animal species, other than nonhuman primates, that develops atherosclerosis spontaneously. In this study we examined the feasibility for creating an apo E-deficient pig model of atherosclerosis using RNA interference (RNAi) and somatic cell nuclear transfer (SCNT). The knockdown efficiency was tested in porcine granulosa cells. It varied from 45% to 82% compared to control cells, as revealed by real-time PCR analysis. Accordingly, short hairpin RNA-expressing vectors were constructed and used to transfect porcine fetal fibroblast cells. Cell lines with stable chromosomal integration were established and used to produce embryos by SCNT. Development of SCNT embryos to the blastocyst stage (33%) was comparable to non-transgenic embryos. The integration of the shRNA into the genome of GFP-expressing embryos was revealed by PCR and gel electrophoresis. These findings indicate that porcine embryos harboring shRNA-specific to apo E created by SCNT may lead to the production of apo E-deficient pigs. These pigs would be a promising new animal model for advancing atherosclerosis research.
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Xiang, Li. "Metabolomics study of regulatory effects of exercise training on db/db type 2 diabetic mice." HKBU Institutional Repository, 2018. https://repository.hkbu.edu.hk/etd_oa/489.
Full textAbstract:
Type 2 diabetes mellitus (T2DM) is mainly caused by genetic modifications and inappropriate life styles. The complexity of T2DM has brought us challenges for a comprehensive understanding of altered metabolic pathways that contributing to the development of T2DM. Therefore, a comprehensive metabolic analysis is needed. To date, taking regular exercise is a common and effective therapeutic way known to antagonize the metabolic disorders of T2DM. However, the regulatory effects of exercise on T2DM or T2DM induced complications have not been clearly characterized. Here, we present the effect of physical activity on biochemical changes in diabetic db/db mice in plasma, urine, skeletal muscle and kidney samples. Based on liquid chromatography coupled with high resolution Orbitrap mass spectrometry (LC-MS) and gas chromatography coupled with mass spectrometry (GC-MS), two major approaches, untargeted and targeted metabolomics studies, have been developed to delineate metabolic signatures in various kinds of biofluid and tissue samples. Targeted quantification methods on acylcarnitines and acyl-CoA have been developed. Untargeted metabolomics analysis by GC-MS and LC-MS have also been developed to draw a more comprehensive view of the metabolic changes in response to T2DM and exercise on db/db diabetic mice. The transcript expressions of mRNA in pathways of interest have also been measured to confirm the hypothesis. Firstly, a targeted quantification method of acylcarnitines by using high resolution parallel reaction monitoring (PRM) on LC-MS platform has been developed. A total of 117 acylcarnitines were detected from plasma and urine samples. The application of targeted profiling of acylcarnitines in db/m+ control and db/db diabetic mice indicated incomplete amino acid and fatty acid oxidation in diabetic mice. Interestingly, the reduction of medium odd-numbered chain acylcarnitines in urine samples was firstly observed between db/m+ and db/db mice. The high resolution PRM method makes it possible to monitor the widespread metabolic changes of the acylcarnitines in response to stimuli. Besides, the accurate MS and MS/MS spectra data of the 117 acylcarnitines could be used as mass spectrometric resources for the identification of acylcarnitines. In addition to targeted metabolomics analysis, untargeted metabolomics profiling analysis in plasma samples indicated that db/db diabetic mice may be more susceptible to exercise for energy expenditure. Interestingly, all the results from plasma, skeletal muscle and kidney samples may demonstrate that physical activity could mitigate insulin resistance in T2DM mice through improving fatty acid β-oxidation (FAO) and eliminating overloaded intermediate which contribute to insulin resistance. Specifically, the results from kidney samples demonstrated that exercise exhibit beneficial effect in reducing hyperlipidemia, expression levels of inflammatory markers (TNFα, IL-6 and COX2) and fibrosis markers (Collagen 1), and alleviating diabetic nephropathy (DN) induced mesangial expansion in kidneys of diabetic mice. The results of metabolic changes in kidney of db/db mice revealed that the accumulation of acyl-CoA, phospholipids and hydroxylated acylcarnitines were substantially ameliorated by exercise, and the reduction of important enzymes CTP1α and Acadl in FAO were partially reversed. In addition, branched-chain amino acids (BCAA) metabolism which positively related to inflammation (TNFα) was down-regulated in DN mice by exercise. What’s more, the accumulation of uric acid, which contributes to inflammation and tubulointestitial fibrosis in kidney disease, together with its six precursors have also been substantially reduced. The results in kidney samples demonstrated that in addition to beneficial effect in alleviating lipotoxicity through improving FAO efficiency, exercise also ameliorated diabetic induced inflammation and fibrosis via promoting BCAA catabolism and accelerating the elimination of uric acid. Together, the mass spectrometry-based metabolomics study is a powerful tool to investigate the regulatory effect of exercise on complex metabolic diseases. The results may provide informative insights into the underlying the mechanism of exercise on T2DM and T2DM induced complications.
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Vetter, Courtney Suzanne. "Time-course of elevated ethanol intake in adolescent relative to adult rats under continuous, voluntary-access conditions." Diss., Online access via UMI:, 2006.
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Tasker, Louisa. "Linking welfare and quality of scientific output in cynomolgus macaques (Macaca fascicularis) used for regulatory toxicology." Thesis, University of Stirling, 2012. http://hdl.handle.net/1893/9801.
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Cynomolgus macaques (Macaca fascicularis) are the most commonly used non-human primate for research and testing in Europe. Their principal use is in preclinical safety testing of new pharmaceuticals to assess risk of adverse effects, as indicated by changes in a core battery of physiological measures before human exposure. Regulatory studies are strictly controlled through legislation and codes of practices underpinned by the principles of humane science, the 3Rs; Replacement, Reduction and Refinement. Despite the link between good welfare and good science now universally made in codes of practice, legislation and the literature, there are few studies aimed at systematically examining the link and almost no quantitative data from cynomolgus macaques used for toxicology. The main aim of this thesis was to examine the link between Refinement, animal welfare and scientific output for this important animal model, piggy-backing on regulatory studies conducted by a large contract research organisation. In the laboratory, animal welfare is formally considered in terms of Refinement which has evolved to include both the reduction of negative welfare states and the proactive enhancement of positive welfare over the animal’s lifetime. A multidisciplinary approach to welfare assessment including measures of behaviour, physiology and physical health, and which built upon current unit procedures was undertaken to produce an overall assessment of welfare in cynomolgus macaques. Macaque facial expressions, vocalisations, activity and position in the home cage, body weight change, body condition and alopecia scores were found to be reliable indicators of welfare state and would be most feasible for care staff to monitor. The concept of quality of scientific output was defined in relation to toxicological findings and includes sensitivity, reliability and repeatability of individual measures in the core battery (e.g. heart rate, blood pressure, haematology, clinical chemistry and organ weights). The link between welfare and quality of scientific output was then systematically explored with Refinements to macaque use in regulatory studies. The first, a data mining study, undertaken to quantify the effects on biological data recorded from cynomolgus macaques, used in regulatory studies over an eight-year period as the CASE sponsor transitioned from single to permanent group housing, found the effects to be highly variable on individual parameters in the core battery and in some instances welfare-positive effects of group housing were confounded by concurrent changes in standard operating procedures. A further study of planned Refinements to macaque-care staff interaction through enhanced socialisation was found to help animals cope better with husbandry and scientific procedures and enhance quality of cardiovascular measures recorded at baseline. In light of these findings a number of recommendations are made including a framework of terms useful for measuring quality of scientific output, a welfare assessment framework and Refinements to husbandry and scientific procedures for cynomolgus macaques used in regulatory toxicology. Because of their capacity to suffer it is both ethically and scientifically important that macaque welfare is maximised and their use results in valid and reliable experimental outcomes informing on the safety and efficacy of new pharmaceuticals prior to human exposure.
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Gao, Jing, and 高晶. "Roles of VAD1.3 in spermatogenesis and fertilization." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B4852170X.
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Vad1.3 is an evolutionarily-conserved, testis-specific gene identified from a retinol-treated Vitamin A-deficiency (VAD) rat model. VAD1.3 is expressed throughout spermiogenesis at the acrosome of spermatids and epididymal spermatozoa, suggesting a role in acrosome biogenesis or acrosome reaction. The present study aimed to explore the functional role of VAD1.3 in spermatogenesis and sperm functions by the cellular and gene-knockout approaches.
Double immunofluorescent microscopy confirmed the co-localization of VAD1.3 and syntaxin 1 in mouse spermatids and spermatozoa. Deletion analysis of the Vad1.3 gene in transfected mouse spermatocyte GC2-spd and human cervical cancer HeLa cells revealed a polarized peri-nuclear/Golgi expression pattern for the N-terminal GFP-VAD fusion proteins which contain a bipartite nucleus localization (BNL) motif, but a nuclear expression pattern for the C-terminal GFP-VAD. The N-terminal sequences of VAD1.3 mediated its interaction with syntaxin 1, as demonstrated by both co-localization and co-immunoprecipitation studies. The full-length GFP-VAD co-localized with the Golgi markers and was redistributed into the endoplasmic reticulum after brefeldin A treatment, suggesting that VAD1.3 was recruited through the ER-Golgi-acrosome pathway.
Vad1.3+/- mice was previously generated by the conventional knockout approach. The heterozygous mice had normal spermatogenesis during postnatal days and adulthood (6-8 weeks). At the age of 8-19 months, 6 out of 17 heterozygous mice but no wild-type exhibited a decrease in the epididymal sperm count and testicular weight (p < 0.05). Histological analyses unveiled disarrangement of the seminiferous epithelium and sloughing of germ cells, predominantly spermatids, which was mediated partially by apoptosis as a higher percentage of TUNEL-positive cells were detected in these heterozygous mice (p < 0.05). This phenotype was associated with a decrease in the mRNA (p < 0.05) and protein levels of VAD1.3 in the testis.
Crossing of the Vad1.3+/- mice produced wild-type and heterozygous offspring in a ratio of 1:3, but no Vad1.3-/- mice were found. There was no significant difference between the heterozygous intercrosses and the wild-type intercrosses in the number of oocytes ovulated, the developmental rate of embryos from zygotes to blastocysts, the number of implantation site, resorption site or the offspring could result from defective fertilization between Vad1.3 null gametes rather than developmental lethality. The role of VAD1.3 in fertilization was supported by the inhibitory effects of the anti-VAD1.3 antibody on in vitro fertilization and progesterone-induced acrosome reaction. Immuno-staining revealed that VAD1.3 was present in the acrosome-intact spermatozoa but not in acrosome-reacted spermatozoa, indicating a role of VAD1.3 in ZP-binding or acrosome reaction rather than sperm-egg fusion. In oocytes VAD1.3 was distributed in the cytoplasm near the cortex. litter size. Only a few Vad1.3-/- embryos were found at the zygotic (3.7%) and 2-cell (3%) stages in the heterozygous intercrosses. These findings suggested that the absence of the Vad1.3-/-
In sum, VAD1.3 may play important roles in fertilization and spermatogenesis in mice. The BNL motif of VAD1.3 directs its Golgi expression and the N-terminal sequence of the protein mediates its interaction with syntaxin 1. The use of tissue-specific knockout approach may help to answer the functional role of VAD1.3 in future.published_or_final_version
Obstetrics and Gynaecology
Doctoral
Doctor of Philosophy
38
Agnelli, Silvia. "Regulation of amino acid catabolism in rats fed diets with different protein content." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/400005.
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Current lifestyle with high-energy diets and characterized by sedentary is triggering an alarming growth in obesity. Obesity along with metabolic syndrome- related co-morbidities (i.e. insulin resistance, atherosclerosis, sleep apnea, depression, asthma, hypertension and the alteration of blood lipid transport) are the most apparent consequence of the excess energy. Under conditions of excess dietary energy, the body cannot easily dispose of the excess amino-N against the evolutively-adapted schemes that prevent its wastage; thus ammonia and glutamine formation and urea excretion are decreased. High lipid and energy availability limit the utilization of glucose, and high glucose spares the production of ammonium from amino acids, decreasing the synthesis of glutamine and its utilization by the intestine and kidney. In contrast, high protein diets enhance protein synthesis and growth, and the synthesis of non-protein-N-containing compounds. But these outlets are not enough; consequently, less- conventional mechanisms are activated, such as increased synthesis of NO∙ followed by higher nitrite (and nitrate) excretion and changes in the microbiota.
In this study we studied how the initial phase of development of metabolic syndrome can affects the function of liver as main site of amino-N metabolism, and to determine whether doubling the protein content in the diet induced significant changes in enzyme of amino acids metabolism along intestine and on liver.
The common result obtained by these studies is that, both in case of hyperlipidic or hyperproteic diets, elimination of excess N is necessary but cannot be easily carried out through the metabolic pathways/tissues we evaluated, although possible alternative pathways have been taken into consideration.L’estil de vida actual amb les dietes d'alt contingut energètic, i caracteritzat pel sedentarisme, està provocant un creixement alarmant de l'obesitat. L'obesitat, juntament amb les comorbiditats relacionades amb la síndrome metabòlica (és a dir, resistència a la insulina, aterosclerosi, apnea del son, depressió, asma, la hipertensió i l'alteració del transport de lípids en la sang) són la conseqüència més evident de l'excés d’energia. En condicions d'excés d'energia de la dieta, el cos no pot eliminar ràpidament l'excés d'amino-N contra els esquemes adaptats evolutivament i que impedeixin el seu deteriorament; així, la formació d'amoníac i de glutamina i l'excreció d'urea disminueixen. Els elevats nivells de lípids i de la disponibilitat d'energia limiten la utilització de la glucosa, i nivells elevats de glucosa estalvia la producció d'amoni a partir dels aminoàcids, disminuint la síntesi de glutamina i la seva utilització per l'intestí i el ronyó. En contrast, les dietes d’elevat contingut en proteïnes incrementen la síntesi de proteïnes i el creixement, i la síntesi de compostos que contenen N i no són proteïnes. Però aquests mecanismes no són suficients i en conseqüència, s'activen mecanismes menys convencionals, com ara augment de la síntesi de NO ∙ seguides per l’augment del nitrit (i nitrat) i la seva excreció, juntament amb canvis en la microbiota. En aquest treball es va estudiar com la fase inicial de desenvolupament de la síndrome metabòlica pot afectar la funció del fetge com lloc principal del metabolisme d'amino-N, i per determinar si la duplicació del contingut de proteïnes en la dieta induïa canvis significatius en els enzims del metabolisme d'aminoàcids al llarg intestí i al fetge. El resultat genèric obtingut per aquests estudis és que, tant en el cas de que la dieta sigui hiperlipídica o hiperproteica, l'eliminació de l'excés de N és necessària, però no es pot dur a terme fàcilment a través de les vies metabòliques / teixits que avaluem, tot i les possibles vies alternatives s'han tingut en consideració.
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Escoda, Francolí Jaume. "Efecto de la matriz de beta-fosfato tricálcico con fibronectina en la reparación de defectos óseos críticos: estudio experimental del potencial de regeneración ósea y su aplicabilidad clínica." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667962.
Full textAbstract:
Estudio experimental, prospectivo y controlado en el que se incluyeron 30 ratas Sprague-Dawley, machos adultos, ex-reproductivos, de 14 semanas de edad y peso entre 250 y 300 g. Los animales se distribuyeron de forma aleatoria a los grupos de estudio mediante una tabla de aleatorización y se recogieron datos en situación basal y a las 6 y 8 semanas de la colocación de los injertos. Se utilizó un defecto de tamaño crítico en la calota craneal de la rata, ya que se trata de un modelo estándar, ventajoso desde el punto de vista económico y adecuado para evaluar la formación ósea en defectos óseos craneales. Las trepanaciones craneales de 5 mms de diámetro se efectuaron en cada lado del cráneo y se les injertaba según la tabla de aleatorización β-FTC con o sin Fn en un lado y nada en el lado contralateral (control); siempre junto a una membrana de colágeno de bovino nativo para evitar el colapso del espacio por el rápido crecimiento del tejido blando. Todos los animales recibieron fluorocromos de oxitetraciclina una semana más tarde, además de 1 dosis de 10 mg/kg de calceina 1 día antes de la eutanasia ambas por via subcutánea, con el fin de estudiar las muestras mediante microscopia de fluorescencia. Los animales fueron sacrificados por exposición a CO2 a las 6 y 8 semanas tras la intervención quirúrgica en función del grupo al que fueron asignados aleatoriamente.
Se evaluó histomorfométricamente a las 6 y 8 semanas con microscopio óptico, cámara digital, lápiz óptico y análisis de la imagen por medición digitalizada con dos programas informáticos de su potencial regenerativo óseo en el área aumentada. Los análisis se efectuaron con el paquete estadístico R v3.12 (Development Core Team 2008). Se estableció un nivel de significación estadística de P < 0,05.
En los resultados destacamos que el tejido ganado (TG) en el área diana era significativamente mayor en los dos grupos de tratamiento que en los controles. No se observaron diferencias estadísticamente significativas entre ambos grupos de tratamiento activo, excepto en el tejido ganado global a las 8 semanas. En la comparación en mm2 entre los grupos β-FTC-Fn y β-FTC a las 8 semanas se observa una diferencia estadísticamente significativa a favor del grupo β-FTC-Fn.
En el grupo de β-FTC-Fn, el porcentaje de TG, definido como la suma de matriz de hueso mineralitzada (MHM) y sustituto óseo (SO), mostraba un aumento significativo en el área diana a lo largo del estudio, en tanto que en el grupo de β-TCP sin Fn parecía estabilizarse a las 6 semanas, sin que se detectara ningún aumento significativo posterior.
Los cambios en la regeneración ósea según los biomateriales utilizados para el relleno de los defectos y el tiempo de exposición, también indican un efecto más favorable para la matriz con Fn, ya que el porcentaje de MHM en el área diana continuaba aumentando de la semana 6 a la semana 8 hasta doblar su cifra mientras que la matriz sin fibronectina mantenía prácticamente el mismo valor.
El uso de β-FTC recubierto con Fn mostró un efecto no significativo y levemente más efectivo que el ß-FTC sin Fn respecto al incremento del volumen de hueso regenerado en los defectos de tamaño crítico de calota de rata como modelo experimental, posiblemente permitiendo un proceso más eficiente de remodelado (mayor ganancia de tejido y mayor mineralización del tejido ganado a igualdad de tiempo).
No se encontraron diferencias claras entre β-FTC y β-FTC-Fn. Se necesitan estudios adicionales en que se extienda el período de seguimiento a más de 8 semanas o en períodos más cortos de 6 semanas para evaluar la capacidad osteogénica de β-FTC-Fn en la reconstrucción de defectos de calota de rata de tamaño crítico, así como estudiar la razón de crecimiento óseo de los defectos tratados mediante microscopio de fluorescencia.OBJECTIVE: This histomorphometric study compared bone regeneration potential of beta-tricalcium phosphate with fibronectin (β-TCP-Fn) in critical-sized calvarial defects (CSDs) in rats to assess whether fibronectin (Fn) improved new bone formation. MATERIAL AND METHODS: CSDs were created in 30 adult male Sprague Dawley rats, which were divided into four groups according to the time of euthanasia (6 or 8 weeks [wks] of healing) and type of filling (β-TCP-Fn/6 wks, β-TCP/6 wks, β-TCP-Fn/8 wks, β-TCP/8 wks). The primary variables related to new bone formation were augmented area (AA) and gained tissue (GT) (sum of mineralized bone matrix [MBM] and bone substitute [BS]). Secondary variables were the diameter of the defect, MBM, non-mineralized tissue (NMT), and BS. RESULTS: A total of 29 rats and 58 histological samples were evaluated, 28 (48.3%) samples obtained at 6 wks and 30 (51.7%) at 8 wks, homogeneously distributed between right and left sides. Thirteen (22.4%) were treated with β-TCP-Fn, 16 (27.6%) with β-TCP and 29 (50%) were controls. At 8 wks, histomorphometric analysis showed significant differences in AA using β-TCP and β-TCP-Fn vs controls (P = 0.001 and P = 0.005, respectively). Bone turnover expressed as % within the target area was slightly higher but not statistically significant in the β-TCP-Fn than in β-TCP (MBM) at 6 wks vs 8 wks (P = 0.067 and P = 0.335, respectively). Finally, total GT area in mm2 was higher using β-TCP-Fn as compared to β-TCP (P = 0.044). CONCLUSIONS: β-TCP-Fn was slightly but non-significantly more effective than β-TCP without Fn for improving the volume of regenerated bone in CSDs of rats, possibly allowing a more efficient bone remodeling process. This effect however should continue being investigated.
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Carney, Katharine W. "Expression patterns and functional roles of amphiregulin in murine CD4+ T cells." Thesis, Royal Veterinary College (University of London), 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.669191.
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Li, Zhuoming, and 李卓明. "Heme oxygenase-1 and endothelial dysfunction in the spontaneously hypertensive rat." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48521735.
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The endothelium is important for the regulation of vascular tone. In diseases like hypertension, the endothelial cells become dysfunctional. This dysfunction is characterized by nitric oxide (NO) deficiency, impairment of endothelium-dependent hyperpolarization (EDH) and the overwhelming production of endothelium-derived contracting factor (EDCF). Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, producing carbon monoxide(CO), bilirubin and free iron. Up-regulation of the inducible isoform (HO-1) of the enzyme lowers blood pressure in animals. The purpose of the present study was to investigate whether or not up-regulation of HO-1by the pharmacological agent hemin improves endothelial function in arteries of spontaneously hypertensive rats(SHR).
Twenty four hours after intraperitoneal injection of hemin (50mg/kg) in 36 weeks old SHR, the expression and activity of HO-1 were augmented, in both the endothelium and vascular smooth muscle. Hemin-treatment potentiated endothelium-dependent relaxations to the muscarinic agonist acetylcholine in both the aorta and the mesenteric artery, whereas the HO inhibitor protoporphyrin IX zinc (II) (ZnPP; 30 mg/kg) prevented the beneficial effect of hemin, suggesting that HO-1 induction improves endothelial function.
Hemin-treatment did not augment acetylcholine-induced NO-mediated relaxations, and did not alter the expression level of either phosphorylated eNOS (Ser1177) or total eNOS, suggesting that the improvement of endothelial function by HO-1 induction cannot be attributed to an increased bioavailability of NO.
In the mesenteric arteries, hemin treatment potentiated acetylcholine-evoked EDH-mediated relaxations in the presence of L-NAME and indomethacin. The IKCa channel blocker TRAM-34andthe Na+-K+-ATPase blocker ouabain significantly impaired these hemin-potentiated relaxations. NS309-induced TRAM-34-and ouabain-sensitive relaxations were enhanced by hemin-treatment. K+-induced ouabain-sensitive relaxations and the expression of Na+-K+-ATPase were increased by hemin-treatment. Taken in conjunction, these observations imply that the improved EDH-mediated relaxations by HO-1 induction is due to an improvement of IKCa-Na+-K+-ATPase pathway. Treatment with an antioxidant apocynin (50mg/kg) showed a similar effect as hemin, and the combined treatment with hemin and apocynin did not cause a greater improvement. In vitro treatment with bilirubin, enhanced EDH responses and K+-induced ouabain-sensitive relaxations. These observations suggest that the effect of HO-1 induction on EDH-mediated relaxations is possibly due to its antioxidant properties and the production of bilirubin.
In the aortae, hemin-treatment reduced endothelium-dependent contractions in response to acetylcholineor to a calcium ionophoreA23187. Production of reactive oxygen species (ROS) was suppressed by hemin-treatment, judging from the results of 2’,7’-dichlorodihydrofluoresein diacetate staining, dihydroethidium staining and lucigenin chemiluminescence, which was attributed to the decreased expressions of NADPH oxidase-2 (Nox2) and cyclooxygenase-1(COX-1). The production of prostacyclin was decreased, which was explained by a lower expression of COX-1. Contractions to vasoconstrictor concentrations of prostacyclin and its mimetic iloprost were attenuated, suggesting that the responsiveness of thromboxane-prostanoid receptors (TP receptors) to prostacyclin was decreased by hemin-treatment. The effects of HO-1 on the suppressed production of ROS and prostacyclin, and the decreased responsiveness of TP receptors, contribute to its inhibitory role on EDCF-mediated response.
Thus, up-regulation of HO-1 improves endothelial function in the SHR by potentiating EDH response and impairing EDCF.published_or_final_version
Pharmacology and Pharmacy
Doctoral
Doctor of Philosophy
42
Sleep, Ronquillo Eduard. "Molecular and cellular mechanisms of heart regeneration in zebrafish." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7216.
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In contrast to mammals, zebrafish do have the ability to regenerate their heart after injury. A better understanding of how regenerationcompetent species do so should help developing strategies to enhance human cardiac regeneration. Here, by genetic lineage-tracing using an inducible Cre/lox system, we show that newly formed cardiomyocytes arise from the proliferation of differentiated heart muscle cells. These results argue against a significant contribution of stem or progenitor cells in this process. Our microarray and electron microscopy data provide evidence that cardiomyocyte proliferation is accomplished by limited cardiomyocyte dedifferentiation and increased expression of cell cycle regulators. One of these genes, polo-like kinase 1 (plk1), is upregulated in the regenerating area of the zebrafish heart and, by specifically inhibiting plk1 activity, we show that it is essential for regeneration. We have also identified a series of additional transcripts differentially expressed during zebrafish heart regeneration that warrant further research. The data presented here offer new insights to understanding heart regeneration in zebrafish and should provide useful information for cardiac repair in humans.De manera oposada als mamífers, els peixos zebra sí tenen la capicitat de regenerar el cor després d'una lesió. Entenent millor com s'ho fan les espècies capaces de regenerar hauria d'ajudar-nos a desenvolupar estratègies per a augmentar la capacitat de regeneració en humans. Aquí, mitjançant un sistema Cre/lox de traçat genètic de llinatge, mostrem que la creació de nous cardiomiòcits prové de la proliferació de cèl·lules cardíaques diferenciades. Aquests resultats discrepen amb una contribució significativa de cèl·lules mare o progenitores en aquest procés. Les dades obtingudes de microarray i de microscòpia electrònica evidencien que la proliferació de cardiomiòcits és deguda a una dediferenciació parcial i a un increment de l'expressió de gens que promouen el cicle cel·lular. Un d'aquests, el polo-like kinase 1 (plk1), augmenta d'expressió a l'àrea regenerant del cor de peix zebra i, un cop inhibida la seva activitat, mostrem que és essencial per a la regeneració. També hem identificat una sèrie adicional de trànscrits que s'expressen de manera diferencial durant la regeneració cardíaca en el peix zebra i que mereixen més investigació. Els resultats aquí presents profunditzen en la comprensió de la regeneració cardíaca en el peix zebra i ofereixen informació rellevant per la teràpia cardíaca en humans.
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Fellows, Matthew R. "Spatiotemporal tuning for position and velocity in primate primary motor cortex neurons /." View online version; access limited to Brown University users, 2005. http://wwwlib.umi.com/dissertations/fullcit/3174598.
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Wickens, Nicolas John. "Histopathological changes in male wistar rats maintained on a water-based sutherlandia frutescens extract." Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/4742.
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In this study a standardized 46 week chronic drinking water toxicity protocol was used to elucidate the toxic potential of Sutherlandia frutescens (S. frutescens) using histopathologic, morphometric and transmission electron microscopic analysis. The histopathologic changes in the duodenum, heart, kidney, liver, lung, pancreas and spleen of male Wistar rats were evaluated. Fifty-four rats were randomly divided into four groups: Group 1 – Normal diet control (ND control), n=7, Group 2 – Normal diet + plant extract (ND + p), n=9, Group 3 – High fat diet control (HFD control), n=19Group 4 – High fat diet + p (HFD + p), n=19In the high fat group male Wistar rats were fed ±55 g/day of a specialised high fat diet over a 46 week period to induce obesity and an insulin resistant state. The treatment groups (groups 2 and 4) received a dose concentration of a tea extract of the S. frutescens plant in their drinking water daily. This study showed that the consumption of S. frutescens significantly reduces weight gain in male Wistar rats on a chronic high fat diet (p≤0.001 vs. HFD control group). S. frutescens appears to propagate periportal and centrilobular glycogen storage in rat hepatocytes in the experimental groups as exemplified by a significantly (p≤0.0001 vs. control groups) increased incidences of Periodic Acid Schiff (PAS) positive staining S. frutescens also reduced intracellular lipid accumulation as made evident by the significantly lower incidence of epicardial adipose tissue (EAT), hepatic steatosis and pancreatic interstitial fat. Obesity was associated with increased fibrotic lesions such as myocardial perivascular fibrosis, centrilobular hepatic fibrosis and pancreatic periductal fibrosis. Obesity associated hypertension contributed to the widespread and significant increase in the average lesion severity of arterial congestion in all organs in the HFD control group. Pulmonary infection was equally prevalent in all rats. Despite the complex histopathology in all groups, differences in the control groups, such as, the presence of a conservative polymorphonuclear leukocyte (PMNL) infiltration, substantial intra-alveolar oedema and focal arterial wall hypertrophy in the control groups was highly suggestive of Sendai viral infection. However histopathologic evidence, in the treatment groups, suggested chronic recurrent viral infection with superimposed Mycoplasma pulmonis (M. pulmonis) bacterial infection. The impact of advanced suppurative pulmonary infection was widespread and exemplified by increased lesion incidences of spontaneous murine progressive cardiomyopathy (MCP) and spontaneous chronic progressive nephropathy (CPN) among others. In conclusion S. frutescens administered for 46 weeks to male Wistar rats significantly lowered intracellular lipid accumulation and obesity associated myocardial, renal, hepatobiliary, pulmonary and pancreatic histopathology. Moreover, duodenal, cardiovascular, hepatobiliary, pulmonary, renal, pancreatic and splenic tissue did not show histopathologic evidence of direct plant extract associated toxicity or carcinogenicity.
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Hsu, Charlie Chun. "Isolation, characterization, and diagnosis of murine noroviruses, a newly recognized pathogen of mice." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4790.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007."December 2007" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.
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Brown, Steven J. "Immunological studies of a glycosylation based mouse model of colitis /." Connect to thesis, 2004. http://eprints.unimelb.edu.au/archive/00000788.
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Thesis (Ph.D.)--University of Melbourne, Dept. of Gastroenterology and the Immunology Research Centre St. Vincents Hospital & Dept of Medicine, 2004.Typescript (photocopy). Includes bibliographical references (leaves 309-343).
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歐穗欣 and Sui-yan Au. "Characterization of the mouse myosin va cargo-binding domain." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31227107.
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Gao, Jing, and 高晶. "Effect of acupuncture on the spermatogenesis of heat-treated rodent testis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41291001.
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Al, Jothery Aqeel Handil Tarish. "Lactation and oxidative stress in small mammals." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=215095.
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During peak lactation female mammals reach a limit in their maximal sustained energy intake (SusEI). The causes of such limits is disputed. In this thesis, I examined the causes of the limits on SusEI at peak lactation, and then explored the consequences of such limits for reproductive performance. Finally I tested a possible physiological mechanism that may underpin the trade-off between reproduction and somatic protection (the oxidative stress theory). To answer these questions, I studied reproductive performance and oxidative stress in two lines of mice previously selected for high and low food intake (MH and ML, respectively). I found that these mice reached a plateau in their food intake around day 13 of lactation. In support of the heat dissipation limits theory, reproductive performance in the MH mice was significantly higher than that of the ML mice. Oxidative damage is expected to be higher among lactating individuals. Moreover, lactating mice with greater reproductive performance are also predicted to experience more oxidative damage. By measuring multiple-markers of oxidative damage and protection in different tissues, I found that lactation resulted in reduced oxidative damage in both brain and serum. Additionally, it did not increase oxidative damage to proteins and DNA in liver. Moreover, multiple measures of oxidative stress in the mammary gland were not significantly different between mice with different reproductive effort. Furthermore, I found that lactating mice with greater reproductive performance (litter size and litter mass) had reduced protein damage in their livers and upregulated protection (HSP70) in their brains. These results were inconsistent with the oxidative stress theory. Finally, I employed a novel approach to assess oxidative stress differences with metabolomics analysis. I found that lactation resulted in significant differences in the metabolome. By focusing on the metabolites that are related to vi oxidative stress, I found that most of these metabolites measured in livers and brains were not affected by lactation which provides more evidence against the oxidative stress theory. My results provide support for the heat dissipation theory as a mechanism explaining the limits on reproductive performance. Moreover it provides comprehensive information against oxidative stress as a mediator of life history trade-offs.
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Gao, Jing. "Effect of acupuncture on the spermatogenesis of heat-treated rodent testis." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41291001.
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