Tesi sul tema "Animal models"
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Yalçin, Biannaz. "QTL mapping in animal models". Thesis, University of Oxford, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410716.
Testo completoMazzola, Carmen. "Neuropharmacology and Behaviural Animal Models". Thesis, Universita' degli Studi di Catania, 2011. http://hdl.handle.net/10761/93.
Testo completoThe study of human disease often involves performing physiological and pharmacological experiments in animal models. Generally, experimental results obtained in these models are extrapolated to the human situation, providing new insights into disease mechanisms and treatment options. To be able to reliably extrapolate results obtained in animal experiments, it is important to consider the validity of the animal model used, i.e., the extent to which the model mimics the disease. This validity is often characterized by 1) the resemblance in symptoms (face validity), 2) shared etiology and underlying pathophysiological mechanisms (construct validity), and 3) similarity of pharmacological responses (predictive validity). Hence, the analysis of face, construct, and predictive validity of animal models constitutes a very important aspect in the study of disease physiology and pharmacology.
Klingström, Jonas. "Hantaviruses : animal models, immunology and pathogenesis /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-071-0/.
Testo completoThomas, Kurt Florian Patrick. "Animal models of retroviral neurological diseases". Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39882.
Testo completoIn a second project, pathological effects associated with a disease determining region contained in the gp70 envelope protein of the Cas-Br-E murine leukemia virus, were investigated. In infected mice, this virus causes hind limb paralysis and a spongiform myeloencephalopathy with gliosis and neuronal loss. Stably transfected fibroblasts that express gp70 were injected into the brains of mice, and the animals were examined for histopathological changes attributable to the effects of gp70. While gp70 protein was detected at the implantation site, this was not accompanied by any specific histological changes. These data suggest that the intracerebral expression of the neuropathogenic gp70 protein alone is not sufficient to cause disease, and lend indirect support to a model according to which gp70 causes disease by altering the cytokine profile of infected mononuclear cells in the central nervous system.
Lydall, Emma Sian. "Palatability and animal models of schizophrenia". Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/55071/.
Testo completoWarren, Nicholas David. "Some stochastic models for animal territories". Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312289.
Testo completoJusof, Felicita Fedelis. "Tryptophan-catabolising enzymes in animal models". Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/13697.
Testo completoZemp, Franz Joseph, e University of Lethbridge Faculty of Arts and Science. "The bystander effect : animal and plant models". Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2008, 2008. http://hdl.handle.net/10133/685.
Testo completoxiv, 141 p. : ill. ; 29 cm.
Birrell, Mark Andrew. "Characterisation of animal models of airway eosinophilia". Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408172.
Testo completoNwosu, V. U. "Peroxisome enzymes in animal models of obesity". Thesis, University of Wolverhampton, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380662.
Testo completoDegrassi, Anna. "MRI studies of animal models for osteoarthritis". Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621774.
Testo completoAllcroft, David John. "Statistical models for short-term animal behaviour". Thesis, University of Edinburgh, 2001. http://hdl.handle.net/1842/11132.
Testo completoHitchen, Barry. "Behavioural evaluation of animal models of diabetes". Thesis, Ulster University, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744769.
Testo completoAtanasova, Nina A. "Animal Models and the Unity of Neuroscience". University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406820028.
Testo completoBierman, Stijn Martinus. "Spatio-temporal models in animal population dynamics". Thesis, University of Aberdeen, 2004. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU195633.
Testo completoLai, Edwin W. "Molecular characterization of animal models of pheochromocytoma". Connect to Electronic Thesis (CONTENTdm), 2009. http://worldcat.org/oclc/454140444/viewonline.
Testo completoTalbot, Nicola A. "Obesity, inflammation and insulin resistance in skeletal muscle". Thesis, Royal Veterinary College (University of London), 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618327.
Testo completoSchofield, Matthew R., e n/a. "Hierarchical capture-recapture models". University of Otago. Department of Mathematics & Statistics, 2007. http://adt.otago.ac.nz./public/adt-NZDU20080129.161029.
Testo completoGlennie, Richard. "Incorporating animal movement with distance sampling and spatial capture-recapture". Thesis, University of St Andrews, 2018. http://hdl.handle.net/10023/16467.
Testo completoTelkes, Ilknur. "Phase Validation Of Neurotoxic Animal Models Of Parkinson". Master's thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614866/index.pdf.
Testo completos disease (PD) is characterized by the progressive loss of dopaminergic nigral neurons and striatal dopamine resulting in serious motor deficits but also some non-motor anomalies. Animal models of human neurodegenerative diseases are essential for better understanding their pathogenesis and developing efficient therapeutic tools. There are many different PD models, however, none of them is fully reproducing all the symptoms of the disease. In addition, different investigators use different behavioral measures which makes even more difficult to compare and evaluate the results. The aim of the present study was to compare motor and cognitive deficits in two most common models of PD: the Rotenone and 6-OHDA model, using a large battery of neurological tests and a probabilistic learning task. To the best of our knowledge, this is the first study to examine the effects of bilaterally induced Rotenone and 6-OHDA through behavioral test batteries assessing the cardinal motor symptoms and the cognitive abnormality of Parkinson&rsquo
s Disease in the same rat population. Also, the present study is unique on the basis of providing both longitudinal observations of behaviour in the same treatment group and the cross-sectional comparisons of the behavioural responses between different groups. In the current study, the neurotoxins were applied at relatively low doses of 3-4 &mu
g, bilaterally to the substantia nigra pars compacta (SNpc). Experiments were conducted on 50 young-adult male Sprague&ndash
Dawley rats randomly assigned to five experimental groups: Rotenone, 6-OHDA, vehicle (DMSO/Saline), and the intact control. The neurological tests included locomotor activity,catalepsy, rearing, stepping, and rotarod/accelerod tests. They were applied prior to, and on days 4-7-10-20-40-150 while the learning task was applied 49 days after drug infusion.During the first 2 postoperational months, both neurotoxins produced progressive deterioration in motor performance but showing no effect on cognitive functions. Five months after the surgery, regression of bradykinesia but persistence of sensorimotor deficits was noted. The tests&rsquo
results suggest different susceptibility of different motor functions to the degeneration of nigro-striatal (N-S) pathway. So, different tests were demonstrated to have different power in detecting similar motor deficits.
Brenner, Eiliv. "Glutamate related metabolism in animal models of schizophrenia". Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for nevromedisin, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-13875.
Testo completoGlutamat-relatert metabolisme i dyremodeller for schizofreni Schizofreni er en alvorlig psykisk lidelse som preges av psykotiske symptomer som vrangforestillinger, hallusinasjoner og andre symptomer som sosial tilbaketrekning og svekket sosial fungering. Epidemiologiske studier har vist at livstidsrisikoen er 0,5-1% i det meste av verdens befolkning. Etiologien og patofysiologien til schizofreni er ikke kjent. De to viktigste patofysiologiske teoriene for schizofreni har vart den såkalte dopaminteorien og glutamatteorien. Disse predikerer henholdsvis økt aktivitet i dopaminerge systemer og redusert aktivitet i visse glutamaterge systemer. Resultater fra studier i den senere tid tyder også på at det finnes forandringer i cytoskjellettet ved schizofreni, for eksempel i mikrotubuliassosierte proteiner. De fleste schizofrenisymptomer er unike for menneskelig atferd. Å kunne reprodusere schizofreni i en dyremodell er derfor vanskelig. Dyremodeller er likevel et viktig verktøy for a identifisere patofysiologiske mekanismener bak schizofreni, og for a komme fram til nye medisiner. Denne avhandlingen inneholder fire publikasjoner hvor vi studerte dyremodeller for schizofreni. I tre av dem ble NMDA-reseptorantagonisten MK-801 brukt til a redusere glutamaterg nevrotransmisjon i rotter. Tre forskjellige forsøksoppsett ble brukt: En enkelt injeksjon av en høy dose MK-801, daglige injeksjoner med høy konsentrasjon i til sammen seks dager, og daglige injeksjoner med en lavere dose MK-801 i seks dager. Den fjerde studien beskriver glutamatrelatert metabolisme ved ustabile mikrotubili. Dette gjorde vi ved å undersøke ”knock out” mus hvor genet for det mikrotubiliassosierte proteinet STOP (Stable Tubule Only Peptide) var satt ut av funksjon. Vi undersøkte glutamatrelatert metabolisme i alle disse modellene. Hjerneekstrakter fra flere hjerneomrader ble analysert med HPLC (High Performance Liquid Chromatography), 13C- og1H-magnetisk resonansspektroskopi. Ved a injisere 1-13 C merket glukose og 1,2- 13 C merket acetat kunne vi se forskjell pa nevron- og astrocyttmetabolisme. En enkelt dose med 0,5 mg/kg kroppsvekt MK-801 skapte flest metabolske forskjeller i temporal lappen. Her var det okte totale mengder av glutamat og glutamin, og dessuten okt innmerkning fra [1-13C]glukose. Vi så liknende forskjeller da vi injiserte 0,1 mg/kg MK-801 i flere påfølgende dager. Da rottene derimot ble injisert med 0,5 mg/ MK-801, fant vi metabolske forskjeller i cingulate-, retrosplenial- og frontalcortex. Her var det ogsa en økt totalmengde av glutamat, men innmerkning fra bade [1-13C]glukose og [1,2-13C]acetat var redusert i flere metabolitter sammenlignet med kontrolldyrene. Reultater i artikkel 4 viser reduserte mengder av bade totalglutamin og glutamin merket fra [1,2-13C]acetat i cerebrum til STOP ”knock out” mus. Når vi sammenligner resultatene våre med data fra studier av pasienter med schizofreni, ser det ut til at repeterte injeksjoner av en høy dose MK-801, kan vare en god dyremodell for schizofreni i et tidlig stadium. STOP ”knock out” modellen viser lignende metabolske forskjeller som hos pasienter med kronisk schizofreni, og derfor kanskje en god dyremodell for mer langtkommen schizofreni. Resultatene fra studiene i denne oppgaven viser at både blokkering av NMDA-reseptoren og ustabile mikrotubili, forstyrrer glutamatglutamin syklus, og det er fristende a påstå at interaksjonen mellom astrocytter og nevroner er undervurdert i schizofreniforskning.
Duncan, Warwick John, e n/a. "Sheep mandibular animal models for dental implantology research". University of Otago. School of Dentistry, 2005. http://adt.otago.ac.nz./public/adt-NZDU20060707.144214.
Testo completoNilsson, Tatjana. "Amyloid precursor protein: cellular studies and animal models /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-832-0/.
Testo completoPålsson, Erik. "Cognitive function studied in animal models of schizophrenia /". Göteborg : Dept. of Pharmacology, Institute of Neuroscience and Physiology, 2006. http://hdl.handle.net/2077/775.
Testo completoArlinde, Christina. "Gene expression profiling in animal models of alcoholism /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-133-4/.
Testo completoNordquist, Niklas. "Genetic Studies of Rheumatoid Arthritis using Animal Models". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5117-9/.
Testo completoRostami, Elham. "Traumatic brain injury in humans and animal models". Doctoral thesis, Stockholm : Reproprint AB, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-212088.
Testo completoIngram, E. "Glial glutamate transporters in animal models of epilepsy". Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604933.
Testo completoGilder, Michael Frederick James. "Molecular investigations in animal models of Huntington's disease". Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325046.
Testo completoDeiana, Serena. "Animal models for novel drug treatments of tauopathies". Thesis, University of Aberdeen, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446226.
Testo completoMatthews, Keith D. "Animal models of affective psychopathology : depression and reward". Thesis, University of Aberdeen, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319857.
Testo completoDevadasu, Venkat Ratnam. "Evaluation of antioxidants encapsulated nanoparticles in animal models". Thesis, University of Strathclyde, 2011. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=16829.
Testo completoSelvan, Nithya. "Reductionist animal models to probe protein O-GlcNAcylation". Thesis, University of Dundee, 2015. https://discovery.dundee.ac.uk/en/studentTheses/6034adb4-fc6a-4c47-ade6-74e0b18d4297.
Testo completoBicer, Sabahattin. "Efficacy/toxicity studies of amiodarone in animal models /". The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486546889383936.
Testo completoLopes, Vanessa Ferreira. "Caracterização funcional das diferentes linhagens de modelos murinos para distrofias musculares". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-04052011-150431/.
Testo completoMuscular dystrophies are a heterogeneous group of genetic diseases characterized by a progressive and irreversible degeneration of the muscles. Dystrophic mouse models, like the mdx, SJL/J, Largemyd and Lama2dy-2J/J, are important tools for studying these diseases. The aim of this study was to establish parameters for functional evaluation aiming its use to elucidate the clinical benefits of future therapies. Thus, we evaluated the four strains of dystrophic mice, at different ages, and compared to normal control. Standardized tests consisted of forced swimming, evaluation of resistance/balance by forelimb and four members, walking on suspended platform, suspension by the tail, grip strength and rota rod. We observed the existence of different patterns of strength, endurance, coordination and learning / memory over the lifetime of each strain, which allowed tracing parameters to be used in future studies of cell and pharmacology therapies.
Pereira, Danilo Florentino. "Metodologia para estimativa de bem-estar de matrizes de frango de corte utilizando monitoramento digital e construção de modelos de simulação". [s.n.], 2003. http://repositorio.unicamp.br/jspui/handle/REPOSIP/257219.
Testo completoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Agricola
Made available in DSpace on 2018-08-05T13:34:42Z (GMT). No. of bitstreams: 1 Pereira_DaniloFlorentino_D.pdf: 4613464 bytes, checksum: f69737da451ffc0d2ceecda7fcdacd9b (MD5) Previous issue date: 2003
Resumo: Esse trabalho propôs o uso de ferramentas de precisão para o monitoramento de matrizes pesadas que sirvam para a coleta de dados comportamentais que contribuem para a predição de bem-estar. Foram conduzidos dois experimentos em câmara climática onde se observaram os efeitos do ambiente, idade e linhagem, nos comportamentos expressos pelas matrizes. Para a gestão dos dados e das informações, foi desenvolvido um software que faz a interface do usuário com um banco de dados relacional FireBird®. Para o monitoramento dos comportamentos, utilizaram-se duas tecnologias de precisão: câmeras de vídeo e identificação eletrônica. Os resultados das análises exploratórias de Componentes Principais e Gráficos de Interação mostraram diferenças importantes nos comportamentos em função dos fatores experimentais idade, linhagem e ambiente. Os resultados foram confirmados através de teste de médias de Tukey e modelos de Regressão Dummy, que utiliza variáveis contínuas e categóricas. A freqüência de ocorrências dos comportamentos Ciscar, Deitar e ida ao Ninho, bem como o tempo médio de duração dos comportamentos Limpar Penas e presença no Bebedouro foram modelados e podem ser usados para ajudar a avaliar o bem-estar das matrizes em alojamentos. Os resultados permitem afirmar que mesmo em amplitudes pequenas de temperatura e amônia, os comportamentos são afetados pelo ambiente e contribuem para o entendimento do bem-estar de matrizes pesadas. A tecnologia associada à metodologia aplicada foi eficiente no registro das informações de produção, permitindo estudar a influência do ambiente no comportamento das matrizes
Abstract: This research proposed the use of precision tools for monitoring female broiler breeders in order to register behavior pattern data that may contribute for welfare prediction. Two experiments were conduced inside an environmental chamber where environment, age and breeding effect in the female broiler breeder behavior were observed. For managing the recorded data and information a software was developed in order to make a user¿s interface with the relational database called FireBird®. For monitoring behavior two precision technologies were used: video camera recording and electronic identification. Exploratory analysis of Principal Components Results and Interaction Graphs showed important differences in the behavior related to the experimental factors such as age, breeding and environmental data. Results were confirmed through average analysis as Tukey Test and Dummy Regression Model that uses continuous and categorical variables. The frequency of behavior occurrence such as foraging, lying down and moving to the nest, as well as the behavior average duration time in preening, staying at the drinker were modeled, and can be used to help evaluating intensive housed broiler breeder welfare assessment. Results allow stating that even in small amplitude of ambient temperature and housing ammonia concentration variation behavior pattern is affect by the environment, and it may contribute for understanding broiler breeder¿s welfare. The technology associated to the methodology was efficient in allowing the study of the environment effect in female broiler breeder behavior
Doutorado
Construções Rurais e Ambiencia
Doutor em Engenharia Agrícola
Gonçalves, Ana Sofia Ribeiro. "Validação do modelo de ansiedade Light / Dark Exploration Test em ratos Wistar". Master's thesis, Instituto Superior de Psicologia Aplicada, 2007. http://hdl.handle.net/10400.12/558.
Testo completoOs modelos elevated plus-maze e light/dark são amplamente utilizados no estudo de compostos ansiolíticos e dos mecanismos neurobiológicos de ansiedade. O elevated plus-maze (EPM) e o open-field (OF) são testes validados para avaliação da ansiedade em ratos e ratinhos. O teste ligh/dark (LD) também é utilizado nos modelos de ansiedade, no entanto, só foi validado para modelos em ratinhos. Para validar o teste LD como um modelo de ansiedade em ratos avaliaram-se os parâmetros: validade construtiva, validade exterior e validade preditiva. Estes parâmetros foram analisados através de avaliações comportamentais. neuroquímicas e hormonais na presença e ausência de compostos ansiolíticos, e de uma análise comparativa destas avaliações nos testes EPM e LD. Foi ainda estabelecida uma análise comparativa dos dados comportamentais entre o teste OF e os testes EPM e LD. Cada rato (estirpe Wistar) (200-220g) foi colocado no centro do aparelho OF e deixado a explorá-lo durante 20 minutos. Os primeiros 5 minutos foram utilizados para avaliar os comportamentos de ansiedade e os últimos 15 minutos para avaliar a actividade locomotora. Uma semana depois cada rato foi colocado no aparelho EPM (n=6) ou no aparelho LD (n=6) durante 5 minutos. Foram ainda submetidos a estes testes, na mesma ordem, indivíduos tratados com diazepam (0,5mg/kg) (n=6 para cada teste) e propranolol (10mg/kg) (n=6 para cada teste) numa solução de soro fisiológico de 2ml/kg e indivíduos tratados com soro fisiológico (n=6 para cada teste). As sessões experimentais foram registadas por uma câmara de vídeo colocada um metro acima do aparelho e as medidas comportamentais foram registadas e analisadas utilizando o software Noldus Observer. Imediatamente após cada sessão de EPM ou LD os animais foram sacrificados, tendo-se recolhido sangue para doseamento hormonal e dissecado a amígdala e o hipocampo para posterior análise neuroquímica. As concentrações de dopamina (DA), serotonina (5-HT) e dos seus metabolitos foram quantificadas por cromatografia líquida de alta performance combinada com detecção electroquímica. Os níveis de corticosterona no plasma foram medidos por ensaio imunoenzimático. Os resultados comportamentais mostram que os testes EPM e LD induzem respostas comportamentais semelhantes sugerindo que os comportamentos registados nos testes reflectem o mesmo estado psicológico - ansiedade. Esta generalização das respostas comportamentais em diferentes modelos de ansiedade contribui para uma possível validade construtiva do modelo LD para ratos. No entanto, este parâmetro de validade é comprometido pelos resultados neuroquímicos destes animais uma vez que não revelam alterações nas concentrações das monoaminas nas áreas cerebrais analisadas. Por outro lado, a semelhança dos resultados neuroquímicos nos testes LD e EPM indica que estes testes são muito influenciáveis pelas condições e procedimentos usados, uma ideia reforçada pelo aumento dos níveis de serotonina no hipocampo dos indivíduos injectados com soro. Estes resultados evidenciam a importância e a necessidade de uniformizar protocolos e de controlar cautelosamente os procedimentos em todas a etapas da experiência, para possibilitar a utilização destes modelos como indutores de ansiedade. O diazepam e o propranolol não causaram efeitos ansiolíticos nas respostas comportamentais, no entanto, não podemos esquecer que as doses aplicadas são inferiores às utilizadas noutros estudos que mostraram efeitos ansiolíticos. Por outro lado, os dados relativos aos efeitos dos agentes ansiolíticos mostram que os fármacos têm efeitos opostos no rato, tanto no EPM como no LD. Além disso, esse efeito reflecte-se a nível comportamental e neuroquímico. A nível comportamental o diazepam induziu uma redução do estado de alerta enquanto que o propanolol induziu um aumento do estado de alerta. A nível neuroquímico o diazepam induziu uma diminuição dos níveis de serotonina no hipocampo ao contrário do propranolol que induziu um aumento dos níveis de serotonina na mesma área cerebral. Estes resultados sugerem que o propranolol parece ter um efeito ansiogénico originado pela manipulação dos animais aliada ao bloqueio, pelo propranolol, dos processos de reconsolidação da memória activa, o que eliminou os efeitos de habituação ao stress induzido pela manipulação. Estas alterações neuroquimicas foram observadas apenas nos ratos expostos ao EPM indicando que o EPM e o LD desencadeiam aspectos distintos de ansiedade. Estes resultados comprometem a validade preditiva do modelo mas os procedimentos realizados são insuficientes para concluir acerca deste parâmetro. Nas respostas hormonais produzidas por estes testes não foi verificado um aumento nos níveis de corticosterona após a exposição aos testes de ansiedade, no entanto, estes dados podem ter sido influenciados por aspectos da variação circadiana o que torna difícil inferir sobre o critério de validade exterior. A heterogeneidade das formas patológicas de ansiedade existentes toma difícil que um modelo de ansiedade reúna os 3 critérios de validade, no entanto, este trabalho indica que o modelo LD não é um modelo de ansiedade ideal para ratos. Os resultados deste estudo são mais uma contribuição para a evidência crescente da importância e necessidade de uma análise complexa baseada em observações comportamentais no aperfeiçoamento da credibilidade e sensibilidade destes modelos animais.
Van, Eeden Willem Daniel. "Human and animal classification using Doppler radar". Diss., University of Pretoria, 2005. http://hdl.handle.net/2263/66252.
Testo completoDissertation (MEng)--University of Pretoria, 2017.
Electrical, Electronic and Computer Engineering
MEng
Unrestricted
Cartón, García Fernando. "Myosin VB in intestinal pathogenesis". Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458251.
Testo completoMyosin VB is a molecular motor protein that uses the energy of ATP to move along actin filaments. It participates in the recycling endosomes trafficking in the subapical cytoplasmic region of non-polarized and polarized cells. It is highly expressed in the small and large intestine, where its role in the establishment of polarized function in enterocytes is also well known. Inactivating mutations of MYO5B have been associated with microvillus inclusion disease (MVID), a rare congenital disorder of the intestinal epithelial cells that presents with persistent life-threatening watery diarrhea. It is characterized by morphological enterocyte abnormalities such as microvillus atrophy and mislocalization of apical and basolateral protein transporters. The molecular pathology of the disease is not well known mainly due to the lack of animal models. In the present study, we report a versatile murine model with targeted inactivation of Myo5b. This model allowed us to generate and characterized a constitutive Myo5b knockout mice and a tamoxifen-inducible intestinal-epithelium-specific Myo5b knockout. In both cases, the mice closely resemble the phenotype of MVID patients, developing watery diarrhea and dehydration causing the death of the animal. Histological study of the intestine showed all the characteristic enterocyte defects observed in MVID patients, including microvillus atrophy and mislocalization of protein markers. Moreover, the inactivation of MYO5B also originated hyperproliferation of the intestinal crypts. Therefore, our mice constitute a useful model to further investigate the underlying molecular mechanism of this disease and to preclinically assess the efficacy of novel therapeutic approaches. In addition, hyperproliferation as well as loss of cell polarity, differentiation, and tissue architecture are hallmarks of advanced metastatic carcinomas and strongly correlate with poor patient prognosis. Specifically, for colorectal cancer, the third most common type of cancer worldwide, we have previously demonstrated that the loss of brush border MYO1A, also involved in cell polarity, promotes cancer progression and has tumor suppressor activity. Other studies have indicated a relationship between MYO5B inactivation and gastric cancer, promoting invasion and motility, but little is known regarding its role in colorectal cancer. To address this question, we have developed novel doxycycline-inducible in vitro models of MYO5B overexpression and downregulation. Moreover, we have generated MYO5B knockout Caco2-BBE cells using CRISPR/Cas9 technology. Our results showed changes in the polarization and differentiation of colon cancer cells, in agreement with previous observations in the normal intestine. Moreover, we have observed a relationship between MYO5B and the motility and invasion capacity of colon cancer cells, indicating a possible role of MYO5B in colon cancer progression. However, the effect of MYO5B loss in cell proliferation observed in our Myo5b knockout mice could not be confirmed in our models in vitro and in vivo, employing cell line-derived xenografts. In addition, using a tissue microarray containing triplicate samples from 155 primary Dukes C colorectal tumors, reduced MYO5B expression was found to be associated with shorter disease-free and overall survival of the patients. Moreover, poorly differentiated tumors showed significantly reduced expression of MYO5B. Collectively, our results indicate that MYO5B plays an important role in the differentiation of the normal intestinal epithelium and colon cancer cells, as well as a possible role in cancer progression promoting cell motility and invasion.
Groppo, Mônica Feresini 1965. "Efeito de uma membrana de PCL impregnada com hidroxiapatita em defeito ósseo induzido na calvária de ratos". [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288467.
Testo completoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O objetivo do presente estudo foi observar o efeito de uma membrana de nanofibras poliméricas a base de poli-epsilon-caprolactona (PCL), impregnadas ou não com hidroxiapatita (HA), na reparação óssea em defeitos críticos produzidos artificialmente na calvária de ratos. Foram utilizados 36 ratos, divididos aleatoriamente em seis grupos de seis animais. Para a indução do defeito ósseo padronizado foram realizadas duas perfurações, por meio de trefina de 3 mm de diâmetro, na calvária dos animais, uma em cada lado, sendo que o lado direito recebeu os tratamentos (HA ou PCL-HA) e os controles (coágulo ou PCL) foram feitos no lado esquerdo. Decorridos 30, 60 e 90 dias da cirurgia, os animais foram mortos por aprofundamento da anestesia. As cabeças foram submetidas à tomografia, considerando um voxel de 0.12 mm, com campo visual de 06 × 16 cm e tempo de aquisição de 40s. Foram utilizados 120 kV, 8 mA e 36.12 mA/s na aquisição. Os diâmetros dos orifícios foram medidos por meio do software Invesalius 3.0. As cabeças foram fixadas com solução de formol tamponado (pH 7,2) em tampão fosfato de sódio a 0,1 M, durante 72 horas e submetidas à descalcificação em solução de EDTA a 7% e formol a 5% até verificação de completa descalcificação (aproximadamente 30 dias). Cortes semi-seriados de 7 ?m foram corados por Hematoxilina-Eosina e foram observadas as características histológicas do processo de cicatrização óssea nas lâminas nos diferentes tempos do estudo. A comparação quantitativa das medidas dos orifícios obtidas com a tomografia foi feita pelo teste de Kruskal-Wallis (teste de Dunn como post hoc), considerando um nível de significância de 5%. As imagens tomográficas revelaram uma tendência de redução do volume do orifício ao longo do tempo, a qual foi maior após 90 dias para todos os tratamentos. O tratamento com PCL+HA mostrou menor volume de orifício do que os outros tratamentos independentemente do período. As medidas histológicas mostraram maior formação de osso induzida pela membrana de PCL com ou sem HA do que os outros tratamentos independentemente do período. A HA mostrou maior aumento da cicatrização óssea com ou sem o PCL. Concluímos que a HA adicionada às nanofibras de PCL melhorou significativamente a cicatrização óssea em defeitos provocados na calvária de ratos
Abstract: The aim of the present study was to observe the effect of a polymeric-nanofiber membrane of poly-epsilon-caprolactone (PCL) with or without hydroxyapatite (HA) on bone healing of critical defects induced in rat calvaria. 36 animals were randomly divided into six groups. The standardized bone defects were obtained by two perforations with 3.0 mm diameter trephine directly into the animals¿ calvaria, one in each side. The right side received the treatments (HA or PCL-HA) and the left side the controls (blood clot or PCL). After 30, 60 and 90 days of the surgical procedure, all animals were killed; the head was sectioned and submitted to tomography (voxel of 0.12 mm, visual field of 6x16 cm, acquisition time of 40s, 120 kV, 8mA and 36.12 mA/s). The perforation diameters were measured using the software Invesalius 3.0. After tomography, all heads were fixed by buffered formol (pH=7.2) in 0.1M sodium-phosphate buffer during 72 hours and submitted to decalcification in 7% EDTA/5% formol solution until complete decalcification (approximately 30 days). Semi-serial 7 µm cuts were stained with Hematoxicilin-Eosin. Histological characteristics of bone healing were observed according to groups and periods. Quantitative comparisons of perforation measurements from both tomography and histological analysis were performed by Kruskal-Wallis (Dunn post hoc) test with a 5% significance level. Tomography images revealed a tendency to reduce the perforation volume along time, which was higher after 90 days for all treatments. The treatment with PCL+HA showed the lower volumes of perforations than the other treatments irrespectively of the period. Histological measurements showed more osseous formation induced by treatment with PCL with or without HA than the other treatments irrespectively of the period. HA appear to increase bone healing with or without PCL. We concluded that HA added to PCL nanofibers significantly improved the bone healing in bone defects of rat calvaria
Mestrado
Anatomia
Mestra em Biologia Buco-Dental
Lariviere, William R. "The bee venom test : a new tonic-pain test". Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23405.
Testo completoSalas, Torras Anna. "Desarrollo de modelos celulares y animales para el estudio de terapia génica no viral anti-angiogénica en retina". Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/456676.
Testo completoAge-‐related macular degeneration (AMD) and diabetic retinopathy (RD) belong to a group of retinal degenerations with complex etiology, influenced by both genetic and environmental factors. Although their origins are different and their molecular mechanisms are complex, both are characterized by progressive neurodegeneration with retinal apoptosis, glial activation, oxidative stress and the emergence of neovascularization in its later stages. These two diseases are the main causes of vision loss in industrialized countries, with more than 30 million people affected by AMD and more than 40 million affected by DR over the world, assuming a very high economic and medical impact. Despite their high prevalence, there are currently no effective treatments for the slowing or reversal of these pathologies, being the most used the anti-‐VEGF antibodies administered intravitreally, with their consequent side effects. In recent years gene therapy has been postulated as one of the most promising therapeutic options in the field of ophthalmology, offering viral and non-‐viral systems capable of promoting the expression of the therapeutic factor by the retinal cells for long time-‐periods. However, the development of pharmaceutically and clinically viable therapeutics depends not only on having an effective and safe vector but also on the provision of good animal models for conducting pre-‐clinical studies. The objective of this work has focused on the study of non-‐viral gene therapy strategies for the overexpression of two anti-‐angiogenic and neuroprotective factors normally expressed in the retina: somatostatin (SST) and pigment epithelium-‐derived factor (PEDF). In order to approach this objective, cellular models of angiogenesis have been generated and the anti-‐angiogenic efficacy of the two factors has been studied. Furthermore, two animal models have been generated and characterized, the streptozotocin-‐induced RD model in a rat and the laser-‐induced choroidal neovascularization AMD model in a mouse, determining the degree of retinal degeneration in both cases. Regarding the study of non-‐viral gene therapy systems, the sub-‐retinal administration model in rat and mouse has been first developed and the transfection capacity of retinal pigment epithelial cells (RPE) has been corroborated. PEDF and SST-‐expressing plasmid vectors have been constructed using regulatory sequences optimized for RPE expression and their expression capacity has been evaluated in RPE cultures. Finally, two nanoparticles as non-‐viral gene therapy systems have been studied: the protein nanoparticles R9-‐GFP-‐H6 and the chitosans O15. These systems have been characterized for their DNA-‐binding capacity and the transfection efficacy has been evaluated in cell cultures and in vivo in the RPE by sub-‐retinal injection. In conclusion, this work has developed a set of tools for the evaluation of new non-‐viral gene therapy strategies for the treatment of DR and AMD and has carried out the first studies of efficacy with protein and chitosan nanoparticles, breaking new ground in the procurement of an effective therapy in the treatment of the major vasoproliferative retinopathies.
Peleg-Raibstein, Daria. "Animal models of schizophrenia: a behavioral and neurochemical investigation /". Zürich : ETH, 2006. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=16488.
Testo completoThomas, Róisín Clare. "Nociceptin/orphanin FQ system and animal models of sepsis". Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38496.
Testo completoSamaranayaka, Ari, e n/a. "Environmental stochasticity and density dependence in animal population models". University of Otago. Department of Mathematics & Statistics, 2006. http://adt.otago.ac.nz./public/adt-NZDU20060907.114616.
Testo completoHaile, Melles. "Studies on new tuberculosis vaccine candidates in animal models /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-327-2/.
Testo completoLindberg, Julia. "Exploring Brain Gene Expression i Animal Models of Behaviour". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8177.
Testo completoAssareh, Neda. "Studies of cannabinoids in animal models of psychiatric disease". Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.537636.
Testo completoBickerdike, Michael John. "CCK/5-HT interactions in animal models of anxiety". Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241150.
Testo completoHough, Sally Jane. "Development of animal models to investigate drug-induced toxicity". Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266265.
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