Siga este link para ver outros tipos de publicações sobre o tema: Animal models.
Teses / dissertações sobre o tema "Animal models"
Crie uma referência precisa em APA, MLA, Chicago, Harvard, e outros estilos
Veja os 50 melhores trabalhos (teses / dissertações) para estudos sobre o assunto "Animal models".
Ao lado de cada fonte na lista de referências, há um botão "Adicionar à bibliografia". Clique e geraremos automaticamente a citação bibliográfica do trabalho escolhido no estilo de citação de que você precisa: APA, MLA, Harvard, Chicago, Vancouver, etc.
Você também pode baixar o texto completo da publicação científica em formato .pdf e ler o resumo do trabalho online se estiver presente nos metadados.
Veja as teses / dissertações das mais diversas áreas científicas e compile uma bibliografia correta.
1
Yalçin, Biannaz. "QTL mapping in animal models." Thesis, University of Oxford, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410716.
Texto completo da fonte
2
Mazzola, Carmen. "Neuropharmacology and Behaviural Animal Models." Thesis, Universita' degli Studi di Catania, 2011. http://hdl.handle.net/10761/93.
Texto completo da fonteResumo:
Lo studio delle patologie umane richiede spesso l'ausilio di sperimentazioni animali. Generalmente i dati ottenuti in questi modelli permettono di ampliare le conoscenze sui meccanismi eziologici e sul trattamento delle patologie. Perche' un modello sperimentale sia considerato attendibile, deve avere specifici requisiti: face validity, construct validity and predictive validity. Rispettare tali criteri e' di enorme importanza per la ricerca in ambito fisiologico e farmacologico.<br>The 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.
3
Klingström, Jonas. "Hantaviruses : animal models, immunology and pathogenesis /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-071-0/.
Texto completo da fonte
4
Thomas, 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.
Texto completo da fonteResumo:
The neuropathogenicity of two retroviruses was investigated. The human immunodeficiency virus, in addition to its profound effect on the immune system, also causes degenerative changes in the brain, the spinal cord and peripheral nerves. In order to elucidate how it affects the nervous system, transgenic mice were generated that express the entire HIV genome in neurons in the anterior thalamus and in the anterior horn of the spinal cord, and examined clinically, neuropsychologically, electrophysiologically and histologically. Animals developed a neurological syndrome characterized by hypoactivity and weakness, and by axonal degeneration in peripheral nerves. These results provide evidence for a role of HIV in affecting both the central and peripheral nervous systems.<br>In 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.
5
Lydall, Emma Sian. "Palatability and animal models of schizophrenia." Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/55071/.
Texto completo da fonteResumo:
Schizophrenia is one of the most serious mental disorders of humankind. It affects about 1% of the population worldwide and has devastating consequences, including suicide in 10% of sufferers (e.g. Lewis & Lieberman, 2000). Schizophrenia also has serious social impact with sufferers accounting for more than one third of the homeless population in western society (Folsom & Jeste, 2002).
6
Warren, Nicholas David. "Some stochastic models for animal territories." Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312289.
Texto completo da fonte
7
Jusof, Felicita Fedelis. "Tryptophan-catabolising enzymes in animal models." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/13697.
Texto completo da fonteResumo:
The first and rate-limiting step of the kynurenine pathway is the metabolism of tryptophan (Trp) to N-formylkynurenine, which is then rapidly converted to kynurenine. This initial step can be catalysed by three enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2, 3-dioxygenase-1 (IDO1) and the most recently discovered, IDO2. In adult mammals, TDO is expressed constitutively in the liver and is involved in the global regulation of tryptophan. IDO1 expression is mainly induced in various tissues during inflammatory conditions. IDO2, detected in the adult liver, may play a role in inflammation and autoimmune diseases. This report demonstrates the cellular localisation of IDO2 in adult mouse liver with Ido2-/- mice as the negative control, as well as the mRNA expression of Trp-catabolising enzymes in embryonic developmental series of zebrafish (tdo2a, tdo2b and ido) and mouse (Tdo2, Ido1 and Ido2). Both tdo2a and tdo2b were detected in zebrafish embryonic liver, whereas all three genes coding for Trp-catabolic enzymes were found in the intestine. In murine developmental tissues, Tdo2, Ido1 and Ido2 were all detectable in the yolk sac and placenta, with the expression of Tdo2 being the highest. Finally, this report also is the first to postulate a possible role for IDO2 in averting inflammation and metabolic dysregulation in the liver.
8
Zemp, Franz Joseph, and 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.
Texto completo da fonteResumo:
Bystander effects are traditionally known as a phenomenon whereby unexposed cells exhibit the molecular symptoms of stress exposure when adjacent or nearby cells are traversed by ionizing radiation. However, the realm of bystander effects can be expanded to include any systemic changes to cellular homeostasis in response to a number of biotic or abiotic stresses, in any molecular system. This thesis encompasses three independent experiments looking at bystander and bystander-like responses in both plant and animal models. In plants, an investigation into the regulation of small RNAs has given us some insights into the regulation of the plant hormone auxin in both stress-treated and systemic (bystander) leaves. Another plant model shows that a bystander-like plant-plant signal can be induced upon ionizing radiation to increase the genome instability of neighbouring unexposed (bystander) plants. In animals, it is shown that the microRNAome is largely affected in the bystander cells in a three-dimensional human tissue model. In silico and bioinfomatic analysis of this data provide us with clues as to the nature of bystander signalling in this human ‘in vivo’ model.<br>xiv, 141 p. : ill. ; 29 cm.
9
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.
Texto completo da fonte
10
Nwosu, 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.
Texto completo da fonte
11
Degrassi, Anna. "MRI studies of animal models for osteoarthritis." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621774.
Texto completo da fonte
12
Allcroft, David John. "Statistical models for short-term animal behaviour." Thesis, University of Edinburgh, 2001. http://hdl.handle.net/1842/11132.
Texto completo da fonteResumo:
This thesis aims to identify appropriate methods for the modelling of animal behaviour data, and in the wider context, any time series of categorical data. We make extensive use of a large dataset of cow feeding behaviour, consisting of full feeding records for a number of cows over one month, the data taking the form of binary time series, i.e. feeding/non-feeding periods. After initial exploratory data analysis, we go on to investigate three classes of model: latent Gaussian, hidden Markov and semi-Markov. The latent Gaussian model assumes the binary data occur from the thresholding of an underlying continuous variable. We identify the one-to-one relationship between the autocorrelation of the observed and latent variables and consider techniques for parameter estimation. For a multivariate stationary Gaussian process we show the asymptotic equivalence of the likelihood written in its spectral and conventional forms, and provide a proof that for short-term memory processes such as ARMA models, a good approximation for the spectral form is obtained using Fourier transforms of correlations at only the first few lags. A simulation study highlights the saving in computing time that this offers, and also shows that, in contrast to the least squares methods considered, the number of lags to retain is not crucial for obtaining efficient parameter estimates. Hidden Markov models also directly model the underlying state of the animal, but the latent variable here is discrete and follows a Markov chain, observations being dependent only on the current state. However, this type of model constrains the durations between feeding events to follow a mixture of geometric distributions, which is seen to be inappropriate for the data considered. Semi-Markov models simply involve the animal moving between a set of feeding and non-feeding states according to a set of transition probabilities, the marginal distributions for durations in each state being specified directly.
13
Hitchen, Barry. "Behavioural evaluation of animal models of diabetes." Thesis, Ulster University, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744769.
Texto completo da fonteResumo:
Diabetes is considered as a prominent threat to the worldwide population, and if left untreated may result in a number of severe complications, cognitive deterioration, and death. For the most prevalent form of the disease, type 2 diabetes, the main contributing factors to the development of the disease is being overweight and obese. There are a number of mediating factors regarding the relationship between excessive weight gain and subsequent development of diabetes, the most widely supported of which is the typical eating behaviours of the individual. While the physiological characteristics of diabetes are well-known, much less is understood in relation to the behavioural consequences. Animal models may aid our understanding of a disease, but the animal model used should not only replicate the physiological symptoms but also the behavioural characteristics. The studies discussed within this thesis encompass a thorough behavioural evaluation of two of the most commonly used diet-induced and chemically-induced animal models of diabetes; the high-fat diet model of obesity induced diabetes and Streptozotocin induced diabetes. The main focus of investigation was on the impact of the disease regarding the food preferences and motivations of mice to obtain food, using a classical method for assessing preference (T-maze) and motivation to respond for different appetitive stimuli on an operant conditioning schedule of food reinforcement (progressive ratio schedule, PR). During the latter phase of experiments, a range of behavioural processes (e.g. food deprivation alterations, prefeeding with or without satiation, and extinction) were also assessed in relation to how these may be affected by the presence of diabetes. In the final study, a new model of PR performance was applied to the results, with the intention of addressing issues relating to the accurate measurement of motivation under a PR schedule. Orderly behavioural data were obtained but neither model of diabetes showed clear effects on food motivation. Results are presented and discussed in relation to the limitations and implications of the research.
14
Atanasova, Nina A. "Animal Models and the Unity of Neuroscience." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406820028.
Texto completo da fonte
15
Bierman, 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.
Texto completo da fonteResumo:
Population dynamics is the study of how and why populations of animals change in distribution and abundance. Thus, the aims of the science of population dynamics are twofold: to document the empirical patterns of population distribution and change, and to determine the mechanisms underlying those observed patterns. Population dynamics data typically have rich and complex spatio-temporal patterns. Modern and flexible statistical methods are needed to describe these patterns, and for the sound estimation of parameters in realistic mathematical models of spatio-temporal population dynamics. Of particular importance has been the development over the past decade of modern computational statistical methods, such as Markov chain Monte Carlo (McMC), that enable rigorous parameter estimation for more realistic models. The work as reported in this thesis has evolved around three case studies, each involving a long-term data set of estimated abundance's of a species at different locations over time, and a specific set of questions of interest: 1) Linking the spatio-temporal variation in recruitment of the Atlantic puffin (Fractercula arctica) to the spatio-temporal variation in densities of nesting herring gulls (Larus argentatus ) and lesser black-backed gulls (Larus fuscus) within the Isle of May natural nature reserve. 2) The use of flexible statistical tools to investigate coincident changes in the spatial and temporal dynamics of cyclic populations of field voles (Microtus agrestis). 3) Investigating the metapopulation dynamics of water voles (Arvicola terrestris) in the Scottish uplands using stochastic patch occupancy models. In each case study, the central aim was to formulate mathematical models that describe the spatio-temporal dynamics of the animal populations, and to develop and investigate the uses of flexible statistical methods that can be used to inform these models using the data.
16
Lai, Edwin W. "Molecular characterization of animal models of pheochromocytoma." Connect to Electronic Thesis (CONTENTdm), 2009. http://worldcat.org/oclc/454140444/viewonline.
Texto completo da fonte
17
Talbot, 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.
Texto completo da fonte
18
Schofield, Matthew R., and n/a. "Hierarchical capture-recapture models." University of Otago. Department of Mathematics & Statistics, 2007. http://adt.otago.ac.nz./public/adt-NZDU20080129.161029.
Texto completo da fonteResumo:
A defining feature of capture-recapture is missing data due to imperfect detection of individuals. The standard approach used to deal with the missing data is to integrate (or sum) over all the possible unknown values. The missing data is completely removed and the resulting likelihood is in terms of the observed data. The problem with this approach is that often biologically unnatural parameters are chosen to make the integration (summation) tractable. A related consequence is that latent variables of interest, such as the population size and the number of births are only available as derived quantities. As they are not explicitly in the model they are not available to be used in the model as covariates to describe population dynamics. Therefore, models including density dependence are unable to be examined using standard methods.
Instead of explicitly integrating out missing data, we choose to include it using data augmentation. Instead of being removed, the missing data is now present in the likelihood as if it were actually observed. This means that we are able to specify models in terms of the data we would like to have observed, instead of the data we actually did observe. Having the complete data allows us to separate the processes of demographic interest from the sampling process. The separation means that we can focus on specifying the model for the demographic processes without worrying about the sampling model. Therefore, we no longer need to choose parameters in order to simplify the removal of missing data, but we are free to naturally write the model in terms of parameters that are of demographic interest. A consequence of this is that we are able write complex models in terms of a series of simpler conditional likelihood components. We show an example of this where we fit a CJS model that has an individual-specific time-varying covariate as well as live re-sightings and dead recoveries.
Data augmentation is naturally hierarchical, with parameters that are specified as random effects treated as any other latent variable and included into the likelihood. These hierarchical random effects models make it possible to explore stochastic relationships both (i) between parameters in the model, and (ii) between parameters and any covariates that are available.
Including all of the missing data means that latent variables of interest, including the population size and the number of births, can now be included and used in the model. We present an example where we use the population size (i) to allow us to parameterize birth in terms of the per-capita birth rates, and (ii) as a covariate for both the per-capita birth rate and the survival probabilities in a density dependent relationship.
19
Glennie, Richard. "Incorporating animal movement with distance sampling and spatial capture-recapture." Thesis, University of St Andrews, 2018. http://hdl.handle.net/10023/16467.
Texto completo da fonteResumo:
Distance sampling and spatial capture-recapture are statistical methods to estimate the number of animals in a wild population based on encounters between these animals and scientific detectors. Both methods estimate the probability an animal is detected during a survey, but do not explicitly model animal movement. The primary challenge is that animal movement in these surveys is unobserved; one must average over all possible paths each animal could have travelled during the survey. In this thesis, a general statistical model, with distance sampling and spatial capture-recapture as special cases, is presented that explicitly incorporates animal movement. An efficient algorithm to integrate over all possible movement paths, based on quadrature and hidden Markov modelling, is given to overcome the computational obstacles. For distance sampling, simulation studies and case studies show that incorporating animal movement can reduce the bias in estimated abundance found in conventional models and expand application of distance sampling to surveys that violate the assumption of no animal movement. For spatial capture-recapture, continuous-time encounter records are used to make detailed inference on where animals spend their time during the survey. In surveys conducted in discrete occasions, maximum likelihood models that allow for mobile activity centres are presented to account for transience, dispersal, and heterogeneous space use. These methods provide an alternative when animal movement causes bias in standard methods and the opportunity to gain richer inference on how animals move, where they spend their time, and how they interact.
20
Telkes, Ilknur. "Phase Validation Of Neurotoxic Animal Models Of Parkinson." Master's thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614866/index.pdf.
Texto completo da fonteResumo:
Parkinson&rsquo<br>s 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<br>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<br>g, bilaterally to the substantia nigra pars
compacta (SNpc). Experiments were conducted on 50 young-adult male Sprague&ndash<br>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<br>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.
21
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.
Texto completo da fonteResumo:
Schizophrenia is a clinical syndrome of variable psychopathology, which involves thought, perception, emotion, movement and behavior. The cumulative effect of the illness is always severe and usually long lasting. Epidemiologic studies indicate that the lifetime expectancy is 0.5-1% worldwide. The etiology and pathophysiology of schizophrenia are unknown. The two predominant pathophysiological hypotheses of schizophrenia are the dopamine hypothesis and the glutamate hypothesis. The former hypothesis states that dopamine neurotransmission is hyperactive in schizophrenia, the latter – that there is a hypofunction of glutamatergic neurotransmission in some areas of the brain. Recent studies also suggest that schizophrenia is associated with cytoskeletal alterations in neuronal architecture, e.g. differences in micro tubule associated proteins (MAP). The symptoms of schizophrenia are mostly unique to human behavior. Consequently, the exact reproduction of schizophrenia in an animal is not possible. However, animal models are important tools for exploring the underlying mechanisms of schizophrenia and for designing new therapies. The present thesis is based on four publications on animal models of schizophrenia. We used the NMDA receptor antagonist MK-801 to induce a state of hypoglutamatergia in rats in the three of them. Three different designs were used: injection of a single high dose, repeated high dose injections over several days and repeated injections of a lower dose. The fourth study was designed to investigate glutamate related metabolism in a state of microtubule instability. Knock out mice were used as a model, in which the gene coding for the microtubule associated protein STOP (Stable Tubule Only Peptide) was deleted. Glutamate related metabolism was investigated in these models by analyzing brain extracts from multiple brain areas, using HPLC (High Performance Liquid Chromatography) and 13C and1H nuclear magnetic resonance spectroscopy. By injecting animals with 1-13C labeled glucose and 1,2-13C labeled acetate, the preferential substrates of neurons and astrocytes, respectively, it was possible to follow metabolic interactions between astrocytes and neurons. A single dose of 0.5 mg/kg MK-801 produced predominantly changes in the temporal lobe with increased total amounts of glutamate and glutamine, and increased labeling from [1-13C]glucose. Similar changes were observed when MK-801 was administered repeatedly at 0.1 mg/kg for 6 consecutive days and all the metabolic alterations were confined to the temporal lobe. However, while 0.5 mg/kg MK-801 was used repeatedly instead of 0.1 mg/kg MK-801, changes were found in the cingulate, retrosplenial and frontal cortices. The total amount of glutamate increased in those areas together with a decrease in labeling from both [1-13C]glucose and [1,2-13C]acetate in several metabolites. In Paper 4 decreased levels of both total glutamine and labeled [4,5-13C]glutamine were reported in the cerebrum of STOP knock out mice. Compared to data from studies of schizophrenic patients, our results indicate that repeated injections of MK-801 in high doses may be a good model for first episode schizophrenia and the STOP KO mouse model show similarities to and may be a good model chronic schizophrenia. Results show that both the NMDA receptor hypofunction and the loss of microtubule stability seem to disrupt the glutamate-glutamine cycle, and it can be stated that astrocytic-neuronal interactions probably are underestimated in schizophrenia research.<br>Glutamat-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.
22
Duncan, Warwick John, and 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.
Texto completo da fonteResumo:
This inquiry investigated the suitability of the jaw of domestic sheep as an animal model for dental implantology research. Initially, parameters for osseous healing of critical size defects (CSD) in the sheep mandible were established. Pilot studies were conducted using machined-surface implants and a surgical protocol established for dental implant placement in ovine mandibular sites. Subsequent experiments considered the utility of this animal model for examination of techniques designed to enhance osseointegration. Hydroxyapatite-coated implants were compared with titanium plasma-sprayed (TPS) implants, either alone or combined with autogenous bone grafts or a bone graft/collagen vehicle loaded with transforming growth factor-beta (TGF-β). Immunofluorescent bone labelling gave information on the mineral apposition rate (MAR). Implant survival and "acceptability" (likelihood of clinical success) were major output variables, along with histomorphometric analysis of percent bone-implant contact (%BIC) and percent peri-implant bone density (%density). Naturally-occurring "broken-mouth" periodontitis in sheep was identified as a potential confounder. Subsequent experiments considered implants with different surfaces. The model was also extended from a two-stage surgical protocol to include single-stage implants. The effect of pre-existing ovine peridontitis was also examined. A systematic review and meta-analysis of published animal implant experiments was conducted in order to validate the candidate sheep model.
Major findings were as follows. The size of non-healing sheep mandibular unicortical CSD is >12mm. Attempts to establish a chronic non-healing CSD were unsuccessful. The sheep diastema proved unsuitable for implant placement. The model was modified to a post-extraction protocol. Implant "acceptability" rates after 3 months integration in the sheep mandible (defined as implant survival with %BIC >10%) ranged from 50% - 100% for different implant surface treatments and placement protocols. Histomorphometriic analyses revealed that %BIC ranged from 11 � 17% to 81 � 29 % for different titanium surfaces and up to 85 � 11% for hydroxyapatite surfaces. Implants with TGF-β plus autogenous bone grafts had %BIC of 36 � 30% compared with 43 � 30% for implants with grafts alone. Bone per unit area (%density) adjacent to, but outside of the implant threads, ranged from 63 � 16% to 86 � 3% and was markedly lower for titanium plasma-sprayed surfaces and for one-stage implants. Within the implant threads, %density varied from 31 � 33% to 73.4 � 8.3%, and was markedly lower for machined titanium surfaces. Sheep periodontitis had little effect on the protocols investigated. The sheep mandibular model was found to be comparable to similar models in other species and merits further development.
23
Nilsson, Tatjana. "Amyloid precursor protein: cellular studies and animal models /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-832-0/.
Texto completo da fonte
24
Pålsson, 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.
Texto completo da fonte
25
Arlinde, Christina. "Gene expression profiling in animal models of alcoholism /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-133-4/.
Texto completo da fonte
26
Nordquist, 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/.
Texto completo da fonte
27
Rostami, 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.
Texto completo da fonte
28
Ingram, 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.
Texto completo da fonteResumo:
The two glial transporters, GLAST (<SUB>L</SUB>-glutamate/L-aspartate transporter) and GLT-1 (<SUB>L</SUB>-glutamate transporter), are critical in regulating extracellular glutamate levels, being responsible for the majority of glutamate reuptake. The present study investigated GLAST and GLT-1 mRNA and protein levels in two animal models of inherited epilepsy: the EL (epileptic) mouse, a convulsive seizure model, and the GAERS (genetic absence epilepsy rat from Strasbourg) rat, a model of absence epilepsy. Additionally, tissue glutamate concentrations were determined in these animals by high pressure liquid chromatography (HPLC). Initially, polyclonal antibodies specific to mouse and rat GLT-1 and GLAST were generated and characterised. These antibodies revealed distribution patterns for the two transporters confirming those previously reported. <I>In situ</I> hybridisation and Western blot analysis revealed widespread reductions in GLT-1 mRNA in the brains of EL mice compared with control animals, accompanied by a decrease in GLT-1 protein in the parietal cortex, a region crucial to seizure initiation in this model. An increase in tissue glutamate concentration in the parietal cortex of EL mice was additionally observed. GLAST mRNA was also reduced in various brain regions of EL mice, with a reduction in protein observed in the hippocampus, a region essential for seizure generalisation. Glial glutamate transporter downregulation in these two regions may therefore play a role in seizure initiation and generalisation in the EL mouse. Similar analyses in GAERS rats revealed upregulation of GLT-1 and GLAST mRNA in thalamic and cortical regions, respectively, when compared with controls.
29
Gilder, 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.
Texto completo da fonte
30
Deiana, 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.
Texto completo da fonteResumo:
A transgenic animal model in which tau protein aggregation is expected to produce behavioural symptoms similar to those observed in certain tauopathies in humans has been examined in this thesis. The transgenic mouse lines, when tested in a heterozygous genetic background, showed no cognitive deficit although non-associative learning was impaired. Fine motor learning and motor coordination, however, were severely compromised suggesting disruption of cerebellar and/or basal ganglia function. This model can be used to test tau aggregation inhibitors, that may be effective in preventing, or even reversing the behavioural symptoms caused by tau-aggregation. Since the cholinergic deficit is a feature of Alzheimer’s disease, the effect of the inhibitors described above was tested on the cholinergic system. This was examined using a pharmacological model in which cholinergic deficit was induced by treatment of mice with scopolamine, a competitive antagonist at M1 muscarinic acetylcholine receptors. For the four tau aggregation inhibitors tested in the present work, there were differing efficacies in reversing the scopolamine-induced cognitive deficit. TRx0014 (methylene blue) was the most effective and more so than rivastigmine, a marketed cholinesterase inhibitor. Co-administration of TRx0014 and rivastigmine at sub-effective doses showed a synergistic effect on the reversal of cholinergic deficits. In conclusion, the present work provided a novel transgenic animal model that closely mimics certain behavioural traits typical of some tauopathies. These animals thus provide a valuable model to test novel tau aggregation inhibitors with potentially disease-modifying consequences. The study also demonstrates that such inhibitors, in addition, are able to reverse the symptoms due to cholinergic disruption in normal mice.
31
Matthews, 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.
Texto completo da fonteResumo:
One approach to the clinical problem of defining the neural substrates of human depressive disorders is to model discrete aspects of affective psychopathology in animals. Two major methodological problems have hindered the development of valid animals models of depression. First, individual responses to the manipulations commonly used to model depression are highly variable. Second, reliable and valid measures of hedonic state remain elusive. This thesis describes experimental work which addresses these methodological concerns. Selective breeding based on individual responses to cholinergic challenge has resulted in a putative genetic model of depression, the <I>Flinders Sensitive Line hypercholinergic rat</I> (FSL). An examination of the affective status of the FSL described in this thesis confirms that selective breeding can generate interesting behavioural and neurochemical phenomena, but does not support the FSL's validity as a model of anhedonia. Problems of measurement of hedonic responsivity are considered both in the description of a novel dependent measure derived from an operant food reward paradigm; and also in an evaluation of the reliability and validity of standard measurement techniques employed with the '<I>chronic unpredictable mild stress model</I>' (CMS) of anhedonia. Initial validating studies suggest that the food reward paradigm may represent a useful method for assessment of affective state. Manipulation of environmental stimuli to induce CMS led to a partial replication of the target behavioural phenomena. However, the effects were not independent of metabolic consequences that seriously confound the interpretation of experiments employing this procedure. It is concluded that future advances in the development of valid models of depression will require a shift of emphasis towards combined manipulations of genetic predisposition and of specific critical environmental stimuli.
32
Devadasu, 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.
Texto completo da fonte
33
Selvan, 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.
Texto completo da fonteResumo:
Protein O-GlcNAcylation is a reversible type of glycosylation of serine and threonine residues of nucleocytoplasmic proteins occurring in all animals examined to date. Its installation on protein substrates is carried out by O-GlcNAc transferase (OGT), and its removal by O-GlcNAc hydrolase (O-GlcNAcase or OGA). A range of proteomics studies have suggested that over a thousand intracellular proteins are O-GlcNAc modified. However, little is known of the role of O-GlcNAc on these proteins. In a search for a reductionist model with a small proteome to dissect the general global mechanisms of protein O-GlcNAcylation, I discovered the presence of functional OGT, OGA and nucleocytoplasmic protein O-GlcNAcylation in the most basal extant animal, the placozoan Trichoplax adhaerens. I show via enzymatic characterization of Trichoplax OGT/OGA and genetic rescue experiments in Drosophila melanogaster that these proteins possess activities/functions similar to their bilaterian counterparts. While Trichoplax is not currently amenable to genetic manipulation, studying protein O-GlcNAcylation in this organism has revealed the presence of OGT, OGA and O-GlcNAc in non-bilaterian animals. Together with the absence of O-GlcNAcylation in lower organisms, this suggests that OGT-dependent reversible protein O-GlcNAcylation is a metazoan innovation, which may have facilitated the rapid and complex signaling mechanisms required for the evolution of multicellular organisms. Various genetic approaches in several animal models have revealed that protein O-GlcNAcylation is required for embryogenesis. Embryonic development in a genetically tractable organism is thus a model in which the mechanisms of protein O-GlcNAcylation can be investigated. Drosophila melanogaster OGT is a polycomb gene, null mutants of which display homeotic transformations and die at the pharate adult stage. However, the identities of the modified proteins involved, and the underlying biology linking these to embryonic development are poorly understood. One of the limiting factors towards characterizing O-GlcNAcylation has been the limited specificity of currently available tools to detect this modification. Harnessing the unusual properties of a catalytically inactive bacterial O-GlcNAcase mutant that binds O-GlcNAc sites with sub-micromolar affinity, I show that protein O-GlcNAcylation is dynamic along Drosophila embryonic development. In addition to immunoprecipitation using the anti-O-GlcNAc antibody RL2, I have used the mutant OGA probe to enrich for O-GlcNAcylated proteins from samples of embryos at various developmental stages, and using mass spectrometry, identified novel conserved O-GlcNAcylated proteins. There is evidence in the literature for some of these O-GlcNAc proteins being involved in the regulation of hox gene expression, suggesting that the lack of O-GlcNAcylation of these proteins may contribute to the homeotic phenotypes observed in ogt null Drosophila mutants. This thesis therefore lays the foundation for the investigation of the mechanisms by which protein O-GlcNAcylation of specific substrates would affect a process such as embryonic development.
34
Bicer, Sabahattin. "Efficacy/toxicity studies of amiodarone in animal models /." The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486546889383936.
Texto completo da fonte
35
Lopes, 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/.
Texto completo da fonteResumo:
As distrofias musculares constituem um grupo heterogêneo de doenças genéticas, caracterizadas por uma degeneração progressiva e irreversível dos músculos. Modelos murinos distróficos, como o mdx, SJL/J, Largemyd e Lama2dy-2J/J, são ferramentas importantes para o estudo destas doenças. O objetivo deste trabalho consistiu em estabelecer parâmetros de avaliação funcional que visem a sua utilização para elucidar os benefícios clínicos de futuras terapias. Para tanto, foram avaliadas as quatro linhagens distróficas, em diferentes idades, e comparadas a controle normal. Os testes padronizados consistiram em nado forçado, avaliação de resistência/equilíbrio pelos membros anteriores e pelos quatro membros, caminhar em plataforma suspensa, suspensão pela cauda, grip strength e rota rod. Comprovou-se a existência de diferentes padrões de força, resistência, coordenação motora e aprendizagem/memória ao longo do tempo de vida de cada linhagem, o que permitiu traçar parâmetros a serem utilizados em futuras pesquisas de terapia celular e farmacológica.<br>Muscular 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.
36
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.
Texto completo da fonteResumo:
Orientador: Irenilza de Alencar Naas<br>Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Agricola<br>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<br>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<br>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<br>Doutorado<br>Construções Rurais e Ambiencia<br>Doutor em Engenharia Agrícola
37
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.
Texto completo da fonteResumo:
Dissertação de Mestrado em Etologia<br>Os 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.
38
Van, Eeden Willem Daniel. "Human and animal classification using Doppler radar." Diss., University of Pretoria, 2005. http://hdl.handle.net/2263/66252.
Texto completo da fonteResumo:
South Africa is currently struggling to deal with a significant poaching and livestock theft problem. This work is concerned with the detection and classification of ground based targets using radar micro- Doppler signatures to aid in the monitoring of borders, nature reserves and farmlands. The research starts of by investigating the state of the art of ground target classification. Different radar systems are investigated with respect to their ability to classify targets at different operating frequencies. Finally, a Gaussian Mixture Model Hidden Markov Model based (GMM-HMM) classification approach is presented and tested in an operational environment. The GMM-HMM method is compared to methods in the literature and is shown to achieve reasonable (up to 95%) classification accuracy, marginally outperforming existing ground target classification methods.<br>Dissertation (MEng)--University of Pretoria, 2017.<br>Electrical, Electronic and Computer Engineering<br>MEng<br>Unrestricted
39
Cartón, García Fernando. "Myosin VB in intestinal pathogenesis." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458251.
Texto completo da fonteResumo:
Miosina VB es una proteína que actúa como un motor molecular usando la energía del ATP para moverse a lo largo de filamentos de actina. Participa en el trafico intracelular de endosomas de reciclaje en la parte subapical de células polarizadas y no polarizadas. Su expresión es muy abundante en el intestino donde participa en el establecimiento y mantenimiento de la polaridad de los enterocitos. Mutaciones en MYO5B causan la enfermedad de inclusión de microvellosidades, in raro trastorno congénito que afecta a las células epiteliales del intestino cursando con diarrea acuosa persistente que suele ser fatal. Esta enfermedad se caracteriza por la presencia de alteraciones morfológicas en los enterocitos, atrofia de las vellosidades y deslocalización de proteínas del polo apical y basolateral del enterocito. Su patología molecular no se conoce, principalmente por la falta de modelos animales. En el presente estudio, describimos un versátil modelo murino con inactivación constitutiva de Myo5b e inactivación condicional en las células epiteliales intestinales inducida por tamoxifeno. En ambos casos, los animales muestras un cuadro clínico muy semejantes al de los pacientes con enfermedad de inclusión de microvellosidades, presentado diarrea y deshidratación que causan la muerte del animal. A nivel histológico, el intestino muestra las mismas alteraciones en los enterocitos que las presentes en pacientes humanos, incluyendo atrofia de vellosidades y deslocalización de marcadores proteicos. Además, la inactivación de Myo5b también provocó hiperproliferación de las criptas intestinales. Por lo tanto, el modelo animal presentado constituye una herramienta muy útil para investigar las causas moleculares de la enfermedad y ensayar de manera preclínica fármacos u otras opciones terapéuticas. Por otro lado, la pérdida de polaridad y diferenciación es también una de las señas de identidad de los carcinomas metastásicos avanzados y correlaciona con un mal pronóstico de los pacientes. En concreto, para el cáncer colorrectal, investigaciones previas llevadas a cabo en nuestro laboratorio ya han demostrado que la pérdida de miosina IA promueve la progresión la enfermedad y tiene actividad supresora de tumores. Dicha proteína es abundante en el borde en cepillo de los enterocitos, y participa en el mantenimiento de la estructura polarizada. Otros estudios han señalado la relación entre la inactivación de MYO5B con un incremento en la motilidad e invasión de células de cáncer gástrico, aunque todavía no se conoce nada de su relación con en el cáncer colorrectal. Para resolver esta cuestión, hemos diseñado modelos in vitro inducibles por doxiciclina para sobre expresar y reducir la expresión de dicha proteína en líneas celulares de cáncer de colon. Además, se ha empleado la tecnología CRISPR/Cas9 para inactivar la expresión de MYO5B en la línea de cáncer de colon Caco2-BBE. Los resultados muestran cambios en la polarización y diferenciación de dichas líneas celulares, de acuerdo con observaciones previas. También se ha observado una posible relación entre MYO5B y la capacidad de movilidad e invasión de las líneas de cáncer de colon. Sin embargo, la hiperproliferación observada en el intestino de los ratones no se reproduce en las líneas de cáncer de colon empleadas tras reducir o sobre expresar MYO5B, o en modelos xenograft subcutáneos in vivo de dichas líneas. Por otro lado, usando un microarray de tejidos con 155 muestras de tumores primarios de pacientes con cáncer colorrectal en estadio Dukes C se ha comprobado que una reducción en la expresión de MYO5B se asocia con una disminución en el tiempo de recaída y en la supervivencia total de los pacientes de cáncer de colon. Además, tumores con un grado de diferenciación bajo también expresan niveles de MYO5B significativamente reducidos. Finalmente, todos estos resultados indican que MYO5B juega un papel importante en la diferenciación del intestino normal y de las líneas de cáncer de colon. De la misma manera, MYO5B también podría desempeñar un papel en la progresión del cáncer colorrectal promoviendo movilidad e invasión de las células tumorales.<br>Myosin 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.
40
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.
Texto completo da fonteResumo:
Orientador: Ana Cláudia Rossi<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba<br>Made available in DSpace on 2018-08-26T07:37:41Z (GMT). No. of bitstreams: 1
Groppo_MonicaFeresini_M.pdf: 1793041 bytes, checksum: 85a537401a5b84975a441824072b9e89 (MD5)
Previous issue date: 2014<br>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<br>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<br>Mestrado<br>Anatomia<br>Mestra em Biologia Buco-Dental
41
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.
Texto completo da fonteResumo:
The present study describes a new test of tonic pain in rats which can be used as an animal model of persistent pain. In the first experiment, the response to subcutaneous injection of various doses of bee venom into the hind paw of the rat was quantified. The second experiment investigated the effect of morphine and aspirin on the response to an intermediate dose of bee venom. Finally, the third experiment examined the response to concurrent injections of bee venom and formalin. Subcutaneous injection of bee venom produced local inflammation, marked edema, and tonic pain responses. Increasing doses of bee venom produced higher mean pain scores and increased durations of responding. Pain responses lasted up to approximately one hour and the inflammation and edema were virtually gone by 8 hours with the lower doses of bee venom tested and by 2 days with the two highest doses tested. Analgesia was produced by morphine and aspirin, indicating that the bee venom test can be used to test analgesic drugs. Concurrent administration of bee venom and formalin produced responses similar to formalin alone, with an increased duration of responding at higher intensities. The data suggest that the bee venom test is a valid animal model of experimental tonic pain.
42
Salas, 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.
Texto completo da fonteResumo:
La
degeneración
macular
asociada
a
la
edad
(DMAE)
y
la
retinopatía
diabética
(RD)
pertenecen
a
un
grupo
de
degeneraciones
de
retina
con
etiología
compleja,
influenciadas
tanto
por
factores
genéticos
como
ambientales.
Aunque
sus
orígenes
son
distintos
y
sus
mecanismos
moleculares
son
complejos,
ambas
se
caracterizan
por
una
neurodegeneración
progresiva
con
presencia
de
apoptosis
en
la
retina,
activación
glial,
estrés
oxidativo
y
la
aparición
de
neovascularización
en
sus
fases
más
avanzadas.
Estas
dos
enfermedades
son
las
principales
causas
de
pérdida
de
visión
en
los
países
industrializados,
con
más
de
30
millones
de
personas
afectadas
de
DMAE
y
más
de
40
millones
afectadas
de
RD
en
todo
el
mundo,
suponiendo
un
elevadísimo
impacto
económico
y
médico.
A
pesar
de
su
elevada
prevalencia,
actualmente
no
existen
tratamientos
eficaces
para
la
ralentización
o
la
reversión
de
estas
patologías,
siendo
los
más
utilizados
los
anticuerpos
anti-‐VEGF
administrados
de
forma
intravítrea,
con
sus
consiguientes
efectos
secundarios.
En
los
últimos
años
la
terapia
génica
se
ha
postulado
como
una
de
las
opciones
terapéuticas
más
prometedoras
en
el
campo
de
la
oftalmología,
ofreciendo
sistemas
virales
y
no
virales
capaces
de
provocar
la
expresión
del
factor
terapéutico
por
las
propias
células
de
la
retina
por
períodos
de
tiempo
muy
prolongados.
Sin
embargo,
el
desarrollo
de
terapéuticos
farmacéuticamente
y
clínicamente
viables
depende
no
sólo
de
tener
un
vector
efectivo
y
seguro
sino
también
de
la
disposición
de
buenos
modelos
animales
para
la
realización
de
los
estudios
pre-‐clínicos.
El
objetivo
de
este
trabajo
se
ha
centrado
en
el
estudio
de
estrategias
de
terapia
génica
no
viral
para
la
sobre-‐expresión
de
dos
factores
anti-‐angiogénicos
y
neuroprotectores
expresados
normalmente
en
retina:
la
somatostatina
(SST)
y
el
factor
derivado
del
epitelio
pigmentado
(PEDF).
Para
el
abordaje
de
este
objetivo
primeramente
se
han
generado
modelos
celulares
de
angiogénesis
y
se
ha
estudiado
la
eficacia
anti-‐angiogénica
de
los
dos
factores.
También
se
han
generado
y
caracterizado
dos
modelos
animales,
uno
de
RD
inducido
con
estreptozotocina
en
rata
y
uno
de
DMAE
mediante
inducción
de
neovascularización
coroidea
con
láser
en
ratón,
determinando
el
grado
de
degeneración
retiniana
en
ambos
casos.
En
cuanto
al
estudio
de
sistemas
de
terapia
génica
no
viral,
primeramente
se
ha
puesto
a
punto
el
modelo
de
administración
sub-‐retiniana
en
rata
y
ratón
y
se
ha
corroborado
la
capacidad
de
transfección
de
las
células
del
epitelio
pigmentado
de
la
retina
(EPR).
Se
han
construido
los
vectores
plasmídicos
de
expresión
de
PEDF
y
SST
usando
secuencias
reguladoras
optimizadas
para
expresión
en
EPR
y
se
ha
estudiado
su
capacidad
de
expresión
en
cultivos
celulares
de
EPR.
Finalmente,
se
han
estudiado
dos
nanopartículas
como
sistemas
de
terapia
génica
no
viral:
las
nanopartículas
proteicas
R9-‐GFP-‐H6
y
los
quitosanos
O15.
Estos
sistemas
se
han
caracterizado
mediante
su
capacidad
de
unión
al
ADN
y
la
eficacia
de
transfección
se
ha
evaluado
en
cultivos
celulares
e
in
vivo
en
el
EPR
mediante
inyección
sub-‐retiniana.
En
conclusión,
este
trabajo
ha
desarrollado
un
conjunto
de
herramientas
para
la
evaluación
de
nuevos
sistemas
de
terapia
génica
no
viral
para
RD
y
DMAE
y
ha
realizado
los
primeros
estudios
de
eficacia
con
nanopartículas
proteicas
y
quitosanos,
abriendo
nuevos
caminos
en
la
obtención
de
una
estrategia
terapéutica
eficaz
en
el
tratamiento
de
las
principales
retinopatías
vasoproliferativas.<br>Age-‐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.
43
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.
Texto completo da fonte
44
Thomas, Róisín Clare. "Nociceptin/orphanin FQ system and animal models of sepsis." Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38496.
Texto completo da fonteResumo:
The nociceptin receptor (NOP) and its ligand nociceptin/orphanin FQ (N/OFQ) have been shown to exert a modulatory effect on immune cells during sepsis. We evaluated the suitability of three different experimental animal models for studying changes in the nociceptin system; lipopolysaccharide (LPS)-induced sepsis, faecal slurry-induced sepsis and caecal ligation and puncture-induced sepsis. Methods. LPS-induced sepsis: C57BL/6mice BALB/c mice and Wistar rats were inoculated with different doses of LPS with or without a nociceptin receptor antagonist (UFP-101 or SB-612111). Fecal slurry-induced sepsis: A human stool batch was processed and a defined volume of stool suspension was injected intraperitoneally. Caecal ligation and puncture-induced sepsis: CLP was performed over 96 hours with and without the nociceptin receptor antagonist SB-612111. Results: In C57BL/6 mice LPS 0.85 mg/kg injection produced no septic response, whereas 1.2 mg/kg produced a profound response within 5 h. In BALB/c mice, LPS 4 mg/kg produced no response, whereas 7 mg/kg resulted in a profound response within 24 h. In Wistar rats LPS 15 mg/kg caused no septic response in 6/10 animals, whereas 25 mg/kg resulted in marked lethargy before 24 h. LPS-treated animals were unaffected by administration of a NOP antagonist. Similarly NOP antagonists had no effect on survival or expression of mRNA for NOP or ppN/OFQ (the N/OFQ precursor) in a variety of tissues. In these animal models, the dose–response curve for LPS was too steep to allow use in survival studies and no changes in the N/OFQ system occurred within 24 h. Faecal slurry-induced sepsis produced a similar dose response curve to LPS and did not produce changes in the N/OFQ system within 24 h however, this model could not be fully evaluated due to licence restrictions preventing the addition of supportive therapy. In the caecal ligation and puncture studies some changes were observed in the N/OFQ system in brain tissues and in serum and in some cases appeared to be reversed by SB-612111. The relevance of these changes to sepsis is not clear. Conclusion: A) LPS-inoculation in rodents is an unsuitable model for studying possible changes in the NOP-N/OFQ system in sepsis B) the faecal slurry-induced sepsis model could possibly be suitable with modifications e.g. with the addition of supportive therapy but further work is needed to evaluate this. C) Caecal ligation and puncture is suitable for studying changes in the nociceptin system.
45
Samaranayaka, Ari, and 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.
Texto completo da fonteResumo:
Biological management of populations plays an indispensable role in all areas of population biology. In deciding between possible management options, one of the most important pieces of information required by population managers is the likely population status under possible management actions. Population dynamic models are the basic tool used in deriving this information. These models elucidate the complex processes underlying the population dynamics, and address the possible consequences/merits of management actions. These models are needed to guide the population towards desired/chosen management goals, and therefore allow managers to make informed decisions between alternative management actions.
The reliability that can be placed on inferences drawn from a model about the fate of a population is undoubtedly dependent on how realistically the model represents the dynamic process of the population. The realistic representation of population characteristics in models has proved to be somewhat of a thorn in the side of population biologists. This thesis focuses in particular on ways to represent environmental stochasticity and density dependence in population models.
Various approaches that are used in building environmental stochasticity into population models are reviewed. The most common approach represents the environmental variation by changes to demographic parameters that are assumed to follow a simple statistical distribution. For this purpose, a distribution is often selected on the basis of expert opinion, previous practice, and convenience. This thesis assesses the effect of this subjective choice of distribution on the model predictions, and develops some objective criteria for that selection based on ecological and statistical acceptability. The more commonly used distributions are compared as to their suitability, and some recommendations are made.
Density dependence is usually represented in population models by specifying one or more of the vital rates as a function of population density. For a number of reasons, a population-specific function cannot usually be selected based on data. The thesis develops some ecologically-motivated criteria for identifying possible function(s) that could be used for a given population by matching functional properties to population characteristics when they are known. It also identifies a series of properties that should be present in a general function which could be suitable for modelling a population when relevant population characteristics are unknown. The suitability of functions that are commonly chosen for such purposes is assessed on this basis.
I also evaluate the effect of the choice of a function on the resulting population trajectories. The case where the density dependence of one demographic rate is influenced by the density dependence of another is considered in some detail, as in some situations it can be modelled with little information in a relatively function-insensitive way.
The findings of this research will help in embedding characteristics of animal populations into population dynamics models more realistically. Even though the findings are presented in the context of slow-growing long-lived animal populations, they are more generally applicable in all areas of biological management.
46
Haile, Melles. "Studies on new tuberculosis vaccine candidates in animal models /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-327-2/.
Texto completo da fonte
47
Lindberg, 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.
Texto completo da fonte
48
Assareh, 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.
Texto completo da fonte
49
Bickerdike, 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.
Texto completo da fonte
50
Hough, 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.
Texto completo da fonte