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1
Dedja, Arben. "Administration of L-citrulline in an animal model of perinatal lung damage." Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422175.
Повний текст джерелаАнотація:
Moderate hyperoxia and induced chorioamnionitis by intrauterine administration of endotoxin LPS into near-term pregnant rats cause alveolar and vascular lung derangement in the newborns. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of L-arginine to L-citrulline in endothelial cells. We investigated whether administering L-citrulline by raising the serum levels of L-arginine and enhancing NO endogenous synthesis, attenuates lung injury in a chorioamnionitis and/or moderate hyperoxia-induced model. Material and Methods. Newborn rats (receiving or not intrauterine LPS) were exposed to FiO2=0.6 or room air till 14 days after birth and were administered L-citrulline. Serum and lung tissues were collected for further analysis. The lung sections were subsequently stained with H&E and photomicrographs were obtained at 10X magnification. For vessel density assessment, sections were stained to reveal the presence of von Willebrand Factor Antigen. VEGF and eNOS protein expression was examined by Western blot. High performance liquid chromatography-mass spectrometry was used for simultaneous determination and quantification of ADMA, SDMA, L-arginine, L-citrulline, NMMA and homo-arginine in the serum. Results. The lung histopathology analysis of the Hyperoxia group showed a pattern typically emphysematous, similar to the LPS exposure group, when compared to controls. Exposure to hyperoxia was associated with an arrested alveolarization, inducing a change in lung morphology with patchy areas of parenchymal thickening interspersed with areas of enlarged air spaces. The lung sections of the CITR+hyperoxia and LPS+CITR rats contained smaller and more numerous air spaces, and were more similar to the control lungs. The mean alveolar size was higher in Hyperoxia group vs. controls, or LPS+CITR, in a post hoc comparison unchanged with respect to CITR+hyperoxia, or LPS, or CITR. The secondary crests were higher in the Control and CITR+hyperoxia and LPS+CITR groups than in the Hyperoxia only, or LPS only groups. VEGF gene expression evaluated by real-time quantitative PCR was lower in the Hyperoxia group, than in the CITR+hyperoxia or Control groups. Also, lung sections from Control and CITR+hyperoxia animals showed a similar vWF expression, whereas staining was weaker in the Hyperoxia group. In the CITR+hyperoxia sections there was also evidence of a better organization of the vessel network than in animals exposed to hyperoxia. The amount of eNOS protein normalized in the lung tissue from the L-citrulline treated animals was higher than in the tissues from the Hyperoxia group. Serum assessment with mass spectrometry did not show major differences in the time course and treatment groups. Conclusions. Our main findings were that: (i) administering L-citrulline proved effective in improving alveolar growth after oxygen-induced and antenatal endotoxin exposure lung damage; (ii) VEGF gene and protein were over-expressed in the group treated with L-citrulline. There may have been further protective effects on the alveolar vascular network and, consequently, on matrix maturation in our model and this may be promising with a view to BPD prevention strategies.La corioamnionite indotta dalla somministrazione intrauterina dell’endotossina LPS e da una moderata iperossia nei primi giorni di vita causano uno squilibrio alveolare e vascolare del polmone nel ratto neonato. L’ossido nitrico (NO) endogeno, che promuove la crescita polmonare, viene prodotto nelle cellule endoteliali dal metabolismo del L-arginina verso il suo prodotto, la L-citrullina. Abbiamo studiato l’efficacia della somministrazione di L-citrullina in un modello di danno indotto da corioamnionite e/o da iperossia nei ratti neonati nell’attenuare il danno polmonare intervenendo sulla sintesi del NO endogeno aumentando i livelli di L-arginina. Materiali e Metodi. I ratti neonati (che ricevono o no LPS nella loro fase intrauterina) vengono esposti a un FiO2=0.6, o ad aria ambiente, per 14 giorni dopo la nascita con la somministrazione, per alcuni di loro, della L-citrullina. A vari time-points sperimentali siero e tessuto polmonare vengono raccolti per ulteriori analisi. Le sezioni polmonari vengono colorate con ematossilina & eosina e fotografate a 10X. Per una valutazione della densità vascolare le sezioni sono colorate per la presenza dell’antigene del Fattore di von Willebrand. La VEGF e l’espressione proteica eNOS vengono esaminati con il Western blot. La HPLC Spettrometria di Massa viene usata per determinare e quantificare nel siero ADMA, SDMA, L-arginina, L-citrullina, NMMA e omo-arginina. Risultati. L’esposizione a moderati regimi di iperossia era associata istologicamente con aree estese di tipo enfisematoso, simile al quadro del gruppo esposto al LPS e, inoltre, con un arresto dell’alveolarizzazione e contestuale variazione eterogenea della morfologia polmonare, e ha indotto un cambiamento nella morfometria polmonare con aree irregolari di inspessimento parenchimatoso intervallate da aree con spazi aumentati. Il gruppo ricevente il farmaco presentava un grado di alveolarizzazione più sviluppata con un incremento del numero degli alveoli per mm2, statisticamente significativo rispetto al gruppo con iperossia. Le sezioni polmonari dei gruppi CITR+iperossia e LPS+CITR contenevano spazi più piccoli e più numerosi, simili ai controlli. Il numero delle creste secondarie era più alto nei controlli e nei gruppi CITR+iperossia e LPS+CITR, che nei gruppi con iperossia solo, o LPS sola. L’espressione genica del VEGF era più bassa nel gruppo dell’iperossia, rispetto al gruppo CITR+iperossia, o ai controlli. Inoltre, le sezioni polmonari da animali di controllo o da trattati con CITR+iperossia presentavano un’espressione vWF simile, mentre la colorazione era più bassa nel gruppo con iperossia. Nei campioni da animali trattati con CITR+iperossia era evidente anche un organizzazione migliore della rete vascolare rispetto agli animali esposti solo all’iperossia. La quantità delle proteine eNOS normalizzate nei tessuti polmonari da animali trattati con L-citrullina era più alta che nei tessuti del gruppo con sola iperossia. La valutazione con spettrometria di massa dei campioni di siero non ha mostrato grandi differenze tra i gruppi trattati. Conclusioni. In conclusione abbiamo provato che: (i) la somministrazione della L-citrullina aiuta la crescita alveolare nel danno polmonare da ossigeno, o da esposizione antenatale a endotossina; (ii) il gene e la proteina VEGF sono over-espressi nel gruppo trattato con L-citrullina. Ulteriori effetti protettivi potranno essere manifesti sul network alveolare e vascolare del polmone e, di conseguenza, sulla maturazione della matrice nel nostro modello di danno polmonare; tutto questo potrà essere promettente in vista di una strategia della prevenzione della broncodisplasia polmonare.
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Gamboa, Teresa Paula Rocha Soeiro Tavares. "Repercussões crónicas nas vias aéreas da hiperóxia neonatal : modelo experimental." Doctoral thesis, Faculdade de Ciências Médicas. Universidade Nova de Lisboa, 2007. http://hdl.handle.net/10362/5516.
Повний текст джерелаАнотація:
RESUMO: O objectivo deste trabalho foi avaliar se a exposição crónica neonatal à hiperóxia mo-derada induz alterações funcionais e estruturais persistentes nas vias aéreas. Desenvolveu-se um modelo animal, no rato, a partir do qual se retiraram implicações para a compreensão das repercussões crónicas da hiperóxia neonatal sobre as vias aéreas de displasia broncopulmonar (DBP), em duas fases distintas: imediatamente após a exposi-ção neonatal a 50%O2 (grupo 50%O2) e após três semanas de recuperação em ar ambiente (grupo 50%O2+Ar).Compararam-se os resultados da resposta do músculo liso de traqueia (MLT) à esti-mulação in vitro com metacolina e salbutamol e avaliaram-se as alterações quantitativas da área de MLT, bem como as alterações qualitativas da estrutura da traqueia. Demonstrou-se que a exposição a 50% de oxigénio não tinha repercussões imediatas sobre a resposta in vitro do MLT à estimulação colinérgica, mas que induzia um aumento do relaxamento em resposta ao salbutamol. A contractilidade do MLT em resposta à estimula-ção com metacolina no grupo 50%O2+Ar foi significativamente superior à do grupo de con-trolo da mesma idade e também superior à observada no grupo 50%O2, enquanto que a resposta ao salbutamol se voltou a aproximar dos valores de controlo após a recuperação em normóxia. Não se observaram diferenças estatisticamente significativas na área de MLT entre os grupos experimental e de controlo, o que se deve provavelmente ao número reduzido de amostras avaliadas e à variabilidade deste parâmetro no grupo de controlo; contudo, verifi-cou-se um aumento médio de 15% imediatamente após a exposição à hiperóxia que persis-tiu após o período de recuperação.As alterações qualitativas sobre a arquitectura da traqueia, avaliadas por microscopia óptica, revelaram no grupo 50%O2 aumentos da espessura da matriz extracelular e da den-sidade de mastócitos desgranulados na submucosa e adventícia vizinhas do MLT, sem outras alterações relativamente ao grupo de controlo com 15 dias. As alterações da matriz extrace-lular foram reversíveis após a recuperação em ar ambiente. A densidade de mastócitos per-maneceu superior à do grupo de controlo de 36 dias de idade, apresentando-se em maior contiguidade com o MLT relativamente ao grupo 50%O2. Em síntese, demonstrou-se que a hiperóxia neonatal crónica em níveis moderados in-duz alterações da resposta contráctil do MLT e da estrutura da traqueia que podem ter ex-pressão funcional após a exposição ter cessado. Assim, o contributo original do presente trabalho foi o desenvolvimento de um modelo animal que permite avaliar os mecanismos pelos quais a hiperóxia é capaz de induzir, isoladamente, alterações crónicas da contracti-lidade, do relaxamento do ML e da estrutura das vias aéreas que podem ser responsáveis pela HRB persistente em doentes sujeitos a oxigenioterapia neonatal.-------------ABSTRACT: The aim of this work was to evaluate whether chronic neonatal exposure to hyperoxia in-duces persistent structural and functional airway changes. An animal model was developed, using neonatal rats, in order to understand the chronic effects of neonatal hyperoxia on the airways, in bronchopulmonary dysplasia, in two distinct phases: immediately after neonatal exposure to 50%O2 (50%O2 group) and after three weeks of recovery at ambient air (50%O2+Ar group).The results from the tracheal smooth muscle (TSM) response to in vitro stimulation with metacholine and salbutamol were compared and quantitative changes in TSM area, as well as qualitative changes in tracheal structure were evaluated. It was demonstrated that while exposure to 50% oxygen had no immediate effects on in vitro TSM response to cholinergic stimulation, it induced an increase in relaxation as a result of salbutamol administration. TSM contractility as a result of methacholine administration in the 50%O2 + Ar group was significantly higher than that of the same-age control group, and also higher than the one observed in the 50%O2 group, whereas the response to salbutamol admini-stration was once again closer to the control values after recovery in normoxia. There were no statistically significant differences in the TSM area between the experi-mental and control groups, which is most likely due to the reduced number of samples evalu-ated and to the variability of this parameter in the control group. However, there was an aver-age increase of 15% immediately after exposure to hyperoxia, which persisted after the recov-ery period. Qualitative changes in tracheal architecture, evaluated by optic microscopy, revealed that the 50%O2 group suffered an increase in the thickness of the extracellular matrix and degranu-lated mast cell density in the submucosa and adventitia adjacent to the TSM, without further changes when compared with the control group at 15 days of age. The changes in extracellular matrix were reversible after recovery in ambient air. Mast cell density remained higher than that of the control group at 36 days of age, and more contiguous to TSM than the 50%O2 group. In conclusion, it has been demonstrated that moderate levels of chronic neonatal hyperoxia in-duce changes in TSM contractile response and tracheal structure, which may be functionally ex-pressed after discontinuation of exposure. Therefore, the original contribution of the present work was the development of an animal model which allows the evaluation of the mechanisms through which hyperoxia alone can induce chronic changes in contractility and relaxation of SM and also in airway structure that can be responsible for the persistent airway hyperrespon-siveness found in patients who were submited to neonatal oxygen therapy.
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Pilley, Elizabeth Sarah. "Effects of antenatal inflammation and postnatal oxygen fluctuation on developing white matter in a rodent model of prematurity." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23619.
Повний текст джерелаАнотація:
Inflammation and oxidative stress are increasingly recognised as important independent mediators of preterm brain injury and have been implicated in the pathogenesis of cerebral palsy and cognitive impairment. Such exposures are common for the premature infant in whom infection and inflammatory morbidities occur in around 60%. Furthermore, many preterm infants require oxygen therapy and respiratory support due to lung immaturity. Epidemiological and experimental studies indicate that in addition to the independent effects of inflammation and extreme hyperoxia on the developing brain, inflammation preconditions the developing brain resulting in variable injury when exposed to subsequent hypoxia-ischaemia. However experimental studies employing exposure to more modest oxygen fluctuations are lacking. This thesis characterises a clinically relevant model of prematurity where the developing brain is exposed to low grade inflammation and oxygen fluctuation around a hyperoxic mean. We hypothesise that antenatal inflammation and postnatal oxygen fluctuation, both alone and in combination, have detrimental effects on developing white matter. Pregnant dams received intraperitoneal lipopolysaccharide (LPS) or saline on G18 and G19. Dams and their pups were then reared in room air or fluctuating hyperoxia (circa 10kPa) for seven days. We measured longitudinal brain and body growth in different experimental groups to 12 weeks. Whole brains were examined for mRNA expression of inflammatory cytokines (TNFα, IL-1β, IL-6 and IL-10) and markers of oxidative injury (iNOS, SOD2). To determine the effect of perinatal insults on developing white matter, we analysed the expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the internal and external capsule. We also examined white matter tracts for differences in microglia (CD68), oligodendrocyte progenitor cells (NG2), oligodendroglial cells (Olig2) and cell death (cleaved caspase3). Behavioural studies (Morris Watermaze Test, Elevated Plus Test and Open Field Test) were undertaken at 12 weeks of age to detect any long-term functional difference between the groups. Antenatal inflammation reduces both brain and body growth at P7. This normalises by P14 unless this inflammatory insult has been followed by postnatal oxygen fluctuation, where brain and body growth restriction persists until P14. We defined our inflammatory response at P1 following antenatal inflammation and did not observe elevation of mRNA at P1. We demonstrated increased SOD2 at this time point, indicating a reparative process. At P7 we observed a significant reduction in the oxidative response following combined exposure to antenatal inflammation and postnatal oxygen fluctuation, indicating a potential limit to, or suppression of, the reparative process. In terms of white matter injury, antenatal inflammation reduces myelination at P7. There is no synergistic effect of inflammation and oxygen fluctuation on MBP immunohistochemistry at P7. However, MBP mRNA expression is increased in pups exposed to both insults compared to those exposed to inflammation alone suggesting that the oxygen fluctuation may stimulate MBP production in response to oxidative injury. MBP mRNA levels and protein expression have all normalised by P14. We observed a reduction in total cell number in the external capsule and corpus callosum in the dual insult group, without an increase in caspase. In keeping with other studies we detected no effect of our perinatal insults on NG2+ve oligodendrocytes. Olig2+ve cell numbers were also consistent between experimental groups. In further characterisation of the cellular response, antenatal inflammation followed by postnatal oxygen fluctuation resulted in a decrease in GFAP mRNA at P7, an effect which was reversed and significantly increased by P14 suggesting delayed activation of the innate immune system. No difference was observed in microglial numbers between experimental groups. There was however, increased microglial cell death (CD68 + caspase) in the group exposed to antenatal inflammation. When this insult was combined with postnatal oxygen fluctuation there was a comparative decrease in microglial cell death, which may reflect an earlier peak of microglial cell death, due to an increased and sustained inflammatory stimulus. Morris Watermaze testing demonstrated that pups exposed to both insults took longer than controls to locate the hidden platform on day 1, which is a measure of spatial learning. The Elevated Plus Test and Open Field Test demonstrated that pups exposed to both insults were less anxious and took more risks than pups exposed to single insults. In conclusion, within a clinically relevant preterm model, antenatal inflammation transiently disrupts both brain and body growth and myelination of the motor tracts of the developing brain. Moreover, when combined with postnatal oxygen fluctuation, detrimental effects on growth are amplified and sustained. Decreased cell numbers are also observed within white matter tracts. In terms of long term functionality, these pups display disinhibition of behaviour as young adults. Collectively, this thesis demonstrates that synergistic actions of common low-grade perinatal insults may alter normal neurodevelopment, and that this may carry a risk of neurodevelopmental sequelae for preterm infants.
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Smit, Elisa. "Effects of hyperoxia and therapeutic hypothermia in an immature rat model of neonatal hypoxicischaemic brain damage." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.685357.
Повний текст джерелаАнотація:
The introduction of therapeutic hypothermia and the guidance on the cautious use of oxygen during resuscitation of newborn infants are two of the greatest advances in neonatal care over the last decade. The combination of the two has not been researched in great detail, but is of great clinical relevance. This thesis discusses and investigates the use of 100% oxygen following resuscitation in an immature rat model of hypoxiaischaemia in combination with therapeutic hypothermia. Pups on postnatal day 7 are traditionally used in this model. However, pups on postnatal day 10 (P10) are more appropriate as a model for term hypoxicischaemic brain damage and this was developed as a new model. An increase in survival with mild brain injury was seen when using 100% oxygen during resuscitation in P10 pups. This will need to be further explored in larger animal models. An improved cerebral cortical blood flux was seen in pups resuscitated in 100% oxygen, which could be an explanation for the reduction in injury seen in survivors. No change in brain injury was seen following resuscitation in 100% oxygen in a model of severe hypoxia-ischaemia. An attempt was made to create a reproducible and more immature rat model for preterm hypoxia-ischaemia using pups on postnatal day 4. This was however difficult and the process is described. Add-on treatments to cooling are the future for infants with hypoxic-ischaemic encephalopathy and some of these will certainly be introduced as standard care in the coming decade. Further research investigating the side-effects of cooling and redefinition of the treatment (time-window, degree of hypothermia, patient selection) as well as investigating the combination of oxygen, therapeutic hypothermia and some of the new add-on treatments is highly desirable and suggested as a new avenue for exploration.
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Brännström, Åke. "Modelling animal populations." Doctoral thesis, Umeå universitet, Matematik och matematisk statistik, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-205.
Повний текст джерелаАнотація:
This thesis consists of four papers, three papers about modelling animal populations and one paper about an area integral estimate for solutions of partial differential equations on non-smooth domains. The papers are: I. Å. Brännström, Single species population models from first principles. II. Å. Brännström and D. J. T. Sumpter, Stochastic analogues of deterministic single species population models. III. Å. Brännström and D. J. T. Sumpter, Coupled map lattice approximations for spatially explicit individual-based models of ecology. IV. Å. Brännström, An area integral estimate for higher order parabolic equations. In the first paper we derive deterministic discrete single species population models with first order feedback, such as the Hassell and Beverton-Holt model, from first principles. The derivations build on the site based method of Sumpter & Broomhead (2001) and Johansson & Sumpter (2003). A three parameter generalisation of the Beverton-Holtmodel is also derived, and one of the parameters is shown to correspond directly to the underlying distribution of individuals. The second paper is about constructing stochastic population models that incorporate a given deterministic skeleton. Using the Ricker model as an example, we construct several stochastic analogues and fit them to data using the method of maximum likelihood. The results show that an accurate stochastic population model is most important when the dynamics are periodic or chaotic, and that the two most common ways of constructing stochastic analogues, using additive normally distributed noise or multiplicative lognormally distributed noise, give models that fit the data well. The latter is also motivated on theoretical grounds. In the third paper we approximate a spatially explicit individual-based model with a stochastic coupledmap lattice. The approximation effectively disentangles the deterministic and stochastic components of the model. Based on this approximation we argue that the stable population dynamics seen for short dispersal ranges is a consequence of increased stochasticity from local interactions and dispersal. Finally, the fourth paper contains a proof that for solutions of higher order real homogeneous constant coefficient parabolic operators on Lipschitz cylinders, the area integral dominates the maximal function in the L2-norm.
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Camus, Sandrine. "Etho-Psychiatry : animal model to model animal : Identification of a « spontaneous » non-human primate model of depressive symptoms." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22032/document.
Повний текст джерелаАнотація:
Plus de 150 millions de personnes souffrent de troubles dépressifs à travers le monde. Malgré le nombre croissant d’études s’intéressant à la physiopathologie de ce trouble, aucune amélioration majeure concernant ses traitements ou la compréhension des mécanismes biologiques sous-jacents n’a été faite. Bien qu’une prédisposition génétique et des évènements stressants aient été proposés comme facteurs de risque, ni les gènes impliqués ni le fonctionnement des interactions gène x environnement ne sont encore connus. Cela peut s’expliquer par le manque de modèles animaux satisfaisants et par le fossé existant entre les connaissances / méthodes de diagnostic appliquées en recherche clinique et celles disponibles en recherche fondamentale. Des manipulations pharmacologiques, lésionnelles, génétiques ou de l’environnement sont quasi exclusivement utilisées chez le rongeur. Certains primates non-humains (PNH), plus proches de nous sur les plans comportementaux et phylogénétiques, montrent pourtant, comme l’Homme, des modifications comportementales et physiologiques atypiques et spontanées en réponse à des conditions de vie stressantes. Malgré les travaux pionniers et prometteurs d’Harlow et de ses collaborateurs dans les années 60, rares sont les équipes qui étudient la dépression chez le macaque aujourd’hui. Nous avons émis l’hypothèse que parmi des grandes populations de PNH captifs, une petite proportion d’individus exprime des comportements atypiques pouvant s’apparenter à des symptômes dépressifs. Mon projet de thèse a eu pour but de proposer une approche novatrice et non invasive d’identification de ces profils « depressive-like » chez le macaque, en combinant les compétences et connaissances de l’éthologie, de la psychiatrie et des neurosciences. L’impact des expériences de vie précoces et de l’espèce a également été abordé. Les comportements, les postures et orientations du corps, les localisations spatiales, les regards et/ou les distances inter-individuelles ont été relevés chez plus de 200 macaques rhésus et cynomolgus d’élevage, nés en captivité ou dans la nature. Des sous-groupes d’individus ont été identifiés à l’aide d’analyses multifactorielles. Dans chaque population observée, un profil « depressive-like » a été mis en évidence par comparaison avec les symptômes décrits dans le Manuel Diagnostique et Statistiques des Troubles Mentaux et avec les modèles animaux existants dans la littérature. La prévalence de ces profils étant supérieure chez les macaques rhésus et chez les animaux nés en captivité, nos résultats concordent avec le rôle suggéré du stress dans l’expression des troubles dépressifs. En plus d’exprimer ce profil comportemental atypique dans leur environnement habituel, les singes « depressive-like » présentaient une réactivité émotionnelle altérée au cours 2 tests comportementaux, associée à des taux élevés de cortisol plasmatique et noradrénaline cérébro-spinale. Pris dans leur ensemble, ces résultats prometteurs confèrent une bonne validité de représentation à notre modèle macaque de symptômes dépressifs. Une caractérisation plus complète de ce modèle est bien sûr nécessaire et pourrait ouvrir de nouvelles perspectives quant à la compréhension de l’étiologie et de la physiopathologie des troubles dépressifsMore than 150 million people worldwide suffer from major depressive disorder (MDD). Although investigations of its pathophysiology have dramatically increased in the last decade, no substantial improvement has been made concerning the treatments and the understanding of its underlying mechanisms. A genetic predisposition and stressful experiences have been acknowledged as risk factors involved in MDD. However, no specific genes have been identified so far and little is known about the gene x environment interactions. This is likely due to the lack of bona fide animal models of depressive-like symptoms. Indeed, there is a huge gap between the knowledge / diagnostic methodology of clinical research and the animal models used in fundamental research, mainly focusing on environmental, pharmacological, lesional or genetic manipulations. Phylogenetically and behaviourally closer to Humans compared to rodents, non-human primates (NHPs) can show spontaneous behavioural and physiological modifications in response to stressful life events. Although promising results had been reported in the 1960’s by the pioneering studies of Harlow and colleagues, the investigation of depressive-like symptoms in macaques are scarce in the current literature. We hypothesize that, among large captive NHP populations, a few individuals will display atypical behaviours that could mimic depressive symptoms. Combining the skills and knowledge of ethology, psychiatry and neurosciences, my PhD project aimed at proposing an innovative non-invasive detection method of such depressive-like profiles. The impact of birth origin and species was questioned as well. Behaviours, body postures, body orientations, spatial location, gaze direction and/or inter-peer distances were collected among more than 200 rhesus and cynomolgus captive- or wild-born farm-bred macaques. Using multifactorial analyses, clusters of individuals displaying distinct behavioural profiles were identified. In each population, a common depressive-like profile was characterised by its similarities with symptoms described in the Diagnostic and Statistical Manual of Mental Disorder and with other animal models of depression. The prevalence of such profiles was increased in the rhesus populations and by captive early life experience, corroborating the role of stress in the development of MDD. In addition to expressing depressive-like features in their home cage, these animals displayed higher levels of plasmatic cortisol and cerebrospinal noradrenaline which correlated with a passive emotional reactivity in 2 behavioural paradigms. Altogether these promising results conferred good face validity to our NHP model of depressive-like symptoms. Further characterization of this model is required and might bring new insights to the understanding of MDD pathophysiology and etiology
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Cullen, J. R. "Sudden hearing loss : an animal model." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326426.
Повний текст джерела
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Devor, Devin Patrick. "Effects of Hyperoxia on Thermal Tolerance and Indicators of Hypoxic Stress in Antarctic Fishes That Differ in Expression of Oxygen-Binding Proteins." Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1362666619.
Повний текст джерела
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Stewart, Richard James. "Aspects of unilateral cryptorchidism : an animal model." Thesis, Queen's University Belfast, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336195.
Повний текст джерела
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Godinho, Sofia Isabel Henriques. "An animal model of acute lung injury." Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424508.
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Parsons, Sven David Charles. "Natural animal model systems to study tuberculosis." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/4505.
Повний текст джерелаАнотація:
Thesis (PhD (Molecular Biology and Human Genetics))--University of Stellenbosch, 2010.ENGLISH ABSTRACT: The growing global epidemic of human tuberculosis (TB) results in 8 million new cases of this disease and 2 million deaths annually. Control thereof will require greater insight into the biology of the causative organism, Mycobacterium tuberculosis, and into the pathogenesis of the disease. This will benefit the design of new vaccines and diagnostic assays which may reduce the degree of both disease transmission and progression. Animal models have played a vital role in the understanding of the aetiology, pathogenesis, and treatment of TB. Much of such insight has been obtained from experimental infection models, and the development of new vaccines, for example, is dependant on these. Nonetheless, studies utilising naturally occurring TB in animals, such as those which have investigated the use of interferon-gamma release assays (IGRA) for its diagnosis, have contributed substantially to the body of knowledge in this field. However, there are few such examples, and this study sought to identify and investigate naturally occuring animal TB in South Africa as an opportunity to gain further insight into this disease. During the course of this study, the dassie bacillus, a distinctly less virulent variant of M. tuberculosis, was isolated from a rock hyrax from the Western Cape Province of South Africa. This has provided new insight into the widespread occurrence of this organism in rock hyrax populations, and has given impetus to further exploring the nature of the difference in virulence between these pathogens. Also investigated was M. tuberculosis infection in dogs in contact with human TB patients. In so doing, the first reported case of canine TB in South Africa was described, v a novel canine IGRA was developed, and a high level of M. tuberculosis infection in these animals was identified. This supports human data reflecting high levels of transmission of this pathogen during the course of human disease. Additionally, the fact that infected companion animals may progress to disease and potentially act as a source of human infection was highlighted. However, an attempt to adapt a flow cytometric assay to study cell-mediated immune responses during canine TB revealed the limitations of such studies in species in which the immune system remains poorly characterised. The use of IGRAs to diagnose TB was further explored by adapting a human assay, the QuantiFERON-TB Gold (In-Tube Method), for use in non-human primates. These studies have shown that such an adaption allows for the sensitive detection of TB in baboons (Papio ursinus) and rhesus macaques (Macaca mulatta) and may be suitable for adaption for use in other species. However, they have also evidenced the limitation of this assay to specifically detect infection by M. tuberculosis. Finally, to contextualise the occurrence of the mycobacterial infections described above, and other similar examples, these have been reviewed as an opinion piece. Together, these investigations confirm that animal models will continue to make important contributions to the study of TB. More specifically, they highlight the opportunities that naturally occuring animal TB provides for the discovery of novel insights into this disease.
AFRIKAANSE OPSOMMING: Wêreldwye tuberkulose (TB) epidemie veroorsaak agt miljoen nuwe gevalle en twee miljoen sterftes jaarliks. Ingryping by die beheer hiervan vereis begrip van die biologie van die mikroörganisme Mycobacterium tuberculosis, die oorsaak van TB, asook van die patogenese van die siekte self. Hierdie kennis kan lei tot ontwerp van nuwe entstowwe en diagnostiese toetse wat gevolglik beide die oordrag- en vordering van die siekte mag bekamp. Dieremodelle speel lankal 'n rol in ons begrip van die etiologie-, patogenese- en behandeling van TB. Insig is grotendeels verkry vanaf eksperimentele infeksiemodelle, en ontwikkeling van entstowwe, onder andere, is afhanklik van soortgelyke modelle. Desnieteenstaande, studies wat natuurlike TB voorkoms in diere ondersoek, byvoorbeeld dié wat op die ontwikkeling van interferon-gamma vrystellingstoetse (IGVT) fokus, het merkwaardige bydrae gemaak tot kennis en begrip in hierdie studieveld. Daar is slegs enkele soortgelyke voorbeelde. Om hierdie rede is die huidige studie uitgevoer waarbinne natuulike diere-TB geïdentifiseer en ondersoek is in Suid-Afrika om verdere kennis en insig te win aangaande TB. Die "dassie bacillus", bekend om beduidend minder virulent te wees as M. tuberculosis, is tydens hierdie studie geïsoleer vanuit 'n klipdassie (Procavia capensis) in die Wes-Kaapse provinsie, Suid-Afrika. Insig in die wydverspreide voorkoms van hierdie organisme in klipdassie bevolkings is gevolglik verkry en verskaf momentum om die aard van verskil in virulensie tussen dié patogene te bestudeer. vii Voorts is M. tuberculosis infeksie bestudeer in honde wat in kontak is met menslike TB pasiënte en word die eerste geval van honde TB dus in Suid-Afrika beskryf. In hierdie groep diere, is 'n hoë vlak van M. tuberculosis infeksie geïdentifiseer deur gebruik te maak van 'n nuut ontwikkelde IGVT vir die diagnose van honde TB. Gevolglik ondersteun dié studie bevindinge van menslike studies wat toon dat besondere hoë vlakke van M. tuberculosis oordrag voorkom gedurende die verloop van die siekte. Verder toon die studie dat geïnfekteerde troeteldiere 'n bron van menslike infeksie kan wees. 'n Poging om 'n vloeisitometriese toets te ontwikkel om die aard van selgefundeerde immuunreaksies te bestudeer in honde met TB toon die beperkings van dergelike studies in spesies waarin die immuunsisteem gebrekkig gekarakteriseer is. Die gebruik van IGVT'e in die diagnose van TB is verder ondersoek deur 'n menslike toets (QuantiFERON-TB Gold, In-Tube Method) aan te pas vir die gebruik van nie-menslike primaat gevalle. Hierdie studies toon gevolglik dat so 'n aanpassing toepaslik is vir hoogs sensitiewe deteksie van TB in chacma bobbejane (Papio ursinus) en rhesus ape (Macaca mulatta), en mag ook aangepas word vir gebruik in ander spesies. Tog word die beperkings van hierdie toets om infeksie wat spesifiek deur M. tuberculosis veroorsaak uitgelig. Ter afsluiting word hierdie studie in konteks geplaas deur 'n oorsig te gee van bogenoemde- en soortgelyke gevalle van dierlike infeksie deur mikobakterieë in Suid-Afrika. Hierdie studies bevestig dat dieremodelle steeds belangrike toevoegings maak tydens die bestudering van TB en lig veral die moontlikhede uit dat bestudering van natuulike TB in diere kan lei tot die ontdekking van nuwe insigte ten opsigte van die siekte self.
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Faig, Martí Jordi. "Nou model animal experimental per a l'artrosi precoç." Doctoral thesis, Universitat de Barcelona, 2003. http://hdl.handle.net/10803/1207.
Повний текст джерелаАнотація:
Introducció: Les malalties que afecten el sistema locomotor produeixen una gran limitació en la funcionalitat de la població, especialment en les edats avançades de la vida. Per progressar en el coneixement de l'artrosi es va engegar el treball que presentem, com a model experimental que permetés estudiar tractaments en un model animal per a les fases inicials d'aquesta malaltia.Material i Mètode: Per portar a terme l'estudi es van utilitzar 15 bens adults de 3 anys d'edat. En condicions d'asèpsia, el grup d'animals és sotmès a una intervenció al genoll esquerre per crear una lesió condral amb una llima als dos còndils femorals i ròtula sense lesionar tot el gruix de cartílag. En cap cas es pretén arribar a l'os subcondral. El genoll dret, que no es toca, servirà de control. Es divideix els animals en 3 subgrups per ser sacrificats a les 28, 48 i 104 setmanes. Es preparen mostres histològiques osteocartilaginoses per a l'estudi histològic. L'estudi de les mostres ha inclòs una part histològica qualitativa i quantitativa, un estudi bioquímic i l'estudi de la línia osteocondral.
Resultats: En el cartílag lesionat es produeix una necrosi cel·lular amb un augment del metabolisme de les cèl·lules restants que es tradueix en un augment en l'activitat replicativa donant lloc als clusters, que en conjunt determinen un augment de la cel·lularitat total a les capes superficials. S'observen canvis histològics i bioquímics típics de l'artrosi com ara disminució de glucosamina (que indica una disminució del queratan sulfat) i augment de galactosamina (que indica un augment de condroitin sulfat). L'estudi de la línia osteocondral no va mostrar diferències en els animals en els que es va crear la lesió respecte als controls. Els resultats s'han analitzat estadísticament per conèixer la significació de les diferències observades entre els grups.
Conclusions: L'escarificació de la superfície del cartílag articular del genoll en el be produeix canvis histològics i bioquímics típics de l'artrosi que no guareixen espontàniament. Als dos anys de produir la lesió s'observa una progressió de les lesions que no permet incloure el grup corresponent dins el model d'artrosi precoç. Així doncs, els experiments que utilitzin aquest model per estudiar el tractament de l'artrosi precoç hauran de realitzar-se abans dels dos anys de crear la lesió del cartílag articular.
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Mercer, David Frederick. "Development of an animal model of hepatitis C." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0009/NQ60004.pdf.
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Munguia, Raymundo. "CiprofloxacinDexamethasone ototoxicity in an animal and human model." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97975.
Повний текст джерелаАнотація:
Introduction. Ototoxicity refers to medication-caused auditory and/or vestibular system dysfunction resulting in hearing loss or dysequilibrium. The potential damage that antibiotics eardrops can produce when placed directly into the middle ear in some cases is still unknown.Objectives. To determine the safety of use of the new ciprofloxacin/dexamethasone otic drops in patients without an intact tympanic membrane.
Materials and methods. Ciprodex/dexamethasone eardrops were tested in an animal and human model. The animal part was performed in 13 adult chinchillas; Auditory Brainstem Response (ABR) was used. For the human part, twenty subjects were enrolled in the study; Distortion Products Otoacoustic Emissions (DPOAE) testing was used.
Results. Animal Part: after the tube insertion ABR threshold mean value was 19.6+/-13.3 dB for all the animals. On the last evaluation (day 60), the mean threshold was 19+/-13 dB for the experimental ears, and 13.7+/-12.2 dB for the control ears, this overall analysis showed no significant effect (p-value = 0.661). Human Part: the mean thresholds for the pre-treatment test were 4.87+/-6,34 dB for the DP value and -0.87+/-7.93 dB for the Ns value. In the post-treatment evaluation the mean thresholds were 3.48+/-4.40 dB for the DP value and -8.02+/-7.57 dB for the Ns value.
Conclusions. The use of CiprodexTM eardrops seems to be safe when instilled in ears without an intact tympanic membrane.
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Qasim, Faieza Jabeen. "Study of an animal model of experimental vasculitis." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361670.
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Hallam, B. "Simulating animal conditioning : investigating Halperin's neuro-connector model." Thesis, University of Edinburgh, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651976.
Повний текст джерелаАнотація:
This dissertation describes simulation work which starts an investigation into Halperin's [1990] claim that her Neuro-Connector model is 'plausible as a general model of vertebrate learning'. One way of testing a claim such as this is to examine the model's ability to reproduce learning phenomena which are not part of the model's development history. Choosing a phenomenon which is not one of those that the model was specifically built to reproduce tests the model's ability to generalise. This gives creedance to the claim that the model represents or explains some actual underlying mechanism. This implementation was made to produce results similar to those of standard animal experiments for the following classical conditioning phenomena: acquisition, extinction, reacquisition of an extinguished response, the effect of interruptions, changing the inter-stimulus interval, the effect of closely-massed trials, pre-exposure to the CS, second-order conditioning, and postponed conditioning. However, in some cases implausible assumptions or starting conditions are necessary in order to achieve these results. The implementation could not produce results mirroring those of animal for the effects of partial reinforcement, variations in US duration, pre-exposure to the US, or varying the trace interval. It can produce backward conditioning under some circumstances; backward conditioning is a source of debate amongst animal researchers. Other classical conditioning phenomena were not investigated. The simulation only implements the main features of the model. An implementation of the full model should be able to reproduce sensory pre-conditioning and probably US duration effects despite these not being possible with the implementation used. Preliminary investigation of instrumental conditioning showed that reward training and an approximation to punishment training were reproducible. Avoidance training and omission training were not possible due to the model failing to deal with the non-occurrence of expected events. The biological plausibility of model and implementation are discussed in the light of the findings reported in this dissertation which, though only a beginning, nevertheless provides an unusually complete examination of the plausibility of the model and a strong experimental basis for its assessment. Some suggestions for improvements to the model are given.
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Leung, Wai-hin, and 梁瑋軒. "Neurogenesis in animal model of systemic lupus erythematosus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/209497.
Повний текст джерелаАнотація:
Systemic Lupus Erythematosus (SLE) is an autoimmune disease which is characterized by high level of autoantibody detected in the body. This disease is female predominant with a male to female ratio 1: 9. SLE could cause damage to different organ systems and central nervous system is one of them. Patients diagnosed with SLE could suffer from psychiatric problems like cognitive dysfunction, depression and anxiety.
Neurogenesis refers to the process by which new neurons are generated. Although it has been widely reported that neurogenesis could be enhanced under pathological conditions such as stroke, Huntington’s disease and epilepsy, study focusing on the relationship between neurogenesis and SLE remains limited.
In the present study, by using NZB/W F1 mice as the animal model of SLE, we could demonstrate that there was dramatic increase of neuronal precursor cells at the corpus callosum after the onset of SLE symptoms. Meanwhile, as IBA-1 positive cells and GFAP positive cells also increased significantly there, this suggested inflammation has taken place. I hypothesized there were upregulation of immunological factors after the onset of SLE symptoms and those factors were responsible for the neurogenesis. In my in vitro study, cytokine- interferon gamma (IFN gamma) has been shown to promote neuronal progenitor cells (NPCs) to differentiate into neuronal linage but it did not obviously affect the cell proliferation and migration. For the other cytokine and chemokines, including interleukin-10 (IL-10), interleukin-8 (IL-8), macrophage-derived chemokine (MDC), stromal cell-derived factor 1 alpha (SDF-1alpha) and thymus and activation regulated chemokine (TARC), all of them had no effect on NPC proliferation and differentiation.
As far as we know, this is the first study to report SLE could enhance neurogenesis. Concerning the role of inflammation and IFN gamma on the neurogenesis in our case, it should be worth for further investigation, which will benefit future development of novel treatment targeting psychiatric symptoms in SLE.published_or_final_version
Anatomy
Master
Master of Philosophy
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Chaniary, Kunal. "Electrophysiological Analysis in an Animal Model of Dystonia." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/93.
Повний текст джерелаАнотація:
Dystonia is a movement disorder characterized by patterned, repetitive, and sustained muscle contractions that cause ineffective and often painful movements. The overall goal of this project was to understand the physiological mechanisms of dystonia in a rodent model as a basis for developing innovative treatments for secondary dystonias. The first half of the project was focused at developing essential techniques for systematically investigating the movement disorder in these animals. For achieving this, an innovative, multi-faceted approach was pursued starting with electromyographic (EMG) analysis for animal model validation, gait analysis for dystonia quantification, and development of a novel stereotaxic apparatus for recording brain activity during awake conditions. The later half of the project was focused on understanding how brain circuitry produces abnormal motor control in dystonia. Single and multi-unit neuronal activity was collected from individual basal ganglia nuclei along with EMG recordings to characterize the abnormal patterns of firing in dystonic animals and determine how neurons within individual nuclei communicate in dystonia, respectively. The findings of the current project have lead to new insights into the pathophysiology and treatment of secondary kernicteric dystonia and other secondary dystonia in humans.
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Chaniary, Kunal Dilip. "Electromyographic Characterization in an Animal model of Dystonia." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/648.
Повний текст джерелаАнотація:
Kernicterus causes damage to the auditory system and the basal ganglia in humans. Although the Gunn rat model of kernicterus has been extensively used to characterize the auditory features, this model has not been utilized to systematically investigate the movement disorder. In the present study, spontaneously jaundiced (jj) 16 day old Gunn rat pups were treated with sulfadimethoxine to exacerbate bilirubin neurotoxicity and compared to saline treated jjs and non-jaundiced (Nj) littermates. Electromyographic (EMG) activity was recorded from antagonistic hip muscles in dystonic and in normal appearing rats. Raw EMG signals were decomposed using the Discrete Wavelet Transform based multi-resolution analysis, and signal coefficients corresponding to the dominant EMG frequency band were chosen. Gunn rats exposed to sulfadimethoxine developed a stable clinical state characterized by prolonged abnormal axial and appendicular postures. Coherence plots revealed 4-7 Hz co-activation in antagonistic muscles that was significantly more prominent in jj sulfa treated dystonic compared to normal rats. The EMG findings support the presence of dystonia in sulfadimethoxine exposed jj Gunn rats.
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Bellwald, Dominik. "The avascular talus : revascularization in an animal model /." Bern : [s.n.], 2004. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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DuBose, Candis Schrelle. "An animal model for discogenic low back pain." Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/794.
Повний текст джерелаАнотація:
Low back pain is a debilitating condition that afflicts millions of people each year. It is characterized by complex biochemical, morphological, and biomechanical changes. However, most believe low back pain arises due to abnormal mechanical loading, inflammation, and disc degeneration. Several studies have investigated radial back pain, but to date, there is only one in vivo animal model for low back pain. Despite advances in science, the causes of low back pain remain unclear and treatments fail to relieve the pain. To better understand the causative factors of low back pain, a reliable animal model is needed. This study was designed to advance the knowledge of the previous in vivo animal model for low back pain by investigating the effects of shear loading on disc degeneration (for a longer duration of time) and discogenic low back pain (in terms of immunohistochemistry) in hopes developing better treatment strategies for low back pain sufferers and to help elucidate the etiology of low back pain.
Adult male Sprague Dawley rats (n=31) were shear loaded for 4- and 8- weeks. Pain behavioral testing was done prior to and after surgery. After sacrifice, immunohistochemistry was used to detect the presence of pain in the intervertebral discs and the spinal cord. Results of this study indicate that the application of an abnormal shear load gives rise to disc degeneration. Histology revealed that all loaded levels as well as the adjacent levels degenerated due to the shear load. Pain behavior testing revealed that the rats did experience pain, however, when combined with the immunohistochemical results, we were able to exclude the pain as pain stemming from the degenerated discs. Surprisingly, we observed that shear loading caused scoliosis of the thoracolumbar spine.
22
Cully, Louise. "Biomechanical and physiological investigations in the IBMPFD animal model." Thesis, University of East Anglia, 2016. https://ueaeprints.uea.ac.uk/59209/.
Повний текст джерелаАнотація:
Inclusion body myopathy associated with Paget’s disease of bone and frontotemporal dementia (IBMPFD; OMIM 167320) is an autosomal dominant inherited multisystem disorder caused by mutations in the valosin-containing protein (VCP) gene. Knock-in mice expressing the common human p.R155H VCP mutation develop a progressive myopathy with ubiquitin-positive inclusion bodies, accumulation of abnormally shaped mitochondria in skeletal muscle and focal bone degradation reminiscent of Paget’s disease of bone. To further assess the physiological effects of this mutation in muscle, we compared the in vitro contractile properties of the extensor digitorum longus (EDL) (fast-twitch muscle) and soleus (slow-twitch muscle) from mice heterozygous for the p.R155H mutation in VCP and wild-type mice. Our results showed that fast-twitch muscle fibres isolated from VCPR155H/+ mutant mice ~12-15 months old not only fatigued faster and to a greater extent, but also recovered significantly slower and to a lesser degree than those of age-matched wild-type mice. Thereafter, the muscles seem to recover and by the time the mice were 27 months old, there was no difference in the fatigue resistance of mutant and wild type mice. These results suggest that VCP may be necessary for maintenance of glycolytic capacity in mouse fast-twitch muscle fibres at 12-15 months only. Investigation of oxidative capacity in 12 and 14 month old VCPR155H/+ mice revealed significantly lower mitochondrial enzyme activity (citrate synthase) in VCPR155H/+ mice at 14 months; concomitant with the reduction in fasttwitch fibre fatigue tolerance. Primary fibroblast cells isolated from our VCPR155H/+ mouse model showed reduced ability of mitochondrial networks to fragment when exposed to oxidative stress, indicating that intact VCP is required for the successful maintenance of mitochondrial network dynamics and quality control.
23
Colantonio, David A. "Troponin modifications, from animal model to the Emergency Department." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2002. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ65612.pdf.
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Richards, Sonja. "An animal model of autism : remediation with tactile stimulation." Thesis, Lethbridge, Alta. : University of Lethbridge, Dept. of Neuroscience, 2011, 2011. http://hdl.handle.net/10133/3126.
Повний текст джерелаАнотація:
This thesis examines both behavioral and anatomical effects of prenatal exposure of
Valproic Acid (VPA) on Long Evans rats. Tactile stimulation (TS) is then used to
investigate its’ effect on remediating any abnormalities VPA may produce. Several
behavioral tests were done to assess the behavioral effects of VPA and TS. It was found
that VPA had an effect of many of the tasks, whereas, TS had almost none with the
exception of an effect on females in the elevated plus maze. However, anatomical data
showed that TS had a profound effect on neuronal branch order, cell complexity, and
spine density in pyramidal neurons in the medial prefrontal cortex, the orbitofrontal
cortex and the amygdala. Where VPA decreased the above in all of these areas, TS
increased neuronal complexity in the aforementioned structures. This study demonstrates
that prenatal exposure to VPA is a viable model of autism in rats and that TS has
significant anatomical effects in these animals as well as in control animalsxi, 98 leaves; 29 cm
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Tucker, Lawrence Maskew. "Neural transplantation in an animal model for Huntington's disease." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362863.
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Najjar, Deborah Anne. "Towards a more ethical animal model in biomedical research." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/120675.
Повний текст джерелаАнотація:
Thesis: S.M., Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2018.Cataloged from PDF version of thesis.
Includes bibliographical references (pages [69]-[75]).
Since the early twentieth century, mice have emerged as the standard mammalian model organism for biomedical research. When pain relief is provided during experimentation, it typically comes in the form of transient and sometimes ineffective analgesics or anesthesia. This thesis proposes an alternative to the current method of research in the form of an engineered mouse model in which pain sensing can be ablated before an experiment. An ERT2-inducible Cre recombinase under the Wntl promoter was designed to be combined with a floxed Nav1.7 ion channel mouse model. When a 4- hydrotamoxifan class small molecule is fed to the mouse, Cre recombinase expression in the peripheral nervous system will disrupt function of the ion channel involved in inflammatory and mechanosensory pain. Additional designs for floxed Nav1.6 ion channel and Nax ion-like channel were made to explore disruption of peripheral cancer-induced neuropathic pain. In parallel with mouse model development, a survey was conducted to understand the potential for adoption of this new animal model by researchers. The survey was sent to IACUC members questioning if this model was needed, as well as how it may be regulated under the existing protocol approval framework. Results indicated that there is a both a need and desire for further refinement strategies within animal research, and that this inducible painfree mouse model could be categorized as alternative analgesic upon sufficient characterization and peer-reviewed publications. Additional input was provided that will shape testing done on the generated animals to assure that this model can mitigate animal suffering while still recapitulating important biological processes investigated in biomedical research.
by Deborah Anne Najjar.
S.M.
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Maglennon, G. A. "Study of papillomavirus latent infection in an animal model." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1306763/.
Повний текст джерелаАнотація:
Papillomaviruses cause a wide spectrum of benign and neoplastic diseases in humans and animals. They may also cause infections that are characterised by the absence of clinical signs of disease and some of these may represent viral latency. Many viruses have a latent stage of their life cycle and papillomaviruses appear to be no different. For example, some low-risk human papillomavirus types such as HPV-11 and HPV-6 can cause infections that resemble latency. It has recently been shown that rabbit oral papillomavirus (ROPV) is an appropriate model of these virus types. Infection of the tongue mucosa with ROPV leads to the formation of benign papillomas that form and regress within a matter of weeks. In this thesis, we show that ROPV is a suitable model system for the study of latent papillomavirus infections. The regression of ROPV papillomas is followed by the persistence of viral DNA and RNA in the absence of clinical signs of disease. Persistence of ROPV DNA is generally restricted to basal epithelial cells at sites of previous infection. Low copy numbers of viral DNA in the basal layer are compatible with infection remaining in only a subset of these cells (possibly epithelial stem cells). Typically there is no amplification of viral DNA in the upper layers of the epithelium. ROPV proteins are undetectable during latency suggesting that the productive stages of the life cycle are not completed. Low levels of ROPV early transcripts are detectable and it is possible that early proteins are necessary to allow stable maintenance of viral episomes in basal epithelial cells. We attempt to demonstrate the ability of latent ROPV infection to reactivate to form clinical disease. Evidence of spontaneous reactivation was seen on one occasion, but efforts to initiate reactivation by immunosuppressing rabbits were hampered by the toxicity of the drugs used. However, our preliminary data suggest that immunosuppression of rabbits can cause reactivation of latent ROPV.
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Pomeroy, Ian. "Neocortical lesions in an animal model of multiple sclerosis." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670186.
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Alexander, Kathleen Shannon. "Elevated Kynurenic Acid as an Animal Model of Schizophrenia." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1304691359.
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Remus, Jennifer Lynn. "Neuroimmune Mechanisms of an Animal Model of Recurrent Depression." Kent State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1429197762.
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Tse, Yiu Chung. "Glutamate receptors in an animal model of Parkinson's disease." HKBU Institutional Repository, 1999. http://repository.hkbu.edu.hk/etd_ra/226.
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Saijo(Kim), Misa. "Generation of transgenic animal model of hyperthyroid Graves' disease." Kyoto University, 2004. http://hdl.handle.net/2433/147457.
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Romano, Eduardo O. "Selection indices for combining marker genetic data and animal model information /." This resource online, 1993. http://scholar.lib.vt.edu/theses/available/etd-09192009-040546/.
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Fry, Christopher Lee. "A source-filter model of birdsong production /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1998. http://wwwlib.umi.com/cr/ucsd/fullcit?p9913150.
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Albertí, i. Fitó Glòria. "Model animal en laminectomia lumbar: factors quirúrgics i variabilitat individual." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/381247.
Повний текст джерелаАнотація:
La cirurgia del raquis lumbar ha augmentat substancialment amb el pas dels anys i això ha condicionat la pràctica de força estudis, tant clínics com experimentals, per millorar les tècniques, fer-les més eficients i segures pel pacient. Malgrat tot, aquestes intervencions presenten un índex de fracassos que es situen entre el 5 i el 50%, segons la literatura. Una de les possibles causes de fracàs és la fibrosi postquirúrgica. Sobre la fibrosi s’han fet nombrosos estudis, tant per acceptar que pot ser causa de dolor postoperatori com per rebutjar aquesta teoria. A més a més ha motivat un plegat de treballs que avaluen l’efectivitat i la necessitat de diferents mètodes que pretenen evitar la formació d’adherències entre aquesta formació fibrosa i les estructures neurals. Alhora, força estudis conclouen que el fracàs de la cirurgia lumbar és un problema multifactorial. Característiques individuals o factors operatoris tan mesurables com l’edat, el pes, el sexe, la duració de la cirurgia, el sagnat o la infecció poden interrelacionar-se i empobrir el resultat histològic i/o clínic de la cirurgia.
Inspirats en aquesta bibliografia, dissenyàrem un estudi experimental on intervinguérem a 13 ovelles adultes per practicar laminectomies en els espais L3 i L5. Es recolliren els paràmetres quirúrgics, les troballes histològiques i les característiques individuals de cada animal.
En primer lloc, compararen entre sí dos dels mètodes barrera més emprats i validats per les publicacions científiques, l’empelt de greix lliure i el gel antiadherent ADCON® - L. En segon lloc, observàrem el procés cicatricial d’una laminectomia lumbar sense implant i, a partir d’aquí, valorarem el possible impacte dels dos implants sobre la histologia del grup control. Tercer, ens plantejàrem si les dades histològiques, individuals i operatòries del nostre estudi es correlacionaven entre elles i, en quart lloc, avaluàrem el maneig dels animals i tot el conjunt del procediment experimental a fi d’explorar la validesa de l’ovella com model experimental en la cirurgia lumbar.
Els nostres resultats conclouen que no hi ha diferències significatives en l’ús del greix o del gel antiadherent. La fibrosi postlaminectomia, tot i presentar-se sempre, no ocasiona cap compromís a les estructures neurals. El pes de l’animal pot influir en el resultat de la cirurgia, no en una variable concreta sinó en una conjunt d’elles. Finalment, podem dir que l’ovella pot ser un bon animal d’experimentació en la cirurgia lumbar.Lumbar spine surgery has increased over the past few years. This has resulted in many experimental and clinical studies aimed to improve the surgical techniques, to make them more efficient and safe. Nevertheless, the index of failure of these procedures ranges from 5 to 50%, being postlaminectomy fibrosis one of the main potential complications. Different studies either support or refuse the idea that postsurgical pain is mainly due to fibrosis. Moreover, many studies have been conducted to explore the need and effectiveness of interventions that could prevent fibrosis and its penetration into the neural canal showing inconclusive results. Some authors believe that lumbar surgery failure has a multifactorial origin. Several studies conclude that individual differences as well as surgical factors like age, weight, gender, duration of surgery, bleeding or infection might be interrelated and could be responsible for negative clinical and histologic results. We designed an experimental animal study where a lumbar laminectomy at L3 and L5 was practiced to 13 sheep. Surgical parameters, histological findings and individual physical data were collected for each animal. First, we wanted to know if two of the most common materials used as barrier methods for fibrosis, a free fat graft and the antiadhesion gel ADCON® - L, would result in different outcomes. Second, we wanted to explore differences in the healing process and the histology between the aforementioned methods and controls where no barrier methods were applied. Third, we wanted to know if histological, individual and surgical variables in our study correlated to each other. Fourth, we explored the scientific validity and the practicality of the sheep as an experimental model in lumbar laminectomy. Our results concluded that there are no significant differences between the free fat graft and the antiadhesion barrier gel. Postlaminectomy fibrosis was present in all cases and did not cause any significant adherence in the neural canal. The multivariate statistical analysis suggests that body weight might influence different parameters related to surgical outcome. From a practical point of view, our study indicates that the domestic sheep could be a good animal model for lumbar laminectomy in human beings.
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Muehlmann, Amber M. "Pharmacological challenges of an animal model of self-injurious behavior." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0011875.
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Diller, James W. "Development of an animal model of choice between aversive events." Morgantown, W. Va. : [West Virginia University Libraries], 2006. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=4916.
Повний текст джерелаАнотація:
Thesis (M.S.)--West Virginia University, 2006.Title from document title page. Document formatted into pages; contains vii, 68 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 63-65).
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Rudissaar, Ruth. "Neuropharmacology of atypical antipsychotics and an animal model of psychosis /." Online version, 2006. http://dspace.utlib.ee/dspace/bitstream/10062/1294/5/rudissaarruth.pdf.
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Schiel, Thomas. "Arthroscopic transfer of osteochondral allografts in a bovine animal model." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq31898.pdf.
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Poirier, Denise Marie. "Nutrient absorption from liquid therapeutic diets in an animal model." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61694.
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Waters, C. M. "A cytochemical evaluation of an animal model of Parkinson's disease." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377231.
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Hawkins, C. A. "Some studies on an animal model of temporal lobe epilepsy." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375246.
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Haberzettl, Robert [Verfasser]. "A validated animal model for the Serotonin Syndrome / Robert Haberzettl." Berlin : Freie Universität Berlin, 2015. http://d-nb.info/1077211929/34.
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Omar, Rumana Zareen. "A multistate model for the analysis of animal tumourigenicity experiments." Thesis, University of Reading, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303167.
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Stapley, Sarah A. "Experimental studies of resuscitation following hypovolaemia in an animal model." Thesis, University of Southampton, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403821.
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Best, Nicholas James. "Paravalbumin-immunoreactive hippocampal neurons in an animal model of epilepsy." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296242.
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Binello, Emanuela. "Efficacy of boron neutron capture synovectomy in an animal model." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/85314.
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Resende, Ana Paula Simões Nunes de. "Study on erythropoietin subconjunctival administration in a glaucoma animal model." Doctoral thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2018. http://hdl.handle.net/10400.5/16041.
Повний текст джерелаАнотація:
Tese de Doutoramento em Ciências Veterinárias na Especialidade de ClinicaGlaucoma is the number one cause of irreversible vision loss worldwide. Death of retinal ganglion cells (RGC), which results in the progressive loss of visual function, occurs in glaucoma and other ocular diseases caused by hypoxia and ischemia. Although glaucoma is a multifactorial neurodegenerative disease, the only currently method of treatment involves reduction of intraocular pressure and, at the present, there is no effective treatment to prevent RGC apoptosis. Notably, it has been reported that erythropoietin (EPO), a cytokine hormone produced in response to hypoxia, has significant neuroprotective and neuroregenerative properties in several types of ocular disorders. Pre-clinical studies in glaucoma animal models involving EPO have yielded very promising results. All studies involving EPO ocular administrations have used systemic, intravitreal or retrobulbar administration to reach retinal desired EPO concentrations. However, EPO chronic systemic administration can lead to adverse side effects related with haematopoiesis stimulation, while intravitreal or retrobulbar administrations are invasive procedures that can induce several complications such as endophthalmitis, retinal detachment, vitreitis, retinitis, choroiditis or cataracts. This thesis aims to clarify if EPO’s neuroprotection could be achieved by a non-invasive and safe periocular administration route without adverse effects. Being so, this work evaluates the subconjunctival route as an alternative for EPO administration in glaucoma disease. After the first in vitro study, where the permeation of EPO across the periocular tissues was quantified, all work was developed in in vivo models. EPO’s ocular permeation after subconjunctival administration was tested, both in physiological and glaucomatous conditions. Furthermore, both retinal morphological and physiological effects of EPO administered by this route were assessed in glaucomatous animals. Results showed that EPO, when administered subconjunctivally, can permeate the main ocular barriers and reach RGC layers, in both physiological and glaucomatous conditions, without significant local or systemic side effects. More than showing that EPO can reach the retina by this route, results also concluded that subconjunctival EPO administration seems to have structural and functional beneficial effects on the retina after glaucoma induction in rats.
RESUMO - Estudo da administração subconjuntival de eritropoietina num modelo animal de glaucoma. - O glaucoma é a principal causa de cegueira irreversível no mundo. A morte das células ganglionares da retina (RGC) causada por hipóxia e isquémia resulta numa progressiva perda de visão. Apesar do glaucoma ser uma doença neurodegenerativa multifatorial, as únicas opções terapêuticas visam o controle da pressão intraocular, não havendo atualmente um tratamento eficaz para prevenir a apoptose das RGC. Estudos recentes demonstraram que a eritropoietina (EPO), uma glicoproteína sintetizada maioritariamente em resposta a estados de hipóxia, tem ação neuroprotetora e neuroregenerativa em várias doenças oculares, tendo revelado resultados promissores em vários modelos animais de glaucoma. Nos estudos experimentais em que a EPO foi utilizada como substância neuroprotetora, foi administrada pelas vias sistémica, intravítrea ou retrobulbar para se obterem concentrações terapêuticas na retina. No entanto, a administração sistémica prolongada de EPO pode produzir efeitos secundários adversos relacionados com o aumento da hematopoiese, enquanto que as administrações intravítrea ou retrobulbar são procedimentos invasivos suscetíveis de causar várias complicações tais como endoftalmite, descolamento de retina, vitreite, retinite, coroidite ou catarata. Esta tese teve por objetivo estudar uma via de administração periocular de EPO não invasiva, segura, eficaz e sem efeitos adversos. Assim, este trabalho avaliou a via subconjuntival como uma alternativa para a administração ocular de EPO em condições de glaucoma. No primeiro estudo in vitro, quantificou-se a permeação da EPO nos tecidos perioculares. O restante trabalho, desenvolvido em modelos in vivo, testou a permeação ocular da EPO após administração subconjuntival, tanto em condições fisiológicas como de glaucoma. O estudo contemplou ainda os efeitos morfológicos e fisiológicos da EPO ao nível da retina em animais glaucomatosos. Os resultados obtidos demostraram que a EPO, quando administrada pela via subconjuntival, pode permear as principais barreiras oculares e atingir as RGC, em ambas as condições testadas, fisiológicas e de glaucoma, sem efeitos adversos locais ou sistémicos apreciáveis. Além disso, revelaram que a administração subconjuntival de EPO parece ter efeitos benéficos estruturais e funcionais na retina após a indução de glaucoma experimental em ratos.
N/A
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Man, James K. C. "Characterisation of a novel animal model for obsessive-compulsive disorder." Thesis, University of Bristol, 2005. http://hdl.handle.net/1983/6cec00ce-f3c1-4d07-ba98-54c137b7524a.
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Schultes, Klaus. "Ultrastructural characterization of ultraviolet induced corneal disease : an animal model." Master's thesis, University of Cape Town, 1994. http://hdl.handle.net/11427/27046.
Повний текст джерелаАнотація:
The majority of ancient people worshipped the sun and viewed it as a health - bringing deity. During the eighteenth and nineteenth century therapeutic benefits of sunlight exposure were beginning to be understood and by the end of the nineteenth century the importance of ultraviolet radiation was being realized. Danish physician Niels Finsen, whom many regard as the father of ultraviolet phototherapy, also stressed that it was ultraviolet radiation in the solar spectrum which cause sunburn. We now recognize that the small portion of ultraviolet radiation which reaches the earth's surface is not necessarily therapeutic, but in fact could be harmful to humans. There are numerous accounts of the harmful effects of UV radiation to the skin and the eye as a whole. These effects may be caused by either acute or chronic exposure to UV radiation. For example, some acute effects of UV-B radiation include conjunctivitis and photokeratitis. "Snow blindness" and "arc welders eye" are further examples of acute ultraviolet damage specifically to the surface of the cornea. On the other hand, chronic exposure to ultraviolet radiation is thought to be responsible for pterygia, climatic droplet keratopathy Hill and Maske (1989), cancers of the external eye, cataracts and various types of retinal diseases. The present study is an extension of ongoing studies on ultraviolet radiation damage to the cornea in the Department of Ophthalmology, University of Cape Town and Groote Schuur Hospital. Their specific interest lies in the causes and treatment of climatic droplet keratopathy. The aims of the present study are: 1) Establish a possible role of ultraviolet B radiation in human corneal diseases such as climatic droplet keratopathy and pterygium using the rabbit as an animal model. 2) Determine by means of SEM the initial effects and subsequent recovery of the epithelium after a 3-hour dose of ultraviolet B radiation. We refer to this study as "acute" response to ultraviolet B radiation. 3) To try and confirm the effects observed by SEM with ultrastructural studies using TEM. 4) In addition, we are also looking at the possible effects after exposing rabbit cornea to a daily dose of low level ultraviolet B radiation, over a long period of time. We refer to this as chronic exposure to ultraviolet B radiation. It is hoped that by exposing rabbits to ultraviolet light, principally ultraviolet B radiation, diseases similar to those found in humans could be simulated and disease progression studied. People are generally exposed to substantial amounts of UV radiation for a very long time. Since people generally live longer they will be exposed to an ever-increasing amount of solar UV radiation and subsequently, there is an increasing risk of developing corneal diseases. The possible threat to the ozone is also a real possibility and could lead to increased levels of ultraviolet radiation reaching the earth's surface. This will require a greater understanding of the very nature of corneal damage due to acute and chronic exposure. This study focusses mainly on the acute response to UV-B radiation since most studies have investigated effects of prolonged exposure to UV light. Accordingly, much less is known about acute exposure. Many people suffering from acute UV B radiation effects probably never visit the ophthalmologist or wait for a couple of days. This could also contribute to the fact that effects of short-term damage is not well documented.