Submitted by Haroudo Xavier Filho (haroudo.xavierfo@ufpe.br) on 2016-02-26T13:49:33Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação corrigida final.pdf: 950101 bytes, checksum: b6b9614b4900e0e5ad1f6c57a29496e2 (MD5) / Made available in DSpace on 2016-02-26T13:49:33Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação corrigida final.pdf: 950101 bytes, checksum: b6b9614b4900e0e5ad1f6c57a29496e2 (MD5) Previous issue date: 2013-08-30 / Nos últimos anos o aumento da população de idosos tem levado a uma crescente na incidência de doenças neurodegenerativas em todo o mundo. Estefato tem proporcionado um ávido interessenosestudosque visam novasestratégiaspara a prevenção e cura destas patologias. Diversosprodutosnaturaissão reconhecidos por possuírem característicasantioxidantes, razãopelaqual têm sido empregados na formulação de fármacos, visando umpotencialefeitoneuroprotetor. A doença de Huntington (DH) é uma afecção neurodegenerativa autossômica dominante caracterizada por movimentos involuntários coreiformes, distúrbios emocionais e demência (RYU et al, 2004). A DH está associada a uma expansão anormal de repetições citosina-adenina-guanina (CAG’s) no braço curto do cromossomo 4, responsável pela codificação da proteína huntingtina, expressa constitutivamente nos tecidos nervosos central e periférico, tanto em vesículas como em mitocôndrias (LI et al., 1996). Vários modelos experimentais têm sido utilizados para estudar as doenças neurodegenerativas, entre os quais alguns modelos transgênicos e outros farmacológicos. O ácido 3-nitropropiônico (3NP) é um inibidor irreversível da succinato desidrogenase, enzima do complexo II da cadeia respiratória e o tratamento com ele produz inibição deste complexo, com consequente liberação de cálcio mitocondrial, estresse oxidativo e morte de neurônios do estriado, resultando em modificações semelhantes à DH (BEAL et al., 1993; ROSENSTOCK et al., 2004). O Tirosol (2-(4-hidroxifenil)etanol) é um composto fenólico que está presente no azeite de oliva e no vinho. É conhecido como potente antioxidante e antiinflamatório (MUKHERJEE, 2009). Estudos prévios foram desenvolvidos para testar a possibilidade de um efeito neuroprotetor, mas não tiveram resultados conclusivos (BU, 2007). O presente estudo tem por objetivo investigar o efeito neuroprotetor do Tirosol em modelo experimental da doença de Huntington. Foram utilizados no experimento ratos Wistar, machos com 300g, sob regime de água e ração ad libitum. O ácido 3-nitropropiônico (3NP) foi administrado por via intraperitoneal em dose de 20mg/kg.O Tirosol foi administrado por via oral, em uma solução aquosa nas doses de 3, 5, 10 e 15mg. Tanto a indução da doença quanto o tratamento com o tirosol, as doses foram administradas por 7 dias consecutivos. Como resultado, temos que o Tirosol, nas doses de 10 e 15mg, foi capaz de melhorar os parâmetros comportamentais e bioquímicos da doença de Huntington induzida pelo 3NP. Assim, podemos concluir que o Tirosol apresenta-se efetivo na proteção dos neurônios ante a doença de Huntington, no que diz respeito a inibir a sua rápida progressão. / In recent years the increase in the elderly population has led to an increasing incidence of neurodegenerative diseases worldwide. This has provided a keen interest in studies aimed at new strategies for the prevention and cure of diseases. Several natural products are recognized to possess antioxidant properties, which is why they have been employed in the formulation of pharmaceuticals, targeting a potential neuroprotective effect. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by involuntary choreiform movements, emotional disturbances and dementia (Ryu et al, 2004). The DH is associated with an abnormal number of repetitions citosine-adenine-guanine (CAG’s) the short arm of chromosome 4 responsible for encoding the huntingtin protein, constitutively expressed in the central and peripheral nervous tissues, both in vesicles as in mitochondria (Li et al. 1996). Experimental models have been used to study neurodegenerative diseases, including some pharmacological and other transgenic models. The 3-nitropropionic acid (3NP) is an irreversible inhibitor of succinate dehydrogenase enzyme complex II of the respiratory chain and the treatment he produces inhibition of this complex, with consequent release of mitochondrial calcium, oxidative stress and neuronal death in the striatum, resulting in Similar to changes DH (BEAL et al. 1993; ROSENSTOCK et al. 2004). The tyrosol (2 - (4-hydroxyphenyl) ethanol) is a phenolic compound that is present in olive oil and wine. It is known as a potent antioxidant and anti-inflammatory (MUKHERJEE, 2009). Previous studies were designed to test the possibility for a neuroprotective effect, but results were not conclusive (BU, 2007). The present study aims to investigate the neuroprotective effect of tyrosol in an experimental model of Huntington's disease.Was used in the experiment male Wistar rats with 300g, under a water and food ad libitum. The 3NP was administered intraperitoneally at a dose of 20mg/kg. The tyrosol was administered orally in an aqueous solution in doses of 3, 5, 10, 15mg. Both the induction of the disease and the treatment with the tyrosol doses were administered for 7 consecutive days. The result is that the tyrosol at doses of 10 and 15 mg, was able to improve the behavioral and biochemical parameters of Huntington's disease induced by 3NP. Thus, we conclude that presents tyrosol effective in the protection of neurons against Huntington's disease, with regard to inhibit its rapid progress.

Submitted by Ramon Santana (ramon.souza@ufpe.br) on 2015-03-05T14:53:16Z No. of bitstreams: 2 Dissertaçao Rafaella da Nóbrega.pdf: 1018853 bytes, checksum: 03c7a8fc62253cea53b1eb9e5b2895ef (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-05T14:53:16Z (GMT). No. of bitstreams: 2 Dissertaçao Rafaella da Nóbrega.pdf: 1018853 bytes, checksum: 03c7a8fc62253cea53b1eb9e5b2895ef (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2013-08 / O envelhecimento da população é um dos maiores triunfos da humanidade e também um dos grandes desafios. No entanto, o crescimento da expectativa de vida da população tem levado a um aumento na incidência de doenças características do envelhecimento e tem proporcionado um interesse, cada vez maior, em estudos que visam novas estratégias para a prevenção e cura destas patologias. Várias evidências têm demonstrado que alterações mitocondriais e elevados níveis de estresse oxidativo estão fortemente associados ao desenvolvimento de muitas doenças típicas do envelhecimento como a doença de Huntington (DH). Vários modelos animais vêm sendo utilizados para estudar as características neuropatológicas e bioquímicas dessas doenças e determinar novas abordagens terapêuticas. O ácido 3-nitropropiônico (3-NP) é uma neurotoxina que inibe a enzima succinato desidrogenase, que está presente no ciclo de Krebs e no complexo II da cadeia respiratória mitocondrial. Sua inibição leva a um déficit energético, alteração na homeostase do cálcio, estresse oxidativo e morte celular, mimetizando muitos dos sintomas motores, cognitivos e psiquiátricos da doença de Huntington. Atualmente, não há nenhum tratamento que possa impedir, retardar ou inverter a progressão da DH, e compostos naturais com atividade antioxidante têm demonstrado efeito neuroprotetor. O eugenol, dentre suas diversas atividades, apresenta ação antioxidante e diante disso pode ter um efeito neuroprotetor frente a DH. Então, objetivo do presente trabalho foi avaliar a atividade neuroprotetora do eugenol sobre parâmetros comportamentais e bioquímicos induzidos pela administração intraperitoneal de 3-NP. Avaliações comportamentais foram realizadas utilizando os modelos de campo aberto, rotarod e labirinto em cruz elevado. Foi avaliada também a atividade antioxidante in vitro do eugenol através do método de captura do radical livre DPPH˙; a atividade antioxidante in vivo, por meio da determinação da peroxidação lipídica (TBARS) e sua toxicidade aguda. A administração intraperitoneal de 3-NP (20 mg/kg por 7 dias) causou significativa perda de peso corporal, déficit motor e perda de retenção de memória quando comparado aos animais controle. Análises bioquímicas revelaram significativo aumento na peroxidação lipídica nas regiões cerebrais analisadas (substância negra, estriado e córtex). O tratamento diário com eugenol, por vial oral, durante os 7 dias em que o 3-NP foi administrado, melhorou significativamente o peso corporal, o desempenho motor e cognitivo quando comparado ao grupo 3-NP. Além disso, o tratamento com eugenol atenuou a peroxidação lipídica. Foi observado que o eugenol apresenta boa atividade antioxidante in vitro (IC50 = 33,12 μg/ml) em comparação com o padrão ácido ascórbico (IC50 = 3,676 μg/mL). A dose letal mínima do eugenol foi superior a 2g/kg. Estes resultados sugerem que o eugenol tem efeito neuroprotetor contra degeneração induzida pela neurotoxina 3-NP, provavelmente por ser um composto fenólico e possuir atividade antioxidante, sendo assim, um possível agente terapêutico para a DH.

Huntington Disease (HD) is a dominantly inherited neurological disease attributed to a CAG expansion within the HD gene. The HD mutation gives rise to a polyglutamine expansion in exon 1 of the protein huntingtin (Htt). Since the discovery of the HD mutation in 1993, various HD gene mouse models have been developed to contain either fragments or full-length copies of the mutant HD gene. The existence of these HD mouse models enables focused therapeutic testing to develop potential treatments for HD. RNA interference (RNAi) therapy is a targeted gene silencing approach whereby synthetic RNA constructs are shuttled into the cell by viral vectors and used by the cell’s endogenous RNAi machinery to silence a gene of interest. RNAi therapy holds promise for mutant huntingtin (muHtt) allele-specific silencing as a treatment for HD. The purpose of this thesis was to develop the tools for pre-clinical testing of RNAi-mediated gene silencing of human muHtt in the YAC128 mouse model of HD. First, AAV serotypes were compared for delivery to striatal neurons, the neurons most affected in HD. From this work AAV serotype 1 was selected as the most effective serotype for construct delivery. Second, synthetic RNAi constructs including short-hairpin RNA (shRNA) and microRNA-based constructs (miR-shRNAs) were compared for silencing of human muHtt expression in vivo. Here, miR-shRNAs were found to have increased gene silencing and improved tolerance in avoiding immune activation compared to shRNAs. Alternatively, the shRNAs induced dramatic immune activation and morbidity in some cases. Ultimately these findings will contribute to a pre-clinical trial in YAC128 mice investigating Htt RNAi-mediated gene silencing in the treatment of HD, which is also discussed in this thesis. This future work provides proof-of-principle for muHtt allele-specific silencing as a treatment of HD. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Les neuroleptiques ou antipsychotiques sont indiqués dans le traitement des troubles psychotiques et selon les molécules, troubles du comportement et traitement de courte durée de l'anxiété. Depuis l'introduction des neuroleptiques de seconde génération, la prescription s'est étendue à plusieurs utilisations, avec ou sans autorisation de mise sur le marché (AMM). Les travaux de thèse ont pour objectif de décrire le profil des patients et les conditions réelles d'utilisation des neuroleptiques en France, permettant ainsi de vérifier le respect des indications de l'AMM et des recommandations. Nous avons également comparé les effets des neuroleptiques sur la cognition dans une pathologie fréquente (la schizophrénie) à partir d'une méta-analyse en réseau et comparé l'efficacité en conditions réelles des traitements neuroleptiques et apparentés dans une maladie rare avec des symptômes différents (la maladie de Huntington).Nos résultats montrent qu'en population générale, 2,23% de la population avait reçu au moins un neuroleptique. Les médicaments les plus couramment remboursés étaient la cyamemazine, la risperidone, l'olanzapine et l'halopéridol. Une utilisation était inappropriée entre 10 et 31% des patients selon les molécules. Les patients traités par neuroleptiques soit dans le cadre de la schizophrénie soit dans le cadre de la maladie de Huntington, présentaient une évolution différente des scores cognitifs selon le neuroleptique utilisé. Ainsi, c'était une benzamide qui se retrouvait être la classe avec l'effet le plus défavorable sur la cognition. / Antipsychotics are indicated for the treatment of psychotic disorders and according to the drugs, behavioral disorders and short-term treatment of anxiety. Since the introduction of second-generation antipsychotics, prescriptions have extended to several uses, with or without marketing authorization. The thesis aims to describe the profile of patients and the actual conditions of use of antipsychotics in France, and to verify compliance with the indications of the marketing authorization and recommendations. We also compared the effects of antipsychotics on cognition in a common disorder (schizophrenia) with a network meta-analysis and compared the efficacy of antipsychotics and related treatments in real conditions, in a rare disease with different symptoms (Huntington's disease).Our results showed that in general population, 2.23% of the population had received at least one antipsychotic. The most common drugs reimbursed were cyamemazine, risperidone, olanzapine and haloperidol. Inappropriate use was between 10 and 31% of patients depending on the drug. Patients treated with antipsychotics as part of schizophrenia or in the context of Huntington's disease, showed a different pattern on cognitive scores depending on antipsychotic use. Thus, it was found that benzamide was the class with the most adverse effect on cognition.

Amino acids and other ninhydrin-positive compounds were measured in post-mortem thalamus from 25 Huntington's choreics, 10 schizophrenics, 5 schizophrenic-like psychotics, and 23 controls dying without neurological disease. Gamma-aminobutyric acid (GABA) was significantly reduced in choreic thalami, in accord with deficiencies found in other brain regions choreics (Perry et al., 1973a,b). GABA was also significantly reduced in schizophrenic thalami, suggesting a biochemical link between these two diseases, and supporting the hypothesis of a defect in the GABA system in schizophrenia (Roberts, 1972). Homocarnosine, a GABA-containing dipeptide, was also low in choreic and 9 out of 10 schizophrenic thalami. One schizophrenic had extremely high homocarnosine. Glycerophosphoethanolamine was significantly elevated in Huntington's choreics, but not in schizophrenics. A number of other variables were considered for their potential influence on amino acid concentrations in thalamus. The majority of amino acids were found to rise in a significantly linear fashion in the interval 3 to 49 hours post-mortem, although other models might have described the change better. GABA, ornithine, histidine and tyrosine were found to decrease significantly with increasing age between 21 and 80 years, in controls. The effects of pre-mortem hypoxia, regional variation within the thalamus, and neuroleptic drug treatment could not be rigorously tested with these data. Neuroleptics were unlikely to have been the cause of group differences in GABA concentration, since they failed to deplete GABA in brain of chronically treated rats. On the other hand, bronchopneumonia and other causes of pre-mortem hypoxia could not be ruled out as potential contributers to reduced GABA in thalamus. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

It has been ten years since the 26-year-old fruit seller set himself on fire to protest corruption in Tunisia. The street vendor created a wave of protests in the Arab world, a campaign for civil resistance, better known as the "Arab Spring". The protests led to the removal of long-standing authoritarian regimes in countries such as Tunisia, Egypt, Yemen and Libya. The civil resistance was a result of an economic crisis, high unemployment and corruption. The citizens of the arab world were demanding freedom of expression and greater civil rights. Tunisia became a successful example, where the country today is a complete democracy. In Egypt, the revolution also led to democratization, but for a short period of time. Egypt became more authoritarian after a coup led by the military. The other states failed and the consequences have been devastating with results of civil wars in Libya and Yemen. The main purpose of this essay was to sort out and understand why Tunisia succeeded to become a democracy after the arab spring 2010, while Egypt failed. A qualitative analysis with a comparative democratization study, composed of a most different system-design. The theoretical framework is based on Samuel Huntington (1991) “third wave democratization” and the author’s criteria on democracy, which includes regime legitimacy, economical modernization, and religious change.

Thesis advisor: Peter Skerry / The United States military imposes restrictions on individual rights virtually nonexistent in the rest of American society. The theoretical perspectives of Huntington and Janowitz provide fruitful ground for understanding the basis of authority for the military to enforce these controls. Each perspective examines the relationship between civilian control over the military and the impact on military effectiveness. These opposing viewpoints offer an analytical framework to evaluate restrictions on service members’ freedom of speech and freedom of religion. This analysis will demonstrate the tendency for the military to adhere to more of the Janowitzian principles since the end of the Cold War by integrating features of civil society. This transition away from the Huntington-dominated military institution is due to an increasingly complex and dangerous international environment and the end of conscription. However, the military is still a distinct society from the larger community. Therefore, the military should adopt more inclusive measures but only to the extent that they do not negatively impact military effectiveness. Finally, when service members undergo an indoctrination period, known as initial entry training, their understanding of rights begins to transition from the American civilian conception to the military conception. As a result, service members tend to be more accepting of rights restrictions because of a belief in the common good and the sense of a higher purpose. / Thesis (MA) — Boston College, 2022. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Political Science.

La maladie de Huntington (MH) est une maladie neurodégénérative, autosomique, dominante. La MH se manifeste par des troubles moteurs, cognitifs, psychiatriques et/ou comportementaux. Les troubles cognitifs sont probablement parmi les mieux documentés dans la MH, perturbant la flexibilité, l’inhibition, la planification et la prise de décision. Des désordres des aptitudes en cognition sociale ont aussi été rapportés chez ces patients, dont en particulier des troubles de la reconnaissance des expressions faciales émotionnelles et de théorie de l’esprit (ToM).Les fonctions émotionnelles et leurs régulations sont actuellement peu caractérisées, tant chez les patients que chez les modèles animaux de la MH.Chez le modèle de rats transgéniques (tgHD rats), des perturbations des réponses émotionnelles et hédoniques ont été caractérisées à un âge précoce.L’objectif de cette thèse était de mieux caractériser les déficits émotionnels et leur impact sur les fonctions exécutives en étudiant (1) différentes tâches cognitives chez des patients MH et chez des modèles animaux de la MH (rats TgHD et rats BACHD) à différents stades de la maladie ; (2) en analysant l’impact d’états émotionnels induits (peur et plaisir) sur la prise de décision chez les patients MH (symptomatiques) et chez les rats BACHD à des âges différents. / Huntington's disease (HD) is an autosomal dominant genetic neurodegenerative disease. HD is characterized by a combination of motor, cognitive, psychiatric and behavioral symptoms. Social cognition skills disorders have also been reported in these patients, including in particular recognition disorders of emotional facial expressions and theory of mind (ToM).Emotional functions and regulations are currently poorly characterized in patients and in animal models of HD. In patients, loss of emotional control, and negative or positive emotions recognition deficits have been described.In the rat model of HD (tgHD rats), disturbances of emotional and hedonic responses were characterized at early stage.The aim of this thesis was to better define the emotional deficits and their impact on executive functions (1) different cognitive tasks among HD patients and in animal models of HD (TgHD and BACHD rats) at different stages of the disease; (2) by analyzing the impact of induced emotional states (fear and pleasure) on decision making in symptomatic HD patients and in BACHD rats at different ages.

No description available.

A quantitative and ecological study of the algal flora of Huntington Canyon, Emery Co., Utah was conducted from March 1971 to April 1972. Data were collected concerning net plankton, nannoplankton, periphyton and visible attached algae. Certain physical and chemical parameters in the waters of Huntington Creek and a small pond along its course also were measured. The algal flora of Huntington Canyon contains a wide diversity of genera and species. Diatoms are the main constituent of the flora of this stream throughout the year. Hydrurus foetidus is prevalent in the creek in Huntington Canyon from late winter to early summer, and filamentous blue-green algae abound in the summer and fall. Cladophora flomerata, Oedogonium sp., and Chara vulgaris are abundant in the creek beyond the mouth of the canyon. Most plankton in Huntington Creek originate on the substrate and in reservoirs. Huntington Creek is a cold, fast flowing, hard water mountain stream, and the algal flora of this creek is typical of such a habitat.