Objectif: Malgré l'intensification du régime de chimiothérapies, la survie de 5 ans des patients atteints d'ostéosarcome métastatique ou récidivant (OsA) reste faible. Le facteur netrin 1 (NTN1) est surexprimé dans de nombreux cancers humains en tant que facteur de survie. Nous avons étudié ici le rôle de l'anticorprs anti NTN1 (Ac aNTN1) dans l'ostéosarcome.Design expérimental : L'expression NTN1 a été quantifiée par RT qPCR à partir d'une cohorte OsA humaine (n = 22). L'efficacité antitumoral et anti-métastatique de l’Ac aNTN1 seul ou combiné à la doxorubicine a été analysée selon un modèle d'OsA de rat orthotopique et métastatique récidivant. Les effets du traitement sur le microenvironnement tumoral ont été effectués par des analyses immuno-histologiques.Résultats: L'ARNm de la NTN1 est fortement exprimé dans les échantillons OsA humains et dans le modèle OsA de rat. Le traitement combiné (Dox + Ac aNTN1) a été capable de réduire la progression de la tumeur, prévient la dissémination tumorale et retarde la rechute d'OsA. La Dox + Ac aNTN1 diminue l'infiltration des LT effecteurs et inhibe la migration des macrophages M2 au centre de l'OsA de rat.Conclusion: Le blocage de la NTN1 potentialise l'efficacité de la chimiothérapie chez les modèles OsA de rat par des modifications dans le microenvironnement tumoral / Purpose: Despite the intensification of chemotherapies regimen, 5 years survival for patients with metastatic or relapsed osteosarcoma (OsA) remains poor. The secreted factor netrin 1 (NTN1) is overexpressed in many human cancers as a survival factor. We investigated here the role of anti NTN1 Ab in osteosarcoma. Experimental design: NTN1 expression was quantified by RT qPCR from human OsA cohort (n = 22). Anti-tumoral and anti-metastatic efficiency of anti NTN1 antibody alone or combined with doxorubicin was analyzed on a progressive and on a relapsed orthotopic and metastatic rat OsA model. Treatment effects on tumor microenvironment were performed by immuno-histological analyzes.Results: NTN1 mRNA is highly expressed in human OsA samples and in rat OsA model. Combined treatment (Dox + aNTN1 Ab) was found able to synergistically to down tumor progression, prevents tumor dissemination, and delays OsA relapse. Dox + aNTN1 Ab decreased T effetors infiltration and inhibited M2 macrophages migration in the center of rat OsA.Conclusion: NTN1 blockade potentiates chemotherapy efficacy in rat OsA models by modifications in tumor microenvironment

O modelo de recaída cue-induced é comumente utilizado para o estudo da recaída ao uso de drogas causada pela exposição dos animais à estímulos ambientais previamente associados à droga. Quando o álcool é a droga a ser estudada, um estímulo contextual (S) e um reforçador condicionado (Sr) são os estímulo frequentemente associados ao seu consumo. Embora esse modelo seja consolidado na área, sua validade de constructo vem sendo criticada; entre essas críticas estão o fato de que apenas o Sr adquire controle sobre a resposta de procura pela droga, além de que pouco se sabe sobre os sistemas neurais envolvidos nessa recaída. Portanto, este trabalho teve como objetivo principal avaliar o papel dos processos operantes no procedimento do modelo de recaída ao uso de álcool cue-induced, além de avaliar a participação de sistemas neurais ligados ao estresse nessa recaída. Ainda, este trabalho teve como objetivo melhorar o procedimento desse modelo animal. Os experimentos apresentados no Capítulo 1 tiveram como objetivo melhorar o controle exercido por S sobre a recaída, aprimorando o modelo, além de avaliar processos de aprendizagem associativa que ocorrem nesse modelo. Dois experimentos foram realizados para atingir esses objetivos. No primeiro, dois grupos de ratos foram treinados no modelo cue-induced, porém um grupo foi treinado sob o esquema de razão fixa 1 (FR1) e o outro sob o esquema de razão variável 5 (VR5). No segundo experimento, os ratos foram treinados nesse modelo, porém os estímulos S e Sr foram apresentados separadamente na fase de treino. Os resultados desses experimentos indicaram que o treino separado foi eficaz em melhorar o controle de S sobre a recaída e que a troca de esquema de reforço não foi eficaz para aumentar esse controle. Os resultados também mostraram que quando os estímulo são treinados em conjunto o Sr sombreia o S e quando eles são treinados separadamente e testados como um composto ocorre somação. Os experimentos apresentados no Capítulo 2 tiveram o objetivo de avaliar se eixos neurais ligados à resposta ao estresse estariam envolvidos na recaída mimetizada pelo modelo cue-induced. Ratos Marchigian Sardinian Preferring (msP) e Wistars foram treinados no modelo cue-induced e, na fase de testes, Antalarmin, Metirapona e corticosterona (CORT) foram injetados i.p. nos animais. Os resultados mostraram que o Antalarmin (dose 20 mg/kg) bloqueou a recaída em ambas as cepas, que a Metirapona (doses 50 mg/kg e 100 mg/kg) bloqueou a recaída nos ratos msP e apenas a dose de 100 mg/kg bloqueou a recaída nos ratos Wistars e que a CORT não teve efeito na em nenhuma das cepas. Esses resultados mostraram o procedimento do modelo de recaída cue-induced pode ser aprimorado principalmente no que tange ao controle do S sobre a recaída. Os resultados também mostraram que respostas ao estresse influenciam a recaída observada nesse modelo / The cue-induced relapse model is a model commonly used to study relapse caused by environmental stimuli. In its procedure, the environmental stimuli are usually a contextual stimulus (S) and a conditioned reinforcer (Sr). Although this model is extensively used its construct validity has been criticized. Between these critics are the fact that only the Sr controls the drug seeking responses because this stimulus overshadows the S, in addition to the fact that little is known about the neural systems that are involved in cue-induced relapse. Therefore, this work had as main purpose to evaluate operant process in the alcohol cue-induced relapse and evaluate the role of stress neural systems in this relapse. In adition, this work had also the purpose to improve the animal model procedure. The experiments presented in Chapter 1 had the purpose to increase the control exercised by S over relapse and to evaluate associative learned in this model procedure. Two experiments were conducted to achieve this goal. In the first one two groups of rats were trained in the cue-induced relapse model but one group was trained under the fixed ratio 1 (FR1) and the other under the variable ratio 5 schedule (VR5). In the second experiment, rats were trained in the cue-induced procedure, but the stimuli S and Sr were presented separately during the training phase. The results showed that separate training was effective in increase the S control over relapse and that changing the schedule of reinforcement was not effective in increase this control. Also, results showed that summation occurred when the stimuli are trained separately and tested as a compound. The experiments presented in Chapter 2 had the purpose to evaluate if neural axis related to organic stress responses are involved in cue-induced alcohol relapse. Also, it was investigated if the HPA is involved in relapse. Marchigian Sardinian Preferring (msP) rats and Wistars rats were trained in the cue-induced model and during the test phase Antalarmin, Metyrapone and corticosterone (CORT) were injected i.p. in the animals. The results showed that Antalarmin (dose 20 mg/kg) blocked relapse produced by environmental cues in both rats strains, Metyrapone (doses 50 mg/kg and 100 mg/kg) blocked relapse in msP rats and only dose 100 mg/kg blocked relapse in Wistar rats and CORT had no effect on relapse in both strains. These results showed that the procedure used in the cue-induced model can be improved mainly in regard to the control from S over relapse. The results also showed that stress responses influence relapse in this model

Premolars are the most commonly extracted teeth to provide space to correct crowding and excessive labial protrusion. After treatment, the extraction spaces have to remain closed. Nevertheless, several studies have shown that there is a tendency for some relapse even in patients finished with an adequate occlusion. The objective of this study was to compare the stability of extraction space closure of the first and second premolars. A sample 72 patients´ dental casts were divided into two groups. Group 1, comprised 29 patients (116 extraction spaces) were treated with first premolar extractions at a mean initial age of 13.78 years and group 2, comprised 43 patients (100 extraction spaces) were treated with second premolar extractions at a mean initial age of 15.20 years. The dental casts obtained at pretrement, posttreament and a between 3 to 4 years postretention were digitized using a 3- dimensional scanner (R700; 3Shape,Copenhagen, Denmark). Chi-Square tests were used to compare the numbers of open and closed extraction spaces after treatment and at long-term posttreatment. T tests were used to compare the amount of spaces at posttreatment and at the long-term posttreatment stages. These tests were also performed in subgroups with completely closed extraction sites at posttreatment. The groups showed similar numbers of extraction sites reopening. First and second premolar extraction space closure present a similar tendency for reopening. Considering only the cases that showed completely closed extraction spaces in the final dental models, extraction space reopening was larger in the first premolar extraction group in the maxillary arch. / Os pré-molares são os dentes mais comumente extraídos para corrigir o apinhamento dentário e à protrusão labial excessiva. Após o tratamento, os espaços das extrações deveriam permanecer fechados. Contudo, muitos estudos demostraram que existe uma tendência à reabertura dos espaços de extrações em pacientes finalizados com uma oclusão adequada. O objetivo deste estudo foi comparar a estabilidade dos espaços de extrações de primeiro e segundo prémolares. A Amostra deste estudo foi composta por 72 modelos dentários dividido em dois grupos. O Grupo 1 composto por 29 pacientes (116 espaços de extração) foram tratados com extrações dos primeiros pré-molares com idade media inicial de 13,78 anos e o grupo 2 composto por 43 pacientes (100 espaços de extração) foram tratados com extrações dos segundos pré-molares com idade media inicial de 15.20 anos. Os modelos dentários obtidos no pré-tratamento, pós-tratamento e 3 a 4 anos de controle e foram digitalizados mediante um scanner 3Shape R700 3D (3Shape A/S, Copenhagen, Dinamarca). Os testes t e do Qui-Quadrado, foram utilizados para comparar o número de espaços de extração abertos e fechados após o tratamento e pós-tratamento em longo prazo. Os resultados demostraram números similares de reabertura do espaço de extração entre os grupos. Concluiu-se que considerando apenas os casos que mostraram espaços de extração completamente fechados no final do tratamento, a quantidade de reabertura dos espaços de extrações dos primeiros pré-molares ocorre mais frequentemente que dos segundos pré-molares no arco superior.

O objetivo deste estudo foi avaliar a estabilidade do fechamento dos diastemas interincisivos superiores, verificando sua correlacao com a largura inicial desses espacos, a sobressaliencia, a sobremordida e o paralelismo de raizes. A amostra foi composta por 30 pacientes com pelo menos um diastema, com largura minima de 0,77mm e media do somatorio dos tres diastemas interincisivos de 2,64mm (DP = 1,46; minimo= 0,77; maximo= 8,04). Todos os pacientes apresentavam os caninos superiores permanentes com, no minimo, a metade da coroa intrabucal. As mensuracoes foram realizadas em modelos de estudo (largura dos diastemas, sobressaliencia e sobremordida) e radiografias panorâmicas (paralelismo de raizes), obtidos nos estagios pre-tratamento, final de tratamento e, pelo menos, 2,4 anos pos-tratamento. Os resultados da analise de variancia para medidas repetidas demonstraram que a recidiva do diastema mediano foi significante (media= 0,45mm, DP= 0,66), mas foi estatisticamente menor do que sua largura inicial, e os diastemas entre os incisivos centrais e laterais permaneceram fechados, na maioria dos casos. Ocorreu recidiva do diastema mediano em 18 pacientes (60% da amostra) e 19 pacientes apresentaram reabertura de pelo menos um dos diastemas interincisivos. De acordo com a analise de regressao multipla, os unicos fatores associados a recidiva do diastema mediano foram a largura pretratamento deste espaco (p=0,000) e a alteracao da sobressaliencia durante o periodo pos-tratamento (p=0,046). Nao foi encontrada associacao entre o paralelismo de raizes e a recidiva dos diastemas interincisivos. / This study evaluated the stability of maxillary anterior diastemas closure and its association with relapse and dental casts variables (interincisor width, overjet and overbite) and also with root parallelism. Sample comprised 30 patients with at least one pretreatment anterior diastema of 0.77mm or greater after eruption of maxillary permanent canines. Data were obtained from dental casts and panoramic radiographs taken pretreatment, posttreatment and at least 2 years postretention. The sum of initial mean width of the diastemas was 2.64mm (SD=1.46, minimum=0.77). Repeated measures analysis of variance demonstrated significant relapse of median diastema (mean=0.45mm, SD=0.66) but this value was statistically slighter than its initial width, and closure of diastemas located between central incisors and lateral incisors showed great stability. Relapse of median diastema occurred in 18 cases, and 19 patients showed at least one space recurrence. Only initial diastema severity width and relapse of overjet showed association with the relapse of median diastema. There was no association between interincisor diastemas relapse and root parallelism.

O objetivo deste estudo retrospectivo foi buscar variáveis oclusais relacionadas com o prognóstico da estabilidade da correção da má oclusão de Classe II, tratada sem e com extrações. Para tanto, foram selecionados 78 registros de documentações, pertencentes ao arquivo da disciplina de Ortodontia da Faculdade de Odontologia de Bauru, com má oclusão inicial de Classe II completa bilateral, divisão 1, tratada pela mecânica Edgewise e acompanhada por um período médio de 10 anos póstratamento. Essa amostra foi dividida em três grupos, de acordo com o protocolo de tratamento: Grupo 1: constituído por 25 pacientes, com idade inicial média de 12,74 anos, tratados sem extrações, por um período médio de 2,41 anos; Grupo 2: contendo 25 pacientes, com idade inicial média de 13,42 anos, tratados com extrações dos primeiros pré-molares superiores, por um período médio de 2,10 anos; Grupo 3: composto por 28 pacientes, com idade inicial média de 12,98 anos, tratados com extrações dos primeiros pré-molares superiores e primeiros ou segundos pré-molares inferiores, por um período médio de 2,10 anos. As avaliações oclusais foram realizadas em modelos de gesso dos pacientes, nas fases inicial (T1), final de tratamento (T2) e na fase pós-tratamento (T3), utilizando os índices PAR e de irregularidade de Little. O percentual de redução do índice PAR, durante o tratamento, foi de 72,58% para o grupo 1, 80,17% para o grupo 2 e 79,37% para o grupo 3. Para comparação intergrupos, utilizaram-se a análise de variância a um critério e o teste não paramétrico do Qui-quadrado. Os grupos apresentaram-se semelhantes quanto ao gênero, idades (fases T1, T2 e T3), tempo de tratamento, percentual de redução do PAR, eficiência do tratamento e no tempo pós-tratamento. A única variável oclusal responsável pela ausência de uma finalização ortodôntica de excelência (PAR T2 = 0) e pela recidiva evidenciada na fase pós-tratamento, foi a oclusão posterior. Ao separar a amostra em grupos bem finalizado (50 pacientes com o PAR T2 5) e mal finalizado (28 pacientes com PAR T2 > 5) em relação às alterações ocorridas no período pós-tratamento (PAR T3 - T2 e Little T3 T2), verificou-se por meio do teste t independente, que ambos os grupos foram estatisticamente semelhantes em relação à recidiva; no entanto, uma boa finalização ortodôntica proporcionou melhores resultados oclusais e funcionais, nas fases T2 e T3. A recidiva do apinhamento ântero-inferior (Little T3 T2) não correlacionou-se com as alterações oclusais ocorridas no período pós-tratamento (PAR T3-T2). / The objective of this retrospective study was to seek oclusal variables related to correction of Class II malocclusion stability prognosis, treated without and with extractions. As such, 78 documentation records were selected, belonging to the Orthodontic Department from the Bauru Dental School, with an initial complete bilateral malocclusion of Class II, division 1, treated with Edgewise mechanics and followed up for an average period of 10 years post-treatment. This sample was divided into three groups, according to the treatment protocol: Group 1: consisted of 25 patients, with average initial age of 12.74 years, treated without extractions, for an average period of 2.41 years; Group 2: consisted of 25 patients, with an average initial age of 13.42 years, treated with extractions of the first superior premolar teeth, for an average period of 2.10 years; Group 3: consisted of 28 patients, with an average initial age of 12.98 years, treated with extractions of the first superior premolar teeth and first or second inferior premolar teeth, for an average period of 2.10 years. Occlusal evaluations were done on the patients cast models, at the initial phase (T1), at the end of treatment (T2) and post-treatment phase (T3), using the PAR index and Little irregularity index. The percentile reduction for the PAR index, during the treatment, was 72,58% for group 1, 80,17% for group 2 and 79,37% for group 3. For the intergroup comparisons, one-way ANOVA and the non-parametric Chi-square tests were used. The groups were similar regarding gender, ages (phases T1, T2 and T3), time of treatment, PAR reduction percentile, treatment efficiency and post-treatment duration. The only occlusal variable responsible for the absence of excellent orthodontic finalization (PAR T2 = 0) and by relapse evidenced in the post-treatment phase, was the posterior occlusion. When separating the sample in groups well finalized (50 patients with PAR T2 5) and with bad finalization (28 patients with PAR T2 > 5) in relation to the alterations occurred in the post-treatment period (PAR T3 - T2 and Little T3 - T2), it was verified by using an independent t test that both groups were statistically similar in relation to relapse, however, good orthodontic finalization provided better occlusal and functional results in phases T2 and T3). Anterior inferior crowding relapse (Little T3 T2) did not correlate with the occlusal alterations occurred in the post-treatment period (PAR T3 -T2).

Bakgrund: Av Sveriges totala befolkning är 5 % beroende och/eller missbrukar alkohol och droger. Det finns samband mellan människors aktivitetsmönster och missbruk, då missbruket har en inverkan på de dagliga aktiviteterna. Strukturen i vardagen har en betydande roll för alkoholkonsumtion och återfall. Arbetsterapeuter som yrkesgrupp förekommer sällan inom beroende och missbruksvård, trots att ett missbruk påverkar de vardagliga aktiviteterna. Personer med alkohol- och/eller drogproblematik känner sig ofta tillfredsställda med vårdprogrammen på behandlingshem men inte med eftervården som ges. Syfte: Beskriva hur personer med drog- och/eller alkoholproblematik hanterar och värderar vardagliga aktiviteter efter avslutad behandling på behandlingshem. Vidare jämförs om det finns någon skillnad i hantering och värdering av vardagliga aktiviteter hos de som haft och inte haft återfall efter avslutad behandling. Metod: Syftet besvarades genom en kvantitativ studie. Enkäter innehållande självskattningsinstrumentet Min Mening och författarnas egna konstruerade bakgrundsfrågor har använts. 35 män och kvinnor som behandlats på behandlingshem för sin alkohol- och eller drogproblematik deltog i studien. Resultat: Det framkom att deltagarnas drogfrihet har påverkat de vardagliga aktiviteterna till det bättre. Deltagarna upplevde att aktiviteterna “Att få gjort det jag behöver göra” och “Att koppla av och roa mig” fungerade minst bra. De värderade aktiviteten “Att sköta min ekonomi” högst. Det framkom skillnader mellan de deltagare som haft och inte haft återfall efter avslutad behandling. Alla vardagliga aktiviteter i denna studie upplevdes fungera bättre för de som inte haft återfall. Slutsats: Resultatet går i linje med den forskning som redan finns vad gäller samband mellan aktivitetsmönster och missbruk samt belyser och uppmärksammar arbetsterapins betydelse inom missbruksområdet vidare. / Background: 5% of the population in Sweden are having substance abuse problems. There is a connection between individual activity patterns and substance abuse, because the substance abuse is affecting the everyday activities. The relation of the everyday life contra alcohol consumption and relapses is significant. Professional occupational therapists are rarely involved in the treatment of substance abusers, despite that substance abuse is affecting the everyday activities. People with substance abuse problems often feel satisfied with the treatment program at a treatment center, but not with the given aftercare. Purpose: Describe how people with substance abuse problems handles and values everyday activities after finished treatment at a treatment center. Furthermore, a comparison is made to evaluate if there are any differences between the participants in the study who have had a relapse and those who have not had a relapse to how they handle everyday activities and how they value them. Method: The purpose was answered through a quantitative study. Surveys containing the instrument Occupational Self-Assessment and the authors’ own constructed questions was used. 35 men and women who have been treated at treatment center for some kind of substance abuse participated in the study. Result: it was revealed that the participants’ drug free living affected their everyday activities. The participants experienced that the activities ”accomplishing what I set out to do” and “relaxing and enjoying myself” were least successful. They valued the activity” managing my finances” the most. It was revealed that there were differences between the participants that have had a relapse and those who have not had a relapse after they finished their treatment. Those who did not have a relapse experienced better function in all the everyday activities in the study. Conclusion: The result is in line with already available research which touches the connection between activity pattern and substance abuse. The importance of occupational therapy within the field of substance abuse is, furthermore, highlighted and brought to attention.

O objetivo deste estudo retrospectivo foi buscar variáveis oclusais relacionadas com o prognóstico da estabilidade da correção da má oclusão de Classe II, tratada sem e com extrações. Para tanto, foram selecionados 78 registros de documentações, pertencentes ao arquivo da disciplina de Ortodontia da Faculdade de Odontologia de Bauru, com má oclusão inicial de Classe II completa bilateral, divisão 1, tratada pela mecânica Edgewise e acompanhada por um período médio de 10 anos póstratamento. Essa amostra foi dividida em três grupos, de acordo com o protocolo de tratamento: Grupo 1: constituído por 25 pacientes, com idade inicial média de 12,74 anos, tratados sem extrações, por um período médio de 2,41 anos; Grupo 2: contendo 25 pacientes, com idade inicial média de 13,42 anos, tratados com extrações dos primeiros pré-molares superiores, por um período médio de 2,10 anos; Grupo 3: composto por 28 pacientes, com idade inicial média de 12,98 anos, tratados com extrações dos primeiros pré-molares superiores e primeiros ou segundos pré-molares inferiores, por um período médio de 2,10 anos. As avaliações oclusais foram realizadas em modelos de gesso dos pacientes, nas fases inicial (T1), final de tratamento (T2) e na fase pós-tratamento (T3), utilizando os índices PAR e de irregularidade de Little. O percentual de redução do índice PAR, durante o tratamento, foi de 72,58% para o grupo 1, 80,17% para o grupo 2 e 79,37% para o grupo 3. Para comparação intergrupos, utilizaram-se a análise de variância a um critério e o teste não paramétrico do Qui-quadrado. Os grupos apresentaram-se semelhantes quanto ao gênero, idades (fases T1, T2 e T3), tempo de tratamento, percentual de redução do PAR, eficiência do tratamento e no tempo pós-tratamento. A única variável oclusal responsável pela ausência de uma finalização ortodôntica de excelência (PAR T2 = 0) e pela recidiva evidenciada na fase pós-tratamento, foi a oclusão posterior. Ao separar a amostra em grupos bem finalizado (50 pacientes com o PAR T2 5) e mal finalizado (28 pacientes com PAR T2 > 5) em relação às alterações ocorridas no período pós-tratamento (PAR T3 - T2 e Little T3 T2), verificou-se por meio do teste t independente, que ambos os grupos foram estatisticamente semelhantes em relação à recidiva; no entanto, uma boa finalização ortodôntica proporcionou melhores resultados oclusais e funcionais, nas fases T2 e T3. A recidiva do apinhamento ântero-inferior (Little T3 T2) não correlacionou-se com as alterações oclusais ocorridas no período pós-tratamento (PAR T3-T2). / The objective of this retrospective study was to seek oclusal variables related to correction of Class II malocclusion stability prognosis, treated without and with extractions. As such, 78 documentation records were selected, belonging to the Orthodontic Department from the Bauru Dental School, with an initial complete bilateral malocclusion of Class II, division 1, treated with Edgewise mechanics and followed up for an average period of 10 years post-treatment. This sample was divided into three groups, according to the treatment protocol: Group 1: consisted of 25 patients, with average initial age of 12.74 years, treated without extractions, for an average period of 2.41 years; Group 2: consisted of 25 patients, with an average initial age of 13.42 years, treated with extractions of the first superior premolar teeth, for an average period of 2.10 years; Group 3: consisted of 28 patients, with an average initial age of 12.98 years, treated with extractions of the first superior premolar teeth and first or second inferior premolar teeth, for an average period of 2.10 years. Occlusal evaluations were done on the patients cast models, at the initial phase (T1), at the end of treatment (T2) and post-treatment phase (T3), using the PAR index and Little irregularity index. The percentile reduction for the PAR index, during the treatment, was 72,58% for group 1, 80,17% for group 2 and 79,37% for group 3. For the intergroup comparisons, one-way ANOVA and the non-parametric Chi-square tests were used. The groups were similar regarding gender, ages (phases T1, T2 and T3), time of treatment, PAR reduction percentile, treatment efficiency and post-treatment duration. The only occlusal variable responsible for the absence of excellent orthodontic finalization (PAR T2 = 0) and by relapse evidenced in the post-treatment phase, was the posterior occlusion. When separating the sample in groups well finalized (50 patients with PAR T2 5) and with bad finalization (28 patients with PAR T2 > 5) in relation to the alterations occurred in the post-treatment period (PAR T3 - T2 and Little T3 - T2), it was verified by using an independent t test that both groups were statistically similar in relation to relapse, however, good orthodontic finalization provided better occlusal and functional results in phases T2 and T3). Anterior inferior crowding relapse (Little T3 T2) did not correlate with the occlusal alterations occurred in the post-treatment period (PAR T3 -T2).

Introduction: Souvent, les recherches sur ce sujet se réalisent dans un environnement de consommation légal. Pourtant, le cas de l'Arabie saoudite devrait donner des résultats différents. pour la théorie cognitive, la dépendance chimique consiste en une forte interaction entre les cognitions (pensée, croyance, schéma), valeur, opinion, attente, supposition, attitude, émotions, connexion familiale et sociale, impact social et procédure naturelle et physiologique. En s’intéressant à explorer ces croyances dans une société interdisant l'alcool et à présenter un protocole d'évaluation complet adapté à cette culture. Méthode: L’étude inclue 144 sujets, séparés en 3 groupes selon la dépendance et le sexe. Résultats: Les positives croyances liées à l'alcool sont plus élevées chez les alcooliques alors qu'il n'y a pas de différence liée au sexe. Une corrélation positive entre le craving et la rechute. Le niveau de trauma est plus élevé chez les alcooliques et positivement lié à la rechute. Conclusion: Les croyances liées à l’alcool comme toutes les variables precitées ont une rôle essentiel dans la compréhension et le traitement de ce problème. / Introduction: Mostly, the researches about this subject are done in legal alcohol consumption environment. Therefore the case of Saudi Arabia should give different results. Regarding cognitive theory, chemical dependence consists of a strong interaction between cognitions (thoughts, convictions, schemas), values, opinions, expectations and suppositions attitudes; emotions; familial and social connections; social impacts; and natural and physiological procedures. We are interested in exploring these beliefs in a society that forbids alcohol and presenting a complete evaluation protocol adapting to Saudi culture. Method: We studied 144 subjects, separated into 3 groups depending on addiction and gender. Results: Higher positive believes related to alcohol in alcoholics while there is no difference between men and women. A positive correlation between craving and relapse. The traumatic experiences are higher in alcoholics and positively correlated with relapse. Conclusion: The beliefs related to alcohol consumption beside all other variables that are mentioned above have a vital role in the comprehension and the treatment of this issue.

O modelo de recaída cue-induced é comumente utilizado para o estudo da recaída ao uso de drogas causada pela exposição dos animais à estímulos ambientais previamente associados à droga. Quando o álcool é a droga a ser estudada, um estímulo contextual (S) e um reforçador condicionado (Sr) são os estímulo frequentemente associados ao seu consumo. Embora esse modelo seja consolidado na área, sua validade de constructo vem sendo criticada; entre essas críticas estão o fato de que apenas o Sr adquire controle sobre a resposta de procura pela droga, além de que pouco se sabe sobre os sistemas neurais envolvidos nessa recaída. Portanto, este trabalho teve como objetivo principal avaliar o papel dos processos operantes no procedimento do modelo de recaída ao uso de álcool cue-induced, além de avaliar a participação de sistemas neurais ligados ao estresse nessa recaída. Ainda, este trabalho teve como objetivo melhorar o procedimento desse modelo animal. Os experimentos apresentados no Capítulo 1 tiveram como objetivo melhorar o controle exercido por S sobre a recaída, aprimorando o modelo, além de avaliar processos de aprendizagem associativa que ocorrem nesse modelo. Dois experimentos foram realizados para atingir esses objetivos. No primeiro, dois grupos de ratos foram treinados no modelo cue-induced, porém um grupo foi treinado sob o esquema de razão fixa 1 (FR1) e o outro sob o esquema de razão variável 5 (VR5). No segundo experimento, os ratos foram treinados nesse modelo, porém os estímulos S e Sr foram apresentados separadamente na fase de treino. Os resultados desses experimentos indicaram que o treino separado foi eficaz em melhorar o controle de S sobre a recaída e que a troca de esquema de reforço não foi eficaz para aumentar esse controle. Os resultados também mostraram que quando os estímulo são treinados em conjunto o Sr sombreia o S e quando eles são treinados separadamente e testados como um composto ocorre somação. Os experimentos apresentados no Capítulo 2 tiveram o objetivo de avaliar se eixos neurais ligados à resposta ao estresse estariam envolvidos na recaída mimetizada pelo modelo cue-induced. Ratos Marchigian Sardinian Preferring (msP) e Wistars foram treinados no modelo cue-induced e, na fase de testes, Antalarmin, Metirapona e corticosterona (CORT) foram injetados i.p. nos animais. Os resultados mostraram que o Antalarmin (dose 20 mg/kg) bloqueou a recaída em ambas as cepas, que a Metirapona (doses 50 mg/kg e 100 mg/kg) bloqueou a recaída nos ratos msP e apenas a dose de 100 mg/kg bloqueou a recaída nos ratos Wistars e que a CORT não teve efeito na em nenhuma das cepas. Esses resultados mostraram o procedimento do modelo de recaída cue-induced pode ser aprimorado principalmente no que tange ao controle do S sobre a recaída. Os resultados também mostraram que respostas ao estresse influenciam a recaída observada nesse modelo / The cue-induced relapse model is a model commonly used to study relapse caused by environmental stimuli. In its procedure, the environmental stimuli are usually a contextual stimulus (S) and a conditioned reinforcer (Sr). Although this model is extensively used its construct validity has been criticized. Between these critics are the fact that only the Sr controls the drug seeking responses because this stimulus overshadows the S, in addition to the fact that little is known about the neural systems that are involved in cue-induced relapse. Therefore, this work had as main purpose to evaluate operant process in the alcohol cue-induced relapse and evaluate the role of stress neural systems in this relapse. In adition, this work had also the purpose to improve the animal model procedure. The experiments presented in Chapter 1 had the purpose to increase the control exercised by S over relapse and to evaluate associative learned in this model procedure. Two experiments were conducted to achieve this goal. In the first one two groups of rats were trained in the cue-induced relapse model but one group was trained under the fixed ratio 1 (FR1) and the other under the variable ratio 5 schedule (VR5). In the second experiment, rats were trained in the cue-induced procedure, but the stimuli S and Sr were presented separately during the training phase. The results showed that separate training was effective in increase the S control over relapse and that changing the schedule of reinforcement was not effective in increase this control. Also, results showed that summation occurred when the stimuli are trained separately and tested as a compound. The experiments presented in Chapter 2 had the purpose to evaluate if neural axis related to organic stress responses are involved in cue-induced alcohol relapse. Also, it was investigated if the HPA is involved in relapse. Marchigian Sardinian Preferring (msP) rats and Wistars rats were trained in the cue-induced model and during the test phase Antalarmin, Metyrapone and corticosterone (CORT) were injected i.p. in the animals. The results showed that Antalarmin (dose 20 mg/kg) blocked relapse produced by environmental cues in both rats strains, Metyrapone (doses 50 mg/kg and 100 mg/kg) blocked relapse in msP rats and only dose 100 mg/kg blocked relapse in Wistar rats and CORT had no effect on relapse in both strains. These results showed that the procedure used in the cue-induced model can be improved mainly in regard to the control from S over relapse. The results also showed that stress responses influence relapse in this model

癌症復發往往伴隨著耐藥性和轉移率的增加。目前我們仍未完全瞭解確切的腫瘤逃脫機制。皮下無水酒精注射（PEI）已經被用於治療肝細胞癌（HCC）幾十年，而PEI治療後的癌症復發仍然是該方法的一個主要限制。最近有許多證據表明癌細胞能夠逆轉化學誘導的細胞凋亡過程而得以存活，這有可能是其中一個導致癌細胞復發的原因。這篇論文的重點在於研究肝癌細胞HepG2經歷乙醇誘導凋亡事件後存活下來的後果。 / 這個研究首先證實肝癌細胞 HepG2能從乙醇誘導凋亡事件後存活下來。然後我們對存活下來的肝癌細胞HepG2進行增殖率，耐藥性，運動性以及侵襲性的研究。結果表明，存活下來的HepG2有46%的乙醇耐藥性和84%的高運動性。然後爲了發現存活下來的HepG2是否對其他臨床常用藥物也同樣具有耐藥性，4種臨床常用藥物包括阿黴素，紫杉醇，順鉑，5-氟尿嘧啶（5Fu）均被用於測試。有趣的是，存活下來的HepG2對5-氟尿嘧啶變得更加敏感，平均敏感性下降了58.2%。 / 總的來說，我們的研究結果表明肝癌細胞可從乙醇誘導凋亡事件中恢復過來。此外，存活下來的細胞變得更具有耐藥性和侵入性。這種恢復過程可能是導致癌症復發的原因之一。出乎意料的是，雖然所有存活下來的細胞對乙醇具耐受性，但是它們對於5-氟尿嘧啶均變得更加敏感。這些結果表明，乙醇和5-氟尿嘧啶的聯合治療可能有助於提高PEI治療效果從而預防肝癌癌症復發。 / Cancer relapse, associated with increased drug resistance and higher rate of metastasis, often occurs after chemotherapy. The cancer escape mechanisms are still incompletely understood. Percutaneous ethanol injection (PEI) has been used for treating hepatocellular carcinoma (HCC) for decades, but the recurrence after PEI treatment remains a major limitation. Recently there are mounting evidences showing that cancer cells could survive from chemical-induced apoptosis, suggesting a potential route through which cancer relapse may occur. This thesis focuses on the consequences of the recovery of HepG2 cells from ethanol-induced apoptotic event. / This study verified that HepG2 cells could recover from ethanol-induced apoptosis. Proliferation rate, drug resistance, motility and invasiveness were investigated in recovered HepG2 cells. On average, the recovered HepG2 cell clones were found to be 46% more resistant to ethanol and 84% higher in motility than the parental cell clones. And then four commonly used clinical drugs were assayed to determine whether the recovered cell clones were also resistant to other clinical drugs, including doxorubicin, docetaxel, cisplatin and 5-fluorouracil (5-Fu). Interestingly, the recovered clones became 58.2% more sensitive to 5-fluorouracil on average. / In conclusion, our findings showed that HepG2 cells can recover from ethanol-induced apoptotic event. In addition, some cell clones recovered from apoptosis became more resistant to ethanol and some became more invasive. Such recovery might be one of the reasons causing cancer recurrence. Unexpectedly, although the recovered cell clones were more resistant to ethanol, they became more sensitive to 5-Fu treatment. These results indicated that ethanol-5-Fu combined treatment might be useful in enhancing the PEI treatment and preventing HCC cancer recurrence. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wang, Shanshan. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 115-130). / Abstracts also in Chinese.