Die zunehmend kritische Betrachtung von Tierhaltungssystemen durch den Verbraucher erfordert eine wissenschaftliche Bewertung der Tiergerechtheit und der arteigenen Bedürfnisse von Nutztieren. Konventionelle ballaststoffarme Schweinemastfutter entsprechen nicht den ethologischen und ernährungsphysiologischen Ansprüchen der Tiere. Verhaltensstörungen sind daher bei Schweinen verbreitet. Der gewählte Forschungsansatz geht davon aus, dass eine erhöhte Befriedigung der Fressmotivation durch rohfaserreiche Futtermittel hier Abhilfe schaffen kann. Daher wurden je 14 Börge über eine Mastperiode mit einer lignocellulosehaltigen Ration gefüttert und mit einer konventionell gemästeten Tiergruppe verglichen. Die Futteraufnahme der Tiere wurde am Fressplatz mit RFID-Respondern registriert. Dabei zeigte sich, dass rohfaserreich gefütterte Schweine langsamer, länger und seltener fraßen und insgesamt weniger Futter aufnahmen. Das lässt auf ein erhöhtes Sättigungsgefühl der Tiere schließen. Das Aktivitäts- und Erkundungsverhalten wurde durch eine Kombination verschiedener Methoden gemessen. Videoanalysen belegten, dass die Tiere beider Gruppen etwa gleich lang ruhten. Die Rohfasertiere zeigten sich dabei weniger empfindlich gegenüber der Umgebungstemperatur. Die Erkundungsintensität, die mittels Respondern gemessen wurde, war ebenfalls nicht durch das Futter beeinflusst. Rohfaserreich gefütterte Schweine zeigten allerdings weniger Interesse an einem Spielzeug und weniger agonistische Auseinandersetzungen. Die Konkurrenz am Futterautomaten war wegen der längeren Fresszeit jedoch erhöht. Vermutlich war die Haltungsumwelt nicht geeignet, bestimmte Unterschiede im Verhalten der Schweine festzustellen. Die Rohfasertiere wuchsen langsamer als die Kontrolltiere, hatten jedoch Schlachtkörper mit erhöhtem Muskelfleischanteil. Die Futterverwertung unterschied sich nicht. Rohfaserreiches Futter verbessert offensichtlich beim Mastschwein die Sättigung und erhöht das Tierwohl. / Animal welfare is of growing importance to consumers of animal products. The development of animal-friendly housing systems and the research on the animal’s requirements are thus aspects of interest. Conventional feeds for fattening pigs are poor in dietary fibre and do not meet the ethologic and nutritional physiologic needs of pigs. This presumably this leads to misdirected behaviour and behavioural disorders, which are widespread in growing pigs. Numerous studies indicate that fibrous feed causes a higher satiation. The thesis on hand is based on the approach that a high level of crude fibre for fattening pigs leads to a reduced motivation to feed and to explore and thus provides relief to the animals. To investigate this, groups of 14 castrated male pigs were fed with a ration containing lignocelluloses during an entire fattening period and were compared to conventionally fed pigs. The feeding pattern of the animals was recorded using RFID responders. Pigs receiving high-fibre feed ate slower, longer and less often and consumed less feed than control pigs. This indicated an improved satiation. Activity and explorative behaviour was measured using various methods. Video analysis showed that both groups performed the same amount of resting behaviour. When choosing a place to rest, high-fibre pigs were less sensitive to their ambient temperature. The intensity of exploration, which was RFID-recorded, was not influenced by the feed. However, high-fibre pigs showed less interest in a toy and less agonistic behaviour. The competition at the feeders was higher, probably because of the prolonged feeding time. Presumably the housing conditions were not suitable for the detection of differences in explorative behaviour between high-fibre and control groups. High-fibre pigs fattened less than control pigs, but delivered better carcasses. The feed conversion was the same for both groups. Fibrous feed apparently enhances satiety in growing pigs and improves animal welfare.

Intervenção nutricional educativa em pacientes submetidos à angioplastia transluminal coronária: ensaio clínico randomizado [Tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo; 2016. INTRODUÇÃO: Mudanças no estilo de vida são estimuladas na prevenção primária e secundária da doença arterial coronária. A educação para promoção de saúde requer uma atividade capaz de problematizar a realidade do indivíduo e capacitá-lo para escolhas conscientes. Considerando os aspectos pluridimensionais da alimentação e a dificuldade de mudanças no comportamento alimentar, o objetivo deste estudo foi analisar a efetividade de uma intervenção nutricional educativa em pacientes submetidos à angioplastia transluminal coronária (ATC) quanto à mortalidade e recorrência de eventos como infarto agudo do miocárdio (IAM), revascularização cirúrgica do miocárdio (RM) ou nova ATC em até um ano de acompanhamento. Os objetivos secundários incluíram consumo alimentar; medidas antropométricas e bioquímicas; estágios de mudança do comportamento alimentar e a ocorrência de eventos cardiovasculares em até quatro anos de seguimento, além de uma análise qualitativa dos fatores socioculturais e atitudinais que influenciaram as práticas alimentares dessa população. MÉTODOS: Foi realizado um ensaio clínico controlado, randomizado e pragmático, com duração de um ano, relativo aos cuidados clínico-nutricionais nos grupos controle e intervenção, sendo neste adicionadas oficinas educativas de nutrição com abordagem construtivista. O ensaio foi complementado com um estudo de coorte para observar eventos cardiovasculares em até quatro anos. Foram alocados 200 pacientes, sendo 101 no grupo intervenção. Ao final do primeiro ano e depois de quatro anos, foram calculadas a redução do risco absoluto e o risco relativo como medidas de incidência cumulativa, respectivamente. RESULTADOS: Ao final de um ano de seguimento, nos grupos intervenção e controle, respectivamente, houve cinco e sete óbitos (p = 0,53); cinco e seis IAM (p = 0,73); quatro e seis re-ATC (p = 0,50); e quatro e quatro RMs (p = 0,98). Após quatro anos, os RR entre os grupos de intervenção e controle foram 0,75 (IC95% 0,35-1,58) para óbito; 0,89 (IC95% 0,34-2,28) para IAM; 0,86 (IC95% 0,40-1,84) para re-ATC e 1,14 (IC95% 0,38-3,40) para RM. Quanto à ingestão alimentar, observou-se redução de gordura saturada (p=0,04) e aumento de fibras (p=0,03) e potássio (p=0,01) no grupo intervenção comparado ao controle. As medidas antropométricas e bioquímicas não apresentaram diferença entre os grupos. A análise estratificada mostrou um efeito protetor para a circunferência da cintura nos subgrupos de idosos [-2.6 cm (IC95% -4,7; -0.6)] e até quatro anos de estudo [-2.5 cm (IC95% -4,9; -0,1)], com interação entre eles (p=0,02). Quanto à mudança de comportamento, houve um aumento no número de indivíduos nos estágios de ação/manutenção de 2,2 vezes (IC95%1,0;5,2) no grupo intervenção, porém sem diferença entre os grupos. Foram identificados fatores socioculturais relacionados ao prazer, hábito, cultura e medo, bem como fatores atitudinais como mudanças declaradas, ambivalência e resistência que permearam as práticas alimentares independente do estágio de mudança, além do conhecimento adquirido, explícito ou ausente. CONCLUSÕES: A intervenção educativa pareceu vantajosa, embora a amostra não tenha sido suficiente para ser conclusiva quanto à ocorrência de eventos cardiovasculares. Houve redução de gordura saturada e aumento no consumo de fibras e potássio, porém sem melhora nas medidas antropométricas e bioquímicas, exceto um menor acúmulo de gordura abdominal em idosos e sujeitos com baixa escolaridade. Há de se fortalecer o debate dos aspectos culturais que constituem o espaço social alimentar e repensar a orientação valorizando as mudanças positivas e escolhas alimentares dentro de um contexto de padrão alimentar saudável / INTRODUCTION: Changes in lifestyle are encouraged in primary and secondary prevention of coronary artery disease. The education for health promotion requires an activity capable of problematizing the individual\'s reality and enabling him to make conscious choices. Considering the multidimensional aspects of feeding and the difficulty of changes in eating behavior, the objective of this study was to analyze the effectiveness of a nutrition education intervention program on mortality and recurrence of events as acute myocardial infarction (AMI), revascularization with re-percutaneous coronary intervention (re-PCI), or coronary artery bypass graft (CABG) surgery after one year of follow-up in patients who previously underwent elective PCI. The secondary objectives included food consumption, anthropometric and biochemical parameters, stages of dietary change, and recurrence of cardiovascular events after four years of follow-up, besides a qualitative analysis of the cultural and attitudinal factors that influenced the dietary practices of this population. METHODS: A controlled, randomized, and pragmatic clinical trial was performed during one-year, related to the clinical and nutritional care in the control and intervention groups, and nutrition education workshops that adopted a constructivist approach were additionally applied to the intervention group. The trial was complemented with a cohort study to observe cardiovascular events up to four years of follow-up. Two hundred patients were allocated, 101 in the intervention group. The absolute risk reduction and the risk ratio were calculated as measures of the cumulative incidence after one and four years, respectively. RESULTS: After one year of follow-up, in the intervention and control groups, respectively, there were five and seven deaths (p=0,53); five and six AMIs (p=0,73); four and six re-PCIs (p=0,50); and four and four CABGs (p=0,98). After four years, the risk ratios between intervention and control groups were 0,75 (95%CI 0,35-1,58) for death, 0.89 (95%CI 0,34-2,28) for AMI, 0,86 (95%CI 0,40-1,84) for re-PCI, and 1,14 (95%CI 0,38-3,40) for CABG. Regarding food consumption, a decrease in saturated fat (p = 0.04) and increase in fiber (p = 0.03) and potassium (p = 0.01) intakes were observed in the intervention group compared to the control group. Anthropometric and biochemical measurements did not show any difference between groups. The stratified analysis showed a protective effect for waist circumference in the elderly [-2.6 cm (95%CI-4,7; -0,6)] and individuals up to four years of study [-2.5 cm (95%CI -4,9 ;-0,1)] subgroups, with interaction between them (p = 0,02). Regarding the change in dietary behaviour, there was an increase in the number of individuals in the action/maintenance stages of 2.2 times (95%CI 1,0; 5,2) in the intervention group, but with no difference between the groups. Factors related to pleasure, habit, culture and fear were identified, as well as attitudinal factors such as stated changes, ambivalence and resistance that permeated eating practices regardless of the stage of change, as well as acquired, explicit or absent knowledge. CONCLUSION: The educational intervention seemed advantageous, although the sample was not enough to be conclusive about the occurrence of cardiovascular events. There was a reduction in saturated fat and an increase in fiber and potassium consumption, but there was no improvement in anthropometric and biochemical measurements, except for a lower accumulation of abdominal fat in the elderly and subjects with low schooling. There is a need to strengthen the debate on the cultural aspects that constitute the food social space and rethink the orientation by valuing positive changes and food choices within a healthy eating pattern

Serotonin (5-HT) has been implicated in energy homeostasis. There is growing evidence that 5-HT, acting through the 5-HT1BR in the paraventricular nucleus of the hypothalamus (PVN), is important to this regulation. To investigate the cellular events underlying 5-HT1BR action, a PVN neuronal cell model was established. The mHypoA-2/30 cell line expresses a complement of markers and neuropeptides specifically localized to the PVN. 5-HT induces neuronal activation in a dose-dependent manner as determined by an elevation in cFos mRNA levels. As 5-HT exerted limited transcriptional control, the integrity of 5-HT signaling machinery was assessed. 5-HT signals through cAMP and calcium secondary messenger systems by suppressing cAMP and elevating intracellular calcium, effects that are mimicked by activating the 5-HT1BR and that are attenuated in the presence of inhibitors. These findings support the use of this novel PVN cell model for delineating components involved in direct 5-HT action in PVN neurons.

Serotonin (5-HT) has been implicated in energy homeostasis. There is growing evidence that 5-HT, acting through the 5-HT1BR in the paraventricular nucleus of the hypothalamus (PVN), is important to this regulation. To investigate the cellular events underlying 5-HT1BR action, a PVN neuronal cell model was established. The mHypoA-2/30 cell line expresses a complement of markers and neuropeptides specifically localized to the PVN. 5-HT induces neuronal activation in a dose-dependent manner as determined by an elevation in cFos mRNA levels. As 5-HT exerted limited transcriptional control, the integrity of 5-HT signaling machinery was assessed. 5-HT signals through cAMP and calcium secondary messenger systems by suppressing cAMP and elevating intracellular calcium, effects that are mimicked by activating the 5-HT1BR and that are attenuated in the presence of inhibitors. These findings support the use of this novel PVN cell model for delineating components involved in direct 5-HT action in PVN neurons.

A pancreatite crônica alcoólica (PCA) tem o álcool como seu principal fator etiológico, a relação entre ingestão de álcool e estado nutricional é complexa e as características nutricionais dos portadores de PCA são pouco conhecidas. Neste trabalho, foram avaliados três grupos de pacientes do sexo masculino, o primeiro (A) com 20 pacientes com PCA, o segundo (B) com 12 etlistas crônicos não pancreatopatas e não hepatopatas e o terceiro (C) com 16 indivíduos não etlistas, não pancreatopatas e não hepatopatas. Para analisar os três grupos utilizaram-se a avaliação antropométrica, a quantificação da ingestão alcoólica, quando existente, o inquérito dietético obtido por Recordatório de 24 horas, a composição corpórea, obtida por bioimpedância elétrica, exames séricos relacionados à avaliação hepática e pancreática, dosagem de vitaminas e de sais minerais, além de marcadores inflamatórios, como proteína C reativa, seroamiloide A e leptina, além de exames de imagem, como ultrassonografia abdominal e/ou tomografia computadorizada de abdômen. A PCA (Grupo A) não se associou à queda da ingestão dietética, porém houve redução da massa magra, evidenciando desnutrição protéica; os etilistas sem pancreatite (Grupo B) apresentaram menor massa magra em relação aos pacientes do grupo C e foi possível demonstrar que a composição corpórea e o perfil inflamatório são distintos e relevantes, não apenas na PCA (Grupo A), mas também nos etilistas sem lesão pancreática (Grupo B), que também devem ser melhor estudados e acompanhados ao longo do seu curso clínico. Em síntese, encontraram-se evidências de subnutrição e aberrações metabólicas tanto nos casos de alcoolismo com lesão pancreática quanto nos etilistas aparentemente sem lesão pancreática ou hepática. Achado até o momento não relatado pela literatura / Alcoholic pancreatitis has alcohol as the primary etiologic factor. The relationship between alcohol intake and nutritional status is complex and the nutritional characteristics of patients with this disease are unknown. In this study, we evaluated three groups of male patients, one (A) with 20 patients with alcoholic pancreatitis, another (B) with 12 alcoholics without pancreatic or liver disease and the last (C) with 16 non - alcoholics , free from any systemic disease or organ insufficiency. To analyze the three groups, we used anthropometric assessment, quantification of alcohol intake, dietary recall, body composition estimated by bioimpedance analysis, biochemical tests related to liver and pancreatic function, dosage of vitamins and minerals, inflammatory markers namely C-reactive protein, leptin and serum amyloid A, in addition to imaging studies such as abdominal ultrasonography and computed tomography of the abdomen whenever required. Group A was not associated with decrease in food intake, but there was a reduction in lean body mass, indicating undernutrition. Alcoholics without pancreatitis (group B) also showed lower lean mass compared to patients in group C, demonstring that changes in body composition and inflammatory status are distinct and relevant also in alcoholics without pancreatic injury (Group B). They should be better studied and monitored throughout their clinical course. In synthesis evidence of undernutrition and metabolic aberrations were demonstrated in both alcoholism with pancreatic damage and in nominally healthy alcoholics, a finding not hitherto reported in the literature

Intervenção nutricional educativa em pacientes submetidos à angioplastia transluminal coronária: ensaio clínico randomizado [Tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo; 2016. INTRODUÇÃO: Mudanças no estilo de vida são estimuladas na prevenção primária e secundária da doença arterial coronária. A educação para promoção de saúde requer uma atividade capaz de problematizar a realidade do indivíduo e capacitá-lo para escolhas conscientes. Considerando os aspectos pluridimensionais da alimentação e a dificuldade de mudanças no comportamento alimentar, o objetivo deste estudo foi analisar a efetividade de uma intervenção nutricional educativa em pacientes submetidos à angioplastia transluminal coronária (ATC) quanto à mortalidade e recorrência de eventos como infarto agudo do miocárdio (IAM), revascularização cirúrgica do miocárdio (RM) ou nova ATC em até um ano de acompanhamento. Os objetivos secundários incluíram consumo alimentar; medidas antropométricas e bioquímicas; estágios de mudança do comportamento alimentar e a ocorrência de eventos cardiovasculares em até quatro anos de seguimento, além de uma análise qualitativa dos fatores socioculturais e atitudinais que influenciaram as práticas alimentares dessa população. MÉTODOS: Foi realizado um ensaio clínico controlado, randomizado e pragmático, com duração de um ano, relativo aos cuidados clínico-nutricionais nos grupos controle e intervenção, sendo neste adicionadas oficinas educativas de nutrição com abordagem construtivista. O ensaio foi complementado com um estudo de coorte para observar eventos cardiovasculares em até quatro anos. Foram alocados 200 pacientes, sendo 101 no grupo intervenção. Ao final do primeiro ano e depois de quatro anos, foram calculadas a redução do risco absoluto e o risco relativo como medidas de incidência cumulativa, respectivamente. RESULTADOS: Ao final de um ano de seguimento, nos grupos intervenção e controle, respectivamente, houve cinco e sete óbitos (p = 0,53); cinco e seis IAM (p = 0,73); quatro e seis re-ATC (p = 0,50); e quatro e quatro RMs (p = 0,98). Após quatro anos, os RR entre os grupos de intervenção e controle foram 0,75 (IC95% 0,35-1,58) para óbito; 0,89 (IC95% 0,34-2,28) para IAM; 0,86 (IC95% 0,40-1,84) para re-ATC e 1,14 (IC95% 0,38-3,40) para RM. Quanto à ingestão alimentar, observou-se redução de gordura saturada (p=0,04) e aumento de fibras (p=0,03) e potássio (p=0,01) no grupo intervenção comparado ao controle. As medidas antropométricas e bioquímicas não apresentaram diferença entre os grupos. A análise estratificada mostrou um efeito protetor para a circunferência da cintura nos subgrupos de idosos [-2.6 cm (IC95% -4,7; -0.6)] e até quatro anos de estudo [-2.5 cm (IC95% -4,9; -0,1)], com interação entre eles (p=0,02). Quanto à mudança de comportamento, houve um aumento no número de indivíduos nos estágios de ação/manutenção de 2,2 vezes (IC95%1,0;5,2) no grupo intervenção, porém sem diferença entre os grupos. Foram identificados fatores socioculturais relacionados ao prazer, hábito, cultura e medo, bem como fatores atitudinais como mudanças declaradas, ambivalência e resistência que permearam as práticas alimentares independente do estágio de mudança, além do conhecimento adquirido, explícito ou ausente. CONCLUSÕES: A intervenção educativa pareceu vantajosa, embora a amostra não tenha sido suficiente para ser conclusiva quanto à ocorrência de eventos cardiovasculares. Houve redução de gordura saturada e aumento no consumo de fibras e potássio, porém sem melhora nas medidas antropométricas e bioquímicas, exceto um menor acúmulo de gordura abdominal em idosos e sujeitos com baixa escolaridade. Há de se fortalecer o debate dos aspectos culturais que constituem o espaço social alimentar e repensar a orientação valorizando as mudanças positivas e escolhas alimentares dentro de um contexto de padrão alimentar saudável / INTRODUCTION: Changes in lifestyle are encouraged in primary and secondary prevention of coronary artery disease. The education for health promotion requires an activity capable of problematizing the individual\'s reality and enabling him to make conscious choices. Considering the multidimensional aspects of feeding and the difficulty of changes in eating behavior, the objective of this study was to analyze the effectiveness of a nutrition education intervention program on mortality and recurrence of events as acute myocardial infarction (AMI), revascularization with re-percutaneous coronary intervention (re-PCI), or coronary artery bypass graft (CABG) surgery after one year of follow-up in patients who previously underwent elective PCI. The secondary objectives included food consumption, anthropometric and biochemical parameters, stages of dietary change, and recurrence of cardiovascular events after four years of follow-up, besides a qualitative analysis of the cultural and attitudinal factors that influenced the dietary practices of this population. METHODS: A controlled, randomized, and pragmatic clinical trial was performed during one-year, related to the clinical and nutritional care in the control and intervention groups, and nutrition education workshops that adopted a constructivist approach were additionally applied to the intervention group. The trial was complemented with a cohort study to observe cardiovascular events up to four years of follow-up. Two hundred patients were allocated, 101 in the intervention group. The absolute risk reduction and the risk ratio were calculated as measures of the cumulative incidence after one and four years, respectively. RESULTS: After one year of follow-up, in the intervention and control groups, respectively, there were five and seven deaths (p=0,53); five and six AMIs (p=0,73); four and six re-PCIs (p=0,50); and four and four CABGs (p=0,98). After four years, the risk ratios between intervention and control groups were 0,75 (95%CI 0,35-1,58) for death, 0.89 (95%CI 0,34-2,28) for AMI, 0,86 (95%CI 0,40-1,84) for re-PCI, and 1,14 (95%CI 0,38-3,40) for CABG. Regarding food consumption, a decrease in saturated fat (p = 0.04) and increase in fiber (p = 0.03) and potassium (p = 0.01) intakes were observed in the intervention group compared to the control group. Anthropometric and biochemical measurements did not show any difference between groups. The stratified analysis showed a protective effect for waist circumference in the elderly [-2.6 cm (95%CI-4,7; -0,6)] and individuals up to four years of study [-2.5 cm (95%CI -4,9 ;-0,1)] subgroups, with interaction between them (p = 0,02). Regarding the change in dietary behaviour, there was an increase in the number of individuals in the action/maintenance stages of 2.2 times (95%CI 1,0; 5,2) in the intervention group, but with no difference between the groups. Factors related to pleasure, habit, culture and fear were identified, as well as attitudinal factors such as stated changes, ambivalence and resistance that permeated eating practices regardless of the stage of change, as well as acquired, explicit or absent knowledge. CONCLUSION: The educational intervention seemed advantageous, although the sample was not enough to be conclusive about the occurrence of cardiovascular events. There was a reduction in saturated fat and an increase in fiber and potassium consumption, but there was no improvement in anthropometric and biochemical measurements, except for a lower accumulation of abdominal fat in the elderly and subjects with low schooling. There is a need to strengthen the debate on the cultural aspects that constitute the food social space and rethink the orientation by valuing positive changes and food choices within a healthy eating pattern

Ce travail vise une meilleure compréhension de l’adaptation aux conditions d’élevage par une approche comportementale basée sur la comparaison de diverses populations de téléostéens pour trois espèces, l’une marine, le bar (Dicentrarchus labrax), les deux autres d’eau douce, l’omble chevalier (Salvelinus alpinus) et la truite commune (Salmo trutta). La thèse s’articule en deux parties qui ont permis : 1) de tester des facteurs biotiques et abiotiques sélectionnés en fonction de leur importance en élevage du bar et de l’omble chevalier. 2) de caractériser les effets de la domestication sur le comportement par le biais d’une comparaison entre des bars ou des truites sauvages et domestiqués à des âges différents et dans des contextes variables (challenges, labyrinthe). Dans la première partie, les travaux réalisés sur l’omble chevalier ont montré que la présence d’un refuge artificiel durant la phase de nutrition endogène induisait une forte diminution de la mobilité accompagnée de meilleures performances de croissance et d’une survie plus importante, que la taille de l’œuf et l’environnement social jouaient un rôle important sur le comportement alimentaire et la mobilité des juvéniles dans les semaines qui suivent la première nutrition exogène. Les travaux réalisés sur le bar ont montré qu’un aliment végétal ne modifiait pas les capacités d’apprentissage en condition d’auto-alimentation ni leurs capacités cognitives en situation de test en labyrinthe, mais qu’il semble réduire l’activité de nage et la libération à court terme du cortisol. Une autre expérience a montré que la pratique du tri et l’environnement social qui en résulte, en conditions d’auto-alimentation, a peu d’influence sur la demande, le rythme, le gaspillage alimentaires, la structure sociale, les performances de croissance et le statut physiologique. Une période de trois semaines de jeûne, enfin, ne modifie pas la structure sociale et les manipulateurs principaux sont les mêmes avant et après cette période, ce qui pourrait être lié à l’existence de traits de personnalité basés sur le pourcentage d’activation de la tige tactile du dispositif d’auto-alimentation. Dans la seconde partie de la thèse, l’expérience sur la truite a mis en évidence un effet de la domestication sur l’activité de nage avant et après application d’un stress lumineux, en utilisant un matériel biologique contrôlé par génotypage (vitesse angulaire plus élevée chez les individus sauvages, vitesse moyenne et distance parcourue plus importantes chez les individus domestiqués). Les expériences réalisées sur le bar ont comparé des populations sauvages capturées à l’état larvaire dans le milieu naturel à des populations standard industrielles. La première a montré l’influence combinée de l’âge et de mécanismes d’ordre ontogénique sur l’activité de nage et le taux de réponse de fuite (diminution chez les deux catégories de larve). L’impact de la domestication se traduit par des différences entre individus sauvages et domestiquées (vitesse angulaire et vigilance plus élevés chez les individus sauvages). En situation de labyrinthe, la domestication ne semble pas avoir d’influence sur le grégarisme et la cognition chez le bar, mais il existe une forte variabilité individuelle. La discrimination de la familiarité, enfin, n’a pu être mise en évidence que chez les individus domestiqués.L’approche comportementale a permis de révéler une plasticité en réponse à quelques facteurs abiotiques et abiotiques, qui constitue un véritable levier adaptatif pour les téléostéens en élevage. L’effet de la domestication sur le comportement a également été démontré ainsi que l’influence de l’âge et des mécanismes ontogéniques dont la nature reste à déterminer. Cette thèse s’inscrit dans la lignée des travaux qui vise à sélectionner les téléostéens sur leurs traits de personnalité dans l’optique d’une adaptation optimale en élevage ou dans la perspective de programmes de repeuplement. / The present work aims at a better understanding of the adaptation to farming conditions through a behavioural approach based on the comparison between wild vs. domesticated populations of three species: a marine species, sea bass (Dicentrarchus labrax), two freshwater species, arctic charr (Salvelinus alpinus) and brown trout (Salmo trutta). The thesis is divided into two parts which objectives were : 1) to test the impact of biotic and abiotic factors selected based on their importance in aquaculture on sea bass and artic charr behavioural plasticity (behavioural modifications in response to environmental changes). 2) to characterize the domestication effect on behaviour through the comparison between wild vs. domesticated sea bass and brown trout at different ages and under different experimental conditions (challenges, maze).In the first part, experiments performed on arctic charr showed that an artificial shelter induced a lower mobility, better growth performances and a higher level of survival during the endogenous feeding period, that egg size and social environment play an important role on feeding behaviour and mobility during the weeks following the first exogenous feeding period. These results illustrated behavioural flexibility in response to abiotic and biotic factors. The findings could be used to improve culture performances and welfare of arctic charr. The experiments performed on sea bass showed that a plant-based diet do neither modify the learning abilities under self-feeding conditions nor the cognition under a test situation in a maze, but has an impact on swimming activity (the mean velocity decreased and the total distance travelled decreased) and on the short-term release of cortisol (plasmatic concentration lower than the control group). Another experiment showed that, under self-feeding conditions, size grading and the resulting social environment have no major influence on feed-demand, feeding rhythm, food wastage, social structure, growth performances and physiological status. At last, a three-week fasting period does not modify the social structure and high-triggering fish are exactly the same individuals before and after the fasting period. Individual’s triggering activity levels could therefore be considered as personality traits but further research is needed to verify this hypothesis.In the second part of the thesis, the experiment performed on brown trout showed an impact of domestication on swimming activity before and after a light-elicited stress, using a biological material controlled by genotyping. Angular velocity was higher in wild fish while mean velocity and total distance travelled were higher in domesticated fish. All the experiments carried out on sea bass compared wild-caught fish (from the larval stage) to domesticated fish (industrial standard). The first one showed the interplay of age and ontogeny on swimming activity and escape response rate. These variables decreased in fish from both origins. The impact of domestication was shown through differences between wild-caught and domesticated larvae (angular velocity and vigilance level higher in wild fish). They showed that domestication has no influence on gregarism, and cognition in sea bass but there was a high individual variability. The ability to discriminate familiarity was shown only in domesticated fish. The behavioural approach developed in this thesis was demonstrated to be relevant to reveal plasticity in response to a few abiotic and biotic factors among the numerous ones that remain to be investigated. Plasticity plays an important role in the adaptation of fish to culture conditions. Domestication impact on behaviour was also demonstrated as well as the interplay of age and ontogeny. This thesis followed the path and brings new insights for research programs targeting fish selection based upon personality traits in order to improve adaptation for aquaculture or restocking purposes.

La presente Tesis Doctoral tiene como objetivo profundizar en los conocimientos sobre ritmos biológicos y comportamiento alimentario de tres especies de peces teleósteos de interés en acuicultura: tenca (Tinca tinca), trucha alpina (Salvelinus alpinus) y lubina (Dicentrarchus labrax).Con este fin se ha investigado la influencia de factores bióticos y abióticos en la sincronización de los ritmos de actividad locomotora y alimentaria, así como el carácter endógeno y/o exógeno de estos ritmos. A su vez, se ha profundizado en el comportamiento individual de truchas alpinas mantenidas en grupo, mediante una nueva metodología que permite estudiar los ritmos de demanda voluntaria de alimento y la autoselección dietaria de los individuos. Asimismo, se ha analizado la influencia de los niveles endógenos de melatonina, modificados mediante la administración de melatonina exógena y de su aminoácido precursor (triptófano) en la dieta, sobre la concentración de cortisol y el ritmo de actividad locomotora en lubina. / This Doctoral Thesis deeps into the knowledge about biological rhythms and feeding behaviour in three teleostean fish species of interest in aquaculture: tench (Tinca tinca), Arctic charr (Salvelinus alpinus) and European sea bass (Dicentrarchus labrax). With this aim, the influence of biotic and abiotic factors has been researched in the field of synchronization of locomotor and feeding rhythms, as far as the endogenous or exogenous character of these rhythms. Moreover, individual feeding behaviour of Arctic charr kept in groups has been studied trying a new methodology which allows the monitoring of feeding demands and dietary self-selection of individuals. Furthermore, influence of endogenous melatonin modified through exogenous melatonin and its precursor amino acid (tryptophan) administration in the diet, in the cortisol levels and locomotor activity rhythms in sea bass were analysed.

L'hétérogénéité de réponses dans un groupe de patients soumis à un même régime thérapeutique doit être réduite au cours d'un traitement ou d'un essai clinique. Deux approches sont habituellement utilisées pour atteindre cet objectif. L'une vise essentiellement à construire une observance active. Cette approche se veut interactive et fondée sur l'échange ``médecin-patient '', ``pharmacien-patient'' ou ``vétérinaire-éleveurs''. L'autre plutôt passive et basée sur les caractéristiques du médicament, vise à contrôler en amont cette irrégularité. L'objectif principal de cette thèse était de développer de nouvelles stratégies d'évaluation et de contrôle de l'impact de l'irrégularité de la prise du médicament sur l'issue thérapeutique. Plus spécifiquement, le premier volet de cette recherche consistait à proposer des algorithmes mathématiques permettant d'estimer efficacement l'effet des médicaments dans un contexte de variabilité interindividuelle de profils pharmacocinétiques (PK). Cette nouvelle méthode est fondée sur l'utilisation concommitante de données \textit{in vitro} et \textit{in vivo}. Il s'agit de quantifier l'efficience ( c-à-dire efficacité plus fluctuation de concentrations \textit{in vivo}) de chaque profil PK en incorporant dans les modèles actuels d'estimation de l'efficacité \textit{in vivo}, la fonction qui relie la concentration du médicament de façon \textit{in vitro} à l'effet pharmacodynamique. Comparativement aux approches traditionnelles, cette combinaison de fonction capte de manière explicite la fluctuation des concentrations plasmatiques \textit{in vivo} due à la fonction dynamique de prise médicamenteuse. De plus, elle soulève, à travers quelques exemples, des questions sur la pertinence de l'utilisation des indices statiques traditionnels ($C_{max}$, $AUC$, etc.) d'efficacité comme outil de contrôle de l'antibiorésistance. Le deuxième volet de ce travail de doctorat était d'estimer les meilleurs temps d'échantillonnage sanguin dans une thérapie collective initiée chez les porcs. Pour ce faire, nous avons développé un modèle du comportement alimentaire collectif qui a été par la suite couplé à un modèle classique PK. À l'aide de ce modèle combiné, il a été possible de générer un profil PK typique à chaque stratégie alimentaire particulière. Les données ainsi générées, ont été utilisées pour estimer les temps d'échantillonnage appropriés afin de réduire les incertitudes dues à l'irrégularité de la prise médicamenteuse dans l'estimation des paramètres PK et PD . Parmi les algorithmes proposés à cet effet, la méthode des médianes semble donner des temps d'échantillonnage convenables à la fois pour l'employé et pour les animaux. Enfin, le dernier volet du projet de recherche a consisté à proposer une approche rationnelle de caractérisation et de classification des médicaments selon leur capacité à tolérer des oublis sporadiques. Méthodologiquement, nous avons, à travers une analyse globale de sensibilité, quantifié la corrélation entre les paramètres PK/PD d'un médicament et l'effet d'irrégularité de la prise médicamenteuse. Cette approche a consisté à évaluer de façon concomitante l'influence de tous les paramètres PK/PD et à prendre en compte, par la même occasion, les relations complexes pouvant exister entre ces différents paramètres. Cette étude a été réalisée pour les inhibiteurs calciques qui sont des antihypertenseurs agissant selon un modèle indirect d'effet. En prenant en compte les valeurs des corrélations ainsi calculées, nous avons estimé et proposé un indice comparatif propre à chaque médicament. Cet indice est apte à caractériser et à classer les médicaments agissant par un même mécanisme pharmacodynamique en terme d'indulgence à des oublis de prises médicamenteuses. Il a été appliqué à quatre inhibiteurs calciques. Les résultats obtenus étaient en accord avec les données expérimentales, traduisant ainsi la pertinence et la robustesse de cette nouvelle approche. Les stratégies développées dans ce projet de doctorat sont essentiellement fondées sur l'analyse des relations complexes entre l'histoire de la prise médicamenteuse, la pharmacocinétique et la pharmacodynamique. De cette analyse, elles sont capables d'évaluer et de contrôler l'impact de l'irrégularité de la prise médicamenteuse avec une précision acceptable. De façon générale, les algorithmes qui sous-tendent ces démarches constitueront sans aucun doute, des outils efficients dans le suivi et le traitement des patients. En outre, ils contribueront à contrôler les effets néfastes de la non-observance au traitement par la mise au point de médicaments indulgents aux oublis / The heterogeneity of PK and/or PD profiles in patients undergoing the same treatment regimen should be avoided during treatment or clinical trials. Two traditional approaches are continually used to achieve this purpose. One builds on the interactive synergy between the health caregiver and the patient to exert the patients to become a whole part of his own compliance. Another attempt is to develop drugs or drug dosing regimens that forgive the poor compliance. The main objective of this thesis was to develop new methodologies for assessing and monitoring the impact of irregular drug intake on the therapeutic outcome. Specifically, the first phase of this research was to develop algorithms for evaluation of the efficacy of a treatment by improving classical breakpoint estimation methods to the situation of variable drug disposition. This method introduces the ``efficiency'' of a PK profile by using the efficacy function as a weight in the area under curve ($AUC$) formula. It gives a more powerful PK/PD link and reveales, through some examples, interesting issues about uniqueness of therapeutic outcome indices and antibiotic resistance problems. The second part of this thesis was to determine the optimal sampling times by accounting for the intervariability in drug disposition in collectively treated pigs. For this, we have developed an advanced mathematical model able to generate different PK profiles for various feed strategies. Three algorithms have been performed to identify the optimal sampling times with the criteria of minimizing the PK intervariability . The median-based method yielded suitable sampling periods in terms of convenience for farm staff and animal welfare. The last part of our research was to establish a rational way to delineate drugs in terms of their ``forgiveness'', based on drugs PK/PD properties. For this, a global sensitivity analysis (GSA) has been performed to identify the most sensitive parameters to dose omissions. Then we have proposed a comparative drug forgiveness index to rank the drugs in terms of their tolerability to non compliance with application to four calcium channel blockers. The classification of these molecules in terms of drug forgiveness is in concordance to what has been reported in experimental studies. The strategies developed in this Ph.D. project and essentially based on the analysis of complex relationships between drug intake history, pharmacokinetic and pharmacodynamic properties are able to assess and regulate noncompliance impact with an acceptable uncertainly. In general, the algorithms that imply these approaches will be undoubtedly efficient tools in patient monitoring during dosing regimen. Moreover, they will contribute to control the harmful impact of non-compliance by developing new drugs able to tolerate sporadic dose omission.

L'hétérogénéité de réponses dans un groupe de patients soumis à un même régime thérapeutique doit être réduite au cours d'un traitement ou d'un essai clinique. Deux approches sont habituellement utilisées pour atteindre cet objectif. L'une vise essentiellement à construire une observance active. Cette approche se veut interactive et fondée sur l'échange ``médecin-patient '', ``pharmacien-patient'' ou ``vétérinaire-éleveurs''. L'autre plutôt passive et basée sur les caractéristiques du médicament, vise à contrôler en amont cette irrégularité. L'objectif principal de cette thèse était de développer de nouvelles stratégies d'évaluation et de contrôle de l'impact de l'irrégularité de la prise du médicament sur l'issue thérapeutique. Plus spécifiquement, le premier volet de cette recherche consistait à proposer des algorithmes mathématiques permettant d'estimer efficacement l'effet des médicaments dans un contexte de variabilité interindividuelle de profils pharmacocinétiques (PK). Cette nouvelle méthode est fondée sur l'utilisation concommitante de données \textit{in vitro} et \textit{in vivo}. Il s'agit de quantifier l'efficience ( c-à-dire efficacité plus fluctuation de concentrations \textit{in vivo}) de chaque profil PK en incorporant dans les modèles actuels d'estimation de l'efficacité \textit{in vivo}, la fonction qui relie la concentration du médicament de façon \textit{in vitro} à l'effet pharmacodynamique. Comparativement aux approches traditionnelles, cette combinaison de fonction capte de manière explicite la fluctuation des concentrations plasmatiques \textit{in vivo} due à la fonction dynamique de prise médicamenteuse. De plus, elle soulève, à travers quelques exemples, des questions sur la pertinence de l'utilisation des indices statiques traditionnels ($C_{max}$, $AUC$, etc.) d'efficacité comme outil de contrôle de l'antibiorésistance. Le deuxième volet de ce travail de doctorat était d'estimer les meilleurs temps d'échantillonnage sanguin dans une thérapie collective initiée chez les porcs. Pour ce faire, nous avons développé un modèle du comportement alimentaire collectif qui a été par la suite couplé à un modèle classique PK. À l'aide de ce modèle combiné, il a été possible de générer un profil PK typique à chaque stratégie alimentaire particulière. Les données ainsi générées, ont été utilisées pour estimer les temps d'échantillonnage appropriés afin de réduire les incertitudes dues à l'irrégularité de la prise médicamenteuse dans l'estimation des paramètres PK et PD . Parmi les algorithmes proposés à cet effet, la méthode des médianes semble donner des temps d'échantillonnage convenables à la fois pour l'employé et pour les animaux. Enfin, le dernier volet du projet de recherche a consisté à proposer une approche rationnelle de caractérisation et de classification des médicaments selon leur capacité à tolérer des oublis sporadiques. Méthodologiquement, nous avons, à travers une analyse globale de sensibilité, quantifié la corrélation entre les paramètres PK/PD d'un médicament et l'effet d'irrégularité de la prise médicamenteuse. Cette approche a consisté à évaluer de façon concomitante l'influence de tous les paramètres PK/PD et à prendre en compte, par la même occasion, les relations complexes pouvant exister entre ces différents paramètres. Cette étude a été réalisée pour les inhibiteurs calciques qui sont des antihypertenseurs agissant selon un modèle indirect d'effet. En prenant en compte les valeurs des corrélations ainsi calculées, nous avons estimé et proposé un indice comparatif propre à chaque médicament. Cet indice est apte à caractériser et à classer les médicaments agissant par un même mécanisme pharmacodynamique en terme d'indulgence à des oublis de prises médicamenteuses. Il a été appliqué à quatre inhibiteurs calciques. Les résultats obtenus étaient en accord avec les données expérimentales, traduisant ainsi la pertinence et la robustesse de cette nouvelle approche. Les stratégies développées dans ce projet de doctorat sont essentiellement fondées sur l'analyse des relations complexes entre l'histoire de la prise médicamenteuse, la pharmacocinétique et la pharmacodynamique. De cette analyse, elles sont capables d'évaluer et de contrôler l'impact de l'irrégularité de la prise médicamenteuse avec une précision acceptable. De façon générale, les algorithmes qui sous-tendent ces démarches constitueront sans aucun doute, des outils efficients dans le suivi et le traitement des patients. En outre, ils contribueront à contrôler les effets néfastes de la non-observance au traitement par la mise au point de médicaments indulgents aux oublis / The heterogeneity of PK and/or PD profiles in patients undergoing the same treatment regimen should be avoided during treatment or clinical trials. Two traditional approaches are continually used to achieve this purpose. One builds on the interactive synergy between the health caregiver and the patient to exert the patients to become a whole part of his own compliance. Another attempt is to develop drugs or drug dosing regimens that forgive the poor compliance. The main objective of this thesis was to develop new methodologies for assessing and monitoring the impact of irregular drug intake on the therapeutic outcome. Specifically, the first phase of this research was to develop algorithms for evaluation of the efficacy of a treatment by improving classical breakpoint estimation methods to the situation of variable drug disposition. This method introduces the ``efficiency'' of a PK profile by using the efficacy function as a weight in the area under curve ($AUC$) formula. It gives a more powerful PK/PD link and reveales, through some examples, interesting issues about uniqueness of therapeutic outcome indices and antibiotic resistance problems. The second part of this thesis was to determine the optimal sampling times by accounting for the intervariability in drug disposition in collectively treated pigs. For this, we have developed an advanced mathematical model able to generate different PK profiles for various feed strategies. Three algorithms have been performed to identify the optimal sampling times with the criteria of minimizing the PK intervariability . The median-based method yielded suitable sampling periods in terms of convenience for farm staff and animal welfare. The last part of our research was to establish a rational way to delineate drugs in terms of their ``forgiveness'', based on drugs PK/PD properties. For this, a global sensitivity analysis (GSA) has been performed to identify the most sensitive parameters to dose omissions. Then we have proposed a comparative drug forgiveness index to rank the drugs in terms of their tolerability to non compliance with application to four calcium channel blockers. The classification of these molecules in terms of drug forgiveness is in concordance to what has been reported in experimental studies. The strategies developed in this Ph.D. project and essentially based on the analysis of complex relationships between drug intake history, pharmacokinetic and pharmacodynamic properties are able to assess and regulate noncompliance impact with an acceptable uncertainly. In general, the algorithms that imply these approaches will be undoubtedly efficient tools in patient monitoring during dosing regimen. Moreover, they will contribute to control the harmful impact of non-compliance by developing new drugs able to tolerate sporadic dose omission.