Em Medicina Veterinária, os avanços em Neonatologia são escassos quando comparados aos da Medicina Humana. Dentre as possíveis causas para esta situação atual destacam-se as particularidades fisiológicas deste período. Os objetivos do presente estudo foram: estabelecer os valores normais de algumas variáveis laboratoriais de neonatos nascidos de parto eutócico, identificar eventuais alterações metabólicas maternas e dos neonatos nascidos em diferentes condições obstétricas, verificar os efeitos da administração de ocitocina sob variáveis neonatais e maternas e mensurar os níveis de cortisol materno e neonatal como forma de estudar as diferentes situações de estresse no momento do parto. Vinte e nove fêmeas caninas foram alocadas em 3 grupos, de acordo com o tipo de parto: eutocia (grupo 1), distocia corrigida por manobras obstétricas ou cesariana (grupo 2) e indução de contrações uterinas com ocitocina (grupo 3). Cinqüenta e um neonatos foram avaliados por meio do sistema Apgar e temperatura corpórea ao nascimento, 5 minutos e 1 hora após o nascimento, bem como por avaliação hemogasométrica, dosagem de cortisol e glicemia ao nascimento e após 1 hora. A avaliação materna constituiu no controle da pressão arterial, monitorização cardíaca, glicemia e dosagem de cortisol em momentos pontuais no pré, intra e pós-parto. Os neonatos dos distintos grupos apresentaram acidose mista associada à hipóxia ao nascimento, com maior comprometimento metabólico nos filhotes do grupo 3. Após 1 hora, recuperaram-se do componente respiratório, mantendo apenas o quadro de acidose metabólica por maior comprometimento da hipóxia. A avaliação neonatal pelo escore Apgar demonstrou que filhotes do grupo 2 nascem em maior depressão que neonatos dos grupos 1 e 3, porém todos apresentam adequada recuperação após 1 hora. Nas parturientes, a administração de ocitocina favoreceu a elevação da pressão arterial para níveis normais durante o trabalho de parto, bem como o aumento da glicemia. Neonatos nascidos por manobra obstétrica ou cesariana apresentaram maior concentração de cortisol plasmático ao nascimento, em comparação aos grupos 1 e 3. Contudo, todos os neonatos apresentaram redução significativa dos níveis de cortisol após 1 hora do nascimento. Por outro lado, foi possível verificar maior concentração sérica deste hormônio após o término do parto nas fêmeas submetidas à infusão de ocitocina. Em conclusão, a administração de ocitocina é responsável por maiores alterações metabólicas em neonatos; na parturiente, a administração de ocitocina promove alterações na pressão arterial, glicemia e aumento da liberação de cortisol; a manobra obstétrica ou cesariana promove maior estresse neonatal ao nascimento. / Studies accomplishing canine neonatology are scarce in Veterinary Medicine comparing to Human Neonatology due to the particularity of this refered period. The aims of the present study were to establish standard laboratorial values of the canine neonate, identify metabolic changes of bitches and neonates born under different obstetric conditionsl, verify the consequences of dystocia treated medically by oxytocin administration on maternal and neonatal variables and to measure maternal and neonatal cortisol levels on distinc stress situations during parturition. Twenty nine canine females were allocated into 3 groups according to the obstetric conditions: eutocia (group 1; n=10), manipulative obstetric assistance or cesarean section (group 2; n=10) and maternal dystocia treated with oxytocin (group 3; n=9). Fifty one neonates were submitted to a clinical evaluation by Apgar scoring and body temperature measurement immediately after birth, at 5 and 60 minutes postnatal; and hemogasometric evaluation, blood glucose and cortisol assay immediately after birth and 60 minutes postnatal. Maternal noninvasive arterial blood pressure, blood glucose and cardiac monitoring were peformed during the first stage of labor, intra-partum, immediately after the last puppy was born and 1 hour later. Neonates from distinct groups showed mixed acidosis in addition to hypoxemia at birth. Neonates remained under metabolic acidosis even after 1 hour of birth due to a detrimental effect on hypoxia. Comparing the results among groups, puppies from group 2 showed significantly lower Apgar score at birth. However, 1 hour later all neonates showed full recovery. Dams subjected to oxytocin infusion showed an increase in blood pressure, hence switching to a normotension status and also presented higher glucose level during parturition. Manipulative obstetric assistance or cesarean section arised neonatal cortisol levels at birth. However, all neonates exhibited significantly lower cortisol concentration after 1 hour of birth. Bitches of group 3 showed significantly higher cortisol level immediatly after whelping. In conclusion, dystocia treated medically by oxytocin infusion resulted in more intense metabolic alterations compared to neonates born under eutocia; oxytocin administration promotes blood pressure enhance, glucose alterations and increase in maternal stress; manipulative obstetric assistance or cesarean section increased neonatal cortisol release at birth.

Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2017-07-25T18:12:15Z No. of bitstreams: 1 2016 - Marimar Mayworm Beck.pdf: 2648068 bytes, checksum: c6ec41428f0e812cecccc4dbfc94a8e9 (MD5) / Made available in DSpace on 2017-07-25T18:12:15Z (GMT). No. of bitstreams: 1 2016 - Marimar Mayworm Beck.pdf: 2648068 bytes, checksum: c6ec41428f0e812cecccc4dbfc94a8e9 (MD5) Previous issue date: 2016-08-31 / Man and animals are constantly subjected to stress, which is a situation caused by a challenge to which a body is subjected. Despite the exercise be a powerful and relatively simple way of treating and preventing diseases, acute exercise is considered an effective tool to study the physiological responses to metabolic stress. Like other forms of stress, acute exercise induces neuroendocrine and autonomic responses characterized mainly by activation of the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal system. Acupuncture is an ancient practice of Traditional Chinese Medicine, used to reduce stress responses in humans and animals. Therefore, the work suggests to study the effect of acute stimulation of acupuncture points on the physiological responses to progressive incremental exercise (PIE) in shelter dogs, by analysis of the variability of the cardiac interval (VIC), lactate and serum cortisol. It is noteworthy that the PIE is an exercise stress test recognized worldwide, that has been used in domestic animals and humans. The experimental procedures were performed in 16 dogs, mix breed, aged between 2 and 5 years, weighing 8-23 kg healthy with vaccinations and deworming updated and untrained to the treadmill. The dogs were subjected to an adaptation to the treadmil that consisted of 5 consecutive days of training 20 min each, with variable speeds (maximum of 5 km / h) and 5% inclination. On the day of the experiment the animals were divided into two groups: control (CTL only submitted to PIE) and acupuncture (treated with acupuncture before PIE). In ACUP group acupuncture needles were inserted into acupoints BP6, E36 and PC6 bilaterally for 20min. The PIE consisted in walking, followed by running in 5 km / h for 5 minutes, then gradually increase 0.5 km / h every 30 seconds, with inclination of 5%, until reaching exhaustion (abrupt stop or coordination loss during exercise). For the analysis of VIC, cardiac intervals were recorded by cardiac frequency meter (Polar); lactate and cortisol were analysed by spectrophotometer and radioimmunoassay, respectively. The EIP was able to significantly increase lactate levels, average HR, LF / HF ratio and LH and decrease the HF in the final three minutes of exercise demonstrating a greater activation of the sympathetic component in relation to the parasympathetic. However PIE was not able to induce significant increase of cortisol. No significant differences were detected between the acupuncture and control groups in any of the parameters analysed. We conclude that an acupuncture session immediately before the EIP was unable to significantly change the autonomic and endocrine responses induced by exercise. / Humanos e animais s?o constantemente submetidos ao estresse, que ? uma situa??o gerada por um desafio ao qual um organismo ? submetido. Apesar do exerc?cio f?sico ser uma forma poderosa e relativamente simples de tratamento e preven??o de doen?as, o exerc?cio agudo ? considerado uma ferramenta eficaz para estudar as respostas fisiol?gicas ao estresse metab?lico. Como outras formas de estresse, o exerc?cio agudo induz respostas neuroend?crinas e auton?micas caracterizadas principalmente pela a ativa??o do eixo hipot?lamo-hip?fise-adrenal e do sistema simpato adreno-medular. A acupuntura ? uma pr?tica milenar da Medicina Tradicional Chinesa, utilizada para reduzir as respostas de estresse em humanos e animais. Desta forma, o estudo prop?e estudar o efeito da estimula??o aguda de pontos de acupuntura nas respostas fisiol?gicas ao exerc?cio incremental progressivo (EIP) em c?es de canil, atrav?s da an?lise da variabilidade do intervalo card?aco (VIC), do lactato e do cortisol s?rico. Os procedimentos experimentais foram realizados em 16 c?es, sem ra?a definida, com idades entre 2 e 5 anos, pesando de 8 a 23 kg, clinicamente saud?veis, com vacinas e vermifuga??o em dia e destreinados ? esteira ergom?trica. Os c?es foram submetidos a um per?odo de adapta??o a esteira que consistiu de 5 dias de treino consecutivos de 20 min cada, com velocidades vari?veis (m?xima de 5 km/h) e 5% de inclina??o. No dia do experimento os animais foram divididos em dois grupos: controle (CTL, apenas submetidos ao EIP, n=8) e acupuntura (tratados com acupuntura antes do EIP, n=8). No grupo ACUP foram inseridas agulhas de acupuntura nos acupontos BP6, E36 e PC6 bilateralmente por 20min. O EIP consistiu de caminhada seguida de corrida de 5 km/h por 5 minutos, seguida de aumento gradual de 0,5 km/h a cada 30 segundos, com inclina??o de 5%, at? o alcance da exaust?o que foi considerada por meio de uma parada abrupta ou perda de coordena??o durante o exerc?cio. Para a an?lise da VIC, os intervalos card?acos foram registrados por frequenc?metro card?aco (Polar), e o lactato e cortisol analisados atrav?s de espectofot?metro, e pela t?cnica de radioimunoensaio, respectivamente. O EIP foi capaz de aumentar significativamente os n?veis de lactato, a FC m?dia, a raz?o LF/HF e o LH e diminuir o HF nos tr?s minutos finais do exerc?cio demonstrando uma maior ativa??o do componente simp?tico em rela??o ao parassimp?tico. No entanto o EIP n?o foi capaz de induzir aumento significativo do cortisol. N?o foi detectada diferen?a significativa entre os grupos acupuntura e controle em nenhum dos par?metros analisados. Conclu?mos que uma sess?o de acupuntura imediatamente antes do EIP n?o foi capaz de alterar significativamente as respostas auton?micas e end?crinas induzidas pelo exerc?cio.

The aim of this study was to compare two ovariectomy techniques (conventional vs laparoscopic) in bitches planning determine which procedure offers the lowest hemodynamic changes, painful stimuli, stress and inflammatory changes in trans and post-operative period. For the experiment were used 17 young mongrel bitches (12,58 ± 4,29 months), weighting 10.16 ± 0,69kg. Animals were placed into two groups according to the technique applied. In the first group (eight animals), ovariectomy (OV) was done by retro-umbilical celiotomy (GC) and in the second group (nine animals), by laparoscopy two-portal access (GV). For the assessment of analgesia were measured hemodynamic parameters (heart rate, respiratory rate, systolic arterial pressure, medium arterial pressure, diastolic arterial pressure, central venous pressure and cardiac output), and used three pain scales as follows: visual analogue (VAS), the University of Melbourne and the scale consists of Glasgow. To evaluate the stress and inflammatory changes were evaluated different parameters (C-reactive protein, cortisol, protein electrophoresis and acetylcholinesterase determination). In both procedures (GV and GC) there were no trans or post-operative complications. This study found that two-portal laparoscopic ovariectomy provides smaller and shorter pain stimuli that conventional ovariectomy when considering the following times and pain scales (two hours after surgery in Melbourne and the scale of 12 and 24 hours postoperative VAS), as well as in assessing the methods used to analyze the inflammatory response and stress, laparoscopic technique provided a lower elevation and a more rapid decline in the levels of C-reactive protein, mainly from six up to 72 hours after surgery, that the conventional technique. / O objetivo deste estudo foi comparar duas técnicas de ovariectomia (convencional vs laparoscópica) em cadelas, buscando determinar qual procedimento oferece menores alterações hemodinâmicas, estímulos dolorosos, estresse e alterações inflamatórias nos períodos trans e pós-operatório. Para o experimento foram utilizadas 17 cadelas jovens (12,58 ± 4,29 meses), sem raça definida, com peso médio de 10,16 ± 0,69kg. Os animais foram alocados em dois grupos, de acordo com a técnica operatória aplicada. No primeiro grupo (oito animais), a ovariectomia (OV) foi efetuada por celiotomia retro-umbilical (GC) e, no segundo grupo (nove animais), pela técnica de videolaparoscopia por dois portais (GV). Para a avaliação hemodinâmica foram aferidos parâmetros FC, , PAS, PAM, PAD, pressão venosa central e débito cardíaco e, para a avaliação álgica, foram empregadas três escalas de dor: visual analógica (EVA), da universidade de Melbourne, e a composta de Glasgow. Para avaliação do estresse e das alterações inflamatórias, foram avaliados diferentes parâmetros: cortisol, proteína C reativa, eletroforese de proteínas e acetilcolinesterase. Em ambos procedimentos (GV e GC) não ocorreram complicações trans ou pós-operatórias. Concluiu-se que a técnica de ovariectomia videolaparoscópica por dois portais propiciou estímulo álgico de menores magnitude e duração que a ovariectomia convencional ao se considerar os seguintes tempos e escalas de dor (duas horas de pós-operatório na escala de Melbourne e nas 12 e 24 horas de pós-operatório na EVA). Ademais, a técnica videolaparoscópica propiciou menor elevação e declínio mais rápido nos níveis séricos de proteína C reativa, sobretudo a partir de seis até 72 horas de pós-operatório, em relação à técnica convencional.

Glucocorticosteroide (GC) spielen für viele endogene Prozesse im Organismus eine wichtige Rolle. Sie regulieren die Gluconeogenese sowie den Lipid- und Proteinstoffwechsel. Außerdem sind sie für die Stressregulierung über die Hypothalamus-Nebennierenrinden-Achse verantwortlich. Therapeutisch kommen die GCs wegen ihrer entzündungshemmenden Wirkung zum Einsatz und werden u.a. bei Asthma und Gelenkentzündungen angewandt. Diese Eigenschaft macht sie auch interessant für den Gebrauch im Sportbereich. Dort wird ihre Anwendung über die Weltantidopingagentur reguliert. Ihr oraler, intramuskulärer, intravenöser und rektaler Gebrauch ist im Wettkampf verboten. Diese Einschränkung bzgl. des Applikationszeitraumes und des Applikationsweges erschwert die diagnostische Aussagekraft von Routinedopingproben, welche im Urin durchgeführt werden. Ein Grenzwert von 30 ng/ml soll einen legalen Gebrauch von einem Missbrauch abgrenzen. Die endogenen Glucocorticosteroide stellen hierbei jedoch einen Graubereich dar. Endogen wird Cortisol in einem zirkadianen Rhythmus produziert und die Produktion ist stressinduziert. Somit kommt es zu ausgeprägten intra- und interindividuellen Streuungen der endogenen Produktion. Dadurch bedingt ist eine Abgrenzung der endogenen Produktion von einer legalen Anwendung bzw. einem Missbrauch im Rahmen der Dopingrichtlinien im Urin nicht möglich. Speziell für den Nachweis von endogenen Substanzen ist es wichtig, eine Methode zu finden, mit der es möglich ist, die endogene Produktion von einer exogenen Bezugsquelle abzugrenzen. Dabei haben sich zwei Wege als hilfreich herausgestellt. Zum einen, wenn die Differenzierung nicht an Hand von Absolutkonzentrationen sondern durch die Anwendung von Analytverhältnissen durchgeführt wird. Zum anderen, wenn zusätzliche Untersuchungen im Speichel oder Haar durchgeführt werden. Haar- und Speichelproben zählen zu den ergänzenden Matrizes der Routineuntersuchungsmedien Urin und Blut und werden bereits in vielen forensischen und klinischen Laboren für diagnostische Fragestellungen verwendet. Diese Matrizes liefern wichtige Hinweise auf den akuten (Speichel) oder chronischen/ zurückliegenden (Haar) Gebrauch bzw. Missbrauch von Medikamenten und Drogen. Sowohl die Haar- als auch Speichelmatrix sollen den physiologisch aktiven Anteil von Substanzen im Blut widerspiegeln und somit korrektere Rückschlüsse auf deren Wirksamkeit zulassen. Das endogene Glucocorticosteroid Cortisol steht seit der Jahrtausendwende im Blickpunkt vieler Forschungen, welche sich mit dessen Bedeutung für die Stressantwort befassen und Cortisol u.a. im Speichel und Haar nachweisen. Auffällig ist dabei, dass die ersten Arbeiten fast ausschließlich mittels immunchemischen Nachweisverfahren erfolgten. Erst in den letzten fünf Jahren wurde vermehrt LC-MS/MS-Verfahren angewandt. Vorteil dieser ist, dass der Nachweis von Substanzen selektiv erfolgt und Kreuzreaktionen nicht stattfinden. Weiterhin ist es vorteilhaft, dass die Konzentrationen von mehreren Analyten mit einer Messung bestimmt werden können. So ist es zum Beispiel möglich Cortisol und andere Steroide, z.B. dem Cortison parallel nachzuweisen. Cortison spielt für die physiologische Wirkung der Glucocorticosteroide im Körper keine Rolle, da es selbst nicht biologisch aktiv ist. Deshalb wurde es in bisherigen Forschungen für diagnostische Aussagen nicht berücksichtigt. Mit Verwendung der LC-MS/MS-Technologie werden jedoch beide endogenen GCs zunehmend nebeneinander bestimmt. Bei der Betrachtung von unterschiedlichen Untersuchungsmedien ist auffällig, dass sich die Konzentrationsverhältnisse Cortisol zu Cortison unterscheiden. Entgegengesetzte Verhält-nisse werden ersichtlich, wenn die GC-Konzentrationen im Blut mit denen im Speichel bzw. Haar verglichen werden. Bisher wurden diese Beobachtungen mit der lokalen Wirksamkeit von Enzymen, welche die Corticosteroide ineinander umwandeln, erklärt. Im Rahmen der vorliegenden Dissertation wurde folgender Fragestellung für die Nachweisbarkeit der Glucocorticosteroide nachgegangen: „Wie hoch ist der Anteil der Plasmaproteinbindung der GCs im Blut und welche Rückschlüsse lassen sich daraus auf die Konzentrationsverschiebung innerhalb der einzelnen Matrizes ziehen?“ Basierend auf die einzelnen Teilprojekte wurden sowohl Plasmaproben als auch Speichel- und Haarproben hinsichtlich ihrer GC-Konzentrationen analysiert. Die Untersuchung von Kontrollproben ermöglichte es, Referenzwerte unter Normalbedingungen zu erheben. Die Ergebnisse aus den Projekten ergaben, dass die beiden endogen GCs Cortisol und Cortison in unterschiedlichen Konzentrationsverhältnissen in den Analysenmedien vorkommen: Plasma: Gesamtkonzentration F:E ca. 3:1 freie Konzentrationen F:E ca. 1:1 Speichel: F:E ca. 1:5 Haar: F:E ca. 1:3 Die Bestimmung der Plasmaproteinbindung (PPB) beider endogener GCs hat gezeigt, dass Cortisol mit ca. 96 % stärker an die Transportproteine CBG und Albumin bindet als Cortison mit ca. 85 %. Dies führt dazu, dass sich die freien, nicht-proteingebundenen Konzentrationen angleichen und es zu einer Verhältnisverschiebung von Cortisol zu Cortison von 3:1 auf 1:1 kommt. Somit stehen vergleichbare Konzentrationen für die Inkorporation ins Haar bzw. die Diffusion in den Speichel zur Verfügung. Es konnte gezeigt werden, dass die freien Plasmakonzentrationen beider GC stark mit den Speichelkonzentrationen korrelieren. Cortisol aber unterproportional und Cortison überproportional vom Plasma in den Speichel übergeht. Dies kann mit zwei weiteren Mechanismen, welche während der Diffusion eine Rolle spielen, der unterschiedlichen Lipophilie und der Inaktivierung durch lokale Enzym-reaktionen, erklärt werden. Weiterhin wurde gezeigt, dass sich die Tagesrhythmik der GC-Produktion im Speichel abbilden lässt und eine starke Korrelation zwischen Cortison und Cortisol vorliegt. Mit Hilfe einer Grenzfunktion können endogene Referenzkonzentrationen definiert und Messdaten eingeordnet werden. Unter anderem wurde gezeigt, dass eine Hormonersatztherapie mit Hydrocortison zu einer Verschiebung der Metabolisierung und der PPB führt und somit ein Gebrauch/Missbrauch von GCs durch abweichende Konzentrationsverhältnisse nachweisbar ist. Speicheluntersuchungen während einer chronischen Stresssituation (Schwangerschaft) zeigen, dass die GC-Produktion stetig ansteigt und sich besonders die morgendlichen Werte unterscheiden. Um die tageszeitlichen und stressbedingten Schwankungen der GC-Produktion auszublenden und eine längere Zeitspanne zu betrachten, wurden zusätzlich Haarproben analysiert. In diesen wurde ein kontinuierlicher Anstieg der GCs in den proximalen Haarsegmenten nachgewiesen, was auf eine kontinuierlich erhöhte Inkorporation während der chronischen Stresssituation schließen lässt. Außerdem wurde gezeigt, dass die Haarkonzentrationen dem Auswascheffekt unterliegen und die nachweisbaren Konzentrationen geringer werden, je älter das Haar wird. Schlussfolgernd kann gesagt werden, dass beide Mechanismen (Einlagerung und Auswaschung) konkurrieren und deshalb Referenzdaten nur für das proximale Segment erhoben werden können. Für weitere Segmente sind die Auswirkungen der individuellen Einflüsse nicht mehr allgemeingültig kalkulierbar und nur noch intraindividuelle Vergleiche nach mehrmaliger Beprobung aussagekräftig. Sind die Effekte der verstärkten Inkorporation größer als die Auswaschung, lassen sich diese auch Monate später erkennen. Zusammenfassend kann gesagt werden, dass die Plasmaproteinbindung der GCs zur Verhältnisverschiebung der Konzentrationen im Blut, Speichel und Haar beiträgt. Etwa 50 % des beobachteten Effekts kann der PPB zugeordnet werden. Weitere Quellen sind die unterschiedliche Lipophilie der GCs und die enzymatische Umwandlung, welche im Rahmen der vorliegenden Arbeit jedoch nicht „quantitativ“ betrachtet wurden. Die enzymatische Inaktivierung wurde bis dato als Hauptverantwortliche für die Konzentrationsverschiebung diskutiert. Mit der aktuellen Arbeit wurde dies widerlegt, und die Plasmaproteinbindung als Hauptquelle identifiziert.

Le travail de cette thèse s’inscrit dans le cadre du projet ANR SUSoSTRESS qui a pour objectif la compréhension des mécanismes moléculaireset génétiques sous-jacents à la variabilité individuelle de réponses de stress et a collecté des données longitudinales à plusieurs niveaux biologiquessur une population d’étude porcine (race Large White). La thèse est organisé en deux partie. La première partie s’articule autour de l’analyse de données cliniques et transcriptomiques collectées à plusieurs pas de temps avant et après application de deux types de stress : injection d’ACTH et de LPS. Dans cettepartie, on cherche à développer d’un modèle fonctionnel permettant de décrire et d’intégrer au mieux l’ensemble des sources de variation génétique du fonctionnement de l’axe corticotrope et plus généralement des réponses de stress dans notre population d’étude. Plus précisément, il s’agit d’élaborer un modèle (au sens biologique du terme) décrivant les différentes réponses biologiques de stress et l’influence des variations génétiques (simples et en interaction), dans le but de prédire les leviers les plus efficaces en fonction de l’objectif de sélection. Ce travail a mis en évidence une liste de 65 gènes différentiellement exprimé au cours des réponses au stress, dont un ensemble de 8 gènes liés au au cortisol (l’hormone principale du stress) par NR3C1, le récepteur aux glucocorticoides. Ces gènes sont des biomarqueurs potentiels pouvant être fournis aux éleveurs en tant que leviers de sélection permettant un meilleur équilibre entre amélioration des caractères de production et des caractères de robustesse. La deuxième partie de ce travail s’articule autour du développement d’un outil d’analyse statistiques adapté à l’intégration de données ’omiques longitudinalesavec une variable cible d’intérêt.Nous proposons la «multiway-SIR », qui étend la méthode dual-STATIS, une méthode d’analyse de données cubiques non supervisée, au cadre de la SIR, une méthode de régression semi-paramétrique pouvant être utilisée à des fins exploratoires. Cette méthode est appliquée sur les données cliniques de l’expérience d’ACTHet permet d’y explorer l’influence de la variabilité de la réponse du cortisol à une injection d’ACTH. / This PhD thesis is part of the SUSoSTRESS project. This ANR funded project aims at improving the knowledge about molecular and genetic mechanisms underlying inter-individual variability in stress responses. Longitudinal data were collected at several biological levels on a porcine population (Large White). This work is structured in 2 parts. The first part is built around clinical and transcriptomic longitudinal data analyses collected before and after 2 types of stress factors : ACTH and LPS injection. The aim of this contribution is to develop a functional model describing all sources of genetic variation in the HPA axis activity and in stress responses in our study population.More precisely, it aims at defining a model describing the different biological stress responses and the influence of genetic variations in order to identify the most efficient selection levers according to selection goals. This work allowed for the identification of 65 differentially expressed genes during stress responses. Among them, 8 genes were highly linked to cortisol (the main stress hormone) through NR3C1 (glucocorticoid receptor (GR)). These genes are potential biomarkers and can be communicated to breeders as selection levers for a better trade-off between production and robustness traits in farmanimals. The second part is built around the development of a statistical tool suited for the data integration of repeated omicmeasurements with a real target variable.We introduce the "multiway-SIR" approach which extends the dual-STATIS (an approach to study 3-way datasets) method to the SIR framework (a semi-parametric regression model that can be used in an exploratory way). This method is illustrated on clinical data from the ACTH experiment. It allows for the exploration of the link between clinical variable response over time and inter-individual variability in the cortisol response to an ACTH injection.

Comment notre cerveau traite l’information de la récompense, et comment un tel traitement est influence par des paramètres tels que la probabilité et le risque sont devenues des questions cruciales des neurosciences cognitives. De plus, des recherches récentes suggèrent un effet modulateur d’un certain nombre d’hormones sur le cerveau et sur le comportement, et également qu’un dysfonctionnement du système de récompense pourrait expliquer des comportements addictifs tels que le jeu pathologique. Durant cette thèse, nous avons eu recours à de l’EEG stéréotaxique (SEEG) et à une combinaison d’Imagerie à Résonnance Magnétique fonctionnelle (IRMf) et d’endocrinologie pour réaliser trois études s’intéressant au traitement de la récompense chez des sujets sains, chez des patients souffrant d’épilepsie chez qui des macroélectrodes ont été implantées, et chez des joueurs pathologiques. Ensemble, nos études améliorent la compréhension de nouveaux aspects du traitement de la récompense chez les sujets sains, chez les patients épileptiques, et chez les joueurs pathologiques / How our brain processes reward information and how such processing is influenced by parameters such as reward probability and risk have become key questions in cognitive neuroscience. In addition, recent researches suggest a modulatory effect of a number of hormones on brain and behavior and a dysfunction of the reward system in a number of behavioral addictions, such as gambling disorder. This Ph.D. used intracranial EEG (iEEG) and combined Functional Magnetic Resonance Imaging (fMRI) and endocrinology to perform four studies investigating reward processing in healthy subjects, patients with epilepsy implanted with depth electrodes and individuals with gambling disorder. Together, our series of studies advance our understanding of new aspects concerning reward processing in healthy subjects, patients with epilepsy and individuals with gambling disorder

A manutenção da saúde, depende, dentre outros aspectos, do controle da massa corporal, uma vez que a obesidade está associada ao desenvolvimento de doenças crônicas. Sendo assim, o exercício pode ser considerado uma ferramenta eficaz nesse controle. Contudo, está evidenciado que o exercício realizado em alta intensidade pode ocasionar maior redução da gordura corporal. Dentre as hipóteses sugeridas para explicar tal fenômeno, a supressão do apetite pós-exercício foi levantada, no entanto, o efeito da intensidade sobre o apetite ainda é incipiente. Além disso, mulheres podem ter maior resposta compensatória que homens. Portanto, o objetivo do estudo foi comparar o efeito da intensidade no controle agudo do apetite, energia ingerida absoluta e relativa (energia ingerida menos o gasto calórico do exercício), percepção de fome e das concentrações sanguíneas de grelina acilada, peptídeo YY3-36, insulina, cortisol, glicose, ácidos graxos, colesterol e triacilglicerol em homens e mulheres. Para isso, 11 homens e 9 mulheres eutróficos, foram submetidos a 6 sessões, sendo a primeira destinada à determinação da potência aeróbia máxima (PAM) em cicloergômetro, e a segunda para realização do exercício intermitente de alta intensidade realizado na máxima intensidade (all out), composto por 60 x 8s:12s (EIAI-A), para determinação do trabalho total, o qual foi utilizado para equalização das demais sessões: a) EIAI-A; b) exercício intermitente de alta intensidade (EIAI) - 60s:60s a 100% da PAM; c) exercício contínuo de intensidade moderada (ECMI) a 60% da PAM; d) sessão controle (sem exercício). Cada visita teve duração de 4h, sendo que os participantes chegaram em jejum e receberam um café da manhã padrão. O exercício foi realizado 1,5h pós-café da manhã, e uma alimentação ad libitum foi servida 4h pós-café da manhã. Coletas de sangue e da percepção de fome (escala analógica visual) foram realizadas em jejum e em 2, 2,5, 3,25 e 4h de experimento e calculada a área sob a curva (ASC) para cada uma dessas variáveis. A comparação das variáveis sanguíneas e da percepção de fome foi feita através de análise de variância a três fatores (condição, sexo e momento), e das variáveis envolvendo a ASC e a energia ingerida foi conduzida através de análise a dois fatores (condição e sexo), seguida do pós-teste de Bonferroni se observada diferença significativa (P<0,05). Não houve diferença para a energia ingerida absoluta, porém, a energia ingerida relativa foi maior no controle quando comparada ao EIAI-A, EIAI, e ao ECMI, sem diferenças entre os tipos de exercício e sexos. A ASC da percepção de fome foi menor somente nos exercícios realizados em alta intensidade comparado com o controle, independentemente do sexo. O PYY3-36 foi inferior nas mulheres em relação aos homens ao passo que o cortisol foi inferior nos homens comparado com as mulheres. Houve interação entre situação e momento de coleta para o cortisol e insulina sendo os valores mais elevados no EIAI-A que no controle às 2,5 horas de experimento para o cortisol e às 3,25h para insulina. Portanto, embora não tenha havido diferença na energia ingerida relativa entre os tipos de exercícios, àqueles realizados em maior intensidade foram capazes de promover efeitos mais pronunciados na supressão do apetite, independentemente do sexo / Maintaining one\'s health depends, among other things, on controlling body weight, since obesity is associated with the development of chronic diseases. Accordingly, exercise is an effective tool in this control. It has been demonstrated that exercise performed at a high intensity can cause greater reduction in body fat. Among the hypotheses put forward of this phenomenon is the suppression of appetite. However, the understanding of the effect of the intensity on appetite is still incipient. In addition, women may have a greater compensatory response than men. Therefore, the aim of the study was to compare the effect of intensity on absolute and relative (energy intake less caloric expenditure of the exercise) energy intake, hunger and blood concentrations of acylated ghrelin, PYY3-36, insulin, cortisol, glucose, fatty acids, cholesterol and triacylglycerol in men and women. Accordingly, 11 men and 9 women, all eutrophic, underwent six sessions. The first was designed to determine their maximum aerobic power (MAP) on a cycle ergometer, and the second involved performing high-intensity intermittent exercise at maximum intensity (all out) for 60 x 8s: 12s (HIIE-A) in order to determine the total work, which was used for the equalization of the other sessions: a) HIIE-A; b) high intensity intermittent exercise (HIIE) - 60s: 60s at 100% of MAP; c) steady-state exercise (SSE) at 60% of the MAP; d) a control session. Each session lasted a total of 4 hours. The participants arrived in fasting and received a standard breakfast upon arrival. The exercise session was performed 1.5 h after breakfast, and an ad libitum meal was served 4 hours post-breakfast. Blood sample collection and perception of hunger were collected when fasting and at 2, 2.5, 3.25 and 4 hours into the experiment and the area under the curve (AUC) for each of these variables was calculated. A comparison of the blood sample variables and rating of hunger was performed by analyzing the variance of three factors (condition, sex, and time) and the analysis of the variables involving the AUC and energy intake was conducted through examination of two factors (sex and condition) followed by a Bonferroni post-test if significant differences (P<0.05) were observed. There was no difference for the absolute energy intake, however, relative energy intake was higher in the control compared to HIIE-A, HIIE, and SSE, with no differences between the types of exercise and sex. The AUC of hunger was lower in exercises performed at high intensity when compared to the control, regardless of sex. There was interaction between condition and time for cortisol and insulin, with higher levels in the HIIE-A than in the control at 2.5 hours for cortisol and 3.25 hours for insulin. Therefore, although there were no differences in energy intake relative to the types of exercises, those performed at a higher intensity promoted more pronounced effects on appetite suppression, regardless of sex

Este estudo compara quatro diferentes intensidades com o volume total similar no exercício supino. Avaliou-se a dor muscular de início tardio (DMIT), atividade de creatina quinase (CK), as concentrações sangüíneas de interleucina (IL)-1<font face=\"symbol\">b, IL-6, fator de necrose tumoral-<font face=\"symbol\">a (TNF-<font face=\"symbol\">a), prostaglandina E2 (PGE2) e o perfil hormonal. A amostra foi composta de soldados do exército brasileiro, divididos em cinco grupos: 50%-1RM, 75%-1RM, 90%-1RM, 110%-1RM e o controle. A DMIT e a atividade plasmática de CK aumentaram significativamente (P<0,05) após a sessão de exercício. A concentração de PGE2 também teve aumento significativo (P<0,05) após a sessão (P<0,05). A concentração plasmática de cortisol após 1h do término do exercício aumentou apenas no grupo 75%-1RM (p < 0,05). Esses resultados sugerem que a intensidade no exercício supino não afeta a magnitude da DMIT, marcadores de lesão muscular, inflamação e na resposta hormonal geral, desde que haja a equalização do volume total, com exceção da concentração plasmática do cortisol, grupo 75%-1RM. / This study compared four different intensities with similar total volume of a bench press exercise for muscle soreness, creatine kinase (CK) activity, interleukin (IL)-1<font face=\"symbol\">b, IL-6, tumor necrosis factor-<font face=\"symbol\">a (TNF-<font face=\"symbol\">a), prostaglandin E2 (PGE2) and hormonal concentrations in the blood. Brazilian Army male soldiers were placed into five groups: 50%-1RM, 75%-1RM, 90%-1RM, and 110%-1RM, and control that did not perform the exercise. Muscle soreness and plasma CK activity increased significantly (p<0.05) after exercise. Serum PGE2 concentration also increased significantly (p<0.05) after exercise. After one hour post exercise cortisol increased in 75%-1RM group, with this response also exceeding the other intensities (p<0.05). These results suggest that the intensity of bench press exercise does not affect the magnitude of muscle soreness and blood markers of muscle damage, inflammation and largely similar hormonal responses, which may be attributed to the equalization of total volume, exception made for the 75%-1RM group for serum cortisol concentration.

Made available in DSpace on 2016-01-26T18:55:29Z (GMT). No. of bitstreams: 1 dissertacao Luciana Alvares Calvo Penha.pdf: 262652 bytes, checksum: c5d5a66986ee73998c29be43156901d5 (MD5) Previous issue date: 2009-11-23 / This study evaluated the effect of probiotic supplementation on both weight gain and serum cortisol concentration in cattle. Forty Nelore calves around 18 months old were randomly assigned to one of two groups (N=20 calves each) which received only mineral mixture (GC) or mineral mixture supplemented with 4.0 g probiotic Proenzime® per animal per day (GP). The cattle were subjected to handling stress by the usual weighing practices in the corral as well as blood sampling on days 0, 75 and 150. Live weight gain increased in GP (8.20 Kg; 17.07%) from day 0 to 75 (P<0.05); no weight differences were detected from day 76 to 150 (P>0.05). Cortisol concentration increased in GC cattle on day 150 (P<0.05). In GP cattle serum cortisol was constant over the experiment (P>0.05). On day 150, cortisol concentration were higher in GC as compared to GP. No correlations were detected between live weight gain and serum cortisol on days 75 (r= -0.005ns) and 150 (r= -0.007ns). These results indicate that: probiotic administration enhances weight gain in cattle for 75 days but not longer; and day 150 probiotic supplementation can lower cortisol concentration in cattle that are frequently stressed by handling and weighing practices in the corral. / Este estudo avaliou o efeito da suplementação com probiótico no cortisol sérico e no ganho de peso em bovinos. Quarenta bezerros Nelore com cerca de 18 meses de idade foram distribuídos aleatoriamente para um dos dois grupos (N = 20 bezerros cada) que receberam apenas mistura mineral (GC) ou mistura mineral suplementado com 4,0g de probiótico Proenzime® (GP) por animal por dia. Os bovinos foram submetidos ao estresse pela prática da manipulação habitual de pesagem no curral, bem como amostragem sangue nos dias 0, 75 e 150. O ganho de peso vivo aumentou no GP (8,20 kg; 17,07%) do dia 0 aos 75 (P < 0,05) e no ganho de peso não foram detectadas diferenças a partir do dia 76 a 150 (P > 0,05). A concentração do cortisol aumentou nos bovinos do GC no dia 150 (P < 0,05) e nos bovinos do GP o cortisol sérico foi constante ao longo do experimento (P > 0,05). No dia 150 as concentrações de cortisol foram maiores no GC em comparação com o GP. Não foram detectadas correlações entre ganho de peso vivo e cortisol sérico nos dias 75 (r =-0.005ns) e 150 (r =-0.007ns). Estes resultados indicam que a administração de probiótico aumentou o peso nos bovinos nos primeiros 75 dias, e no dia 150 a suplementação diminuiu a concentração sérica de cortisol do qual se encontram freqüentemente submetidos a movimentação e a prática da pesagem no curral.

Made available in DSpace on 2016-01-26T18:55:31Z (GMT). No. of bitstreams: 1 Dissertacao.pdf: 371163 bytes, checksum: 00d67c3200895b27fd357306527c561c (MD5) Previous issue date: 2011-03-18 / The objective of this work was to study the seasons influence (spring, summer, autumn and winter) on semen characteristics and hormones (testosterone and cortisol) in Nelore and Simental bulls. Five Nelore and five Simental bulls were 48-72 months old, extensively managed, were evaluated for sexual soundness using physical and morphological characteristics of semen and hormonal serum levels. There was decreased motility and vigor semen (P<0.05) during winter in Simental bulls. There was correlation between serum testosterone and cortisol (P<0.01) to motility and vigor in either Nelore and Simental bulls. In conclusion, these results showed a hormonal and semen characteristics variation throughout the season change the semen quality. Bulls from Nelore breed differed from Simental, demonstrating adaptability to the field conditions. / O objetivo desse trabalho foi estudar a influência das quatro estações do ano: (primavera, verão, outono e inverno), nas características do sêmen e nos níveis de testosterona e cortisol em touros Nelore e Simental. Cinco touros Nelore e cinco Simental com 48-72 meses de idade, criados extensivamente, foram avaliados andrologicamente por meio de exame físico e das características morfológicas do sêmen, concentrações séricas de testosterona e cortisol. Houve queda na motilidade e vigor do sêmen no inverno (p<0,05) para a raça Simental. Houve correlação entre a concentração sérica de testosterona e cortisol (P<0,01) para a motilidade e vigor espermático para os touros Nelore e Simental. Conclui-se que houve variação hormonal e nas características do sêmen ao longo das estações modificando a qualidade do sêmen. Os touros da raça Nelore diferiram dos da raça Simental, demonstrando adaptabilidade às condições do campo.