Il a été suggéré que lorsqu’une trace de mémoire consolidée est rappelée (réactivée), elle devient instable et sujette aux modifications avant de se stabiliser à nouveau en mémoire à long terme. Nous avons récemment démontré que lorsque la réactivation d’un souvenir négatif est couplée à l’exposition à un stress psychosocial, le souvenir de l’évènement négatif est augmenté de façon durable. En se basant sur ces résultats, le but de cette thèse est de préciser le rôle du stress psychologique et physiologique (hormones de stress) sur la modulation de souvenirs réactivés. Plus précisément, la première étude visait à déterminer si le cortisol, hormone de stress majeure, est un joueur clé dans la modulation des souvenirs réactivés. Pour ce faire, nous avons inhibé pharmacologiquement les niveaux de cortisol au moment de la réactivation d’un souvenir contenant des segments neutres et négatifs. Les résultats démontrent que la réactivation du matériel négatif est amoindrie lorsque les niveaux de cortisol sont inhibés, et cet effet est toujours présent quatre jours plus tard. Étant donné que les stimuli utilisés jusqu’à maintenant ont une faible validité écologique, nous avons voulu déterminer si d’autres types de mémoires pouvaient également être modulables lors de leur réactivation. L’objectif de la deuxième étude était donc de déterminer si les mémoires autobiographiques collectives sont modulables par le stress au moment de leur réactivation. Pour ce faire, nous avons exposé les participants à de vrais extraits de journaux, neutres ou négatifs, afin de réactiver les mémoires collectives associées à ces évènements. Par la suite, tous les participants ont été exposés à un stress psychosocial et leur mémoire des extraits a été évaluée la journée suivante. Les résultats démontrent que les femmes ayant lu les nouvelles négatives avaient une réactivité physiologique accrue face au stresseur et une mémoire augmentée de ces mêmes nouvelles le jour suivant. Ce phénomène n’était cependant pas observable chez les hommes. Le but de la troisième étude était de déterminer si les mémoires autobiographiques personnelles sont modulables par le stress au moment de leur réactivation. Nous avons demandé aux participants de se remémorer deux évènements de leur passé, négatifs ou neutres. Par la suite, ils ont été exposés à un stress psychosocial et leur mémoire pour ces mêmes évènements a été évaluée à nouveau la journée suivante. Les résultats démontrent que les mémoires autobiographiques personnelles réactivées ne semblent pas être modulables par l’exposition à un stresseur. Globalement, les résultats de cette thèse démontrent que le cortisol a la capacité de moduler des souvenirs négatifs réactivés, mais que la nature (extrinsèque vs. intrinsèque) et l'intensité des souvenirs réactivés sont des facteurs déterminants pour que ce phénomène prenne place. / It has been suggested that when a consolidated memory trace is recalled (reactivated), it becomes active and sensitive to modifications before stabilizing again in the long-term memory system. We have recently demonstrated that when the reactivation of a negative memory is followed by exposition to a psychosocial stressor, the memory for the negative material is enhanced in a long-lasting manner. Based on these results, the goal of this thesis is to clarify the role of physiological (stress hormones) and psychological stress on the modulation of reactivated memories. More precisely, the first study aimed to determine whether cortisol, a major stress hormone, is a key player in the modulation of reactivated memories. To do so, we have pharmacologically inhibited cortisol levels at the time of reactivating a memory composed of neutral and negative segments. Results showed that the reactivation of the negative material is decreased when cortisol levels are inhibited and this effect is still present four days later. Given that the stimuli used so far have a weak ecological validity, we wanted to determine whether other types of memories could also be modified upon their reactivation. The goal of the second study was to examine whether collective autobiographical memories were sensitive to the effects of stress at the time of reactivation. To do so, we have exposed participants to real newspaper excerpts, either neutral or negative, in order to reactivate the collective memories associated to these events. We have then exposed all the participants to a psychosocial stressor and their memory for the excerpts was assessed the following day. Results showed that women who have read negative news excerpts had a more pronounced physiological reactivity to the stressor and an increased memory for these news the following day. This phenomenon, however, was not observed in men. The goal of the third study was to determine whether personal autobiographical memories were sensitive to the effects of stress at the time of their reactivation. We have asked participants to recall two personal events, either negative or neutral. We then exposed them to a stressor and their memory for these events was tested the following day. The results showed that reactivated personal autobiographical memories were not sensitive to stress. Globally, the results of this thesis show that cortisol has the capacity to modulate reactivated negative memories, but that the nature (extrinsic vs. intrinsic) and the intensity of the memories are determining factors for this phenomenon to occur.

Mit dieser Arbeit sollte erforscht werden, welchen Einfluss Umsetzung und Vergesellschaftung von Grevy- bzw. Böhm-Zebras in Zoologischen Gärten auf die Produktion von Stressund Sexualhormonen haben. Dafür wurden vor, während und nach dem Umsetzungs- und Vergesellschaftungsprozess Kotproben der Zebras gesammelt,bei -20°C gelagert, mit einem Methanol-Wasser-Gemisch extrahiert und anschließend deren Gehalt an Cortisol-, Progesteron-, Östradiol- und Testosteronmetaboliten analysiert. Dabei konnte gezeigt werden, dass sowohl bei den adulten Grevy-Zebrastuten als auch bei deren Jungtieren (Zoo Leipzig) im Untersuchungszeitraum 2004 das ranghöchste und rangniedrigste Tier, 2008 nur das dominante Tier die höchsten Cortisolspiegel der Gruppe aufwiesen. Das in der Rangordnung den mittleren Platz einnehmende Zebra zeigte signifikant niedrigere Cortisolspiegel. Von den drei untersuchten Böhm-Zebras (Zoo Halle) besaß der Hengst signifikant niedrigere Cortisolwerte als die beiden Stuten, deren Cortisolspiegel sich vor der Umsetzung nicht signifikant voneinander unterschieden. Die Umsetzung der Grevy- Zebras in die Kiwara-Savanne und die Vergesellschaftungen mit Säbelantilopen, Straußen und Giraffen und auch die Umsetzung der Böhm-Zebras in ihr neues Gehege erhöhten jedoch nur bei den subdominanten Tieren den Basiswert des Cortisols signifikant. Zusätzliche Faktoren, wie z. B. sozialer Status (dominant vs. subdominant), soziale Ordnung und weitere exogene Einflüsse scheinen somit eine entscheidende Rolle bei der Stress-Verarbeitung von in Zoologischen Gärten gehaltenen Zebras einzunehmen. Die Adaptation der Zebras an ihre neue Umgebung nahm in den beiden Zoos unterschiedliche Zeitspannen in Anspruch. Bei den Grevy-Zebras war es aus tiergärtnerischen Gründen nicht möglich, diese AdaptationsZusammenfassung zeit zu definieren, da nur bis zwei Monate nach der Umsetzung eine individuelle Kotprobensammlung erfolgte und zu dieser noch bei einzelnen Tieren erhöhte Cortisolwerte messbar waren. 2008 konnten jedoch bei den adulten Stuten signifikant niedrigere Cortisolspiegel gemessen werden als 2004 im alten Gehege. Bei den drei untersuchten Steppenzebras fielen ca. vier Wochen nach der Umsetzung die Cortisolkonzentrationen deutlich ab und waren bei den beiden Stuten signifikant niedriger als im alten Gehege und als in der Zeit direkt nach der Umsetzung. Dies lässt die Schlussfolgerung zu, dass die neuen Gehege günstigere Umweltbedingungen bieten als die alten Zebra-Anlagen. Bei der Auswertung der Sexualhormone wurde deutlich, dass alle drei Grevy-Zebrastuten im nicht tragenden Zustand sehr ähnliche Sexualhormonspiegel zeigten. Nach der Umsetzung war weder für Progesteron noch für Östradiol ein charakteristischer Zyklusverlauf zu erkennen. Es ist also anzunehmen, dass hier der durch die Umsetzung und Vergesellschaftung hervorgerufene Stress und damit das Ansteigen der Cortisolproduktion einen negativen Einfluss auf die Reproduktionsfähigkeit der untersuchten Zebras hatte. Die Böhm-Zebras waren während der Umsetzung tragend. Die Narkose und die neue Umgebung hatten keinen messbaren Einfluss auf die Sexualhormone und am Ende einer physiologischen Tragezeit wurden zwei gesunde Jungtiere geboren. Bei den beiden Böhm-Zebrastuten konnten des Weiteren die Östradiol- und Progesteronexkretionsprofile über drei Jahre hinweg aufgenommen und somit die Trächtigkeitsdauer und der Hormonverlauf während der Trächtigkeit beschrieben werden. Das Hormonprofil des Östradiol gleicht weitestgehend dem bei Grevy- Zebras geschilderten Verlauf mit der maximalen Ausscheidung während des zweiten Trimesters. Die Konzentration der Progesteronmetabolite weicht jedoch deutlich von dem bei Grevy- Zebras beschriebenen Profil ab. Hier konnte ein stetiges Ansteigen der Werte ermittelt werden, wobei frühestens ab der 8. Woche a.p. Werte über 200ng/g erreicht wurden und die höchsten Konzentrationen ca. 12 bis einen Tag a.p. bzw. einen Tag post partum gemessen wurden. Die durchschnittliche Trächtigkeitsdauer betrug 343±15 Tage. Mit dieser Arbeit konnte gezeigt werden, dass mittels Hormonbestimmungen im Kot von Zebras Veränderungen im Hormonhaushalt sowohl von Stress- als auch von Sexualhormonen sehr gut quantifiziert werden können. Dadurch besteht die Möglichkeit, den Einfluss tiergärtnerisch wichtiger Verfahren, wie das Umsetzen und Vergesellschaften von Zebras oder die Kontrolle von Trächtigkeiten wissenschaftlich auszuwerten und Aussagen über die Qualität der Haltungsbedingungen zu treffen. Des Weiteren können über die individuellen Cortisolmetabolitkonzentrationen Rückschlüsse auf die soziale Stellung innerhalb der Gruppe gezogen und die Auswirkungen dieser auf den Umgang mit „Stress“ charakterisiert werden.

Migraine is a disabling neurological disorder with high prevalence, the clinical manifestations of which are highly dependent on stress. The overall theme of the present thesis was to address aspects of stress in migraine. A multimodal behavioral treatment (MBT) program was developed specifically designed for migraine and focusing on stress as a trigger and an intervention was performed using this Internet-administered program. Migraine symptoms were followed via an Internet administered diary and questionnaires were answered at regular intervals during the 11-month study period. The thesis is based on four papers: In Paper I, life events and current stress, personality traits, and gender were studied cross-sectionally in 106 women and 44 men with migraine, who suffered at least two attacks a month at inclusion. Paper II describes a randomized controlled trial of the MBT program performed on 58 women and 25 men recruited from participants of the study described in Paper I. In the MBT study participants were randomized into one control group and two MBT groups, one of which received hand massage as part of the treatment. In Paper III, complete migraine drug use and changes in use and in drug efficacy during the MBT program were studied. In Paper IV, the salivary cortisol levels of MBT participants were evaluated as a biological stress marker. The MBT program proved effective in decreasing migraine headache; it was feasible and there was low attrition. Moreover, MBT resulted in decreased migraine drug use and increased drug efficacy, but had no discernible effects on salivary cortisol profiles. No effect of hand massage on migraine headache frequency was seen. Personality trait profiling revealed high scores for the neuroticism factor. Stress susceptibility was the single most aberrant personality trait and correlated highly with the reported level of current stress and with experienced negative life events. Gender differences included higher scores for women on trait anxiety, negative life events, depressive mood, anxiety, tension type headache, use of triptans, and efficacy of analgesics, whereas men displayed higher use of analgesics. In conclusion, the efficacy and low attrition associated with the present MBT program appears promising and timely with regard to the development of better and more accessible migraine treatment. Stress susceptibility, gender, negative life events and psychosomatic comorbidity are important factors to consider in relation to the care of persons with migraine.

No description available.

L’état de stress post-traumatique (PTSD) est un trouble anxieux, lié au stress, souvent observé chez les soldats revenant de conflits armés, les victimes de guerre ou de catastrophes naturelles, mais qui peut également survenir après exposition à des situations plus « communes » dans les pays occidentaux en temps de paix, tels les accidents de la route ou les agressions sexuelles. Le PTSD est caractérisé par des troubles des fonctions exécutives (attention, mémoire de travail), associés à des anomalies cérébrales morphologiques et fonctionnelles. Cette thèse de doctorat a permis de caractériser les effets morphologiques et fonctionnels des différents traitements actuellement reconnus de première ligne pour les troubles anxieux et le trouble dépressif majeur, indiquant un effet « top-down » de normalisation des aires frontales par les traitements psychothérapiques, alors que les traitements pharmacologiques semblent avoir un effet « bottom-up » de normalisation des aires limbiques. De plus, dans une seconde étude, nous avons montré l’importance de l’étude de réseaux cérébraux impliqués dans la performance de tâches cognitives telles des tâches de mémoire. Ces réseaux se trouvent dérégulés dans la pathologie post-traumatique, conduisant à leur inefficacité, et provoquant une impossibilité pour les patients de pouvoir répondre correctement à la tâche proposée. Finalement, nous avons pu mettre en place un protocole de recherche clinique ambitieux de part son design longitudinal (visite à 1 mois, puis suivi à 6 mois) permettant de comprendre les étapes précoces du développement du PTSD chez des victimes d’agressions sexuelles. Cette étude allie mesures neuropsychologiques des fonctions exécutives, mesures biologiques de l’axe hypothalamo-hypophyso-surrénalien (cortisol salivaire) et des mesures de neuroimagerie structurale (IRM, DTI), fonctionnelle (IRMf, ASL), incluant des mesures de connectivité cérébrale (structurale, fonctionnelle). / Posttraumatic stress disorder (PTSD) is an anxiety, stress-related disorder, often seen in soldiers returning from armed conflict, victims of war or natural disasters, but can also occur after exposure to more « common » situations in Western countries, such as motor vehicle accidents or sexual assault. PTSD is characterized by executive functioning impairments (attention, working memory) associated with morphological and functional brain abnormalities. This thesis aimed to characterize the morphological and functional effects of different treatments currently recognized as first line for anxiety disorders and major depressive disorder, indicating a « top-down » effect of normalization of frontal areas for psychotherapeutic treatments, while pharmacological treatments seem to lead to a « bottom-up » normalization effect in limbic areas. In addition, in a second study, we demonstrated the importance of the study of brain networks involved in the performance of cognitive tasks such as memory tasks. These networks are deregulated in PTSD, leading to their inefficiency, and therefore to PTSD patient’s inability to perform the required task correctly. Finally, we have set up an ambitious longitudinal (1 month and 6 months) clinical research protocol, investigating early stages of PTSD development in victims of sexual assault. This study combines neuropsychological measures of executive functions, biological measures of the hypothalamic-pituitary-adrenal axis (salivary cortisol) and measures of structural (MRI, DTI) and functional imaging (fMRI, ASL), including measures of brain connectivity (structural, functional).

A leptina é um hormônio peptídico multifuncional, produzido principalmente pelo tecido adiposo, possuindo receptores (Ob-Rs) nos órgãos reprodutivos, hipotálamo e hipófise. Os glicocorticóides, como o cortisol, também influenciam diretamente a produção de leptina. A importância desses dois hormônios na atividade reprodutiva tem sido descrita por diversos autores, que observaramo envolvimento de ambos, na melhoria dos índices reprodutivos, seja por sua influência direta no eixo hipotalâmico-hipofisário-gonadal, na maturação dos oócitos ou na preparação uterina para receber o concepto. No entanto, quando em excesso na circulação, podem influênciar negativamente o sistema reprodutivo. Marcadores como a leptina e seu receptor funcional de cadeia longa, estão sendo estudados no endométrio de espécies como humanos, bovinos e suínos, apresentando resultados que correlacionam a diminuição destes, com a infertilidade ou perda embrionária, porém até o momento não foi possível encontrar estudos que abordassem esse tema em equinos. Neste estudo foram avaliados: 1) a presença de leptina (Ob) e seu receptor (Ob-Rb) no endométrio de éguas, observando a influência da obesidade e do ciclo estral nesses marcadores e 2) em uma condição de manejo adverso e estressante, a influência do cortisol intrafolicular, nos níveis de leptina no fluido folicular (FF) e nos marcadores de Ob e Ob-Rb no endométrio durante as fases do ciclo estral. Os resultados demonstraram que existe a presença da leptina e seu receptor (Ob-Rb) no endométrio de equinos, com imunomarcação no epitélio luminal e glandular em todas as fases do ciclo estral avaliadas, apresentando, no entanto, uma marcação imunológica mais intensa nos Ob-Rb (142.68±4.97, P< 0,0001) no epitélio glandular durante o diestro em éguas de escore corporal moderado. Não foi possível observar a influência do aumento do cortisol intrafolicular (FF) nas variáveis avaliadas, pois o cortisol se manteve dentro dos valores fisiológicos para a espécie, no entanto pode-se verificar uma correlação positiva entre os níveis intrafoliculares de cortisol e leptina, estando o cortisol aumentado 8 (30.1±0.07ng/ml, P< 0,05) nos folículos mais próximos a ovulação. Pode-se perceber também, que a marcação imunológica do receptor de leptina no epitélio glandular foi mais intensa (144.52±3.17, P< 0,0001) nos animais que apresentavam folículos até 22 mm, estando a imunomarcação de ambos Ob e Ob-Rb correlacionado de forma negativa (r: -0.7836; P < 0.0001, r:- 0.7343; P < 0.0001), com os níveis de cortisol no FF. / Leptin is a multifunctional peptidic hormone, mainly produced by adipose tissue, having receptors (Ob-Rs) in the reproductive organs, hypothalamus and pituitary. Glucocorticoids, such as cortisol, also directly influence leptin production. The importance of these two hormones in reproductive activity has been described by several authors, who observed the involvement of both, in the improvement of reproductive indices, either by their direct influence on the hypothalamic-pituitary-gonadal axis, oocyte maturation or the uterine preparation to receive the concept. However, when in excess in circulation, they can negatively influence the reproductive system. Markers such as leptin and its long-chain functional receptor are being studied in the endometrium of species such as humans, cattle and pigs, presenting results that correlate the decrease of these with infertility or embryonic loss, but to date it has not been possible to find studies to address this issue in horses. In this study we evaluated: 1) the presence of leptin (Ob) and its receptor (Ob-Rb) in the endometrium of mares, observing the influence of obesity and estrous cycle on these markers and 2) in an adverse and stressful management condition, the influence of intrafollicular cortisol, leptin levels in the follicular fluid (FF), and the Ob and Ob-Rb markers in the endometrium during the estrous cycle phases. The results showed that leptin and its receptor (Ob-Rb) are present in the equine endometrium, with immunostaining in the luminal and glandular epithelium in all stages of the estrous cycle evaluated, however, showing a more intense immunological labeling in Ob -Rb (142.68 ± 4.97, P <0.0001) in the glandular epithelium during the diestrous in mares of moderate body score. It was not possible to observe the influence of intrafollicular cortisol (FF) on the variables evaluated, because cortisol remained within the physiological values for the species, however a positive correlation can be observed between intrafollicular cortisol and leptin levels, being the 10 cortisol increased (30.1 ± 0.07ng/ml, P <0.05) in the follicles closest to ovulation. It can also be noticed that the immunological labeling of the leptin receptor in the glandular epithelium was more intense (144.52 ± 3.17, P <0.0001) in the animals that presented follicles up to 22 mm, and the immunostaining of both Ob and Ob-Rb correlated negatively (r: -0.7836; P <0.0001, r: - 0.7343; P <0.0001), with cortisol levels in FF.

O estresse na equipe de enfermagem pode acarretar danos à saúde que se manifestam tanto no rendimento individual quanto profissional desse indivíduo. O objetivo deste estudo foi avaliar o nível de estresse no trabalho da equipe de enfermagem, a partir da medida do cortisol salivar e de escalas nas unidades cirúrgica, emergência e do centro de tratamento intensivo de um Hospital universitário. Consistiu em um estudo transversal, descritivo e analítico, realizado no Hospital de Clínicas de Porto Alegre, com amostra de 90 mulheres das unidades cirúrgicas, emergência e CTI. Para avaliação do estresse, utilizou-se a coleta de cortisol salivar em três momentos: ao acordar, 30 minutos após acordar e antes de dormir. A escala de Estresse Percebido (EP) foi utilizada para avaliar a autopercepção do estresse, e para análise do estresse no trabalho foi utilizado a Job Stress Scale. Os dados obtidos indicaram que 78 % da equipe apresentaram níveis de cortisol salivar diurno acima de 19,7 nmol/L, valor que foi considerado como limiar para estresse nesse estudo. No entanto, não houve diferença significativa entre as três unidades. O escore médio de estresse percebido foi de 24,37 + 7,23. Houve correlação positiva significativa entre: os níveis de cortisol antes de dormir e a demanda de trabalho; entre escore da escala de EP e a pressão arterial sistólica (PAS); entre o escore da JSS_demanda e PAS; e houve correlação negativa entre o apoio social e o estresse autopercebido, assim como entre o apoio social e PAS. O cortisol salivar, sendo um importante biomarcador do estresse, além de ser potencialmente mais sensível do que a autopercepção do estresse, detectou alta prevalência de estresse na equipe de enfermagem. Essa avaliação pode ser útil na prevenção precoce de distúrbios que tragam danos para a saúde e também ao ambiente laboral. Os resultados alertam para alguns aspectos relacionados ao processo de trabalho que podem contribuir para o planejamento de melhorias tanto pessoais como profissionais. / Stress in the nursing team may be harmful to health and impair someone´s personal and professional achievements. The aim of this study was to evaluate the level of stress at work of the nursing staff from the surgical, emergency and intensive care units of a university hospital. This was a cross-sectional, descriptive and analytical study performed at the Hospital de Clinicas de Porto Alegre. The sample consisted of 90 women from surgical, emergency and intensive care units. Salivary cortisol was evaluated upon waking, 30 minutes after waking and at bedtime. The Perceived Stress Scale (PSS) and the Job Stress Scale (JSS) were used to assess self-perceived stress and stress at work. Data indicated that 78% of the staff had salivary cortisol levels above 19.7 nmol/L in the morning, threshold used in this study be considered as stressed. However, no significant difference was found between the three units The mean score of perceived stress was 24.37 + 7.23. There was a significant positive correlation between: cortisol levels before bedtime and self-perceived work demands; between PSS score and systolic blood pressure (SBP) between SBP and JSS_demand score; a negative correlation was found between social support and stress, as well as social support and SBP. Salivary cortisol, as an important stress biomarker, in addition to being potentially more sensitive than self-perceived stress, signaled high levels of stress among the nursing staff. This evaluation may be useful for early prevention of disorders that are harmful to the employee health and also to the work environment. These results emphasize some aspects related to the work process that can contribute to the planning of both personal and professional improvement. / El estrés en el personal de enfermería puede conducir a problemas de salud que se manifiestan tanto en el rendimiento individual, cuanto profesional de este individuo. El objetivo de este estudio fue evaluar el nivel de estrés en el trabajo del personal de enfermería, a partir de la medición de cortisol salival y de escalas en las unidades quirúrgicas, urgencias y en la unidad de cuidados intensivos de un hospital universitario. Consistió en un estudio transversal, descriptivo y analítico, realizado en el Hospital de Clínicas de Porto Alegre, con una muestra de 90 mujeres de las unidades quirúrgicas, emergencia y CTI. Para evaluar el estrés, se utilizó la colecta de cortisol salival en tres momentos: al despertar, a 30 minutos después de despertarse y antes de dormir. La Escala de Estrés Percibido (EP) se utilizó para evaluar la auto-percepción del estrés y para el análisis del estrés en el trabajo, se utilizó la Job Stress Scale. Los datos indicaron que el 78% del personal tenía los niveles de cortisol salivar diurnos por encima de 19,7 nmol / L, valor que fue considerado umbral para el estrés en este estudio. Sin embargo, no hubo diferencia significativa entre las tres unidades. La puntuación media de estrés percibido fue 24,37 + 7,23. Hubo una correlación positiva significativa entre: los niveles de cortisol antes de dormir y la demanda de trabajo; entre el escore de la escala EP y la presión arterial sistólica (PAS); entre la puntuación de JSS_demanda y PAS; y hubo una correlación negativa entre el apoyo social y el estrés auto-percibido, así como entre el apoyo social y PAS. El cortisol salival, que es un marcador biológico importante del estrés, además de ser, potencialmente, más sensible que el estrés auto-percibido, detectó una alta prevalencia de estrés en el equipo de enfermería. Esta evaluación puede ser útil en la prevención temprana de los trastornos que traen daño a la salud y al ambiente de trabajo. Los resultados ponen de manifiesto algunos aspectos relacionados con el proceso de trabajo que pueden contribuir para la planificación de mejorías, tanto personales como profesionales.

Made available in DSpace on 2015-07-22T20:49:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-06-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Em pacientes com diabetes mellitus tipo 1 (DM1) foram observadas respostas normais ou aumentadas de GH apos estimulos. O eixo hipotalamo- hipofiseadrenal tem sido menos estudado. A ghrelina e um secretagogo de GH que tambem aumenta os niveis de ACTH e de cortisol, de forma semelhante ao GHRP-6. Nao existem estudos sobre os efeitos da ghrelina em pacientes com DM1. O objetivo do presente trabalho foi avaliar as respostas do GH, ACTH e cortisol a ghrelina e ao GHRP-6 em 9 pacientes com DM1 (HbA1c: 11.7 } 1,3%; media } SE) e em 9 individuos normais. A liberacao de GH induzida por GHRH tambem foi estudada. A media dos niveis basais de GH (ƒÊg/L) foi maior nos pacientes com DM1 (3.5 } 1.2) do que nos controles (0.6 } 0.3). Analisando AASC GH (ƒÊg/L.120min), nao foram observadas diferencas significantes entre os diabeticos (ghrelina: 3.148 } 427; GHRP-6: 1428 } 299; GHRH: 885 } 184) e os controles (ghrelina: 3228 } 1036 ; GHRP-6: 1271 } 217; GHRH: 643 } 178). Em ambos os grupos, a liberacao de GH induzida pela ghrelina foi maior do que apos GHRP-6 e GHRH. Houve uma tendencia (p = 0.055) a elevacao dos niveis de cortisol basal (ƒÊg/dL) nos pacientes com DM1 (11.7 } 1.5) comparado aos controles (8.2 } 0.8). Nao foram observadas diferencas significantes nos valores de AASC cortisol (ƒÊg/dL.90min) entre os grupos apos ghrelina (DM1: 303 } 106; controles: 467 } 86) e GHRP-6 (DM1: 135 } 112; controles: 187 } 73). A media de valores basais de ACTH (pg/mL) foi semelhante nos diabeticos (19.9 } 3.4) e nos controles (14.5 } 2.3). Nao foram observadas diferencas nos valores de AASC ACTH (pg/mL.90min) entre os grupos apos ghrelina (DM1: 1372 } 771; controles: 1394 } 327) e GHRP-6 (DM1: 257 } 291; controles: 423 } 211). Em resumo, os pacientes com DM1 tem resposta normal do GH a ghrelina, GHRP-6 e GHRH. A liberacao de ACTH e cortisol apos ghrelina e GHRP-6 tambem e semelhante aos controles. Nossos resultados sugerem que a hiperglicemia cronica do DM1 nao interfere com a liberacao de GH, ACTH e cortisol estimulada por estes peptideos. / In type 1 diabetes mellitus (T1DM), GH responses to provocative stimuli are normal or exaggerated while the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH-secretagogue which also increases ACTH and cortisol levels, similarly to GHRP-6. Ghrelin Ls effects in patients with T1DM have not been evaluated. We, therefore, studied GH, ACTH and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1D1 (HbA1c: 11.7 }1.3%; mean }SE) and 9 control subjects. GHRH- induced GH release was also evaluated. Mean basal GH levels (Rg/L) were higher in T1DM (3.5 }1.2) than in controls (0.6 }0.3). Analyzing ƒ¢AUC GH values (Rg/L.120min), no significant differences were observed in T1DM (ghrelin: 3148 }427; GHRP-6: 1428 }299; GHRH: 885 }184) compared to controls (ghrelin: 3228 }1036; GHRP-6: 1271 }217; GHRH: 643 }178). In both groups, ghrelin-induced GH release was higher than after GHRP-6 and GHRH. There was a trend (p=0.055) to higher mean basal cortisol values (Rg/dL) in T1DM (11.7 }1.5) compared to controls (8.2 }0.8). No significant differences were seen in ƒ¢AUC cortisol values (Rg/dL.90min) in both groups after ghrelin (DM1:303 }106; controls: 467 }86) and GHRP-6 (DM1:135 }112; controls: 187 }73). Mean basal ACTH values (pg/mL) were similar in T1DM (19.9 }3.4) and controls (14.5 }2.3). No differences were seen in ƒ¢AUC ACTH levels (pg/mL.90min) in both groups after ghrelin (DM1:1372 }771; controls: 1394 }327) and GHRP-6 (DM1: 257 }291; controls: 423 }211). In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6 and GHRH. ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH, ACTH and cortisol releasing mechanisms stimulated by these peptides. / TEDE / BV UNIFESP: Teses e dissertações

A leptina é um hormônio peptídico multifuncional, produzido principalmente pelo tecido adiposo, possuindo receptores (Ob-Rs) nos órgãos reprodutivos, hipotálamo e hipófise. Os glicocorticóides, como o cortisol, também influenciam diretamente a produção de leptina. A importância desses dois hormônios na atividade reprodutiva tem sido descrita por diversos autores, que observaramo envolvimento de ambos, na melhoria dos índices reprodutivos, seja por sua influência direta no eixo hipotalâmico-hipofisário-gonadal, na maturação dos oócitos ou na preparação uterina para receber o concepto. No entanto, quando em excesso na circulação, podem influênciar negativamente o sistema reprodutivo. Marcadores como a leptina e seu receptor funcional de cadeia longa, estão sendo estudados no endométrio de espécies como humanos, bovinos e suínos, apresentando resultados que correlacionam a diminuição destes, com a infertilidade ou perda embrionária, porém até o momento não foi possível encontrar estudos que abordassem esse tema em equinos. Neste estudo foram avaliados: 1) a presença de leptina (Ob) e seu receptor (Ob-Rb) no endométrio de éguas, observando a influência da obesidade e do ciclo estral nesses marcadores e 2) em uma condição de manejo adverso e estressante, a influência do cortisol intrafolicular, nos níveis de leptina no fluido folicular (FF) e nos marcadores de Ob e Ob-Rb no endométrio durante as fases do ciclo estral. Os resultados demonstraram que existe a presença da leptina e seu receptor (Ob-Rb) no endométrio de equinos, com imunomarcação no epitélio luminal e glandular em todas as fases do ciclo estral avaliadas, apresentando, no entanto, uma marcação imunológica mais intensa nos Ob-Rb (142.68±4.97, P< 0,0001) no epitélio glandular durante o diestro em éguas de escore corporal moderado. Não foi possível observar a influência do aumento do cortisol intrafolicular (FF) nas variáveis avaliadas, pois o cortisol se manteve dentro dos valores fisiológicos para a espécie, no entanto pode-se verificar uma correlação positiva entre os níveis intrafoliculares de cortisol e leptina, estando o cortisol aumentado 8 (30.1±0.07ng/ml, P< 0,05) nos folículos mais próximos a ovulação. Pode-se perceber também, que a marcação imunológica do receptor de leptina no epitélio glandular foi mais intensa (144.52±3.17, P< 0,0001) nos animais que apresentavam folículos até 22 mm, estando a imunomarcação de ambos Ob e Ob-Rb correlacionado de forma negativa (r: -0.7836; P < 0.0001, r:- 0.7343; P < 0.0001), com os níveis de cortisol no FF. / Leptin is a multifunctional peptidic hormone, mainly produced by adipose tissue, having receptors (Ob-Rs) in the reproductive organs, hypothalamus and pituitary. Glucocorticoids, such as cortisol, also directly influence leptin production. The importance of these two hormones in reproductive activity has been described by several authors, who observed the involvement of both, in the improvement of reproductive indices, either by their direct influence on the hypothalamic-pituitary-gonadal axis, oocyte maturation or the uterine preparation to receive the concept. However, when in excess in circulation, they can negatively influence the reproductive system. Markers such as leptin and its long-chain functional receptor are being studied in the endometrium of species such as humans, cattle and pigs, presenting results that correlate the decrease of these with infertility or embryonic loss, but to date it has not been possible to find studies to address this issue in horses. In this study we evaluated: 1) the presence of leptin (Ob) and its receptor (Ob-Rb) in the endometrium of mares, observing the influence of obesity and estrous cycle on these markers and 2) in an adverse and stressful management condition, the influence of intrafollicular cortisol, leptin levels in the follicular fluid (FF), and the Ob and Ob-Rb markers in the endometrium during the estrous cycle phases. The results showed that leptin and its receptor (Ob-Rb) are present in the equine endometrium, with immunostaining in the luminal and glandular epithelium in all stages of the estrous cycle evaluated, however, showing a more intense immunological labeling in Ob -Rb (142.68 ± 4.97, P <0.0001) in the glandular epithelium during the diestrous in mares of moderate body score. It was not possible to observe the influence of intrafollicular cortisol (FF) on the variables evaluated, because cortisol remained within the physiological values for the species, however a positive correlation can be observed between intrafollicular cortisol and leptin levels, being the 10 cortisol increased (30.1 ± 0.07ng/ml, P <0.05) in the follicles closest to ovulation. It can also be noticed that the immunological labeling of the leptin receptor in the glandular epithelium was more intense (144.52 ± 3.17, P <0.0001) in the animals that presented follicles up to 22 mm, and the immunostaining of both Ob and Ob-Rb correlated negatively (r: -0.7836; P <0.0001, r: - 0.7343; P <0.0001), with cortisol levels in FF.

O estudo avaliou o efeito do nível de consumo e do método de desaleitamento sobre o desempenho, metabolismo e fisiologia de bezerros leiteiros. Em delineamento fatorial 2x2, utilizando-se 36 bezerros leiteiros, os animais foram classificados em grupos com alto (>350 g/d) ou baixo (<350 g/d) consumo de concentrado na quinta semana de e alocados a dois métodos de desaleitamento: abrupto ou gradual. Os animais foram alojados em abrigos individuais, receberam 4L/d de dieta líquida, água e concentrado inicial à vontade (até 2 kg/dia). O desaleitamento abrupto foi realizado na oitava semana de vida. Animais desaleitados de forma gradual, receberam 4L/dia até a sexta semana, 3 L/dia da sexta até a sétima semana, 2L/dia da sétima semana até dois dias antes de completarem 8 semanas e 1L/dia até a 8a semana, quando foram desaleitados. O consumo de concentrado foi avaliado diariamente. Semanalmente foram realizadas pesagens, medidas corporais e coletadas amostras de sangue para análise de glicose, ?-hidroxibutirato (BHBA) e proteína total sérica (PT), até a 10a semana de vida, quando se encerrou o período experimental. Foram realizadas observações de comportamento dos animais nos dias -14, -7, -2, 0, 2, 7 relativos ao desaleitamento. Nestes dias foram colhida amostras de sangue para determinação de cortisol e glicoproteínas solúveis em ácido (GSA). Não houve interação entre os dois fatores estudados para nenhuma das variáveis analisadas. O consumo de concentrado não diferiu (P<0,05) entre os métodos de desaleitamento, havendo efeito da idade (P<0,001) de acordo com o nível de consumo . Animais com alto consumo de concentrado consumiram mais feno na nona semana de vida (P<0,05). O método de desaleitamento não afetou as variáveis: ganho de peso, peso vivo e medidas corporais (P<0,05), porém, houve diferença significativa para estas variáveis em função dos níveis de consumo (P<0,05). Não houve interação entre os fatores estudados para parâmetros sanguíneos; os valores de BHBA para os animais de alto consumo de concentrado foram maiores durante praticamente todo período; os valores de PT e de cortisol não diferiram entre os tratamentos ou com a idade dos animais (P<0,05). Não houve efeito do método de desaleitamento sobre as medidas fisiológicas dos animais. Os níveis de consumo tiverem efeito (P>0,05) sobre as frequências cardíacas as 6:00, 12:00, 18:00; e temperatura retal as 18:00. Animais desaleitados gradualmente passaram mais tempo consumindo concentrado (P>0,05) e o tempo ruminando e o tempo consumindo concentrado aumentaram conforme a idade do animal (P>0,05). O número de vocalizações foi maior (P>0,05) no dia do desaleitamento e no segundo dia subseqüente, normalizando após uma semana. O método de desaleitamento afetou o número de vocalizações no segundo dia pós desaleitamento (P>0,05), de forma que bezerros desaleitados de forma gradual vocalizaram menos que os demais. O método de desaleitamento não teve influência no desempenho, metabolismo ou bem estar dos animais. No entanto, o nível de consumo teve influência no desempenho e parâmetros sanguíneos dos bezerros. O consumo de concentrado é mais importante que o método de desaleitamento no que diz respeito ao desempenho, metabolismo e nível de estresse. / The study evaluated the effect of the level of concentrate intake at the 5th week of age and the weaning method on the performance, metabolism and physiology of dairy calves. In a 2x2 factorial design, using 36 dairy calves, animals were classified as presenting high (>350g/d) or low (<350 g/d) concentrate intake at the 5th week of life, and distributed in two weaning methods: abrupt or gradual. Animals were individually housed in hutches, had free access to water and concentrate (up to 2kg/d) and were fed 4L of milk-replacer. The abrupt weaning was done at the 8th week of age. Animals weaned gradually received milk-replacer at the rate of 4l/d until the 6th week of age, 3L/d from the 6th until the 7th week, 2L/d from the 7th until 2 days before weaning, and 1L/d until weaning at the 8th week of age. Concentrate intake was monitored daily. Animals were weighted and corporal measures, as well as, blood samples were taken weekly for glucose, ?-hydroxybutyrate (BHBA) and serum total protein (TP), until the 10th week of age when the experimental period ended. Animal behavior was monitored on days -14, -7, -2, 0, 2, 7 relative to weaning. On those days blood samples were drawn for cortisol and acid soluble glycoprotein (ASG) levels determination. There was no significant interaction of the studied factors for all the analyzed variables. Average concentrate intake was not affected by the weaning method (P>0.05), however there was an significant age effect (P<0.001) according to the level of intake at the 5th week of age. Animals at the high intake level group presented higher hay intake at the 9th week of age (P<0.05). Weaning method had no effect on: live weight, daily gain or corporal measures (P>0.05); however, there was a significant difference for those variables according to the level of intake (P<0.05). There was no significant interaction of the intake level at the 5th week and the weaning method for blood parameters. BHBA concentrations were higher for animals at the higher concentrate intake level for almost the whole period. Cortisol and TP were not affected by the studied factors or by the animals age (P>0.05). Weaning methods had no effect on physiological measures. Concentrate intake level affected (P<0.05) heart rate at 6:00, 12:00, 18:00; and rectal temperature at 18:00. Animals gradually weaned spent more time consuming concentrate (P<0.05); and time ruminating and consuming concentrate were increased as animals aged (P<0.05). The number of vocalizations were higher (P<0.05) at the weaning day and the second day after that, getting back to normal a week after. The weaning method affected the number of vocalizations at the second day after weaning (P<0.05), with animals weaned gradually presenting lower numbers. The weaning method had no effect on performance, metabolism or well-being of dairy calves. However, the intake level had impact on performance and blood parameters. In spite of performance, metabolism and stress level of the animals the concentrate intake level is more important than the method of weaning.