Despite recent research advances, there are still several common medical conditions whose underlying mechanisms are poorly understood. In conditions with few or diffuse physical findings, it can be difficult to diagnose and determine the state of the condition and its effects on working ability or performance, and the health care practitioners have to rely on the patient’s self-reports. Identification of objective measurements that are sensitive enough to aid in diagnosis or determination of the state of these conditions would thus be valuable. Psychophysiological measurements are generally non-invasive and have the potential to serve as such diagnostic or prognostic tools. In this thesis, psychophysiological reactions to different stressors were recorded in two selected medical conditions; namely motion sickness and chronic trapezius myalgia (musculoskeletal pain). These subjective conditions are unpleasant, unwanted and apparently serve no survival purpose. It is therefore important to elucidate any physical findings associated with them to, eventually, find new means to prevent the development of these conditions or to ameliorate symptoms. The overall aim of the thesis was to explore the development of psychophysiological responses to stressors in relation to performance and subjective reports in healthy individuals and in women with chronic trapezius myalgia. More in detail, the purpose was to identify psychophysiological responses that could provide information about the mechanisms behind, or serve as candidates for characterization of motion sickness and chronic trapezius myalgia, respectively. Responses to motion sickness, triggered by optokinetic stimulation, were studied in healthy individuals, whereas responses to repetitive low-force work and psychosocial stress were studied in women with chronic trapezius myalgia and in pain-free controls. In both medical conditions, the psychophysiological responses were accompanied by subjective reports. The effects of motion sickness on two different aspects of memory performance were tested during exposure to optokinetic stimulation. In the studies of chronic trapezius myalgia, psychophysiological responses were also related to health status, i.e., being a patient or a pain-free control and measurements of pain intensity, psychological symptoms, sleep-related problems and quality of life. The psychophysiological responses to optokinetic stimulation were inconclusive. Moderate levels of motion sickness did not affect memory performance, whereas decreased short term memory performance was seen in subjects reporting high levels of motion sickness. The autonomic responses and stress hormone secretion in response to low-force repetitive work and psychosocial stress in the chronic trapezius myalgia group were similar to those of the pain-free controls. However, muscle activity in the trapezius muscle was generally higher in the chronic trapezius myalgia group. There were indications of negative psychological states being related to a slower response and lower circadian variations of stress hormone secretion. With the present methods, it was possible to measure general stress responses but none of the measurements showed sufficient specificity to serve as predictors or indicators of motion sickness and chronic musculoskeletal pain, respectively. Summarizing, I cannot objectively measure how you feel; I still have to rely on your description of your condition.

The affective disorders (anxiety and depression) are common psychiatric disorders that primarily involve disturbances in mood and represent the second leading source of disease burden world-wide. A wide base of evidence supports a significant genetic contribution to these disorders. Polymorphic variation in the promoter region (5-HTTLPR) of the human serotonin transporter (hSERT) gene, which leads to a life-long alteration in serotonin transporter (SERT) expression and functioning, has been implicated in the aetiology of both anxiety and depression. Despite the strong evidence implicating a role for this polymorphism in affective psychopathology the underlying mechanism by which genetically determined SERT bioavailability influences affective functioning are not understood. In these studies I attempt to elucidate the alterations in cerebral, serotonin (5-HT) system and hypothalamo-pituitary-adrenal (HPA) axis functioning which may relate to the effect of the 5-HTTLPR on affective functioning by characterising these parameters in an animal model of genetically increased SERT expression (hSERT over-expressing mice; hSERT OVR). Furthermore, as gender influences both the likelihood of developing affective disorders and the impact of the 5-HTTLPR on affective functioning, with a greater effect being observed in females than in males, we characterise these parameters in mice of both genders. The data presented in this thesis demonstrate that the life-long increase in SERT bioavailability present in hSERT OVR mice produces profound alterations in cerebral, serotonin system and HPA axis functioning. Furthermore, the influence of increased SERT expression upon cerebral and serotonin system functioning is greater in females than in males. Additionally, a number of sexually dimorphic variations in serotonin system functioning were identified. Thus this thesis extends the currently available information regarding the underlying mechanisms by which gender and a life-long alteration in SERT expression may influence the risk of affective psychopathology.

Opiate addiction is now a major public health problem. Pregnant women continue to use opiates during gestation; up to 5.4% of pregnant women report using illicit drugs during pregnancy. Previous studies have shown that perinatal insults and exposure to opiates such as morphine in utero can affect the development of the hypothalamic-pituitary-adrenal (HPA)-axis of the offspring and are associated with higher risk of developing neurobehavioral problems. Oxycodone, a semisynthetic putative kappa opioid receptor and partial mu opioid receptor agonist is now one of the most frequently abused pain killers during pregnancy, however limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters the development and functions of the HPA-axis, the related stress axis and neurobehavioral outcomes of the offspring. Data from these experiments have provided novel evidence that POE indeed is associated with sex-specific changes in the HPA-axis in response to stress that persist beyond the neonatal period. 1) POE is associated with an increased adrenocorticotropic hormone (ACTH) response to corticotropin-releasing hormone (CRH), but not the corticosterone (CORT) response to CRH stimulation in late adolescent male offspring. 2) POE is associated with increased CORT, but not ACTH response to restraint stress test in adult female offspring. These changes in the HPA-axis response to stress may be partially explained by 1) an increase in the subpopulation of CRH neurons that also contain estrogen receptor-beta immunoreactivity following POE which then can exaggerate the stimulation of the HPA-axis, and 2) a decrease in mineralocorticoid receptor-mRNA expression in the hippocampus which may be associated with impaired negative feedback control of the HPA-axis by the limbic system. POE is also associated with cardiovascular changes in response to stress during a classical conditioning paradigm; adolescent male POE rats have a larger blood pressure increase than the control group. Although POE male rats can properly discriminate the stress versus non-stress cues in the conditioning paradigm, they do not retain this memory when retested during adulthood. When tested for learning and memory in a water maze, however, we did not find any differences between control rats and rats exposed to high dose oxycodone in utero. In addition, we demonstrated that exposure to the lower dose of oxycodone in utero is associated with hyperactivity in adult rats when tested in an open field. Our results make a significant contribution to the literature because they extend our knowledge about the effects of oxycodone on the developing brain and the resulting outcomes in animal models that are actually relevant to a current major public health problem in humans and will provide a platform for us to further study the underlying mechanisms and interventions that may mitigate these effects.

Les transistors à base de nitrure de gallium (GaN) ont, de par leurs propriétés physiques, des performances inégalables par les technologies classiques à base de silicium pour l’amplification de puissance hyperfréquence. Cependant, cette technologie souffre d’effets mémoires basses fréquences inhérents aux défauts présents dans la structure du transistor : les effets de pièges. La première partie de cette thèse vise à caractériser et modéliser les effets de pièges. La séparation des effets de pièges ayant des constantes de temps courtes (quelques ms) à ceux ayant des constantes de temps longues (quelques s) a été montrée à travers des mesures I-V impulsionnelles spécifiques. Un nouveau modèle électrique, basé sur la physique, a été développé au sein d’un simulateur CAO pour prendre en compte les effets de pièges lents. Ce modèle, une fois greffé à un modèle de transistor GaN déjà existant, est validé par comparaison avec des mesures en régime grand signal. La deuxième partie de cette thèse traite la conception d’une architecture d’amplificateur reconfigurable en fréquence et en puissance pour une application E/R aéroportée. Un démonstrateur a été réalisé avec des transistors GaN sur circuit imprimé à 10 GHz. Les mesures grand signal de cet amplificateur ont démontré la reconfigurabilité de l’architecture d’amplificateur équilibré à charge modulée (LMBA). Par ailleurs, deux amplificateurs de puissance GaN ont été conçus pour servir de briques de base à une version intégrée (MMIC) de l’architecture bi-mode : un forte puissance bande X (employant un combineur de puissance innovant) et un moyenne puissance bande C à X. / GaN based High Electron Mobility Transistors (HEMT) present outstanding performances for microwave power amplification with respect to their silicon-based counterparts. However, this technology still suffers from low frequency memory effects originated from defaults in the structure, the so-called trapping effects. First part of this thesis aims to characterize and model the trapping effects. It has been shown that the slow-rate trapping effects could be separated from the fast-rate ones, by carrying specific pulsed I-V measurements. Consequently, a new, physic based, electrical model has been developed in order to take into account the slow traps. This model, added into an already existing GaN CAD model, has been validated through large signal measurements. Secondly, the thesis goal is to design a reconfigurable power amplifier architecture between a high power X band mode and a medium power C to X band mode for airborne T/R modules. A 10 GHz, encapsulated GaN transistors based PCB demonstrator has been realized in order to demonstrate both the power and the frequency bandwidth reconfigurability of the Load Modulated Balanced Amplifier (LMBA) architecture. Moreover, two GaN integrated power amplifiers have been designed in order to be reused in a full MMIC version of the architecture.

A poluição marinha por petróleo e seus derivados é uma preocupação crescente de caráter global. O litoral norte do estado de São Paulo é hoje caracterizado como a região mais altamente impactada por esses contaminantes de toda a costa Sul e Sudeste do país. Dentre as substâncias que compõem esses produtos estão os Hidrocarbonetos Aromáticos Policíclicos (HPAs), como o fenantreno, que apresentam potencial de alterar o sistema endócrino de peixes, gerando desajustes hormonais de alto risco para o processo reprodutivo dos animais expostos. Com base nestes fatos, o presente trabalho buscou verificar efeitos do fenantreno como desregulador endócrino em juvenis de E. marginatus. Essa espécie se caracteriza pelo hermafroditismo protogínico, de modo que os juvenis costumam apresentar altas concentrações de esteroides gonadais, o que gera preocupação quanto os efeitos reprodutivos decorrentes de alterações no padrão de produção de esteroides, especialmente em uma espécie que já vem sofrendo declínios populacionais por conta da sobrepesca. A CL50 encontrada para juvenis de E. marginatus foi 1,51 mg⁄L. Em seguida, foi realizado um bioensaio subletal (96h) com quatro grupos experimentais (n=5) em duplicata: grupo controle; duas concentrações distintas de fenantreno (0,1 mg⁄L e 1 mg⁄L) e grupo exposto ao veículo de diluição (0,004% de etanol). Foram dosadas as concentrações de 17β-estradiol (E2), testosterona (T) e 11-cetotestosterona (11-KT) plasmáticos por ELISA. Gônadas, fígado e baço foram processados para análise histológica. Foi conduzido bioensaio in vitro com incubação de fragmentos gonadais sob ação de fenantreno (50μM) ou etanol. Os níveis dos mesmos esteroides também foram dosados por ELISA. A exposição in vivo ao fenantreno resultou em aumento na área dos hepatócitos, bem como no número de centro melanomacrofágicos e hemossiderose no baço. O etanol induziu efeitos similares no baço. Os níveis de E2 e T não se alteraram no plasma ou no meio de incubação in vitro. O fenantreno reduziu a concentração de 11-KT in vitro e in vivo. No plasma, o etanol também causou esse decréscimo. Considerando a importância do 11-KT no desenvolvimento dos ovários em teleósteos, o fenantreno parece causar desregulação da esteroidogênese em juvenis de E. marginatus, possivelmente gerando disfunções durante a inversão sexual / Marine pollution by crude oil and its residual products is a growing global concern. The Northern coast of São Paulo is characterized as the highly impacted area by these contaminants through Brazil\'s South and Southeast coast. Polycyclic aromatic hydrocarbons (PAH), such as phenanthrene, are the main crude oil components and have a significant toxic potential to biota, acting as endocrine disruptors (ED) and negatively impacting reproduction. This study aimed to investigate the effects of phenanthrene as ED on gonadal steroidogenesis in E. marginatus juveniles. As a hermaphrodite protogynous species, E. marginatus juveniles maintain high levels of plasma steroids as substrates for sex inversion, which causes concern about reproductive effects of disruptions in steroid production patterns, especially in an overfished species. LD50 to E. marginatus exposed to phenanthrene was established in 1.51 mg⁄L. An in vivo sublethal exposure (96 h) to phenanthrene was carried out at two concentrations (0.1mg⁄L and 1 mg⁄L); exposure to the vehicle (ethanol) was also performed. Plasma levels of 17β-estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were measured by ELISA. Gonads, liver and spleen were processed for histological analysis. In an in vitro bioassay, gonad fragments were incubated with phenanthrene (50μM) or ethanol. Steroid levels in the culture media were also measured by ELISA. The in vivo exposure to phenanthrene triggered an increase of the area of the hepatocytes, increased number of melanomacrophagic centers and hemosiderosis in the spleen. Ethanol also induced similar effects on spleen. E2 and T levels did not change neither in plasma nor in vitro media. Phenanthrene sharply reduced 11-KT levels in vitro and in vivo. In plasma, ethanol also decreased 11-KT levels. Considering the importance of 11-KT in fish developing ovaries, phenanthrene seems to disrupt steroidogenesis in juvenile grouper, possibly being able to cause dysfunctions during sex change

Os hidrocarbonetos policíclicos aromáticos (HPA) são poluentes formados por dois ou mais anéis aromáticos que podem causar efeitos mutagênicos, carcinogênicos e teratogênicos aos seres humanos. Os HPA não são suscetíveis à degradação pela maioria dos micro-organismos devido a sua baixa solubilidade em água e a sorção destes poluentes na parte mineral e orgânica do solo. Uma forma de tratamento é o uso de processos oxidativos que podem degradar inúmeros contaminantes orgânicos e minerizá-los a gás carbônico e água. Neste trabalho foi avaliada a eficiência da degradação do isômeros fenantreno e antraceno, dois tipos de HPA, em areia padrão, utilizando-se como oxidantes o permanganato, peróxido de hidrogênio e persulfato ativado. De acordo com a matriz e o contaminante, após 24 horas de tratamento, verificou-se a degradação de 95 a 98% utilizando-se como oxidantes permanganato e de 34 a 62% utilizando-se a reação de Fenton. Foi identificada a antraquinona como produto do antraceno, independentemente do oxidante utilizado. Dentre os oxidantes, avaliou-se o persulfato ativado com ferro para a aplicação em solos arenosos contaminados com HPA. Quando se utilizou persulfato ativado com ferro em areia padrão houve a decomposição, após 24 horas de tratamento, de 60 e 95%, de fenantreno e antraceno, respectivamente. Em solos arenosos utilizando-se o persulfato, a degradação dos contaminantes foi predominantemente inferior devido ao possível efeito de matriz. Em contrapartida praticamente não houve a decomposição das substâncias húmicas. Esta é característica favorável, pois não houve a competição da matéria orgânica com o contaminante pelo persulfato, além de não promover alterações no teor de carbono presente no solo / Polycyclic aromatic hydrocarbons (PAH) are pollutants formed by two or more aromatic rings that can be mutagenic, carcinogenic and teratogenic to humans. PAH do not undergo degradation by most microorganisms due to this low water solubility and adsorption in the mineral and organic soil phase. One form of treatment is the use of oxidative processes that can degrade numerous organic contaminants and mineralize them to carbon dioxide and water. In this study, it was evaluated the efficiency of phenanthrene and anthracene degradation, in standard sand soil using permanganate, hydrogen peroxide and activated persulfate as oxidants. Depending on the contaminant and the matrix, over 24h of treatment, it was found the degradation 95 to 98% using permanganate and 34 to 62% using reaction Fenton. Anthraquinone was identified as product of anthracene, independent of the oxidant used. Among the oxidants, persulfate activated with iron was evaluated in the degradation of PAH in sandy soils. In standard sand, this process promoted,over 24 hours of treatment, a degradation level up to 60 % phenanthrene and 95% for anthracene. In sand soils, the degradation of the contaminants was lower due to possible matrix effect. In constrast there was no decomposition of humic substances, indicating no competition between the organic matter and the PAH by persulfate, and no change in the soil carbon content

A ouabaína (OUA), um inibidor da Na+ ,K+-ATPase, foi identificada como uma substância endógena presente no plasma humano, e parece estar envolvida na resposta ao estresse agudo, em animais e seres humanos. O estresse crônico é um importante fator agravante de doenças psiquiátricas, incluindo depressão e ansiedade. Além disso, problemas cognitivos são cada vez mais reconhecidos como importantes componentes da ansiedade e depressão. Diante disto, o presente trabalho buscou investigar os efeitos da OUA (1,8 <font face = \"symbol\">mg/kg) na hiperatividade do eixo HPA, na neuroinflamação, na expressão de receptores e proteínas envolvidos na plasticidade sináptica, nos efeitos comportamentais (como déficit de memória de longa duração, depressão e ansiedade) e atividade da Na+,K+-ATPase induzidos pelo protocolo de estresse crônico imprevisível (CUS) realizado ao longo de 14 dias em ratos. Nossos resultados demonstraram que o tratamento intermitente com OUA é capaz de reverter a hiperatividade do eixo HPA induzido pelo CUS, por meio da redução de glicocorticoide, redução na expressão de CRH-CRHR1, bem como diminuir a neuroinflamação, e aumentar os níveis de BDNF e fazer o que na expressão dos receptores CRHR2. Essas alterações bioquímicas contribuíram para uma reversão nos prejuízos na memória de longo prazo induzida pelo CUS. Ademais os animais tratados apenas com OUA, bem como os submetidos ao CUS e tratados com OUA obtiveram uma melhora na memória emocional, averiguada no teste comportamental de condicionamento da memória ao medo. Os resultados encontrados sugerem que o protocolo de CUS por 14 dias promove uma adaptação neuronal facilitando a redesignação da memória ao medo, aqui configurado pelo choque, e o tratamento com a OUA abrevia esse processo. Em conclusão os nossos resultados sugerem que o tratamento intermitente com OUA suscita uma adaptação no eixo HPA, por meio de alterações na expressão dos receptores para CRH no hipocampo e hipotálamo, resultando em uma adaptação na memória emocional relacionada ao medo. / Ouabain (OUA), an inhibitor of Na+, K+ -ATPase, has been identified as an endogenous substance present in human plasma, and appears to be involved in the response to acute stress in animals and humans. Chronic stress is an important aggravating factor of psychiatric illness, including depression and anxiety. In addition, cognitive problems are increasingly recognized as important components of anxiety and depression. The present work aimed to investigate the effects of OUA (1.8 <font face = \"symbol\">mg/kg) on HPA axis hyperactivity, neuroinflammation, expression of receptors and proteins involved in synaptic plasticity, behavioral effects (such as long-term memory deficit duration, depression and anxiety) and Na+,K+-ATPase activity induced by the unpredictable chronic stress protocol (CUS) performed over 14 days in rats. Our results demonstrated that intermittent treatment with OUA was able of reversing CUS-induced HPA axis hyperactivity, by reducing glucocorticoid levels, CRH-CRHR1 expression, as well as reducing CUS-induced low-grade neuroinflammation, and increase BDNF levels and expression of CRHR2 receptors. These biochemical changes contributed to a reversal in CUS-induced long-term memory impairment. In addition, animals treated only with OUA, as well as those submitted to CUS, and also treated with OUA obtained an improvement in emotional memory, which was explored in the fear conditioning test. These results suggest that the CUS protocol of 14 days promotes a neural adaptation facilitating a reassignment of the memory to the fear, here configured by the shock, and the treatment with the OUA shortens that process. In conclusion, our results suggest that intermittent treatment with OUA induces an adaptation on the HPA axis, through alterations in the expression of receptors for CRH in the hippocampus and hypothalamus, resulting in an adjustment in fear-related emotional memory.

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-07-03T14:05:15Z No. of bitstreams: 1 DIS_CAROLINA_LUFT_PARCIAL.pdf: 1363434 bytes, checksum: d818669691f31ae3818b9580af4ca189 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-07-03T14:05:24Z (GMT) No. of bitstreams: 1 DIS_CAROLINA_LUFT_PARCIAL.pdf: 1363434 bytes, checksum: d818669691f31ae3818b9580af4ca189 (MD5) / Made available in DSpace on 2017-07-03T14:05:32Z (GMT). No. of bitstreams: 1 DIS_CAROLINA_LUFT_PARCIAL.pdf: 1363434 bytes, checksum: d818669691f31ae3818b9580af4ca189 (MD5) Previous issue date: 2017-03-03 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq / INTRODUCTION: Potential threats to homeostasis may occur during the in utero period, promoting programming effects on both neurological development and hypothalamic-pituitary-adrenal (HPA) axis function. The HPA axis acts as a control and regulatory center of the body that connects the central nervous system to the hormonal system. The axis responds to the stressor stimulus and assists the body to maintain homeostasis, as well as being essential to the normal regulatory physiological functioning. Physically fit and physically active individuals exhibit a lower rate of health problems, especially when faced with stressful situations, contributing to reduced levels of anxiety and depression. OBJECTIVE: To evaluate the effects of physical exercise before the gestational period on changes due to prenatal stress in adult mice. METHODS: Balb/c female and male mice were divided into three groups: control (CTLE), prenatal restraint stress (PNS) and physical exercise before the gestational period and prenatal restraint stress (EX+PNS). The weight of the animals was evaluated during gestation, days 1, 10 and 21 of life and also as adults. Animals were then maintained until adulthood (60 days of life) when fear/anxiety behaviors were evaluated in the elevated plus maze, and depression was evaluated using the preference for sucrose and the ingestion of sucrose test. In addition, real-time PCR gene expression of corticotrophin releasing hormone (CRHR1) type 1 receptor in the prefrontal cortex, glucocorticoid receptor (GR) and mineralocorticoid (MR) receptor in the hippocampus, as well as plasmatic concentrations of corticosterone were evaluated. RESULTS: During gestation, females of the EX+PNS group presented greater weight in relation to the CTLE group. Regarding the offspring weight, animals of the EX+PNS group showed an increase in weight on days 1, 10 and 21 of life, compared to the PNS group. During the adult life, animals stressed in the prenatal period presented lower weight, while the pregestational exercise promoted an increase in the offspring weight in relation to the CTLE group. In relation to behavioral tests, there was a significant decrease in the time spent in the open arms of the elevated plus maze in the PNS and EX+PNS groups, in both sexes, demonstrating an increase in fear/anxiety behavior. Prenatal stress increased the preference for sucrose in females and sucrose intake in both sexes. However, exercise promoted a significant decrease in sucrose intake in males and females. CRHR1 expression decreased in the prefrontal cortex of EX+PNS females compared to the PNS group. On the other hand, pregestational exercise was not able to reverse the significant decrease in basal GR concentrations caused by prenatal stress in adult females. There were no significant differences between groups in GR gene expression in males, as well as in MR and corticosterone in both females and males. CONCLUSION: Physical exercise on the treadmill before the gestational period seems to be able to reduce the effects of prenatal stress on important markers of the HPA axis response in a sex-dependent manner. / INTRODU??O: Potenciais amea?as para a homeostasia podem ocorrer durante a vida in utero, promovendo efeitos de programa??o tanto no desenvolvimento neurol?gico quanto na fun??o do eixo hipot?lamo-pituit?ria-adrenal (HPA). O eixo HPA ? o centro controlador e regulador do organismo que conecta o sistema nervoso central com o sistema hormonal. Este eixo responde ao est?mulo estressor e auxilia o organismo a manter a homeostasia, al?m de ser essencial para auxiliar no funcionamento fisiol?gico normal. Indiv?duos fisicamente aptos e que praticam frequentemente atividades f?sicas exibem um menor ?ndice de problemas de sa?de, especialmente quando se deparam com situa??es de estresse, contribuindo na redu??o dos n?veis de ansiedade e depress?o. OBJETIVO: Avaliar os efeitos do exerc?cio f?sico antes do per?odo gestacional sobre altera??es decorrentes do estresse pr?-natal em camundongos adultos. METODOLOGIA: F?meas e machos Balb/c foram divididos em tr?s grupos: controle (CTLE), estresse pr?-natal por conten??o (PNS) e exerc?cio f?sico antes do per?odo gestacional e estresse pr?-natal por conten??o (EX+PNS). O peso dos animais foi avaliado durante a gesta??o, e nos dias 1, 10 e 21 de vida e na vida adulta. Esses animais foram mantidos at? a idade adulta (60 dias de vida) quando foram avaliados os comportamentos de medo/ansiedade, no aparato de labirinto em cruz elevada, e depress?o, por meio do teste de prefer?ncia e ingest?o de sacarose. Al?m disso, foi avaliada a express?o g?nica, atrav?s da t?cnica de PCR em tempo real, do receptor tipo 1 do horm?nio liberador de corticotrofina (CRHR1) no c?rtex pr?-frontal, do receptor de glicocorticoide (GR) e do receptor de mineralocorticoide (MR) no hipocampo e as concentra??es plasm?ticas de corticosterona foram avaliadas. RESULTADOS: Durante a gesta??o, as f?meas do grupo EX+PNS apresentaram maior peso em rela??o ao grupo CTLE. Em rela??o ao peso da prole, os animais do grupo EX+PNS exibiram um aumento no peso nos dias 1, 10 e 21 de vida, comparados com o grupo PNS. Durante a vida adulta, os animais estressados no per?odo pr?-natal apresentaram menor peso, enquanto o exerc?cio pr?-gestacional promoveu um aumento no peso da prole, em rela??o ao grupo CTLE. Em rela??o aos testes comportamentais, houve uma diminui??o significativa no tempo gasto no bra?o aberto do aparato de labirinto em cruz elevada nos animais dos grupos PNS e EX+PNS, em ambos os sexos, demonstrando um aumento no comportamento de medo/ansiedade. O estresse pr?-natal aumentou a prefer?ncia por sacarose em f?meas e a ingest?o de sacarose em ambos os sexos. No entanto, o exerc?cio promoveu uma diminui??o significativa na ingest?o de sacarose, em machos e f?meas. A express?o de CRHR1 diminuiu no c?rtex pr?-frontal de f?meas do grupo EX+PNS em rela??o ao grupo PNS. Por outro lado, o exerc?cio antes da gesta??o n?o foi capaz de reverter a diminui??o significativa nas concentra??es basais de GR provocadas pelo estresse pr?-natal em f?meas adultas. N?o houve diferen?as significativas entre os grupos na express?o g?nica de GR em machos e de MR e corticosterona em f?meas e machos. CONCLUS?O: O exerc?cio f?sico em esteira antes do per?odo gestacional parece ser capaz de reduzir os efeitos do estresse pr?-natal em marcadores importantes da resposta do eixo HPA de uma maneira dependente do sexo.

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2016-10-19T16:18:10Z No. of bitstreams: 1 Dissertação CLARISSA RIBEIRO BASTOS.pdf: 4376745 bytes, checksum: 05e26e833e53a5a4c385cc5908d0bbcc (MD5) / Made available in DSpace on 2016-10-19T16:18:10Z (GMT). No. of bitstreams: 1 Dissertação CLARISSA RIBEIRO BASTOS.pdf: 4376745 bytes, checksum: 05e26e833e53a5a4c385cc5908d0bbcc (MD5) Previous issue date: 2016-02-26 / Introduction: Suicide is one of the ten leading causes of death worldwide, emerging from a complex interaction between genetic, environmental and psychosocial factors. In this aspect studies found that individuals with suicidal tendencies have elevations in the levels of pro-inflammatory cytokines and alterations in the functioning of the HPA axis. Objective: Investigate the association of the polymorphism in the CRHR1 gene (rs110402) with the suicidal behavior, as well as the genotype effects on IL-1β levels. Methods: Sample consisted in 171 individuals that participated in the study, from which 15 were at risk of suicide, 20 had attempted suicide and 136 were controls. We perform genotyping of individuals by real-time PCR and IL-1β levels measured by ELISA technique. Results: Individuals with a clinical diagnosis of attempted suicide carrying the A allele of SNP rs110402 showed increased IL-1β levels (19.3 IQR: 6.84 to 36.47) compared to the control group (4.91 IQR: 3.22 to 6.39; p = 0.027). Ratings isolated from the levels of this interleukin and genotypes of the rs10402 SNP showed no relationship with suicidal behavior. Conclusion: Our results suggest that alterations in CRHR1 gene can affect the levels of pro-inflammatory molecules, showing the complex interactions of biological markers in suicidal behavior. / Introdução: O suicídio é umas das dez principais causas de morte no mundo, emergindo de uma interação complexa entre fatores genéticos, ambientais e psicossociais. Neste aspecto, estudos identificaram que indivíduos com tendências suicidas apresentam elevações nos níveis de citocinas pró-inflamatórias e alterações no funcionamento do eixo HPA. Objetivo: Investigar a associação de um polimorfismo gene do CRHR1 (rs110402) com o comportamento suicida, bem como os efeitos do genótipo sobre os níveis de IL-1β. Métodos: A amostra foi composta de 171 indivíduos, e destes 15 apresentavam risco de suicídio, 20 já haviam tentado o suicídio e 136 eram controles. Realizamos a genotipagem dos indivíduos por PCR em tempo real e a dosagem de IL-1β pela técnica de Elisa. Resultados: Indivíduos com um diagnóstico clínico de tentativa de suicídio que carregavam o alelo A do SNP rs110402 mostraram aumento dos níveis de IL-1β (19,3 IQR: 6,84 - 36,47) em relação ao grupo controle (4,91 IQR: 3,22-6,39; p = 0,027). Avaliações isoladas em relação aos níveis dessa interleucina e aos genótipos desse polimorfismo não mostraram relação com o comportamento suicida. Conclusão: Nossos resultados sugerem que alterações no gene do CRHR1 podem afetar os níveis de moléculas pró-inflamatórias, mostrando as interações complexas de marcadores biológicos no comportamento suicida.

Os hidrocarbonetos policíclicos aromáticos (HPA) são poluentes formados por dois ou mais anéis aromáticos que podem causar efeitos mutagênicos, carcinogênicos e teratogênicos aos seres humanos. Os HPA não são suscetíveis à degradação pela maioria dos micro-organismos devido a sua baixa solubilidade em água e a sorção destes poluentes na parte mineral e orgânica do solo. Uma forma de tratamento é o uso de processos oxidativos que podem degradar inúmeros contaminantes orgânicos e minerizá-los a gás carbônico e água. Neste trabalho foi avaliada a eficiência da degradação do isômeros fenantreno e antraceno, dois tipos de HPA, em areia padrão, utilizando-se como oxidantes o permanganato, peróxido de hidrogênio e persulfato ativado. De acordo com a matriz e o contaminante, após 24 horas de tratamento, verificou-se a degradação de 95 a 98% utilizando-se como oxidantes permanganato e de 34 a 62% utilizando-se a reação de Fenton. Foi identificada a antraquinona como produto do antraceno, independentemente do oxidante utilizado. Dentre os oxidantes, avaliou-se o persulfato ativado com ferro para a aplicação em solos arenosos contaminados com HPA. Quando se utilizou persulfato ativado com ferro em areia padrão houve a decomposição, após 24 horas de tratamento, de 60 e 95%, de fenantreno e antraceno, respectivamente. Em solos arenosos utilizando-se o persulfato, a degradação dos contaminantes foi predominantemente inferior devido ao possível efeito de matriz. Em contrapartida praticamente não houve a decomposição das substâncias húmicas. Esta é característica favorável, pois não houve a competição da matéria orgânica com o contaminante pelo persulfato, além de não promover alterações no teor de carbono presente no solo / Polycyclic aromatic hydrocarbons (PAH) are pollutants formed by two or more aromatic rings that can be mutagenic, carcinogenic and teratogenic to humans. PAH do not undergo degradation by most microorganisms due to this low water solubility and adsorption in the mineral and organic soil phase. One form of treatment is the use of oxidative processes that can degrade numerous organic contaminants and mineralize them to carbon dioxide and water. In this study, it was evaluated the efficiency of phenanthrene and anthracene degradation, in standard sand soil using permanganate, hydrogen peroxide and activated persulfate as oxidants. Depending on the contaminant and the matrix, over 24h of treatment, it was found the degradation 95 to 98% using permanganate and 34 to 62% using reaction Fenton. Anthraquinone was identified as product of anthracene, independent of the oxidant used. Among the oxidants, persulfate activated with iron was evaluated in the degradation of PAH in sandy soils. In standard sand, this process promoted,over 24 hours of treatment, a degradation level up to 60 % phenanthrene and 95% for anthracene. In sand soils, the degradation of the contaminants was lower due to possible matrix effect. In constrast there was no decomposition of humic substances, indicating no competition between the organic matter and the PAH by persulfate, and no change in the soil carbon content