Uma classe de compostos presente no material particulado atmosférico que desperta particular interesse e constitui-se em motivo de preocupação são os chamados hidrocarbonetos policíclicos aromáticos (HPA). Estes caracterizam-se por possuir dois ou mais anéis aromáticos condensados e são formados pela queima de combustíveis orgânicos na presença de quantidade limitada de oxigênio. Além dos próprios HPA, são importantes, sob o ponto de vista ambiental, seus derivados nitrados e oxigenados. Sua identificação e quantificação são passos importantes no processo de se esclarecer os mecanismos que conduzem à formação desses derivados. Neste trabalho, estudou-se reações fotoquímicas de HPA e nitro-HPA adsorvidos sobre o fotocatalisador dióxido de titânio (TiO2) ou sobre sílica (SiO2) através de técnicas de espectroscopia Raman. Foram conduzidos também estudos espectroeletroquímicos dos HPA através de espectroscopia eletrônica e Raman intensificada (efeito SERS) visando a caracterização vibracional dos produtos de processos faradáicos desses compostos sobre eletrodos, para comparação com os produtos de fotodegradação. Os HPA estudados foram: antraceno, 9-nitroantraceno, fenantreno, fluoreno, fluoranteno, pireno e criseno. Para o estudo das reações fotoquímicas foi feita uma pré-adsorção dos diversos HPA e nitro-HPA sobre TiO2 ou SiO2, que foram então irradiados em 254 nm em intervalos de tempo pré-determinados. Verificou-se mudanças nas estruturas das moléculas em função da exposição à luz ultravioleta. Os resultados obtidos revelaram a formação de intermediários oxidados, com grupamentos C=O. A combinação de dados da fotodegradação de HPA com seu estudo via eletroquímica - utilizando técnicas espectroscópicas para a identificação e caracterização de produtos - trouxe correlações importantes para esclarecer as transformações envolvidas nas etapas iniciais da fotodegradação dessas substâncias. A comparação das estruturas dos intermediários de fotodegradação e dos produtos de oxidação eletroquímica de HPA mostra que o início do processo fotocatalítico de HPA envolve uma etapa de oxidação de maneira análoga ao processo eletroquímico. / One class of chemicals that is present in the particulate matter in the atmosphere is of the so-called polycyclic aromatic hydrocarbons (PAH). They are object of special interest and concern due to their mutagenic properties and carcinogenic effects. PAH are characterized by the presence of two or more aromatic rings in their structure, and they are produced by the burning of organic fuels in a limited amount of oxygen. The study of the photochemical behavior of PAHs is relevant for clarifying some aspects of these complex systems. In this work, we perform experiments that include the UV irradiation of PAH, to observe which species are produced in such condition. Such investigations include the use of a photocatalysts, titanium dioxide – TiO2 – and that will allow the comparison between degradation products in the absence and in the presence of catalysts. Spectroscopic techniques were employed to monitorate the intermediates formed in the photoinduced degradation of PAH and their nitro derivates adsorbed or not on the photocatalyst TiO2. To perform the study of the photochemical reactions, the several PAH and nitro PAH were pre-adsorbed on TiO2 or SiO2, and then irradiated in 254 nm, in pre-determined time intervals. Changes in the structure of the molecules were observed after the exposure to the ultraviolet radiation. Results thus obtained revealed the production of oxidized intermediates bearing the C=O group. The joint analysis of the photodegradation data with those produced by electrochemical means - using spectroscopic techniques to the identification and characterization of the products - lead to important correlations that helped to clarify the transformations that take place in the initial steps of the photodegradation of PAH. By comparing the structures of the intermediates formed both in the photodegradation processes and in the electrochemical oxidation of PAH, it was possible to conclude that the first part of the photocatalytical degradation of those PAH include an oxidation step that is analogous to the electrochemical process.

Cortisol is one of the stress hormones produced as a result of stimulus to the hypothalamus triggering the hypothalamic-pituitary-adrenal axis (HPA).The result of cortisol production after this trigger is to return the body and its relevant systems back to homeostasis. This is a desired state of physiologic equilibrium in the body. A number of physiological and environmental conditions trigger the HPA pathway. This includes hypoglycemia (low blood sugar), dehydration (low blood volume), exercise, which are considered stress triggers, and changes to the circadian cycle. It is no wonder then that extreme diet and exercise can impact the HPA axis due to the stress caused by such activities or lifestyle choices. Fortunately, the production of cortisol in response to exercise has been extensively studied. Generally, studies have shown that the level of plasma cortisol levels increase proportionally during high intensity exercise, while a general decrease has been observed during moderate or low intensity exercise (Davis & Few, 1973). In addition, several scientific texts provide substantial information on the correlation between hypoglycemia and cortisol synthesis. This information in addition to other sources has proven useful for assessing the effect of extreme dieting on cortisol production. The aim of this thesis is to expand on the changes in cortisol caused by extreme exercise and diet as well as elaborate on the physiological effects that these cortisol levels in turn may have.

Made available in DSpace on 2014-06-11T19:29:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2002-06-07Bitstream added on 2014-06-13T19:38:00Z : No. of bitstreams: 1 azevedo_rc_me_araiq.pdf: 304556 bytes, checksum: ded49f14a2e14cead8af1a701b99e4ec (MD5) / Os hidrocarbonetos policíclicos aromáticos nitrados (NHPAs) constituem a classe de compostos aromáticos que têm pelo menos um grupo nitro (-NO2) ligado à cadeia aromática de um hidrocarboneto policíclico aromático (HPA). Nos anos 70 a descoberta das propriedades mutagênicas destes compostos, presentes em material particulado atmosférico e na exaustão de motores a diesel, aumentaram o interesse científico sobre a ocorrência dos mesmos no ambiente. Estes compostos, como os HPAs, estão associados a fontes de combustão como automóveis, sistemas de aquecimento (baseados na queima de biomassa ou de combustíveis fósseis); queima de biomassa (cigarro, florestas, culturas agrícolas, etc), por causa disso pode-se prever que tenham uma distribuição abrangente no ambiente. Os NHPAs são produtos da reação dos HPAs com óxidos de nitrogênio na atmosfera, apresentando-se em concentrações muito baixas neste compartimento ambiental. A análise de NHPAs é muito difícil, principalmente pelos artefactos de amostragem e pela interferência analítica causada por HPAs e outros compostos. Assim sendo, a investigação de métodos alternativos que sejam sensíveis e seletivos são de extrema importância na determinação de NHPAs em amostras atmosféricas. Neste trabalho estudou-se um método para determinação de 1-nitropireno em material particulado proveniente da queima de cana-de-açúcar. O método inclui a redução do grupo nitro a amino, com posterior determinação por HPLC/fluorescência. O método proposto tem limite de detecção de 0,930ng mL-1 e limite de determinação de 1,250ng mL-1, apresentando recuperação entre 77,00 e 86,34%, para 5,00 e 50,00ng mL-1 respectivamente. / Nitrated Polycyclic Aromatic Hydrocarbons (NPAHs) are the class of aromatic compounds with at least one nitro group (-NO2) enhanced to aromatic chain of a Polycyclic Aromatic Hydrocarbon (PAH). In 70’s the discovery of mutagenic properties of these compounds present in atmospheric particulate matter and in gas exhaust of diesel motors are increased the scientific interess on occurrence of NPAHs into environment. These compounds, as PAHs, are associated with combustion sources as automobiles; harming systems (biomass and combustible based); burning of biomass (cigarette, florest, agricultural cultures, etc), because this they have a ubicous dissemination on environment. NPAHs are product of reaction of PAHs with nitrogen oxides on atmosphere, and they are present there at very low concentrations. The analysis of NPAHs in atmospheric samples is very difficult, because of artefacts of sampling process and PAH and other compounds interference on analytical determination. Because this, investigation of alternative methods sensitive and selective is necessary for NPAHs determination in atmospheric samples. In this work is studied a method for determination of 1-nitropyrene from particulate matter of sugar cane burning. The method include reduction of nitro group to amino, and analysis by HPLC/ Fluorescence. The proposed method has detection limit of 0, 930ng mL-1 and quantification limit of .1,250ng mL-1 showing recovery ranged between 77,00 and 86,34% for concentrations of 5,00 and 50,00ng mL-1, respectively.

Uma classe de compostos presente no material particulado atmosférico que desperta particular interesse e constitui-se em motivo de preocupação são os chamados hidrocarbonetos policíclicos aromáticos (HPA). Estes caracterizam-se por possuir dois ou mais anéis aromáticos condensados e são formados pela queima de combustíveis orgânicos na presença de quantidade limitada de oxigênio. Além dos próprios HPA, são importantes, sob o ponto de vista ambiental, seus derivados nitrados e oxigenados. Sua identificação e quantificação são passos importantes no processo de se esclarecer os mecanismos que conduzem à formação desses derivados. Neste trabalho, estudou-se reações fotoquímicas de HPA e nitro-HPA adsorvidos sobre o fotocatalisador dióxido de titânio (TiO2) ou sobre sílica (SiO2) através de técnicas de espectroscopia Raman. Foram conduzidos também estudos espectroeletroquímicos dos HPA através de espectroscopia eletrônica e Raman intensificada (efeito SERS) visando a caracterização vibracional dos produtos de processos faradáicos desses compostos sobre eletrodos, para comparação com os produtos de fotodegradação. Os HPA estudados foram: antraceno, 9-nitroantraceno, fenantreno, fluoreno, fluoranteno, pireno e criseno. Para o estudo das reações fotoquímicas foi feita uma pré-adsorção dos diversos HPA e nitro-HPA sobre TiO2 ou SiO2, que foram então irradiados em 254 nm em intervalos de tempo pré-determinados. Verificou-se mudanças nas estruturas das moléculas em função da exposição à luz ultravioleta. Os resultados obtidos revelaram a formação de intermediários oxidados, com grupamentos C=O. A combinação de dados da fotodegradação de HPA com seu estudo via eletroquímica - utilizando técnicas espectroscópicas para a identificação e caracterização de produtos - trouxe correlações importantes para esclarecer as transformações envolvidas nas etapas iniciais da fotodegradação dessas substâncias. A comparação das estruturas dos intermediários de fotodegradação e dos produtos de oxidação eletroquímica de HPA mostra que o início do processo fotocatalítico de HPA envolve uma etapa de oxidação de maneira análoga ao processo eletroquímico. / One class of chemicals that is present in the particulate matter in the atmosphere is of the so-called polycyclic aromatic hydrocarbons (PAH). They are object of special interest and concern due to their mutagenic properties and carcinogenic effects. PAH are characterized by the presence of two or more aromatic rings in their structure, and they are produced by the burning of organic fuels in a limited amount of oxygen. The study of the photochemical behavior of PAHs is relevant for clarifying some aspects of these complex systems. In this work, we perform experiments that include the UV irradiation of PAH, to observe which species are produced in such condition. Such investigations include the use of a photocatalysts, titanium dioxide – TiO2 – and that will allow the comparison between degradation products in the absence and in the presence of catalysts. Spectroscopic techniques were employed to monitorate the intermediates formed in the photoinduced degradation of PAH and their nitro derivates adsorbed or not on the photocatalyst TiO2. To perform the study of the photochemical reactions, the several PAH and nitro PAH were pre-adsorbed on TiO2 or SiO2, and then irradiated in 254 nm, in pre-determined time intervals. Changes in the structure of the molecules were observed after the exposure to the ultraviolet radiation. Results thus obtained revealed the production of oxidized intermediates bearing the C=O group. The joint analysis of the photodegradation data with those produced by electrochemical means - using spectroscopic techniques to the identification and characterization of the products - lead to important correlations that helped to clarify the transformations that take place in the initial steps of the photodegradation of PAH. By comparing the structures of the intermediates formed both in the photodegradation processes and in the electrochemical oxidation of PAH, it was possible to conclude that the first part of the photocatalytical degradation of those PAH include an oxidation step that is analogous to the electrochemical process.

Orientador: Giovanni Faria Silva / Resumo: A hepatite C tem sido associada a manifestações reumatológicas (MR-VHC). Clinicamente, a MR-VHC pode ser indistinguível dos sintomas que ocorrem nas doenças difusas do tecido conjuntivo (MR-DDTC), dificultando o diagnóstico diferencial. Fatores genéticos do hospedeiro, como os polimorfismos do Antígeno Leucocitário Humano (HLA), foram associados à infecção pelo HCV, no entanto, não há estudos que discriminem a MR-VHC e MR-DDTC. Assim, o objetivo do estudo foi verificar as associações entre polimorfismos HLA-DRB1 e MR em pacientes com hepatite C crônica, buscando distinguir entre MR relacionada ao DDTC e MR relacionada ao VHC. Para tanto, participaram do estudo 152 indivíduos de ambos os sexos, com idade entre 18 e 80 anos e acometidos por hepatite C crônica. Foram incluídos apenas casos de RNA-VHC detectáveis, com identificação do genótipo do VHC, nenhum tratamento prévio para hepatite C (pacientes ingênuos) e estágio conhecido de fibrose ou diagnóstico clínico de cirrose por imagem. Foram excluídos os voluntários com coinfecção por VHB/HIV, insuficiência renal crônica, transplante de fígado ou rim, doenças hepáticas e outras doenças difusas do tecido conjuntivo, incluindo artrite reumatóide. Os pacientes foram submetidos a exame físico reumatológico e foi realizada tipagem de HLA classe II (HLA-DRB1) por PCR-SSO (“Oligonucleotídeos Específicos da Sequência de Reação em Cadeia da Polimerase”). Foi observado um número significativo de pacientes com queixas reumatológicas (73%)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Hepatitis C has been associated with rheumatologic manifestations (HCV-related RM). Clinically, HCV-related RM may be indistinguishable from the symptoms that occur in diffuse connective tissue diseases (DCTD-related RM), making the differential diagnosis a difficult. Host genetic factors, such as the Human leukocyte antigens polymorphisms (HLA) were associated with HCV infection, however, there are no studies that discriminate HCV-related RM and DCTD-related RM. The study focused on verifying associations between HLA-DRB1 polymorphisms and RM in patients with chronic hepatitis C, seeking to distinguish between DCTD-related RM and HCV-related RM. The participants were 152 individuals of both genders, aged between 18 and 80 years and affected by chronic hepatitis C. We only included detectable HCV-RNA cases, with identification of HCV genotype, no previous hepatitis C treatment (naïve patients) and known fibrosis stage or clinical diagnosis of cirrhosis by image. Volunteers with HBV/HIV co-infection, chronic renal insufficiency, liver or renal transplantation, liver diseases and other diffuse connective tissue diseases, including rheumatoid arthritis, were excluded. The patients underwent rheumatologic physical examination and HLA-class II (HLA-DRB1) typing was performed by PCR-SSO (“Polymerase Chain Reaction-sequence Specific Oligonucleotides). A significant number of patients with rheumatologic complaints (73%) not attributed to other causes was observed. There is not suscep... (Complete abstract click electronic access below) / Doutor

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This study creates and analyzes a model of the Hypothalamus-Pituitary-Adrenal axis to better understand cortisol rhythmicity perpetuated by circadian inputs, system dynamics and feedback inherent within the system. Differential equations are created to model human physiology with cortisol and precursor hormone outputs fit to physiologic data. The model is created with an input of circadian cues from the hypothalamus which are designed to create a more realistic stimulation of the cortisol cascade over predecessors. The study also incorporates additional signaling pathways unique to this model. The project explores the properties of the model under mathematical analysis; then, the simulation of known medical pathologies is used to analyze the model's predictive ability. It is found that incorporating the additional signaling pathway of Arginine Vasopressin increases the model's predictive capability in certain pathological conditions over predecessor models. Additionally, the origination of ultradian rhythm is explored through simulation and two possible explanations are found. First, pulsatile release of Adrenocorticotropic Hormone combined with negative feedback into the system from glucocorticoid receptors elicits the observed ultradian oscillations in humans. Additionally, simulations of increased hypothalamic monitoring and control of cortisol concentrations create a natural oscillation within the desired period. Results from numerical perturbation simulations and dynamic sensitivity analysis are employed to offer justification for known pathological conditions developing from circadian dysregulation. / Master of Science / This study aims to better understand the body's natural cortisol rhythm by creating a mathematical model of the Hypothalamus-Pituitary-Adrenal axis. The model uses differential equations to simulate human physiology and includes circadian cues from the suprachiasmatic nucleus to create a more accurate representation of how cortisol is released in the body. The study also incorporates additional signaling pathways and interactions unique to this model. By analyzing the model and simulating known medical conditions, it was found found that incorporating these additional signaling pathways improved the model's predictive ability in certain situations. Then, numerical simulations were used to investigate how circadian dysregulation can lead to pathological conditions.The study also explored the origin of ultradian rhythm, or short-term fluctuations in cortisol levels, and found two possible explanations. One explanation is the pulsatile release of Adrenocorticotropic Hormone combined with negative feedback from glucocorticoid receptors. Another explanation is increased hypothalamic control of cortisol concentrations. Overall, this study provides insights into the complex dynamics of the Hypothalamus-Pituitary-Adrenal axis and the origination of pathology in the system.

Background: Studies with experimental administration of alcohol offer inconsistent approaches and interpretations in which ways an acute alcohol exposure affects the HPA-system and the cortisol secretion. So far published alcohol experiments differ in alcohol application, the possibility of alcohol self-administration at the subjects own discretion as well as the age of the participants. Question: Is cortisol secretion modified by gender during alcohol infusion? Do men and women show different cortisol levels under alcohol exposure when compared to the baseline? Is there a dose-response relationship between cortisol secretion and acute alcohol exposure? Have family history, smoking habits and alcohol induced side effects like nausea an influence on the cortisol secretion under alcohol exposure? Materials and methods: 48 18 year old subjects participated in two identical sessions in which they were able to regulate their maximum blood alcohol concentration up to a safety limit of 1.2 ‰ (i.e., 0.12%). The experiment was conducted by using a special software for self-infusion of ethanol (CASE) which guided the participants through a two and a half hours long experiment. CASE is founded on a validated physiologically-based pharmacokinetic model and involves calculating the infusion volume needed to increase the blood alcohol concentration in a linear manner. The BAC increases after each alcohol request by 0,075 ‰ (i.e., 0.0075%) within in two and a half minutes. If the subject infuses no alcohol the blood alcohol concentration will decrease by 0.01 ‰ (i.e., 0.001%) per minute. Through the precise calculation of the infusion rate, individual differences can be eliminated. Cortisol levels were measured at five time points: an initial baseline measurement and four measurements at fixed time points during the alcohol self-administration of subjects with two completed alcohol experiments. As an appropriate measure to examine the effect of alcohol self-administration on cortisol secretion, the maximum blood alcohol concentration was determined. In addition the day of experiment, gender and family history were observed as well as exploratory maximum nausea and smoking habits. Results: In conclusion, the results confirmed that women have higher cortisol levels than men at baseline and under alcohol influence. Blood alcohol concentration as examined influencing variable was shown to have different effects on the HPA system on day one and two. On the first day of experimentation there was no effect of blood alcohol concentration on the HPA system. On the second day a dose-response relationship could be identified between cortisol secretion and acute alcohol exposure. Individually higher blood alcohol concentrations attenuated cortisol stronger in comparison to subjects with lower blood alcohol concentrations. Family history, smoking habits and unpleasant side effects (nausea) did not affect the cortisol secretion under alcohol exposure in this series of experiments. Conclusions: Current data suggests that alcohol experiments affect the cortisol secretion in young social drinkers. These findings could be detected for the first time. Up to this point there has not been an experimental study that investigated and evaluated the dose-effect relationship between cortisol secretion and alcohol in a study design which uses intravenous alcohol self-administration. It can be theorized that the first day of experimentation is suitable as a settling-in phase due to unspecific confounding factors, whereas the second day can be considered, in an identical setting, apt for hypothesis testing. The increased cortisol level in women when compared to men is consistent with previous studies and there was no indication that family history, smoking habits and alcohol induced unpleasant side effects have an influence on cortisol secretion.

La maladie d'Alzheimer (MA) est une maladie neurodégénérative caractérisée par la présence d'enchevêtrements neurofibrillaires et de plaques séniles. Le composant majoritaire des plaques séniles est le peptide amyloïde Aβ.Dans une première partie de cette thèse, l'objectif a été de caractériser la toxicité du peptide Aβ25-35 après son injection au niveau des ventricules latéraux chez le rat au cours du temps. Nous avons ainsi pu démontrer, entre autre, qu'une seule injection, engendre des déficits mnésiques à court et à long terme qui persistent six semaines après l'injection. Nous avons également montré, entre autre, une astrogliose, une microgliose, une élévation du stress oxydant, ainsi que des phénomènes apoptotiques dans les différentes structures cérébrales étudiées. Le deuxième objectif de cette thèse a été de caractériser le rôle du peptide Aβ25-35 dans la régulation de l'axe hypothalamo-hypophyso-surrénalien (HPA) au cours du temps. Dans un premier temps nous avons démontré une hyperactivité de l'axe, qui se caractérise par une modification de l'expression des hormones et une modification d'expression et de localisation des récepteurs aux glucocorticoïdes (GC). Nous avons montré que l'injection d'Aβ25-35 induisait un comportement anxieux. Néanmoins la fonctionnalité du rétrocontrôle négatif des GC reste intacte. Alors que l'injection de l'Aβ25-35 modifie la réponse de l'axe HPA à un stress. Nos résultats, dans un modèle pathomimétique, de la MA, montrent que la toxicité amyloïde modifie la fonctionnalité et la réactivité de l'axe HPA, ce qui pourrait participer à la pathophysiologie de la MA. / Alzheimer's disease (AD) is characterized by neurofibrillary tangles and seniles plaques. The major component of senile plaques is the amyloid-β peptide (Aβ). In a first part of this thesis, we characterized the time course toxicity effect of the Aβ25-35 intracerebroventricular (icv) injection in the rat brain. We particulary demonstrated, that only one injection induced memories impairments at short and long term which persisted six weeks after the icv injection. We also shown, a sustain astrogliosis and microgliosis, oxidative stress, apoptotics processes in the differents brain structure of interest.In a second part of this thesis, we characterized the time course impact of Aβ25-35 on hypothalamo-pituitary-adrenal axis during the time. First, we demonstrated an the hyperactivity of the axis, which is characterized by modifications of hormonal concentration associated with modification of the expression and localization of glucocorticoids (GC) receptors. We also demonstrated Aβ25-35 an anxious behavioural in animals. Nevertheless, the functionality of negative feedback is not modified. However, Aβ25-35 injection modify the HPA axis reactivity after acute stress. In conclusions, we shown, in a pathomimetic model of AD that the Aβ25-35 toxicity modifes the reactivity and the functionality of HPA axis, that could be partly involved in the pathophysiology of AD.