Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-05-19T12:41:10Z No. of bitstreams: 1 DIS_ALEXANDRE_ANTONIO_MARQUES_COELHO_COMPLETO.pdf: 1873139 bytes, checksum: c32a6b63bb7f49213c1a5b16f0ae1ead (MD5) / Made available in DSpace on 2016-05-19T12:41:10Z (GMT). No. of bitstreams: 1 DIS_ALEXANDRE_ANTONIO_MARQUES_COELHO_COMPLETO.pdf: 1873139 bytes, checksum: c32a6b63bb7f49213c1a5b16f0ae1ead (MD5) Previous issue date: 2015-11-12 / Adolescent pregnancy and abortion are frequent causes of health problems and death. We studied women 18 to 60 years old selected from the Brazilian Internet Study on Temperament and Psychopathology, a web-based survey in which participants provided details on abortion and pregnancy history, and completed the Affective and Emotional Temperament Composite (AFECT) Scale. A total of 53833 women comprised the sample, from which 11.4% of the participants had induced at least one abortion and 3.9% have had a child before the age of 18. Depressive, Cyclothymic, Irritable, Hyperthymic and Euphoric types were associated with a 25%-64% higher chance of having a child before completing 18 years old when compared to Euthymics. Except for the avoidant type, all affective types were associated with the chance to have provoked an abortion, particularly Euphoric (OR=1.83), Volatile (OR = 1.65) and Cyclothymic (OR=1.54). Volition was the only dimensional trait associated with the age of the first child. In contrast, a history of abortion was associated with higher scores for Anger and Desire and lower scores for Caution, Coping and Control. Women who have abortions had prominent externalizing traits, suggesting a reduced ?moral constraint?, whereas adolescent pregnancy was weakly associated with temperament traits. / Gravidez na adolesc?ncia e aborto s?o frequentes causas de doen?as e morte entre as mulheres. Mulheres de 18 a 60 anos foram selecionadas do Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP), uma pesquisa atrav?s da internet na qual as participantes responderam quest?es relacionadas ? hist?ria de gesta??es e aborto, e completaram a escala Affective and Emotional Composite Temperament (AFECT). Foram selecionadas 53833 mulheres, das quais 11,4% haviam induzido pelo menos um aborto, e 3,9% haviam tido um filho antes dos 18 anos. Os tipos Depressivo, Ciclot?mico, Irrit?vel, Hipert?mico e Euf?rico foram associados com uma chance 25-64% maior de ter um filho antes dos 18 anos em compara??o com os Eut?micos. Com a exce??o do tipo Evitativo, todos os tipos afetivos foram associados com a chance de ter provocado um aborto, particularmente o Euf?rico (OR=1,83), Vol?til (OR = 1,65) e Ciclot?mico (OR = 1,54). Vontade foi o ?nico tra?o dimensional associado ? idade ao nascimento do primeiro filho. Por outro lado, quanto maior o n?mero de abortos, maiores os escores de Raiva e Desejo, e menores os escores de Cautela, Maturidade e Controle. As mulheres que cometeram abortos apresentaram proeminentes tra?os de externaliza??o, o que sugere reduzidas restri??es morais, enquanto o nascimento de filhos na adolesc?ncia foi fracamente associado com os tra?os de temperamento.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-05-19T12:54:32Z No. of bitstreams: 1 DIS_ROBERTA_MONTEIRO_KATZAP_COMPLETO.pdf: 1440611 bytes, checksum: 60581bcd966d13bb2ed8592af3528373 (MD5) / Made available in DSpace on 2016-05-19T12:54:32Z (GMT). No. of bitstreams: 1 DIS_ROBERTA_MONTEIRO_KATZAP_COMPLETO.pdf: 1440611 bytes, checksum: 60581bcd966d13bb2ed8592af3528373 (MD5) Previous issue date: 2016-03-02 / Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul - FAPERGS / Chronic kidney disease patients on peritoneal dialysis therapy are susceptible to infections, with peritonitis being the primary cause of technique failure. Peritoneal fluid culture is one of the essential elements for proper diagnosis and treatment of peritonitis. The aim of this study was to compare the time required to obtain a positive culture using different laboratory methods. An in vitro cross-sectional study comparing different laboratory techniques for preparation and culture of bacteria in peritoneal fluid. The research was conducted with 21 sterile dialysis fluid bags with 1.5% glucose concentration, and 21 peritoneal dialysis bags containing peritoneal fluid drained from patients without peritonitis, assisted at the Nephrology Unit from HSL-PUCRS. Fluids from the 42 peritoneal dialysis bags were contaminated by injecting a coagulase-negative Staphylococcus suspension and then prepared for culture using four distinct techniques - A (direct culture), B (post-centrifugation culture), C (direct culture after 4h sedimentation), and D (culture after 4h sedimentation and centrifugation) ? followed by seeding. In the 21 contaminated sterile bags, the mean times to obtain a positive culture with techniques D (19.6 h ?2.6) and C (19.1 h ?2.3) were longer in comparison to A (15.8 h ?3.0; p<0.01), but not statistically different from group B mean (19.0 h ?3.2). The same occurred in the 21 bags drained from patients, with mean times for techniques D (14.0 h ?1.9) and C (14.5 h ?1.7) being longer than technique A (12.22 h ?1.94; p<0.05), however not statistically different from technique B (13.2 h ?1.3). The sedimentation and centrifugation steps were unnecessary and may delay antibiotics sensitivity test result by approximately 8 hours. / Pacientes com doen?a renal cr?nica que realizam terapia de di?lise peritoneal est?o suscet?veis a infec??es, sendo peritonite a principal causa de fal?ncia do m?todo. A cultura do l?quido peritoneal ? um dos elementos essenciais para o manejo cl?nico e tratamento adequados da peritonite. O objetivo deste estudo foi comparar o tempo necess?rio para obter uma cultura positiva, com diferentes m?todos laboratoriais. Estudo transversal, in vitro, comparando diferentes t?cnicas laboratoriais de preparo e cultura para bact?rias em l?quido peritoneal. O estudo foi feito com 21 bolsas de l?quido de di?lise peritoneal est?reis, com concentra??o de 1,5% de glicose, e em 21 bolsas contendo l?quido peritoneal drenado de pacientes sem peritonite, atendidos pelo Servi?o de Nefrologia do HSL-PUCRS. O dialisado das 42 bolsas de di?lise peritoneal foi contaminado, injetando-se suspens?o de Staphylococcus coagulase negativa e, em seguida, submetido a quatro t?cnicas distintas ? A (cultura direta); B (cultura p?s-centrifuga??o); C (cultura ap?s sedimenta??o de 4 h); e D (cultura ap?s sedimenta??o de 4 h e centrifuga??o) ? de preparo e semeadura. Nas 21 bolsas est?reis contaminadas se verificou que as m?dias de tempo para positivar a cultura nas t?cnicas D (19,6 h ?2,6) e C (19,1 h ?2,3) foram maiores, comparadas ? A (15,8 h ?3,0; p<0,01), mas estatisticamente n?o diferentes da m?dia do grupo B (19,0 h ?3,2). O mesmo aconteceu nas 21 bolsas drenadas dos pacientes, com tempos m?dios para as t?cnicas D (14,0 h ?1,9) e C (14,5 h ?1,7) superiores ao tempo da t?cnica A (12,22 h ?1,94; p<0,05), por?m n?o estatisticamente diferente da t?cnica B (13,2 h ?1,3). As etapas de sedimenta??o e centrifuga??o foram desnecess?rias, podendo postergar em quase oito horas o resultado final da cultura, comparativamente ? cultura direta, atrasando o resultado do teste de sensibilidade aos antibi?ticos.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-05-19T13:08:14Z No. of bitstreams: 1 TES_LUIZ_CARLOS_PORCELLO_MARRONE_COMPLETO.pdf: 11632116 bytes, checksum: 2546c03c25eed68601cf00144a3d5888 (MD5) / Made available in DSpace on 2016-05-19T13:08:14Z (GMT). No. of bitstreams: 1 TES_LUIZ_CARLOS_PORCELLO_MARRONE_COMPLETO.pdf: 11632116 bytes, checksum: 2546c03c25eed68601cf00144a3d5888 (MD5) Previous issue date: 2016-03-11 / Introduction: The Posterior Reversible Encephalopathy Syndrome (PRES) is a clinicoradiologic entity characterized by headache, altered level of consciousness, seizures and visual abnormalities, which is associated with an encephalic white matter edema, predominantly affecting the occipital and parietal lobes. The pathophysiology of PRES remains unclear. In a previous study, we developed an experimental model to better understand the cerebral changes of this syndrome in cases related to pregnancy disorders. The use of microPET-CT with 18F-FDG is a way of assessing brain metabolism changes related to PRES, allowing perform a follow up of these changes in subsequent exams. Objectives: The aim of this study is to evaluate the changes of the glucose cerebral metabolism and the permeability of blood brain barrier in pregnant rats submitted to Reduced Uterine Perfusion Pressure (RUPP) in comparison with pregnant control rats. Methods: Pregnant rats were divided in two groups: RUPP group and control group. Animals of the RUPP group underwent the procedure to reduce uteroplacental perfusion pressure. The animals of both groups were submitted to two microPET-CT scans with 18F-FDG (before and after the delivery) and then, we evaluate the permeability of blood brain barrier using Evans blue. Results: Evaluating the results of microPET-CT scans with 18F-FDG in the ten animals that were submitted to RUPP procedure in comparison with the six pregnant controls animals, there is a cerebral hypometabolism in the exam realized in period before the delivery in the group of rats underwent RUPP. In the postpartum period this result is reversed and the group of animals subjected to the procedure presents a cerebral hypermetabolism when compared to control group. Evaluating the permeability of the blood-brain barrier with Evans blue, 8 of 10 animals (80%) that were submitted to RUPP procedure had the pigment in brain parenchyma, which was not found in any of six animals of the control group. Conclusion: In this study we described a pattern of lower brain metabolism in Wistar rats submitted to RUPP procedure when compared to pregnant control rats before the delivery using microPET-CT with 18F-FDG for this evaluation. After delivery, there is an inversion and the group of animals submitted to RUPP procedure becomes hypermetabolic when compared to the control group using the same technique for measurement of glucose metabolism. The Evans Blue impregnating maintains the same brain tissue after passing seven days of the completion of delivery, and microscopic changes also persist. / Introdu??o: A S?ndrome da Encefalopatia Revers?vel Posterior (Posterior Reversible Encephalopathy Syndrome - PRES) ? uma entidade clinico-radiol?gica caracterizada por cefal?ia, altera??o do n?vel de consci?ncia, crises convulsivas e altera??o visual, a qual est? associada a edema na subst?ncia branca encef?lica, predominantemente acometendo os lobos occipitais e parietais. A fisiopatologia do PRES permanece desconhecida. Em estudo pr?vio desenvolvemos modelo experimental para melhor entender as altera??es cerebrais dessa s?ndrome nos casos relacionados a dist?rbios da gesta??o. O uso de microPET-CT com 18F-FDG ? um modo de avaliar as modifica??es de metabolismo cerebral relacionadas ao PRES, permitindo o acompanhamento dessas modifica??es em exames subsequentes. Objetivos: O objetivo desse trabalho ? avaliar as modifica??es do metabolismo de glicose cerebral e da permeabilidade da barreira hematoencef?lica em ratas gravidas submetidas ao procedimento RUPP em rela??o a ratas gravidas controle. M?todos: Ratas gravidas foram divididas em dois grupos: grupo RUPP e grupo controle. Os animais do grupo RUPP realizaram o procedimento para redu??o da press?o de perfus?o ?tero-placent?ria. Os animais dos dois grupos foram submetidos a dois exames de microPET-CT com 18F-FDG (antes e ap?s o parto) e, posteriormente a avalia??o da permeabilidade da barreira hematoencef?lica com uso de azul de Evans. Resultados: Avaliando-se o resultado dos exames de microPET-CT com 18F-FDG nos dez animais que foram submetidos ao procedimento da RUPP em rela??o aos seis animais controles encontramos que ocorre um hipometabolismo nas ratas que foram submetidas ? RUPP no per?odo antes do parto. J? no per?odo de puerp?rio, esse resultado se inverte e o grupo de animais submetido ao procedimento apresenta um hipermetabolismo quando comparado ao controle. Ao avaliar-se a permeabilidade da barreira hematoencef?lica ao azul de Evans, encontramos que em 8 dos 10 animais (80%) submetidos ? RUPP havia a presen?a do pigmento, o qual n?o foi encontrado em nenhum dos seis animais do grupo controle. Conclus?o: Nesse estudo encontramos um padr?o de menor metabolismo cerebral em ratas Wistar submetidas ? RUPP quando comparado ?s ratas do grupo controle antes da realiza??o do parto utilizando microPET-CT com 18F-FDG para essa avalia??o. Ap?s o parto, ocorre uma invers?o e o grupo de animais submetidos ? RUPP passa a ser o de maior metabolismo em compara??o aos animais do grupo controle utilizando a mesma t?cnica para aferi??o do metabolismo de glicose. O azul de Evans mant?m impregnando o tecido cerebral mesmo ap?s a passagem de sete dias da realiza??o do parto, assim como as altera??es microsc?picas tamb?m persistem.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-05-19T13:18:00Z No. of bitstreams: 1 TES_LUCIANA_ALVES_TISSER_COMPLETO.pdf: 3990484 bytes, checksum: f8629e9f12dd38cf3317ee45374ed21e (MD5) / Made available in DSpace on 2016-05-19T13:18:00Z (GMT). No. of bitstreams: 1 TES_LUCIANA_ALVES_TISSER_COMPLETO.pdf: 3990484 bytes, checksum: f8629e9f12dd38cf3317ee45374ed21e (MD5) Previous issue date: 2016-03-14 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introduction: The cognitive and behavioral impact of epilepsies affecting children and adolescents has a strong clinical relevance and is influenced by a number of factors, such as age of onset, underlying etiology, location of epileptogenic focus and effects of antiepileptic drugs on monotherapy or polytherapy. The aim of this study was to evaluate the impact of uncontrolled and controlled epilepsy on the cognitive and behavioral development, quality of life and sleep of children and adolescents. Methods: Cross-sectional study comprising children and adolescents aged between 6 and 18 years, divided into three groups, uncontrolled epilepsy, controlled epilepsy and normal controls. Data were collected by reviewing medical records for allocation to groups. Uncontrolled subjects who had at least two monthly crises over three months prior to the study were included in the uncontrolled epilepsy group and subjects without seizures for at least six months were included in the controlled epilepsy group. In an interview with a neuropsychologist, the following tests were applied: the Wechsler Abbreviated Scale of Intelligence (WASI) to evaluate intellectual capacity; Child and Adolescent Behavior Inventory (CABI) for behavioral assessment; Quality of Life Questionnaire for children with epilepsy (QVCE50) to assess quality of life; and Children?s Sleep Habits Questionnaire to evaluate sleep characteristics. Results: The sample consisted of 70 patients, 33 males (47.1%) and 37 (52.9%) females whose average age was 12.2 years (standard deviation 3.2 years), all from a low socioeconomic class. Epilepsy group with uncontrolled seizures (n = 22), mean age 13.0 ? 3, 45.5% of females. Epilepsy group with controlled seizures (n = 18), mean age 12.3 ? 3.8, 22.2% of females. Control group (n = 30), mean age 11.5 ? 2.9, 76.7% of females. Patients in the control group had a mean IQ of 93.07, differing significantly from the epilepsy groups (P = <0.001). Patients with uncontrolled epilepsies had an IQ of 57.21, and those with controlled epilepsies showed an IQ of 61.44. The uncontrolled epilepsy group presented more behavioral problems when compared with the other groups. In the uncontrolled epilepsy group, there was a correlation between quality of life and onset of seizures (r = 0.58, P = 0.036) and epilepsy time (r = -0.60, P = 0.014). In the controlled epilepsy group, there was a correlation between the CBCL social competence score and epilepsy time (r = -0.62 P = 0.011). In both epilepsy groups there was a correlation between the CBCL total competence score and onset of seizures, r=0.55, P=0.029 in uncontrolled epilepsies and r=0.51, P=0.035 in controlled epilepsies, respectively. Sleep assessment showed a significantly worse quality in both epilepsy groups compared to healthy children. There was a significant difference in quality of life between the two epilepsy groups, the uncontrolled group showing a worse result. Conclusion: Epilepsies with uncontrolled seizures occurring in children and adolescents have a negative impact on several areas of development and on quality of life. / Introdu??o: O impacto cognitivo e comportamental das epilepsias que acometem crian?as e adolescentes tem forte relev?ncia cl?nica e ? influenciado por uma s?rie de fatores, tais como a idade de in?cio, a etiologia subjacente, a localiza??o do foco epileptog?nico e os efeitos das drogas antiepil?pticas em mono ou politerapia. O objetivo deste estudo foi avaliar o impacto da epilepsia n?o controlada e controlada no desenvolvimento cognitivo, comportamental, na qualidade de vida e do sono de crian?as e adolescentes. M?todos: Estudo transversal composto por crian?as e adolescentes com idade entre 6 e 18 anos, divididos em tr?s grupos, epilepsia n?o controlada, epilepsia controlada e controles normais. A coleta de dados foi realizada atrav?s de revis?o de prontu?rio para alocamento nos grupos. Foram inclu?dos no grupo das epilepsias n?o controladas sujeitos que apresentaram pelo menos duas crises mensais nos tr?s meses anteriores do estudo e no grupo das epilepsias controlada sujeitos com aus?ncia de crises h?, pelo menos, seis meses. Em entrevista com neuropsic?loga foram aplicados os seguintes testes: a Escala de Intelig?ncia Wechsler Abreviada (WASI), para avaliar capacidade intelectual; Invent?rio de Comportamentos da Inf?ncia e Adolesc?ncia (CBCL) para avalia??o comportamental; Question?rio de Qualidade de Vida para crian?as com epilepsia (QVCE50) para avalia??o da qualidade de vida; e Question?rio sobre h?bitos e qualidade de sono, para avaliar caracter?sticas do sono. Resultados: A amostra foi composta por70 pacientes, 33 do sexo masculino (47,1%) e 37 (52,9%) do sexo feminino, cuja m?dia de idade foi de 12,2 anos (desvio padr?o de 3,2 anos), todos de classe socioecon?mica baixa. Grupo com epilepsia com crise n?o controladas (n=22), m?dia de idade 13,0?3, 45,5% do sexo feminino. Grupo com epilepsia e crises controladas (n= 18), m?dia de idade 12,3?3,8, 22,2% do sexo feminino. Grupo-controle (n=30), m?dia de idade de 11,5?2,9, 76,7% do sexo feminino. Os pacientes do grupo-controle apresentaram m?dia de QI 93,07, diferindo de forma significativa dos grupos com epilepsia (p=<0,001). Os pacientes com epilepsias n?o controladas apresentaram QI 57,21 e os com epilepsias controladas QI 61,44.O grupo com epilepsias n?o controladas apresentou mais problemas comportamentais quando comparado aos outros grupos. No grupo de epilepsias n?o controladas houve correla??o entre qualidade de vida e in?cio das crises (r=0,58, P=0,036) e tempo de epilepsia (r=-0,60, P=0,014). No grupo de epilepsias controladas, houve correla??o entre a compet?ncia social do CBCL e o tempo de epilepsia (r=-0,62 P=0,011). Em ambos os grupos de epilepsia houve correla??o entre compet?ncia total do CBCL e o in?cio das crises, respectivamente r=0,55, P=0,029 nas n?o controladas e r=0,51, P=0,035nas controladas. A avalia??o do sono evidenciou de forma significativa pior qualidade em ambos os grupos com epilepsia quando comparados ao grupo de crian?as saud?veis. Houve diferen?a significativa na qualidade de vida entre os dois grupos de epilepsia, apresentando piora no grupo n?o controlado. Conclus?o: Epilepsias com crises n?o controladas que ocorrem em crian?as e adolescentes tem um impacto negativo em diversas ?reas do desenvolvimento e na qualidade de vida.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-05-19T14:23:34Z No. of bitstreams: 1 DIS_SABRINA_CHAPUIS_DE_ANDRADE_COMPLETO.pdf: 1382114 bytes, checksum: 34b5038149ceb6daf77404d0620886d2 (MD5) / Made available in DSpace on 2016-05-19T14:23:34Z (GMT). No. of bitstreams: 1 DIS_SABRINA_CHAPUIS_DE_ANDRADE_COMPLETO.pdf: 1382114 bytes, checksum: 34b5038149ceb6daf77404d0620886d2 (MD5) Previous issue date: 2016-02-29 / Objectives: The aim of this study was to determine the prevalence of weight control behaviors (WCBs) in a large sample of web-based inquiries of Brazilian nationals and the correlation with body mass index (BMI) and weight-based self-perception. Method: The data were collected by the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP) in 27,501 volunteers (30.4% men) with a mean age of 28.9 ? 8.7 years. Results: The most prevalent WCBs for men and women were exhaustive physical exercise and prolonged fasting, respectively (p<0.001). Vomiting, intake of appetite suppressant medications, diuretics and laxatives were 3-8 times more common in women than in men. Frequent exhaustive physical exercise was the only behavior more often adopted by men. BMI was positively associated with WCBs, reaching high frequency in obese subjects (20-30% in male and ~40% of female). About 15% of normal weight women reported using diuretics and laxatives, and 12.2% reported vomiting at least sometimes. The prevalence of frequent WCBs in the thin and very thin groups was lower than in the normal weight group. For subjects whom body weight was highly regarded in their self-perception, there was a strong positive association with all WCBs, at similar degrees, in both genders. Compared to those who never base their intrinsic personal value on body weight, those who do it very frequently have 25-30 times higher risk of inducing vomiting (OR 30.70, 95%CI 9.38-100.49 for men and OR 25.49, 95%CI 17.50-37-13 for women). Conclusion: The prevalence of participants adopting WCBs was high, especially in women and obese subjects. Weight-based self-evaluation was more strongly associated to WCBs than BMI. / Objetivo: O objetivo deste estudo foi determinar a preval?ncia de comportamentos voltados ? perda de peso em uma grande amostra coletada pela internet, em brasileiros, e a correla??o com o ?ndice de massa corporal (IMC) e a autopercep??o baseada no peso corporal. M?todos: Os dados foram coletados pelo Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP) em 27.501 volunt?rios (30,4% homens) com uma m?dia de idade de 28,9 ? 8.7 anos. Resultados: Os comportamentos mais prevalentes realizados por homens e mulheres para perder peso foram exerc?cio f?sico exaustivo e jejum prolongado, respectivamente (p<0.001). V?mitos, ingesta de medicamentos para emagrecer, diur?ticos e laxantes foram 3 a 8 vezes mais comuns em mulheres do que em homens. A realiza??o frequente de exerc?cio f?sico exaustivo foi o ?nico comportamento mais adotado por homens. O IMC foi diretamente associado com comportamentos voltados ? perda de peso, alcan?ando as maiores preval?ncias em participantes obesos (20-30% em homens e ~40% em mulheres). Em torno de 15% das mulheres com IMC normal referiram uso de diur?ticos e laxantes, e 12,2% referiu vomitar ao menos ?s vezes. A preval?ncia de comportamentos frequentes para perder peso nos participantes magros e muito magros foi menor do que no grupo com IMC normal. Para participantes que atribuem maior valor ? autopercep??o com base no peso corporal houve uma forte associa??o com a realiza??o de comportamentos voltados ? perda de peso, de forma similar, em ambos os g?neros. Comparados aos que responderam que nunca relacionaram sua autopercep??o ao peso corporal, os que fazem frequentemente t?m de 25 a 30 vezes mais risco de provocar v?mitos (OR 30,70, 95%CI 9,38-100,49 para homens e OR 25,49, 95%CI 17,50-37,13 para mulheres). Conclus?o: A preval?ncia de participantes que realizam comportamentos voltados ? perda de peso foi alta, especialmente em mulheres e em obesos. A autoavalia??o com base no peso corporal foi mais fortemente associada com a realiza??o de comportamentos do que o IMC.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-06-10T17:07:06Z No. of bitstreams: 1 DIS_ADRIANA_DA_SILVA_LOCKMANN_COMPLETO.pdf: 2573373 bytes, checksum: 05d0a654c45129e9df1c0777c6646eb8 (MD5) / Made available in DSpace on 2016-06-10T17:07:06Z (GMT). No. of bitstreams: 1 DIS_ADRIANA_DA_SILVA_LOCKMANN_COMPLETO.pdf: 2573373 bytes, checksum: 05d0a654c45129e9df1c0777c6646eb8 (MD5) Previous issue date: 2016-03-16 / This study aimed to investigate the association between dietary intake and nutritional status with depressive and anxiety symptoms in institutionalized elderly. They selected 80 elderly people with normal cognitive status by the Mini-Mental State three long-term care facilities served by the Bank of the Rio Grande do Sul Food. We collected demographic data through a short questionnaire. Nutritional status was assessed by Miniavalia??o Nutrition (MNA?) in full, including the calculation of body mass index (BMI). The nutrient intake was analyzed by averaging three dietary recalls Surveys 24 hours and depressive and anxiety symptoms were investigated by Beck Depression Inventory (BDI and BAI). Depressive and anxiety symptoms were found in 45 (56.3%) and 42 (52.5%) elderly, respectively. There was a positive association between nutritional status, the score MNA?, and depressive and anxiety symptoms, indicating greater nutritional risk in elderly patients with these symptoms (MNA? the score average of 23.74?3.41 and 23.54?3.35 on). There were statistical differences associated nutrients monounsaturated fat (p=0.039), calcium (p=0.025), phosphorus (p=0.001), potassium (p=0.002) and ascorbic acid (p=0.024) of the classification categories for the symptoms depression (BDI). Seniors with depressive symptoms (BDI ?10) showed higher calcium intake and lower intake of monounsaturated fat, phosphorus, potassium and ascorbic acid compared to those without depressive symptoms elderly (BDI ?9). Comparing food intake in relation to classification categories for anxiety symptoms (BAI), there was an indication of the significance of niacin (p = 0.059). We conclude that nutritional status and food intake are directly associated with mood (depressive and anxiety symptoms), more efforts are needed to encourage the intake of these nutrients in institutionalized elderly. / Este estudo teve o objetivo de verificar a associa??o da ingest?o alimentar e do estado nutricional com os sintomas depressivos e ansiosos em idosos institucionalizados. Foram selecionados 80 idosos que apresentaram estado cognitivo normal pelo Miniexame do Estado Mental de tr?s institui??es de longa perman?ncia atendidas pelo Banco de Alimentos do Rio Grande do Sul. Foram coletados dados sociodemogr?ficos atrav?s de um curto question?rio. O estado nutricional foi avaliado pela Miniavalia??o Nutricional (MNA?) na forma completa, incluindo o c?lculo do ?ndice de Massa Corporal (IMC). O consumo de nutrientes foi analisado pelo c?lculo da m?dia de tr?s Inqu?ritos Recordat?rios de 24 horas e os sintomas depressivos e ansiosos foram investigados pelos Invent?rios de Depress?o de Beck (BDI e BAI). Os sintomas depressivos e ansiosos foram encontrados em 45 (56,3%) e 42 (52,5%) idosos, respectivamente. Houve associa??o positiva entre o estado nutricional, pela pontua??o da MNA?, e os sintomas depressivos e ansiosos, apontando risco nutricional maior em idosos com esses sintomas (m?dia do escore da MNA? de 23,74?3,41 e 23,54?3,35 respectivamente). Houve diferen?a estat?stica quando associados os nutrientes gordura monoinsaturada (p=0,039), c?lcio (p=0,025), f?sforo (p=0,001), pot?ssio (p=0,002) e ?cido asc?rbico (p=0,024) ?s categorias de classifica??o para os sintomas depressivos (BDI). Os idosos com sintomas depressivos (BDI ?10) mostraram maior ingest?o de c?lcio e menor ingest?o de gordura monoinsaturada, f?sforo, pot?ssio e ?cido asc?rbico em rela??o aos idosos sem sintomas depressivos (BDI ?9). Comparando a ingest?o alimentar em rela??o ?s categorias de classifica??o para sintomas ansiosos (BAI), houve um indicativo de signific?ncia da niacina (p=0,059). Conclu?mos que estado nutricional e ingest?o alimentar est?o diretamente associados ao estado de humor (sintomas depressivos e ansiosos), sendo necess?rios mais esfor?os para incentivar a ingest?o desses nutrientes em idosos institucionalizados.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-06-17T19:39:46Z No. of bitstreams: 1 TES_ALINE_DEFAVERI_DO_PRADO_COMPLETO.pdf: 1737423 bytes, checksum: 77ee581083f58c46dd10a545b62097a5 (MD5) / Made available in DSpace on 2016-06-17T19:39:46Z (GMT). No. of bitstreams: 1 TES_ALINE_DEFAVERI_DO_PRADO_COMPLETO.pdf: 1737423 bytes, checksum: 77ee581083f58c46dd10a545b62097a5 (MD5) Previous issue date: 2016-03-28 / Introduction: Rheumatoid Arthritis (RA) is an autoimmune, inflammatory and chronic disease. Muskuloskeletal ultrasound (MSUS) has been increasingly used for diagnostic evaluation and monitoring of patients. Regulatory T cells (Tregs) and lymphocytes producers of IL 17 (Th17) imbalance and disfuntion, as well as pro inflammatory cytokines, have been implicated in the pathogenesis of RA. There are few studies on the association of circulating lymphocites subtypes and cytokines with MSUS findings in RA. Methods: One hundred and one RA patients (1987 American College of Rheumatology criteria) treated with disease-modifying antirheumatic drugs (DMARDs) were included in this cross sectional study. A blood sample was taken just before clinical and ultrasonographic evaluation, which were all performed on the same day, consecutively and in a blinded fashion. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate regulatory FoxP3+ T cells and IL-17+ cells. Plasma Th1-Th2-Th17 cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF e IFN-?) and VEGF were searched using a Cytometric Bead Array (CBA; BD biosciences) kit by flow cytometry. Disease acitivity and disability were measured using Disease Activity Score in 28 joints (DAS28) and Health Assessment Questionnaire (HAQ). MSUS (MyLab 60, Esaote, Genova, Italy, 18 MHz linear probe) was performed consecutively by two ultrassound-trained rheumatologists on the wrists, 2th and 3th metacarpophalangeal and 2th and 3th proximal interphalangeal joints of both hands. Gray-scale synovial hypertrophy (PS) and power Doppler signal (pD) were searched using a semi-quantitative scale (0-3). Erosions were classified as present or absent. The sum of the individual joint scores for PS and pD (10-joint PS and pD scores) was calculated and used to correlate with clinical and laboratory data. Mann-Whitney test, Kruskal-Wallis test and Spearman correlation coefficient (rS) were used for statistical analysis, as well as liner multivariate regression. Interater agreement was tested using kappa statistics and intraclass correlation. Results: Among 101 patients, we were able to measure Treg/Th-17 in 90 individuals. Plasma cytokines were searched in 64 patients. Clinical and demographic features were: mean age, 55.8 ? 11 years; female gender, 80%; Caucasians, 85%; median (interquartile range) disease duration 6 (2-13) years; mean ? SD DAS28, 4.28 ? 1.64; mean ? SD HAQ score, 1.11 ? 0.85. Interobserver agreement (kappa) for US features varied from 0.53 to 1.0. Intraclass correlation for 10-joint PS score was 0.964 (95% CI 0.899-0.986, P <0.000) and for 10-joint pD score was 0,859 (95% CI 0.646-0.941, P <0.001). There was no significant correlation of 10-joint PS and pD scores with DAS28 and HAQ score. The presence of bone erosions was associated with 10-joint PS and pD scores (p=0.002), but not with DAS 28 (p=0.079) or HAQ (0.057). Swollen joint count, but not tender joint count, was correlated with 10-joint PS and pD scores (rS=0.54, P<0.001 and rS=0.39, P<0.001; respectively), as well as associated with bone erosions (P<0.001). There was no significant correlation of with 10-joint PS and pD scores with peripheral Tregs (rS=0.122, P=0.254 and rS=0,056, P=0.602) and Th17 cells (rS=-0.083, P=0.438 and rS=-0.060, P=0,575). Tregs and Th17 cells were not associated with erosions (p= 0,831 and p=0,632, respectively). Among all tested cytokines, IL-6 was correlated with DAS28 (rs 0.31 IC95% 0.07 to 0.52), eritrocyte sedimentation rate (rs 0.43 IC95% 0.19 to 0.62) and swollen joint count (rs 0.39 95%CI 0.15 a 0.59). IL-6 was also correlated with 10-joint pD score (rs 0.33 IC95% 0.07 to 0.56), right and left wrists pD (rs 0.34 IC95% 0.11 to 0.54 and rs 0.45 IC95% 0.21 to 0.64), and right and left PS (rs 0.40 IC95% 0.20 to 0.59 and rs 0.35 IC95% 0.08 to 0.57). Using multivariate linear regression model, 10-joint pD score was positively associated with IL-6 independently of DAS28 (P=0.025). There was no association of any of the tested cytokines with bone erosions (P? 0.17 for all tests). Conclusions: In established RA patients, treated with non biological DMARDs, we observed the following: lack of correlation of 10-joint PS and pD scores and DAS28 and HAQ; positive association of 10-joint PS and pD scores with bone erosions; positive association of swollen joint count, but not tender joint count, with MSUS synovitis and erosions; lack of correlation of MSUS features and circulating Treg and Th-17 cells; positive correlation of plasma IL-6 and MSUS synovitis. The association of IL-6 with 10-joint pD score was independent of DAS28. / Introdu??o. A artrite reumatoide (AR) ? uma doen?a autoimune inflamat?ria cr?nica com envolvimento articular proeminente. O ultrassom de alta resolu??o (US) tem sido empregado de maneira crescente na avalia??o diagn?stica e monitoriza??o da doen?a. O desequil?brio entre as fun??es de linf?citos T regulat?rios (Treg) e Th-17, bem como o papel de citocinas pr? inflamat?rias s?o centrais em sua patog?nese. H? escassez de estudos sobre a associa??o entre os achados ultrassonogr?ficos de atividade da AR e dano estrutural com subtipos linfocit?rios e citocinas no sangue perif?rico. M?todos: Neste estudo transversal, foram inclu?dos 101 pacientes com AR de acordo com os crit?rios de 1987 em tratamento com drogas remissivas n?o-biol?gicas. Uma amostra de sangue foi coletada imediatamente antes das avalia??es cl?nica e ultrassonogr?fica, que foram feitas todas no mesmo dia, em sequ?ncia. Os linf?citos foram isolados e imunofenotipados por citometria de fluxo para identificar c?lulas T reg FoxP3+ e linf?citos produtores de IL-17. Citocinas do perfil Th1-Th2-Th17 (IL-2, IL-4, IL-6, IL-10, IL-17, TNF e IFN-?) e VEGF foram quantificadas no plasma por citometria de fluxo utilizando-se o kit Cytometric Bead Array (CBA; BD biosciences). Atividade da doen?a foi quantificada por DAS28 e capacidade funcional, pelo HAQ, ambos realizados por reumatologista treinado, cegado em rela??o aos achados de US. Dois reumatologistas (cegados em rela??o aos dados cl?nicos) com treinamento em ultrassonografia realizaram avalia??o de sinovite e presen?a de eros?es em punhos, 2? e 3? articula??es metacarpofalangeanas e 2? e 3? interfalangeanas proximais bilateralmente utilizando aparelho de alta resolu??o (MyLab 60, Esaote, It?lia, transdutor linear de 18 mHz). Prolifera??o sinovial na escala de cinzas (PS) e capta??o de power Doppler (pD) foram avaliadas utilizando uma escala semi-quantitativa com varia??o de 0 a 3. Eros?es foram classificadas como presentes ou ausentes. A soma dos escores individuais de PS e pD foi calculada (escore 10 PS e escore 10 pD) e utilizada para correlacionar com dados cl?nicos e de laborat?rio. Teste de Mann-Whitney, Kruskal-Wallis e coeficiente de correla??o de Spearman foram usados na an?lise estat?stica, bem como regress?o linear m?ltipla. Correla??o intraclasse e estat?stica kappa foram usados para concord?ncia interobservador. Resultados: Dentre os 101 pacientes inclu?dos, obtivemos quantifica??o de c?lulas Treg e Th-17 em 90 pacientes e dosagem de citocinas em 64 indiv?duos. Em sua maioria, a amostra foi composta por mulheres (80%) da ra?a branca (85%), com m?dia de idade de 55,8 anos (?11.1anos), tempo de dura??o de doen?a de 6 (2-13) anos (mediana e IIQ). A m?dia do DAS 28 (VSG) foi de 4.28 (?1.64) e do HAQ 1.11 (?0.85). Valores de kappa para a concord?ncia interobservador para o exame ultrassonogr?fico variaram de 0.53 a 1; a correla??o intraclasse para o escore 10 PS foi de 0.964 (IC95% 0.899-0.986, P <0.001) e, para o escore 10 pD, 0.859 (IC95% 0.646-0.941, P <0.001). N?o houve correla??o entre escore 10 PS e escore 10 pD com DAS28 e HAQ. Eros?es ?sseas foram associadas ao escores 10 PS e pD (p=0.002), mas n?o com DAS 28 (P=0,079) e HAQ (P =0,057). Observamos correla??o entre contagem de articula??es edemaciadas com escore 10 PS e escore 10 pD (rS=0.54, P<0.001 e rS=0.39, P<0.001; respectivamente), bem como associa??o com a presen?a de eros?es (P<0.001). N?o observamos correla??o entre contagem de articula??es dolorosas com escore 10 GS (rS = -0.071 P = 0.524), escore 10 pD (rS = -0.196 P = 0.078) ou associa??o com presen?a de eros?es (P=0.248). N?o houve correla??o significativa de escore 10 PS e pD com Treg (rS=0.122, P=0.254 e rS=0,056, P=0.602, respectivamente) e Th-17 perif?ricas (rS=-0.083, P=0.438 e rS=-0.060, P=0,575, respectivamente). N?o se observou associa??o entre percentual de c?lulas Treg e Th-17 e presen?a de eros?es (P=0.831 e P=0.632, respectivamente). A concentra??o de IL-6, mas n?o de outras citocinas, se correlacionou ao DAS28 (rs 0.31 IC95% 0.07 a 0.52), VSG (rs 0.43 IC95% 0.19 a 0.62) e contagem de articula??es edemaciadas (rs 0.39 95%CI 0.15 a 0.59), bem como com escore 10 pD (rs 0.33 IC95% 0.07 a 0.56), capta??o de pD em punhos direito e esquerdo (rs 0.34 IC95% 0.11 a 0.54 e rs 0.45 IC95% 0.21 a 0.64, respectivamente) e PS em punhos direito e esquerdo (rs 0.40 IC95% 0.20 a 0.59 e rs 0.35 IC95% 0.08 a 0.57, respectivamente). Utilizando-se modelo de regress?o linear m?ltipla, observou-se que o escore 10 pD foi positivamente associado a IL-6 independente de DAS28 (P=0.025). N?o houve associa??o entre nenhuma das citocinas testadas e a presen?a de eros?es ?sseas (P? 0.17 para todos os testes). Conclus?es: Em pacientes com AR estabelecida sob uso de remissivos sint?ticos, observamos: aus?ncia de associa??o de escore 10 PS e pD com DAS28 e HAQ; associa??o entre escore 10 PS e pD e eros?es ?sseas; associa??o de contagem de articula??es edemaciadas, mas n?o de articula??es dolorosas, com sinovite e eros?es no US; aus?ncia de associa??o entre achados de US e linf?citos Treg e Th-17 no sangue perif?rico; associa??o entre IL-6 plasm?tica e achados de sinovite no US. A associa??o entre IL-6 e escore pD ocorreu independente do DAS28.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-06-22T19:22:17Z No. of bitstreams: 1 TES_DANIEL_RODRIGO_MARINOWIC_COMPLETO.pdf: 16202491 bytes, checksum: 5bb7aaf0de3a700a163c7437ecf2adef (MD5) / Made available in DSpace on 2016-06-22T19:22:17Z (GMT). No. of bitstreams: 1 TES_DANIEL_RODRIGO_MARINOWIC_COMPLETO.pdf: 16202491 bytes, checksum: 5bb7aaf0de3a700a163c7437ecf2adef (MD5) Previous issue date: 2016-03-03 / Changes in the cerebral cortex development are presented as a group of distinct defects with a not well-defined pathogenesis. The focal cortical dysplasia (FCD) is one of the most frequent form of cortical development malformation, that encompasses multiple types of changes both in the cortical architecture and cytological abnormalities. It is an underlying pathology of a significant proportion of partial epilepsy refractory to drug treatment. Especially the limited number of cases and the lack of suitable experimental models rarely document the mechanisms involved with the genesis of FCD. The scarse predictive preclinical models that can be used to study the pathophysiology and to translate the therapeutic discovery from animal models to human use, strengthens the need to study the brain development from cells originated from patients that harbor these central nervous systems diseases. The generation of iPSC cells and the differentiation into specific cells and tissues will provide important testing and an unique ability to study the development and progress of CNS diseases. The objective of this study was to establish a cellular model of focal cortical dysplasia through the generation of induced pluripotent stem cells (iPSC) from fibroblasts derived from affected patients. Human fibroblasts were obtained from skin biopsies from two patients and cultured up to the fifth passage. Immunofluorescence analysis of AKT/mTOR signaling pathways was performed in the dysplastic brain tissue. iPSC cells were generated from fibroblasts through transfection with a viral vector containing the genes OCT4, KLF4, SOX2, and C-MYC and characterized by immunohistochemistry. Cell migration co-cultured with fibroblast and iPSC was investigated. Morphological and molecular characterization of neurodifferentiated iPSC were performed by immunohistochemistry and PI3K/ATK/mTOR signaling pathway analysis. Both patients were diagnosed with FCD type IIb. The AKT and mTOR phosphorylated and non-phosphorylated was higher in brain sections from patient 01. iPSC clones from patients and controls were generated from skin fibroblasts. Both iPSC from patients and controls showed polarization and morphology similar to nerve cells. In the cell migration assay, fibroblasts derived from FCD migrate with greater intensity within 24 hours (p<0,0001) and 48 hours (p<0,001), and iPSC cells did not present difference in cell migration. During neurodifferentiation, iPSC cells from patients with FCD showed lower values of 4EBP-1, ?-catenin, CIAP-1, CIAP-2 and PI3K, and higher values of MCL 1 gene expression. Changes in cell migration in adult tissue, uncontrolled cell proliferation, cell adhesion protein deficiency, and alterations in the expression of genes responsible for apoptosis and PI3K pathway that are implicated with an complete and well successful CNS formation. Alterations in some of these were detected in cells and iPSC from patients with FCD and may be related to the ethiopathology of the disease. / As altera??es do desenvolvimento do c?rtex cerebral apresentam-se como um grupo de malforma??es com uma distin??o e patog?nse ainda n?o bem definidas. A displasia cortical focal (DCF) ? uma das formas mais frequentes de malforma??es do desenvolvimento cortical, sendo a patologia subjacente a uma parcela significativa de epilepsias parciais refrat?rias ao tratamento medicamentoso. A displasia cortical focal engloba m?ltiplos tipos de altera??es tanto na arquitetura cortical quanto em anormalidades citol?gicas. Palmini e colaboradores classificaram as displasias corticais focais de acordo com observa??es na subst?ncia branca e na arquitetura da camada cortical. Os mecanismos envolvidos na g?nese da DCF s?o pouco investigados, principalmente pelo n?mero limitado de casos e a falta de modelos experimentais adequados e suas causas provavelmente est?o relacionadas a muta??es som?ticas. A falta de modelos pr?-cl?nicos preditivos que possam ser utilizados no estudo da fisiopatologia e o hist?rico enfraquecido quando se trata em traduzir a descoberta terap?utica de modelos animais para o uso humano, fortalece a necessidade de estudar o desenvolvimento cerebral a partir de c?lulas originadas do pr?prio paciente. A gera??o de c?lulas iPSC e diferencia??o tecidual espec?fica de c?lulas de pacientes acometidos por doen?as neurol?gicas relevantes possui um valor inestim?vel para a realiza??o de testes al?m de fornecerem uma capacidade adicional e ?nica para estudar o desenvolvimento inicial e a progress?o das patologias associadas ao SNC. O objetivo do presente trabalho ? estabelecer um modelo celular de Displasia Cortical Focal atrav?s da gera??o de c?lulas-tronco pluripotentes induzidas (iPSC) a partir de fibroblastos de pacientes afetados. Fibroblastos humanos foram obtidos de bi?psias de pele de dois pacientes com DCF e foram cultivados at? a quinta passagem. Foi realizada an?lise imunopatol?gica e das vias de sinaliza??o AKT/mTOR no tecido cerebral displ?sico. C?lulas iPSC foram geradas a partir dos fibroblastos atrav?s da exposi??o a vetores virais contendo os genes OCT4, KLF4, SOX2, e C-MYC e caracterizadas por imunohistoqu?mica. Foi realizado ensaio de migra??o celular dos fibroblastos (24h, 48h e 72h) e das iPSC (3 dias e 7 dias). As c?lulas iPSC foram neurodiferenciadas e analisadas nos per?odos de 14 dias, 22 dias e 35 dias. Nesses per?odos, foram realizadas an?lises morfol?gicas, imunohistoqu?mica (polariza??o) e moleculares (genes relacionados a via PI3K/ATK/mTOR). Ambos os pacientes foram diagnosticados com DCF tipo IIb. O paciente 01 apresentou valores maiores que o paciente 02 em rela??o ? ?rea marcada das vias AKT e mTOR, tanto na via fosforilada como n?o fosforilada no tecido cerebral, com diferen?as estatisticamente significativas. Clones iPSC dos pacientes e controles foram gerados e caracterizados a partir dos fibroblastos de pele. Tanto as iPSC dos pacientes quanto do controle apresentaram morfologia e polariza??o semelhante a c?lulas nervosas ap?s protocolo de neurodiferencia??o. No ensaio de migra??o celular, fibroblastos com DCF migraram com mais intensidade em 24 horas (p<0,0001) e 48 horas (p<0,001). As c?lulas iPSC n?o apresentaram diferen?a no potencial de migra??o celular nos per?odos analisados. Durante o protocolo de neurodiferencia??o, as c?lulas iPSC dos pacientes com DCF apresentaram valores menores de express?o dos genes 4EBP-1, ?-Catenina, CIAP-1, CIAP-2 e PI3K, e valores mais elevados da express?o de MCL 1. Altera??es na migra??o celular no tecido adulto e em processos como de prolifera??o celular acentuada, defici?ncia de prote?na de ades?o celular, altera??o na express?o de genes respons?veis pelo controle de apoptose e altera??o na via PI3K respons?vel no sistema nervoso central pela sobreviv?ncia celular, controle de apoptose, migra??o neuronal, desenvolvimento morfol?gico dos neur?nios e forma??o das neurotransmiss?es, puderam ser evidenciadas nas c?lulas dos pacientes com DCF em rela??o aos pacientes controle e podem estar relacionadas com a forma??o do c?rebro com displasia.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-06-22T19:27:40Z No. of bitstreams: 1 TES_TALITA_CARNEIRO_BRANDAO_PEREIRA_COMPLETO.pdf: 639031 bytes, checksum: 5fa4cd79fd277a716b47890fcca5b580 (MD5) / Made available in DSpace on 2016-06-22T19:27:40Z (GMT). No. of bitstreams: 1 TES_TALITA_CARNEIRO_BRANDAO_PEREIRA_COMPLETO.pdf: 639031 bytes, checksum: 5fa4cd79fd277a716b47890fcca5b580 (MD5) Previous issue date: 2016-02-29 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / First identified in Saccharomyces ceresvisie, the sirtuins (SIRTs) are a diverse family of histones deacilases that act as deacetilases, ADP-ribosil transferases, desuccinilases and demalonilases; using nicotinamide adenine dinucleotide (NAD+) as co-substrate. Their regulatory involvement targeting histones, structural proteins and transcription factors implicate them in a broad range of biological processes and raised promising roles as therapeutic targets in apoptosis, oxidative stress and inflammation, among many others. These processes in turn, can be easily modeled in zebrafish (Danio rerio), a model organism with great developmental, genetic and economical advantages. Despite growing interest in this fresh water teleost as model organism and the regulatory and therapeutical potential of sirtuins in inflammation and associated processes, next to nothing is known about sirtuins in zebrafish. In order to contribute to this scenario and accelerate zebrafish potential as screening platform for sirtuins modulators, this work aimed to characterize sirtuins roles in a copper-induced inflammation model in zebrafish larvae. Alterations in locomotor behavior, sirtuin-related genes expression pattern and gene expression of inflammation, oxidative stress and apoptosis markers were observed after copper exposure. In order to further evaluate SIRT1 contribution to this scenario, a SIRT1 knockout line was developed using CRISPR-Cas9 technology, which showed an exarcebated inflammatory response after copper exposures. Additional studies will help to elucidate sirtuin roles in inflammation and associated processes, taking advantage of zebrafish?s translational potential. / Inicialmente identificadas em Saccharomyces cerevisie como reguladores de silenciamento de informa??o, as sirtu?nas (SIRTs) s?o uma diversa fam?lia de histonas desacilases da classe III (HDACs) que atuam como desacetilases, mono-ADP-ribosil transferases, desuccinilases e demalonilases; todas dependentes de nicotinamida adenina dinucleot?deo (NAD+). Presentes em todos os dom?nios de vida e tamb?m em v?rus, as sirtu?nas se tornaram promissores alvos terap?uticos devido seu envolvimento em diversos processos biol?gicos, incluindo apoptose, estresse oxidativo e inflama??o. Estes por sua vez s?o considerados denominadores comuns de diversas patologias e podem ser facilmente estudados utilizando os transl?cidos embri?es e larvas do zebrafish (Danio rerio) como organismo modelo. Apesar do crescente uso deste pequeno tele?steo de ?gua doce em diversas ?reas de estudo, e das sirtu?nas terem um promissor, mas pouco esclarecido, papel em eventos de inflama??o, apoptose e estresse oxidativo, pouco se sabe sobre as sirtu?nas no zebrafish - retardando seu uso como ferramenta de screening de drogas potencialmente moduladoras das SIRTs. Sob este cen?rio, o objetivo deste trabalho foi caracterizar o papel das sirtu?nas em modelo de inflama??o induzido por sulfato de cobre em larva de zebrafish. Altera??es em comportamento explorat?rio da larva, express?o de genes associados a sirtu?nas, bem como em marcadores de inflama??o, estresse oxidativo e apostose foram observados ap?s a exposi??o ao cobre. Para investigar o papel do mais conhecido e abrangente membro das sirtu?nas, desenvolvemos uma linhagem nocaute para SIRT1 utilizando a tecnologia CRISPR/Cas9, a qual apresentou reposta inflamat?ria exarcebada quando exposta ao cobre. Estudos adicionais neste modelo podem contribuir com descobertas sobre a biologia e modula??o das SIRTs ao usufruir do potencial translacional do zebrafish.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-06-03T17:07:06Z No. of bitstreams: 1 DIS_VALERIA_DE_CARVALHO_FAGUNDES_COMPLETO.pdf: 9189842 bytes, checksum: 56668b6b0efefbfeb3b5640951076368 (MD5) / Made available in DSpace on 2016-06-03T17:07:06Z (GMT). No. of bitstreams: 1 DIS_VALERIA_DE_CARVALHO_FAGUNDES_COMPLETO.pdf: 9189842 bytes, checksum: 56668b6b0efefbfeb3b5640951076368 (MD5) Previous issue date: 2016-03-01 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The Deep Brain Stimulation (DBS) for the treatment of Parkinson's disease (PD) involves the implantation of four microelectrodes in the subthalamic nucleus (STN). Although usually safe from a cognitive point of view, the SNT DBS has been linked to a decrease in verbal fluency (VF) in nearly all studies comparing preoperative to postoperative period. The decline can be attributed to surgical effects, but the real contributions of the stimulation frequency effects are not known. This research aims to investigate the impact of the frequency of SNT DBS in the performance of VF in patients with PD, comparing the VF and the motor performance at low frequency (60 Hz) and high-frequency (130 Hz), assessing the quality of life and correlating the demographic factors such as age and educational level and reading and writing habits with VF. It is a randomized double-blind experimental study. The initial sample consisted of 25 individuals, but 5 were excluded for not meeting the inclusion criteria. Thus, 20 subjects were included in the sample, from 30 to 75 years of age (56.7 ? 10.7), with average schooling 10.1 (? 5.2), and 16 were males and 4 females. Participants were evaluated with phonetic and categorical VF tasks, motor scale (UPDRS III), quality of life questionnaire (PDQ-39) and reading and writing habits. The evaluation of motor and VF was assessed after one hour from the frequency setting for high (130 Hz) and low (60 Hz), the frequency adjustment order being randomized. Patients with PD who underwent SNT DBS showed a decrease in phonemic VF in high frequency. There was no correlation regarding age and educational level of participants when compared to VF. The high frequency (130 Hz) of the SNT DBS caused a decline in VF and there was no correlation with socio-demographic factors such as age and educational level. / A Estimula??o Cerebral Profunda (ECP) para o tratamento da doen?a de Parkinson (DP) envolve o implante de quatro microeletrodos no N?cleo Subtal?mico (NST). Embora geralmente seguro do ponto de vista cognitivo, a ECP no NS tem sido associada a uma diminui??o da Flu?ncia Verbal (FV) em praticamente todos os estudos que compararam o per?odo pr?-cir?rgico ao p?s-cir?rgico. O decl?nio pode ser atribu?do aos efeitos cir?rgicos, mas as contribui??es relativas dos efeitos da frequ?ncia da estimula??o n?o s?o conhecidas. Esta pesquisa visa investigar o impacto das frequ?ncias da ECP no NST no desempenho da FV nos pacientes com DP, comparando a FV e o desempenho motor na frequ?ncia baixa (60 HZ) e na frequ?ncia alta (130 Hz), avaliando a qualidade de vida e correlacionando os fatores sociodemogr?ficos, como idade e escolaridade e os h?bitos de leitura e escrita com a FV. ? um estudo experimental randomizado duplo-cego. A amostra inicial foi composta por 25 indiv?duos, sendo que 5 foram exclu?dos por n?o cumprirem os crit?rios de inclus?o. Assim, foram inclu?dos na amostra 20 sujeitos de 30 a 75 anos de idade (56,7 ? 10,7), com escolaridade m?dia de (10,1 ? 5,2), sendo 16 homens e 4 mulheres. Os participantes foram avaliados por tarefas de FV fon?mica e categ?rica, por uma escala motora (UPDRS III), por um question?rio de qualidade de vida (PDQ-39) e por h?bitos de leitura e escrita. A avalia??o da FV e motora foi realizada ap?s uma hora do ajuste da frequ?ncia em alta (130 Hz) e baixa (60 Hz), sendo que a ordem de ajuste das frequ?ncias foi randomizada. Os pacientes com DP submetidos a ECP-NST apresentaram decl?nio na FV fon?mica na frequ?ncia alta. N?o houve correla??o quanto ? idade e escolaridade dos participantes quando comparados ? FV. A frequ?ncia alta (130 Hz), da ECP-NST, causou decl?nio na FV e n?o houve correla??o com fatores sociodemogr?ficos, como idade e escolaridade.