We can construct asymmetric glutarimide while using [3+3] annulation.Then we can build substituent group in C6 position after choosing regioselective addition reaction, and then apply it to synthetic studies toward polysubstituted pyridin-2-ones and Vitamin B6 derivatives.

none

No abstract available. / Thesis (M.Sc.)-University of Durban-Westville, 1990.

We investigated the effect of pyridoxine supplementation on the utilization of protein in a low-protein, plant-based diet in four subjects (2 men and 2 women), aged 21 to 38 years. Following two days of a negligible protein diet, this 34 day study was divided into three dietary periods: the subjects received a low-protein, plant-based diet during period I for 10 days (no pyridoxine supplement), the same diet but with the addition of 50 mg pyridoxine HCl during period II for 7 days, and their self-chosen diets during period III for 15 days (no pyridoxine supplement). Data for period III will be reported elsewhere. The greatest portion of protein in the experimental diet was furnished by pinto beans (1.02 g nitrogen) and peanut butter (0.86 g nitrogen); nitrogen intake was kept constant at 4.56 g/d for the men and 4.15 g/d for the women during periods I and II. These diets administered during periods I and II provided 0.907 mg of vitamin B-6 for the men and 0.758 mg of vitamin B-6 for the women and was adequate in other nutrients except for protein. Overall, the effect of 50 mg pyridoxine HC1 supplementation on the utilization of protein in a low-protein plant-based diet was not statistically significant (p > 0.05) on the basis of a paired t-test for the parameters measured: nitrogen balance, apparent protein digestibility, as well as plasma and urinary urea nitrogen. Furthermore, we obtained conflicting results, when the subjects received pyridoxine, their plasma urea nitrogen increased slightly (suggesting increased protein degradation), while the percent of total urinary nitrogen excretion as urea nitrogen decreased (suggesting decreased protein degradation). These changes were not statistically significant, but limitations in the nitrogen balance technique and the analytical procedures we used may have contributed to these conflicting results. We suggest that a longer study with more subjects may show a greater improvement of plant protein utilization than we had observed. / Graduation date: 1990

Graduation date: 1993

Thesis (Ph. D.)--Oregon State University, 2008. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (Ph. D.)--Oregon State University, 2008. / Includes bibliographical references.

Thesis (M.Sc. (Nutrition))--Mahidol University, 1979.

Made available in DSpace on 2014-12-17T14:05:22Z (GMT). No. of bitstreams: 1 LeonamGC_TESE.pdf: 2406262 bytes, checksum: 604659dd8ff62335f952679dda971b6e (MD5) Previous issue date: 2013-03-19 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-?. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition / A meningite bacteriana (MB) ? uma doen?a infecciosa que permanece com altas taxas de mortalidade e morbidade em todo o mundo, principalmente em pa?ses subdesenvolvidos, apesar dos avan?os na antibioticoterapia. Um dos principais mecanismos associados ?s sequelas durante a MB ? a elevada resposta inflamat?ria, que promove uma exacerbada quantidade de esp?cies reativas de oxig?nio (ERO) levando ?s c?lulas a apoptose ou necrose. A ativa??o de enzimas de reparo de DNA durante o estresse oxidativo tem sido demonstrada nas mais diversas desordens. Uma importante enzima envolvida neste processo ? a endonuclease apur?nica/apirimidinica1/fator redox-1 (APE1/Ref-1). Ela ? uma prote?na multifuncional envolvida no reparo de DNA e na redu??o de fatores envolvidos com a resposta inflamat?ria, tais como o fator nuclear kappa B (NFkB) e prote?na ativadora 1 (AP-1). Este estudo teve como objetivo identificar o envolvimento de APE1/Ref-1 na resposta inflamat?ria visando a possibilidade de sua utiliza??o como alvo terap?utico na redu??o de sequelas durante a MB. Para isto, inicialmente foi realizado uma an?lise no perfil de express?o de citocinas em l?quor de pacientes com meningite causada por Streptococcus pneumoniae e Neisseriae meningitidis visando selecionar moduladores inflamat?rios de interesse para ensaios em cultura de c?lula subsequentes. Em seguida, utilizando um modelo celular de indu??o com LPS foi avaliado o efeito da inibi??o da atividade de reparo e redox de APE1 sobre a express?o de citocinas inflamat?rias. Por fim, foi observada a express?o de APE1 no c?rtex (CX) e hipocampo (HC) de ratos com MB frente a uma terapia adjuvante com vitamina B6. Nossos resultados mostraram um perfil de moduladores inflamat?rios muito semelhante no l?quor dos pacientes com MB causada pelos pat?genos estudados, embora interferon gama (IFNy) tenha sido VI significativamente mais expresso em pacientes com S. pneumoniae do que N. meningitidis. Quanto ao uso dos inibidores das fun??es, redox e de reparo, de APE1/Ref-1 no modelo in vitro, houve redu??o significativa na express?o de algumas citocinas, principalmente o fator de necrose tumoral-alfa (TNF-?). Al?m disso, os inibidores demonstraram uma redu??o nos n?veis de ERO nas c?lulas estimuladas com LPS. No modelo animal, a express?o prot?ica de APE1/Ref-1, no CX e HC dos ratos, foi modulada ap?s introdu??o da vitamina B6. Portanto, esses dados fornecem um novo olhar para a fisiopatologia da MB, em que citocinas como IFNy podem ser usadas em um diagn?stico diferencial entre meningites causadas por S. pneumoniae e N. meningitidis. A prote?na de reparo de DNA, APE1/Ref-1, parece ser um alvo potencial na modula??o da resposta inflamat?ria e do estresse oxidativo, bem como a terapia adjuvante com vitamina B6 mostra ter um papel sobre a express?o de APE1/Ref-1. Consequentemente, o conhecimento obtido neste estudo pode ser importante na melhoria do progn?stico da MB, al?m de contribuir para entender a associa??o entre o reparo de DNA e inflama??o / 2020-01-01 / 2020-01-01

Made available in DSpace on 2015-04-17T15:03:00Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 925146 bytes, checksum: 6a5a1d5bf083b5c0885403bb087cc93a (MD5) Previous issue date: 2013-03-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The objective this study was to investigate the potential anxiolytic Magnesium and Vitamin B6 in college students using a model of experimental induction of anxiety, through the assessment of physiological and psychological parameters. The study was an experimental, randomized and controlled. It was composed of sixty students, female, distributed in one of four experimental groups: Control; Magnesium, Magnesium + B6, Vitamin B6. The human anxiety was induced by Simulated Public Speaking (TSFP) and was assessed by physiological parameters (Systemic Blood Pressure, Heart Rate, Temperature of Extremity , Electrical Skin Conductance) and psychological parameters (State - Trait Anxiety Inventory). The behavior of physiological and psychological measures was accompanied on the four times of testing, Baseline (B), Pre - stress (PT), Performance (S) and Final (F) and were evaluated in two ways: behavior between the supplemented groups and between the phases in each respective time groups. During speech, the diastolic blood pressure was lower in B6 versus control (P <.05), there was also a decrease in the conductance B6 group (P <0.01) in the Magnesium + B6 group (P <0.05) and group B6 (P <0.05) compared to the control group. In the final moment, the conductance was lower in B6 compared with controls (P <0.05). The STAI-T showed that the university had moderate levels of anxiety (STAI-T 40-60 points). In the comparison between groups was observed that all individuals of the respective groups already started the test with a moderate degree of anxiety (STAI-E 40 - 60 points). At the last moment there was a decrease in E-STAI score in both groups, where they began to be classified with low levels of anxiety (STAI-E <40 points) (P> 0.05). The use of magnesium and vitamin B6, at a concentration of 200 mg enough results showed that proves its efficacy in controlling some symptoms of anxiety induced experimentally here, exhibited lower values for CEP and anticipatory anxiety having vitamin B6 submitted lower values of DBP at the performance of the speech, which means to say that in the control group participants showed less variability. / O objetivo deste estudo foi investigar o potencial ansiolítico do Magnésio e da Vitamina B6 em estudantes universitárias utilizando um modelo de indução experimental de ansiedade, por meio da avaliação dos parâmetros fisiológicos e psicológicos. O estudo teve caráter experimental, randomizado e controlado. Foi composto por sessenta estudantes, do sexo feminino, distribuídas em um dos quatro grupos experimentais: Controle; Magnésio; Magnésio + B6; Vitamina B6. A ansiedade humana experimental foi induzida pelo Teste de Simulação de Falar em Público (TSFP) e foi avaliada por meio de parâmetros fisiológicos (Pressão Arterial Sistêmica, Frequência Cardíaca, Temperatura de Extremidades, Condutância Elétrica da Pele) e de parâmetros psicológicos (Inventário de ansiedade Traço e Estado). O comportamento das medidas fisiológicas e psicológicas foi acompanhado nos quatro momentos do teste, Basal (B), Pré - estresse (PT), Performance (S) e Final (F) e foram avaliados de duas formas: comportamento entre os grupos suplementados e entre as fases em cada um dos respectivos grupos.No momento do discurso a pressão arterial diastólica foi menor no grupo B6 comparado ao controle (P<0,05), houve ainda diminuição da condutância no grupo B6 (P<0,01), no grupo Magnésio + B6 (P<0,05) e no grupo B6 (P<0,05) comparados ao grupo controle. No momento final a condutância foi menor no grupo B6 comparado ao controle (P<0,05). O IDATE-T demonstrou que as universitárias apresentavam níveis de ansiedade moderado (IDATE-T 40-60 pontos). Na comparação entre os grupos observou-se que todos os indivíduos dos respectivos grupos já iniciavam o teste com um grau de ansiedade moderada (IDATE-E 40 - 60 pontos). No momento final houve diminuição no escore do IDATE-E em ambos os grupos, onde os mesmos passaram a ser classificados com grau de ansiedade baixa (IDATE-E < 40 pontos) (P>0,05). A utilização de Magnésio e de vitamina B6, na concentração de 200 mg apresentou resultados suficientes que comprovam sua eficácia no controle de alguns sintomas da ansiedade, aqui induzida de forma experimental, apresentando menores valores de CEP durante a ansiedade antecipatória e tendo a vitamina B6 apresentado valores menores da PAD no momento da performance do discurso, o que significa afirmar que em relação ao grupo controle as participantes apresentaram menor variabilidade.