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Made available in DSpace on 2014-06-11T19:27:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-12Bitstream added on 2014-06-13T20:56:35Z : No. of bitstreams: 1 oliveira_aps_me_arafcf.pdf: 946584 bytes, checksum: 6c4fbb82549dc1046e8b7771847a8f5b (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A família Eriocaulaceae possui cerca de 1200 espécies divididas em 10 gêneros e suas espécies de plantas são conhecidas como sempre-vivas, por sua grande durabilidade e coloração paleácea. Neste trabalho foram estudadas as espécies: Eriocaulon ligulatum, Leiothrix flavescens e Leiothrix spiralis, as quais foram avaliadas quanto à mutagenicidade e estrogenicidade e algumas substâncias isoladas foram utilizadas para um estudo de relação estrutura-atividade mutagênica e estrogênica. Para avaliação da mutagenicidade, utilizou-se o teste de Ames, e o teste RYA (Recombinant Yeast Assay) foi o empregado para avaliação da estrogenicidade. Os resultados da atividade mutagênica demonstraram que apenas E. ligulatum foi considerado mutagênico e isso foi atribuído às isocumarinas e flavonóides agliconas. Os estudos de relação estrutura-atividade mutagênica mostraram que esta ação foi devida à presença de hidroxilas em posições estratégicas e à ausência de glicosilações, metoxilações, ou qualquer outro tipo de substituição. Para complementar os estudos de relação estrutura-atividade mutagênica com as isocumarinas, utilizou-se resultados já publicados de mutagenicidade de moléculas semelhantes à isocumarina eriocaulina, isolada de E. ligulatum. Verificou-se que os dímeros de isocumarinas têm a sua mutagenicidade influenciada pela conformação espacial, pela presença de grupos hidroxilas mais afastados de grupos volumosos, e pelo tipo de ligação que une os seus monômeros. Quando o potencial estrogênico foi avaliado, apenas a L. flavescens apresentou resultados positivos e que esses são devidos à presença de flavonas agliconas, como a luteolina e a metoxiluteolina. As mesmas isocumarinas, pertencentes a outras espécies da família Eriocaulaceae, avaliadas no teste de Ames, foram avaliadas no teste RYA... / Eriocaulaceae family comprises around 1200 species, divided into 10 genera, and their plant species are known as “sempre-vivas” (everlasting flowers) for its durability and color. In this work the species Eriocaulon ligulatum, Leiothrix flavescens and Leiothrix spiralis were studied. These species were evaluated for the mutagenic and the estrogenic potential and some of their isolated compounds were used for a study of structuremutagenic and estrogenic activities. To assess mutagenicity we used Ames test and the Recombinant Yeast Assay (RYA test) was used for evaluation of estrogenicity. The results of mutagenic activity showed that only E. ligulatum presented mutagenicity and that these results were due to its naphthopyranones and flavonoid aglicons. The structuremutagenic activity studies shown that this action were due to the presence of hydroxyl groups in strategic positions and no glycosylations, methoxylation or any type of substitutions. To complement the studies of structure-mutagenic activity with the naphthopyranones, we use results already published of the mutagenicity of similar compounds to the naphthopyranone eriocaulina, isolated from E. ligulatum, and compare them with the data from ericauline. It was found that the dimers of naphthopyranones have their mutagenicity influenced by its spatial conformation, for the presence of hydroxyl groups furthest away from large groups, and the type of connection that join their monomers. When the estrogenic potential was assessed, we found that only L. flavescens showed positive results and that these results are due to the presence of flavones in the form of aglycones, such as luteolin and methoxyluteolin. The same naphthopyranones belonging to other species of Eriocaulaceae family, evaluated in the Ames test, were assessed in the RYA test. Their results were crucial for the establishment of structureestrogenic activity... (Complete abstract click electronic access below)

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Thesis (Th. M.)--Calvin Theological Seminary, 1990. / Abstract. Includes bibliographical references (leaves [234]-250).

Thesis (Th. M.)--Calvin Theological Seminary, 1990. / Abstract. Includes bibliographical references (leaves [234]-250).

Thesis (Ph. D.)--Columbia University, 1942. / Reproduced from type-written copy. "This study ... is part of a projected full length biography of David A. Wells."--Pref. Vita. Bibliography: p. [317]-330.

Ames dwarf mice have a spontaneous homozygous Prophet of Pituitary Factor 1 (Prop1) loss-of-function mutation. The Prop1 mutation results in a lack of differentiation of lactotrophs, thyrotrophs, and somatotrophs in the anterior pituitary. Without these endocrine cell types, Ames dwarf mice have essentially no circulating levels of growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin, and exhibit downstream hormonal deficiencies including insulin-like growth factor 1 (IGF-1), 3’,3,5-triiodothyronine (T3), and thyroxine (T4). Ames dwarf mice are exceptionally long-lived (40% to over 60% depending on sex and diet). They are also extremely insulin sensitive, have a delayed incidence of cancer, and have improved energy metabolism. While the extended lifespan and the many characteristics of an extended healthspan have been known for some time in Ames dwarf mice, the revelation that dwarf mice have improved energy metabolism was less than a decade ago. This finding came about at the molecular level (improved efficiency of the electron transport chain) and at the whole-animal level (increased oxygen consumption and decreased respiratory quotient). To date, however, few studies have been directed at furthering our understanding of the possible mechanism(s) by which Ames dwarf mice have altered energy metabolism. The goal of the studies presented in this dissertation is to delineate these mechanisms and to lay the groundwork for future studies that broaden our understanding of the role(s) of energy metabolism in the aging process. Project 1 examines the effects of early-life T4 replacement therapy in Ames dwarf mice. Previous work established that life-long T4 replacement therapy shortens lifespan in Snell dwarf mice (these mice have endocrine deficits that are essentially identical to those of Ames dwarf mice), while short-term replacement therapy during the early postnatal period of Ames dwarf mice does not. We hypothesized that T4 replacement therapy causes transient impairment of energy metabolism, which is why long-term T4 replacement therapy shortens longevity, and short-term replacement therapy does not. Supporting our hypothesis, we showed that short-term T4 replacement therapy during the early postnatal period transiently impaired energy metabolism as measured by indirect calorimetry. Following early-life T4 replacement therapy, we also observed an accelerated rate of sexual development, as well as lasting effects on bone physiology. Project 2 continued our investigation of energy metabolism by examining a highly metabolic tissue: brown adipose tissue (BAT), which is responsible for non-shivering thermogenesis. Our laboratory has already demonstrated functional alterations in visceral adipose tissue of Ames dwarf mice, and given the altered energy metabolism of Ames dwarf mice, we hypothesized that BAT may also be functionally unique compared to their normal littermates. Supporting our hypothesis, we observed alterations in gene expression, relative weight, and histological structure of BAT in Ames dwarf mice. Moreover, surgical removal of the interscapular BAT depot resulted in a unique physiological response, where Ames dwarf mice lost adiposity in their subcutaneous, perirenal, and epididymal white adipose tissue depots, thus contrasting with normal mice that gained adiposity. Project 3 built upon the findings of our second study, where we continued to examine the role of non-shivering thermogenesis and core body temperature in Ames dwarf mice. To further understand the role of non-shivering thermogenesis in glucose homeostasis and energy metabolism, we housed a cohort of Ames dwarf mice and their normal littermates at room temperature (23˚C), and another cohort at thermoneutrality (for mice this is 30˚C). We found that Ames dwarf mice placed at thermoneutrality had impaired glucose homeostasis and energy metabolism. This is an important finding because we and others believe both of these metabolic processes are important factors for longevity. Taken together, these studies indicate that the improved energy metabolism in Ames dwarf mice is dependent upon several factors, including a loss of thyroid hormone signaling and improved non-shivering thermogenesis.

This study characterizes 21 wastewater samples collected from Al-Amal hospital between the period of 12 April till 8 July 2020. Al Almal is a hospital that provides drug addiction and psychological treatment to patients. Using solid-phase extraction and liquid chromatography with tandem mass spectrometry (LC-MS/MS), chemical contaminants profiles in these wastewater samples were determined in a non-targeted manner. These chemicals were then individually analyzed in an in-silico manner by checking against databases and literature to determine if they were mutagenic. By determining the proportion of mutagenic chemicals against the non-mutagenic ones, we aim to determine if untreated hospital wastewater may potentially negatively impact the downstream municipal biological wastewater treatment process. It was determined that 64% of the identified chemicals were not tested for their mutagenic effect, and hence no prior information is available in the literature and databases. Instead, we further performed in-vitro mutagenicity tests using Ames test to determine if the wastewater sample, with all of its chemical constituents, would be mutagenic. Ames test results showed that majority of the samples were non-mutagenic except for 1 sample that imposed a mutagenic effect on Salmonella enterica serovar Typhimurium TA98 and 3 samples with mutagenic effect on TA100. In addition, 1 sample showed a toxic effect on TA100. However, in all 5 instances, these samples only imposed a mutagenic and toxic effect at high concentrations of > 10x. The findings in this study suggest that a specialty hospital like Al Amal does not contribute substantially to mutagenic wastewater streams to the municipal sewer, and hence unlikely to significantly perturb the downstream biological treatment processes. However, there may still be a need to consider ad-hoc contributions of mutagenic and/or toxic wastewater streams from the hospitals.

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