No description available.

Liu, Yanan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 87-98). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Selenium (Se) is an essential trace element, which, with multiple oxidation states and six stable isotopes, has the potential to be a powerful paleo-environmental proxy. In this study, Se concentrations and isotopic compositions were analyzed in a suite of about 120 samples of fine-grained marine sedimentary rocks and sediments spanning the entire Phanerozoic. While the selenium concentrations vary greatly (0.22 to 72 ppm), the δ82/76Se values fall in a fairly narrow range from -1 to +1 , with the exception of laminated black shales from the New Albany Shale formation (Devonian), which have δ82/76Se values of up to +2.20 . Black Sea sediments (Holocene) and sedimentary rocks from the Alum Shale formation (Late Cambrian) have Se/TOC ratios and δ82/76Se values close to those found in modern marine plankton (1.72x10-6±1.55x10-7 mol/mol and 0.42±0.22 ). (Note: TOC = total organic carbon.) For the other sedimentary sequences, the Se/TOC ratios indicate enrichment in selenium relative to marine plankton. Additional input of isotopically light terrigenous Se (δ82/76Se ≈ -0.42 ) may explain the Se data measured in recent Arabian Sea sediments (Pleistocene). The very high Se concentrations in sedimentary sequences that include the Cenomanian-Turonian Ocean Anoxic Event (OAE) 2 possibly reflect a significantly enhanced input of volcanogenic Se to the oceans. As the latter has an isotopic composition (δ82/76Se ≈ 0 ) not greatly different from marine plankton, the volcanogenic source does not impart a distinct signature to the sedimentary Se isotope record. The lowest δ82/76Se values are observed in the OAE2 samples from Demerara Rise and Cape Verde Basin cores (δ82/76Se = -0.95 to 1.16 ) and are likely due to fractionation associated with microbial or chemical reduction of Se oxyanions in the euxinic water column. In contrast, a limiting availability of seawater Se during periods of increased organic matter burial is thought to be responsible for the elevated δ82/76Se values and low Se/TOC ratios in the black shales of the New Albany Shale formation. Overall, our results suggest that Se data may provide useful information on paleodepositional conditions, when included in a multi-proxy approach.

No description available.

Experiments were conducted to examine the role of dietary selenium (Se) and changes in antioxidant capacity during DMBA-induced mammary carcinogenesis. Weanling rats were fed graded amounts of Se in an AIN-76 diet, modified to approximate the amount and type of dietary fat consumed in Canada. Animals fed 3-4 ppm Se had a reduced tumor incidence but there was evidence of chronic Se toxicity. Low Se did not elevate tumor incidence. Thus, supplemental dietary Se did not offer any protection in reducing the incidence of cancer when rats were fed a diet representative of North American intakes of fat. Blood GSHPx activity was elevated in rats that remained free of tumors (NT group) compared to animals that would eventually develop tumors (WT group). SOD activity was reduced in WT and NT rats, but appeared to be related to carcinogen administration. These differences were observed before tumor development and over a wide range of Se intakes. WT rats excreted more $ sp{75}$Se compared to both control and NT rats. These changes, however, were not reflected in elevated lipid peroxidation. Thus, one of the protective mechanisms during carcinogenesis may be the capacity of the animal to elevate GSHPx activity.

Thesis (Ph. D.)--University of Sydney, 1999. / Title from title screen (viewed Apr. 21, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Dept. of Chemical Engineering, Graduate School of Engineering. Includes bibliography. Also available in print form.

Thesis (M. Sc.)--University of Alberta, 2010. / Title from pdf file main screen (viewed on June 18, 2010). A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Ecology, Department of Biological Sciences, University of Alberta. Includes bibliographical references.

En Chine, une grave maladie musculo-squelettique appelée la maladie de Kashin-Beck (KBD) se retrouve distribué sur une large zone géographique. Cette maladie touche plus de deux millions d'individus, notamment dans le centre de la Chine, et il est admis que plus de 30 millions d’individus seraient à risque. Des études géologiques et épidémiologiques ont montré une forte corrélation entre les zones de déficience en Se dans les sols et de KBD. KBD est une ostéoarthropathie, caractérisée par la destruction des chondrocytes du cartilage, très douloureuse et invalidantes, pouvant conduire à des déformations articulaires importantes. Le sélénium (Se) est présent partout dans l'environnement (eau, air, sols) et nos besoins physiologiques en Se sont couverts par notre alimentation quotidienne (eau, céréales). Bien que cet élément trace soit un nutriment essentiel pour la fonction cellulaire normale, ses mécanismes d’action ainsi que les transformations métaboliques de ses composés dans le corps humain ne sont toujours pas bien déterminés. Toutefois, à une dose un peu supérieure à la dose recommandée, il peut, selon la forme chimique ingéré, devenir toxique. Par conséquent, on retrouve le Se en très faible quantité (µg/L) dans l'organisme, ce qui rend difficile sa localisation et l’analyse de son rôle dans le métabolisme. Le Se fait partie de sites biologiquement actifs de protéines impliquées dans les mécanismes antioxydants de défense et le contrôle rédox des réactions intracellulaires. En outre, plusieurs études ont mis en évidence le rôle que joue de Se dans le développement des tissus tels que le cartilage articulaire. Cette action semble être médiée par l'intermédiaire de sélénoprotéines et seraient indirectement impliqués dans la croissance du cartilage normal et l'homéostasie. Aux Etats-Unis, une étude clinique a montré des preuves solides de l’influences d’un déficit en Se dans le métabolisme du cartilage conduisant un environnement favorable à l'apparition et la progression de l'arthrose. Même si le Se n’est pas le seul facteur dans le développement de maladies, il est fort probable que son absence impacte la croissance et le développement du cartilage articulaire. Un modèle in vitro de maturation accélérée du cartilage articulaire (explants) nous a permis d’analyser l'impact du sélénium dans la croissance et le développement de ce tissu. Des expériences biologiques, biophysiques et chimiques ont été réalisées pour comprendre comment la présence de Se affecte l'organisation des tissus. Un schéma récurrent de la distribution du Se dans le tissu a été découvert. Il semble être localisé au niveau des interfaces cellule-matrice, offrant des hypothèses intéressantes pour de futures études sur le rôle potentiel du Se dans la signalisation cellulaire ou transduction mécanique. Des analyses biomécaniques, structurelles et moléculaires ont été faites pour caractériser la matrice extracellulaire du cartilage articulaire traités avec différentes concentrations de Se. Il semble être localisé au niveau des interfaces cellule-matrice, ce qui suggère que le Se joue un rôle dans la signalisation cellulaire ou transduction mécanique. Des analyses biomécaniques, structurelles et moléculaires ont été faites pour caractériser la matrice du cartilage articulaire traités avec différentes concentrations de Se. Nous avons découvert qu’un déficit en Se peut induire à une morphologie proche de celle de l'arthrose lors de la maturation du cartilage immature. Cependant, le rôle exact de ce déficit en Se induisant ce type de phénotype reste inconnu. Ce projet contribue à une meilleure compréhension du Se dans le cartilage tout en montrant les difficultés d’étude du Se dans les milieux biologiques et les techniques permettant d’y répondre, mais aussi souligne l’importance de prendre en compte le Se comme élément important de traitements régénérateurs ou préventifs pour ce types de maladies. / In China, a severe musculoskeletal disease called Kashin-Beck disease (KBD) is largely endemic over a large geographical area. It has been reported that more than 2.5 million people in China suffer from KBD and about 30 million people are at risk. Geological and epidemiological investigations have shown that a strong correlation exists between the location of selenium (Se) deficient soils and the distribution of KBD in the population. The disease is manifested as degradation of the matrix, cell necrosis mainly in the articular and growth plate cartilage, which can result in growth retardation, secondary osteoarthrosis, and disability in daily life. The worst forms of this disease tend to start in childhood, which may lead to dwarfism. Selenium is present everywhere in the environment (water, air, soils) and it is mainly incorporated to the human organism through the daily diet (water, cereals). Although this trace nutriment element is essential for normal cellular function. Most of the selenium-related -functions and pathways remain incompletely understood. Whilst vital for normal function, it is toxic at concentration slightly higher than that required by the body. Consequently, it is present within the organism in parts per billion (microgram per liter) making it difficult to localize and analyze its role in metabolism. Despite being a trace element it is an essential component of antioxidant and anti-inflammatory-related proteins that protect cells against oxidative attack. Furthermore, several studies have exposed the role selenium plays in tissue development such as in articular cartilage. This action seems to be mediated via selenoproteins that are indirectly involved in normal cartilage growth and homeostasis. In the USA, a clinical study has shown strong evidence that Se-deficiency influences cartilage metabolism inducing a favorable environment for the onset and the progression of osteoarthritis. Even if the selenium is not the only factor in the development of degenerative joint disease, it is highly likely that its absence impacts its growth and development of articular cartilage. The main focus of this study was then to understand better the role of Se in the normal metabolic processes of articular cartilage. Cultures of articular cartilage explants were used on a previously validated in vitro model of tissue maturation to analyze the role of selenium in growth and development. Physical and chemical experiments were preformed to understand how the presence of selenium affects tissue organization. It has been possible to determine a fundamental recurrent pattern of Se-distribution in the tissue. It appears to be localized at cell-matrix interfaces and it can be hypothesized that Se plays role in cell signaling or mechanotransduction. Biomechanical, structural and molecular analyses have been made to characterize the extracellular matrix of articular cartilage treated with different concentrations of Se-level. We discovered that Se-deficiency induces morphological changes in the cartilage matrix during the fast maturation-like process, which could be related to degenerative-like morphology of the cartilage. This could potentially be associated with degenerative changes that occur in KBD patient during childhood. This project is a prospective work for a potential future enhancement of the regenerative or preventive treatments for specific musculoskeletal diseases with a metabolic component.

To investigate the whole body metabolism of selenium (Se), isotope kinetic studies were undertaken in which indwelling catheters were implanted in the jugular veins of pregnant and nonpregnant ewes as well as the inferior vena cava and saphenous veins of 110-120 day (d) old ovine fetuses. A single injection of ⁷⁵Se-sodium selenite was administered and blood samples were obtained at various times. A 5 d Se balance trial, which commenced on the day of tracer experiment, was also undertaken. The plasma ⁷⁵Se specific activity data were used for determining the kinetic parameters of Se metabolism and the placental transfer rates. Using the Se balance and tracer data the net absorption and the fecal losses of Se were calculated. The fractional rate constants and T½ Se utilization in individual tissues were estimated by sacrificing the ewes and the fetuses at different times after the tracer injection and determining the tissue ⁷⁵Se specific activities. The effect of Se deficiency on the kinetics, placental transfer, net absorption and tissue metabolism was studied in a similar manner by feeding the ewes with Se deficient rations. The mean plasma Se concentrations in the positive nonpregnant and pregnant ewes were 142 187 ng/ml and were significantly higher than Se and the corresponding values (82 and 69 ng/ml) in the Se deficient ones respectively. The plasma Se levels in the Se positive fetuses (46 ng/ml) were not significantly different from the deficient ones (53 ng/ml). The irreversible disposal (ID) rates of Se were 7 ug/d/kg body weight (B.W.) in both nonpregnant and pregnant ewes, whereas, these values declined to 2 ug/d/kg B.W. under deficiency conditions. The ID values in the Se positive and deficient fetuses were 20 and 11 ug/d/kg B.W. respectively. These results indicated that the plasma Se turnover was lower in Se deficient animals than in the positive ones and that the fetuses had a higher turnover than adult ewes irrespective of the maternal Se status. Values for net Se absorption (% Se intake) and fecal Se losses (ug/d) in the Se positive nonpregnant ewes were 51% and 272 ug/d versus 97% and 25 ug/d in the Se deficient ones. The corresponding values for the Se positive pregnant ewes were 56% and 241 ug/d as against 84% and 27 ug/d in the deficient ones. These results suggested that the efficiency of net Se absorption expressed as the percent of Se intake decreased with increasing Se intakes and that the fecal route exerted a homeostatic control on Se metabolism in ewes. The tissue Se concentrations were significantly higher in the Se positive animals than in the deficient ones, whereas, the tissue fractional rate constant values were higher in the Se deficient animals than in the positive ones. These results implied that the tissue Se concentrations were significantly decreased under Se deficiency conditions and that the Se turnover was higher in tissues when the dietary Se intake was minimal. The placental transfer studies showed that there was a bidirectional exchange of Se across the placenta. The placental Se transfer rates from ewe to fetus declined from 53 ug/d in the positive ewes to 29 ug/d in the deficient ones. The rate of Se transfer from fetus to ewe also decreased from 24 ug/d in the positive ewes to 12 ug/d in the deficient ones. The net placental Se transfer was found to be reduced under conditions of decreased maternal dietary supply. The nutritional implications of Se status of the pregnant ewes on the availability of the trace mineral to the fetus have been discussed. / Land and Food Systems, Faculty of / Graduate

Gas chromatography mass spectrometry (GCMS) and inductively coupled plasma mass spectrometry (ICPMS) were evaluated for the measurement of selenium (Se) and Se stable isotope ratios. GCMS and ICPMS were found to be accurate for quantitative Se analysis in biological matrices by isotope dilution using Se-78 and Se-76 as internal standards, respectively. A higher precision was obtained for ICPMS than GCMS enabling a smaller quantity of the tracer to be administered to subjects in labelling experiments. The isotopes of choice for metabolic tracers were Se-76 when sample analysis was by GCMS and Se-77 and Se-82 when analysis was by ICPMS. The influence of copper (Cu) on endogenous fecal Se excretion and true absorption of Se in nonlactating Holstein cows was examined by the use of Se stable isotopes as tracers. The method involved the application of conventional balance techniques in conjunction with isotopic enrichment of the body Se pools. Selenium in several tissues following oral and intravenous routes of isotope administration were evaluated as the precursors of endogenous fecal Se. Two cows fed a Se deficient diet (0.035 mg kg⁻¹) were administered 4 mg Se-76 orally, daily, for 5 d. After a 10-d equilibration period total collection of feces was made daily for two 5-d periods. The animals were then sacrificed and samples obtained from all major tissues and fluids. Se-7 6 enrichment (tracer/tracee mass percent, TTMP) in tissues was variable (< 0.56 - 13.4). However, enrichment was similar (9.8 - 12.9) in the tissues considered as potential contributors to endogenous fecal Se (serum, epithelium of the stomach, liver, bile, pancreas, small intestine and colon). Enrichment in serum and liver was used to calculate endogenous fecal Se. Apparent absorption of Se in the two cows was negative (-37 and -147 µg d⁻¹). Correction of apparent absorption for the fecal Se of endogenous origin gave a true Se absorption (% of intake) of 10 and 16%. The percentage of total fecal Se of endogenous origin was 23 and 36%. In two trials, 5 or 6 cows were assigned to one of two Cu-supplemented treatment diets: 0 mg kg⁻¹ or 17 mg kg⁻¹. The basal diet contained 0.19 mg Se kg⁻¹ and 13 mg Cu kg⁻¹. To each cow ~4.6 mg Se-77 and ~1.3 mg Se-82 were administered by oral and intravenous routes, respectively. After a 14-d equilibration period, total collection of feces and urine were made daily for two 5-d periods. Serum was collected on the first, third and fifth days of each period. Liver biopsies were taken 2 d following the completion of the balance periods. The estimates of endogenous fecal Se ( d⁻¹) from enrichment in the serum (256) and liver (235) following oral administration of the tracer and from enrichment in serum (241) following intravenous administration were not significantly different (P>0.05) but were higher than the estimate from the enrichment in liver (197) (P<0.05). No significant differences (P>0.05) were present when true absorption ( µg d⁻¹) was determined from enrichment in serum (290) or liver (268) following oral administration or from enrichment in serum (274) or liver (230) following intravenous administration. It was concluded the analysis of serum or liver with oral administration or the analysis of serum with intravenous administration of the tracer would provide reliable methods for estimation of endogenous fecal Se and true absorption. There was no effect of Cu on endogenous fecal Se excretion or true absorption of Se. Apparent and true absorption were 3.2 and 11%, respectively. Approximately 90% of the total Se excreted was in the feces, of which, 9.7% was of endogenous origin. The use of Se stable isotopes as metabolic tracers in dairy cattle provided a safe alternative to the use of radioactive tracers and enabled experiments requiring multi-isotopic enrichment to be performed. / Land and Food Systems, Faculty of / Graduate