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Fresen, John Lawrence. "Statistical aspects of bioavailability." Master's thesis, University of Cape Town, 1985. http://hdl.handle.net/11427/17004.
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Includes bibliography.In 1984 it became legal for pharmacists to offer customers a cheaper generic alternative for a given prescription. The motivation for this was the excessively high cost of brand name drugs. The substitution of a generic alternative for a brand name drug is based on the assumption that drugs with a comparable chemical composition will have a similar therapeutic effect. The fact that this supposition is not always true has been demonstrated by a number of particular drugs, digoxon being perhaps the most vivid example. The objective of this thesis is to review the statistical aspects associated with (i) measuring the bioavailability of a drug (Chapter 2) (ii) establishing the equivalence of a new and standard formulation of a drug (Chapter 3). In the process of reviewing the literature two problems were identified. Firstly, it is commonly assumed that bioavailability parameters follow either the normal or lognormal distribution. This assumption is difficult to defend, hence procedures based on such assumptions became suspect. Secondly, bioavailability is inherently multivariate whereas in practice univariate procedures are employed. Efren's bootstrap method, which does not rest on assumptions about the underlying distribution, is proposed as a tool for assessing bioequivalence. A new measure of bioequivalence, the Index of Concordance, is proposed. This index can be computed with equal ease for univariate or multivariate data using the bootstrap (Chapter 5). The bootstrap idea of resampling the data can also be applied to compartmental modelling of bioavailability data. One result of this is a nonparametric estimate of the underlying distribution of the bioavailability parameters (Chapter 6). The bootstrap is, on its own, a fascinating concept. A review of the bootstrap is given in Chapter 4.
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Menjoge, A. R. "Enhancing bioavailability of drugs." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2006. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2512.
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Montaseri, Hashem. "Taxol, solubility, stability, and bioavailability." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/nq21604.pdf.
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Stroud, Jacqueline L. "Bioavailability of hydrocarbons in soils." Thesis, Lancaster University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441365.
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Jaganath, Indu Bala. "Dietary flavonoids : bioavailability and biosynthesis." Thesis, University of Glasgow, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418903.
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Jugdaohsingh, Ravin. "Soluble silica and aluminium bioavailability." Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312026.
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Re, Roberta. "Lycopene : antioxidant properties and bioavailability." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248044.
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Muchow, Marc. "Nanocarriers for oral bioavailability enhancement." Thesis, Nancy 1, 2009. http://www.theses.fr/2009NAN10073/document.
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Le but général de ce travail correspond à l’amélioration de la biodisponibilité de principes actifs connus pour leur faible biodisponibilité (testostérone) ou pour leur caractère lipidique (acides gras oméga 3). Des systèmes nanoparticulaires à base de lipides et des systèmes nanocristaux ont été développés notamment dans le cas de la testostérone, afin d’obtenir une biodisponibilité supérieure au système oral actuellement commercialisé, Andriol Testocaps®. L’autre partie de ce travail consistait en la conception d’une formule d’acides gras omega -3 dans des nanoparticules lipidiques, susceptibles malgré l’utilisation d’une huile de poisson bon marché comme source d’acides gras omega-3, de n’avoir que peu d’effets sur le goût et l’odorat tout en s’avérant stable. Le développement de systèmes oraux à base de testostérone a été possible autant sur la base de la technologie des nanoparticules lipidiques (Nanostructured Lipid Carriers, NLC), que sur celle des nanocristaux. Dans les deux cas, les systèmes développés ont permis de répondre aux exigences en matière d’incorporation (NLC) et de stabilité (NLC et suspensions Nano). Les NLC ont permis d’incorporer jusqu’à 30% d’undecanoate de testostérone en phase lipidique. La formulation a également été possible avec différents lipides, susceptibles, d’augmenter l’absorption lymphatique et de ce fait également la biodisponibilité de l’hormone. Les nanocristaux ont pu être produits à partir de la testostérone (T) ainsi que d’undecanoate de testostérone (TU), avec des tailles moyennes respectives d’environ 470 nm (TU) et 860 nm (T). Cette taille particulaire doit permettre une absorption lymphatique accrue. Les biodisponibilités des systèmes développés à base de NLC, se sont avérées, chez le rat Wistar, toujours plus élevées que la formulation commerciale, quand ils ont été administrés sans lipides additionnels ce qui permet de supposer, que l’influence simultanée de l’absorption de nourriture sur la biodisponibilité devrait être moins prononcée qu’elle ne l’est pour l’Andriol Testocaps®. En partant de ces résultats, à savoir l’augmentation de la biodisponibilité orale avec les nanoparticules lipidiques, le développement d’un système de nanoparticules avec les acides gras oméga-3 d’huile de poisson bon marché était un pas logique. La biodisponibilité orale des acides gras oméga-3 est largement supérieure à celle du TU (environ 70 %). L’utilisation de la technologie NLC a ainsi permis la réduction de l’odeur et du goût du produit. La formulation avait un pourcentage remarquablement élevé de 70 % en phase lipidique tout en restant pâteuse et redispersible. Ceci permet d’envisager son utilisation dans des boissons et dans la nutrition ce qui facilitera l’assistance des patients (et donc la biodisponibilité) avec les acides gras omega-3 essentielsThe overall goal of this work consisted in ameliorating the bioavailability of drugs known for their poor hydrosolubility (testosterone) or for their lipidic character (omega-3 fatty acids). This was achieved using lipid nanoparticle systems and nanocrystals In case of testosterone the work consisted of the development of an oral dosage form with superior properties compared to the currently commercially available oral system (Andriol Testocaps®). The other part of this work was the design of a lipid nanoparticle-based omega- 3 fatty acid formulation, which, despite the use of cheap fish oil as source of omega-3 fatty acids, has low smell and taste properties while nevertheless being stable. The development of the oral testosterone drug delivery system was accomplished on the basis of lipid nanoparticles technology and also using drug nanocrystal technology. In both cases, systems could be developed that met the requirements with regards to drug loading (NLC) and stability (NLC and drug nanocrystals). Up to 30 % of testosterone undecanoate could be incorporated into the lipid phase of the NLC. Furthermore, the production of particles with different lipids, which are supposed to promote lymphatic absorption and hence the bioavailability of the hormone. Drug nanocrystals of testosterone (T) and testosterone undecanoate (TU) were prepared with a mean size of about 470 nm (TU) and 860 nm (T). Also with this system, an enhanced lymphatic absorption was expected. The bioavailabilites of the developed NLC based drug delivery systems were all higher than the bioavailability of the product on the market when no additional lipid was supplied. This gives reason to believe, that the influence of co-administered food on the bioavailability of the systems is less pronounced than with Andriol Testocaps®. Based on the findings that lipid nanoparticles can improve oral bioavailability, the development of an omega-3 fatty acids nanoparticulate system (NLC) out of cheap fish oil was a logic step. The oral bioavailability of the omega-3 fatty acids is much higher than the one of TU (about 70 %). Through the use of NLC technology, the taste and smell is even more reduced. It was rather unexpected that we achieved to have a formulation that consisted of 70 % lipid phase (and 30 % water) but still was paste-like and easy to redisperse. This makes the use of the paste as an additive in food and beverages possible to better supply the patient with essential omega-3 fatty acids
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Koprivnjak, Jean-François. "Natural Organic Matter: Isolation and Bioavailability." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/14564.
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Electrodialysis (ED) experiments were conducted on reverse osmosis (RO)-concentrated solutions of NOM from six rivers. The ED processes successfully recovered 88 11% of TOC, and removed 83% 19% of SO42- and 67% 18% of H4SiO4. More importantly, the molar ratios of SO42- /TOC and H4SiO4 /TOC were reduced to a mean value of 0.0046 and 0.032, respectively, surpassing the goal for removal of SO42- (0.008) and almost achieving the goal for removal of H4SiO4 (0.021). The ED process can lower the SO42- /TOC ratio in samples whose initial SO42- /TOC ratios are already far below the limit of 0.008 used in this study. The coupled RO/ED process that has been described here offers a fast, simple, chemically mild (relative to other methods), and reproducible method of isolation of large quantities of relatively unfractionated, low-ash NOM from freshwaters.
RO/ED was also successfully used for isolating and concentrating marine dissolved organic matter (DOM). The effort successfully recovered a median of 72% of the TOC from 200 L samples within six to nine hours of processing through a combination of ED and RO, greatly exceeding the current norm of 30%. The relatively high recovery of DOM implies that classes of DOM previously missing are included in these samples and should yield new insight into the chemistry of marine DOM.
Freshwater samples processed by electrodialysis were analyzed for elemental composition and by capillary zone electrophoresis (CZE), 1H and 13C nuclear magnetic resonance spectroscopy (NMR), and electro-spray ionization mass spectrometry (ESI-MS). Bulk elemental composition, 1H- and 13C-NMR, and ESI-MS data provide evidence linking bioavailabilty to the bulk chemistry of NOM: the H/C and N/C molar ratios are positively and strongly correlated with bioavailability, as hypothesized.
Using an independent dataset (STORET) of water quality parameters, calculated BOD/TOC ratios were found to be moderately correlated with measured bioavailabilities and can be used as a surrogate for bioavailability of geochemically diverse riverine DOM.
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Koprivnjak, Jean-Franȯis. "Natural organic matter isolation and bioavailability /." Available online, Georgia Institute of Technology, 2007, 2007. http://etd.gatech.edu/theses/available/etd-04082007-154052/.
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Thesis (Ph. D.)--Earth and Atmospheric Sciences, Georgia Institute of Technology, 2007.Perdue, E. Michael, Committee Chair ; Ingall, Ellery, Committee Member ; Stack, Andrew, Committee Member ; Nenes, Athanasios, Committee Member ; Pfromm, Peter, Committee Member.
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Voigt, Astrid. "Bioavailability of trace metals to plants." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19561.
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Soil quality guidelines are currently based on total trace metal loads. There is a need to define indices of bioavailability to allow reasonable predictions for plant metal uptake and toxicity in soils. Trace metal toxicities to plants often correlate best with free metal ion activities. The first objective was to develop a plant bioassay that is sensitive to trace metals at concentrations realistic for soils. The root elongation of lettuce Lactuca sativa 'Buttercrunch' was used as toxicological endpoint. This endpoint was sensitive and reproducible to environmentally relevant concentrations of Cd, Cu, Ni, Pb and Zn. The second objective was to test whether free metal ion activities are constant predictors of metal toxicities in synthetic solutions and in soil extracts that differ in their concentrations of cations and ligands. The root elongation assay was used to test this hypothesis. In synthetic solutions, the rhizotoxicity of Cd, Cu, Ni, Pb and Zn decreased with increasing Ca and H concentrations. This could not be explained with the effect of higher cationic concentrations on root growth or on solution speciation. It was concluded that Ca and H inhibited the rhizotoxicity of all metals tested. The rhizotoxicity of Cu and Cd was further examined in soil extracts. Both metals became less rhizotoxic at higher H and dissolved organic matter concentrations. The rhizotoxicity endpoints from the experiments in synthetic solution were used to develop parameters for a Biotic Ligand Model (BLM) for Cd, Cu, Ni, Pb and Zn. The BLM accounts for solution speciation and interprets cationic inhibition of rhizotoxicity as competition of metals with Ca and H for potential sites of rhizotoxicity. The BLM predicted metal rhizotoxicity better than the free metal ion activity in synthetic solutions and in soil extracts. Different models were tested against literature rhizotoxicity data for metals at different Ca and H concentrations. Predictions for metal rhizotoxicity given by BLM, Gouy-Chapman-Stern model and Freundlich equation model were compared with predictions based on free metal ion activities in solution. The BLM predicted rhizotoxicity most accurately. The BLM seems promising for predictions of metal toxicity and metal bioavailability in soils to support site-specific environmental risk assessments.
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Yates, Kyari. "Bioavailability of organic contaminants in sediments." Thesis, Robert Gordon University, 2008. http://hdl.handle.net/10059/588.
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The bioavailability of polycyclic aromatic hydrocarbons (PAHs) and chlorobiphenyls (CBs) in sediments is largely dependent on the freely dissolved concentration of these pollutants. However, measuring these is challenging, due to the low concentrations of lipophilic contaminants in the environment and their strong affinity for particles and for traditional sampling (filtration and centrifugation) equipment. An equilibrium passive sampling device made of silicone rubber was developed in this research to measure the freely dissolved concentrations of lipophilic contaminants and other parameters (water extractable proportions and sediment-water partition coefficients) that describe the availability of these contaminants in the environment. Equilibration between sampler and sediment for PAHs and CBs was found to be adequately achieved after 20 days shaking of a silicone rubber sampler in sediment slurry on an orbital shaker at 200 rpm. The reproducibility of uptake was better than 5 %. Silicone rubber-water partition coefficients for 34 PAHs and 32 CBs were measured in the laboratory using a co-solvent method using methanol as co solvent. Strong linear correlations of log sr w K , with octanol-water partition coefficients (log ow K ) ( log 0.97 log 0.01; 2 0.94 , K = K − r = sr w ow & log 1.17 log 1.82; 2 0.90 , K = K − r = sr w ow ) were found for PAHs and CBs, with a systematic difference in correlations observed for the different classes of compounds which was attributed to structural differences of the compounds. The silicone rubber samplers were then used to measure concentrations of PAHs in the pore water of sediments from the Fladen Ground of the North Sea, Loch Shell, Firth of Forth, Firth of Clyde, Loch Etive and Aberdeen Harbour in Scotland and the Vefsn fjord, Norway. A proportion of the PAHs were found to be unavailable for exchange into the aqueous phase, and this was reflected in the high log oc K measured in all the sediments studied. The sediment-water partition coefficients also correlated positively with the octanol-water partition coefficients. Accumulation of PAHs in Nereis virens from sediments was better predicted from literature bio concentration factors and pore water concentrations obtained using the silicone rubber samplers than from sediment concentrations traditionally used in risk assessments. Participation in an International Council for the Exploration of the Seas (ICES) passive sampling trial survey using silicone rubber in sediments and water is described, and demonstrated the potential of passive sampling in monitoring environmental pollution. The log BCF (bio concentration factor) for PAHs in mussels increased with increasing log ow K at both Loch Etive and Aberdeen Harbour locations, and could be used to estimate concentrations in mussels directly. The survey data also showed the use of silicone rubber in assessing the diffusive exchange of PAHs across sediment-water interfaces.
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Niwat, Chutamat. "Bioavailability and nutritional effects of phyochemicals." Thesis, University of Reading, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553070.
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Recent epidemiological studies have shown that consuming a diet rich in fruits and vegetables is associated with a reduced risk of cardiovascular disease and cancer. The hypothesis of this thesis is that increasing the consumption of fruits and vegetables in the form of soups and drinks will increase the plasma phytochemical concentrations, antioxidant status and improve the oxidative stability of LDL ex vivo. The thesis describes two intervention studies. The first was a chronic study, which investigated the bioavailability of carotenoids and beneficial effects of carotenoid-rich foods in the Carotenoid-Rich Soup and Juice Study (CARS). The second study was an acute intervention, which investigated the effects of fruit and vegetable puree-based drinks (FVPD) in the Flavonoid Kinetics Study (FLaKS). The studies showed that the consumption of fruit and vegetables in the form of soups and puree drink, equivalent to five portions of fruits and vegetables, increased plasma phytochemicals in a chronic intervention, and increased plasma phytochemicals and plasma antioxidant capacity in the acute intervention. However, there was no significant effect of the interventions on the resistance of LDL to copper-induced oxidation. The ability of caffeic acid and rutin to bind to LDL and to affect the susceptibility of LDL to oxidation was studied. The current study showed that the polyphenol compounds did not bind to LDL or increase the oxidative stability, except when added rutin was present. In conclusion, the thesis showed that increasing the consumption of fruits and vegetables in the form of soups and drinks, equivalent to five portions of fruits and vegetables, will increase the plasma phytochemical concentrations, and postprandial antioxidant capacity. Possible effects on vascular reactivity need further study.
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Keaveney, Edel M. "Bioavailability and bioactivity of wholegrain components." Thesis, University of Ulster, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.554199.
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Epidemiological evidence suggests that a diet rich in whole grains protects against the development of chronic diseases such as vascular disease. Whole grain fractions bran and aleurone are relatively good sources of to cop hero Is, trace minerals and methyl donors: folate, choline and betaine; components which may confer benefit through improving antioxidant status and lowering plasma homocysteine. The aim of this work was to evaluate the uptake of to cop hero Is and methyl donors from wheat bran and aleurone fractions, and to assess the effects of longer-term consumption of aleurone-enriched foods on plasma status of to cop hero Is, methyl donors, trace minerals and total homocysteine. A postprandial study assessed the effects of consumption of minimally processed wheat bran and aleurone fractions and results demonstrated that plasma betaine was significantly increased following consumption of both fractions; however plasma tocopherols, folate, and choline were unaffected. A four-week parallel intervention study which assessed the effects of consumption of aleurone-enriched bread and cereal showed significant increases in plasma betaine and significant decreases in plasma total homocysteine, however, plasma tocopherols, trace minerals, folate and choline did not change. These results are relevant as an elevated plasma homocysteine concentration is an independent risk factor for heart disease and stroke, diseases which are a common cause of death in the UK. Previous studies have shown that high doses of supplemental methyl donors lower plasma total homocysteine; however, this research shows that foods enriched with aleurone, a novel natural food ingredient rich in methyl donors, also have the potential to lower plasma total homocysteine. This research further adds to the knowledge on how whole grain fractions are beneficial to health, and may have implications for the development of novel grain-based food products.
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Rogers-Boss, S. M. "Intestinal metabolism and bioavailability of ethinyloestradiol." Thesis, University of Liverpool, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382118.
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Osmundsen, Sugrunn Anne. "Particulate strategies for improving oral bioavailability." Thesis, University of Strathclyde, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417335.
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McCullough, Fiona S. W. "Vitamin A - gut integrity and bioavailability." Thesis, University of Ulster, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326129.
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Attanayake, Chammi. "Bioavailability of contaminants in urban soils." Diss., Kansas State University, 2014. http://hdl.handle.net/2097/17601.
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Doctor of PhilosophyDepartment of Agronomy
Ganga M. Hettiarachchi
Urban soils may contain harmful levels of potentially toxic contaminants. These contaminants transfer to humans via two exposure pathways: direct transfer (soil-humans by soil ingestion, dermal exposure and inhalation) and food chain transfer (soil-plant-humans). Soil amendments alter the speciation of the contaminants in soils and thereby modify their bioavailability. The objectives of this research were to access the plant availability of lead (Pb), arsenic (As), and polycyclic aromatic hydrocarbons (PAHs); bioaccessibility and speciation of soil Pb, and As; and dermal absorption of soil PAHs in contaminated urban soils; and effectiveness of soil organic amendments on reducing contaminant bioavailability. Two field experiments were conducted in Kansas City, MO and Indianapolis, IN. Both sites had elevated concentrations of Pb in soils (Kansas City site: 30-380 mg kg⁻¹ and Indianapolis site: 200-700 mg kg⁻¹) . Indianapolis site’s soils also had elevated concentrations of As (40-100 mg kg⁻¹) and PAHs (benzo[a]pyrene: 1-10 mg kg⁻¹) . A control treatment (no-compost) and compost-types (leaf compost and/or composted biosolids, non-composted biosolids, mushroom compost) were used as treatments. A leafy vegetable, a fruiting vegetable and a root crop were grown for two growing seasons. The treatments were arranged in split-plot design (main plot factor: compost; sub-plot factor plant-type). An in vitro steady fluid experiment was conducted using human skins to examine the dermal transfer of soil PAHs. The concentrations of Pb, As, and PAHs in the vegetables were low, except Pb in root crops. Compost reduced the bioaccessibility of Pb, but did not change the bioaccessibility of As. Selected soil samples were analyzed for speciation of Pb using extended x-ray absorption fine structure spectroscopy. The predominant Pb species were Pb sorbed to Fe oxy(hydr)oxide and to organic C. Stable Pb phosphates (pyromorphite) was formed during the in vitro extraction. Dermal transfer experiments showed PAHs in the contaminated soils did not transfer through the skin. Stratum conium of the skin acted as a barrier for dermal transfer of soil PAHs. In general, the risk of food chain transfer of soil Pb, As, and PAHs were low in the studied sites and can be further reduced by compost addition. Bioaccessibility of Pb and As in urban soils were low. Dermal absorption of soil PAHs was insignificant.
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Onogbosele, Cyril Oziegbe. "Bioavailability of organic contaminants in rivers." Thesis, Brunel University, 2015. http://bura.brunel.ac.uk/handle/2438/11050.
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In rivers, association of organic contaminants with dissolved organic carbon may limit freely dissolved or bioavailable fractions and toxicity of organic contaminants. Consequently, assessment of toxicity of organic contaminants on the basis of their total chemical concentrations may lead to overestimation of risks to organic contaminants. Therefore, to achieve reliable and accurate risks assessment for organic contaminants, determination of bioavailability is important. The influence of humic acid on the bioavailability of organic contaminants in rivers was studied, using three chemicals with different properties as model contaminants, which at the start of the study were detected in wastewater effluents. It was hypothesized that in the presence of dissolved organic carbon, a fraction of the total concentration of an organic contaminant would not be bioavailable in river water. Therefore, the aim of the study was to determine bioavailability and its impact on toxicity. Bioavailability in the presence of humic acid was determined chemically and using a yeast estrogen screen assay. The chemical method comprised solid-phase extraction and liquid chromatography-mass spectrometry to determine freely dissolved and the fraction of the chemicals associated with dissolved organic carbon. The results indicated increased binding to dissolved organic carbon with the hydrophobicity of the test compounds except for perfluorooctane sulfonate. The dissolved organic carbon-water partition coefficient for ethinylestradiol was determined to be Log KDOC 2.36. Log KDOC values of 4.15 and 4.41 at 10 and 100 mg/L humic acid, respectively, were derived for hexabromocyclododecane indicating greater binding than ethinylestradiol due to the more hydrophobic character. The yeast estrogen screen was used as a biological method to measure the effect of humic acid on the bioavailability of ethinylestradiol and a more hydrophobic compound, dichlorodiphenyltrichloroethane. Results of the yeast estrogen screen indicated that the presence of humic acid had no effect on bioavailability of either of the chemicals.
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Lau, Yeuk Tin. "Bioavailability and bioactivity enhancement by nanomization /." View abstract or full-text, 2009. http://library.ust.hk/cgi/db/thesis.pl?BIEN%202009%20LAU.
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Gustavsson, Jenny. "Cobalt and Nickel Bioavailability for Biogas Formation." Doctoral thesis, Linköpings universitet, Tema vatten i natur och samhälle, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-73113.
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Supplementation of trace metals such as Co and Ni may improve anaerobic digestion of organic material for biogas formation. Which trace metals that are needed and the quantity to apply are, at least partly, related to metal speciation and bioavailability. According to the common perception, metals have to be dissolved to be available for microbial uptake. However, the impact of trace metal speciation on bioavailability is still unclear. The purpose of the present study was to investigate the effect of Fe-, Co- and Ni-addition on the biogas process performance of stillage-fed lab-scale biogas tank reactors. Metal speciation was determined by sequential extraction (SE), extraction of acid volatile sulfides (AVS) and continuously extracted metals (AVS-Me). Sulfur forms, which may be associated to metal speciation, were studied with S XANES (sulfur X-ray absorption near edge structure). The effect of different Co- and Ni-concentrations on process microflora composition was examined with quantitative PCR (qPCR) and 454-pyrosequencing. The results showed that Co- and Ni-supplementation stimulated and stabilized the biogas process performance by increasing methane production and substrate utilization and by establishing low concentrations of volatile fatty acids. 10-20% of the total Co-amount was found in the dissolved phase, which shows that Co was relatively available for microbial uptake. Nickel was entirely associated to organic matter/sulfides and AVS, and was therefore considered to be non-bioavailable. Nevertheless, Ni-supplementation had stimulatory effects on the biogas process performance. This implies that Ni was available for microbial uptake despite its extensive association to sulfides and that other mechanisms than solubility govern the availability of this trace metal. The microbial analyzes revealed that it was primarily the methane producers which were affected by the concentration of Co and Ni. At stimulatory Co- and Ni-concentrations, the archaeal methanogenic community was dominated by aceticlastic Methanosarcinales. At lower Co- or Ni-levels, when biogas process performance was poor, an increase in hydrogenotrophic Methanomicrobiales was observed. This indicates a shift in the methanogenic flora, from being dominated by acetate utilizers to increased importance of hydrogen utilizers, and that the former was more dependent on Co and Ni.Tillsats av spårmetaller kan förbättra rötning av organiskt material till biogas. Typ och mängd av respektive spårmetall som behöver tillsättas för att uppnå stimulerande effekter, varierar mellan processer. Detta är delvis kopplat till specieringen och biotillgängligheten av metallerna. Endast fria metalljoner och vissa metallkomplex antas vara tillgängliga för mikrobiellt upptag. Det är dock i många fall oklart hur metallernas speciering påverkar biotillgängligheten. Syftet med föreliggande studie var därför att undersöka effekten av tillsats av Fe, Co och Ni för biogasproduktion från drank, en restprodukt i produktion av bioetanol från spannmål, samt att undersöka hur dessa metallers speciering påverkar deras biotillgänglighet. Effekten av tillsatserna av Fe, Co och Ni undersöktes på biogasreaktorer i lab-skala. Metallernas speciering bestämdes genom sekventiell extraktion (SE), extraktion av AVS (acid volatile sulfide) och kontinuerligt extraherade metaller (AVS-Me). Svavelformer med betydelse för metallspeciering studerades med S XANES (sulfur X-ray absorption near edge structure). Effekten av olika Co- och Ni-koncentrationer på processens mikroflora undersöktes molekylärbiologiskt med kvantitativ PCR (qPCR) och 454-pyrosekvensering. Resultaten visade att Co och Ni stimulerade och stabiliserade biogasprocessen genom ökad metanproduktion, ökad utrötningsgrad samt låga halter av flyktiga fettsyror i det studerade systemet. 10-20% av totala mängden Co återfanns i löst fas, vilket visar att Co var relativt lättillgängligt för mikroorganismerna. Nickel var däremot enbart bundet till organiskt material/sulfider och AVS och kunde alltså betraktas som otillgängligt. Trots detta hade även tillsatsen av Ni stimulerande effekter på biogasprocessen. Det innebär att mikroorganismerna har förmåga att komma åt Ni bundet i svårlösliga sulfidföreningar och att andra mekanismer än löslighet reglerar tillgängligheten av denna spårmetall. De molekylärbiologiska analyserna visade att framför allt de metanbildande mikroorganismerna påverkades av halten av Co och Ni. De halter, som gav välfungerande processer, dominerades helt av acetiklastiska Methanosarcinales. Vid lägre halter av Co eller Ni, då processerna gick sämre, tillkom vätgasutnyttjande metanogener. Det tyder på ett skift i bildningen av metan från att ha dominerats av acetatklyvning till att vätgasutnyttjarna fått större betydelse och att de förra är mer beroende av Co och Ni.
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Mohteshamzadeh, Mobin. "Hypertension, insulin resistance and vitric oxide bioavailability." Thesis, University of Newcastle upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270768.
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Bramwell, Debbie-Ann. "Surfactant solubilization and subsequent bioavailability of phenanthrene." FIU Digital Commons, 1997. http://digitalcommons.fiu.edu/etd/1787.
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Contamination of soil, sediment and groundwater by hydrophobic organic compounds (HOCs) is a matter of growing concern because groundwater is a valuable and limited resource, and because such contamination is difficult to address. This investigation involved an experimental evaluation of the addition of several surfactant solutions to aqueous and soil-water systems contaminated with phenanthrene, a selected HOC. The results are presented in terms of:
* phenanthrene solubilization achieved through surfactant addition
* observed effects of surfactant addition on the mineralization of phenanthrene
* estimation of relative toxicities of various surfactants using toxicity assays
* literature-reported biodegradability/persistence of selected surfactants
* surfactant sorption/precipitation onto soil and its impacts on proposed use of surfactant-amended remediation
Surfactants were observed to facilitate the transfer of phenanthrene from the soil-sorbed phase to the aqueous pseudophase, however, surfactant solubilization did not translate into enhanced phenanthrene biodegradation.
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Mereish, Kulthoum A. "Alteration of cyclosporin : a bioavailability through complexation /." Ann Arbor : University Microfilms International, 1985. http://www.gbv.de/dms/bs/toc/01641747x.pdf.
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Knight, Bruce Philip. "Heavy metal speciation and bioavailability to microbes." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243803.
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Judy, Jonathan D. "Bioavailability of Manufactured Nanomaterials in Terrestrial Ecosystems." UKnowledge, 2013. http://uknowledge.uky.edu/pss_etds/18.
Full textAbstract:
Manufactured nanomaterials (MNMs) from the rapidly increasing number of consumer products that contain MNMs are being discharged into waste streams. Increasing evidence suggests that several classes of MNMs may accumulate in sludge derived from wastewater treatment and ultimately in soil following land application as biosolids. Little research has been conducted to evaluate the impact of MNMs on terrestrial ecosystems, despite the fact that land application of biosolids from wastewater treatment will be a major pathway for the introduction of MNMs to the environment. To begin addressing this knowledge gap, we have conducted a series of experiments designed to test how bioavailable MNMs are to terrestrial ecoreceptors when exposed through a variety of pathways.
First, we used the model organisms Nicotiana tabacum L. cv Xanthi (tobacco) and Triticum aestivum (wheat) to investigate plant uptake of 10, 30 and 50 nm diameter gold (Au) MNMs coated with either tannate (T-MNMs) or citrate (C-MNMs). Both C-MNMs and T-MNMs of each size treatment bioaccumulated in tobacco, but no bioaccumulation of MNMs was observed for any treatment in wheat.
In a second exposure, we investigated the potential for bioaccumulation of MNMs from contaminated plant surfaces by a terrestrial secondary consumer, tobacco hornworm (Manduca sexta). We found that hornworms bioaccumulate Au MNMs, but that the assimilation efficiency of bioaccumulation was low. Hornworms eliminate ingested Au MNMs rapidly from 0-24 h, but very slowly from 1 d to 7 d.
Finally, we used the model organisms tobacco and tobacco hornworm to investigate the potential for trophic transfer of Au MNMs. Biomagnification of Au MNMs was observed in the hornworms.
We have demonstrated that MNMs of a wide range of size and with different surface chemistries are bioavailable to plants, that MNMs resuspended by wind, rain, biota, and mechanical disturbance from soil onto plant surfaces are bioavailable to terrestrial consumers, and that trophic transfer and biomagnification of plant accumulated MNMs can occur. These results have important implications for risks associated with nanotechnology, including the potential for human exposure.
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Dingle, Pope Nicholas. "The bioavailability of sediment-bound tributyltin (TBT)." Thesis, University of Plymouth, 1998. http://hdl.handle.net/10026.1/2606.
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Tributyltin is arguably the most toxic compound ever to be deliberately introduced into the marine environment as an ingredient of antifouling paints. It has had widespread toxic effects on a range of marine organisms, with some gastropod species being particularly sensitive. Effects of TBT on non-target species have resulted in partial bans on its use in many countries, so that new inputs to the water column have decreased in most areas. One of the physicochemical features of TBT is that it is readily sequestered by suspended particulates due to its low solubility and its hydrophobicity, therefore becoming incorporated into estuarine sediments. The availability of this sediment-bound TBT has been investigated through its potential for re-release back to the water column, and directly from the sediment using the sediment dwelling gastropod Hinia reticulata. The sorption process itself has been investigated using natural components to determine the sediment-water partition coefficient (Kd) together with factors affecting its magnitude. Sorption by sediments has been shown to be rapid (minutes), although the achievement of equilibrium may take longer (hours), and exhibits a Freundlich-like dependence on the TBT concentration due to the variable energies of TBT sorption sites on sediment particles. The major determinant of Kd is sediment type, greater adsorption occurring in fine-grained organic rich sediments compared to low organic sands; although both salinity and pH modify the degree of adsorption. The sorption process has been shown to be reversible, so that previously contaminated sediments may act as reservoirs of TBT, releasing the compound back to the overlying water for many years. Hinia reticulate has been shown to be an effective and quantitative accumulator of both dissolved and sediment-bound TBT, principally acquiring TBT from water across the respiratory surfaces. When additionally exposed to sediments, significantly higher body burdens were accumulated, with up to 80% of the total attributable to the sediment. Uptake of TBT across the surface of the headtfoot appears to be an important pathway for sediment-exposed Hinia reticulata, while the ingestion of contaminated sediment does not appear to occur. Hinia reticulata is capable of metabolising TBT to lesser butylated and presumably less toxic products which are excreted, making its accumulated body burdens responsive to changing environmental TBT levels, and increasing its value as a biomonitor When exposed to a range of TBT contaminated sediments, Hinia reticulata showed there to be greater TBT availability from sediments with a low sorptive capacity (sands), principally through desorption of TBT to the overlying water. Fine-grained organic-rich muds, which have a greater capacity for TBT, produced lower accumulated burdens in Hinia reticulata, but may represent more important long-term sources of TBT to benthic organisms in estuaries.
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Bryce, Steven Alan. "Regulation of the bioavailability of CCR7 ligands." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5904/.
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The efficient functioning of the immune system is dependent on the coordinated movement and positioning of immune cells. These cells patrol the body and facilitate the clearance of pathogens, whilst maintaining self-tolerance and inducing adaptive immunity. The coordinated migration of cells into and within tissues is mediated by chemokines, a family of small chemotactic cytokines that are potent inducers of cellular movement. Chemokines and their cognate receptors have been shown to play key roles in health, and in a broad spectrum of diseases. After their secretion, chemokines can be controlled by proteases and interactions with atypical chemokine receptors that structurally resemble conventional chemokine receptors but cannot couple to the signaling pathways that they use. Instead, they are thought to degrade, transport or buffer extracellular chemokines to regulate their access to cells bearing conventional chemokine receptors. However, their functions in vivo remain to be fully defined. CCRL1, a member of the atypical chemokine receptor family, binds to CCL19, CCL21 and CCL25 and is proposed to be a scavenger of these chemokines. Post-translational regulation of these chemokines is important because their interactions with cognate, conventional receptors CCR7 and CCR9, are critical for the development and functioning of the immune system. The work in this thesis primarily explores the importance of CCRL1 in regulating CCR7 ligands, but also considers the impact of protease-mediated ‘clipping’ on the function of CCL21 and other extended chemokines. Whilst in vitro evidence, and a growing body of in vivo evidence, supports the idea that CCRL1 serves an important role in the chemokine control, the true biological function of CCRL1 remains unclear. Therefore, the principal aim of this thesis was to further our understanding of the biology of CCRL1, mainly through the characterisation of CCRL1-deficient mice. Firstly, the effect of CCRL1 deletion on dendritic cell (DC) migration from the skin was investigated. Four distinct subsets of migratory DCs were examined in skin-draining lymph nodes at steady state and after induction of cutaneous inflammation. Under inflammatory conditions, skin-derived DCs were identified by FITC painiting or by photoconverting the skin of Kaede transgenic mice. CCRL1 deficiency was found to result in a specific reduction in the abundance of Langerin+ skin-derived DCs in inguinal lymph nodes at rest, and although the initial inflammation-driven arrival of DCs at skin-draining lymph nodes showed no requirement for CCRL1, DCs that took longer to reach these organs were substantially reduced in CCRL1-deficient mice. All DC subsets were affected, but overall it was epidermal Langerhans cells that showed the greatest requirement for CCRL1. Defective DC arrival at lymph nodes was accompanied by DC retention in resting and inflamed skin, and these cells struggled to leave CCRL1 deficient skin in ex vivo ‘crawl out’ assays. Further experiments demonstrated that, as expected, DC arrival at lymph nodes draining inflamed skin was heavily dependent on CCR7 in the models being used, and that increased levels of bioavailable CCL19 and CCL21 accompanied CCRL1 deficiency in inflamed skin. This suggested CCRL1 regulates chemokine to prevent DCs from becoming disorientated in the skin and failing to efficiently egress this tissue. I hypothesised that dysregulation of CCL19 rather than CCL21 may be particularly significant because of its greater diffusivity, and strikingly, inflammation-driven DC migration defects observed in CCRL1 deficient mice were completely reversed by genetic deletion of CCL19 in the same animals. To place these findings in an anatomical context, expression of CCRL1 in skin and lymph node was explored using CCRL1+/gfp ‘knock-in’ receptor mice and anti-CCRL1 antibodies. In skin, CCRL1 was abundantly expressed by keratinocytes, and found on lymphatic endothelial cells (LECs) that are traversed by migrating DC as they leave the skin. In lymph nodes draining the skin, LECs in the supcapsular sinus (SCS) were strongly CCRL1+. Although some leukocytes were found to express very low levels of eGFP in CCRL1+/gfp, the data suggested that CCRL1-mediated scavenging of CCL19 by keratinocytes and LECs facilitates CCR7-driven DC migration from resting and inflamed skin. CCRL1 expression in other secondary lymphoid tissues was examined and its role in regulating leukocyte populations residing in or around the SCS was explored. As in the inguinal lymph node, CCRL1 was restricted to the SCS LECs in other lymph nodes, such as the mesenteric lymph nodes that drains the intestine. In the spleen, endothelial cells lining venules adjacent to the white pulp marginal zone specifically expressed CCRL1. The overall cellularity and microanatomy of lymph nodes and the spleen appeared normal in CCRL1-deficient mice, as was the recruitment of CCR7+ cells into the spleen two hours after adoptive transfer. However, NK cells, iNKT cells and γδ T cells, which are thought to reside in intrafollicular regions, were less abundant in CCRL1-deficient inguinal and mesenteric lymph nodes, although they were present at normal frequency in the spleen. CD169+ macrophages are intimately associated with CCRL1+ endothelial cells in the spleen. CCRL1 deficiency had no clear impact on these cells in the inguinal lymph nodes, and only resulted in a small increase in the abundance of these cells in the spleen, without obviously affecting their position. Strikingly, however, in mesenteric lymph nodes, CD169+ macrophages, and LECs with which they associate, were far more abundant when CCRL1 had been deleted and were aberrantly distributed throughout the lymph node parenchyma. The reason this phenotype is restricted to the mesenteric lymph node is unclear, but it might be related to the fact the intestine, unlike other non-lymphoid tissues, is an abundant source of CCL25. This, along with the immunological implications of these observations, requires further investigation. There is a lot of evidence that macrophages regulate lymphangiogenesis. The close association between LECs and CD169+ macrophages in lymph nodes, and the phenotype in CCRL1-deficient mesenteric lymph nodes, stimulated experiments to explore functional interactions between these cells. Inflammation in the footpad induced lymphangiogenesis in draining popliteal and inguinal lymph nodes. When clodronated liposomes were used to specifically deplete macrophages from the popliteal lymph node of WT mice, lymphangiogenesis appeared suppressed while it continued unabated in the inguinal lymph node where the CD169+ macrophage population was intact. WT and CCRL1-deficient mice responded similarly, and although preliminary, these data suggest that CD169+ macrophages play an important role in stimulating lymph node lymphangiogenesis. In addition to the CCRL1 studies above, other mechanisms that might regulate chemokines after their secretion were explored. Work published at the beginning of my PhD showed that CCL21, which carries an extended C-terminus that anchors it to the extracellular matrix, can be cleaved by bone marrow-derived DCs (BMDCs) to release a more freely diffusible version. These findings were reproduced here using in vitro-derived human or mouse DCs. DCs were far better at cleaving CCL21 than other leukocytes, and they could also cleave CCL2, a pro-inflammatory chemokine with an extended C-terminus. Interestingly, a truncated version of CCL21 was detected in mouse secondary lymphoid tissues. It was larger than the version generated by BMDCs in vitro, and the nature of its truncation is not clear, but this shows that CCL21 processing occurs in vivo. If this form of CCL21 is more diffusible than the full-length protein, then it might be more available for regulation by CCRL1.However, neither forms of CCL21 were more abundant in CCRL1-deficient secondary lymphoid tissues than equivalent tissues from WT mice. CCR7 plays a critical role in directing DC egress from tissues, their entry into lymph nodes, and their movement within these tissues. The work presented in this thesis provides evidence of two mechanisms that regulate CCR7 ligands: CCRL1-mediated CCL19 scavenging and DC-mediated CCL21 cleavage. It reveals that, under certain circumstances, CCRL1 is critical for facilitating DC egress from peripheral tissues to the lymph nodes, and plays an indispensible role in regulating LECs and CD169+ macrophages in lymph nodes. These studies extend our understanding of CCRL1 and the chemokine networks at work in lymph nodes and other tissues, and form the foundation on which to explore the immunological importance of the regulation of extracellular chemokines.
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Jing, Jung. "Bioavailability of cadmium in municipal sewage sludge /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487683049375578.
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Winstanley, Henry Fletcher. "Mathematical modelling of biofilm growth and bioavailability." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589760.
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This thesis relates to the mathematical modelling of biofilm in two primary areas: biofilm growth, and the effect of microbial immobilisation in biofilm on environmen- tal contaminant transport in the Earth's subsurface. For biofilm growth we construct a model based on polymer solution theory. Parameter estimates motivate a very different model from two published biofilm models also based on polymer solution theory. Analysis of ID solutions provides an expression for growth rate suitable for comparison with experiment. Stability analysis of spatial perturbations to a growing planar front reveals an interfacial instability mechanism similar to that found in a published theoretical study not based on a specific material model. We derive a stability criterion as a critical external nutrient boundary layer thickness, and for the travelling wave solution we identify the finite perturbation wavenumber selected by the instability. For environmental contaminant transport, we identify dissolution of organic phase contaminants and sorption of hydrocarbons onto solid grains as primary lim- itations on bioavailability. We build a pore scale model including both organic phase dissolution and micro- bial uptake and use it to parameterise pore scale Sherwood and Damkohler numbers with respect to pore Peclet number. We illustrate their relation to effective macro- scopic parameters for varying organic phase size relative to pore size. A simple intraparticle diffusion sorption model is extended by considering an external biofilm layer on the particles. A larger scale model considers contaminant transport in a ID flow through a bed of such particles. A physically reasonable pa- rameter regime is suggested, providing analytical solutions for breakthrough curves.
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GIANNINO, VALENTINA. "BIOAVAILABILITY ENHANCEMENT OF POORLY WATER SOLUBLE DRUGS." Doctoral thesis, Università degli studi di Pavia, 2020. http://hdl.handle.net/11571/1321847.
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CORRIAS, FRANCESCO. "Nanocarriers for drug targeting and improved bioavailability." Doctoral thesis, Università degli Studi di Cagliari, 2014. http://hdl.handle.net/11584/266439.
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This PhD thesis debates, mostly, on two main topics:
- Drug delivery to brain
- Nanosuspensions for different applications
The objective of the first topic was the development of liposomes to which anti-TfR-monoclonal antibodies (Ox26) or lactoferrin was bounded to transport the selective NK3 receptor agonist senktide to CNS across the BBB. NK3 receptors are widely expressed in the CNS and their stimulation by senktide (ICV) increase extracellular DA. Liposomes were prepared using the film hydration method. In vivo microdialysis studies were performed to estimate the responsiveness of NAc shell DA to senktide as a consequence of its CNS delivery. Senktide given ICV or loaded into Ox26/lactoferrin-liposome (0.5 μg/kg iv) elicited a significant increase of dialysate DA in the NAc shell of rats whilst senktide given iv (0.1 mg/kg) or loaded in control stealth liposomes did not affect NAc shell DA. Liposomes formulation here described represent an effective way of CNS delivering of senktide following intravenous administration the TfR-transport system. On the other hand, three different types of nanosuspensions were formulated and studied:
- Tretinoin nanosuspensions for topical delivery
- Piroxicam nanosuspensions loaded in oral disintegrating tablet (ODT) for oral delivery
- Quercetin nanosuspensions loaded in fast dissolving films for oral delivery
The aims of the first work were to improve cutaneous targeting and photostability of tretinoin by using nanosuspension formulation. Tretinoin is a drug widely used in the topical treatment of various dermatological diseases. The tretinoin nanosuspension was prepared by precipitation
method and then characterized by photo correlation spectroscopy for mean size and size distribution, and by transmission electron microscopy for morphological studies. An oil in water tretinoin nanoemulsion was also prepared and used as a control. Dermal and transdermal delivery of both tretinoin nanosuspension and nanoemulsion were tested in vitro by using Franz diffusion cells and newborn pig skin. Photodegradation studies were carried out by UV irradiation (1 h, λ=366 nm) of the tretinoin nanosuspension in comparison with the nanoemulsion and a methanolic solution of the drug. During 8 h percutaneous experiments, no permeation of tretinoin through the whole skin thickness was detected but the drug was deposited into the skin layers, mainly in the stratum corneum, similarly to the nanoemulsion. UV irradiation of the nanosuspension showed a great improvement of tretinoin stability in comparison with both controls. Overall results show that nanosuspension might be a useful formulation for improving tretinoin dermal delivery and stability. Piroxicam (PRX) is a non-steroidal anti-inflammatory drug characterized by a poorly water solubility and consequently by a low oral bioavailability. Different nanocrystals orally disintegrating tablets (ODT) were prepared to enhance piroxicam dissolution velocity and saturation solubility. Nanosuspensions were prepared using high pressure homogenization technique. Different ODT formulations were prepared using the same nanosuspension but changing different excipients in order to optimize dissolution properties. PRX nanocrystals size and zeta potential were determined by photon correlation spectroscopy (PCS). Characterization of PRX nanocrystals ODT was carried out by infrared spectroscopy (FTIR), X-ray powder diffractometry (XRPD), differential scanning calorimetry. Dissolution study of PRX ODT was performed in distilled water (pH 5.5) and was compared with PRX coarse suspension ODT, PRX/poloxamer 188 physical mixture, bulk PRX samples and a piroxicam commercial ODT (Feldene). All PRX nanocrystals ODT formulations showed a higher drug dissolution rate than coarse PRX ODT. PRX nanocrystals ODT prepared using gelatin or croscaramellose as excipient showed a higher PRX dissolution rate compared with the commercial formulation and with ODT prepared using xanthan gum. The improvement in PRX dissolution rate is mainly caused by the increased surface-to-volume ratio due to the submicron
dimension of the drug nanocrystal, however, also the presence of the correct excipients (as disgregant) seem to play an essential role. Finally, quercetin nanosuspensions loaded fast dissolving films were formulated and studied. The aim of this work was to investigate the possible use of maltodextrin IT6 (MDX) to prepare fast-dissolving films, loaded by quercetin nanocrystals. Quercetin nanosuspensions were prepared using an high pressure homogenizer, meanwhile drug loaded films were obtained drying in a siliconized polyester sheet quercetin nanosuspensions with the others compounds in a oven at 60 °C. Films were finally cut and packed within sealed aluminium pouches. Quercetin nanocrystals were characterized by photo correlation spectroscopy for mean size and size distribution and by transmission electron microscopy for morphological studies. On the other hand, quercetin nanosuspensions loaded films were characterized in term of flexibility, tensile strength and thickness. Finally, dissolution studies in distilled water were performed, comparing release profiles of quercetin loaded films, quercetin raw material and quercetin nanosuspensions.
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Cooney, Rita A. "Speciation and identification of selenium compounds in biological matrices." Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/30258.
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Young, Riki G. "Effect of organic matter and contact time on the sorption and bioavailability of chlorophenols." Thesis, This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-12042009-020047/.
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Lønborg, Christian. "Bioavailability of dissolved organic matter in coastal waters." Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=59094.
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Quattrini, Federico. "Emerging Techniques for Inorganic Metal Speciation and Bioavailability." Doctoral thesis, Universitat de Lleida, 2018. http://hdl.handle.net/10803/664422.
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El coneixement profund de la especiació dels metalls pesants és clau per a determinar la seva biodisponibilitat. Per això cal complementar la informació sobre les concentracions amb la informació sobre els fluxos d’internalització. Diverses tècniques analítiques han estat desenvolupades amb aquesta fi, i algunes d’elles aprofiten les propietats de les resines d’intercanvi iònic o quelants.
D’una banda, aquesta tesi investiga la velocitat d’acumulació d’ions metàl·lics a la resina Chelex 100, sigui experimentalment o a través d’un model teòric. Aquesta interpretació permet descriure els efectes dels lligands competidors i determinar les constants de dissociació dels complexes.
D’altra banda, dues noves tècniques analítiques han estat desenvolupades. La primera deriva de la IET, una tècnica comunament utilitzada en equilibri, però n’extreu informació dinàmica. La segona és una modificació del popular DGT, que s’ha emprat un cop el sistema ha assolit l’equilibri.El conocimiento profundo de la especiación de los metales pesados es clave para determinar su biodisponibilidad. Por eso es necesario complementar la información sobre las concentraciones con la información sobre los flujos de internalización. Diversas técnicas analíticas han sido desarrolladas con este fin, y varias aprovechan propiedades de las resinas de intercambio iónico o quelantes. Por un lado esta tesis investiga la velocidad de acumulación de iones metálicos en la resina Chelex 100, tanto experimentalmente, como a través de un modelo teórico. Esta interpretación permite, asimismo, describir los efectos de los ligandos competidores y determinar las constantes de disociación de los complejos. Por otro lado, dos nuevas técnicas analíticas han sido desarrolladas. La primera deriva de la IET, una técnica comúnmente utilizada en equilibrio, pero extrae información dinámica de ella. La segunda es una modificación del popular DGT, que se ha empleado una vez el sistema ha alcanzado el equilibrio.
A deep knowledge of heavy metal ions speciation is key to assessing their bioavailability. In this regard, data about concentrations should be complemented with data about the internalization fluxes. Several analytical techniques have been developed to this purpose, and many of them exploit properties of ion-exchange or chelating resins. On the one hand, this thesis studies the rate of metal ions uptake on Chelex 100 resin, both experimentally and through a theoretical model. This interpretation also allows describing the effect of competing ligands and determining the dissociation constants of the complexes. On the other hand, two new analytical techniques are developed. The first one stems from IET, a technique commonly used at equilibrium, but aims at extracting dynamic information from it. The second one is a modification of the well-known DGT, devised to provide information once equilibrium has been attained.
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Cook, Nicola. "Bioavailability of trace metals in urban contaminated soils." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0007/NQ44391.pdf.
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Proulx, Amy Katheryn. "Diversified strategies for improving iron bioavailability of maize." [Ames, Iowa : Iowa State University], 2007.
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Cook, Nicola. "Bioavailability of trace metals in urban contaminated soils." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=34934.
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There are two main components to the research: the theoretical and the experimental. Chapter 2 contains an analysis of the state of soil quality guidelines and the scientific methods used to determine them. A number of recommendations to improve soil quality criteria for trace metals are offered including the importance of considering bioavailability and the need to use realistic conditions, trace metal sources and organisms.A critical review of the literature dealing with predicting the availability of trace metals to plants is presented in Chapter 3. We found little agreement among hundreds of similar studies which relate plant metal uptake to the amount of metal extracted by selective chemical dissolution procedures. An extensive summary of the data shows clearly that the extraction methods are not widely applicable. Differences between individual soils, their metal retention capacities, as well as plant factors and environmental conditions contribute to the variability of the results. Alternative ways of assessing bioavailability are suggested.
The experimental component of the thesis focuses on the availability of trace metals to plants. In Chapter 4 the uptake of Cu from different soil pools was examined and the free metal ion (Cu2+) was found to be the best predictor of uptake by lettuce (Latuca sativa cv. Buttercrunch), ryegrass (Lolium perenne cv. Barmultra) and radish (Raphanus sativus cv. Cherry Belle).
In Chapters 5 and 6 we examined the effect of low-cost in-situ treatments on the availability of metals to plants in greenhouse and field experiments. Synthetic zeolites, P amendments, organic matter and clean soil were used and their effect on the bioavailability of Cd, Cu, Pb, Ni and Zn evaluated. The plants for the experimental work were lettuce and perennial ryegrass. Only the clean soil treatment was consistently effective in reducing the concentration of metals in the plant. We also wanted to determine whether the trace metals in the plant tissue came from the soil or from direct deposition of pollutants on the leaf surfaces. We found little evidence that metals in plants were a result of atmospheric fallout.
A method for the accurate analysis of total metal concentrations in a range of contaminated soils including those containing oil and grease was developed (Chapter 7). For this research the trace metals of concern are Cd, Cu, Ni, Pb and Zn---all commonly found in urban/industrial soils. The proposed method using HNO3/HClO4 has several advantages over the common HNO3/H2O2 procedure. We were able to digest larger soil samples and hence the final concentration of trace metals was usually in the range for analysis by inductively coupled plasma atomic absorption spectrometry or flame atomic absorption spectrometry.
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Hills, Elizabeth Eileen. "The prediction of human oral bioavailability of drugs." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1444302/.
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The aim of this project was to develop a model for prediction of bioavailability of drug compounds from structural features. Literature bioavailability data was gathered for over 700 compounds. This data was evaluated and assigned a quality score. Prodrugs and drugs known to be actively transported were excluded from the dataset. The factors that affect bioavailability include solubility, permeability and first-pass metabolism. Each of these factors was considered. The first stage was to develop a model to predict solubility and to study the effects of pH on solubility. Solubility was measured in water for a set of 99 compounds selected from the bioavailability dataset, using HPLC as the analytical method. Solubility was also measured in simulated gastric fluid, SGF (pH 1.2), and simulated intestinal fluid (fed state and fasted state), FeSSIF and FaSSIF at pH 6.5. An equation for change in solubility with pH was shown to perform quite well. An Abraham equation was developed to account for solubility enhancement due to the presence of micelles in simulated intestinal fluid. Abraham equations were derived for prediction of diffusion in water and in ethanol using literature data. Diffusion in ethanol was predicted best and was used in place of permeability to classify the bioavailability data according to the Biopharmaceutics Classification System. A compound which is highly metabolised will have low bioavailability. Human plasma clearance data was used as a measure of the degree of metabolism of a drug. A molecular fragment-based approach using PLS statistics was used to develop a model of human plasma clearance of drugs for over 400 drugs. The final stage of this work was to develop a model of bioavailability. The best model used PLS statistics and included chain-based molecular fragments in combination with calculated aqueous solubility, diffusion coefficients (in ethanol) and plasma clearance.
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Hamill, Lesley L. "Whole grain components : bioavailability and bioactivity in humans." Thesis, University of Ulster, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.554200.
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Epidemiological evidence indicates that increased consumption of whole grain foods is associated with decreased incidence of chronic diseases. The mechanisms underlying these effects are poorly understood but may be due to the antioxidant effects of phenolics or other components. The first postprandial study assessed the effects of consumption of minimally processed wheat bran and aleurone fractions on ferulic acid responses and antioxidant measures in humans. Results showed that both fractions significantly increased urinary total phenolics and plasma and urinary ferulic acid, and that plasma MetSO was significantly reduced after consumption of aleurone. The second postprandial study, which assessed the effects of consumption of aleurone, incorporated into breads, with or without iron addition, showed significant increases in plasma and urinary ferulic acid, and significant decreases in plasma MetSO; the addition of iron did not influence these responses. The third study, which assessed the effects of longer term consumption of aleurone enriched products on antioxidant, inflammatory and other disease risk factors in a parallel, four week intervention study, showed significant decreases in hs CRP and LDL-cholesterol, but other lipids and biomarkers of inflammatory status were unaffected. Furthermore, there were no significant effects on fasting plasma ferulic acid, or antioxidant, anthropometric or blood glucose measures. Overall, the results indicated that wheat bran and aleurone fractions can impact on postprandial ferulic acid levels, and antioxidant measures, and that longer term consumption of wheat aleurone enriched products can ameliorate inflammatory and lipid biomarkers. Future studies should further assess these effects, and extend this work to other components and mechanisms underlying the health benefits of whole grains.
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Fenlon, Katie Alexandra. "Fate, Behaviour and Bioavailability of Pesticides in Soils." Thesis, Lancaster University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504165.
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Rinze, Ruth E. "Regulation of endothelial cell growth by tetrahydrobiopterin bioavailability." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555298.
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The vascular endothelium plays a critical role in the regulation of vascular homeostasis. Endothelial cell injury, loss, survival and regeneration are important aspects in the response to vascular injury and pathogenesis of vascular disease. Re- endothelialization has been shown to be a key event in vascular repair after injury. Nitric oxide (NO) produced by endothelial nitric oxide synthase (eN OS) is a key regulator of endothelial cell biology. Loss of NO bioavailability in endothelial dysfunction states is an early step in the development of atherosclerosis. The cofactor tetrahydrobiopterin (BH4) is essential for eNOS catalytic activity; when BH4 is limiting eNOS becomes enzymatically uncoupled, leading to the generation of superoxide instead of NO. eNOS function has been shown to be an important regulator of endothelial cell proliferation and survival as well as endothelial progenitor cell function. There is increasing evidence that the essential eNOS cofactor BH4 may enhance endothelial cell proliferation and endothelial progenitor function, both of which have the potential of enhancing vascular repair. The aim of this thesis is to evaluate the effect of BH4 bioavailability on endothelial cell growth in the absence and presence of vascular disease using primary endothelial cells from mice with genetic modifications in BH4 availability. Endothelial progenitor cell availability in lungs and bone marrow was investigated to address a second source for endothelial repair and potential therapeutic target. The duration of culture proved to be a major determinant of the biological phenotype of primary endothelial cells. Transgenic BH4 augmentation improved in vitro growth of primary endothelial cells in the presence but not in the absence of vascular disease. Endothelial progenitor cell content in lung tissue and bone marrow did not appear to be affected by transgenic BH4 augmentation. This thesis provides important new knowledge about the use of primary mouse endothelial cells in vascular research and insight into the role of BH4 availability on endothelial growth in a vascular disease setting.
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Ripszam, Matyas. "Bioavailability of organic contaminants in a changing climate." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-98828.
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The effects of predicted future climate change was investigated with special emphasis on the association of organic contaminants with dissolved organic carbon (DOC) in the Baltic Sea. An automated method was developed for the measurements of DOC - water distribution constants at realistic DOC concentrations in brackish water. The method proved to be valid for 30 organic contaminants with different structural elements in the 5 – 100 mg car bon/L DOC concentration range. There were limitations of this method. Firstly, its applicability is limited towards contaminants with lower affinity to DOC. Secondly, at higher (>100 mg carbon/L) DOC concentrations the sorption of contaminants was underest imated. Afterwards, water samples were collected from 15 points within the Baltic Sea in a north - south gradient t o examine the spatial differences in DOC characteristics and sorption properties . The DOC samples were analyzed using proton nuclear magnetic resonance and ultraviolet spectroscopy. Results from both techniques indicated that the aromatic nature of the DOC pool increased towards the northern Baltic Sea. This was expected as the freshwater inflow has high significance in controlling the hydrograp hic conditions in the Bothnian Bay. Sorption of organic contaminants was subsequently measured in the same samples. The results showed decreased sorption from north to south for hydrophobic contaminants such as chlorinated benzenes but for contaminants lik e tributyl - phosphate no spatial tendencies were observed. The data generated was used to determine molecular descriptors of DOC using linear free energy relationships. The results indicated a higher significance of hy drogen bond donor/acceptor functional g roups of the DOC in the south. Changes in contaminant distribution were simulated in model pelagic ecosystems at possible endpoints predicted by future climate change scenarios. Separate and combined effects of temperature a nd DOC were studied in mesocosms. The results indicated interesting tendencies. Increased temperature resulted in increased losses in the amounts of organic contaminants. Increased DOC levels promoted sedimentation and sorption of contaminants to particulate matter and biota. Hi gher amounts of contaminants were retained. The combined effects of the two factors led to and overall decrease in dissolved amounts. Higher losses or increased sedimentation and sorption to particles were also observed depending on contaminant properties.EcoChange
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Russell, Lisa Maria. "Dermatopharmacokinetics : an approach to evaluate topical drug bioavailability." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512306.
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Skin, more specifically the outermost skin layer, the stratum corneum (SC), forms an extremely effective barrier, preventing both the loss of heat and water, and the ingress of micro-organisms and chemicals. Assessing the rate and extent of drug permeation into or through the skin is important both to evaluate the usefulness of a drug for topical or transdermal delivery, and to compare different formulations to assess their bioequivalence. Prediction of drug permeation is logistically, ethically and economically preferable to in vivo measurements. The recent progress that has been made with empirical and mechanistic mathematical models, along with in vitro diffusion cell techniques has been reviewed. However, currently, in vivo measurements, in man, are still required. For new chemical entities, the need for clinical trials is clear. In the case of generic products, however, there is considerable effort currently being expended to replace expensive, subjective clinical trials with objective, validated measurements of drug permeation, in vivo, in particular to assess bioequivalence. The tape stripping technique has emerged as a promising technique to objectively measure drug permeation through skin, and is the focus of this thesis. After formulation application and removal, layers of SC are sequentially removed by adhesive tapes. As the SC performs the main barrier function of the skin, measuring the rate and extent of drug permeation through this layer is assumed to be related to overall topical bioavailability. The work in this thesis concentrates on performing tape stripping studies such that all tapes are analysed individually, and drug concentration as a function of SC depth is measured. The concentration depth profiles across the SC may be fitted to an appropriate solution of Fick's second law of diffusion to obtain estimates of the vehicle-SC partition coefficient and the drug's diffusivity in the membrane. These dermato-pharmacokinetic parameters may be compared for different formulations.
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Lim, Jina. "EVALUATION OF L-METHIONINE BIOAVAILABILITY IN NURSERY PIGS." UKnowledge, 2015. http://uknowledge.uky.edu/animalsci_etds/54.
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DL-Methionine (Met) has been conventionally used in swine diets with assumption of similar bioefficacy with L-Met. However, because L-Met is the form that is utilized by animals for protein synthesis, L-Met could, theoretically, be more available. Four experiments were conducted to evaluate L-Met bioavailability in nursery pigs with 21-day growth trials. A total of 105,105,112 and 84 crossbred pigs were used in Exp. 1, 2, 3 and 4, respectively. Each experiment had a low Met basal diet and 3 levels of the Met sources (DL-Met and L-Met). In addition to the basal diet, supplementation levels were 0.053%, 0.107% and 0.160% in Exp. 1, 0.040%, 0.080% and 0.120% in Exp. 2, 0.033%, 0.067% and 0.100% in Exp.3, 0.040%, 0.080% and 0.120% in Exp. 4. Body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), gain: feed (G:F) were measured and plasma urea nitrogen (PUN) was analyzed in blood samples weekly. In Exp. 3 and 4, preference studies were conducted with the basal diet and the second highest level of each Met source. When additional DL-Met or L-Met were supplemented to the basal diet, BW, ADG, ADFI, and G:F ratio increased (P < 0.05). In the comparison between the DL-Met and L-Met diets in Exp. 1, pigs in the L-Met group had greater ADG and G:F ratios in the d 0-7 (P < 0.05) period than those in the DL-Met group. However, there were no differences for the overall experimental period. In Exp. 2, pigs in the DL-Met group had greater BW (P < 0.05), ADG (P < 0.05) and ADFI (P < 0.05) than those in the L-Met group for the overall period whereas no differences were observed in G:F ratios and PUN concentrations. In Exp. 3 and 4, there were no differences in BW, ADG, ADFI, G:F ratios or PUN concentrations between L-Met and DL-Met groups for the overall period. There was no preference exhibited for either the DL-Met or L-Met diet. In the results of relative bioavailability of L-Met to DL-Met, the values was 111.1% for d 0-14 based on the estimation by ADG in Exp. 1; L-Met bioavailability was lower than DL-Met based on all response measures in Exp. 2. However, in Exp. 3, relative bioavailability of L-Met to DL-Met was 100.4, 147.3, and 104.1% for d 0-14 ADG, G:F ratio and PUN concentrations. In Exp 4, the relative bioavailability of L-Met was 92.9, 139.4 and 70.4% for d 0-14 ADG, G:F ratio and PUN concentrations. In conclusion, using L-Met in the nursery diet demonstrated no consistent beneficial effect on ADG, G:F ratio or relative bioavailability compared to conventional DL-Met.
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Magnus, Ashley Denis. "Aspects of the bioavailability of topical corticosteroid formulations." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1009516.
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Two possible variables of the McKenzie/Stoughton blanching assay, namely amount applied to the test site and occlusion time have been investigated. Subsequently, two topical steroid preparations, Synalar cream (0,025% fluocinolone acetonide) and Betnovate cream (0,1% betamethasone 17-valer ate) were extemporaneously diluted with five and six placebo bases respectively. Taking cognizance of the two possible variables, these diluted preparations were assessed in vivo using a modified version of the McKenzie/Stoughton blanching assay for blanching activity over a 14 month period. It was found that the base E45, which is slightly alkali, had the greatest effect on both preparations. In the case of betamethasone 17-valerate this base c aused the conversion to the less active isomer, betamethasone 21-valerate whereas at the end of the 14 month test period it was found that the Synalar/E45 dilution contained no fluocinolone acetonide. Quantitative analysis of all the diluted preparations by high performance liquid chromatography using a reverse-phase system was performed. The data obtained f r om the systematic stUdies of the effects of varying concentrations and occlusion times were presented at the Eleventh National Congress of the South African Pharmacological Society.KMBT_363
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Conder, Jason M. "Bioavailability and toxicity of 2,4,6-trinitrotoluene in sediment." Thesis, University of North Texas, 2004. https://digital.library.unt.edu/ark:/67531/metadc5549/.
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TNT (2,4,6-trinitrotoluene) is a persistent contaminant at many military installations and poses a threat to aquatic ecosystems. Data from environmental fate and toxicity studies with TNT revealed that sediment toxicity test procedures required modification to accurately assess sediment TNT toxicity. Key modifications included aging TNT-spiked sediments 8-14 d, basing lethal dose on measured sediment concentrations of the molar sum of TNT and its main nitroaromatic (NA) transformation products (SNA), basing sublethal dose on average sediment SNA concentrations obtained from integration of sediment SNA transformation models, avoiding overlying water exchanges, and minimizing toxicity test durations. Solid phase microextraction fibers (SPMEs) were investigated as a biomimetic chemical measure of toxicity and bioavailability. Both organism and SPME concentrations provided measures of lethal dose independent of exposure scenario (TNT-spiked sediment or TNT-spiked water) for Tubifex tubifex. Among all benthic organisms tested (Chironomus tentans, Ceriodaphnia dubia, T. tubifex) and matrixes, median lethal dose (LC50) estimates based on SPME and organism concentrations ranged from 12.6 to 55.3 mmol SNA/ml polyacrylate and 83.4 to 172.3 nmol SNA/g tissue, ww, respectively. For Tubifex, LC50s (95% CI) based on SNA concentrations in sediment and SPMEs were 223 (209-238) nmol SNA/g, dw and 27.8 (26.0-29.8) mmol SNA/ml, respectively. Reproductive effects occurred at slightly lower exposures. Median effective dose (EC50) estimates (95% CI) for Tubifex cocoon production, based on sediment and SPME concentrations, were 118 (114-122) nmol SNA/g, dw and 21.8 (21.2-22.4) mmol SNA/ml, respectively. Bioconcentration experiments with Tubifex revealed that compound hydrophobicity predicted the toxicokinetics and bioconcentration of these compounds from water, however, there was a large discrepancy between the toxicokinetics of absorbed versus metabolically-generated aminodinitrotoluenes. A large portion of bioconcentrated, radiolabeled TNT transformation products could not be identified. In addition to their ability to provide matrix-independent measures of dose, SPME concentrations were more accurate indicators of bioavailable NAs than were sediment concentrations.
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Meyer, Eric. "Comparative bioavailability and ranking of topical corticosteroid formulations." Thesis, Rhodes University, 1985. http://hdl.handle.net/10962/d1001471.
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Numerous experiments in recent years have indicated differences in the bioavailability of corticosteroids from seemingly identical topical dosage forms. The human blanching assay was utilized in this study to assess the comparative blanching activities of various locally manufactured proprietary corticosteroid preparations. The first experiment was performed to assess the relative blanching activities of six semi - solid preparations containing the same concentration of betamethasone 17-valerate. The preparations used were Betnovate cream and ointment, Persivate cream and ointment and Celestoderm-V cream and ointment. This was followed, in the second experiment, by the investigation of the blanching activities of two lotions containing betamethasone 17-valerate (Betnovate and Celestoderm-V) and a lotion containing betamethasone 17,21- dipropionate (Diprosone). The third experiment involved a study of six semi-solid proprietary corticosteroid-containing formulations, viz. Dermovate (clobetasol propionate) cream and ointment, Betnovate (betamethasone 17-valerate) cream and ointment and Eumovate (clobetasone butyrate) cream and ointment. This investigation was prompted by claims in advertisements in the medical media that Dermovate is therapeutically more efficacious than Betnovate which is more efficacious than Eumovate. The penultimate experiment in this study served the purpose of finding a corticosteroid-containing preparation that falls into the moderately potent group of corticosteroid formulations, as described in the United Kingdom MIMS. This preparation was used in the final experiment which was undertaken to ascertain the potency category of Florone (diflorasone diacetate) cream and ointment.
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Öhrvik, Veronica. "Folate bioavailability in vitro experiments and human trials /." Uppsala : Dept. of Food Science, Swedish University of Agricultural Sciences, 2009. http://epsilon.slu.se/200963.pdf.
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