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Sediments can act as both reservoir and source of legacy organic contaminants such as polychlorinated biphenyls (PCBs). Due to their chemical stability and ubiquity, these contaminants remain as model class of compounds in the field of sediment contamination. Whole sediment and organism concentrations have been often used as exposure metrics for ecological risk assessments. However, whole sediment concentrations often overestimate the potential for exposure to contaminants; while organism concentrations based on bioassay provide a better estimate of exposure, bioassays can also be labor intense, time consuming and expensive. Alternatively, accessiblity-based techniques such as Tenax extractions have been gaining ground, in the last few decades, as a rapid, reliable, and cost-effective approach to estimate exposure to organic contaminants from sediments. Tenax extractions measure the bioaccessible fraction of the contaminant that desorbes from sediment. Despite the simplicity, accuracy and robustness of the Tenax technique to estimate bioaccessibility of organic contaminants, there are still some remaining questions regarding the methodological standardization, and the applicability of the technique in sediments containing diverse carbonaceous sorbents associated adsorption/desorption of the contaminant. Therefore, the chapters of this dissertation were designed to address these questions. To this end, PCBs were chosen as a model compound class to represent a wide range of physicochemical properties of persistent organic contaminants, and because these compounds remain a worldwide legacy contamination problem. The dissertation goals were to: determine the best operational conditions for Tenax technique (Chapter 2); monitor the changes in bioaccessibility of field-collected sediments with different holding time conditions (Chapter 3); examine the effects of the type and quantity of organic carbon on bioaccessibility (Chapter 4); and evaluate the applicability of the Tenax technique to assess remediation success in contaminated marine sediments (Chapter 5). To address the methodological standardization of the Tenax technique, the operational parameters of solvent extract volume, Tenax sorption rate from water, and Tenax:OC (Tenax:Organic Carbon) ratios were investigated in Chapter 2. The highest efficiency of extraction of sorbed PCBs from Tenax resulted from using a 10 mL per each solvent wash during Tenax extraction procedure. For the Tenax sorption, it was found that 0.01 g of Tenax cleared PCB in 40 mL of water in 30 min, thus it would clear the water 48 times in 24 h. When this is extrapolated to the 0.5 of Tenax, typical amount used, it was found that the amount should clear the typical volume of water used on Tenax extraction about 2400 times. This represents unequivocal evidence that the Tenax resin would remove PCBs dissolved in the liquid phase (e.g., overlying or interstitial water) present in the sediment sample and be limited only by compound desorption and not by the Tenax sorption capacity. The results examining the impact of the relationship between the amount of Tenax required and the amount of organic carbon in the sediment extraction indicated that a minimum of 5:1 Tenax:OC ratio be used to conduct Tenax extractions. This will reduce (eliminate) the possibility of re-adsorption by the native OC in the sediment in competition with the Tenax. After ascertaining the best operational conditions for Tenax extractions, two additional methodological uncertainties, the effect of storage time after collection and the preservation method associated with the handling of collected sediment samples were investigated in Chapter 3. The effect of holding time and the preservation method on PCB concentrations from field-collected sediments was examined for a period of 196 d. All samples were held at 4 ºC in the dark and several holding times were chosen. The parameters to track the changes in PCB concentration in two sediments used three exposure metrics: exhaustive solvent extraction, tissue concentrations and Tenax extractions (Chapter 3). The results showed that the total exhaustive concentrations representing the whole sediment concentrations did not significantly change (ANOVA, p> 0.05) in either sediment over the course of 196 d. Similar results were also found for the total Tenax concentrations that represented the bioaccessible sediment concentrations, and for the total organism tissue concentrations representing exposure. The likely equilibrium of PCB in the sediment, their chemical stability of PCB and slow degradation can be underlined as the main factors leading to these results. The long time that legacy contaminants such as PCBs have been in contact with contaminated sites (e.g., Superfund sites) might have contributed to an equilibrium to be reached between the sediment particles and PCB molecules. The significance of this chapter is that sediments collected from PCB-contaminated sites can be stored longer than the 14 d as recommended by current standard protocols without disturbing the measures of bioavailability. The role of organic carbon composition within sediment on contaminant sorption was also investigated to ascertain the effects of type and quantity of OC from different origins on the bioaccessibility of PCBs in contaminated sediments (Chapter 4). Changes in PCB bioaccessibility in sediments amended at either 3 or 6% by dry weight with black carbon (BC), humic acid (HA) or sawdust (SD), showed that the lowest and highest PCB bioaccessibilities were observed in the BC and SD amendments, respectively. Specifically, the total amount of PCBs desorbed ranges from 3 to 27% for BC amendments, 12 to 55% for HA amendments and 16 to 80% for SD amendments. The results showed the influence of OC quantity on bioaccessibility having a much slower desorption of PCBs in 6% amendments compared to 3% amendments, and this finding was most evident in HA and BC amendments. The results also showed that the Tenax technique can be applied to tract the variation in type of carbon and quantity of OC in contaminated sediment to estimate exposure. Finally, the applicability of the Tenax technique as tool to assess the remediation success of PCB-contaminated marine sediments upon AC amendment at either 4.3 or 0.026% AC by dw was examined in Chapter 5. The results showed that bioaccessibility of PCBs was greatly reduced in sediment amended at the higher AC dose (4.3%); while, reduction was also observed even in the sediment amended at 0.026% AC. Furthermore, the results revealed that Tenax concentrations reflected the PCB reduction among AC amended sediments in the same direction as the PCB reduction in the organism bioaccumulation. Overall, this dissertation provides further evidence that the Tenax technique is a rapid, reliable, and cost-effective tool for estimating exposure to recalcitrant organic contaminants such as PCBs from contaminated sites. The applicability of the technique to estimate bioaccessible compound from both freshwater and marine aquatic sediments underline the robustness of the technique to widen its use among risk ecological assessor and researchers.

Chicken breast muscle was cooked to an internal temperature of 165oF by four methods: boiling, baking, sautéing and deep-frying. All cooking methods led to a decrease in formation of dialyzable iron, formed by both extraction and digestion in vitro, compared to raw muscle. After cooking most of the dialyzable iron formed results from extraction and the formation of dialyzable iron by digestion is essentially eliminated. Cooking also decreased the levels of cysteine and histidine; these losses may contribute to the loss in dialyzable iron.

A research report submitted in partial fulfilment of Mathematical Statistics Masters by Coursework and Research Report to the Faculty of Science, University of the Witwatersrand, Johannesburg, 2019 / The growing demand for generic drugs has led to an increase in the generic drug industry. As a result, there has been a growing demand for bioequivalence studies. The challenges with the bioequivalence studies arose with the method used to quantify bioavailability. Bioavailability is commonly estimated by the area under the concentration-time curve (AUC), which is traditionally estimated by Non-Compartmental Analysis (NCA) such as interpolation in aid of the trapezoidal rule. However, when the number of samples per subject is insufficient, the NCA estimates may be biased and this can result in incorrect conclusions about bioequivalence. Alternatively, AUC can be estimated by the Non-Linear Mixed Effect Model (NLMEM). The objective of this study is to evaluate bioequivalence on lnAUC estimated by using a NCA approach to those based on the lnAUC estimated by the NLMEM approach. The NCA and NLMEM approaches are compared on the resulting bias when the linear mixed effect model is used to analyse the lnAUC data estimated by each method. The methods are evaluated on simulated and real data. The 2x2 crossover designs of different sample sizes and sampling time intensities are simulated using two null hypotheses. In each crossover design, concentration profiles are simulated with different levels of between-subject variability, within-subject variability and residual error variance. A higher bias is obtained with the lnAUC estimated by the NCA approach for trials with a limited number of samples per subject. The NCA estimates provide satisfactory global TypeI-error results. The NLMEM fails to distinguish between the existing formulation differences when the residual variability is high. / TL (2020)

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<p>Methionine (Met) is an essential amino acid (EAA) and is often considered one of the first limiting amino acids (AA) for milk production in dairy cattle. In diets of lactating dairy cattle, in the United States (U.S.), Met is considered limiting due to its low abundance in commonly fed ingredients like soybean and corn and its high degradability in the rumen. To circumvent this problem, rumen-protected Met (RPM) products were produced and are currently supplemented to dairy cattle. Supplemental RPM products protect Met from degradation in the rumen and deliver Met to the intestine to be absorbed into circulation, increasing metabolizable Met supply. Due to Met important roles in protein synthesis and as a methyl donor, dairy producers have supplemented RPM for decades. The primary benefit for supplementing RPM is improved milk protein concentration, which is important as a majority of dairy farms in the U.S. are paid based on milk components. </p> <p>Research is focused on finding a more economically viable RPM product that provides similar or better bioavailability of Met compared to commercially available products. This has led to the development of a novel rumen-protected Met product (EMT 3.4) in which Met is added to the soluble portion of distillers and incorporated with distillers grains. The result is distillers grains with solubles (DDGS) with elevated Met concentration. Incorporating Met into the solubles portion of DDGS has shown to protect Met from degradation when analyzed in vitro but has not been assessed in vivo. Thus, the primary objective of this study was to evaluate the bioavailability of EMT 3.4 via dilution of selenomethionine (SeMet) in milk protein and secondarily its impact on milk production and body composition. Dietary selenium (Se) yeast will deliver SeMet to the intestines and subsequently be absorbed. After adequate time feeding Se yeast, SeMet will label the different pools of Met similar to feeding radiolabeled nitrogen (N). Once pools of Met are labeled with SeMet, milk Se, a proxy for SeMet, can be measured in the milk. Concentrations of milk Se will fluctuate based on entry of Met, and as Met increases in the milk, the concentration of Se will decrease. To asses bioavailability milk Se is divided by milk N (Se:N) and the ratios of the treatments can be compared.</p> <p>The objective of this study was to evaluate the bioavailability of a novel rumen protected Met product and its effect on milk production and body composition compared to positive and negative controls. Dietary treatments consisted of a negative control treatment (NCT), not supplemented with RPM, a positive control treatment (PCT), supplemented Met via Smartamine M, and the experimental Met treatment (EMT), supplemented Met via EMT 3.4. Cattle fed PCT and EMT exhibited improved bioavailability indicated by a reduction in milk Se to milk N ratio when compared to NCT cows. Using milk Se concentration as an indicator of entry rate and amount of Met in the milk pool, PCT cows had a significantly lower milk Se concentration compared to NCT. Lower milk Se concentration of PCT cows indicates greater amount of Met in milk and subsequently a significantly greater milk protein yield was observed in PCT. Although EMT had similar bioavailability to PCT, the EMT cows had an intermediate response in milk Se but no production responses. The lack of production responses in EMT was observed alongside an elevated milk urea nitrogen (MUN) and a negative change in longissimus dorsi depth (LDD). A negative change in body weight (BW) was observed in NCT cows. Changes in body composition, as the ones observed in this study, are not usually observed unless cattle are energy or protein deficient. Given that diets of this study were formulated to meet requirements for producing 40 kg/day of milk and on average cattle were producing less, it is unlikely that cattle were energy or protein deficient. Results demonstrated that EMT provided similar Met bioavailability as Smartamine M in PCT demonstrated by responses in milk Se:N. The PCT tended to increase milk yield and increased milk protein, whereas EMT provided no observable production responses in this study.</p> <p><br></p>

京都大学 / 新制・課程博士 / 博士(薬科学) / 甲第24548号 / 薬科博第165号 / 新制||薬科||18(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 山下 富義, 教授 髙倉 喜信, 教授 寺田 智祐 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM