Thesis (M.Sc.) -- Memorial University of Newfoundland, 1984. / Bibliography : leaves 139-147. Also available online.

Thesis (Ph.D.) - University of Queensland, / Includes bibliography.

No description available.

No description available.

Calcium bioavailability was investigated using isotopic intestinal absorption, and balance study techniques with bone mineralization and biomechanics as endpoint determinants of calcium utilization. In experiment 1, lactose enhancement of paracellular calcium absorption was confirmed, and it was suggested that a critical luminal concentration of lactose was necessary for its action. Despite the enhanced intestinal absorption of calcium in animals fed the 50% lactose containing diet, bone mineralization was not different from controls; and further, a decrease in bone strength of these animals was found to be secondary to nutrient malabsorption. In this study, there was no evidence to indicate a difference in the bioavailability of calcium from milk (colloidal) or yogurt (ionized) sources. In experiment 2, the absorption of calcium from the ileum was significantly enhanced in[formula omitted] normal Wistar rats fed milk protein diets containing casein as compared to whey and soy protein diets. The increase in absorbed calcium was shown to have little physiological significance in bone mineralization and biomechanics when animals were fed a diet adequate in dietary calcium. In experiment 3, paracellular calcium absorption was similar between genetically spontaneously hypertensive (SHR) and normotensive control Wistar-Kyoto (WKY) rats, suggesting that differences in calcium metabolism between these two strains was not due to differences in ileal calcium transport. The effect of casein and soy protein diets containing high (2.0%), adequate (0.5%) and low (0.05%) levels of calcium, respectively on calcium bioavailability and subsequent utilization was determined in SHR and WKY animals. Ileal calcium absorption was greater in casein fed animals than those fed soy at the adequate and low levels of calcium. Femur calcification was enhanced by casein diets at the high and medium levels of dietary calcium only. Femur biomechanics were not influenced by dietary protein source, but were however, adversely affected by the low dietary calcium level. In experiment 4, the effect of dietary fortification with casein phosphopeptides (CPP) was investigated in casein and soy fed SHR animals. CPP added to casein and soy protein diets appeared to result in a greater ileal absorption of calcium. This increase in calcium bioavailability from the casein diet had little effect however, on bone mineralization and biomechanical strength, due to the excretion of excess absorbed calcium. In experiment 5, severe thermal processing of dietary proteins was shown to reduce in vitro digestibility. Animals fed heat denatured casein and soy diets exhibited reduced intestinal calcium absorption, calcium balance as well as bone mineralization and biomechanics. These effects were influenced by the nutrient malabsorption experienced by these animals. In experiment 6, a low (6%) protein, low phosphorus diet resulted in decreased food intake and animal growth. However, ileal calcium absorption (% dose) was similar between 6% and 20% protein fed animals. A low level of dietary protein influenced calcium balance and utilization for bone mineralization and biomechanical strength. These results indicate that paracellular calcium absorption may not necessarily equate with those obtained from a calcium balance study. Notwithstanding, calcium bioavailability from the ileum was shown to be enhanced in animals fed casein, which was likely due to the production of bioactive peptides (CPP) that are involved in sequestering calcium and retaining it in a soluble form. By reducing protein digestibility with heat denaturation, this effect was lost. Reducing the protein content in the diet however, did not reduce the enhancement of calcium bioavailability observed in casein fed animals. Finally, bone mineralization and biomechanical parameters were shown to be sensitive indicators of calcium utilization from diets that varied in calcium content or bioavailability of this mineral. / Land and Food Systems, Faculty of / Graduate

The current period of human history is considered to be the plastics age due to its versatile characteristics, especially the lightweight, durability and low production cost. Plastics can be manufactured to suit multifarious functions, for example, for personal care products, food/drink storage and medical purposes. Thus, the use of plastics is unavoidable now, finally contributing to the severe pollution worldwide. In 2018 alone, the global plastics production amount has exceeded 359 million tons, around 10% of which ultimately become waste persisting in the environment. When plastic wastes exposed to the sun's radiation, climate change and mechanic abrasion, degradation and fragmentation may occur. Once the size of the fragmentation products is less than 5 mm, they are commonly defined as microplastics (MPs) by the National Oceanographic and Atmospheric Administration. Currently, microplastics have been regarded as the most pervasive environmental pollution problems, not only because of their physical hazards but also due to their interactions with other pollutants in the environment. Pollution can be attributed by the release of additives from MPs, as well as the MPs with adsorbed toxic contaminants. Moreover, MPs additives together with adsorbed chemicals can be easily uptaken by animals, which may cause further propagated effects on the ambient ecosystem. Through the bioaccumulation and biomagnification effect, MPs can even be accumulated in the organisms from different trophic levels and cause serious impacts on aquatic ecology and human health. Despite growing number of evidences that have confirmed the presence and consequential effects of microplastics, researches on microplastic pollution are still lacking. Investigations on occurrence, determination and environmental fate of MPs in aquatic systems are clearly needed. Therefore, the major objective of this study is to elucidate the distribution of MPs in natural environment, to develop novel determination methods to characterize the micro-(nano-)plastics (MNPs), and to study the interactions of MPs with other contaminants in different conditions, as well as their consequential fate in different matrices (e.g. freshwater, cold-blooded intestine, and warm-blooded intestine). The spatial-temporal distribution of the MPs along the Maozhou River was investigated for both the surface water and sediments from 17 sites. Results showed that MPs were widely and unevenly distributed along the river. The MP abundances in dry season ranged from 4.0 ± 1.0 to 25.5 ± 3.5 items·L-1 in water and 35 ± 15 to 560 ± 70 item·kg-1 in sediments, which were relatively higher than those observed in wet season (water: 3.5 ± 1.0 to 10.5 ± 2.5 items·L-1; sediments: 25 ± 5 to 360 ± 90 item·kg-1; p value < 0.05). The dominant types of MPs were identified as: polyethylene (PE, water: 45.0%, sediments: 42.0%), polypropylene (PP, water and sediments: 12.5%), polystyrene (PS, water: 34.5%; sediments 14.5%) and polyvinyl chloride (PVC, water: 2.0%; sediments: 15%). Moreover, metals such as Al, Si, Ca were discovered on the rough surface of the MPs, indicating the interactions between the MPs and the aquatic environment. After obtaining the occurrence of the MPs in the aquatic systems, we proposed an accurate method for MNPs identification and quantification with the employment of the matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). By optimizing the conditions (e.g. the laser energy, matrix, analyte, cationization agent and their ratio), the peaks of PS and polyethylene terephthalate (PET) were successfully identified. A quantitative correlation was built between the normalized signal intensity and ln[polymer concentration], with a correlation coefficient above 0.96 for low-molecular-weight (LM-) polymers and 0.98 for high-molecular-weight (HM-) polymers. Furthermore, two types of environmental MPs samples were prepared, including the particles of an aviation cup as the fresh plastics and the aged MPs extracted from river sediment. By using MALDI-TOF MS, the PS-related micro-(nano-)plastics (in both aviation cup and sediment) consisted of C8H8 and C16H16O oligomers, while the PET-related MNPs (only found in sediment) were identified with compositions of C10H8O4 and C12H12O4. The contents of PS and PET MNPs in sediment were quantified as 8.56 ± 0.04 and 28.71 ± 0.20 mg·kg-1, respectively. Also, the interaction between MPs and bisphenols was investigated. PVC was selected as the representative target because it is comparatively easy to decompose into MPs with the release of additives, especially the bisphenols. The released bisphenols may then be readsorbed by the PVC MPs and cause consequential pollution to the ecosystem. To elaborate on the interactions mechanism, a systematic study was carried out to determine the adsorption mechanisms of five bisphenol analogues (BPA, BPS, BPF, BPB, and BPAF) on PVC MPs. The equilibrium adsorption numbers of the bisphenols on PVC MPs are 0.19 ± 0.02 mg/g (BPA), 0.15 ± 0.01 mg/g (BPS), 0.16 ± 0.01 mg/g (BPF), 0.22 ± 0.01 (BPB), 0.24 ± 0.02 mg/g (BPAF), respectively. Intraparticle diffusion modeling (kinetics) divided the adsorption process into three stages: external mass transport, intraparticle diffusion and dynamic equilibrium. The isotherm results showed a better fit of the adsorption to the Freundlich model. Furthermore, the adsorption mechanisms of the five bisphenol analogues were explored intensively, with respect to hydrophobic interaction, electrostatic force and noncovalent bonds. Besides the adsorption process, the transfer and release behaviors of contaminated MPs are of critically importance in the exploration of their role as culprits and/or vectors for the aforementioned toxicity. Therefore, experiments were performed to examine desorption behaviors and cytotoxicity performance of contaminated MPs in aquatic surroundings and intestinal environment after ingestion by organisms (cold-/warm-blooded). The kinetic study showed that the rate of desorption for bisphenols could be enhanced threefold under simulated warm intestinal conditions. The Freundlich isotherms indicated multiple-layer desorption of the bisphenols on the heterogeneous surfaces of PVC MPs. Hysteresis was detected in the adsorption/desorption of bisphenols in a water environment, but no adsorption/desorption hysteresis was observed in the simulated intestinal conditions of warm-blooded organisms. Due to the enhanced bioaccessibility, the desorption results implied that the environmental risk of contaminated PVC MPs might be significantly increased after ingestion at a high bisphenols dosage. Although with different IC50, the five bisphenols released under the intestinal conditions of warm-blooded organisms can cause higher proliferation reduction in fish and human cell lines than the bisphenols released in water. In summary, this study elucidated the spatial-temporal distribution behaviors of MPs, developed effective determination methods for MNPs revealed the interactions mechanisms of MPs with other contaminants, and explored their consequential fate in different environments. The obtained results are helpful of better understanding on the land-based input of MPs from the intensively affected inland waters, realizing the role of microplastics as both source and carrier for emerging organic pollutants, and providing a novel alternative for MPs determination in future studies.

The gastrointestinal tract has a large functional reserve. This is particularly true of the small intestine, and early studies by Flint in 1912, showed that dogs could withstand 50%-70% small intestinal resection, returning to normal health after an initial period of weight loss and malabsorption. No doubt, this reserve is in part due to the very high rate of epithelial proliferation in small bowel mucosa. Intestinal adaptation is the result of morphological and functional changes, and while these parameters can be accurately appreciated, the mechanisms by which these changes take place, are still under active investigation. This section summarises the changes, both structural and functional, in the adaptive process, and this is followed by a review of the background work done on the possible mechanism of adaptation. The normal anatomy of intestinal mucosa is however, considered first. Most of the work done to date in the field of intestinal adaptation, involves the small bowel, and this part of the gut will be discussed predominantly, but data available on colonic growth will be mentioned.

The current period of human history is considered to be the plastics age due to its versatile characteristics, especially the lightweight, durability and low production cost. Plastics can be manufactured to suit multifarious functions, for example, for personal care products, food/drink storage and medical purposes. Thus, the use of plastics is unavoidable now, finally contributing to the severe pollution worldwide. In 2018 alone, the global plastics production amount has exceeded 359 million tons, around 10% of which ultimately become waste persisting in the environment. When plastic wastes exposed to the sun's radiation, climate change and mechanic abrasion, degradation and fragmentation may occur. Once the size of the fragmentation products is less than 5 mm, they are commonly defined as microplastics (MPs) by the National Oceanographic and Atmospheric Administration. Currently, microplastics have been regarded as the most pervasive environmental pollution problems, not only because of their physical hazards but also due to their interactions with other pollutants in the environment. Pollution can be attributed by the release of additives from MPs, as well as the MPs with adsorbed toxic contaminants. Moreover, MPs additives together with adsorbed chemicals can be easily uptaken by animals, which may cause further propagated effects on the ambient ecosystem. Through the bioaccumulation and biomagnification effect, MPs can even be accumulated in the organisms from different trophic levels and cause serious impacts on aquatic ecology and human health. Despite growing number of evidences that have confirmed the presence and consequential effects of microplastics, researches on microplastic pollution are still lacking. Investigations on occurrence, determination and environmental fate of MPs in aquatic systems are clearly needed. Therefore, the major objective of this study is to elucidate the distribution of MPs in natural environment, to develop novel determination methods to characterize the micro-(nano-)plastics (MNPs), and to study the interactions of MPs with other contaminants in different conditions, as well as their consequential fate in different matrices (e.g. freshwater, cold-blooded intestine, and warm-blooded intestine). The spatial-temporal distribution of the MPs along the Maozhou River was investigated for both the surface water and sediments from 17 sites. Results showed that MPs were widely and unevenly distributed along the river. The MP abundances in dry season ranged from 4.0 ± 1.0 to 25.5 ± 3.5 items·L-1 in water and 35 ± 15 to 560 ± 70 item·kg-1 in sediments, which were relatively higher than those observed in wet season (water: 3.5 ± 1.0 to 10.5 ± 2.5 items·L-1; sediments: 25 ± 5 to 360 ± 90 item·kg-1; p value < 0.05). The dominant types of MPs were identified as: polyethylene (PE, water: 45.0%, sediments: 42.0%), polypropylene (PP, water and sediments: 12.5%), polystyrene (PS, water: 34.5%; sediments 14.5%) and polyvinyl chloride (PVC, water: 2.0%; sediments: 15%). Moreover, metals such as Al, Si, Ca were discovered on the rough surface of the MPs, indicating the interactions between the MPs and the aquatic environment. After obtaining the occurrence of the MPs in the aquatic systems, we proposed an accurate method for MNPs identification and quantification with the employment of the matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). By optimizing the conditions (e.g. the laser energy, matrix, analyte, cationization agent and their ratio), the peaks of PS and polyethylene terephthalate (PET) were successfully identified. A quantitative correlation was built between the normalized signal intensity and ln[polymer concentration], with a correlation coefficient above 0.96 for low-molecular-weight (LM-) polymers and 0.98 for high-molecular-weight (HM-) polymers. Furthermore, two types of environmental MPs samples were prepared, including the particles of an aviation cup as the fresh plastics and the aged MPs extracted from river sediment. By using MALDI-TOF MS, the PS-related micro-(nano-)plastics (in both aviation cup and sediment) consisted of C8H8 and C16H16O oligomers, while the PET-related MNPs (only found in sediment) were identified with compositions of C10H8O4 and C12H12O4. The contents of PS and PET MNPs in sediment were quantified as 8.56 ± 0.04 and 28.71 ± 0.20 mg·kg-1, respectively. Also, the interaction between MPs and bisphenols was investigated. PVC was selected as the representative target because it is comparatively easy to decompose into MPs with the release of additives, especially the bisphenols. The released bisphenols may then be readsorbed by the PVC MPs and cause consequential pollution to the ecosystem. To elaborate on the interactions mechanism, a systematic study was carried out to determine the adsorption mechanisms of five bisphenol analogues (BPA, BPS, BPF, BPB, and BPAF) on PVC MPs. The equilibrium adsorption numbers of the bisphenols on PVC MPs are 0.19 ± 0.02 mg/g (BPA), 0.15 ± 0.01 mg/g (BPS), 0.16 ± 0.01 mg/g (BPF), 0.22 ± 0.01 (BPB), 0.24 ± 0.02 mg/g (BPAF), respectively. Intraparticle diffusion modeling (kinetics) divided the adsorption process into three stages: external mass transport, intraparticle diffusion and dynamic equilibrium. The isotherm results showed a better fit of the adsorption to the Freundlich model. Furthermore, the adsorption mechanisms of the five bisphenol analogues were explored intensively, with respect to hydrophobic interaction, electrostatic force and noncovalent bonds. Besides the adsorption process, the transfer and release behaviors of contaminated MPs are of critically importance in the exploration of their role as culprits and/or vectors for the aforementioned toxicity. Therefore, experiments were performed to examine desorption behaviors and cytotoxicity performance of contaminated MPs in aquatic surroundings and intestinal environment after ingestion by organisms (cold-/warm-blooded). The kinetic study showed that the rate of desorption for bisphenols could be enhanced threefold under simulated warm intestinal conditions. The Freundlich isotherms indicated multiple-layer desorption of the bisphenols on the heterogeneous surfaces of PVC MPs. Hysteresis was detected in the adsorption/desorption of bisphenols in a water environment, but no adsorption/desorption hysteresis was observed in the simulated intestinal conditions of warm-blooded organisms. Due to the enhanced bioaccessibility, the desorption results implied that the environmental risk of contaminated PVC MPs might be significantly increased after ingestion at a high bisphenols dosage. Although with different IC50, the five bisphenols released under the intestinal conditions of warm-blooded organisms can cause higher proliferation reduction in fish and human cell lines than the bisphenols released in water. In summary, this study elucidated the spatial-temporal distribution behaviors of MPs, developed effective determination methods for MNPs revealed the interactions mechanisms of MPs with other contaminants, and explored their consequential fate in different environments. The obtained results are helpful of better understanding on the land-based input of MPs from the intensively affected inland waters, realizing the role of microplastics as both source and carrier for emerging organic pollutants, and providing a novel alternative for MPs determination in future studies.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Aim. Baicalein is a bioactive flavonoid component isolated from the root of Scutellaria baicalensis, which has been used as a traditional Chinese medicinal herb for the treatment of inflammation for centuries. Although various pharmacological effects of baicalein have been demonstrated, only limited studies in rats reported pharmacokinetic of baicalein, which exhibited a low oral bioavailability due to extensive first-pass metabolism. In addition, no investigation on human oral absorption or metabolic kinetic profile was reported previously. The current project conducted a series of mechanistic studies aiming to elucidate the intestinal absorption, metabolism and disposition of baicalein. Since glucuronidation plays an important role in the first-pass metabolism of flavonoids including baicalein, additional studies on the relationship between human intestinal glucuronidation activities and chemical structures of flavonoids have also been performed. / Conclusion. Baicalein is well absorbed at intestine but subjected to extensive intestinal glucuronidation resulting in low oral bioavailability. The glucuronidation of baicalein is catalyzed by multiple UGT isozymes. The disposition of baicalein 7-O-glucuronide, the major metabolite of baicalein in vivo, is mediated by the MRP and OATP transporters. The nucleophilicity and stereo-conformation of -OH substituents are crucial for the intestinal glucuronidation of flavonoids. / Methods. For investigation on intestinal absorption, metabolism and disposition of baicalein, human Caco-2 cell monolayer model, rat in situ intestinal perfusion model, and in vitro metabolism model were employed in the present study. For the further investigation on the position preference on glucuronidation of flavonoids at human intestine, the in vitro rates of glucuronidation among seven commercially available mono-hydroxyflavones, namely 3-, 5-, 6-, 7-, 2'-, 3'- and 4'-mono-hydroxyflavones were determined and compared. / Results. The satisfactory permeabilities of baicalein obtained from both Caco-2 cell model and rat intestinal perfusion model indicated its potential good absorption at gastrointestinal tract. Therefore, absorption should not be the rate-limiting factor causing the low oral bioavailability of baicalein. However, extensive glucuronidation occurred in the rat intestine perfusion model with over 90% of baicalein being metabolized after intestinal absorption. Consistent findings were also observed in the in vitro enzyme kinetic studies of baicalein. The biotransformation of baicalein to baicalein 7-O-glucuronide was extensive in human liver microsome, human jejunum microsome, rat liver microsome, and rat jejunum microsome with intrinsic clearances (Vmax/Km) of 618, 446, 436, 298 mul/min/mg, respectively, which are orders of magnitude greater than those of most of western drugs that share the same metabolic pathway. Further enzyme kinetic studies using human recombinant glucuronosyltransferases (UGT) isozymes showed that UGT 1A1, 1A3, 1A8, 1A9, 1A7 and 2B15 were involved in the glucuronidation of baicalein with different kinetic profiles. Mechanistic studies on the disposition of baicalein 7-O-glucuronide formed from a rapid glucuronidation of baicalein in intestine demonstrated that this intracellularly formed glucuronide of baicalein could be actively extruded to both the apical and basolateral sides (the so called efflux) in Caco-2 cell model as well as rat intestinal perfusion model. It was also found that the efflux of the baicalein 7-O-glucuronide followed saturable enzyme kinetics and was effectively inhibited by multi-drug resistance associated proteins (MRP) and organic anion transporters (OATP) inhibitors. Further study on the relationship between flavonoid structures and glucuronidation activities using seven monohydroxyflavones demonstrated that the conjugation rates of 6- and 3'-monohydroxyflavones (HF) were much greater than those of 3-, 4'-, 7-, 2'-HF, while 5HF was the lowest. / Zhang Li. / "August 2006." / Advisers: Zhong Joan Zuo; Ge Lin. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1587. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 186-223). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.