The aim of the present thesis was to further increase our understanding of mechanisms contributing to and maintaining cellular insulin resistance in type 2 diabetes (T2D). For this reason, the effects of high glucose and insulin levels on glucose transport capacity and insulin signaling, with emphasis on insulin receptor substrate 1 (IRS-1) were assessed in fat cells. Altered levels of IRS-1 have previously been observed in adipose tissue from insulin-resistant and T2D subjects. A high glucose level (≥15 mM) for 24 h exerted only a minor impairment on glucose transport capacity in human adipocytes, as opposed to rat adipocytes. However, when combined with a high insulin level (104 µU/ml), basal and insulin-stimulated glucose transport was significantly impaired in both human and rat adipocytes. This was associated with a depletion of IRS-1 and IRS-2 protein levels in rat adipocytes, as a result of post-translational changes and altered gene transcription, respectively. In human adipocytes was only IRS-1 protein levels reduced. The high glucose/high insulin setting achieved maximal impairment of glucose transport within 6 h. Subsequent incubations of rat adipocytes under physiological conditions could partially restore insulin sensitivity. Interestingly, in both human and rat fat cells, decreased levels of IRSs occurred after the establishment of impaired glucose transport, suggesting that the observed depletion of IRSs is a consequence rather than a cause of insulin resistance. Nonetheless, IRS depletion is likely to further aggravate insulin resistance. Tyrosine phosphorylation of IRS-1 upon insulin stimulation activates the signaling pathway that mediates glucose transport. Pre-treatment of human adipocytes with high glucose and insulin levels was not associated with any alterations in the total IRS-1 Tyr612 phosphorylation following 10 min insulin stimulation. However, a significant increase in basal Tyr612 phosphorylation was observed. Furthermore, a rise in basal IRS-1 Ser312 phosphorylation was found. This is associated with reduced IRS-1 function and is considered to target IRS-1 to degradation pathways, and thus could potentially explain the observed decrease in IRS-1 protein levels. Our results imply an enhanced activation of insulin’s negative-feedback control mechanism that inhibit IRS-1 function. This could potentially have contributed to the observed impairment of insulin action on glucose transport in these cells. Accordingly, we have also shown that the downstream activation of protein kinase B upon insulin-stimulation is significantly impaired in human adipocytes exposed to the high glucose/high insulin setting, indicating a defect in the signaling pathway mediating glucose transport. We also investigated whether there are humoral factors in the circulation of T2D patients that contribute to peripheral insulin resistance. Human adipocytes cultured for 24 h in medium supplemented with 25% serum from T2D subjects, as compared to serum from non-diabetic subjects, displayed significantly reduced insulin-stimulated glucose uptake capacity. The effect could neither be attributed to glucose, insulin, FFA, TNF-α or IL-6 levels in the serum, but other circulating factor(s) seem to be of importance. In conclusion, chronic conditions of elevated glucose and/or insulin levels all impair insulin action on glucose turnover, but to different extents. A clear distinction between rat and human fat cells in the response to these different milieus was also observed. Alterations in the function of the key insulin signaling protein IRS-1 might be involved in the mechanisms underlying the impaired glucose uptake capacity. IRS-1 reduction however, occurs after but probably aggravates the existing insulin resistance. The effects of high glucose and/or insulin levels may be of importance in T2D, but additional novel factors present in the circulation of T2D patients seem to contribute to cellular insulin resistance.

In this study, pharmaceutical-grade and food-grade linker-based lecithin self-emulsifying delivery systems (SEDS) were developed with a combination of lipophilic and hydrophilic linkers. These additives at suggested concentrations are safe for pharmaceutical and food applications. The ratio of surfactant lecithin and linkers in these systems was optimized to develop surfactant in oil preconcentrates. The preconcentrates containing different surfactant concentrations and oil were diluted with fed state simulated intestinal fluid to produce pseudo-ternary phase diagrams and to identify the formulations that produced self-emulsifying or self-microemulsifying delivery systems. Optimal SEDS preconcentrates were evaluated using a dialyzer model to simulate intestinal uptake. An uptake of 39.6 mg/cm2 for the pharmaceutical-grade SEDS was obtained within 72 minutes, which promises substantial improvement in the bioavailability of hydrophobic actives. The optimal uptake of 12.2 mg/cm2 for food-grade SEDS suggests enhancement in the bioavailability of omega-3 fatty acids.

In comparison to other Pseudomonas, P. aeruginosa grows poorly in L-lysine as a sole source of nutrient while fast growth mutants can be obtained. The proposed catabolic pathway involves lysine decarboxylation to cadaverine and its subsequent degradation through g-glutamylation pathway to d-aminovalerate and glutarate. The lysine decarboxylase A (ldcA) gene, previously identified as a member of the ArgR regulon of L-arginine metabolism, was found essential for L-lysine catabolism. The ldcA gene encodes a decarboxylase which takes L-lysine but not L-arginine as substrate. Contrarily, the ldcA expression was inducible by L-arginine but not by L-lysine. This peculiar arginine control on lysine utilization was also noted from uptake experiments. The lack of lysine-responsive control on lysine catabolism and its tight connection to arginine regulatory network provided an explanation of lysine as poor nutrient for P. aeruginosa. Catabolism of cadaverine, a product from lysine decarboxylation, was investigated and compared to that of putrescine, another diamine of similar biochemical properties that is derived from arginine and ornithine. While the g-glutamylation pathway was first reported in E. coli for putrescine utilization, an expanded version of this pathway was found in P. aeruginosa with redundant enzymes for polyamine degradation. The PauR protein was identified as a transcriptional repressor of genes for the catabolism of putrescine and cadaverine, as well as their corresponding downstream metabolites, g-aminobutyrate (GABA) and d-aminovalerate (AMV). PauR shows distinct dimer configuration after glutaraldehyde crosslinkage, and possible conformational changes could be triggered by the presence of putrescine and cadaverine, but not GABA. A newly identified ABC transport system, encoded by the agtABCD operon, was found important for the uptake of GABA and AMV; and expression of which is controlled by the AgtSR two-component system. The CbrAB two-component system was proposed to regulate the catabolite repression control protein Crc through a small RNA CrcZ. A consensus CbrB recognition sequence was proposed based on the conserved palindromic nucleotide sequence in the upstream activating sequence of the crcZ promoter. Genetic studies indicated utilization of arginine, lysine and diamines (but not histidine, GABA and AMV) might be under CbrAB regulation through the CbrAB/CrcZ/Crc system in P. aeruginosa.

The assessment of volatile organic compounds (VOCs) has become an area of particular interest in the field of atmospheric pollution due to their adverse health and environmental effects. This study is aimed to identify, quantify and characterize VOC in different urban areas and industrial areas in Bursa. The spatial distribution, seasonal variation as well as health risks assessment of VOC were discussed. Air samples were collected by means of sorbent passive sampling at over 50 sampling points in Bursa and analyzed by GC-thermal desorption. A total of seven weekly measurement periods were completed across the city center from 2005 to 2007. The source of VOC was apportioned with the commonly used receptor model, namely Factor Analysis. Motor vehicles and industrial solvent usage are the most abundant VOC sources to contribute to urban atmosphere in Bursa, 63% and 20%, respectively. The health risks of VOC were also evaluated. The questionnaire was filled out by selected people living in Bursa to obtain time-activity pattern for health risk assessment. Lifetime cancer risks were estimated with the measured VOC data. All the statistical parameters used to represent cancer risks for the selected compounds exceeded the stated level. Benzene had the highest adverse health effect among these compounds according to USEPA (2009) calculation with the mean cancer risk 3x10-4. In addition to intensive field sampling campaigns conducted in Bursa, the VOC measurement were completed for a period of six months to evaluate uptake rate of VOC in Ankara. Uptake rate equations depending on relative humidity and wind speed were developed for 25 VOCs.

<p>This thesis evaluates the performance of a deammonification system designed as a two-step tech-nology consisting of an initial partial nitritation followed by an Anammox process. Operation of a technical-scale pilot plant at the Himmerfjärden Wastewater Treatment Plant (Grödinge, Swe-den) has been assessed. Oxygen Uptake Rate (OUR) to evaluate the respiration activity of nitrifi-ers in the system and batch tests to assess reaction rates have also been applied in the study. It was found that the total inorganic nitrogen elimination strongly depended on the nitrite-to-ammonium ratio in the influent to the Anammox reactor, which was correlated with the per-formance of the partial nitritation phase. Therefore, a control strategy for oxidation of ammo-nium to nitrite has been proposed. Controlled oxygen supply to the partial nitritation reactor is obligatory to obtain a proper pH drop indicating oxidation of ammonia to nitrite at the adequate ratio. A very high nitrogen removal efficiency (an average of 84%) and stable operation of the system have been reached. Conductivity measurements were also used to monitor the system influent nitrogen load and the nitrogen removal in the Anammox reactor. The data gathered from the operation of the pilot plant enabled the use of multivariate data analysis to model the process behaviour and the assessment of the covariances between the process parameters. The options for full-scale implementation of the Anammox systems have been proposed as a result of the study.</p>

Includes vita. / Title from PDF of title page. / Document formatted into pages; contains 185 pages. / Thesis (Ph.D.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: Seagrass communities are composed of numerous organisms that depend on water-column nutrients for metabolic processes. The rate at which these organisms remove a nutrient from the water column can be controlled by physical factors such as hydrodynamic regime or by biological factors such as speed of enzyme reactions. The impact of hydrodynamic regime on rates of nutrient uptake for seagrass (Thalassia testudinum) communities and for organisms that comprise the community (seagrass, epiphytes, phytoplankton, and microphytobenthos) was quantified in a series of field flume experiments employing the use of 15N-labeled ammonium and nitrate. Rates of ammonium uptake for the entire community and for seagrass leaves and epiphytes were significantly dependent on bulk velocity, bottom shear stress, and the rate of turbulent energy dissipation. / ABSTRACT: Relationships between uptake rates and these parameters were consistent with mass-transfer theory and suggest that the effect of water flow on ammonium uptake is the same for the benthos as a whole and for the organisms that form the canopy. In addition, epiphytes on the surface of T. testudinum leaves were shown to depress leaf uptake by an amount proportional to the area of the leaf covered by epiphytes. Water flow influenced rates of nitrate uptake for the community and the epiphytes; however, uptake rates were depressed relative to those for ammonium suggesting that uptake of nitrate was also affected by biological factors such as enzyme activity. Epiphytes reduced uptake of nitrate by the leaves; however, the amount of reduction was not proportional to the extent of epiphyte cover, which provided further evidence that nitrate uptake by T. testudinum leaves was biologically limited. / ABSTRACT: As an additional component of the research, hydrodynamic regime of a mixed seagrass and coral community in Florida Bay was characterized using an acoustic Doppler velocimeter. Hydrodynamic parameters estimated from velocity data were used in mass-transfer equations to predict nutrient uptake by the benthos over a range of water velocity. Measured rates of uptake from field flume experiments conducted in the same community confirmed that hydrodynamic data could be used to accurately predict nutrient transport to the benthos under natural flow conditions. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

In the U.S. and other developed countries, humans spend the vast majority of their time within the built environment. As a result, a substantial portion of our collective exposure to airborne pollutants, even those of outdoor origin, occurs in indoor environments. In addition, building construction materials and operational practices are changing as we endeavor to reduce the energy burden of the built environment. These changes result in barriers and opportunities in mitigating exposure to indoor pollutants and the accompanying implications for human health. This dissertation advances knowledge regarding low-energy control of indoor ozone. Ozone is often considered a pollutant of outdoor concern. However, ozone in indoor environments presents important challenges regarding exposure, intake, and chemistry in the built environment. The investigations in this dissertation extend the state understanding of indoor transport and transformation of ozone, and the potential for using material-surface interactions in buildings to suppress concentrations of indoor ozone. The first objective relates to the determination of magnitudes of ozone removal and product emissions at room or building scales. This objective provides new data on reactive uptake and product generation in large-scale environments, develops Monte Carlo models describing indoor ozone removal by materials in homes, and compares active and passive methods of indoor ozone removal. The second objective addresses the need to develop improved air cleaning materials through experiments and modeling that address material-ozone reactions in porous materials. This objective advances the state of modeling heterogeneous reactive uptake of ozone by characterizing material physical properties and transport phenomena, determining their impact on ozone removal, and using these data to develop a more mechanistic model of material-ozone reactions. Ultimately, these investigations advance the engineering concepts that support the development of passive indoor pollutant controls, an important tool for reducing concentrations of indoor pollutants while supporting low-energy building initiatives. The combination of experimental characterization of ozone deposition velocities and product emission rates, whole-building Monte Carlo modeling, and mechanistic material/pollutant models provide important new data and approaches that expand the state of knowledge of the fate and transport of reactive pollutants in indoor environments. / text

No description available.

Objectives To assess physical fitness in pregnancy and to evaluate its effect on perceived health, back pain, blood pressure and duration of gestation. Also, to evaluate the effect of serum relaxin levels on blood pressure and duration of gestation. Material and methods A prospective cohort of 520 pregnant women were examined in early pregnancy and five months postpartum with regard to socio-demographic characteristics and estimated peak oxygen uptake (V̇O2 peak, est.). Serum concentrations of relaxin were carried out in early pregnancy. Physical exercise, possible back pain and blood pressure were measured repeatedly throughout pregnancy. Results Absolute V̇O2 peak, est. in early pregnancy was positively correlated to perceived health, which was lower during than after pregnancy. The average absolute V̇O2 peak, est. in early pregnancy of 2.4 l/minute was 0.02 l/minute less than the V̇O2 peak, est. postpartum, while regular physical exercise decreased throughout pregnancy. Absolute V̇O2 peak, est. in early pregnancy was not associated to the incidence of any low back pain location in pregnancy or postpartum, but inversely to intensity of back pain and diastolic blood pressure and positively with duration of gestation. Elevated serum relaxin levels were associated with decreased diastolic blood pressure and higher duration of gestation among women with miscarriage. Conclusions Perceived health, diastolic blood pressure and duration of gestation were positively affected by physical fitness while no effect was shown on the incidence of back pain. The effect of physical fitness on duration of gestation and diastolic blood pressure might have clinical implications as well as the increased serum relaxin levels on miscarriages.

<p>The aim of this study was to investigate the effect the plant matrix and the structure of the flavonoid (i.e. whether aglycone or glycoside) may have on the gastrointestinal uptake and metabolism of luteolin derivatives from Artemisia afra traditional plant medicine. Specifically, how these two factors influenced the intestinal uptake and disposition of luteolin derivatives in pure and in Artemisia afra plant extract forms were to be assessed by investigating the uptake and metabolism of the luteolin derivatives in human intestinal epithelial Caco-2 cells and the perfused rat intestinal loop. To realize this aim, the following were determined: (1) identification and characterization of major luteolin derivatives found in Artemisia afra, (2) the effect of the plant matrix on the uptake of luteolin derivatives in Artemisia afra aqueous-extract forms across the Caco-2 cell monolayer, (3) the effect of the plant matrix on the absorption and metabolism of luteolin derivatives in Artemisia afra aqueous-extract forms in the perfused rat small intestine, (4) the effect of gut contents on the uptake and metabolism of luteolin derivatives in intestinal loop and (5) the metabolic profiles of luteolin derivatives obtained for the pure solutions versus plant aqueous extract solutions in Caco-2 cells and the rat intestine.</p>