| 1. |
- Dunder, Linda
(författare)
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Exposure to Bisphenol A (BPA) and Metabolic Disruption
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metbolic disorders such as obesity, type 2 diabetes, liver lipid disorders and metabolic syndrome are increasing rapidly and have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence showing that other environmental factors, including environmental chemicals, may contribute to the rapid increase in the incidence of these metabolic diseases. Of particular growing concern is low-dose developmental exposure to endocrine disrupting chemicals (EDCs). The developing period is an extremely sensitive window of exposure to environmental stressors, including EDCs, and early life exposure has been linked to metabolic disorders later in life. Consistent with hormones, EDCs can act at very low serum concentrations and even small changes in the endocrine system may lead to extensive effects. The overall aim of this thesis has been to investigate potential metabolic disruption following exposure to Bisphenol A (BPA), which is a known EDC. The experimental animal study demonstrated that male and female rat offspring generally exhibited differential susceptibility to developmental exposure to BPA (0.5 µg/kg BW/day or 50 µg/kg BW/day). The main results showed that the lowest dose of BPA induced increased plasma triglyceride levels and increased adipocyte cell density in inguinal white adipose tissue in female offspring. Further, this low dose increased fatty acid indices and altered the fatty acid composition in male offspring and enhanced insulin secretion in pancreatic islets from male and female offspring and dams. Contrastingly, the higher BPA-dose decreased insulin secretion in pancreatic islets from male and female offspring and dams. The increased fatty acid indices, and the altered fatty acid composition together with enhanced insulin secretion may be early risk factors for insulin resistance. Furthermore, depending on the tissue, dose and sex, BPA altered the expression of genes involved in lipid and adipocyte homeostasis.The epidemiological study with a meta-analysis of data from the National Health and Nutrition Survey (NHANES) did not disclose any associations between urinary BPA and dyslipidemia. However, considering the cross-sectional nature of the present study, this should rather be investigated in carefully designed prospective cohort studies with repeated BPA measurements. Nonetheless, we hope that this paper can encourage researchers to evaluate NHANES data using meta-analyses instead of pooling of data.This thesis concludes that exposure to BPA, which is a known EDC, most likely is a contributor, along with genetic, social and behavioral factors, to the development of metabolic disorders.
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| 2. |
- Rönn, Monika, 1965-
(författare)
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Environmental Contaminants and Obesity
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is a worldwide problem affecting both children and adults. Genetic, physiological, environmental, psychological, social and economic factors interact in varying degrees, influencing body weight and fat distribution and the progress of obesity. Moreover, some anthropogenic chemicals have proven to be endocrine disrupting chemicals (EDCs) with the potential to interfere with different actions of hormones in the body. EDCs may thereby disrupt homeostasis, modifying developmental, behavioral and immune functions in humans and animals, and also promoting adiposity. Because hormones generally act at low concentrations, small changes in the endocrine system may lead to extensive effects. Based on data from experimental and epidemiological studies this thesis elucidates the relationship between a large number of environmental contaminants and obesity.The experimental studies demonstrated that fructose supplementation in the drinking water resulted in unfavorable metabolic alterations such as a higher liver somatic index (LSI), an increase in plasma triglycerides and increased plasma levels of apo A-I. Fructose in combination with exposure to bisphenol A (BPA) increased liver fat content and plasma levels of apo A-I in juvenile female Fischer 344 rats. The experimental studies also showed that the retro-peritoneal fat, which in rats is a distinct fat depot easy to distinguish and dissect, correlated well with the measurements of total fat mass analyzed with MRI, and could therefore be used as a substitute for total fat mass in rats.The epidemiological studies showed that circulating levels of persistent organic pollutants (POPs) were related to fat mass measured by DXA. OCDD, HCB, TNC, DDE and the less chlorinated PCBs were positively related to fat mass, while the more highly chlorinated PCBs showed a negative association. Further, circulating levels of BPA were positively associated with levels of the hormones adiponectin and leptin, but negatively related with ghrelin, hormones which are involved in the regulation of hunger and satiety. However, serum BPA levels were not related to measures of fat mass in the elderly individuals in the PIVUS cohort.This thesis concludes that environmental contaminants such as BPA and POPs most likely are contributors, along with genetic, social and behavioral factors, to the development of obesity.
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| 3. |
- Lampa, Erik, 1977-
(författare)
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Mixture Effects of Environmental Contaminants
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chemical exposure in humans rarely consists of a single chemical. The everyday exposure is characterized by thousands of chemicals mainly present at low levels. Despite that fact, risk assessment of chemicals is carried out on a chemical-by-chemical basis although there is a consensus that this view is too simplistic.This thesis aims to validate a statistical method to study the impact of mixtures of contaminants and to use that method to investigate the associations between circulating levels of a large number of environmental contaminants and atherosclerosis and the metabolic syndrome in an elderly population. Contaminants measured in the circulation represented various classes, such as persistent organic pollutants, plastic-associated chemicals and metals.There was little co-variation among the contaminants and only two clusters of PCBs could be discerned. Gradient boosted CARTs were used to assess additive and multiplicative associations between atherosclerosis, as measured by the intima-media thickness (IMT) and the echogenicity of the intima-media complex (IM-GSM), and prevalent metabolic syndrome.Systolic blood pressure was the most important predictor of IMT while the influence of the contaminants was marginal. Three phthalate metabolites; MMP, MEHP and MIBP were strongly related to IM-GSM. A synergistic interaction was found for MMP and MIBP, and a small antagonistic interaction was found for MIBP and MEHP. Associations between the contaminants and prevalent metabolic syndrome were modest, but three pesticides; p,p’-DDE, hexachlorbenzene and trans-nonachlor along with PCBs 118 and 209 and mercury were the strongest predictors of prevalent metabolic syndrome.This thesis concludes that many contaminants need to be measured to get a clear picture of the exposure. Boosted CARTs are useful for uncovering interactions. Multiplicative and/or additive effects of certain contaminant mixtures were found for atherosclerosis or the metabolic syndrome.
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| 4. |
- Tavanti, Monica, 1972-
(författare)
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On the Relative Utility of 3D Interfaces
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Three-dimensional (3D) interfaces are made with the ambition to reinvent traditional two-dimensional (2D) displays into intuitive 3D environments that allow natural interactions and guarantee users’ satisfaction. However, reality is far from the expectations and 3D interfaces remain experimental. The results of empirical studies comparing 2D and 3D interfaces are incoherent and do not indisputably endorse the development of 3D applications. The reason behind this incoherency is that empirical comparisons often discard several factors that go beyond the specific style of the interface itself although they play a major role in human performance. Specifically: perceptual factors, factors related to semantics, contextual factors.The identification of these factors was carried out through a set of empirical studies tackling two applications domains: information management (namely, the retrieval of data and on spatial memory tasks) and Air Traffic Control. Concerning the first domain, the results suggest that 3D interfaces can support spatial memory if the 3D interface is provided with a spatial structure that has also a semantic function. Also, the specific content of the objects disseminated in the 3D structure seem to affect performance. It is argued that when there is a strategic coupling of the semantics of the spatial structure with the meanings of the objects, 3D interfaces could enhance spatial memory. Concerning the second domain, the results indicate that 3D interfaces could support controllers’ tasks only for a limited set of activities. These do not include standard monitoring tasks where the presence of 3D would actually cause detriment to the performance due to perceptual biases. Finally, it is claimed that the idea of familiarity with an interface style can affect the way people interact with it and, despite the fuzziness of the concept, familiarity may represent a real challenge in users’ acceptance of 3D interfaces.
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