The purpose of this study was to resolve a critical gap in depression literature through assessment of the temporal relationship between depression and low LDL. A systematic review and meta-analysis was conducted to investigate the overall cross-sectional association between serum LDL and depression. Inconsistent findings suggest that more work must be done to clarify the link between LDL and depression. Next, Cox regression was used to explore the association between LDL and the subsequent onset of depressive symptoms within a subset of the Women’s Health Initiative cohort and evaluate the potential for effect modification by lipid-lowering medication use. This study provides evidence toward an association between low LDL and the subsequent onset of depressive symptoms, with increased risk confined to LDL below 100 mg/dL. Elevated risk was not associated with lipid-lowering medication use. The final study examined the differences in the magnitude and direction of change in serum LDL levels among individuals experiencing new-onset depression, and examines the potential for physical activity, energy intake, and total body weight to mediate the depression-LDL relationship. This study provides no evidence of an association between depression and subsequent serum LDL changes. Altogether, this data suggests that LDL that is below 100 mg/dL without the use of lipid-lowering medication may predispose individuals to a greater risk of depression, and also suggests that low LDL is not likely a state brought about by physiological or behavioral changes following the onset of depression.

Coral reefs are threatened in Florida and worldwide. Successful resource management requires rapid identification of anthropogenic sources of stress before they affect the reef community. I tested a multi-scale approach for assessing reef condition at seven reefs within the Florida Keys National Marine Sanctuary and Biscayne National Park between 2001 and 2003. I examined multiple environmental parameters to identify potential sources of stress. I utilized the Atlantic and Gulf Rapid Reef Assessment Biotic Reef Index to assess benthic community structure and an indicator species of Foraminifera (Amphistegina gibbosa) to determine if environmental conditions were suitable for calcareous organisms that host algal endosymbionts. Small tissue samples were extracted from colonies of Montastraea annularis species complex to assay a suite of cellular biomarkers to elucidate possible mechanisms of the coral stress response. I monitored regeneration rates of the resultant lesions to determine if the coral colonies were capable of recovering from damage. Multivariate data analyses indicated that corals at all study sites were experiencing stress with different degrees of response and decline. On reefs with coarse grain sediments that are adjacent to an intact mangrove shoreline, the Cellular Diagnostic System indicated that corals were responding to a xenobiotic stress but appeared to be compensating as evidenced by consistently high lesion regeneration rates, a high percentage of healed lesions, low coral mortality and high abundances of A. gibbosa. On reefs with silt-sized sediments adjacent to developed coastlines, corals also were responding to xenobiotic stresses, but were negatively affected as evidenced by low regeneration rates, a low percentage of healed lesions, high coral mortality, and low abundances of A. gibbosa. Corals at an 18 m offshore site exhibited abnormally low biomarker levels and some died during the study, indicating that sampled colonies were incapable of upregulating necessary protective proteins. Further research will be required to determine stressor sources. This study demonstrates that a multiple-indicator approach, spanning scales from cellular to community, can provide marine resource managers with data linking decline of coral populations to specific environmental conditions and events, thereby providing potential for early detection of stressors allowing for preventive management.

The environmental health of aquatic ecosystems depends amongst others, on the chemical pollution coming from activities in the catchment's area. In the Swan River Estuary, Western Australia, the chemical pollutants of concern released into the river are petroleum hydrocarbons and sodium pentachlorophenate (NaPCP). Decreased water quality causes a loss of biotic diversity especially amongst fish populations. The health of aquatic ecosystems can be monitored by fish health, especially fish located at higher levels in the food chain. Pink snapper (Pagrus auratus), an endemic Western Australian fish species, was tested for its potential as a bioindicator of aquatic environmental health. This thesis presents data on the responsiveness of pink snapper to the contaminants of concern, using biomarkers such as serum sorbitol dehydrogenase (SDH), mixed function oxygenase (MFO), metabolic enzymes such as citrate synthase (CS), cytochrome C oxidase (CCO) and lactate dehydrogenase (LDH) and the histological alteration such as hepatic cell lesions (hyperplasia and hypertrophy), and glycogen and lipid droplets. The metabolic enzymes CCO and LDH as well as the hepatic MFO induction and histopathology were proven to be the most suitable biomarkers for use for routine monitoring of the Swan River Estuary using pink snapper as a bioindicator. However, CS activity and hepatic cell lesions (hyperplasia and hypertrophy) did not respond to exposure to contamination and are therefore not suited as biomarkers of effects in pink snapper. The first phase of the study aimed at investigating the responsiveness of juvenile pink snapper to an MFO inducer. Polychlorinated biphenyl isomer # 126 was selected as a model MFO inducer for this study. In the initial experiment, MFO activity was measured as a biomarker of exposure, and serum SDH activity was assessed as a biomarker of liver damage. / MFO and SDH activities were of special interest as these biochemical tools have not previously been validated for any Western Australia fish species. Juvenile pink snapper were injected intraperitoneally (i.p.) with 0, 10, 100, 500, 1000 microgram PCB-126 per kilogram. Fish were sacrificed 10 days postinjection, and liver and blood were collected for MFO and SDH analysis, respectively. Doses of 10 and 100 microgram PCB-126 per kilogram caused the highest MFO induction, while doses of 0 and 1000 microgram PCB-126 per kilogram did not result in higher MFO activity relative to carrier-injected (peanut oil) control fish. SDH activities were not significantly different among treatments indicating that hepatocellular damage was not responsible for the reduced MFO activity at the highest dose. Metabolic enzymes in pink snapper exposed by NaPCP were studied in the second phase of the experiment. The aim of this second experiment was to test the responsiveness of pink snapper to contaminants known to cause metabolic perturbations in vertebrates. Juvenile pink snapper were intraperitoneally (i.p.) injected with 0, 5, 10, 20 mg per kilogram. Oxidative enzymes were assessed by measuring CS and CCO activities and glycolytic enzyme was assessed by measuring LDI-1 activity in liver and white muscle tissues. CS activity remained unchanged in both the white muscle and in the liver. CCO activity was significantly enhanced in liver in all treated fish relative to control fish, but not in the white muscle. LDH activity was also higher in liver in all treated fish as compared to control fish, while in white muscle, LDH activity significantly increased at the highest dose injected. / The use of a suite of biochemical markers is useful in determining the effects of xenobiotic exposure of aquatic organisms, because it provides a holistic approach with biomarkers at different levels of biological organization. For the third and final phase of the study the suite of biomarkers selected were MFO, metabolic enzyme (CS, CCO and LDH) activities, and histological alternations in combination with physiological indices. The aim of this last experiment was to investigate if a modified liver metabolic activity would alter the MFO induction potential. To test if altered liver metabolism would influence liver detoxication capacities, juvenile pink snapper were i.p. injected with peanut oil (control), or pentachlorobiphenyl # 126 (PCB 126), with sodium pentachlorophenate (NaPCP), or combination of PCB 126+NaPCP. Relative to controls, ethoxyresorufin-O-deethylase (EROD) activity was induced in the PCB 126 and PCB 126+NaPCP fish, but not in the NaPCP group. In the liver, CCO activity was enhanced by the treatments while CS activity remained unchanged and LDH activity was increased in the NaPCP treatment only. In the white muscle, only the PCB 126+ NaPCP treatment enhanced CCO activity, with all other enzymatic activities remaining unchanged. Low serum sorbitol dehydrogenase (sSDH) activity and histopathology of the liver indicated no significant alteration of cellular structure, albeit the lipid droplet size was increased in the PCB 126 and in the PCB 126+NaPCP treatments. / It is concluded that the hepatic metabolic changes correspond to histopathological observations, but an altered metabolic capacity does not influence the metabolism of xenobiotics by liver enzymes, as measured by EROD activity. These experiments answered the need to identify a suitable fish species for routine monitoring of the aquatic environment in Western Australia. It also identified the most suitable biochemical markers of exposure and effects, and the suitability of the pink snapper as a bioindicator. Finally, the experiments investigated interactions between biomarkers and provided new knowledge useful to scientists using MFO and/or metabolic enzymes in field or laboratory toxicology.

<p>In recent years, the use of alcohol and psychoactive drugs in combination withdriving has recieved increased attention. The lack of in-vehicle devices capable ofdetecting recent drug consumption and the difficulties associated with the breathbasedalcolocks in use today makes it interesting to investigate methods that areable to non-invasivelly measure analytes directly in the blood.</p><p>The assignment of this project, commissioned by Volvo Technology Corporationand Volvo Car Corporation, is to map substances that constitute a possible threatto traffic safety, identify suitable detection markers as a proof of administrationof these substances, and study possible non-invasive techniques to detect thesemarkers. The objective is to present for Volvo if and how to continue evaluatingand developing a non-invasive detection device.</p><p>The project has been carried out by performing an extensive literature study and averification experiment. From the literature review, a number of substances affectingdriving performance could be identified, and a metabolic study was performedfor each drug to map suitable biomarkers. Furthermore, two potential techniquesfor non-invasive detection, near-infrared Raman spectroscopy and near-infraredspectroscopy, were found and evaluated. The experiment was conducted usingnear-infrared Raman spectroscopy, with the aim of investigating the sensitivityand linearity of the method for ethanol detection.</p><p>Based on the theoretical evaluation, both near-infrared Raman spectroscopy andnear-infrared spectroscopy are expected to have potential for non-invasive detectionof ethanol. The experiment further proved the theoretical conclusionsmade for near-infrared Raman spectroscopy. However, neither of the techniquesis thought to have potential for drug detection.Altogether, we believe that non-invasive ethanol detection is possible, but suggestfurther experiments in order to determine which technique to be preferred.</p>

<p>Lung cancer is the cancer form that has the highest mortality worldwide and inaddition the survival of lung cancer is very low. Only 15% of the patients are alivefive years from set diagnosis. More research is needed to understand the biologyof lung cancer and thus make it possible to discover the disease at an early stage.Early diagnosis leads to an increased chance of survival. In this thesis 179 lungcancer- and 116 control samples of blood serum were analyzed for identificationof metabolomic biomarkers. The control samples were derived from patients withbenign lung diseases.Data was gained from GC/TOF-MS analysis and analyzed with the help ofthe multivariate analysis methods PCA and OPLS/OPLS-DA. In this thesis it isinvestigated how to pre-treat and analyze the data in the best way in order todiscover biomarkers. One part of the aim was to give directions for how to selectsamples from a biobank for further biological validation of suspected biomarkers.Models for different stages of lung cancer versus control samples were computedand validated. The most influencing metabolites in the models were selected andconfoundings with other clinical characteristics like gender and hemoglobin levelswere studied. 13 lung cancer biomakers were identified and validated by raw dataand new OPLS models based solely upon the biomarkers.In summary the identified biomarkers are able to separate fairly good betweencontrol samples and late lung cancer, but are poor for separation of early lungcancer from control samples. The recommendation is to select controls and latelung cancer samples from the biobank for further confirmation of the biomarkers.NyckelordLung cancer is the cancer form that has the highest mortality worldwide and inaddition the survival of lung cancer is very low. Only 15% of the patients are alivefive years from set diagnosis. More research is needed to understand the biologyof lung cancer and thus make it possible to discover the disease at an early stage.Early diagnosis leads to an increased chance of survival. In this thesis 179 lungcancer- and 116 control samples of blood serum were analyzed for identificationof metabolomic biomarkers. The control samples were derived from patients withbenign lung diseases.Data was gained from GC/TOF-MS analysis and analyzed with the help ofthe multivariate analysis methods PCA and OPLS/OPLS-DA. In this thesis it isinvestigated how to pre-treat and analyze the data in the best way in order todiscover biomarkers. One part of the aim was to give directions for how to selectsamples from a biobank for further biological validation of suspected biomarkers.Models for different stages of lung cancer versus control samples were computedand validated. The most influencing metabolites in the models were selected andconfoundings with other clinical characteristics like gender and hemoglobin levelswere studied. 13 lung cancer biomakers were identified and validated by raw dataand new OPLS models based solely upon the biomarkers.In summary the identified biomarkers are able to separate fairly good betweencontrol samples and late lung cancer, but are poor for separation of early lungcancer from control samples. The recommendation is to select controls and latelung cancer samples from the biobank for further confirmation of the biomarkers.Nyckelord</p>

South Africa is one of the most important mining countries in the world, hosting the world's largest reserves of platinum group metals (PGMs). Even though mining is clearly an important activity in South Africa, contributing approximately US$ 7.4 billion annually to the countries' gross domestic product (GDP), the costs to the environment are not insignificant. One of the most severe environmental aspects associated with mining is the storage of mineral waste on tailings storage facilities due to their impacts on air quality, ground water quality, aesthetics and land use. It is also unknown whether the environmental effects of tailings storage facilities increase or decrease over time. The aim of this study was to determine the ecotoxicity of platinum tailings storage facilities of different ages by means of soil physical and chemical analysis, earthworm ecotoxicological studies, dehydrogenase activity and soil mesofauna studies. Samples were obtained from three platinum tailings storage facilities of different ages of which two were already rehabilitated while the third was still operational at the time this study was performed. The latter was used as a negative control for the purpose of the study. Soil samples were physically and chemically analysed. Earthworm ecotoxicological studies were conducted to determine changes in biomass, reproduction, mortality, neutral red retention times and tissue metal concentrations. Dehydrogenase activity was determined before the introduction of earthworms and manure, after introductions of manure and after introductions of earthworms and manure. Soil mesofauna were extracted and identified in order to determine species richness, diversity, abundance and functional grouping. Soil chemical analysis indicated that concentrations of certain heavy metals, especially chrome (Cr), present in platinum tailings materials could have a potential effect on microorganisms, microbial processes and earthworms. Earthworm ecotoxicological results indicated that earthworms that bioaccumulated higher levels of heavy metals showed poor hatchability of cocoons. Dehydrogenase activity indicated that earthworms play a significant role in increasing the number and biomass of soil microbes because significant increases in dehydrogenase activity were noticed after the addition of earthworms to platinum tailings materials. Results from the earthworm ecotoxicological studies, dehydrogenase activity, and soil mesofauna composition indicated that environmental impacts of tailings storage facilities did not increase with age, but is more likely to be an indication of the rehabilitation measures administered to the different tailings storage facilities. / Thesis (M. Environmental Science)--North-West University, Potchefstroom Campus, 2009.

Cave (Petrochelidon fulva) and cliff swallows (Petrochelidon pyrrhonota) were collected along the Rio Grande and evaluated as potential indicators of environmental contamination. The Rio Grande receives toxic substances from agricultural, industrial, municipal, and non-point sources; consequently, high levels of contaminants have been detected in birds, mammals, fishes and sediments. Swallows were obtained from 8 sites between Brownsville and El Paso, as well as from a reference site in Burleson County, 320 miles north of the nearest site of the Rio Grande. Blood samples were analyzed by flow cytometry, a technique that allows the detection of DNA damage in blood and other tissues. Plasma samples were analyzed for thyroid hormones using a radioimmunoassay technique. Organochlorines and trace metal analysis was limited to a few samples. DDE and PCB levels were below levels known to cause reduced hatching, embryo mortality, and deformities, Hg, Pb, and As were below detection, and Se, Ni and Cr concentrations were lower than levels known to cause harm in birds. Neither species showed sex-related differences in chromosome damage. Cave swallows from the Del Rio area had the highest levels of DNA variation, which may be indicative of DNA damage, possibly from PAHs exposure. Previous studies indicate that sediment samples from tributaries near Del Rio have high levels of chromium compared to other sites along the Rio Grande. A significant increase in DNA variation between sampling years was detected in cave swallows from Llano Grande Lake. Wildlife samples collected from Llano Grande Lake have recorded high levels of DDE and PCBs; in addition, this urban/agricultural contaminant sink appears to be affected by PAH exposure. T3 levels were below the detection limit of the radioimmunoassay. There were no gender related differences in T4 levels in cave swallows. Cave swallows sampled from Laredo had significantly higher T4 levels than those from birds at other sites during 1999. It was not possible to determine thyroid hormone disruption in plasma samples. Thyroid hormone and flow cytometry data were useful in establishing baseline data. Areas of concern based on genotoxic data include Llano Grande Lake, Del Rio, and El Paso.

Ecotoxicology studies attempt to evaluate the consequences of exposure to environmental contaminants by defining exposure and effects parameters across multiple levels of biological organization. Genetic markers are well-suited for these studies as they can track both somatic and evolutionary effects. In the studies reported here, connections among contaminant levels in environmental media and biota, in vitro bioassay results, and changes in individual- and population-level biomarkers were explored. Sediment and/or wildlife samples were collected from each of three sites of documented environmental contamination, Sumgayit and Baku in the Republic of Azerbaijan and East Fork Poplar Creek in Tennessee. Sumgayit and Baku are heavily contaminated with petroleum and petrochemical wastes. Sediments from several areas and tissues from turtles inhabiting a contaminated wetland contained high levels of several compounds, including mercury, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and organochlorine pesticides. Sediment extracts produced variable responses in the Salmonella/microsome mutagenicity assay and did not necessarily reflect contaminant burden. Micronucleus counts in European pond turtles were not statistically different from counts in the same species from an uncontaminated reference site. The counts were statistically correlated with tissue levels of mercury, heptachlor, DDD, hexachlorobenzene, and trans-nonachlor. These results confirmed that Sumgayit and Baku are heavily contaminated with a complex mixture of pollutants and demonstrated that genotoxic effects from exposure to contaminated sediments appear to be slight. East Fork Poplar Creek is a stream that receives contaminant influx from a former Department of Energy nuclear weapons production facility and several point and non-point sources around the city of Oak Ridge, Tennessee. In this study, coefficient of variation in cellular DNA content and randomly amplified polymorphic DNA markers were examined in central stonerollers and compared to previous studies in which the same markers were evaluated in red-breasted sunfish from the same sites. While assay responses were attenuated in stonerollers compared to the sunfish, there is some evidence of genetic damage in both species at the most contaminated sampling site. A common problem in the wildlife studies was high within sample variability combined with small sample size, which most likely masked potential contaminant-induced differences in markers used in these studies.

In recent years, the use of alcohol and psychoactive drugs in combination withdriving has recieved increased attention. The lack of in-vehicle devices capable ofdetecting recent drug consumption and the difficulties associated with the breathbasedalcolocks in use today makes it interesting to investigate methods that areable to non-invasivelly measure analytes directly in the blood. The assignment of this project, commissioned by Volvo Technology Corporationand Volvo Car Corporation, is to map substances that constitute a possible threatto traffic safety, identify suitable detection markers as a proof of administrationof these substances, and study possible non-invasive techniques to detect thesemarkers. The objective is to present for Volvo if and how to continue evaluatingand developing a non-invasive detection device. The project has been carried out by performing an extensive literature study and averification experiment. From the literature review, a number of substances affectingdriving performance could be identified, and a metabolic study was performedfor each drug to map suitable biomarkers. Furthermore, two potential techniquesfor non-invasive detection, near-infrared Raman spectroscopy and near-infraredspectroscopy, were found and evaluated. The experiment was conducted usingnear-infrared Raman spectroscopy, with the aim of investigating the sensitivityand linearity of the method for ethanol detection. Based on the theoretical evaluation, both near-infrared Raman spectroscopy andnear-infrared spectroscopy are expected to have potential for non-invasive detectionof ethanol. The experiment further proved the theoretical conclusionsmade for near-infrared Raman spectroscopy. However, neither of the techniquesis thought to have potential for drug detection.Altogether, we believe that non-invasive ethanol detection is possible, but suggestfurther experiments in order to determine which technique to be preferred.

Programmed Cell Death 4 (PDCD4) is a known tumour suppressor, lost in carcinomas of the breast, prostate, colon, lung and ovary. This study found significantly reduced levels of PDCD4 mRNA and protein in both primary patient oral squamous cell carcinomas (OSCCs) and OSCC cell lines. Moreover, lower PDCD4 mRNA levels were significantly correlated with nodal metastasis (P=0.019). To determine the functional significance of PDCD4 down-regulation in OSCC we asked whether PDCD4 played a role in invasion. In fact, over-expression of PDCD4 decreased invasion of OSCC lines. We then sought to determine a mechanism for PDCD4 down-regulation in OSCC. Previous studies in breast and colon carcinomas suggested that reduced PDCD4 expression was due to over-expression of miR-21. Interestingly, miR-21 was inversely correlated to PDCD4 mRNA (P=0.002) and PDCD4 protein (P<0.001) levels in OSCC patient samples. Moreover, we found that miR-21 directly regulated PDCD4 protein expression in OSCC cell lines. This is the first report in OSCC that demonstrates that PDCD4 is down-regulated by miR-21 and may play a role in OSCC invasion.