Thesis (D.P.H.)--University of Michigan, 1994.

Thesis (D.P.H.)--University of Michigan, 1994.

No description available.

Organophosphorus compounds (OPs), both nerve agents and insecticides, may induce damage leading to long-term neurological deficits. Oxime 20, the lead compound from a platform of substituted phenoxyalkyl pyridinium oximes (US Patent 9,227,937), is an oxime that reactivates OP-inhibited acetylcholinesterase (AChE) and has displayed neuroprotection within the brain of rats in in vivo tests where the currently approved treatment, pralidoxime (2-PAM), has not. This research investigated the neuroprotective effect of novel oxime therapy. Gene expression in rat piriform cortex was analyzed to determine if neurotoxicity, stress, and synaptic plasticity-associated genes were down-regulated by Oxime 20 following a sublethal dose of sarin surrogate 4-nitrophenyl isopropyl methylphosphonate (NIMP). Significant therapeutic changes from the NIMP+Oxime20 group relate to cell viability and attenuation of neuroinflammation, while networks formed by Ingenuity Pathway Analysis (IPA) emphasize neuroinflammatory and cell death pathways. Neuropathology cell biomarkers glial fibrillary acidic protein (GFAP), neuronal nuclear antigen (NeuN), ionized calcium-binding adapter molecule 1 (IBA-1), and cyclooxygenase-2 (COX-2) were measured immunohistochemically in rat CA1 region of the hippocampus following a lethal dose of NIMP plus Oxime 20 or 2-PAM therapy. For GFAP and IBA-1, an expected trend of NIMP activation and Oxime 20 recovery was seen and was more pronounced in the apex CA1 region. Loss of neurons were observed most often in the NIMP experimental group. A platform of novel oximes was selected based on percent brain AChE reactivation (24–35% and 10–17%) following exposure of rats to NIMP to determine if interactions between ATP-binding cassette efflux transporters of the blood-brain barrier, p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), contribute to oxime in vivo efficacy. In vitro human P-gp and BCRP membrane assays determined activation and inhibition measurements of total ATPase activity. Human P-gp transport was variable among oximes. Oxime 55 was the only oxime transported by BCRP. Therefore, the lower efficacy of 10-17% in the reactivation oxime group was not due to greater P-gp or BCRP efflux. The explanation might lie with different transporter or mechanism. These tests support our laboratory testing OP inhibited AChE reactivators to understand their efficacy and evaluate neuroprotection from damage caused by OP exposure

<p>Cadium (Cd) is a naturally occurring metal with well documented toxic effects on humans and animals. MT is an endogenous protein that binds Cd and other metals; its role in relation to metabolism, homeostasis and detoxication of metals has yet to be fully elucidated. The dynamics of Cd and Mt were studied in individual rats (3 per group. Each rat served as its own control with blood sampled collected at -20, 0, 6, 12, 24, , 48, 72, and 96h via surgically inserted jugular cannula. Several cadmium chloride concentrations (2.5, 1.25, and 0.25 mg Cd/kg) or saline were investigated as a short course (single IP injection at T=Oh) or subchronic (multiple injections over 2 months) with 3 rates per dose. Feces, urine and whole blood were collected at each time point and blood was separated into whole blood, plasma, erythrocytes (RBC), polymorphonuclear leukocytes (PMN), lymphocytes (Ly) and monocytes (M). Liver, kidney, spleen and lung were collected at T=96h when the animals were euthanized. Quantitative determinations were made by electrothermal atomic absorption spectrometry (EAAS) for total Cd and by the Cd Saturation Assay (CSA) for MT. Cd and MT levels were elevated in a dose-response manner for all tissues and blood components except in the PMNs. The sequence of control (basal) blood MT concentrations was: plasma > RBC > M > Ly >PMN, compared to plasma > *M ≥ *Ly > RBC > PMN, for the 1.25 mg/kg (medium) exposure group at T = 12h. Similarly, the sequence of basal blood Cd concentrations was: whole blood > plasma > RBC ≥ Ly ≥ M ≥ PMN, compared to "whole blood > *RBC >> plasma > *M ≥ *Ly ≥ PMN for the medium exposure group at T = 2h. Significant differences (*p<0.05) were evident in longitudinal comparisons (concentration versus time) and between doses in both experimental protocols.</p> <p>The evidence presented in this thesis clearly establishes Cd levels in RBCs and whole blood as reliable short-and long-term indices of exposure and possible of body burden. MT levels in plasma and RBCs constitute similar markers. Further, Cd in lymphocytes shows promise as a long-term indicator and in monocytes as a short-term index of exposure. Post mortem examination of subchronic organs did not support the contention of Cd-induced MT protection, but rather that of Cd accumulation and dose-dependent toxicity.</p> <p>The in vivo jugular cannulation approach developed has both advantages and disadvantages. Body fluid samples can be collected over a 96-h time period from the same animal, thereby reducing inter-animal variation. The dynamics of Cd uptake and distribution and MT induction can thus be assessed in a single animal and be linked to the corresponding tissue results. The main disadvantage is that replicate sampling at a specific time point is limited by the volume of blood that can be drawn. However, this limitation is partially compensated by the ability to collect many samples over an extensive time period permitting longitudinal statistical comparisons with fewer animals. Another limitation is that the sample collection period is short compared to the time involved in chronic exposures.</p> / Doctor of Philosophy (PhD)

<p> Our earth has begun its sixth extinction and our culture thrives in ideological third nature and the era of technology. Hardcore pornography demonstrates a fear-based split in the relationship between the Great Mother and Terrible Mother archetypes, and the consumption of violent sexual material is indicative of existential death-avoidance, or despair. The archetypes present in the Moms/Hot Mom/Mother/MILF, Youth/Teen, and 18 and Abused categories of porn evoke the fear of the feminine as related to Mother Earth, and elucidate the collective&rsquo;s split feminine archetypes. This research uses heuristic and alchemical hermeneutic research methods to discern how these archetypes within hardcore pornography explicate our cultural complex regarding Mother Nature. What results is a call to consciousness and a clinical aim toward shadow integration, the assimilation of masculine and feminine parts of self, and a cohesive relationship toward imagery and imagination, lest they be altogether replaced by pornography.</p>

<p> This study examines the natural background concentrations of arsenic in the soils of southwest Oregon, using new samples in addition to data collected from previous theses (Khandoker, 1997 and Douglas, 1999). The original 213 samples were run by ICP-AES with a reporting limit of 20 ppm, and only three samples had detected values. The original samples were tested again (2013) at a lower reporting limit of 0.2 ppm by ICP-MS, as were 42 new samples (2013), to better ascertain the natural levels of arsenic in undisturbed soils. The aim is to add to the existing DEQ data set, which has been used to establish new regulatory levels based on natural levels in the environment that are both safer and more economically viable than the former risk-based remediation levels (DEQ, 2013). </p><p> The maximum and mean concentrations, respectively, for each province (with high formation map unit) are 85.4 and 21.99 ppm for South Willamette Valley (Tfee), 45.4 and 5.42 ppm for the Klamath Mountains (Jub), 11.9 and 2.76 ppm for the Cascade Range (Tbaa), 10.6 and 5.15 ppm for the Coast Range (Ty), 2.32 and 1.29 ppm for the Basin and Range (Qba) and 1.5 and 1.20 ppm for the High Lava Plains (Tmv). </p><p> In addition, the distribution and variance of arsenic in the A and B soil horizons is assessed in this study by comparing deviation at a single site, and also by comparing A and B horizons of 119 PSU sites. One of 18 new sites sampled for this study (distinguished with the HH prefix), site HH11, was randomly chosen to evaluate differences at a single location. Site HH11 is an Inceptisol soil above volcanic rock (KJdv map unit) located at 275 meters elevation in Douglas County within the Klamath province. Five samples were taken from the A and from the B horizons at site HH11. The means and standard deviations were 3.74 &plusmn; 0.44 for the A horizon and 4.53 &plusmn; 0.39 for the B horizon. The consistency and low deviation within each horizon indicate that a single sample within a horizon is a good representative of that horizon and supports the field methodology used in this study of taking only one sample in the A horizon and one sample in the B horizon. </p><p> Wilcoxon Rank-Sum test determined that A and B horizons for the 119 sites that had data for both the A and B horizons were not statistically different (p-value 0.76). Arsenic concentration is not associated with a particular horizon for these sites. However, differentiation between soil horizons increases with age (Birkeland, 1999), as does accumulation of the iron oxides and sulfide minerals on clay surfaces (McLaren et al., 2006) which concentrate in the B horizon. These associations warrant further study to see how they relate to arsenic level, soil development and age in Oregon soils. </p><p> Lastly, this study statistically examines six potentially important environmental predictors of naturally occurring arsenic in southwestern Oregon: site elevation, geomorphic province, mapped rock type and age, and sample soil order and color (redness). A Classification and Regression Tree Model (CART) determined soil order, elevation and rock type to be of significant importance in determining arsenic concentrations in the natural environment. According to the regression tree, arsenic concentrations are greater within Alfisol and Ultisol/Alfisol and Vertisol soil orders, at lower elevations below 1,207 meters, and within soils from sedimentary, mixed volcanic/sedimentary and unconsolidated rock types.</p>

In recent decades, concerns about potential health effects resulting from exposure to contaminants that cause indoor air pollution have dramatically increased. The purpose of this study was to assess the indoor air quality of three buildings at Western Kentucky University and to examine and characterize indoor levels of basic comfort parameters, carbon dioxide, and fungi as well as occupants' perceptions of poor indoor air quality and the role of fungi on reported health symptoms. The three buildings included in the study were: Tate Page Hall (TPH), Jones Jagger Hall (JJH) and Science and Technology Hall (STH). Fifty-three questionnaires were completed by faculty and staff in the three buildings. The questionnaires, in addition to a walkthrough inspection and information from the Environmental Health and Safety Director and building coordinators formed the basis for classification of the three buildings (TPH and STH as complaint and JJH as noncomplaint). Comfort parameters, CO2, and fungi were measured indoors at selected offices for approximately five hours each day in summer of 2004. Measurements were also made outdoors for comparison of indoor samples. Airborne samples for viable fungi were collected onto malt Extract Agar using a single-stage Impactor calibrated at a flow rate of 28 liters per minute (L/min) for five minutes. Air samples for non-viable fungi were collected with Air-O-Cell Cassettes using the SKC Bio-Pump at a flow rate of 15L/min for ten minutes. Additionally, bulk samples were collected from areas with visible molds. The fungal samples were sent to two contract and accredited laboratories for analysis. The basic parameters were analyzed using descriptive statistics and analysis of variance. The results of the questionnaires showed response rates of 35 % for STH and TPH, and 30 %, for JJH. The most common indoor air quality (IAQ) complaints were allergies (27%), mold (27%), dust in the air (17%), temperature (13%), lack of airflow or stuffiness (10%), and physical symptoms (7%). The average indoor levels of basic parameters were within the American Society of Heating, Refrigerating and Air Conditioning Engineers (ASHRAE's) recommended limits for both complaint buildings. ANOVA results showed that the levels of environmental measurements differed significantly across buildings. Airborne indoor concentrations of fungi were significantly higher than the outdoor in STH and TPH. Whereas JJH had less than 50% indoor fungi compared to outdoor. The most prevalent fungi were Aspergillus, Acremonium Cladosporium, Penicillium, and Yeast. However, certain toxin producing fungi (Penicillium, Aspergillus, and Stachybotrys species) that have been associated with human health effects such as asthma and allergies were isolated from a number of indoor samples at higher levels in the complaint buildings than the non-complaint building. The presence of higher indoor (compare to outdoor) levels and more species of toxigenic fungi would indicate inadequate ventilation and poor indoor air quality. Poor indoor air quality resulting from allergic diseases has been associated with increased rate of Absenteeism and reduced productivity. Remedial actions are recommended for improved building design, operation and maintenance with a view to improving indoor air quality, occupants comfort, and public health.

<p> Organic and inorganic contaminants accumulate on snow grain surfaces. In an urban environment, snowpacks can retain a high load of anthropogenic contaminants that, upon melting, can deliver concentrated contaminant pulses into the aquatic environment. In climates with an extended period of snowfall accumulation, such as in Anchorage, Alaska, contaminant amplification within meltwater may affect aquatic ecosystem health. A spatiotemporal study of benzotriazoles on snow, meltwater and soils was performed in association with three urban snow disposal facilities. Benzotriazole elution from engineered snow disposal sites behaved similarly to inorganic salt and dissolved organic carbon (DOC) during the initial melt period, with maximum concentrations between 2.23-7.39 &mu;g/L; similar elution behavior was observed in creeks. Assays of disposal site soils revealed the presence of tolytriazole. Furthermore, using fluorescence spectroscopy and Parallel Factor Analysis (PARAFAC) analysis, a modeled component representative of benzotriazoles was identified, containing peaks at Ex/Em 200/306 and Ex/Em 270/387-402. It was determined that this component as well as another modeled component may be utilized as an indicator of anthropogenic input rather than a unique indicator for benzotriazole compounds. Confirmation of suspected consumer antifreeze and windshield wiping fluids containing benzotriazoles exhibited maximum tolytriazole concentrations of 644 mg/L and 138 &mu;g/L respectively.</p>

<p> Hawaii Island has the highest incidence of rat lungworm disease (RLWD) of all the Hawaiian Islands and the mainland United States. The relatively recent introduction of the semi-slug <i>Parmarion martensi,</i> an effective intermediate host, and the wide-spread use of rainwater catchment systems may play a role. Studies were designed to investigate the ability of drowned gastropods to shed larvae, the location in a water column where larvae would most likely be found, the potential for larval passage through a 20&micro;m filter, and the ability of the larvae to survive outside the slug/snail host. Whole <i>P. martensi</i> shed many, viable <i> A. cantonensis</i> larvae with >90% of larvae found in samples taken from the bottom of the water column, suggesting they may settle near the bottom of a catchment tank. Larvae that were able to pass through a 20&micro;m sieve could not survive acid, were active for at least 56 days outside the slug host, and tested positive for RLW by qPCR. Larvae that could not pass through a 20&micro;m sieve were able to survive HCl-pepsin, were active for at least 21 days, and tested positive for RLW. First stage larvae can survive gut acid when swallowed after migration from the lungs but cannot withstand acid immersion again until they become third stage larvae.The study results merit further investigation into the potential link between poorly maintained rainwater catchment systems and the high incidence of RLWD on Hawaii Island, and the studies clearly demonstrate the need for control of hosts of <i>Angiostrongylus cantonensis.</i> </p><p> Hawaii&rsquo;s remote location makes food security an important issue. State-wide efforts to promote the Grow Local, Eat Local movement are reflected in the growing number of residential gardens, small farms, farmers&rsquo; markets, school and youth garden projects, and the recent passage of the Farm to School Bill. However, efforts to educate farmers, food handlers, and consumers about rat lungworm disease and the need for disease prevention and host control has not been similarly supported. In collaboration with five partner schools on Hawaii Island, the University of Hawaii, Daniel K. Inouye College of Pharmacy&rsquo;s Hawaii Island Rat Lungworm Working Group worked with students and teachers to develop an integrated pest management plan for school garden projects. Integrated pest management allows for the careful consideration of applications available to control a pest event and chooses those practices that are least harmful to human and environmental health. These best practices include preventative cultural practices, monitoring, mechanical control, biological control, and the responsible use of pesticides. Students were intensively educated about RLWD, the parasite&rsquo;s life cycle, and prevention measures. Using best management practices, we set up traps and collected data on gastropod species abundance, and shelter-type capture rate. Integrating STEM curriculum makes the project attractive to schools as it supports student academic success. Adoption of this management project by the many school and youth garden projects in areas of RLWD can exponentially increase community awareness, encourage control efforts, and potentially map disease risk.</p>