Pharmacology, Toxicology and Environmental Health Commons^™

Differential Transcriptome Analysis Reveals That Cache Valley Pm2.5 Triggers The Unfolded Protein Response In Human Lung Cells, Morgan Eggleston

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Worldwide, exposure to air pollution is a serious human health threat. Particulate matter (PM) air pollution is a mixture of suspended solid and/or liquid particles and particle size is determined by its aerodynamic diameter. Fine, or “respirable” particles, typically from vehicle emissions, manufacturing, power generation, agriculture, as well as secondary photochemical reactions, are classified as ≤2.5μm in diameter (PM_2.5). Upon inhalation, PM_2.5 particles can reach the lower, more sensitive regions of the lung, enter the bloodstream, and be distributed to other areas in the body. Large-scale epidemiology studies have shown that PM_2.5 air pollution is associated …

Toxicity And Mitochondrial Delivery Of Flavonol-Based Carbon Monoxide-Releasing Molecules, Hector Jose Esquer Heredia

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Despite the reputation of carbon monoxide (CO) as a silent killer, new evidence suggests that this gaseous molecule has anti-inflammatory, anti-cancer and vasoprotective properties. Unfortunately, little is known about the role of CO in the body. However, proteins present in mitochondria are believed to be important targets. We previously synthesized a class of novel and structurally modifiable flavonol-based CO-releasing molecules (CORMs). Flavonols are commonly found in fruits and vegetables. The base structure, Flav-1, is fluorescent, exhibits low toxicity, and releases CO after exposure to visible light. Previous reports indicate that addition of a triphenylphosphonium (TPP) tail allows chemical structures to …

Investigation Of The Tailoring Steps In Pradimicin Biosynthesis, Kandy L. Napan

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This research focused on the investigation of the late steps in the biosynthetic pathway of the novel antifungal and antiviral pradimicins A-C. Pradimicins were first isolated from the soil bacterium Actinomadura hibisca. These bioactive molecules are assembled by a type II polyketide biosynthetic pathway. Although the biosynthetic gene cluster of pradimicin has been identified, the functions of the biosynthetic genes and how they work collaboratively to form the final structures of pradimicins remain unknown. This research aims to functionally characterize the enzymes involved in the late steps of the biosynthetic route.

The early biosynthetic steps of pradimicins have been …

Selected Neuropharmacology Of Resurgence, Adam D. Pyszczynski

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The reemergence of problem behavior (i.e., relapse) is a key concern in most behavioral interventions. Resurgence refers to the reappearance of a previously rewarded behavior when reward for an alternative behavior is also discontinued. It is especially relevant to the reappearance of problem behavior because many behavioral interventions discontinue reward for aberrant behavior while simultaneously rewarding an appropriate response.

Understanding the underlying neuropharmacology of behavioral phenomena such as resurgence is important because it helps elucidate the neural processes at the root of such behavior, and also has implications for pharmacotherapies. Existing information about the neuropharmacology of resurgence is scarce, but …

Continental-Scale Characterization Of Molecular Variation In Quaking Aspen, Colin M. Callahan

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Quaking aspen has the largest natural distribution of any tree native to North America, ranging from Alaska through the breadth of Canada and south to mid-Mexico. Recent studies suggest a general decline of aspen throughout much of the range since at least the mid-20th century, though these findings remain inconclusive. Regardless, factors such as climate change, periods of drought, soil nutrient deficiencies, pathogens, insects, and encroachment by other tree species all pose risks to the health and maintenance of aspen across the continent. This situation is exemplified in the western United States where climate change is forecasted to have an …

Great Salt Lake Watershed: Its Role In Maintaining The Wetlands Of The Great Salt Lake, Danny C. White Jr.

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

The following bioregional planning study is a direct result of the 2009- 2010 studio project initiated by the United States Fish and Wildlife Service (FWS). The FWS contacted the study team and asked them to determine how the future growth and development of the Bear River Watershed would impact the Bear River Migratory Bird Refuge (BRMBR). The study looked at all of the physical and biophysical systems within the Bear River Watershed to identify the issues that had an effect on the BRMBR.

It became apparent from the original project that the future of the BRMBR and other Great Salt …

Causes, Extent, And Consequences Of Lead-Pellet Ingestion By Chukars (Alectoris Chukar) In Western Utah: Examining Habitat, Search Images, And Toxicology, R. Justin Bingham

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Lead ingestion adversely affects humans and over 130 species of wildlife. Wild chukars (Alectoris chukar) are documented to ingest lead, but the causes and consequences of this ingestion are poorly understood. The objectives of this research were to 1) examine the influence of habitat use, the hunting season, and seasonal climate on the extent and severity of lead ingestion by chukars in western Utah, 2) assess the effects of habitat use, feeding behaviors, and lead density on the causes of lead-pellet ingestion in captive and wild chukars, and 3) investigate the consequences of lead-pellet ingestion in captive chukars as a …

Quantifying Legacy Effects Of Managed Disturbance On Sagebrush Steppe Resilience And Diversity, Julie Ripplinger

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Land-use legacies can affect landscapes for decades to millennia. A long history of shrub management exists in the sagebrush steppe of the Intermountain West where shrub-removal treatments, a type of managed disturbance, have been implemented for over 50 years to reduce sagebrush cover. The assumption behind managed disturbances is that they will increase forage for domestic livestock and improve wildlife habitat. However, the long-term effects of managed disturbance on plant community composition and diversity are not well understood. We investigated the legacy effects of three common types of managed disturbance (chemical, fire, and mechanical treatments) on plant community diversity and …

Smoking, Anemia, And Risk Of Oral Clefts In Utah, Melinda Michelle Moss

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Cigarette smoke contains sufficient carbon monoxide to induce maternal and fetal hypoxia. Hypoxia is a known teratogen, and consequently maternal smoking has been the focus of many studies on adverse birth outcomes, including cleft lip and palate. Current literature of epidemiological studies on smoking and clefts suggests a modest but statistically significant increase in risk of clefting associated with maternal smoking. A biological condition that may also contribute to hypoxia is anemia. Data from the Utah Child and Family Health Study was used to assess the effects of hypoxia-inducing conditions, maternal smoking, anemia, and their interaction, on the risk of …

The Effects Of Alternative-Site Blood Glucose Monitoring On Testing Frequency, Pain Rating, And Glycosylated Hemoglobin, Nancy Bennion

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

A crossover design study was conducted to determine if reducing pain, by using alternative sites off the finger tip, would increase testing frequency and improve clinical outcome as measured by glycosylated hemoglobin. Subjects with type 1 and type 2 diabetes tested with the FreeStyle alternative-site meter (group 1) or tested with their original meter (group 2). After 3 months the subjects used the alternate meter. Testing frequency and blood glucose concentrations were recorded for the month before the study began and monthly thereafter. Glycosylated hemoglobin was tested initially, at the crossover point, and at study conclusion. Insulin users increased testing …

4-H Summer Camp Program For Youth-At-Risk, Carol A. Daniels

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

To grow up healthy, young people need support, love, and encouragement from caring, principled adults. They need homes, schools, congregations, and communities that are accepting, affirming, and safe (Roehlkepartain , 1997). Youth and Families with Promise (YFP), a mentoring program for youth-at-risk sponsored by Utah State University Extension, is one such community endeavor. The YFP program is offered as a community service with the goal of increasing social, emotional, family, and educational assets of youth between the ages of 8-14. The program is designed to improve the youth's chances of success and to increase their ability to become and remain …

The Effects Of Retinoic Acids On The Angiogenic Growth Factors Produced By Solid Tumors, Lynn C. Burgess

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

These studies investigated the effects of retinoic acid (RA) on angiogenesis. Three human, neoplastic cell lines were used to examine angiogenic promotion and/or inhibition. The cell lines, U-373MG glioblastoma, DU-145 prostate carcinoma, and TCCSUP bladder transitional cell carcinoma, were treated with the following: all-trans, 9-cis, or 13-cis RA, at doses from 0.0001 to 100 μM. Hypoxia was used to assist the expression of the angiogenic phenotype. Conditioned media (CM) were prepared by growing the tumor cells in the presence of RA and hypoxia for 24 hours, and then the CM was transferred to bovine, capillary endothelial …

Alteration In Basic Macrophage And Lymphocyte Cytokines From Benzene And Phenol In The Drinking Water Of Male Institute Of Cancer Research Mice, Jay C. Albretsen

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Groundwater contamination is a concern due to the large number of people that can become exposed to the contaminant. The chemicals benzene and phenol are known groundwater contaminants. The main health problem caused by benzene or phenol is bone marrow toxicity. Benzene and phenol are also immunotoxins reported to cause decreased thymic weights, altered lymphocyte mitogenic responses, and lower antibody production.

Cytokines are key signaling molecules produced by the cells of the immune system to activate other cells in the immune system, produce antibodies, and recruit other cells to sites of inflammation. The purpose of this study was to determine …

Alteration Of Key Cytokine Levels By Aflatoxin B1 And T-2 Toxin In Male Cd-1 Mice, Raviprakash R. Dugyala

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Aflatoxin B₁ and T-2 toxin are mycotoxins, which produce their immunotoxic effects by affecting nonspecific and acquired immunity in different species. The mechanisms of their immunotoxicity are still obscure. Cytokines are the key signaling molecules during the immune response. In this study, expression of macrophage-produced cytokines Interleukin-lα (IL-lα), tumor necrosis factor (TNF), and IL-6, and lymphocyte-produced cytokines IL-2, interferon y (IFNy), and IL-3 was measured at the mRNA and protein levels, after in vitro activation with mitogens in AFB₁-and T-2-toxin-exposed mice.

Significant changes in the organ weights, especially in the mice exposed to a high dose of …

Metabolism Of Selected Antiviral Agents In Cells Infected With Drug-Resistant And Wild-Type Strains Of Murine Cytomegalovirus, Kevin M. Okleberry

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Resistance of human viral pathogens to various antiviral drugs is a serious medical problem. Two modes of drug resistance in cytomegalovirus infections have been observed, the first being altered (decreased) drug metabolism by the infected cells, and the second reduced sensitivity of the viral deoxyribonucleic acid polymerase enzyme to the active form of the drug. Mice infected with the murine cytomegalovirus have been used extensively as an animal model for the human cytomegalovirus, and drug-resistant strains in this model have been identified. To better understand the mode of drug resistance of the virus, the metabolism of two antiviral drugs, 9-(1,3-dihydroxy-2-propoxymethyl)guanine …

Molecular Toxicology Of Pyrrolizidine Alkaloids, Hea-Young Kim

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Pyrrolizidine alkaloids are cytotoxic, carcinogenic, and anti-carcinogenic in vivo and in vitro, and they produce many hazardous effects in humans and animals. Pyrrolizidine alkaloids (PAs) also cross-link with DNA and/or protein. However, whether such cross-linking is important to the toxic action of PAs is not known. In addition, the exact mechanism underlying these DNA cross-links or cytotoxicity is also not clear.

In three separate studies, I characterized the nature of PA-induced DNA cross-links and the relationships between PA structures and cross-linking potency. In the first study (Chapter II), I found that cross-linking potency of PA congeners coincided with their …

Influence Of 2,5-Hexanedione, Acrylamide, Tri-O-Tolyl Phosphate, Leptophos And Methylmercury On Endogenous Levels Of Tryptophan, Serotonin And 5-Hydroxyindoleacetic Acid And Serotonin Turnover Rates In Rat Brain, Craig H. Farr

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Several industrial and environmental chemicals cause distal and/or central neuropathy among other diverse toxic effects. Spague-Dawley derived rats were fed doses of 2,5-hexanedione, acrylamide, tri-o-tolyl phosphate, Leptophos and methylmercury via gavage. The dose levels and administration periods were established in previous experiments designed to assess clinical neuropathy using rats trained to walk on a rotorod apparatus fitted with an electrode floor. After intravenous injections of ³H-Tryptophan, whole rat brain homogenates were analyzed using liquid scintillation and spectrofluorometric techniques for levels of tryptophan, serotonin and 5-hydroxyindoleacetic acid. Serotonin turnover rates were calculated using the specific activities of tryptophan and serotonin …

Biological Detoxification Of Mercury Contaminated Soil, Shiying Zhang

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This study examined biological mercury removal from soil using mercury-resistant bacteria in soil microcosms. Mercuric chloride was used to artificially contaminate Kidman soil to mercury concentrations of 5 ppm and 10 ppm. Soil moisture content was maintained at three levels, 20%, 30% and 50%. Mercury resistant-bacteria were added to soil samples and the mercury removal rate was compared to control samples without added bacteria. Mercury removal rate was initially enhanced by the addition of bacteria. After 30 days, no difference was observed between samples and controls with initial mercury concentration of 5 ppm when soil moisture content was 20%. At …

Immunosuppression By Aflatoxin B1 In C57bl/6 Mice And Its Relationship With Neuroendocrine Mechanisms, Yasuhiko Hatori

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Aflatoxin B₁ (AFB₁), a secondary metabolite of Aspergillus flavus and Aspergillus parasiticus, is known for its potent carcinogenicity and immunosuppressive effects. It is also known that AFB₁ toxicity appears in different degrees in different animal species and strains.

The present study was performed to reveal the involvement of the hypothalamus-pituitary-adrenal gland (HPA) axis in the immunosuppressive effects of AFB₁ on C57BL/6 mice. Splenic lymphocytes were assayed to investigate their phenotyping using flow cytometry, proliferative response against mitogen and allogenic lymphocytes, cytolytic cell activity, and IL-2 production. In addition, antibody-mediated immunocompetence was checked using sheep …

Immunologic, Hematologic, And Endocrine Responses To Subacute And Subchronic Exposures To Graded, Subanesthetic Levels Of Nitrous Oxide In Cd-1 Mice, Charles E. Healy

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Nitrous oxide (N₂O) oxidizes vitamin B12. disrupting deoxyribonucleic acid (DNA) synthesis. Occupational exposures to subanesthetic levels of the gas have been documented that may result in suppressed proliferative cell activities. Male CD-I mice were exposed to 0, 50, 500, and 5000 parts of N₂O per million parts of air (ppm) for 6 hr/day, 5 days/week for 2 and 13 weeks. Splenic lymphocytes were assayed for responsiveness to mitogens and for the ability to produce interleukin-2 (lL-2) . Tritiated-thymidine ([³H]-TdR) uptake was measured in CD-I splenic lymphocytes cultured in a mixed-lymphocyte culture (MLC). Cytolytic cell …

A Quantitative Assessment Of Minerals Of Toxicological Importance In Utah Fast Foods, Lisa R. Williams

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

X-ray flourescence (XRF) and atomic absorption spectrophotometry (AAS) measurements for manganese, iron, copper, and zinc were compared for 96 samples of 21 foods from different sources. Correlation coefficients were 0.94 for manganese, 0.99 for iron, 0.93 for copper, and 0.91 for zinc for XRF vs. AAS determinations.

Similiar comparisons were performed on 228 samples of fast foods purchased in Utah retail outlets. Correlation coefficients ranged from 0.91 for copper to 0.97 for iron and zinc. Comparisons of values generated by XRF for manganese, iron, copper, zinc, selenium, arsenic, and aluminum to values certified by the National Bureau of Standards indicated …

Selenium And Iron In The Rat Intestine: Effects On Lipid Peroxidation, Sileny Vega

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Effects of Fe and Se status on GSHPx activity and lipid peroxidation in liver and intestinal mucosa were studied. Rats were Se and Fe supplemented (+Se+Fe), Se-deficient and Fe-supplemented (-Se+Fe), Se supplemented and Fe overloaded (+Se++Fe) by intramuscular injection, or Se deficient and Fe overloaded (-Se++Fe) for 20d. Fe overloaded tissues had more Fe, but hemoglobin was unaffected. Liver and mucosal GSHPx activity was low in Se-deficient rats. Thiobarbituric acid reactive substances (TBARS) were higher in Fe overloaded and -Se++Fe vs +Se++Fe tissues. Mucosal TBARS was higher in -Se++Fe rats gavaged with CBrCl₃. In experiment 2, Fe overload …

The Immunological And Neurochemical Toxicity Of Benzene And Its Interaction With Toluene In Mice, Gin-Chang Hsieh

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Benzene and toluene are known groundwater contaminants . Male CD-I mice were continuously exposed to 0, 31, 166, and 790 mg/ L benzene and 0, 17, 80, and 405 mg/L toluene, respectively, in drinking water for four weeks. Benzene caused a reduction of leukocytes, lymphocytes and erythrocytes, and resulted in a macrocytic anemia. Lymphocyte response to both B- and T-cell mitogens, mixed lymphocyte response to alloantigens, and the ability of cytotoxic lymphocytes to lyse tumor cells were enhanced at the lowest dose of benzene and depressed in the higher dosage animals. Benzene at doses of 166 and 790 mg/L decreased …

Effects Of Antiepileptic Drugs On Immune Function In Human Subjects And Mice, Nadine C. Margaretten

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

A number of immune abnormalities have been found in epileptic patients treated with antiepileptic drugs (AED). The alterations seen range from mild suppression of immunoglobulins to severly impaired humoral and cellular immunities. There is evidence for both drug effects and genetic or acquired factors as contributors to these abnormalities. In order to examine the basis for immune abnormalities in patients with epilepsy, a number of experimental designs were employed: clinical studies, in vitro studies, and use of an animal model.

Peripheral blood mononuclear cells (PBMC) isolated from epileptic patients currently receiving AED were found to have a reduced OKT4+/0KT8+ ratio. …

Synthesis Of 6-Aminopenicillanic Acid-Protein Conjugates For Development Of Enzyme Immunoassay For B-Lactam Antibiotics, Alice Ann Heth

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

An enzyme immunoassay specific for several β-lactam antibiotics rather than individual antibiotics was investigated. The goal to develop an enzyme immunoassay for analysis of a whole class of compounds at one time is different than the goal of most enzyme immunoassays which desire specificity for drugs or hormone levels. Detection of the presence of all β-lactam antibiotics is wanted and identification of specific antibiotics is not needed.

6-Aminopenicillanic acid, the common structural moiety of β-lactam antibiotics was used tin this investigation. Methods of preparation of 6-aminopencillanic acid conjugates and antibodies needed for enzyme immunoassays have been developed. 6-Aminopenicillanic acid was …

Effects Of 3, 5, 6-Trichloro-2-Pyridinol On Thyroid Function, Charles Franklin Luke

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

3,5,6-trichloro-2-pyridinol, when administered in the diet, increases the feed efficiency (the ratio of weight gain to feed consumed) in various species of domestic animals and also appears to be retained in the liver at low concentrations, possibly by binding to a specific macromolecule. Because of its structural similarities to the outer ring of the thyroid hormones, trichloropyridinol and three structural analogs (2,4,5-trichlorophenol, 4-bromo-2,5-dichlorophenol, or 4-iodo-2,5-dichlorophenol) were tested for ability to compete in vitro with 3,5,3'-triiodothyronine (T₃) for nuclear receptors specific for the thyroid hormones. All four of the halogenated compounds were found to be weakly competitive for the …

Natural Killer Cell Activity And Beta-Endorphin In The Mink (Mustela Vison) And The In Vitro Effect Of Beta-Endorphin In Immunologic Assays, Nancy Cathleen Pace

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The purpose of this study was to investigate natural killer cell activity and the possible role of beta- endorphin in a natural model of autoimmune orchitis, the dark mink.

An assay was developed to study natural killer cell activity in the mink and base-line levels of activity in this specie were determined. Natural killer cell activity was assessed in fertile mutation mink, primary infertile dark mink and secondary infertile Utah dark mink with autoimmune orchitis. The study included three sampling times: November, March and April. Natural killer cell activity was significantly lower in mink studied in April than it was …

Pharmacokinetic Assessment Of The Influence Of Dietary Fiber On The Absorption And Disposition Of Selected Model Xenobiotics As It Relates To Colon Cancer, Joseph Donald Debethizy

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Selected drugs are being utilized as models of putative colon carcinogens in a study of the influence of major types of dietary fiber upon drug pharmacokinetics. Adult, male Wistar rats were pretreated with standardized, isocaloric hydrated gelatin diets containing no fiber or 15% (w/w) cellulose, lignin, hemicellulose (metamucil), or pectin for 30 days. An additional group was fed lab chow ad libitum as a reference control.

The pharmacokinetics of acetaminophen, FD & C Red No. 2 and mirex were examined following oral administration in three separate experiments. Among fiber types, pectin and hemicellulose (Metamucil) caused higher peak plasma concentrations of …

Evaluation Of Allergic Hypersensitivity To 2,4-D, Malathion, And Captafol In Mice, Janette R. Cushman

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

2,4-D-specific IgE antibodies were detected in serum of BALB/c mice using the rat passive cutaneous anaphylaxis (PCA) test following the second intraperitoneal immunization with 1, 10, or 100 ug of 2,4-D0keyhole limpet hemocyanin (KLH) conjugate administered with aluminum hydroxide adjuvant. The groups that received 1 ug of 2,4-D conjugate had the highest antibody titers (geometric mean of 60). A paper radioallergosorbent test (PRAST) was developed for determination of 2,4-D-specific IgE. The PRAST was equally as sensitive as and showed a positive correlation with the PCA assay.

The anhydride of the diacid metabolite of malathion (MMA) coupled to KLH elicited MMA-specific …

Influence Of Lipophilicity On The Accumulation And Distribution Of Halogenated Phenols And A Pyridinol As Metabolites Of Pesticides In The Rat, Assed A. Attumi

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Exposure to halogenated phenols and pyridinols is of increasing concern because of their wide use and distribution. This research was initiated to determine the distribution, accumulation, and depletion of a group of halogenated phenols and a pyridinol in selected tissues of male weanling rats at different time intervals following a single oral dose of 0.33 or 1.66 m moles per kg body weight. The halogenated phenols and pyridinol were distributed differently in every tissue sampled following their administration, even though the amount administered was the same in each case. The concentrations in tissue were found in the order: 2,4,5-trichlorophenol > 4-bromo-2,5-dichlorophenol …