Pharmacology, Toxicology and Environmental Health Commons^™

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

Computational Studies And Design Of Pparγ And Glut1 Inhibitors, Suliman Almahmoud

Theses & Dissertations

The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor of the nuclear receptor superfamily that controls the expression of a variety of genes involved in fatty acid metabolism, adipogenesis, and insulin sensitivity. PPARγ is a target for insulin-sensitizing drugs, and it plays a significant function in prostate cancer. PPARγ antagonists have anti-proliferative effects in a broad range of hematopoietic and epithelial cell lines. The ligand binding domain (LBD) of PPARγ is large and has orthosteric and allosteric binding sites. Several PPARγ-ligand co-crystal structures show two bound molecules, one to the orthosteric pocket and a second to the allosteric …

Screening The Cultivable Cave Microbial Mats For The Production Of Antimicrobial Compounds And Antibiotic Resistance, Jerneja Ambrožič Avguštin, Patricia Petrič, Lejla Pašić

International Journal of Speleology

The current work extends the phenotypic characterization of a bacterial culture collection obtained from white, yellow, grey or pink microbial cave wall colonies that are common in the caves of Slovenian Karst. We have determined antibiotic resistance to 22 natural and synthetic antibiotics in 69 isolates from the microbial mats. Thirty-eight isolates (52%) were resistant to 1-5 antibiotics; another 27 isolates (37%) were resistant to 6-10 antibiotics; and 7 isolates (0.1%) were resistant to 11-17 antibiotics. We screened for production of antimicrobial compounds by growing cave isolates on five different media and overlaying individual cultures with ten Gram-positive and Gram …

An Electronic Medical Records-Based Approach To Identify Idiosyncratic Drug-Induced Liver Injury In Children., Tracy L. Sandritter, Jennifer Goldman, Clayton J Habiger, James F. Daniel, Jennifer Lowry, Ryan T. Fischer

Manuscripts, Articles, Book Chapters and Other Papers

Drug-induced liver injury (DILI) is the leading cause of liver failure in the United States and the most common cause of drug recall. As opposed to the recognized direct toxicity of super-therapeutic acetaminophen or chemotherapeutic agents in children, limited data exists for pediatric populations on the incidence of idiosyncratic DILI (iDILI) that may develop independently of drug dose or duration of administration. To improve the detection of adverse drug reactions at our hospital, we utilized electronic medical records-based automated trigger tools to alert providers of potential iDILI. Clinical criteria concerning for iDILI were defined as serum ALT > 5x or serum …

An Investigation Into The Relationships Between Bullying, Discrimination, Burnout And Patient Safety In Nurses And Midwives: Is Burnout A Mediator?, Judith Johnson, Lorraine Cameron, Lucy Mitchinson, Mayur Parmar, Gail Opio-Te, Gemma Louch, Angela Grange

HPD Articles

BACKGROUND: Bullying and discrimination may be indirectly associated with patient safety via their contribution to burnout, but research has yet to establish this. AIMS: The aims of this study were to investigate the relationships between workplace bullying, perceived discrimination, levels of burnout and patient safety perceptions in nurses and midwives and to assess whether bullying and discrimination were more frequently experienced by Black, Asian and minority ethnic than White nurses and midwives. METHODS: In total, 528 nurses and midwives were recruited from four hospitals in the United Kingdom to complete a cross-sectional survey between February and March 2017. The survey …

Cytotoxicity And Mutagenicity Of Disinfection Byproduct Mixtures Formulated Using Free Chlorine And Monochloramine, Yonas Ghebremedhin

Graduate Theses and Dissertations

Bioassays have been used extensively to assess various toxicity endpoints of drinking water disinfection byproducts (DBPs), but an emphasis on single compounds prevails. In this research, DBP mixtures were assessed using a cytotoxicity test with Chinese Hamster Ovary (CHO) cells and an Ames fluctuation test with Salmonella typhimurium TA-98 and TA-100 with and without S9 rat liver homogenate. Seven whole mixture DBP concentrates were formulated using reconstituted natural organic matter (NOM) extracts from the Upper Mississippi River using scaled disinfectant dosing protocols with free chlorine and monochloramine in the presence and absence of added bromide. DBPs were identified by gas …

Characterizing The Roles Of Neutral Ceramidase In Cisplatin-Induced Kidney Injury., Sophia M. Sears

Electronic Theses and Dissertations

Cisplatin is a commonly used chemotherapeutic agent with a dose-limiting nephrotoxicity. 30% of patients given cisplatin develop acute kidney injury (AKI). AKI increases risk of chronic kidney disease (CKD) development and mortality. Patients that don’t develop clinical AKI are still at risk for long term declines in renal function. Currently, there are no FDA approved agents to treat or prevent cisplatin-induced kidney injury (CDDP-KI). In this study, we demonstrated that neutral ceramidase (nCDase) knockout provides protection from AKI in the high-dose model of CDDP-KI. However, in the repeated low dose cisplatin (RLDC) model of injury and we found nCDase knockout …

Therapeutic Potential Of Withaferin A Against Non-Small Cell Lung Cancer., Al Hassan Kyakulaga

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer-related deaths worldwide and in the United States. Despite recent advancements in treatment approaches, chemoresistance and metastasis remain a major therapeutic challenge. Withaferin A (WFA), a plant-derived compound has recently emerged as a promising antitumor agent. In the present study, we explored the therapeutic potential of WFA against advanced NSCLC. Briefly, WFA was evaluated for its efficacy, toxicity and pharmacokinetic properties against advanced NSCLC using in vitro and in vivo models. Two human NSCLC cell lines, H1299 and A549 were used in cell culture to determine the anticancer properties of WFA. Repeat dose …

Acute Exposure To Tcdd Increases Liver Disease Progression In Mice With Carbon Tetrachloride-Induced Liver Injury, Giovan N. Cholico

Boise State University Theses and Dissertations

Liver disease is a worldwide problem and the 9^th leading cause of death in the United States. Common causes of liver disease include alcohol abuse, virus infection, and nonalcoholic fatty liver. Regardless of etiology, liver damage elicits inflammation and drives the activation of hepatic stellate cells (HSCs), which deposit collagen throughout the liver. During chronic injury, excessive collagen deposition, referred to as fibrosis or “scarring”, can progress to cirrhosis, cancer, and organ failure. Emerging evidence indicates a strong association between liver disease and exposure to environmental chemicals. This research investigated mechanisms by which exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo- …

Effects Of Mercury On The Dopamine Transporter Cell Surface Expression In Pc12 Cells, Christina Hui

Student Theses

Environmental factors, such as heavy metal exposures, have been suggested to have an impact not only on neurodegenerative disease, such as Parkinson’s disease, but also on psychostimulants abuse and their toxicity. In this study, two questions were addressed: 1) effects of mercuric chloride on parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP⁺) induced cytotoxicity and 2) effects of mercuric chloride on cell surface dopamine transporter. Pheochromocytorma cells (PC12) were treated with various concentrations of mercuric chloride (0.02~2.0 ppm) for 4 hours with and without 0.1 mM MPP⁺. Significant potentiation of toxicity was observed when there was co-treatment with 0.5 ppm …

The Effects Of Ship Wakes In The Venice Lagoon And Implications For The Sustainability Of Shipping In Coastal Waters, Gian Marco Scarpa, Luca Zaggia, Giorgia Manfe, Giuliano Lorenzetti, Kevin E. Parnell, Tarmo Soomere, John Rapaglia, Emanuela Molinaroli

Biology Faculty Publications

We analyse the impact of ship traffic in the vicinity of navigation channels in a wide shallow waterbody. The crucial hydrodynamic driver in this situation is the depression (Bernoulli) wake that may be transferred into a long-living solitary wave of depression over the shoals. The analysis considers navigation channels in the Venice Lagoon using a new large dataset of approximately 600 measured wake events associated to specific ships whose data are provided by the AIS system. Since the development of the modern industrial port and the opening of the Malamocco–Marghera channel in the late 1960s, growing pressure on the lagoon …

Amélioration De La Justesse Des Modèles D’Hygiène Du Travail Utilisés Pour Estimer Des Expositions Professionnelles À Des Vapeurs De Solvants, Spéro Abattan, Stéphane Hallé, Daniel Drolet, Ali Bahloul, Patrick Eddy Ryan, Wejden Chouchene, Carlos Castro Ruiz, Jérôme Lavoué, Maximilien Debia

Rapports de recherche scientifique

Chaque année, des travailleurs québécois subissent des effets sur leur santé après avoir été exposés à des substances chimiques, notamment à des solvants. La modélisation des expositions professionnelles occupe une place importante dans la prévention des risques. Cette recherche vise à étudier différents aspects de la modélisation pour estimer des expositions professionnelles à des vapeurs de solvants dans le but d’en améliorer la justesse de prédiction. Le travail de recherche a été effectué en deux volets. Grâce à la mise en œuvre de tests à petite échelle (volet I) et à échelle humaine (volet II), les travaux présentés dans cette …

The Role Of Omega-3 Polyunsaturated Fatty Acids In Blood Pressure Regulation And Secondhand Smoke-Induced Vascular Dysfunction, Emily Anna Wheeler

Biomedical Sciences ETDs

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) may lower cardiovascular disease risk by reducing blood pressure (BP). We hypothesized that fat-1 transgenic mice, which convert n-6 PUFAs to n-3 PUFAs, would have improved vascular function in BP regulation and following secondhand smoke (SHS) exposure, compared to wild type (WT) mice.

BP was recorded in mice fed an n-6 PUFA, or standard chow diet. On the n-6 PUFA diet fat-1 mice had a lower mean arterial pressure and a greater decrease in diastolic BP when treated with an ACE inhibitor, compared to WT mice. No differences were observed on the chow diet. …

Sustainable Solutions, Fall/Winter 2020, Issue 41

Sustain Magazine

No abstract provided.

Effect Of Biosurfactant And Biochar On Ecosystem Functions And Oil Remediation In Crude Oil Contaminated Wetland Soils, Zhuo Wei

LSU Doctoral Dissertations

Decontamination of oil spill from coastal wetland soils requires a delicate approach. Remediation strategies using biochar, biosurfactant, and nutrient additions have been proposed. However, there is little information on application of these with combination for treatment of crude oil-contaminated wetland soil. Therefore, incubation studies were carried out to investigate the impact of biochar and rhamnolipid (RL) biosurfactant along with nitrogen (N) application on petroleum hydrocarbon degradation in a Louisiana coastal saline marsh and their impacts on greenhouse gas (GHG) emission. Additionally, the toxicity of crude oil as well as remediation materials on coastal wetland ecosystem were assessed at three levels: …

Qualitative Approach To Comparative Exposure In Alternatives Assessment, William Greggs, Thomas Burns, Peter Egeghy, Michelle R. Embry, Peter Fantke, Bonnie Gaborek, Lauren Heine, Olivier Jolliet, Carolyn Lee, Derek Muir, Kathy Plotzke, Joseph Rinkevich, Neha Sunger, Jennifer Y. Tanir, Margaret Whittaker

Public Health Sciences Faculty Publications

Most alternatives assessments (AAs) published to date are largely hazard-based rankings, thereby ignoring potential differences in human and/or ecosystem exposures; as such, they may not represent a fully informed consideration of the advantages and disadvantages of possible alternatives. Building on the 2014 US National Academy of Sciences recommendations to improve AA decisions by including comparative exposure assessment into AAs, the Health and Environmental Sciences Institute's (HESI) Sustainable Chemical Alternatives Technical Committee, which comprises scientists from academia, industry, government, and nonprofit organizations, developed a qualitative comparative exposure approach. Conducting such a comparison can screen for alternatives that are expected to have …

Exposures At Day Labor Corners: Using Existing Georeferenced Data To Describe Features Of Urban Environments, Maria Eugenia Fernández-Esquer, Amy E Hughes, Sandi L Pruitt

Faculty, Staff and Student Publications

PURPOSE: Latino day laborers are male immigrants from mainly Mexico and Central America who congregate at corners, that is, informal hiring sites, to solicit short-term employment. Studies describing the occupational environment of Latino day laborers traditionally measure jobsite exposures, not corner exposures. We sought to elucidate exposures at corners by describing their demographic, socioeconomic, occupational, business, built, and physical environmental characteristics and by comparing corner characteristics with other locations in a large urban county in Texas.

METHODS: We used multiple publicly available data sets from the U.S. Census, local tax authority, Google's Nearby Places Application Programming Interface, and Environmental Protection …

Drinking Water Quality And Human Dimensions Of Cholera Patients To Inform Evidence-Based Prevention Investment In Karonga District, Malawi., Prince Kaponda, Suresh Muthukrishnan, Rory Barber, Rochelle H. Holm

Faculty and Staff Scholarship

Cholera remains a problem in sub-Saharan Africa, especially in Malawi. Our aim was to investigate drinking water source quality compared with water treatment, risk perception and cholera knowledge for patients who had reported to a health center for treatment in the 2017-2018 outbreak in Karonga District, Malawi. The study analyzed 120 drinking water samples linked to 236 cholera patients. Nearly 82% of the samples met the national criteria for thermotolerant coliforms of 50 cfu/100 ml, while 50% met the more stringent World Health Organization criteria of 0 cfu/100 ml. In terms of the human dimensions, 68% of survey respondents reported …

Chlorophyll A And Primary Productivity Dynamics In Kentucky Lake Mainstem And Embayment Habitats., Morgan Franklin

Scholars Week

Chlorophyll α (Chl α) has been used as a proxy for phytoplankton biomass, while primary productivity (PP), the rate at which carbon is fixed into phytoplankton cells, is an indicator of how quickly carbon is turned over within the phytoplankton community. The purpose of this research was to examine the spatial distribution of and the relationship between Chl α and PP seasonally in the main channel of Kentucky Lake reservoir and two embayments of contrasting land use. Correlation coefficients (r) for Chl α versus PP were 0.45 in Ledbetter embayment, 0.55 in Panther embayment, and 0.57 in the main …

Gut Dna Virome Diversity And Its Association With Host Bacteria Regulate Inflammatory Phenotype And Neuronal Immunotoxicity In Experimental Gulf War Illness, Ratanesh K. Seth, Rabia Maqsood, Ayan Mondal, Dipro Bose, Diana Kimono, Larinda A. Holland, Patricia Janulewicz Lloyd, Nancy Klimas, Ronnie Horner, Kimberly Sullivan, Efrem S. Lim, Saurabh Chatterjee

Faculty Publications

Gulf War illness (GWI) is characterized by the persistence of inflammatory bowel disease, chronic fatigue, neuroinflammation, headache, cognitive impairment, and other medically unexplained conditions. Results using a murine model show that enteric viral populations especially bacteriophages were altered in GWI. The increased viral richness and alpha diversity correlated positively with gut bacterial dysbiosis and proinflammatory cytokines. Altered virome signature in GWI mice also had a concomitant weakening of intestinal epithelial tight junctions with a significant increase in Claudin-2 protein expression and decrease in ZO1 and Occludin mRNA expression. The altered virome signature in GWI, decreased tight junction protein level was …

Changes In Pm2.5 Peat Combustion Source Profiles With Atmospheric Aging In An Oxidation Flow Reactor, Judith C. Chow, Junji Cao, Lung-Wen Anthony Chen, Xiaoliang Wang, Qiyuan Wang, Jie Tian, Steven Sai Hang Ho, Adam C. Watts, Tessa B. Carlson, Steven D. Kohl, John G. Watson

Environmental & Global Health Faculty Research

Smoke from laboratory chamber burning of peat fuels from Russia, Siberia, the USA (Alaska and Florida), and Malaysia representing boreal, temperate, subtropical, and tropical regions was sampled before and after passing through a potential-aerosol-mass oxidation flow reactor (PAM-OFR) to simulate intermediately aged (∼2 d) and well-aged (∼7 d) source profiles. Species abundances in PM2.5 between aged and fresh profiles varied by several orders of magnitude with two distinguishable clusters, centered around 0.1 % for reactive and ionic species and centered around 10 % for carbon. Organic carbon (OC) accounted for 58 %–85 % of PM2.5 mass in fresh profiles with …

Dysbiosis-Associated Enteric Glial Cell Immune-Activation And Redox Imbalance Modulate Tight Junction Protein Expression In Gulf War Illness Pathology, Diana Kimono, Sutapa Sarkar, Muayad Albadrani, Ratanesh K. Seth, Dipro Bose, Ayan Mondal, Yuxi Li, Amar N. Kar, Mitzi Nagarkatti, Prakash Nagarkatti, Kimberly Sullivan, Patricia Janulewicz, Stephen Lasley, Ronnie Horner, Nancy Klimas, Saurabh Chatterjee

Faculty Publications

About 14% of veterans who suffer from Gulf war illness (GWI) complain of some form of gastrointestinal disorder but with no significant markers of clinical pathology. Our previous studies have shown that exposure to GW chemicals resulted in altered microbiome which was associated with damage associated molecular pattern (DAMP) release followed by neuro and gastrointestinal inflammation with loss of gut barrier integrity. Enteric glial cells (EGC) are emerging as important regulators of the gastrointestinal tract and have been observed to change to a reactive phenotype in several functional gastrointestinal disorders such as IBS and IBD. This study is aimed at …

Réduire L’Exposition Des Travailleurs Aux Gaz, Odeurs, Poussières Et Agents Pathogènes Humains Présents Dans Les Bâtiments Porcins, Matthieu Girard, Caroline Duchaine, Stéphane Godbout, Ariane Lévesque, Valérie Létourneau, Stéphane P. Lemay

Rapports de recherche scientifique

Les éleveurs de porcs du Québec sont quotidiennement exposés à d’importantes quantités de gaz, d’odeurs, de poussières et de bioaérosols. Par conséquent, ils sont à risque de développer des problèmes respiratoires (ex. asthme) ainsi que des maladies infectieuses telles qu’une méningite à Streptococcus suis. Le risque de développer un problème de santé est lié au nombre d’heures passées à l’intérieur des bâtiments d’élevage ainsi qu’aux concentrations des différents contaminants. De plus, les travailleurs peuvent être en contact avec des bactéries résistantes aux antibiotiques soit des bactéries sélectionnées par l’emploi d’agents antimicrobiens utilisés lors de l’engraissement des animaux. Finalement, de …

Petri Nets As A Unifying Tool To Link Physiologically Based Toxicokinetic (Pbtk) Models To Adverse Outcome Pathways (Aops), Ian Edhlund

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Gut-Microbiome In Gulf War Veterans: A Preliminary Report, Patricia A. Janulewicz, Ratanesh K. Seth, Jeffrey M. Carlson, Joy Ajama, Emily Quinn, Timothy Heeren, Nancy Klimas, Steven M. Lasley, Ronnie Horner, Kimberly Sullivan, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study; GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different …

Biophysical And Biomechanical Properties Of Neural Progenitor Cells As Indicators Of Developmental Neurotoxicity, Gautam Mahajan, Moo-Yeal Lee, Chandrasekhar R. Kothapalli

Chemical & Biomedical Engineering Faculty Publications

Conventional in vitro toxicity studies have focused on identifying IC50 and the underlying mechanisms, but how toxicants influence biophysical and biomechanical changes in human cells, especially during developmental stages, remain understudied. Here, using an atomic force microscope, we characterized changes in biophysical (cell area, actin organization) and biomechanical (Young's modulus, force of adhesion, tether force, membrane tension, tether radius) aspects of human fetal brain-derived neural progenitor cells (NPCs) induced by four classes of widely used toxic compounds, including rotenone, digoxin, N-arachidonoylethanolamide (AEA), and chlorpyrifos, under exposure up to 36 h. The sub-cellular mechanisms (apoptosis, mitochondria membrane potential, DNA damage, glutathione …

Acetaminophen Protein Adducts In Hospitalized Children Receiving Multiple Doses Of Acetaminophen., Sibo Jiang, Valvanera Vozmediano, Susan M. Abdel-Rahman, Stephan Schmidt, Laura P. James

Manuscripts, Articles, Book Chapters and Other Papers

Previous reports have questioned the safety of multiple doses of acetaminophen administered to ill children. Acetaminophen protein adducts (adducts) are a biomarker of acetaminophen-induced liver injury and reflect the oxidative metabolism of acetaminophen, a known mechanism in acetaminophen toxicity. In this prospective observational study, we analyzed adduct concentrations in 1034 blood samples obtained from 181 hospitalized children (1 to 18 years inclusive) who received 2 or more doses of acetaminophen. Linear regression analysis showed that serum adduct concentrations increased as a function of the cumulative acetaminophen dose, which could be attributed, in part, to a long half-life of adducts (2.17 …

Microcystin Exposure And Liver Injury Outcomes In Nafld, Muayad Albadrani

Theses and Dissertations

Non-alcoholic fatty liver disease (NAFLD) is an emerging worldwide pandemic which is highly prevalent among obese individuals including children and adults. In a NAFLD condition, exposure to environmental contaminants or toxins can act as a second/ multiple hit, which leads to the progression of simple steatosis to NASH and ultimately may result in liver cirrhosis. With climate change today, elevated levels of microcystins are an emerging problem in fresh water bodies, which are a source of drinking water. Individuals are therefore at risk of exposure to microcystin through consuming contaminated water. In the progression of NAFLD from one clinical stage …

Study Of The Inflammatory And Fibrotic Pathology In The Gut Following Microcystin Exposure Under Conditions Of Non-Alcoholic Fatty Liver Disease., Sutapa Sarkar

Theses and Dissertations

Non-alcoholic fatty liver disease (NAFLD) has become a global pandemic with increased risks of chronic inflammation in obese and elderly population. It has become a major public health concern due to the unavailability of proper therapeutic approaches. NAFLD is a condition of the liver involving wide spectrum of events including accumulation of fat in the liver and inflammation, which can progress to a fibrotic and cirrhotic phenotype, often termed as non-alcoholic steatohepatitis (NASH). In this backdrop, exposure to environmental toxins from harmful algal blooms could prove detrimental to the overweight, obese or elderly population. NAFLD not only affects the liver …