Medical Toxicology Commons^™

A Rare Delayed Neuropsychiatric Encephalopathy After Hyperbaric Oxygen Treatment For Carbon Monoxide Poisoning: A Couple’S Case Report, Sabrina Kasha, William J. Naber Ii, Michael Reimer

Graduate Medical Education Research Journal

Background: Carbon monoxide (CO) poisoning is caused when carbon monoxide builds up in the blood, most specifically due to its high binding affinity for the heme structure in hemoglobin. This can lead to serious tissue damage and even be fatal. CO poisoning is primarily the result of incomplete combustion of fuels, with common sources domestically and internationally including furnaces, gas heaters, generators, and motor vehicles.2 Symptoms tend to present as neuropsychiatric symptoms, such as dementia, psychosis, parkinsonism, and incontinence. There are few well-researched CO poisoning specific treatments, which suggest supplemental oxygen and hyperbaric oxygen are most effective. We present a …

Determining The Bioaccumulation Of Minor Cannabinoids In Zebrafish Larvae, Kamdyn A. Holt

Honors Theses

Due to the increasing prevalence of cannabis product availability and usage in the modern United States, particularly among pregnant individuals, evaluating the bioaccumulation of minor cannabinoids to further understand the adverse effects of cannabinoids during early development is critical. This study quantitated the uptake of eight minor cannabinoids ((∆8-tetrahydrocannabinol (∆8-THC), ∆9-THC, ∆10-THC, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), tetrahydrocannabivarin (THCV), and hexahydrocannabinol (HHC)) in zebrafish larvae following water-borne 2 µM exposures from 6 to 96 hours post fertilization (hpf). Larvae were homogenized at 96 hpf and analyzed using a gas chromatography- mass spectrometry (GC-MS) method developed in this study. Bioconcentration …

Diabetes Mellitus And Associated Vascular Disease: Pathogenesis, Complications, And Evolving Treatments, Kazi Islam, Rahib Islam, Ivan Nguyen, Hassan Malik, Humza Pirzadah, Barsha Shrestha, Isabella B. Lentz, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Diabetes mellitus is a metabolic disorder, characterized by elevated blood sugar levels (hyperglycemia) and insulin dysregulation. This disease is associated with morbidity and mortality, including significant potential vascular complications. High levels of hyperglycemia lead to not only elevated levels of reactive oxygen species but also advanced glycation end products, which are detrimental to the vascular endothelium and reduce protective compounds such as nitric oxide and prostacyclin. This damage contributes to the development of both macrovascular and microvascular complications. The present investigation explores the pathophysiological mechanisms of diabetic vascular complications and evaluates current management strategies, including lifestyle modifications, pharmacological treatments, and …

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

Implications Of Glyphosate-Based Herbicides On The Female Reproductive System And Reproductive Outcomes, Alexandra Stone, Olivia G. Camp Ms, David Bai Md, Awoniyi Awonuga, Husam M. Abu-Soud

Medical Student Research Symposium

Background

Glyphosate-based herbicides (GBHs) are the most widely used herbicides in the United States, accounting for 19% of estimated global use. Although the Environmental Protection Agency has reaffirmed that the active ingredient glyphosate (GLY) is safe for humans, recent studies on exposure have suggested an association with cancer, metabolic disorders, endocrine disruption and infertility, and Alzheimer’s and Parkinson’s disease. Recently, we have shown that GLY exposure deteriorates metaphase II oocyte quality through zinc deficiency, ROS accumulation, and chromosome disruption. In this work, we review the mechanisms of GLY toxicity in the female reproductive tract and discuss the potential clinical implications …

Microglial Disruption In Young Mice With Early Chronic Exposure To Lead, Christina Sobin, Mayra Flores Montoya, Natali Parisi, Tanner Schaub, Miguel Cervantes, Rodrigo Armijos

Departmental Papers (PH)

The mechanisms by which early chronic lead (Pb) exposure alters brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) …

A Bland–Altman Comparison Of The Lead Care® System And Inductively Coupled Plasma Mass Spectrometry For Detecting Low-Level Lead In Child Whole Blood Samples, Christina Sobin, Tanner Schaub, Natali Parisi, Eva De La Riva

Departmental Papers (PH)

Chronic childhood lead exposure, yielding blood lead levels consistently below 10 μg/dL, remains a major public health concern. Low neurotoxic effect thresholds have not yet been established. Progress requires accurate, efficient, and cost-effective methods for testing large numbers of children. The LeadCare® System (LCS) may provide one ready option. The comparability of this system to the “gold standard” method of inductively coupled plasma mass spectrometry (ICP-MS) for the purpose of detecting blood lead levels below 10 μg/dL has not yet been examined. Paired blood samples from 177 children ages 5.2–12.8 years were tested with LCS and ICP-MS. Triplicate repeat tests …

Evaluating Dry Air Personnel Decontamination Of Methyl Salicylate As A Chemical Agent Surrogate In Extreme Cold Environments To Reduce Airborne Risks Using A Manikin, Lance E. Campbell

Theses and Dissertations

This research investigated a mobile air shower as an alternative to water washing for personnel chemical decontamination in Arctic environments, where traditional methods like disrobing and rinsing are impractical. Interest in Arctic operations has grown with recent U.S. military focus on strategic advancements by Russia and China, yet research on air shower effectiveness for chemical decontamination remains limited. This study examined whether a commercial off-the-shelf air shower could effectively decontaminate methyl salicylate (MES), a surrogate for chemical warfare blister agents, from a manikin outfitted in military cold-weather gear. Researchers used a ppbRAE 3000 photo-ionization detector to measure MES concentrations following …

A Galleria Mellonella Study: Protective Effects Of Sulforaphane On Immune Function In Binge Alcohol Exposure, Robert Kento Darby, Braydon Black, Vincent Tran, Dallen James, Scott Quimby

Annual Research Symposium

Alcohol is associated with increased mortality and morbidity. Pulmonary infections with opportunistic pathogens can occur in healthy humans; however, hazardous alcohol exposure like binge alcohol intoxication (≥ 0.08% BAC) is a major risk factor. We’ve previously investigated the efficacy of Sulforaphane (SFN) prophylaxis in protecting human and murine alveolar macrophage function against opportunistic infections when exposed to binge alcohol conditions in vitro. However, an in vivo model investigating SFN and hazardous alcohol exposure in the context of infection is not well understood. The aim of this study is to 1) establish a G. mellonella larvae model by determining the LD50 …

Poor Birth Outcomes Related To Cannabis Use In Pregnancy, Reese Weissenfluh, Madison Hall, Branden Kadlubowski, Makayla Eversole, Elizabeth Clary, Layla Dials, Brenna Hissong, Brianna Lu, Joshua Honaker, Manoranjan D'Souza

Pharmacy and Wellness Review

Pregnancy, a period of dynamic physiological changes, necessitates careful consideration of external influences on maternal and fetal health. Despite increasing legalization and prevalence, the impact of cannabis use during gestation remains a topic of significant concern and investigation.

Recent studies have shed light on the consequences of in utero cannabis exposure, encompassing both fetal and maternal outcomes. Notably, several studies have identified associations between cannabis exposure during pregnancy and adverse fetal outcomes, including small-for-gestational-age birth, altered neurodevelopment, preterm birth, and increased risk of neonatal morbidity. Evidence to date underscores the urgent need for education, intervention, and regulatory oversight regarding cannabis …

Alpha-2 Agonist And Fentanyl Reinforcement Interactions In Male And Female Sprague Dawley Rats, Angeline Lopez, Allison Ortiz, Matthew L. Banks

IRBEH/Spit for Science Publications and Presentations

In the two studies that I participated in, a behavioral economic demand curve and choice procedure, we assessed whether two alpha-2 adrenergic agonists (i.e., xylazine, clonidine, and lofexidine) altered fentanyl reinforcement in male and female sprague dawley rats. We hypothesized that xylazine and clonidine would enhance fentanyl reinforcement in a proportion-dependent manner. Lofexidine interactions with fentanyl were more difficult to predict. The data showed that xylazine did not enhance fentanyl reinforcement. Furthermore, these results were consistent with those of clonidine and lofexidine. In opposition to xylazine, clonidine and lofexidine are approved for human use for antinociception, reduction of blood pressure, …

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …

Cardiac Injury Regulates Neuroinflammation Through Extracellular Vesicle–Mediated Heart-Brain Crosstalk, Qingxuan Li, Ramzi H. Hamdalla, Neha Dhyani, Lijun Sun, Lie Gao, Tara L. Rudebush, Irving H. Zucker, Changhai Tian

Toxicology and Cancer Biology Faculty Publications

Cognitive impairment is common in heart failure patients, contributing to morbidity and mortality. This impairment may be linked to neuroinflammation in heart failure. However, the primacy of the heart-brain axis remains to be completely understood. Here, we elucidate the potential effects of myocardial injury on pathways and inflammatory mediators responsible for cognitive impairment using a rodent myocardial injury model. The results demonstrate direct extracellular vesicle (EV)-mediated heart-brain crosstalk and the glial uptake of cardiac EVs. In addition, brain inflammation was also elicited following myocardial injury. Moreover, cardiac EVs promote brain microglial cell activation in vitro, potentially mediated by EV-enriched micro-RNAs …

Decoding Tattoo And Permanent Makeup Pigments: Linking Physicochemical Properties To Absorption, Distribution, Metabolism, And Elimination Profiles Using Quantitative Structure-Activity Relationship (Qsar)-Based New Approach Methodologies (Nams), Girija Bansod, Ajay Vikram Singh, Preeti Bhardwaj, Tulika Rai, Sweta Vijay Nakhale, Amruta Shelar, Rajendra Patil, Peter Laux, Andreas Luch, Christopher J. Osgood, Michael W. Stacey

Biological Sciences Faculty Publications

The safety and quality of tattoo and permanent makeup (PMU) pigments are subject to increased scrutiny due to their potential to cause adverse effects like anaphylaxis, photoallergic responses, and long-term toxicity. These undesirable reactions governed by their chemical structure possess varied physicochemical properties and absorption, distribution, metabolism, and elimination (ADME) characteristics. These properties control the pigment behavior during application, stability, and interaction with human tissue. The correlation between these physicochemical characteristics and ADME parameters of tattoo/PMU pigments remain under-explored despite the current advances in toxicology. Our study aims to address and bridge the gap by leveraging open-access QSAR computational toxicology …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

Facilitation Of Chemotherapy Efficacy Through Targeted Drug Delivery In Lung Cancer Cells Via Ultrasound And Implications On Health Interventions, Ibrahim Nasim

Honors Undergraduate Theses

Lung Cancer (small cell and non-small cell) is the leading cause of cancer death in the US, accounting for about 20% of all cancer deaths. Paclitaxel (PTX) is a chemotherapeutic agent commonly used to treat lung cancer. It works by slowing and stopping cancer growth by stiffening microtubules within cells, promoting mitotic halt and cell death. Carboplatin (CP) is another agent given to lung cancer patients containing platinum and works via direct damage of oncolytic DNA. The exact mechanism of how PTX and CP cause cell death is still an under-studied area. This thesis aims to provide insight into how …

Nf-Κb-Mediated Oxidative Stress Drives Cigarette Smoke-Induced Emt In Human Bronchial Cells, Sarah M. Alqithami

Theses and Dissertations--Toxicology and Cancer Biology

Cigarette smoke contains over 7,000 chemicals, many being carcinogens and proinflammatory agents contributing to chronic respiratory diseases like COPD and lung cancer. This study investigated responses of human bronchial epithelial cells (HBECs) to cigarette smoke condensate (CSC), focusing on oxidative stress and NF-κB signaling. Three HBEC lines were exposed to non-cytotoxic CSC doses for 48 hours, inducing morphological changes consistent with epithelial-to-mesenchymal transition (EMT). RNA sequencing revealed transcriptomic shifts in all cell lines, particularly affecting genes related to oxidative stress, inflammation, hypoxia, and metabolism. Enrichment analyses confirmed activation of NRF2 antioxidant, NF-κB and IL-17 inflammatory, and hypoxiainducible factor pathways, indicating …

Elucidating The Adverse Effects Of Chronic Pfos Exposure On Gastrointestinal Pathology And Colorectal Cancer, Jerika Durham

Theses and Dissertations--Toxicology and Cancer Biology

Commonly referred to as "forever chemicals," per- and polyfluoroalkyl substances (PFAS) have been linked to a number of detrimental health effects, including an elevated risk of cancer. One "long-chain" subtype of PFAS, perfluorooctanesulfonic acid (PFOS), has a long elimination half-life and a significant propensity for bioaccumulation. Because PFOS is commonly found in drinking water, the gastrointestinal system absorbs it at a high rate. Recent studies demonstrate that PFAS exposures promote intestinal inflammation and gut barrier dysfunction. However, how a long-term PFOS exposure affects colorectal cancer (CRC) progression is not known. Therefore, the purpose of this research is to understand how …

Investigating Plk1 In Pulmonary Fibrosis, Tempany Arbogast

Theses and Dissertations--Toxicology and Cancer Biology

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease, with a median survival of only 2–3 years following diagnosis. In the United States, the disease contributes to more than 40,000 deaths annually, underscoring its severe clinical burden. Alveolar type II (AT2) lung epithelial cells serve as progenitors that maintain alveolar integrity by replenishing epithelial populations and producing surfactants, while fibroblasts and myofibroblasts regulate the extracellular matrix and structural support. In pulmonary fibrosis (PF) injury to AT2 cells promotes cytokine and growth factor release, driving inflammation, fibroblast proliferation, myofibroblast accumulation, and excessive extracellular matrix deposition. Aberrant AT2 cell …

Firearm Access, Carriage And Use In An Ethnically Diverse Sample Of Young Adults In Texas, Usa, Yu Lu, Elizabeth Baumler, Annalyn Saludares Demello, Leila Wood, Hillary Mcguire, Jeff R Temple

Faculty, Staff and Student Publications

Background Despite the high rates of firearm ownership and firearm-related injuries and mortalities in Southern US states, understandings on the factors contributing to these are lacking.

Methods Using wave 10 (2021) data from a longitudinal study, we examined firearm-related experiences among 636 ethnically diverse young adults (mean age=26 years; 62% female) in Texas, USA.

Results Just over half of participants had ready access to firearms, with 22.3% having carried a firearm outside of their home, 4.9% having been threatened with a firearm by a romantic partner and 4.4% by a non-romantic partner. More firearm access and carriage were reported in …