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Full-Text Articles in Medical Toxicology

Tumor Necrosis Factor Alpha Inhibition Improves Fetal Growth In A Rat Model Of Preeclampsia, Laura E. Coats, Nathan Campbell, Dylan Solise, Gabrielle M. Chamoun, Adam Z. Rawls, Alexandra Demesa, Ty Turner, Baoying Zheng, Barbara T. Alexander, Babbette Lamarca Feb 2026

Tumor Necrosis Factor Alpha Inhibition Improves Fetal Growth In A Rat Model Of Preeclampsia, Laura E. Coats, Nathan Campbell, Dylan Solise, Gabrielle M. Chamoun, Adam Z. Rawls, Alexandra Demesa, Ty Turner, Baoying Zheng, Barbara T. Alexander, Babbette Lamarca

Physiology & Biophysics

Introduction

Tumor necrosis factor alpha (TNF-α) is elevated 2-fold in women with preeclampsia. Preclinical investigation shows TNF-α blockade reduces maternal blood pressure in reduced uterine perfusion pressure (RUPP) rats and attenuates the reduction in fetal weight. However, the benefits versus harms of this therapy on fetal growth and underlying pathogenesis are unknown. Thus, this study tested the hypothesis that maternal treatment with the soluble TNF-α inhibitor Etanercept (Etan) during late gestation improves placental perfusion, nutrient transport, and morphology, thereby improving fetal growth in the RUPP model of preeclampsia compared with Sham controls. We further …


Inhibition Of Fatty Acid Synthase Enhances Therapeutic Efficacy And Delays Acquired Resistance To Braf-Targeted Therapy In Colorectal Cancer, Mariah E. Geisen, Elisane W. Tessmann, Courtney O. Kelson, Daheng He, Chi Wang, Abu Saleh Mosa Faisal, Ellen J. Beswick, Yasmine Baca, Stephanie Rock, Jill M. Kolesar, Yekaterina Y. Zaytseva Jan 2026

Inhibition Of Fatty Acid Synthase Enhances Therapeutic Efficacy And Delays Acquired Resistance To Braf-Targeted Therapy In Colorectal Cancer, Mariah E. Geisen, Elisane W. Tessmann, Courtney O. Kelson, Daheng He, Chi Wang, Abu Saleh Mosa Faisal, Ellen J. Beswick, Yasmine Baca, Stephanie Rock, Jill M. Kolesar, Yekaterina Y. Zaytseva

Toxicology and Cancer Biology Faculty Publications

The presence of BRAF V600E mutations is associated with poor prognosis in colorectal cancer (CRC). Although the FDA-approved combination of encorafenib and cetuximab provides clinical benefit in this population, only 22% of patients respond and most eventually develop resistance. This study investigated the mechanisms of resistance to PLX8394, a second-generation BRAF inhibitor. Using primary and established BRAF V600E CRC cells, we show that the development of resistance to PLX8394 results in cross-resistance of cells to encorafenib. Moreover, the acquired resistance is associated with increased proliferation, invasion, and upregulation of lipid metabolism, including increased expression of fatty acid synthase (FASN), a …


A Hybrid Response Surface Methodology And Machine Learning Framework For Quantifying Effects Of Physicochemical Parameters On Pfas Distribution, Harsh V. Patel, Jazmin Green, Hyoshin Park, Stephanie Luster-Teasley Pass, Renzun Zhao Jan 2026

A Hybrid Response Surface Methodology And Machine Learning Framework For Quantifying Effects Of Physicochemical Parameters On Pfas Distribution, Harsh V. Patel, Jazmin Green, Hyoshin Park, Stephanie Luster-Teasley Pass, Renzun Zhao

Engineering Management & Systems Engineering Faculty Publications

Predicting PFAS adsorption across diverse adsorbents and environmental matrices remains challenging because adsorbent physicochemical properties, PFAS molecular descriptors, and operational conditions simultaneously influence adsorption. This study develops and evaluates a unified hybrid modeling framework that integrates Response Surface Model (RSM) with machine-learning algorithms to quantify how six key variables, surface area, Log Kow, pHpzc, pKa, log dose, and log-initial concentration, affect PFAS distribution coefficients (Log Kd). A data set of more than 1000 adsorption observations spanning 15 PFAS compounds, multiple adsorbent types, and a broad operational range was compiled and preprocessed using …


Brain-Derived Extracellular Vesicles Potentially Mediate Crosstalk With Peripheral Organs In Neurodegenerative Diseases, Ramzi H. Hamdalla, Vibha B. Bhaskar, Changhai Tian Jan 2026

Brain-Derived Extracellular Vesicles Potentially Mediate Crosstalk With Peripheral Organs In Neurodegenerative Diseases, Ramzi H. Hamdalla, Vibha B. Bhaskar, Changhai Tian

Toxicology and Cancer Biology Faculty Publications

Brain-Derived Extracellular vesicles (BDEVs) are emerging mediators of intra- and interorgan communication in neurodegenerative diseases (NDs) such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). A growing body of evidence suggests that BDEVs play an important role in modulating intercellular communication within the central nervous system in the pathogenesis of many NDs. By transporting non-coding RNAs (e.g., miRNAs) and important pathological proteins, BDEVs also influence peripheral organs and contribute to the progression of disease in the central nervous system (CNS). This review extends the understanding of NDs beyond solely brain dysfunction and gives a novel framework for the progression of …


Thyroid Storm At Sea: A Case Report Of Algae-Induced Thyrotoxicosis, Alynna Knaub, Amanda Cecchini, John Janousek, Laura Strojny, Jairo Noreña, Zachary Pawlikowski Jan 2026

Thyroid Storm At Sea: A Case Report Of Algae-Induced Thyrotoxicosis, Alynna Knaub, Amanda Cecchini, John Janousek, Laura Strojny, Jairo Noreña, Zachary Pawlikowski

Department of Medicine Faculty Publications

Iodine-induced thyrotoxicosis (IIT), also known as the Jod-Basedow phenomenon, is a rare yet recognized cause of hyperthyroidism. While iodinated contrast is the most frequent trigger, iodine-rich supplements such as seaweed products or supplements can also precipitate thyrotoxicosis, particularly in individuals with prior chronic iodine deficiency or preexisting thyroid nodular disease. We present a case of thyroid storm following short-term ingestion of Irish sea moss as part of a “crash diet.” A 37-year-old woman with type 1 diabetes mellitus, well controlled on subcutaneous insulin therapy, presented with nausea and vomiting after 6 days of following a restrictive diet consisting solely of …


At1-Aa Induced Hypertension During Pregnancy Contributes To Developmental Programming Of Hypertension In Female Offspring, Nathan Campbell, James P. Lemon, Melissa Helmich, Dylan Solise, Alexandra Demesa, Ella Goolsby, Evan Lamarca, Evangeline Deer, Denise C. Cornelius, Ty Turner, Lorena M. Amaral, Baoying Zheng, Babbette Lamarca Nov 2025

At1-Aa Induced Hypertension During Pregnancy Contributes To Developmental Programming Of Hypertension In Female Offspring, Nathan Campbell, James P. Lemon, Melissa Helmich, Dylan Solise, Alexandra Demesa, Ella Goolsby, Evan Lamarca, Evangeline Deer, Denise C. Cornelius, Ty Turner, Lorena M. Amaral, Baoying Zheng, Babbette Lamarca

Pharmacology and Toxicology

Preeclampsia (PE), new-onset hypertension during pregnancy, is accompanied by organ dysfunction, in addition to placental dysfunction, and is associated with chronic inflammation and fetal growth restriction. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA) are produced in PE women and induce a PE-like phenotype when infused into pregnant rats. PE offspring are at higher risk for cardiovascular disease and hypertension; however, AT1-AA’s role in these risks is unknown. Therefore, we hypothesized that AT1-AA exposure during pregnancy contributes to hypertension in adult offspring. We infused AT1-AA (1:40) starting on gestational day (GD) 14, allowed the dams to give birth, …


Vestibular Migraine And Ssri Withdrawal: A Case Report, Grace Fairchild, Sarah Redding, Ashley G. Flagge Nov 2025

Vestibular Migraine And Ssri Withdrawal: A Case Report, Grace Fairchild, Sarah Redding, Ashley G. Flagge

Ashley Flagge Publications

Vestibular migraine (VM) has been described as a diagnosis of exclusion, with no one singular definitive assessment for diagnosis. It has been suggested that possible pharmaceutical intervention for VM can include antidepressant drugs, but this is potentially complicated by the fact that dizziness is a common side effect of both use and withdrawal for certain types of antidepressant medications. This article describes the case of a 56-year old with probable VM, who was previously diagnosed with depression and treated with the selective serotonin reuptake inhibitor (SSRI) Citalopram. Following discontinuation with no taper, the patient experienced a series of withdrawal side …


Computational Insights Into The Structural Basis For Reduced Hepatotoxicity Of Novel Nonopioid Analgesics, Claire Coderch, Hernan A. Bazán, Nicolas G. Bazan, Bhattacharjee Surjyadipta, Julio Alvarez-Builla, Beatriz De Pascual-Teresa Oct 2025

Computational Insights Into The Structural Basis For Reduced Hepatotoxicity Of Novel Nonopioid Analgesics, Claire Coderch, Hernan A. Bazán, Nicolas G. Bazan, Bhattacharjee Surjyadipta, Julio Alvarez-Builla, Beatriz De Pascual-Teresa

School of Graduate Studies Faculty Publications

Acetaminophen (ApAP) toxicity arises from the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI), a degradation product known to cause significant liver damage and kidney injury. This toxicity is a major concern associated with the widespread use of ApAP, a commonly used nonsteroidal anti-inflammatory drug. To address this important issue, a series of novel nonopioid analgesic candidates with reduced toxicity have been recently reported. However, the molecular and atomic-level mechanisms underlying their decreased toxicity remain largely unexplored. In this study, computational analyses is performed to investigate the dynamic behavior, physicochemical properties, and ligand-receptor interactions of these new chemical entities (NCEs). The findings provide …


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 Apr 2025

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 …


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 Apr 2025

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 Mar 2025

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 Mar 2025

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 …


Alpha-2 Agonist And Fentanyl Reinforcement Interactions In Male And Female Sprague Dawley Rats, Angeline Lopez, Allison Ortiz, Matthew L. Banks Jan 2025

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 Jan 2025

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 Jan 2025

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 Jan 2025

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 …


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 Nov 2024

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 …


Influences Of Quality Of Maternal Care And Environmental Enrichment On Associative Memory Function In Rats With Early Life Lead Exposure, Jay S. Schneider, Courtney Williams, Shamaila Zafar, Jaehyun Joo, Blanca E. Himes Sep 2024

Influences Of Quality Of Maternal Care And Environmental Enrichment On Associative Memory Function In Rats With Early Life Lead Exposure, Jay S. Schneider, Courtney Williams, Shamaila Zafar, Jaehyun Joo, Blanca E. Himes

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

INTRODUCTION: Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent-child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure.

METHODS: Long-Evans female rats were randomly assigned to Control (no Pb), Early Postnatal (EPN: birth through weaning), or Perinatal (PERI: 14 days pre-mating through weaning) Pb exposure groups. From …


Parasitic Contamination Of Soil In The Southern United States, Christine Crudo Blackburn, Sally Mingshuang Yan, David Mccormick, Lauren Nicholas Herrera, Roumen Borilov Iordanov, Mark Daniel Bailey, Maria Elena Bottazzi, Peter J Hotez, Rojelio Mejia Sep 2024

Parasitic Contamination Of Soil In The Southern United States, Christine Crudo Blackburn, Sally Mingshuang Yan, David Mccormick, Lauren Nicholas Herrera, Roumen Borilov Iordanov, Mark Daniel Bailey, Maria Elena Bottazzi, Peter J Hotez, Rojelio Mejia

Faculty, Staff and Students Publications

Parasites are generally associated with lower income countries in tropical and subtropical areas. Still, they are also prevalent in low-income communities in the southern United States. Studies characterizing the epidemiology of parasites in the United States are limited, resulting in little comprehensive understanding of the problem. This study investigated the environmental contamination of parasites in the southern United States by determining each parasite's contamination rate and burden in five low-income communities. A total of 499 soil samples of approximately 50 g were collected from public parks and private residences in Alabama, Louisiana, Mississippi, South Carolina, and Texas. A technique using …


Communities Disproportionately Affected By Carbon Monoxide Exposure After Winter Storm Uri, Elyse N Portillo, Casandra Quiñones, Zachary C Foughty, Ryan Ramphul, Asha T Morrow, Kathryn Fisher, Stephen A Harding, Elizabeth A Camp, Shubhada Hooli, Eric A Russell Sep 2024

Communities Disproportionately Affected By Carbon Monoxide Exposure After Winter Storm Uri, Elyse N Portillo, Casandra Quiñones, Zachary C Foughty, Ryan Ramphul, Asha T Morrow, Kathryn Fisher, Stephen A Harding, Elizabeth A Camp, Shubhada Hooli, Eric A Russell

Faculty, Staff and Students Publications

Extreme cold in February 2021 precipitated prolonged power failure in Texas. In Houston, many patients presented for carbon monoxide exposure from neighborhoods with lower per capita income, higher rates of limited English proficiency, and greater median Social Vulnerability Indices than Greater Houston. Weather-related disasters disproportionately affect socially vulnerable communities.


Enolase Inhibitors As Therapeutic Leads For Naegleria Fowleri Infection, Jillian E Milanes, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian N Dominy, Daniel C Whitehead, Steven W Millward, Madison Bolejack, Roger Shek, Logan Tillery, Isabelle Q Phan, Bart Staker, E Ashley Moseman, Xiang Zhang, Xipeng Ma, Audriy Jebet, Xinmin Yin, James C Morris Aug 2024

Enolase Inhibitors As Therapeutic Leads For Naegleria Fowleri Infection, Jillian E Milanes, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian N Dominy, Daniel C Whitehead, Steven W Millward, Madison Bolejack, Roger Shek, Logan Tillery, Isabelle Q Phan, Bart Staker, E Ashley Moseman, Xiang Zhang, Xipeng Ma, Audriy Jebet, Xinmin Yin, James C Morris

Faculty, Staff and Student Publications

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used …


Comparative Toxicological Assessment Of 2 Bisphenols Using A Systems Approach: Evaluation Of The Behavioral And Transcriptomic Responses Of Danio Rerio To Bisphenol A And Tetrabromobisphenol A, Michael G Morash, Morgan W Kirzinger, John C Achenbach, Ananda B Venkatachalam, Jessica Nixon, Susanne Penny, Joëlle Pinsonnault Cooper, Deborah E Ratzlaff, Cindy L A Woodland, Lee D Ellis Aug 2024

Comparative Toxicological Assessment Of 2 Bisphenols Using A Systems Approach: Evaluation Of The Behavioral And Transcriptomic Responses Of Danio Rerio To Bisphenol A And Tetrabromobisphenol A, Michael G Morash, Morgan W Kirzinger, John C Achenbach, Ananda B Venkatachalam, Jessica Nixon, Susanne Penny, Joëlle Pinsonnault Cooper, Deborah E Ratzlaff, Cindy L A Woodland, Lee D Ellis

Faculty, Staff and Student Publications

The zebrafish (Danio rerio) is becoming a critical component of new approach methods (NAMs) in chemical risk assessment. As a whole organism in vitro NAM, the zebrafish model offers significant advantages over individual cell-line testing, including toxicokinetic and toxicodynamic competencies. A transcriptomic approach not only allows for insight into mechanism of action for both apical endpoints and unobservable adverse outcomes, but also changes in gene expression induced by lower, environmentally relevant concentrations. In this study, we used a larval zebrafish model to assess the behavioral and transcriptomic alterations caused by subphenotypic concentrations of 2 chemicals with the same structural backbone, …


The F Plasmid Conjutome: The Repertoire Of E Coli Proteins Translocated Through An F-Encoded Type Iv Secretion System, Abu Amar M Al Mamun, Kimberley Kissoon, Yang Grace Li, Erin Hancock, Peter J Christie Jul 2024

The F Plasmid Conjutome: The Repertoire Of E Coli Proteins Translocated Through An F-Encoded Type Iv Secretion System, Abu Amar M Al Mamun, Kimberley Kissoon, Yang Grace Li, Erin Hancock, Peter J Christie

Faculty, Staff and Student Publications

Bacterial conjugation systems pose a major threat to human health through their widespread dissemination of mobile genetic elements (MGEs) carrying cargoes of antibiotic resistance genes. Using the Cre Recombinase Assay for Translocation (CRAfT), we recently reported that the IncFV pED208 conjugation system also translocates at least 16 plasmid-encoded proteins to recipient bacteria. Here, we deployed a high-throughput CRAfT screen to identify the repertoire of chromosomally encoded protein substrates of the pED208 system. We identified 32 substrates encoded by the Escherichia coli W3110 genome with functions associated with (i) DNA/nucleotide metabolism, (ii) stress tolerance/physiology, (iii) transcriptional regulation, or (iv) toxin inhibition. …


Trends In Shortages Of Lead Chelators From 2001 To 2022, James D Whitledge, Pelayia Soto, Kieran M Glowacki, Diane P Calello, Erin R Fox, Maryann Mazer-Amirshahi Jun 2024

Trends In Shortages Of Lead Chelators From 2001 To 2022, James D Whitledge, Pelayia Soto, Kieran M Glowacki, Diane P Calello, Erin R Fox, Maryann Mazer-Amirshahi

Faculty, Staff and Student Publications

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022.

METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated.

RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was …


Pharmacokinetic Analysis Of A Phenobarbital Overdose Treated With Urinary Alkalinization Alone, Justin Seltzer, Jeremy Hardin, Henrik Galust, Nathan Friedman, Bryan Corbett, Richard F Clark Jun 2024

Pharmacokinetic Analysis Of A Phenobarbital Overdose Treated With Urinary Alkalinization Alone, Justin Seltzer, Jeremy Hardin, Henrik Galust, Nathan Friedman, Bryan Corbett, Richard F Clark

Faculty, Staff and Student Publications

Phenobarbital is a long-acting barbiturate used to treat alcohol withdrawal and epilepsy. Acute overdoses present with varying levels of central nervous system depression and large overdoses can be life threatening. Phenobarbital is an attractive candidate for enhanced elimination using urinary alkalinization given it is a weak acid with a long half-life and extensive urinary elimination. Limited human data exist regarding use of urine alkalinization for the treatment of phenobarbital overdose. We present a fourteen-year-old female who was treated with urinary alkalinization alone following an intentional ingestion of 3800 mg (84.4 mg/kg) of phenobarbital tablets. Urine drugs of abuse screening was …


Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked To Morbidity And Mortality A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Camille M. Robichaux, Mark V. Frolov, Mark M. Dupaquier, Julia E. Fox, Jeffrey Sterritt, Jibin Mathew, Sahar Shekoohi, Adam M. Kaye, Amber N. Edinoff May 2024

Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked To Morbidity And Mortality A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Camille M. Robichaux, Mark V. Frolov, Mark M. Dupaquier, Julia E. Fox, Jeffrey Sterritt, Jibin Mathew, Sahar Shekoohi, Adam M. Kaye, Amber N. Edinoff

School of Dentistry Faculty Publications

Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. …


Assessment Of Potentially Toxic And Mineral Elements In Paddy Soils And Their Uptake By Rice (Oryza Sativa L) With Associated Health Hazards In District Malakand, Pakistan, Asghar Khan, Muhammad Saleem Khan, Munib Ahmed Shafique, Qaisar Khan, Ghulam Saddiq Apr 2024

Assessment Of Potentially Toxic And Mineral Elements In Paddy Soils And Their Uptake By Rice (Oryza Sativa L) With Associated Health Hazards In District Malakand, Pakistan, Asghar Khan, Muhammad Saleem Khan, Munib Ahmed Shafique, Qaisar Khan, Ghulam Saddiq

Faculty, Staff and Student Publications

Rice, a primary food source in many countries of the world accumulate potentially harmful elements which pose a significant health hazard to consumers. The current study aimed to evaluate potentially toxic and mineral elements in both paddy soils and rice grains associated with allied health risks in Malakand, Pakistan. Rice plants with intact root soil were randomly collected from paddy fields and analyzed for mineral and potentially toxic elements (PTEs) through inductively coupled plasma optical emission spectrometry (ICP‒OES). Through deterministic and probabilistic risk assessment models, the daily intake of PTEs with allied health risks from consumption of rice were estimated …


The Role Of Computational Methods In Cardiovascular Medicine: A Narrative Review, Salvatore Facciorusso, Stefania Spina, Alessandro Picelli, Alessio Baricich, Gerard E Francisco, Franco Molteni, Jörg Wissel, Andrea Santamato Apr 2024

The Role Of Computational Methods In Cardiovascular Medicine: A Narrative Review, Salvatore Facciorusso, Stefania Spina, Alessandro Picelli, Alessio Baricich, Gerard E Francisco, Franco Molteni, Jörg Wissel, Andrea Santamato

Faculty, Staff and Student Publications

Botulinum toxin type-A (BoNT-A) has emerged as a key therapeutic agent for the management of spasticity. This paper presents a comprehensive bibliometric and visual analysis of research concerning BoNT-A treatment of spasticity to elucidate current trends and future directions in this research area. A search was conducted in the Web of Science database for articles focused on the use of BoNT-A in spasticity published between 2000 and 2022. We extracted various metrics, including counts of publications and contributions from different countries, institutions, authors, and journals. Analytical methods in CiteSpace were employed for the examination of co-citations, collaborations, and the co-occurrence …


A Dynamic Model Of Inorganic Arsenic-Induced Carcinogenesis Reveals An Epigenetic Mechanism For Epithelial–Mesenchymal Plasticity, Matthew Rea, Greg Kimmerer, Shania Mittendorf, Xiaopeng Xiong, Megan Green, Darrell Chandler, Wesley Saintilnord, Jessica S. Blackburn, Tianyan Gao, Yvonne N. Fondufe-Mittendorf Apr 2024

A Dynamic Model Of Inorganic Arsenic-Induced Carcinogenesis Reveals An Epigenetic Mechanism For Epithelial–Mesenchymal Plasticity, Matthew Rea, Greg Kimmerer, Shania Mittendorf, Xiaopeng Xiong, Megan Green, Darrell Chandler, Wesley Saintilnord, Jessica S. Blackburn, Tianyan Gao, Yvonne N. Fondufe-Mittendorf

Markey Cancer Center Faculty Publications

Inorganic arsenic (iAs) causes cancer by initiating dynamic transitions between epithelial and mesenchymal cell phenotypes. These transitions transform normal cells into cancerous cells, and cancerous cells into metastatic cells. Most in vitro models assume that transitions between states are binary and complete, and do not consider the possibility that intermediate, stable cellular states might exist. In this paper, we describe a new, two-hit in vitro model of iAs-induced carcinogenesis that extends to 28 weeks of iAs exposure. Through week 17, the model faithfully recapitulates known and expected phenotypic, genetic, and epigenetic characteristics of iAs-induced carcinogenesis. By 28 weeks, however, exposed …


Amiodarone And Dronedarone Causes Liver Injury With Distinctly Different Clinical Presentations, Alexander Pop, Dina Halegoua-De Marzio, Huiman Barnhart, David Kleiner, Mark Avigan, Jiezhun Gu, Naga Chalasani, Jawad Ahmad, Robert J. Fontana, William Lee, A. Sidney Barritt, Francisco Durazo, Paul H. Hayashi, Victor J. Navarro Feb 2024

Amiodarone And Dronedarone Causes Liver Injury With Distinctly Different Clinical Presentations, Alexander Pop, Dina Halegoua-De Marzio, Huiman Barnhart, David Kleiner, Mark Avigan, Jiezhun Gu, Naga Chalasani, Jawad Ahmad, Robert J. Fontana, William Lee, A. Sidney Barritt, Francisco Durazo, Paul H. Hayashi, Victor J. Navarro

Einstein Health Papers

OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database.

METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020.

RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with …