Pharmacology, Toxicology and Environmental Health Commons^™

Comparative Impact Of Canagliflozin Versus Pioglitazone On Biomarkers Of Diabetic Kidney Disease In Db/Db Mice, Siri Chandana Minikuri

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Diabetes mellitus is a leading cause of chronic kidney disease (CKD), primarily through dysregulation of the renin-angiotensin system (RAS), characterized by elevated Ang II which promotes vasoconstriction, oxidative stress, and renal fibrosis, along with increased urinary shedding of angiotensin converting enzyme 2 (ACE2), which can exacerbate the imbalance of RAS and tubular injury. Previous studies demonstrated that rosiglitazone, a PPAR-γ agonist, attenuated hyperglycemia, glycosuria, albuminuria, and decreased urinary ACE2 shedding in db/db mice, suggesting a RAS-mediated renoprotective mechanism. Building on this evidence, the current study compared the renal effects of pioglitazone (a PPAR-γ agonist) and canagliflozin (an SGLT2 inhibitor) in …

The Role Of Base Excision Repair In Dna Damage Responses In Human Keratinocytes Exposed To Solar Simulating Uv Radiation, Mobolaji Eniola Alabi

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Ultraviolet (UV) radiation from the sun is the most prominent source of exogenous UV damage to DNA. UV directly causes damage by forming UV photoproducts, including pyrimidine-pyrimidone (6-4) photoproducts ((6-4) PPs), which significantly distort the helical structure of DNA and interfere with transcription and replication processes. The only known repair process of these photoproducts in human cells is nucleotide excision repair (NER). However, a recent study reported an APE1-dependent base excision repair (BER) of a subset of UV photoproducts. The study showed that deletion or inhibition of APE1, PARP1, NTH1, XRCC1, and FEN1 led to a 2-fold increase in sensitivity …

Characterization Of Atr Kinase Function In Quiescent Keratinocytes Exposed To Solar Simulating Uv Radiation, Mohamed Sameer Cholakkathody

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This study examines the role of Ataxia Telangiectasia and Rad3-related kinase in quiescent human keratinocytes exposed to solar-simulated UV radiation (SSL). The ATR inhibitor VE-822 did not significantly affect cell viability in the absence of UV exposure, showing that ATR kinase activity is not essential for quiescent cell survival in the absence of additional genotoxic stress. After SSL exposure, ATR inhibition did not impact acute cell viability but reduced the cells’ long-term ability to proliferate. Western blot analysis demonstrated that VE-822 potently suppressed phosphorylation of ATR target proteins KAP1 and CHK2 in a dose-dependent manner after SSL exposure, confirming strong …

Screening Of Suppressor Mutants That Confer The Suc22 S239f Mutant Cells Resistance To Hydroxyurea, An Inhibitor Of Ribonucleotide Reductase, Sairam Pasam

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Ribonucleotide reductase (RNR) is a key enzyme for the biosynthesis of dNTPs for DNA replication and repair. It is composed of a large subunit, Cdc22, and a small subunit, Suc22, in the fission yeast S. pombe. We have recently reported a suc22-S239F mutation in the small subunit of RNR, causing replication stress and hypersensitivity to hydroxyurea (HU), an inhibitor of RNR. Interestingly, this mutation does not sensitize the cell to acute treatment with HU, which mainly generates replication stress, suggesting that the mechanism of HU sensitivity in the suc22-S239F mutant remains to be fully understood. To better understand the cell-killing …

Characterization Of An Unknown Mutant C3 With A High Level Of Endogenous Replication Stress In Fission Yeast, Neha Singh

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To maintain genome stability, which is essential for cell proliferation and survival, cells rely on cell cycle checkpoint pathways to deal with perturbed DNA replication or replication stress. The fission yeast Schizosaccharomyces pombe serves as a powerful model organism for studying checkpoint mechanisms because its fundamental cellular processes are highly conserved in higher eukaryotes. During a genetic screening for mutants affecting genome integrity, we identified a novel mutant called C3 that exhibits a unique phenotype. Unlike wild-type cells, where phosphorylation of the checkpoint mediator Mrc1 is typically observed only in response to exogenously induced replication stress, such as the treatment …

Characterizing The Microvesicle Particles From Keratinocytes Stimulated With Multiple Stressors, Muslima Begum

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Many types of environmental and physical stressors act upon the skin and can initiate inflammation, systemic effects, and even damage to internal organs. Recent studies have identified that these harmful events are driven by the release of subcellular microvesicle particles (MVPs), an inflammatory process promoted by the glycerophosphocholines-derived lipid mediator, Platelet-activating Factor (PAF). These harmful effects are driven by the release of MVPs, a process promoted by the inflammatory lipid mediator, PAF. We have previously demonstrated that exposure of human HaCaT keratinocyte and mouse skin to stressors such as thermal burn injury, ultraviolet B (UVB) radiation, and topical photodynamic therapy …

Integrated Pest Management: State Infrastructure Status After 50 Yr Of Federal Support (1973 To 2023), Daren S. Mueller, Laura C. Iles, Carol L. Pilcher, Adam J. Sisson, Roger Magarey, Ryan Adams, Wanda I. Almodovar, Diane Alston, Patrick Beauzay, Ricardo Bessin, Mandy Bish, Mary Burrows, Alejandro Calixto, Rakesh Chandran, Jed B. Colquhoun, Mary Concklin, Amy J. Dreves, Peter C. Ellsworth, Paul D. Esker, James J. Farrar, Alfred Fournier, Daniel Frank, Kelly Hamby, George Hamilton, Anthony Hanson, Ann Hazelrigg, Natalie Hein-Ferris, David Held, James Jasinski, Heather M. Kelly, David Kerns, Miranda Kersten, Lauren Kerzicnik, Janet Knodel, Glen Koehler, Heidi Kratsch, Christian H. Krupke, Norman C. Leppla, Erin Lizotte, Casey Matney, Rebecca A. Melanson, Frannie Miller, Marion Murray, David Owens, Diane Plewa, Francis P. F. Reay-Jones, Silvia I. Rondon, Tom A. Royer, Philip A. Rozeboom, Hilary A. Sandler, Scott P. Schell, Marissa Schuh, Timothy Seipel, Danesha Seth Carley, Ashfaq Sial, Raghuwinder Singh, Damon L. Smith, Tim Stock, Glenn Studebaker, Adrianna Szczepaniec, Lisa Tewksbury, John Tooker, Adam J. Varenhorst, Amber Vinchesi-Vahl, Doug Walsh, Desiree Wickwar, Robert J, Wright, Simon Zebelo

Department of Entomology: Faculty Publications

Integrated pest management uses a variety of tools coupled with historical, current, and projected information for economical pest protection of crops and other resources while accounting for risk to humans and the environment. Following the 1972 US Federal IPM Policy, funding for integrated pest management programming has continued for 50+ years. However, multifaceted changes during this time have significantly affected state-level integrated pest management infrastructure, prompting a comprehensive survey to assess conditions, limitations, and growth potential of US integrated pest management programs. A survey was sent to 50 US states and 3 territories with integrated pest management programs in November …

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 …

Tick Responses To Diverse Chemical Attractants To Enhance Tick Surveillance Methods' Efficacy, Pamela Kelman, Tyler Chavers, Emily Owens Pickle, Daniel Sonenshine, Melissa S. Nolan, Holly Gaff

Biological Sciences Faculty Publications

Amblyomma maculatum Koch (Acari: Ixodidae), Ixodes scapularis Say, and Dermacentor variabilis Say are three hard-bodied ticks responsible for vectoring pathogens that cause most human tick-borne diseases in the United States of America (USA). Tick surveillance is critical to elucidate high-risk areas for targeted vector control and public health interventions. Despite tick-borne diseases having a higher annual incidence compared to mosquito-borne diseases in the USA, tick traps used for surveillance are grossly under-developed compared to the suite of sophisticated mosquito traps available on the commercial market. This study sought to identify potential prospective tick trap improvements by evaluating the relative attraction …

Évaluation Et Caractérisation De L'Exposition Aux Fumées De Soudage Et Leurs Composantes Métalliques Lors D'Activités De Soudage Au Québec, Michèle Bouchard, Jairo Buitrago-Cortes, Naïma El Majidi, Jonathan Côté, Denis Dieme, Marc Mantha, Philippe Sarazin, Capucine Ouellet, Loïc Wingert

Rapports de recherche scientifique

Problématique et objectifs :

Les fumées de soudage sont classées comme cancérogènes chez l’humain et sont associées à un risque accru de plusieurs autres effets sur la santé des soudeurs. L’objectif général de cette recherche était d’établir la nature et le niveau d’exposition aux composantes métalliques lors d'activités de soudage chez des apprentis soudeurs au Québec, en effectuant des mesures dans différentes matrices biologiques et dans l’air lors d’un suivi longitudinal.

Méthode :Cette recherche a été réalisée dans des écoles d'apprentis soudeurs de la région de Montréal, où les techniques de soudage les plus courantes sont utilisées. Elle a …

Identification Of Fentanyl And Fentanyl Analogs Found In Human Urine Using Gas Chromatography-Mass Spectrometry, Adam M. Fisher

Electronic Theses & Dissertations (2024 - present)

Identification of fentanyl and its analogs in unknown samples is a frequent practice completed in forensic crime labs, as the fentanyl epidemic continues. With the continued increase in illicit drug use, crime labs are not able to keep up with the flooding of new fentanyl analogs being developed, resulting in new analogs slipping past the crime labs’ authority. This research is to start to develop a database of commonly found fentanyl analogs in New York State. Gas Chromatography-Mass Spectrometry (GC-MS) is a widely used method for the detection and identification of illicit drugs in forensic crime labs. A database that …

Heterogeneous Being: The Inhumanities And The Creative-Scientific Aesthetic, Steven L. Ogden

Electronic Theses & Dissertations (2024 - present)

Heterogeneous Being attempts to set the often-disunited aspects of the sciences and humanities in congruence and to extol and advance a hybrid creative-scientific aesthetic that moves beyond any restricted dimensions of its previously segregated fields of study. It likewise expresses the need to perpetuate that hybrid form of inquiry and representation to successfully address or convey the precarious realities of Earth’s ecological and environmental conditions. Heterogeneous Being asks readers to observe the inexhaustible proofs of our pluralized configurations with the nonhuman world, to recognize the agentic potentialities nonhuman subjects may hold both in and outside of those inhuman enmeshments, and …

Mdma Enantiomers: An Exploration Into 5-Ht2ar Necessity In Non-Hallucinogen Induced Frontal Cortex Plasticity, Maya C. Gaines-Smith

Theses and Dissertations

Entactogen 3,4-methylenedioxymethamphetamine (MDMA) has gained increasing attention as a potential psychotherapeutic, particularly for psychiatric disorders that have proven to be resistant to traditional treatments. Despite its growing popularity, the complete neurobiological mechanism of MDMA enantiomers, as well as the role of sex in these mechanisms, remains to be fully elucidated. Current ongoing research implicates agonism of the serotonin (5-HT) 2A receptor (5-HT_2AR) and neuroplastic growth in the success of other psychoactive and hallucinogenic pharmacotherapeutics, highlighting the importance of understanding the role that the 5-HT_2AR plays in the therapeutic mechanism of action of MDMA enantiomers. The culmination …

Scopolamine-Induced Modulation Of Serotonin And Dopamine Transporters Activity: Behavioral And Molecular Insights Into Rapid Antidepressant Action, Deepak Karunakaran

Theses and Dissertations

Major depressive disorder (MDD) affects over 350 million individuals worldwide and is characterized by profound dysregulation of serotonin (5-HT) and dopamine (DA) systems that govern mood, reward processing, and motivation. The serotonin transporter (SERT) and dopamine transporter (DAT), both dynamically regulated through phosphorylation, serve as critical determinants of synaptic monoamine signaling. Despite decades of therapeutic development, current antidepressants require 4-6 weeks to achieve efficacy, and approximately one-third to half of patients develop treatment-resistant depression. The emergence of rapid-acting antidepressants like ketamine represents a paradigmatic shift, demonstrating symptom relief within hours; however, ketamine's therapeutic potential remains constrained by abuse liability, dissociative …

Unleashing Serine Palmitoyltransferase In Test Tubes And Mice, Matthew W. Peart

Theses and Dissertations

Canonically known both for structural contributions to lipid bilayers and roles in cell signaling, the sphingolipids comprise a dynamic, multifaceted class of molecules which are studied to understand homeostatic cell biology as well as pathophysiology. Sphingolipids contribute to tissue-specific structures such as myelin, a multilayer membrane that allows for rapid conduction of action potentials along neuronal axons. All sphingolipids are downstream products of the rate-limiting and initiating enzyme in the de novo sphingolipid synthesis pathway, Serine palmitoyltransferase (SPT). Demonstrative of its status as the enzyme that catalyzes a crucial step in a biochemical pathway, SPT activity is strictly regulated. This …

Detection Of Tetrahydrozoline In Alcoholic Beverage Residue Related To Drug-Facilitated Sexual Assault Using Gc-Ms, Alyssa Simone Hampton

All ETDs from UAB

Drug-facilitated sexual assault (DFSA) is an ongoing issue that remains significant in the United States and the World. DFSA can be either proactive or opportunistic, where a victim becomes impaired and is unable to provide consent. Common drugs found in DFSA cases are ethanol and cannabis. However, alternative drugs are increasingly being used to incapacitate a victim and enable a sexual assault. These include tetrahydrozoline (THZ), commonly found in over-the-counter eye drops, such as Visine®. Minimal research surrounds THZ, in which agencies may process case samples with a general drug screen, which may only detect common drugs, while THZ goes …

An Investigation Into The Effects Of Preservatives On Ss-Hydroxybutyrate Concentrations Measured By Commercial Ketone Meter And Gas Chromatography-Mass Spectrometry, Kerry F. Murr

All ETDs from UAB

Ketoacidosis occurs when fatty acids are metabolized into ketone bodies in the liver and released into the bloodstream. This condition, which can be fatal, is commonly observed in diabetics, alcoholics, and individuals who experienced starvation or hypothermia. Although the ketone ß-hydroxybutyrate (BHB) is an accepted biomarker of ketoacidosis, the effects of preservatives on BHB concentrations in postmortem blood are unaddressed. The first aim of this research was to determine whether preservatives affect ketone levels as measured by a point-of-care device. Paired preserved and unpreserved blood samples were obtained from the Jefferson County morgue: preserved samples in grey top tubes and …

Environmental Exposure To Metals In Children And Their Effects On Autism Spectrum Disorder, Oludesola Ogunesan

All ETDs from UAB

ABSTRACT As scientific understanding of environmental determinants of health advances, growing attention has turned to the role of toxic metal exposures in exacerbating neurodevelopmental outcomes, particularly in vulnerable populations such as children with autism spectrum disorder (ASD). This dissertation investigates the intersection of environmental metal exposure, biomonitoring innovation, and social factors shaping ASD severity in Alabama. Using a multidisciplinary framework, four interrelated studies explore biological, environmental, and participatory dimensions of ASD research and public health. The first study evaluates the utility of Volumetric Absorptive Microsampling (VAMS) for measuring exposure to cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), and mercury …

Exploring Environmental Health Awareness And Knowledge In 9th – 12th Grade Students: A Mixed Methods Approach, Crystal Stephens

All ETDs from UAB

EXPLORING ENVIRONMENTAL HEALTH AWARENESS AND KNOWLEDGE IN 9TH – 12TH GRADE STUDENTS: A MIXED METHODS APPROACH CRYSTAL T. STEPHENS ENVIRONMENTAL HEALTH SCIENCES ABSTRACT Safe environments provide accessibility and community protections preventing residents from exposure to contaminants or facing health risks. Unfortunately, environmental exposures such as air pollution and neighborhood-level concerns can adversely impact human health. Environmental justice communities are overburdened with increased adverse environmental exposures and subsequent health disparities. Adolescents may be more vulnerable to exposure risks and provide an opportunity to introduce environmental health education. With their power of peer association and determination, adolescents can influence the health and …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …