Medical Toxicology Commons^™

Quantifying Black Carbon Concentrations In Georgia And Analyzing Associated Public Health Risks, Khloe R. Osborne

Honors Theses

Quantifying Black Carbon Concentrations in Georgia and Analyzing Associated Public Health Risks

One of the most daunting challenges of the industrial world is air pollution. Within this broad spectrum, there is an inhalable particle group named PM2.5, which contains black carbon. Black carbon has evidence that supports the generation and worsening of adverse health impacts, which may include birth complications, cognitive deficits in children, pulmonary aggravation, asthma, cardiovascular issues, neurological degenerative patterns, and cancer risk. This is especially seen in vulnerable populations, like children, elderly, and those who already suffer from weakened health, many of which reside in the southern …

In Vitro Dihalobenzene Nephrotoxicity In Isolated Kidney Cells, Jana Ahmed Sherif

Theses, Dissertations and Capstones

Brominated and chlorinated benzenes are common industrial chemicals linked to kidney injury. This study evaluated the nephrotoxicity of several mono- and dihalogenated derivatives using isolated kidney cells from male Fischer 344 rats. LDH release and trypan blue exclusion were measured after 30- and 60-minute exposures to 0.25–1.0 mM to test compounds. Toxicity increased with increased concentration and longer times. Mixed-halogen bromobenzenes, particularly 1-bromo-4-chlorobenzene, showed one of the highest toxicity levels, while 1,4dichlorobenzene was the most toxic chlorobenzene. Antioxidants (glutathione, ascorbate, and αtocopherol) markedly reduced injury, indicating oxidative mechanisms play a role in toxicity. cytochromes P450 (CYP) inhibitors (piperonyl butoxide and …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

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 …

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 …

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 …

Beyond Mitragynine: Composition Survey And Stability Assessment Of Kratom Tea Ordered Via Food Delivery Platforms In Bangkok, Thailand, Yuta Tokuda, Apinya Tubtimrattana, Nat Tansrisawad, Kornvalee Meesilpavikkai, Parath Thirati

Chulalongkorn Medical Journal

Background: Kratom is a native tree to Southeast Asia. Kratom leaves have long been used medicinally and recreationally due to their stimulative and opioid-like effects attributed to high endogenous levels of mitragynine and related alkaloids. Kratom is widely consumed as tea and is now publicly sold, including on food delivery platforms, after recent decriminalization despite selling of kratom products being still considered illegal by other acts.

Objectives: To assess the formulas of kratom teas sold on Thai food delivery platform together with their consistency and the stability of refrigerated teas.

Methods: Kratom alkaloids, mitragynine and 7-hydroxymitragynine, and additive contents of …

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

Evaluating Functional Inhibitors Of Acid Sphingomyelinase As Potential Negative Modulators Of Microvesicle Particle Release In Response To Skin Stressors, Taskin Sabit

Browse all Theses and Dissertations

Many diseases including lupus erythematosus, atopic eczema, and rosacea can be associated with photosensitivity, which is an abnormal response to sunlight. Recent studies by our group have implicated microvesicle particles (MVP) as playing an important role in causing inflammation and systemic immunosuppression. Previous studies show that functional inhibitors of acid sphingomyelinase (FIASMA) can block MVP release in response to ultraviolet B (UVB) radiation or Platelet-activating Factor (PAF) agonist, which are skin stressors. However, more research needs to be conducted to evaluate the role of PAF, UVB and FIASMA in MVP generation and to formulate a therapeutic medication to be potentially …

Fentanyl And Methamphetamine Mixture Interactions On Drug Choice In Male And Female Sprague Dawley Rats, Voisava Bokciu, Nick Heslep, Allison Ortiz, Matthew L. Banks Phd

IRBEH/Spit for Science Publications and Presentations

No abstract provided.

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

Acetaminophen, A Therapeutic Or An Extremely Toxic Remedy – A Review, Genica Caragea, Oana Avram, Andreea Pauna, Andreea Cristina Costea, Miruna Tudosie

Journal of Mind and Medical Sciences

When a new coronavirus appeared in the late 2019, identified as the cause of several cases of pneumonia in Wuhan, Paracetamol was initially reported to be the preferable antipyretic medication, choice which was detrimental to the use of other drugs. People have resorted to buying large stocks of Paracetamol and some have used it in large doses, regardless of the consequences. However, the Paracetamol (Acetaminophen) overdose remains the leading cause of death or transplantation due to acute liver failure in many parts of the world. This review aims at presenting the pharmacokinetics, the clinical signs, and the risk factors for …

Comparative Metabolism Of Aflatoxin B1 In Two Quail Genera Coturnix Japonica And Callipepla Californica, Sean Moody

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

Avian species are highly susceptible to the hepatotoxic mycotoxin aflatoxin B₁ (AFB₁). Domesticated turkeys are exquisitely sensitive, due to a combination of highly-efficient hepatic cytochrome P450 (CYP)-mediated bioactivation, and to dysfunctional alpha-class glutathione S-transferases (GSTAs) which typically detoxify the bioactivated electrophilic metabolite exo-AFB₁-8,9-epoxide (AFBO). Wild turkeys are relatively resistant to AFB₁ in large part due to expression of functional GSTAs. Quail, a related Galliforme, are slightly less sensitive in vivo to AFB₁, but whether this is related to the hepatic metabolic profiles of these two critical enzymes has not been rigorously evaluated. …

Urinary Bile Acid Indices As Prognostic Biomarkers For The Complications Of Liver Diseases, Wenkuan Li

Theses & Dissertations

Hepatobilary diseases cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may lead to an unfavorable prognosis. In this study, we compared the urinary BA profile in 257 patients with hepatobilary diseases during a 7-year follow-up period. We investigated the use of the urinary BA profile to develop logistic regression models to predict the prognosis of hepatobiliary diseases in terms of developing disease-related complications, especially for ascites. The urinary BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. All patients had high …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

Urinary Bile Acid Indices As Diagnostic And Prognosic Biomarkers For Liver Diseases, Jawaher Alamoudi

Theses & Dissertations

Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis. We compared the urinary BA profile between 300 patients with hepatobiliary diseases vs. 103 healthy controls. Also, we investigated the use of the urinary BA profile to develop survival models to predict the prognosis of hepatobiliary diseases. The urinary BA profile, a set of non-BA parameters, and the adverse events of liver transplant and/or death were monitored in patients with cholestatic liver diseases for up to 7 years. The BA profile was characterized by calculating …

Use Of Botulinum Toxin In Central Nervous System Disorders, Julie Puvogel, Paige Torbet, Jourdan Ujlaki, Rebecca Worden, Lindsey Peters

Pharmacy and Wellness Review

Botulinum toxin is a neurotoxin that is produced by Clostridium botulinum. At one time, this toxin was only seen as a lethal substance, but now scientists have found many medical uses for it. There are eight distinctive toxins (A-H), but only A and B currently have clinical uses. Botulinum toxin A has three different versions that are U.S. Food and Drug Administration (FDA) approved: onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®). Botulinum toxin B is also FDA approved as rimabotulinumtoxinB (Myobloc®). The toxins work by inducing reversible, local, dose-dependent chemodenervation by inhibiting acetylcholine release from presynaptic terminals. These drugs are approved …

A Pharmacist's Role In Educating On The Health Risks Of Smoking During Pregnancy And Helping Patients With Smoking Cessation, Alexandra Herman, Cassandra Hacker, Emily Wells, Brian Heilbronner, Brittany L. Long

Pharmacy and Wellness Review

While many people know smoking causes cancer, heart disease and other major health problems, smoking during pregnancy causes additional fetal health complications including birth defects, premature birth and infant death. Cigarettes contain carbon monoxide and nicotine, both of which can cause a decrease in oxygen delivery to the fetus' developing tissues causing organs like the brain, lungs, kidneys and ears not to develop properly. If children are exposed to these toxins through secondhand smoke after birth, they are more likely to experience severe health problems such as ear infections, cataracts, lung cancer and heart disease. It is also known that …

Latest Trends In The Heroin Epidemic And The Responsibility Of The Pharmacist In Controlling Heroin Abuse, Alexandra Herman, Cassandra Hacker, Emily Wells, Sabrina Hamman, Manoranjan D'Souza

Pharmacy and Wellness Review

Over the last few years, there has been an exponential increase in morbidity and mortality associated with heroin abuse. The current rise in heroin abuse and overdose is attributed to widespread use and abuse of prescription opioids, which can produce significant euphoric effects in humans. In fact, reports suggest that heroin abusers initially become addicted to prescription opioids but subsequently switch to heroin because it is cheaper and more easily available than prescription opioids. Over the years, the purity of heroin available for illicit use has been on the decline. Smugglers and heroin vendors have started mixing heroin with other …

Medication Overdoses In The Emergency Department: Oral Hypoglycemic Agents, Atypical Antipsychotic Agents, Beta-Blockers, Calcium Channel Blockers, And Digoxin, Brooke Marlowe, Tara Tokar, Kayti Kintner, Kelsey Fink, Grant Walliser

Pharmacy and Wellness Review

The number of medication toxicities has been steadily increasing with more patients presenting to the emergency department for both intentional and unintentional overdoses. Oral hypoglycemics, atypical antipsychotics, betablockers, calcium channel blockers and digoxin overdoses are some of the more common medication toxicities health care professionals may see in practice. Toxic doses of oral hypoglycemic agents, beta-blockers, calcium channel blockers and digoxin have more definitive options for treatment, while atypical antipsychotic overdoses are managed with supportive care. Pharmacists in particular play a pivotal role in identifying presenting symptoms and recommending appropriate treatment options in toxicological emergencies.

Drugs Of Abuse: A Review Of Tramadol Abuse, Brittany Crowe, Tiffany Kneuss, Benjamin Finley, Kelsey Fink, Manoranjan S. D'Souza

Pharmacy and Wellness Review

Prescription drug abuse is the fastest growing drug problem in America. Among the different prescription drugs being abused, analgesics are the most commonly abused group of drugs. In the last few years, there is increasing evidence of abuse of tramadol, which is an atypical, centrally acting opioid analgesic. The increasing abuse of tramadol has prompted regulatory authorities to strengthen the product labeling of tramadol with respect to its abuse potential. Furthermore, several states have added tramadol to their controlled substances list. In this article, we will review the pharmacology of tramadol and some of the preclinical and clinical studies that …

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …

Role Of Cytochrome P450 2b6 Polymorphisms In Unexpected Methadone Death, Taha Ahmad

Theses, Dissertations and Capstones

Methadone is a synthetic, long-acting opioid prescribed as an analgesic for chronic pain. It has a single chiral center forming two enantiomers, (R)-methadone and (S)-methadone, each having specific pharmacological actions. Concentrations of (R)- and (S)-methadone above therapeutic levels have the ability to cause serious, life-threatening, and fatal side effects. Cardiotoxicity is caused by elevated (S)-methadone levels by prolonging the QT interval of the heart’s electrical cycle. In 2014, methadone accounted for only 1% of all opioids prescribed for pain, but was responsible for 3,400 of the 14,838 individuals (~23%) who died in the United States from overdoses due to prescription …

A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp

Electronic Theses and Dissertations

Cisplatin is a potent chemotherapeutic used for the treatment of many solid cancers, including testicular, ovarian, and lung cancer. Cisplatin causes many adverse side effects, of which nephrotoxicity leading to acute kidney injury is dose-limiting. Approximately 30% of patients will develop nephrotoxicity with cisplatin, and will either have their next dose of cisplatin lowered, skipped, or be switched to a less nephrotoxic chemotherapeutic altogether. These outcomes are not ideal when trying to treat cancer. Previously, it was believed that patients could recover from cisplatin-induced acute kidney injury with little to no lasting effects, but recent longitudinal studies have shown this …

Characterization Of The Hepatotoxicity Of Rifampicin And Isoniazid, Christopher T. Brewer

Theses and Dissertations (ETD)

In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase of protoporphyrin ix (PPIX), the penultimate heme precursor. Excess PPIX is believed to bind to bile acids, precipitate in bile canaliculi, and form bile plugs leading to cholestasis fol owed by liver injury. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to up-regulate Alas1 but down-regulate Fech protein levels in mice; however the mechanism of isoniazid mediated heme synthesis …

Conformational Switching In The Coiled-Coil Domains Of A Proteasomal Atpase Regulates Substrate Processing, Aaron Snoberger, Evan J. Brettrager, David M. Smith

Faculty & Staff Scholarship

Protein degradation in all domains of life requires ATPases that unfold and inject proteins into compartmentalized proteolytic chambers. Proteasomal ATPases in eukaryotes and archaea contain poorly understood N-terminally conserved coiled-coil domains. In this study, we engineer disulfide crosslinks in the coiled-coils of the archaeal proteasomal ATPase (PAN) and report that its three identical coiled-coil domains can adopt three different conforma- tions: (1) in-register and zipped, (2) in-register and partially unzipped, and (3) out-of-register. This conformational heterogeneity conflicts with PAN’s symmetrical OB-coiled-coil crystal structure but resembles the conformational heterogeneity of the 26S proteasomal ATPases’ coiled-coils. Furthermore, we find that one coiled-coil …

Maternal Engineered Nanomaterial Inhalation During Gestation Alters The Fetal Transcriptome, P.A. Stapleton, Q.A. Hathaway, C.E. Nichols, A.B. Abukabda, M.V. Pinti, D.L. Shepherd, C.R. Mcbride, J. Yi, V.C. Castranova, J.M Hollander, Timothy Robert Nurkiewicz

Faculty & Staff Scholarship

Background: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. …

A Ninja Initiative At Children's Mercy, Richard Ogden, Bradley A. Warady, Vimal Chadha, Wendy Hoebing

Posters

No abstract provided.

Loss Of Fructose-1,6-Bisphosphatase Induces Glycolysis And Promotes Apoptosis Resistance Of Cancer Stem-Like Cells: An Important Role In Hexavalent Chromium-Induced Carcinogenesis, Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang

Toxicology and Cancer Biology Faculty Publications

Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance. BEAS-2B-Cr-CSC are metabolic inactive as evidenced by reductions in oxygen consumption, glucose uptake, ATP production, and lactate …

Doxorubicin Cytotoxicity In A Human Proximal Tubular Epithelial Cell Line Was Attenuated By The Natural Product Resveratrol, Morghan Schuyler Getty

Theses, Dissertations and Capstones

The cancer chemotherapeutic agent doxorubicin (DOX), Adriamycin, is part of the treatment regimen for breast, ovarian, small cell lung cancer and acute/chronic lymphoid leukemia. Adverse effects associated with DOX are cardiotoxicity and nephrotoxicity. Interventions are needed to reduce DOX nephrotoxicity. Resveratrol (RES) is a phytochemical contained in grapes, berries and nuts, which possesses antioxidant and anticancer properties. This study tested the hypothesis that RES will attenuate DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial (HK-2) cells and that RES will reduce DOX mediated changes in mitochondrial function. HK-2 cells were plated and grown for 48 hours (h). Cells …