Medical Toxicology Commons^™

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 …

C6-Ceramide Treatment Inhibits The Proangiogenic Activity Of Multiple Myeloma Exosomes Via The Mir-29b/Akt Pathway, Liping Liu, Qinmao Ye, Langni Liu, Ji Chen Bihl, Yanfang Chen, Jing Liu, Qian Cheng

Pharmacology and Toxicology Faculty Publications

Background The increased bone marrow angiogenesis is involved in the progression of multiple myeloma (MM) with the underlying mechanism poorly understood. Cancer-released exosomes could play an important role in the pathological angiogenesis through exosomal microRNAs (miRs) delivery. It is reported that miR-29b played an important role in regulating the tumor angiogenesis. Methods In this study, we explored the role of C6-ceramide (C6-cer, a Ceramide pathway activator) in the angiogenic effect of MM exosomes and its potential mechanism. MM cells (OPM2 and RPMI-8226) treated with C6-cer were studied for its effects on the endothelial cell (EC) functions. Results Our results showed …

Mechanisms Of Chromate-Induced Suppression Of Rad51: A One Environmental Health Approach., Rachel M. Speer

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer death. Lung cancer is commonly associated with smoking, however, 1 in 5 women and 1 in 12 men who develop lung cancer are never-smokers. Environmental exposures, therefore, account for a significant portion of lung cancer cases. Hexavalent chromium [Cr(VI)] is a global environmental contaminant and known human lung carcinogen. Cr(VI) and other carcinogenic metals induce chromosome instability, an early event in lung cancer. Structural chromosome instability arises in part due to failed DNA repair. Particulate Cr(VI), the most potent form of Cr(VI), induces DNA double strand breaks and inhibits the high-fidelity DNA …

Mobilizing Toxins For Cancer Treatment: Historical Perspectives And Current Strategies., Jessica Kopenhaver, Robert D Carlson, Adam E Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The level of complexity in a disease like cancer presents a number of challenges for effective treatment development, which require significant innovation to overcome [...].

Resolving Metabolic Heterogeneity In Experimental Models Of The Tumor Microenvironment From A Stable Isotope Resolved Metabolomics Perspective, Teresa W-M Fan, Richard M. Higashi, Yelena Chernayavskaya, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

The tumor microenvironment (TME) comprises complex interactions of multiple cell types that determines cell behavior and metabolism such as nutrient competition and immune suppression. We discuss the various types of heterogeneity that exist in solid tumors, and the complications this invokes for studies of TME. As human subjects and in vivo model systems are complex and difficult to manipulate, simpler 3D model systems that are compatible with flexible experimental control are necessary for studying metabolic regulation in TME. Stable Isotope Resolved Metabolomics (SIRM) is a valuable tool for tracing metabolic networks in complex systems, but at present does not directly …

Mir-132-3p Priming Enhances The Effects Of Mesenchymal Stromal Cell-Derived Exosomes On Ameliorating Brain Ischemic Injury, Qunwen Pan, Xiaoli Kuang, Shuyun Cai, Xiang Wang, Donghui Du, Jinju Wang, Yan Wang, Yanyu Chen, Ji Chen Bihl, Yanfang Chen, Bin Zhao, Xiaotang Ma

Pharmacology and Toxicology Faculty Publications

Backgrounds/aims: Mesenchymal stromal cell-derived exosomes (MSC-EXs) could exert protective effects on recipient cells by transferring the contained microRNAs (miRs), and miR-132-3p is one of angiogenic miRs. However, whether the combination of MSC-EXs and miR-132-3p has better effects in ischemic cerebrovascular disease remains unknown. Methods: Mouse MSCs transfected with scrambler control or miR-132-3p mimics were used to generate MSC-EXs and miR-132-3p-overexpressed MSC-EXs (MSC-EXsmiR-132-3p). The effects of EXs on hypoxia/reoxygenation (H/R)-injured ECs in ROS generation, apoptosis, and barrier function were analyzed. The levels of RASA1, Ras, phosphorylations of PI3K, Akt and endothelial nitric oxide synthesis (eNOS), and tight junction proteins (Claudin-5 and …

Analysis Of The Soil Lead Contamination Issue Of South Chattanooga, Tesros Cherian

Honors Theses

Childhood lead poisoning is an ongoing health threat despite actions taken by governmental bodies to remove lead from gasoline, paint, and other various household objects in which lead is found. In South Chattanooga specifically, lead has been found in the soil at such a level it is considered a public health threat, especially to children under the age of six. This situation has caused the Environmental Protection Agency (EPA) to name the South Chattanooga area as a Superfund site known as the Southside Chattanooga Lead Superfund site. This designation has resulted in multiple community meetings between EPA officials and Chattanooga …

The Effect Of Β-Caryophyllene On Isoproterenol-Induced Myocardial Infarction, Farah M. Jamal Laham

Theses

Cannabinoid type 2 receptors (CB2), a key member of the endocannabinoid system have recently emerged as a crucial therapeutic target for cardiovascular diseases (CVDs). Downregulation of CB2 receptors has been witnessed in various cancers, neurological and cardiovascular disorders. Thus, the activation of CB2 receptors may protect against ISO-induced myocardial infarction (MI) in rats. The present study investigates the cardioprotective effect of a selective cannabinoid type 2 receptor agonist β-caryophyllene (BCP), a dietary phytocannabinoid, and a natural bicyclic sesquiterpene against isoproterenol (ISO)-induced MI in rats. Male albino Wistar rats were pre-and co-treated with β-caryophyllene (50 mg/kg, orally) twice daily for 10 …

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

Graduate Theses/Dissertations

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …

Protection Against Ionizing Radiation And Chemotherapy Toxicity Via Latexin Regulation, Gary Van Zant, Ying Liang, Yi Liu

Internal Medicine Faculty Patents

The present invention relates to methods for protecting against damage caused by radiation and/or chemotherapy, and methods for treating bone marrow damage by reducing/ inhibiting Latexin expression and/or Latexin activity. The methods comprise administering to a subject in need thereof a pharmaceutical composition comprising an antagonist that reduces expression and/or activity of latexin, wherein latexin is a latexin polynucleotide variant and/or a latexin polypeptide variant that binds to the antagonist.

Renal Safety And Racial Disparity In Patients On Antiviral Treatment For Chronic Hepatitis B, Matthew Miller, Sindhuri Benjaram, Raya Kutaimy, Paul Naylor, Elizabeth May, Murray Ehrinpreis, Milton Mutchnick

Medical Student Research Symposium

Background:

Many African Americans (AA) are chronically infected with Hepatitis B (HBV). While antiviral therapy is highly effective, clinical trials suggest a treatment-related decline in kidney function is possible. Given that chronic HBV predominately affects Asians worldwide, most studies have contained few AA patients. We evaluated these treatment-related kidney function changes in our predominately AA patient population.

Methods:

From 225 HBV patients, we identified 42 patients who were not co-infected with HIV or HCV, had a recent visit, and at least one earlier visit (before Jan 2017). If on treatment with antivirals it must have been for at least 2 …

A Phantom Of The Past: Withdrawal From Meprobamate Presenting With Focal Seizures., Thomas M. Zink, John E. Erickson

Journal of Maine Medical Center

Introduction: Meprobamate (Miltown, Equinil) is a sedative-hypnotic medication that first gained popularity as an anxiolytic and later as a muscle relaxant. It is a major metabolite of the more commonly used muscle relaxant carisoprodol (Soma). In vitro and electroencephalogram studies demonstrated that meprobamate modulates gama-aminobutyric acid (GABA) receptors, similar to barbiturates. Withdrawal from meprobamate manifests in symptoms ranging from mild anxiety to severe autonomic instability and death. Meprobamate is rarely prescribed, but is still given to a small subset of elderly patients.

Clinical findings: In this case of meprobamate withdrawal, the patient initially displayed altered mental status and recurrent seizures …

The Role Of Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 9 In Enhanced Aggressiveness Of Hexavalent Chromium Transformed Bronchial Epithelial Cells, Peter Van Wie

Theses and Dissertations--Toxicology and Cancer Biology

Hexavalent chromium (Cr(VI)) is classified as a confirmed human carcinogen by the International Agency for Research and Cancer (IARC) and by the U.S. Environmental Protection Agency (EPA). Chronic exposure to (Cr(VI)) causes malignant cell transformation in human bronchial epithelial BEAS-2B cells. These Cr(VI)-transformed cells exhibit a highly aggressive phenotype including increased migration, invasion, and angiogenesis. The Cas family protein neuronal precursor developmentally down regulated protein 9 (NEDD9/Cas-L/HEF1) was dramatically overexpressed in Cr(VI)-transformed cells compared to normal BEAS-2B cells. Knockdown of NEDD9 by its shRNA reduced migration and invasion in vitro measured by migration and invasion assays. shNEDD9 reduced tumor formation …

The Effects Of Autophagy And Senescence On Sensitivity To Cisplatin In Head And Neck Cancer, Zara H. Siddiqui

Theses and Dissertations

While current treatments in cancer, such as chemotherapy and radiation, can generally be effective in eliminating disease in patients, there also exists the possibility of recurrence of cancer cells over time. In patients diagnosed with locally advanced head and neck carcinoma, about 50-60% develop a loco-regional recurrence within two years, and 20-30% of patients develop metastatic disease at distant sites in the body [5]. On a cellular level, one mechanism for this survival may be that natural mechanisms such as autophagy and senescence play a role in allowing cells to survive after undergoing treatment. One standard of care chemotherapy for …

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 …

Extracellular Vesicle-Mediated Macrophage Activation: An Insight Into The Mechanism Of Thioredoxin-Mediated Immune Activation, Chontida Yarana, Hannah Thompson, Luksana Chaiswing, D. Allan Butterfield, Heidi L. Weiss, Subbarao Bondada, Sara S. Alhakeem, Suriyan Sukati, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Extracellular vesicles (EVs) generated from redox active anticancer drugs are released into the extracellular environment. These EVs contain oxidized molecules and trigger inflammatory responses by macrophages. Using a mouse model of doxorubicin (DOX)-induced tissue injury, we previously found that the major sources of circulating EVs are from heart and liver, organs that are differentially affected by DOX. Here, we investigated the effects of EVs from cardiomyocytes and those from hepatocytes on macrophage activation. EVs from H9c2 rat cardiomyocytes (H9c2 EVs) and EVs from FL83b mouse hepatocytes (FL83 b EVs) have different levels of protein-bound 4-hydroxynonenal and thus different immunostimulatory effects …