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Chemical and Pharmacologic Phenomena Commons

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Hexavalent Chromium-Induced Cytotoxicity And Mutagenicity: A Study Of Protection By Ascorbic Acid And Epigallocatechin Gallate, Timothy P. Mayotte 2019 Olivet Nazarene University

Hexavalent Chromium-Induced Cytotoxicity And Mutagenicity: A Study Of Protection By Ascorbic Acid And Epigallocatechin Gallate, Timothy P. Mayotte

Honors Program Projects

Hexavalent chromium, or Cr(VI), is a potent oxidizer and known carcinogen, that is found at varying levels in the water sources of more than 200 million Americans. However, the exact mechanism of carcinogenicity remains unknown, and though the government currently regulates total chromium levels, they have yet to determine a permissible exposure limit for Cr(VI). Moreover, there is currently no preventative treatment for Cr(VI). Because of Cr(VI)’s strong oxidative power, we hypothesized that it causes DNA mutation and cell death via oxidation and that antioxidants could prevent this from occurring. To test this, we first ...


Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro MD, Komal Sodhi 2019 Marshall University

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Joseph I Shapiro MD

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group ...


Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro MD, Komal Sodhi 2019 Marshall University

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Komal Sodhi

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group ...


An Investigation Of Stimulants: Reviewing Their Effects On The Brain, Including Memory And Microglia, Michael Douchey 2019 University of Nebraska at Omaha

An Investigation Of Stimulants: Reviewing Their Effects On The Brain, Including Memory And Microglia, Michael Douchey

Student Research and Creative Activity Fair

Stimulants are a class of drugs that have a variety of effects on the brain, including changes in receptor activity in the brain areas responsible for- memory, attention, emotion, motor control, and the reward pathway. Stimulants may be generally classified by their availability. For example, prescription stimulants, which include drugs such as methylphenidate (Concerta™, Ritalin™) and mixed amphetamine salts (Adderall™), must be prescribed by medical professionals. Another regulated stimulant, albeit one available without a prescription, is nicotine; a highly addictive chemical that is age-restricted by the U.S. federal government. Nicotine is found in tobacco products, and in tobacco-free alternatives ...


Icatibant Is Not Helpful For The Treatment Of Ace Inhibitor-Induced Angioedema, Samantha R. Schwartz 2019 Wayne State University School of Medicine

Icatibant Is Not Helpful For The Treatment Of Ace Inhibitor-Induced Angioedema, Samantha R. Schwartz

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sinert R, Levy P, Bernstein JA, et al. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017; 5(5): 1402-1409. doi: 10.1016/j.jaip.2017.03.003.


Leucine Supplementation In Cuprizone-Induced Oligodendrocyte Toxicity, Michael Ley 2019 The University of Akron

Leucine Supplementation In Cuprizone-Induced Oligodendrocyte Toxicity, Michael Ley

Williams Honors College, Honors Research Projects

Cuprizone is a copper chelator that induces demyelination in the central nervous system when fed to mice. This compound is thought to target Complex IV and disrupt mitochondrial metabolism leading to loss of myelin-producing oligodendrocytes. In this proposal, we further examine the chemical and toxicological properties of cuprizone. Immunofluorescence imaging and microarray data on MO3.13 cells treated with cuprizone revealed the possibility of alterations in lysosomal function, as well as mitochondrial disruption via mTOR and Electron Transport Chain (ETC) related pathways. Cell viability assays conducted suggest that addition of Branched-Chain Amino Acids, most commonly used from literature, leucine, can ...


Family Medicine Resident Education On Perioperative Management Of Patients On Anticoagulation, Hanna Mathers 2019 University of Vermont

Family Medicine Resident Education On Perioperative Management Of Patients On Anticoagulation, Hanna Mathers

Family Medicine Clerkship Student Projects

Family Medicine residents at CMMC in Lewiston, Maine manage patients in an outpatient clinic as well as on an inpatient family medicine teaching service. Many patients in the community are anticoagulated for native valve atrial fibrillation and undergo surgical procedures both in the inpatient and outpatient setting. Residents are often asked on to determine the necessity and timing of anticoagulation discontinuation for patients that they see. With patients on newer oral anticoagulants and various degrees of risk, it can be a challenge to make an informed choice. Residents have found that they would feel more confident in perioperative management of ...


Natural Product Induction In Pencillium And Human Caspase Crystallography, kelly j. mcgrath 2019 University of Montana, Missoula

Natural Product Induction In Pencillium And Human Caspase Crystallography, Kelly J. Mcgrath

Graduate Student Theses, Dissertations, & Professional Papers

No abstract provided.


Is Tpmt Testing A Predictor Of Duration Of Use Or Long-Term Benefit Of Thiopurine Agents?, Shatoya R. Wilson 2018 Grand Valley State University

Is Tpmt Testing A Predictor Of Duration Of Use Or Long-Term Benefit Of Thiopurine Agents?, Shatoya R. Wilson

Masters Theses

Background: Inflammatory Bowel Disease (IBD) affects as many as 1.3 million Americans and includes both ulcerative colitis (UC) and Crohn’s disease (CD). Recent practices have moved towards using immunomodulators early in the course of disease to prevent disease progression. Patients have shown improved outcomes on immunomodulators compared to aminosalicylates, and reduced risk for tachyphylaxis compared to corticosteroid treatment. Thiopurine agents such as azathioprine and 6-mercaptopurine are immunomodulators often used to treat IBD. Unfortunately, many patients experience cytotoxicity from thiopurine use. Recent studies have shown that patients deficient in thiopurine-S-methyltransferase (TMPT), produce an overabundance of the therapeutic end product ...


Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty 2018 University of Louisville

Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty

Electronic Theses and Dissertations

This dissertation describes how poly-chlorinated biphenyls (PCBs) exacerbate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). While PCBs were banned in 1979, they still persist in contaminated biota, including food, and are detected in human plasma and adipose. The body burden of PCBs is associated with elevation of liver enzymes and necrosis markers in humans, characteristic of NAFLD. PCB exposure in high-fat diet fed mice leads to steatohepatitis that recapitulate the findings seen in exposed humans. The global estimate of people diagnosed with NAFLD is up to 1 in 4 people, unrelated to dietary or genetic factors. The hepatic mechanisms ...


Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen 2018 Stanford University

Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen

Pharmacy Faculty Articles and Research

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the ...


30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman 2018 Augustana College, Rock Island Illinois

30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman

Celebration of Learning

There are no controlled studies of acetaminophen toxicity in horses. The objective was to test the hypotheses that oral acetaminophen administered at a dosage 25% higher than that sometimes used in horses would result in measurable hepatic toxicity as seen in humans and other species. Six healthy adult horses were administered 25 mg/kg acetaminophen powder in corn syrup twice daily for 30 days. Three other horses served as negative controls receiving only corn syrup. Jugular venous blood samples were obtained on days 7 and 1 before treatment; on treatment days 1, 2, 5, 8, 12, 15, 19, 22, 26 ...


Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti 2018 University of Massachusetts Medical School

Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti

GSBS Dissertations and Theses

Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.

We established that cholesterol-conjugated siRNAs passively associate ...


Treatment Of Opioid Dependence And Overdose, Jessi Jeffries 2018 University of Wyoming

Treatment Of Opioid Dependence And Overdose, Jessi Jeffries

Honors Theses AY 17/18

Every day in America, 90 individuals die from overdosing on prescription pain relievers or synthetic opioids. From 1999 to 2015, American deaths from opioid drug overdoses increased from 8,048 to 33,091 (National Institute on Drug Abuse, 2017). Approximately two million Americans in 2015 abused prescription pain relievers, which increased from 2014. Opioid receptors reside in the reward pathway of the brain, releasing the neurotransmitter dopamine, providing users with euphoria and analgesia. Long term drug use induces chronic constipation, drug tolerance, immune suppression, hormonal changes, and increased sensitivity to pain (Dennis, B., Naji, L., et al., 2014). Opioid use ...


Linear Ubiquitin Chain-Binding Domains, Lilian Fennell, Simin Rahighi, Fumiyo Ikeda 2018 Vienna BioCenter

Linear Ubiquitin Chain-Binding Domains, Lilian Fennell, Simin Rahighi, Fumiyo Ikeda

Pharmacy Faculty Articles and Research

Ubiquitin modification (ubiquitination) of target proteins can vary with respect to chain lengths, linkage type, and chain forms, such as homologous, mixed, and branched ubiquitin chains. Thus, ubiquitination can generate multiple unique surfaces on a target protein substrate. Ubiquitin‐binding domains (UBDs) recognize ubiquitinated substrates, by specifically binding to these unique surfaces, modulate the formation of cellular signaling complexes and regulate downstream signaling cascades. Among the eight different homotypic chain types, Met1‐linked (also termed linear) chains are the only chains in which linkage occurs on a non‐Lys residue of ubiquitin. Linear ubiquitin chains have been implicated in immune ...


Factors Involved In Suppression Of Human Vγ9vδ2 T-Lymphocytes And Impact Of Checkpoint Blockades On The Effector Functions Of Vγ9vδ2 T-Lymphocytes, MinJi Choi, Andrew Wiemer, Andrea Hubbard, Brian Aneskievich 2018 School of Pharmacy

Factors Involved In Suppression Of Human Vγ9vδ2 T-Lymphocytes And Impact Of Checkpoint Blockades On The Effector Functions Of Vγ9vδ2 T-Lymphocytes, Minji Choi, Andrew Wiemer, Andrea Hubbard, Brian Aneskievich

University Scholar Projects

Chronic antigenic stimulation leads to T cell exhaustion, which drastically dampens T cell effector functions. Upon exhaustion, T cells progressively lose their proliferative capacity, cytokine production, and cytotoxic effector functions against tumors. T cell exhaustion involves programmed cell death-1 (PD-1), which is an inhibitory co-stimulation receptor. Limited scope of studies has been done regarding impact of PD-1 expression on the effector functions of γδ T cells. In this study, we investigated expression of PD-1 and its impact on effector functions of human γδ T cells. When γδ T cells were stimulated with phosphoantigens (HMBPP and POM2-C-HMBP) and analyzed ...


Donated Chemical Probes For Open Science, Susanne Muller, Paul R. Thompson, Anke Mueller-Fahrnow 2018 Goethe University

Donated Chemical Probes For Open Science, Susanne Muller, Paul R. Thompson, Anke Mueller-Fahrnow

Open Access Articles

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of ...


Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar 2018 Guru Nanak Dev University

Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar

Pharmacy Faculty Articles and Research

Huisgen’s azide-alkyne cycloaddition reaction was employed to synthesize a series of 1H-1,2,3-triazole-tethered uracil-ferrocenyl chalcone conjugates with the aim of evaluating their in vitro anti-proliferative efficacy on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines. Cytotoxic evaluation studies identified a number of synthesized conjugates that inhibited the proliferation of leukemia cancer cells by ~70% after 72 h. The selected synthesized conjugates were found to be significantly less cytotoxic against normal kidney cell line (LLC-PK1) when compared with CCRF-CEM cancer cells.


Marijuana And The Teenage Brain: Public Health Impact, Katie C. Warther 2018 University of Vermont

Marijuana And The Teenage Brain: Public Health Impact, Katie C. Warther

Family Medicine Clerkship Student Projects

This project explores the neurobiological impact of teenage marijuana use, and the ways that public health interventions can help educate adolescents and delay the onset of use.


Characterization Of A Ulk1 Agonist, Michael Garneau 2018 University of Iowa

Characterization Of A Ulk1 Agonist, Michael Garneau

Honors Theses at the University of Iowa

The purpose of this project was to identify an agonist of autophagy. The agonist had to work specifically through increasing the expression level of ULK1 within the cell. ULK1 was used as the main marker of autophagy as it has an established role in the formation of the autophagosome, a step that is known to be crucial in the autophagy process, especially in the degradation of mitochondria. Autophagy is a cellular process that serves to breakdown and recycle cellular components that are malfunctioning or collecting above a useful level. Specifically, autophagy’s role in the degradation of poorly functioning mitochondria ...


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