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Articles 241 - 270 of 1065
Full-Text Articles in Pharmacy and Pharmaceutical Sciences
Quantification Of Observable Behaviors Following Oral Administration Of Oxycodone And Nalfurafine In Male Rhesus Monkeys, Sally L. Huskinson, Donna M. Platt, Zachary R. Smith, William S. Doyle, C. Austin Zamarripa, Kristen Dunaway, Thomas E. Prisinzano, Kevin B. Freeman
Quantification Of Observable Behaviors Following Oral Administration Of Oxycodone And Nalfurafine In Male Rhesus Monkeys, Sally L. Huskinson, Donna M. Platt, Zachary R. Smith, William S. Doyle, C. Austin Zamarripa, Kristen Dunaway, Thomas E. Prisinzano, Kevin B. Freeman
Pharmaceutical Sciences Faculty Publications
BACKGROUND: Recent preclinical studies have investigated the atypical kappa-opioid receptor (KOR) agonist, nalfurafine, as a co-formulary with mu-opioid receptor (MOR) agonists as a potential deterrent for misuse. However, no study has investigated effects of nalfurafine combined with a MOR agonist using an oral route of administration. The objective of the current study was to measure behavioral effects of orally administered oxycodone and nalfurafine, alone and combined, in rhesus monkeys using a quantitative behavioral observation procedure.
METHODS: Adult male rhesus monkeys (N=5) were orally administered vehicle, oxycodone (0.56-1.8mg/kg), nalfurafine (0.001-0.0056mg/kg), or mixtures (1.0mg/kg oxycodone/0.001-0.0056mg/kg nalfurafine) in a Jell-O vehicle at multiple …
Equine In Vivo Metabolite Profiling Of The Selective Androgen Receptor Modulator Lgd-3303 For Doping Control, Malin Nilsson Broberg, Heather Knych, Ulf Bondesson, Curt Pettersson, Börje Tidstedt, Scott Stanley, Mario Thevis, Mikael Hedeland
Equine In Vivo Metabolite Profiling Of The Selective Androgen Receptor Modulator Lgd-3303 For Doping Control, Malin Nilsson Broberg, Heather Knych, Ulf Bondesson, Curt Pettersson, Börje Tidstedt, Scott Stanley, Mario Thevis, Mikael Hedeland
UK CARES Faculty Publications
LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg⋅kg 1 LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizing ultra-high performance liquid …
Unleashing The Potential Of 1,3-Diketone Analogues As Selective Lh2 Inhibitors, Juhoon Lee, Hou-Fu Guo, Shike Wang, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Zhifeng Jing, Rae M. Sammons, Eun Jeong Cho, Pengyu Ren, G. Andrés Cisneros, Jonathan M. Kurie, Kevin N. Dalby
Unleashing The Potential Of 1,3-Diketone Analogues As Selective Lh2 Inhibitors, Juhoon Lee, Hou-Fu Guo, Shike Wang, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Zhifeng Jing, Rae M. Sammons, Eun Jeong Cho, Pengyu Ren, G. Andrés Cisneros, Jonathan M. Kurie, Kevin N. Dalby
Markey Cancer Center Faculty Publications
Lysyl hydroxylase 2 (LH2) catalyzes the formation of highly stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), thus promoting lung cancer metastasis through its capacity to modulate specific types of collagen cross-links within the tumor stroma. Using 1 and 2 from our previous high-throughput screening (HTS) as lead probes, we prepared a series of 1,3-diketone analogues, 1−18, and identified 12 and 13 that inhibit LH2 with IC50’s of approximately 300 and 500 nM, respectively. Compounds 12 and 13 demonstrate selectivity for LH2 over LH1 and LH3. Quantum mechanics/molecular mechanics (QM/MM) modeling indicates that the selectivity of 12 and 13 may stem from …
Discovery Of A Potent Highly Biased Mor Partial Agonist Among Diastereomeric C9-Hydroxyalkyl-5-Phenylmorphans., Joshua A. Lutz, Agnieszka Sulima, Eugene S. Gutman, Eric W. Bow, Dan Luo, Sophia Kaska, Thomas E. Prisinzano, Carol A. Paronis, Jack Bergman, Gregory H. Imler, Andrew T. Kerr, Arthur E. Jacobson, Kenner C. Rice
Discovery Of A Potent Highly Biased Mor Partial Agonist Among Diastereomeric C9-Hydroxyalkyl-5-Phenylmorphans., Joshua A. Lutz, Agnieszka Sulima, Eugene S. Gutman, Eric W. Bow, Dan Luo, Sophia Kaska, Thomas E. Prisinzano, Carol A. Paronis, Jack Bergman, Gregory H. Imler, Andrew T. Kerr, Arthur E. Jacobson, Kenner C. Rice
Pharmaceutical Sciences Faculty Publications
All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around the C9 substituent in our search for potent MOR partial agonists. These compounds were designed to lessen the lipophilicity observed with their C9-alkenyl substituted relatives. Many of the 12 diastereomers that were obtained were found to have nanomolar or subnanomolar potency in the forskolin-induced cAMP accumulation assay. Almost all these potent compounds were fully efficacious, and three of those chosen for in vivo evaluation, 15, 21, and 36, were all extremely G-protein biased; none of the three compounds recruited beta-arrestin2. Only one of the …
Controlled Release Of Dna Binding Anticancer Drugs From Gold Nanoparticles With Near-Infrared Radiation, Gracie Fitzgerald, Daniel Low, Luc Morgan, Cole Hilt, Micai Benford, Caleb Akers, Skyler Hornback, J. Zach Hilt, Daniel Scott
Controlled Release Of Dna Binding Anticancer Drugs From Gold Nanoparticles With Near-Infrared Radiation, Gracie Fitzgerald, Daniel Low, Luc Morgan, Cole Hilt, Micai Benford, Caleb Akers, Skyler Hornback, J. Zach Hilt, Daniel Scott
UK CARES Faculty Publications
Traditional chemotherapies target rapidly developing cells in the human body resulting in harsh side effects including fatigue, immune system suppression, and nausea, among others. Delivery systems to focus the active pharmaceutical ingredients (APIs) to the diseased tissue can diminish the negative side effects while improving treatment outcomes. Gold nanoparticles (AuNP) offer many unique advantages as drug delivery vehicles, including being biologically inert, easily adaptable to various shapes and sizes, able to create a strong Au-thiol bond, and able to generate heat upon the absorption of near-infrared light. To this end, a AuNP delivery vehicle was engineered to load and release …
Carboxylic Acids And Light Interact To Affect Nanoceria Stability And Dissolution In Acidic Aqueous Environments, Matthew L. Hancock, Eric A. Grulke, Robert Yokel
Carboxylic Acids And Light Interact To Affect Nanoceria Stability And Dissolution In Acidic Aqueous Environments, Matthew L. Hancock, Eric A. Grulke, Robert Yokel
Nanobiotechnology Center Faculty Publications
Cerium atoms on the surfaces of nanoceria (i.e., cerium oxide in the form of nanoparticles) can store or release oxygen, cycling between Ce3+ and Ce4+; therefore, they can cause or relieve oxidative stress within living systems. Nanoceria dissolution occurs in acidic environments. Nanoceria stabilization is a known problem even during its synthesis; in fact, a carboxylic acid, namely citric acid, is used in many synthesis protocols. Citric acid adsorbs onto nanoceria surfaces, limiting particle formation and creating stable dispersions with extended shelf life. To better understand factors influencing the fate of nanoceria, its dissolution and stabilization have …
Macrophage Polarization Status Impacts Nanoceria Cellular Distribution But Not Its Biotransformation Or Ferritin Effects, Uschi M. Graham, Alan K. Dozier, David James Feola, Michael T. Tseng, Robert Yokel
Macrophage Polarization Status Impacts Nanoceria Cellular Distribution But Not Its Biotransformation Or Ferritin Effects, Uschi M. Graham, Alan K. Dozier, David James Feola, Michael T. Tseng, Robert Yokel
Nanobiotechnology Center Faculty Publications
The innate immune system is the first line of defense against external threats through the initiation and regulation of inflammation. Macrophage differentiation into functional pheno- types influences the fate of nanomaterials taken up by these immune cells. High-resolution electron microscopy was used to investigate the uptake, distribution, and biotransformation of nanoceria in human and murine M1 and M2 macrophages in unprecedented detail. We found that M1 and M2 macrophages internalize nanoceria differently. M1-type macrophages predominantly sequester nanoceria near the plasma membrane, whereas nanoceria are more uniformly distributed throughout M2 macrophage cytoplasm. In contrast, both macrophage phenotypes show identical nanoceria biotransformation …
A Mor Antagonist With High Potency And Antagonist Efficacy Among Diastereomeric C9-Alkyl-Substituted N-Phenethyl-5-(3-Hydroxy)Phenylmorphans, Dana R. Chambers, Agnieszka Sulima, Dan Luo, Thomas E. Prisinzano, Arthur E. Jacobson, Kenner C. Rice
A Mor Antagonist With High Potency And Antagonist Efficacy Among Diastereomeric C9-Alkyl-Substituted N-Phenethyl-5-(3-Hydroxy)Phenylmorphans, Dana R. Chambers, Agnieszka Sulima, Dan Luo, Thomas E. Prisinzano, Arthur E. Jacobson, Kenner C. Rice
Pharmaceutical Sciences Faculty Publications
The 5-(3-hydroxy)phenylmorphan structural class of compounds are unlike the classical morphinans, 4,5-epoxymorphinans, and 6,7-benzomorphans, in that they have an equatorially oriented aromatic ring rather than the axial orientation of that ring found in the classical opioids. This modified and simplified opioid-like structure has been shown to retain antinociceptive activity, depending on its stereochemistry and substituents, and some of them have been found to be much more potent than morphine. A simple C9-hydroxy-5-(3-hydroxy)phenylmorphan enantiomer was found to be about 500 times more potent than morphine in vivo. We have previously examined C9-alkenyl and hydroxyalkyl substituents in the N-phenethyl-5-(3-hydroxy)phenylmorphan class of compounds. …
Potent Mor Agonists From 2′-Hydroxy-5,9-Dimethyl-N-Phenethyl Substituted-6,7-Benzomorphans And From C8-Hydroxy, Methylene And Methyl Derivatives Of N-Phenethylnormetazocine, Madhurima Das, George W. Ward, Agnieszka Sulima, Dan Luo, Thomas E. Prisinzano, Gregory H. Imler, Andrew T. Kerr, Arthur E. Jacobson, Kenner C. Rice
Potent Mor Agonists From 2′-Hydroxy-5,9-Dimethyl-N-Phenethyl Substituted-6,7-Benzomorphans And From C8-Hydroxy, Methylene And Methyl Derivatives Of N-Phenethylnormetazocine, Madhurima Das, George W. Ward, Agnieszka Sulima, Dan Luo, Thomas E. Prisinzano, Gregory H. Imler, Andrew T. Kerr, Arthur E. Jacobson, Kenner C. Rice
Pharmaceutical Sciences Faculty Publications
(−)-5,9-Dimethyl-6,7-benzomorphan (normetazocine) derivatives with a para-OH or ortho-F substituent in the aromatic ring of the N-phenethyl moiety were synthesized and found to have subnanomolar potency at MOR, and both were fully efficacious in vitro. These new compounds, (1R,5R,9R)-6,11-dimethyl-3-(2-fluorophenethyl)-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d]azocin-8-ol and (1R,5R,9R)-6,11-dimethyl-3-(4-hydroxyphenethyl)-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d] azocin-8-ol, were more potent than the unsubstituted compound N-phenethylnormetazocine and about 30 or 40 times more potent than morphine, respectively. A variety of substituents in the ortho, meta, or para position in the aromatic ring of the N-phenethyl moiety were synthesized, 25 of these compounds, and found to have varying effects on potency and efficacy as determined by the forskolin-induced …
The Prevalence Of Opioid Use Disorder In Kentucky’S Counties: A Two-Year Multi-Sample Capture-Recapture Analysis, Katherine L. Thompson, Joshua A. Barocas, Chris Delcher, Jungjun Bae, Lindsey R. Hammerslag, Jianing Wang, Redonna Chandler, Jennifer Villani, Sharon L. Walsh, Jeffery Talbert
The Prevalence Of Opioid Use Disorder In Kentucky’S Counties: A Two-Year Multi-Sample Capture-Recapture Analysis, Katherine L. Thompson, Joshua A. Barocas, Chris Delcher, Jungjun Bae, Lindsey R. Hammerslag, Jianing Wang, Redonna Chandler, Jennifer Villani, Sharon L. Walsh, Jeffery Talbert
Pharmacy Practice and Science Faculty Publications
Background: Kentucky has one of the highest opioid overdose mortality rates in the United States. Accurate estimates of people with opioid use disorder (OUD) are critical to plan for the scope of interventions required to reduce overdose and opioid misuse. Commonly used household surveys are known to underestimate OUD at the state-level and do not provide county-level estimates.
Methods: We performed a multi-sample capture-recapture analysis to estimate OUD prevalence in Kentucky in 2018 and 2019. We utilized four statewide datasets that were linked at the individual level: 1) Registry of Vital Statistics, 2) Emergency Medical Services (EMS), 3) Kentucky’s Prescription …
Anti-Inflammatory And Analgesic Effects Of Highly Selective Microsomal Prostaglandin E2 Synthase-1 (Mpges-1) Inhibitors, Madeline Stewart
Anti-Inflammatory And Analgesic Effects Of Highly Selective Microsomal Prostaglandin E2 Synthase-1 (Mpges-1) Inhibitors, Madeline Stewart
Theses and Dissertations--Pharmacy
Lipid messenger prostaglandin E2 (PGE2) is a prostanoid that plays a key role in the generation of the inflammatory response. Currently available non-steroid anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX)-1 and/or COX-2, all with significant cardiovascular, cerebrovascular, and gastrointestinal risks that have limited their utilization. Microsomal PGE2 synthase 1 (mPGES-1), an inducible enzyme responsible for overproduction of PGE2, may be a more promising target for a new type of anti-inflammatory drug without the adverse effects associated with the COX-1/2 inhibition. There have been extensive efforts to design and discover inhibitors targeting mPGES-1. Unfortunately, within the previously …
Investigating The Use Of Mpges-1 Inhibitors For The Treatment Of Abdominal Aortic Aneurysms, Lauren M. Weaver
Investigating The Use Of Mpges-1 Inhibitors For The Treatment Of Abdominal Aortic Aneurysms, Lauren M. Weaver
Theses and Dissertations--Pharmacy
The cardiovascular field is still searching for a treatment for abdominal aortic aneurysms (AAA). This inflammatory disease is a deadly, permanent ballooning of the aortic artery. It often goes undiagnosed until a late stage where associated rupture has a high mortality rate. Surgery is the only option available to patients, but it is risky. There are currently no FDA-approved pharmacological treatments for AAA available. Historically, drugs that have been examined in interventional clinical trials for treatment of AAA were repurposed therapeutics. Novel treatments have been unable to reach the clinic, stalling out in pre-clinical studies. Exceedingly few murine studies have …
Effectiveness Of A Long-Acting Cocaine Hydrolase In Metabolizing Cocaine And Its Physiologically Active Metabolites, Linyue Shang
Effectiveness Of A Long-Acting Cocaine Hydrolase In Metabolizing Cocaine And Its Physiologically Active Metabolites, Linyue Shang
Theses and Dissertations--Pharmacy
Cocaine is a widely abused, hepatotoxic drug without an FDA-approved pharmacotherapy specific for cocaine addiction or overdose. Cocaine-induced toxicity in animals and humans is due to its multiple physiological effects on the central nervous system, cardiovascular system, etc. The toxicity of cocaine is highly complex, as its metabolites also contribute to the toxicity. Notably, the combination of cocaine and alcohol is common among drug users and can produce additional metabolites. Some of the metabolites are more toxic than cocaine itself. Hence, to develop an ideal therapeutic candidate, the candidate should not only account for cocaine but should also detoxify other …
Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana
Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana
Theses and Dissertations--Pharmacy
Cancer remains a real and present threat to global health. In the United States, according to cancer statistics, almost 40% of people will be diagnosed with cancer at some point in their lifetime. Conventional chemotherapy has become the mainstay for cancer treatment option. However, chemotherapeutic agents are plagued with problems such as poor aqueous solubility, chemical degradation, Bio instability, and off-site toxicity due to non-specificity. New drug modalities are needed to tackle the ever-growing burden on cancer. In recent times, the promise of nanotechnology has aided to develop drug delivery vehicles to facilitate the administration of potent chemotherapeutics. Nanoformulations such …
Striving For Appropriate Antibiotic Use: A Biomarker Initiative, And Outcomes Associated With Azithromycin Exposure, Amanda Gusovsky
Striving For Appropriate Antibiotic Use: A Biomarker Initiative, And Outcomes Associated With Azithromycin Exposure, Amanda Gusovsky
Theses and Dissertations--Pharmacy
The introduction of antibiotics into clinical practice is considered the greatest medical breakthrough of the 20thcentury. However, the use of antibiotics can contribute to the development of resistance. In the United States (U.S.), approximately 2.8 million people are infected with antibiotic-resistant bacteria each year, and more than 35,000 people die as a result. Moreover, some antibiotics are known to cause cardiac side effects including QT prolongation, hypotension, and ventricular arrythmias. The U.S. Centers for Disease Control and Prevention (CDC) defines appropriate antibiotic use as the effort to use “the right antibiotic, at the right dose, for the right …
Optimization Of Orally Bioavailable Inhibitors Of Defective In Cullin Neddylation 1 (Dcn-1), Leah Kovalic
Optimization Of Orally Bioavailable Inhibitors Of Defective In Cullin Neddylation 1 (Dcn-1), Leah Kovalic
Theses and Dissertations--Pharmacy
Ubiquitin (UB) and ubiquitin-like protein (UBL) pathways have emerged as important targets for oncology drug discovery based on the success of proteasome inhibitors (bortezomib or carfilzomib), E3 inhibitors, and the NEDD8 E1 inhibitor pevonedistat (MLN42924). Chemical inhibitors have also proven to be useful probes for identifying and dissecting multifactor UB and UBL regulatory networks. Toward this end, we have pursued approaches to target NEDD8 ligation to Cullins, through developing small molecule inhibitors of DCN1 (defective in Cullin Neddylation 1). DCN1 was discovered as a potentiating RBX1-dependent NEDD8-ligation, through recognizing the acetylated N-terminal methionine of the NEDD8 E2s UBE2M and UBE2F. …
Genetic And Pharmacogenetics Associations Of Cancer Disparities In Appalachia, Nan Lin
Genetic And Pharmacogenetics Associations Of Cancer Disparities In Appalachia, Nan Lin
Theses and Dissertations--Pharmacy
Individuals residing in Appalachian regions have significant health disparities, including higher cancer incidence and mortality rates. Previous studies have addressed the impact of socioeconomic status and environmental risk factors on Appalachia cancer disparities, while few studies have evaluated genetic risk factors.
Germline whole exome sequencing samples from 7,078 individuals with cancer (759 Appalachians) were evaluated. Demographics and relatedness were assessed using KING. Ethnicity was verified by principal component analysis using TRACE, which included 6,034 individuals (85%) of European genetic ancestry. After QC filtering, 5,980 individuals were analyzed. To assess the overall predisposition of hereditary disease, gene level frequency of likely …
Bioinformatic Analysis Of Proteomic And Genomic Data From Nsclc Tumors On Prognostic And Predictive Factors Of Immunotherapy Treatment, Mark Wuenschel
Bioinformatic Analysis Of Proteomic And Genomic Data From Nsclc Tumors On Prognostic And Predictive Factors Of Immunotherapy Treatment, Mark Wuenschel
Theses and Dissertations--Pharmacy
Recent lung cancer research has led to advancements in molecular immunology, resulting in development of small molecule inhibitors, or immune checkpoint inhibitors, that propagate an anti-tumor T cell response. Despite increased overall and progression-free survival with reduced adverse effects compared to traditional chemotherapy, treating advanced stage lung adenocarcinoma patients remains non-curative, and evidence of non-responders or tumor recurrence to immune checkpoint inhibitor therapy is growing. Also, compared to traditional chemotherapy, there is a lower percentage of patients who respond to small molecule inhibitors. In this analysis of proteomic and genomic data from The Cancer Proteome Atlas and Global Data Commons …
Population-Based Evaluation Of Treatment Patterns, Drug-Drug Interactions, And Cardiovascular Risk In Patients With Metastatic Castration-Resistant Prostate Cancer, Yue Cheng
Theses and Dissertations--Pharmacy
Prostate cancer has the highest increasing rate and new cases among all cancer in men in the United States and has a higher risk in elderly men. Metastatic castration-resistant prostate cancer (mCRPC) is the late stage of prostate cancer and associated with poor prognosis (median survival 13 months). Androgen deprivation therapy (ADT) use with novel hormone therapy or standard chemotherapy are recommended for mCRPC treatment. Although, the treatment options expanded significantly in recent years, new challenges are present because of the aging population, larger treatment spectrum and co-administrated medication use for other underlying medical conditions, especially for cardiovascular disease (CVD), …
Design And Synthesis Of Small Molecular Inhibitors Of Dcn1-Ube2m Interaction, Tucker J. Moseley
Design And Synthesis Of Small Molecular Inhibitors Of Dcn1-Ube2m Interaction, Tucker J. Moseley
Theses and Dissertations--Pharmacy
Over the last century, advancements in medicine have been made to improve cancer patients' outcomes. The discovery of new druggable targets is essential to achieving this goal. Defective in Cullin Neddylation 1 is a proven oncogenetic driver that may lead to better clinical outcomes when targeted. In efforts to further improve a series of novel small molecular inhibitors of the DCN1 and UBE2M protein-protein interaction, the Guy lab has designed and synthesized 26 new compounds. These compounds were designed to specifically target the UBE2M N-Acetyl sub-pocket on DCN1 that was not occupied by compounds previously described in the literature.
Investigation Of Folate-Poly(Glutamic Acid)/Polyethylenimine/Dna Complexes For In Vitro Gene Delivery, Caleb Akers
Investigation Of Folate-Poly(Glutamic Acid)/Polyethylenimine/Dna Complexes For In Vitro Gene Delivery, Caleb Akers
Theses and Dissertations--Pharmacy
Gene therapy is currently being studied as a treatment for a variety of indications, including cancer, infectious disease, and cardiovascular diseases, among others. While many of the early treatments in the field involved the use of viral delivery methods, various safety, ethical, and financial concerns limit the potential uses of this methodology. As such, more recent research has focused on developing non-viral delivery platforms to alleviate some of the issues inherent in viral delivery. Recently, the release of the COVID-19 vaccines from Pfizer and Moderna represents a promising use of non-viral delivery as both utilized a lipid-based delivery vector.
Despite …
An Epidemiological And Pharmacokinetic-Pharmacodynamic Investigation Into The Impact Of Carbapenem-Resistant Enterobacterales, Justin Clark
An Epidemiological And Pharmacokinetic-Pharmacodynamic Investigation Into The Impact Of Carbapenem-Resistant Enterobacterales, Justin Clark
Theses and Dissertations--Pharmacy
Background: According to the 2019 CDC Antibiotic Resistance Threats Report, more than 2.8 million antibiotic-resistant infections occur in the United States each year, leading to more than 35,000 deaths. Among the most urgent threats identified by the CDC are carbapenem-resistant Enterobacterales (CRE). Despite efforts to control the spread of these organisms, the number of estimated cases between 2012 and 2017 remained stable. In 2017, an estimated 13,100 hospitalized cases of CRE led to approximately 1,100 deaths and $130 million attributable healthcare costs. This dissertation seeks to address this issue from both a pharmacokinetic/pharmacodynamic and epidemiological perspective.
Methods: We evaluated the …
Developing A Biocatalytic Toolbox To Aid In Understanding Nucleoside Antibiotics, Jasmine Brianna Woods
Developing A Biocatalytic Toolbox To Aid In Understanding Nucleoside Antibiotics, Jasmine Brianna Woods
Theses and Dissertations--Pharmacy
Antibiotic resistance happens when bacteria develop the ability to survive medications that normally terminate them. Instead, these super germs are able to survive in the body and produce a community of antibiotic resistance germs which can cause human fatalities. It is important to discover and develop new compounds and molecules that will improve this clinical obstacle. This research focused on analyzing the biosynthesis that incorporates distinctive chemical characteristic of various nucleoside antibiotics, ß-hydroxy amino acids and α-methyl-amino acids. ß-hydroxy amino acids and α-methyl-amino acids are considered an important class of industrially useful compounds, particularly for pharmaceutical development, and are found …
New Tools For Biocatalysis: Studies On The Carminomycin 4-O-Methyltransferase Dnrk, Elnaz Jalali
New Tools For Biocatalysis: Studies On The Carminomycin 4-O-Methyltransferase Dnrk, Elnaz Jalali
Theses and Dissertations--Pharmacy
Methyltransferases (MTs) are ubiquitous enzymes commonly involved in biosynthesis and regulation. The fundamental goal of this thesis was to explore the permissive nature of methyltransferases and leverage this unique biocatalytic feature to develop a new platform for chemoselective intramolecular cyclization reactions. To realize this ambitious goal, this thesis project set out to probe the substrate specificity of multiple natural product tailoring enzymes (MTs and glycosyltransferases), identify model substrates common to multiple such tailoring enzymes and subsequently establish multi-enzyme tandem reactions that would set the stage for a subsequent chemoselective intramolecular cyclization reaction. Chapter One highlights current state of the art …
Studies Of Polypharmacy And Medication Therapy Management In Population-Based Cohorts, Ximena A. Oyarzun Gonzalez
Studies Of Polypharmacy And Medication Therapy Management In Population-Based Cohorts, Ximena A. Oyarzun Gonzalez
Theses and Dissertations--Epidemiology and Biostatistics
According to the United States Census Bureau, 16.8% of the population was 65 years and older in 2021, and it is expected that by 2060 that number will increase to about 30% (about 114 million people). Aging is associated with physiological changes in all systems of the body. These changes impact the pharmacodynamics and pharmacokinetic characteristics of drugs. Furthermore, older adults usually have several chronic conditions, which increases their exposure to medications. Increased vulnerability combined with increasing exposure puts elderly people at higher risk for drug interactions and adverse events.
Charlesworth et al. (2014) found that the prevalence of polypharmacy, …
Synthesis And Characterization Of D5-Barbarin For Use In Barbarin-Related Research, Sucheta Kudrimoti, Jacob Machin, Adedamola S. Arojojoye, Samuel G. Awuah, Rodney Eisenberg, Clara Fenger, George Maylin, Andreas F. Lehner, Thomas Tobin
Synthesis And Characterization Of D5-Barbarin For Use In Barbarin-Related Research, Sucheta Kudrimoti, Jacob Machin, Adedamola S. Arojojoye, Samuel G. Awuah, Rodney Eisenberg, Clara Fenger, George Maylin, Andreas F. Lehner, Thomas Tobin
Maxwell H. Gluck Equine Research Center Faculty Publications
Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d5-barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D5-barbarin synthesis commenced with production of d5-2-oxo-2-phenylacetaldehyde oxime (d5-oxime) from d5-acetophenone via butylnitrite in an ethoxide/ethanol solution. This d5-oxime was then reduced with lithium aluminum …
Cerium Dioxide, A Jekyll And Hyde Nanomaterial, Can Increase Basal And Decrease Elevated Inflammation And Oxidative Stress, Robert Yokel, Marsha L. Ensor, Hemendra J. Vekaria, Patrick G. Sullivan, David J. Feola, Arnold Stromberg, Michael T. Tseng, Douglas A. Harrison
Cerium Dioxide, A Jekyll And Hyde Nanomaterial, Can Increase Basal And Decrease Elevated Inflammation And Oxidative Stress, Robert Yokel, Marsha L. Ensor, Hemendra J. Vekaria, Patrick G. Sullivan, David J. Feola, Arnold Stromberg, Michael T. Tseng, Douglas A. Harrison
Pharmaceutical Sciences Faculty Publications
It was hypothesized that the catalyst nanoceria can increase oxidative
stress/inflammation from the basal state and reduce it from the elevated state .
Nanoceria are cleared by macrophages. To test the hypothesis, M0 (non-polarized),
M1- (classically activated, pro-inflammatory), and M2-like (alternatively activated,
regulatory phenotype) RAW 264.7 macrophages were nanoceria exposed. Responses
were quantified by arginase activity, IL-1ß level, cell oxygen consumption rate (OCR),
the glycolysis stress test (GST), morphology determined by light microscopy,
macrophage phenotype marker expression and morphology using a novel three
dimensional immunohistochemical method, and RT-qPCR. Nanoceria blocked
arginase and IL-1ß effects, increased M0 cell OCR and GST …
Evaluation Of Anemia In Communities Served By Shoulder To Shoulder Global: A Cross-Sectional Study In Santo Domingo, Ecuador, Kevin J. Mercer, Daniela Claudia Moga, Steven Fleming, Cristian Carrión, Melody Ryan
Evaluation Of Anemia In Communities Served By Shoulder To Shoulder Global: A Cross-Sectional Study In Santo Domingo, Ecuador, Kevin J. Mercer, Daniela Claudia Moga, Steven Fleming, Cristian Carrión, Melody Ryan
Pharmacy Practice and Science Faculty Publications
Background Shoulder to Shoulder Global (STSG) recognizes anemia as a cause of morbidity among patients in Santo Domingo, Ecuador. Little research has been done to assess targetable anemia risk factors to serve as a foundation for future pharmacotherapeutic interventions. This study sought to characterize anemia in this population to lay the foundation for future preventive intervention.
Methods Cross-sectional data obtained from existing clinic records from 2010 to 2016 included hemoglobin/hematocrit, age, sex, pregnancy status, and respective community. Chi-square compared means to examine risk factors associated with anemia. Logistic regression and odds ratios (OR) were used to estimate risk factors associated …
Preliminary Research On A Covid-19 Test Strategy To Guide Quarantine Interval In University Students, Jill M. Kolesar, Tyler Gayheart, Lance Poston, Eric Monday, Derek Forster, Elizabeth Belcher, Rani Jaiswal, J. Kirsten Turner, Donna K. Arnett, Eric B. Durbin, Joseph Monroe, Frank Romanelli, Susanne M. Arnold, C. Darrell Jennings, Heidi Weiss, Robert Dipaola
Preliminary Research On A Covid-19 Test Strategy To Guide Quarantine Interval In University Students, Jill M. Kolesar, Tyler Gayheart, Lance Poston, Eric Monday, Derek Forster, Elizabeth Belcher, Rani Jaiswal, J. Kirsten Turner, Donna K. Arnett, Eric B. Durbin, Joseph Monroe, Frank Romanelli, Susanne M. Arnold, C. Darrell Jennings, Heidi Weiss, Robert Dipaola
Pharmacy Practice and Science Faculty Publications
Following COVID-19 exposure, the Centers for Disease Control (CDC) recommends a 10–14-day quarantine for asymptomatic individuals and more recently a 7-day quarantine with a negative PCR test. A university-based prospective cohort study to determine if early polymerase chain reaction (PCR) negativity predicts day 14 negativity was performed. A total of 741 asymptomatic students in quarantine was screened and 101 enrolled. Nasopharyngeal swabs were tested on days 3 or 4, 5, 7, 10, and 14, and the proportion of concordant negative results for each day versus day 14 with a two-sided 95% exact binomial confidence interval was determined. Rates of concordant …
Age Adjusted Comorbidity Risk Index Does Not Predict Outcomes In An Autologous Hematopoietic Stem Cell Transplant Population, Dylan Barth, Michael Singleton, Gregory Monohan, Brian Mcclune, Val Adams
Age Adjusted Comorbidity Risk Index Does Not Predict Outcomes In An Autologous Hematopoietic Stem Cell Transplant Population, Dylan Barth, Michael Singleton, Gregory Monohan, Brian Mcclune, Val Adams
Pharmacy Practice and Science Faculty Publications
The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to prognosticate morbidity and mortality of patients undergoing allogeneic hematopoietic stem cell transplantation. Recently, the HCT-CI was updated to include an age component (HCT-CI-age). Although other studies have validated this tool in allogeneic stem cell transplant recipients, it has never been studied in an autologous transplant patient population. We retrospectively reviewed 181 patients who underwent their first autologous hematopoietic stem cell transplant. We aimed (1) to assess whether an HCT-CI score of 3 or greater is associated with greater mean transplant hospital days, greater total hospital days, …