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Pharmacy and Pharmaceutical Sciences

University of Kentucky

2020

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Full-Text Articles in Medicine and Health Sciences

Recovery Of Hippocampal-Dependent Learning Despite Blunting Reactive Adult Neurogenesis After Alcohol Dependence, Chelsea G. Nickell, K. Ryan Thompson, James R. Pauly, Kimberly Nixon Dec 2020

Recovery Of Hippocampal-Dependent Learning Despite Blunting Reactive Adult Neurogenesis After Alcohol Dependence, Chelsea G. Nickell, K. Ryan Thompson, James R. Pauly, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Background:

The excessive alcohol drinking that occurs in alcohol use disorder (AUD) causes neurodegeneration in regions such as the hippocampus, though recovery may occur after a period of abstinence. Mechanisms of recovery are not clear, though reactive neurogenesis has been observed in the hippocampal dentate gyrus following alcohol dependence and correlates to recovery of granule cell number.

Objective:

We investigated the role of neurons born during reactive neurogenesis in the recovery of hippocampal learning behavior after 4-day binge alcohol exposure, a model of an AUD. We hypothesized that reducing reactive neurogenesis would impair functional recovery.

Methods:

Adult male rats were …


Epigenetic Regulation Of Wnt Signaling By Carboxamide-Substituted Benzhydryl Amines That Function As Histone Demethylase Inhibitors, Wen Zhang, Vitaliy M. Sviripa, Yanqi Xie, Tianxin Yu, Meghan G. Haney, Jessica S. Blackburn, Charles A. Adeniran, Chang-Guo Zhan, David S. Watt, Chunming Liu Dec 2020

Epigenetic Regulation Of Wnt Signaling By Carboxamide-Substituted Benzhydryl Amines That Function As Histone Demethylase Inhibitors, Wen Zhang, Vitaliy M. Sviripa, Yanqi Xie, Tianxin Yu, Meghan G. Haney, Jessica S. Blackburn, Charles A. Adeniran, Chang-Guo Zhan, David S. Watt, Chunming Liu

Molecular and Cellular Biochemistry Faculty Publications

Aberrant activation of Wnt signaling triggered by mutations in either Adenomatous Polyposis Coli (APC) or CTNNB1 (β-catenin) is a hallmark of colorectal cancers (CRC). As part of a program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing either aryl or heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors of the Wnt pathway. A biotinylated variant of N-((5-chloro-8-hydroxyquinolin-7-yl) (4-(diethylamino)phenyl)-methyl)butyramide (CBA-1) identified KDM3A as a binding partner. KDM3A is a Jumonji (JmjC) domain-containing demethylase that is significantly upregulated in CRC. KDM3A regulates the demethylation of histone H3's lysine …


Cd47 Differentially Regulates White And Brown Fat Function, Heather Norman-Burgdolf, Dong Li, Patrick G. Sullivan, Shuxia Wang Dec 2020

Cd47 Differentially Regulates White And Brown Fat Function, Heather Norman-Burgdolf, Dong Li, Patrick G. Sullivan, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Mechanisms that enhance energy expenditure are attractive therapeutic targets for obesity. Previously we have demonstrated that mice lacking cd47 are leaner, exhibit increased energy expenditure, and are protected against diet-induced obesity. In this study, we further defined the physiological role of cd47 deficiency in regulating mitochondrial function and energy expenditure in both white and brown adipose tissue. We observed that cd47 deficient mice (under normal chow diet) had comparable amount of white fat mass but reduced white adipocyte size as compared to wild-type mice. Subsequent ex vivo and in vitro studies suggest enhanced lipolysis, and not impaired lipogenesis or energy …


Synthesis, Characterization, And Antiproliferative Activity Of Novel Chiral [Quinoxp*Aucl2]+ Complexes, Adedamola S. Arojojoye, R. Tyler Mertens, Samuel Ofori, Sean R. Parkin, Samuel G. Awuah Dec 2020

Synthesis, Characterization, And Antiproliferative Activity Of Novel Chiral [Quinoxp*Aucl2]+ Complexes, Adedamola S. Arojojoye, R. Tyler Mertens, Samuel Ofori, Sean R. Parkin, Samuel G. Awuah

Chemistry Faculty Publications

Herein is reported the synthesis of two Au(III) complexes bearing the (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (R,R-QuinoxP*) or (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (S,S-QuinoxP*) ligands. By reacting two stoichiometric equivalents of HAuCl4.3H2O to one equivalent of the corresponding QuinoxP* ligand, (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (1) and (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) were formed, respectively, in moderate yields. The structure of (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) was further confirmed by X-ray crystallography. The antiproliferative activities of the two compounds were evaluated in a panel of cell lines and exhibited promising results comparable to auranofin and cisplatin with …


Clinically Relevant Interactions Between Atypical Antipsychotics And Anti-Infective Agents, Edoardo Spina, Maria Antonietta Barbieri, Giuseppe Cicala, Jose De Leon Dec 2020

Clinically Relevant Interactions Between Atypical Antipsychotics And Anti-Infective Agents, Edoardo Spina, Maria Antonietta Barbieri, Giuseppe Cicala, Jose De Leon

Psychiatry Faculty Publications

This is a comprehensive review of the literature on drug interactions (DIs) between atypical antipsychotics and anti-infective agents that focuses on those DIs with the potential to be clinically relevant and classifies them as pharmacokinetic (PK) or pharmacodynamic (PD) DIs. PubMed searches were conducted for each of the atypical antipsychotics and most commonly used anti-infective agents (13 atypical antipsychotics by 61 anti-infective agents/classes leading to 793 individual searches). Additional relevant articles were obtained from citations and from prior review articles written by the authors. Based on prior DI articles and our current understanding of PK and PD mechanism, we developed …


Treatment Of Headache In Aneurysmal Subarachnoid Hemorrhage: Multimodal Approach, Garrett B. Hile, Aaron M. Cook Dec 2020

Treatment Of Headache In Aneurysmal Subarachnoid Hemorrhage: Multimodal Approach, Garrett B. Hile, Aaron M. Cook

Pharmacy Practice and Science Faculty Publications

Sudden severe headache is a cardinal symptom and the most common complaint amongst patients presenting with aneurysmal subarachnoid hemorrhage. The multifactorial etiology of these headaches makes pharmacotherapy problematic. Current aneurysmal subarachnoid hemorrhage guidelines have limited or no recommendations for headache treatment. Our institution utilizes a multimodal pharmacotherapy protocol in the management of aneurysmal subarachnoid hemorrhage headache. The purpose of this study was to evaluate the efficacy of the current aneurysmal subarachnoid hemorrhage headache treatment approach at our institution. This was a retrospective cohort study of patients presenting with aneurysmal subarachnoid hemorrhage. A multimodal aneurysmal subarachnoid hemorrhage headache treatment protocol was …


Development, Implementation And Outcomes Of A Quality Assurance System For The Provision Of Continuous Renal Replacement Therapy In The Intensive Care Unit, Eloy F. Ruiz, Victor M. Ortiz-Soriano, Monica Talbott, Bryan A. Klein, Melissa L. Thompson Bastin, Kirby P. Mayer, Emily B. Price, Robert Dorfman, Brandi N. Adams, Lisa J. Fryman, Javier A. Neyra, The University Of Kentucky Crrt Quality Assurance Group Nov 2020

Development, Implementation And Outcomes Of A Quality Assurance System For The Provision Of Continuous Renal Replacement Therapy In The Intensive Care Unit, Eloy F. Ruiz, Victor M. Ortiz-Soriano, Monica Talbott, Bryan A. Klein, Melissa L. Thompson Bastin, Kirby P. Mayer, Emily B. Price, Robert Dorfman, Brandi N. Adams, Lisa J. Fryman, Javier A. Neyra, The University Of Kentucky Crrt Quality Assurance Group

Physical Therapy Faculty Publications

Critically ill patients with requirement of continuous renal replacement therapy (CRRT) represent a growing intensive care unit (ICU) population. Optimal CRRT delivery demands continuous communication between stakeholders, iterative adjustment of therapy, and quality assurance systems. This Quality Improvement (QI) study reports the development, implementation and outcomes of a quality assurance system to support the provision of CRRT in the ICU. This study was carried out at the University of Kentucky Medical Center between September 2016 and June 2019. We implemented a quality assurance system using a step-wise approach based on the (a) assembly of a multidisciplinary team, (b) standardization of …


Rna Nanoparticles And Method Of Use Thereof, Peixuan Guo, Hui Li, Wei Luo Nov 2020

Rna Nanoparticles And Method Of Use Thereof, Peixuan Guo, Hui Li, Wei Luo

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to an artificial RNA nanostructure and method of use thereof. In particular, the presently-disclosed subject matter relates to RNA nanoparticles and RNA dendrimers, and methods of disease diagnosis and treatments using the RNA nanostructure and RNA dendrimers.


Acute Skeletal Muscle Wasting And Dysfunction Predict Physical Disability At Hospital Discharge In Patients With Critical Illness, Kirby P. Mayer, Melissa L. Thompson Bastin, Ashley A. Montgomery-Yates, Amy M. Pastva, Esther E. Dupont-Versteegden, Selina M. Parry, Peter E. Morris Nov 2020

Acute Skeletal Muscle Wasting And Dysfunction Predict Physical Disability At Hospital Discharge In Patients With Critical Illness, Kirby P. Mayer, Melissa L. Thompson Bastin, Ashley A. Montgomery-Yates, Amy M. Pastva, Esther E. Dupont-Versteegden, Selina M. Parry, Peter E. Morris

Physical Therapy Faculty Publications

BACKGROUND: Patients surviving critical illness develop muscle weakness and impairments in physical function; however, the relationship between early skeletal muscle alterations and physical function at hospital discharge remains unclear. The primary purpose of this study was to determine whether changes in muscle size, strength and power assessed in the intensive care unit (ICU) predict physical function at hospital discharge.

METHODS: Study design is a single-center, prospective, observational study in patients admitted to the medicine or cardiothoracic ICU with diagnosis of sepsis or acute respiratory failure. Rectus femoris (RF) and tibialis anterior (TA) muscle ultrasound images were obtained day one of …


Risk Factors For Delayed Viral Suppression On First-Line Antiretroviral Therapy Among Persons Living With Hiv In Haiti, 2013-2017, Shannan N. Rich, Robert L. Cook, Lusine Yaghjyan, Kesner Francois, Nancy Puttkammer, Ermane Robin, Jungjun Bae, Nadjy Joseph, Luisa Pessoa-Brandão, Chris Delcher Oct 2020

Risk Factors For Delayed Viral Suppression On First-Line Antiretroviral Therapy Among Persons Living With Hiv In Haiti, 2013-2017, Shannan N. Rich, Robert L. Cook, Lusine Yaghjyan, Kesner Francois, Nancy Puttkammer, Ermane Robin, Jungjun Bae, Nadjy Joseph, Luisa Pessoa-Brandão, Chris Delcher

Institute for Pharmaceutical Outcomes and Policy Faculty Publications

Studies of viral suppression on first-line antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLHIV) in Haiti are limited, particularly among PLHIV outside of the Ouest department, where the capital Port-au-Prince is located. This study described the prevalence and risk factors for delayed viral suppression among PLHIV in all geographic departments of Haiti between 2013 and 2017. Individuals who received viral load testing 3 to 12 months after ART initiation were included. Data on demographics and clinical care were obtained from the Haitian Active Longitudinal Tracking of HIV database. Multivariable logistic regression was performed to predict delayed viral …


Liposomal Delivery Of Azithromycin Enhances Its Immunotherapeutic Efficacy And Reduces Toxicity In Myocardial Infarction, Ahmed Al-Darraji, Renée R. Donahue, Himi Tripathi, Hsuan Peng, Bryana M. Levitan, Lakshman Chelvarajan, Dalia Haydar, Erhe Gao, David Henson, John C. Gensel, David J. Feola, Vincent J. Venditto, Ahmed K. Abdel-Latif Oct 2020

Liposomal Delivery Of Azithromycin Enhances Its Immunotherapeutic Efficacy And Reduces Toxicity In Myocardial Infarction, Ahmed Al-Darraji, Renée R. Donahue, Himi Tripathi, Hsuan Peng, Bryana M. Levitan, Lakshman Chelvarajan, Dalia Haydar, Erhe Gao, David Henson, John C. Gensel, David J. Feola, Vincent J. Venditto, Ahmed K. Abdel-Latif

Gill Heart & Vascular Institute Faculty Publications

A growing body of evidence shows that altering the inflammatory response by alternative macrophage polarization is protective against complications related to acute myocardial infarction (MI). We have previously shown that oral azithromycin (AZM), initiated prior to MI, reduces inflammation and its negative sequelae on the myocardium. Here, we investigated the immunomodulatory role of a liposomal AZM formulation (L-AZM) in a clinically relevant model to enhance its therapeutic potency and avoid off-target effects. L-AZM (40 or 10 mg/kg, IV) was administered immediately post-MI and compared to free AZM (F-AZM). L-AZM reduced cardiac toxicity and associated mortality by 50% in mice. We …


Development And Implementation Of An Influenza Point-Of-Care Testing Service In A Chain Community Pharmacy Setting, Rachel Hardin, Pheli Roberts, Brooke Hudspeth, Angela Tracy, Lauren Baldwin, Michael Raque, Clark D. Kebodeaux Oct 2020

Development And Implementation Of An Influenza Point-Of-Care Testing Service In A Chain Community Pharmacy Setting, Rachel Hardin, Pheli Roberts, Brooke Hudspeth, Angela Tracy, Lauren Baldwin, Michael Raque, Clark D. Kebodeaux

Pharmacy Practice and Science Faculty Publications

Point-of-care testing is becoming increasingly commonplace in community pharmacy settings. These tests are often used in the management of chronic disease, such as blood sugar, hemoglobin A1c and lipid levels, but can also be used for acute conditions such as influenza infection and group A streptococcus pharyngitis. When used for these acute infections, point-of-care tests can allow for pharmacist-initiated treatment. In this study, an influenza point-of-care testing service was developed and implemented in a chain community pharmacy setting and a retrospective review was conducted to assess the service. Of patients tested, 29% tested positive for influenza A and/or B; 92% …


The Acute Effects Of The Atypical Dissociative Hallucinogen Salvinorin A On Functional Connectivity In The Human Brain, Manoj K. Doss, Darrick G. May, Matthew W. Johnson, John M. Clifton, Sidnee L. Hedrick, Thomas E. Prisinzano, Roland R. Griffiths, Frederick S. Barrett Oct 2020

The Acute Effects Of The Atypical Dissociative Hallucinogen Salvinorin A On Functional Connectivity In The Human Brain, Manoj K. Doss, Darrick G. May, Matthew W. Johnson, John M. Clifton, Sidnee L. Hedrick, Thomas E. Prisinzano, Roland R. Griffiths, Frederick S. Barrett

Pharmaceutical Sciences Faculty Publications

Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the …


A Thorough Analysis And Categorization Of Bacterial Interrupted Adenylation Domains, Including Previously Unidentified Families, Taylor A. Lundy, Shogo Mori, Sylvie Garneau-Tsodikova Oct 2020

A Thorough Analysis And Categorization Of Bacterial Interrupted Adenylation Domains, Including Previously Unidentified Families, Taylor A. Lundy, Shogo Mori, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

Interrupted adenylation (A) domains are key to the immense structural diversity seen in the nonribosomal peptide (NRP) class of natural products (NPs). Interrupted A domains are A domains that contain within them the catalytic portion of another domain, most commonly a methylation (M) domain. It has been well documented that methylation events occur with extreme specificity on either the backbone (N-) or side chain (O- or S-) of the amino acid (or amino acid-like) building blocks of NRPs. Here, through taxonomic and phylogenetic analyses as well as multiple sequence alignments, we evaluated the similarities and …


Haiti's Hiv Surveillance System: Past, Present, And Future, Chris Delcher, Ermane G. Robin, Daniella Myriam Pierre Oct 2020

Haiti's Hiv Surveillance System: Past, Present, And Future, Chris Delcher, Ermane G. Robin, Daniella Myriam Pierre

Pharmacy Practice and Science Faculty Publications

No abstract provided.


Rna Nanoparticle For Treatment Of Gastric Cancer, Peixuan Guo, Daxiang Cui, Dan Shu, Yi Shu, Chunlei Zhang Sep 2020

Rna Nanoparticle For Treatment Of Gastric Cancer, Peixuan Guo, Daxiang Cui, Dan Shu, Yi Shu, Chunlei Zhang

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to RNA-based composition and method to treat gastric cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a gastric cancer targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat gastric cancer in a subject having or at risk of having gastric cancer.


Cocaine Hydrolase-Fc Fusion Proteins For Cocaine And Methods For Utilizing The Same, Chang-Guo Zhan, Fang Zheng, Hsin-Hsiung Tai, Xiabin Chen, Liu Xue, Shurong Hou Sep 2020

Cocaine Hydrolase-Fc Fusion Proteins For Cocaine And Methods For Utilizing The Same, Chang-Guo Zhan, Fang Zheng, Hsin-Hsiung Tai, Xiabin Chen, Liu Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter includes isolated polypeptides that comprise a butyrylcholinestrase (BChE) polypeptide and a second polypeptide. The BChE polypeptide as well as the second polypeptide can be variants and/or fragments thereof. The presently-disclosed subject matter also includes a pharmaceutical composition that comprises the present isolated polypeptide and a suitable pharmaceutical carrier. Further still, methods are provided for treating cocaine-induced conditions, and comprise administering the isolated polypeptide and/or pharmaceutical compositions thereof to an individual.


Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu Sep 2020

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …


Efficient Cocaine Degradation By Cocaine Esterase-Loaded Red Blood Cells, Luigia Rossi, Francesca Pierigè, Marco Agostini, Noemi Bigini, Veronica Termopoli, Yingting Cai, Fang Zheng, Chang-Guo Zhan, Donald W. Landry, Mauro Magnani Sep 2020

Efficient Cocaine Degradation By Cocaine Esterase-Loaded Red Blood Cells, Luigia Rossi, Francesca Pierigè, Marco Agostini, Noemi Bigini, Veronica Termopoli, Yingting Cai, Fang Zheng, Chang-Guo Zhan, Donald W. Landry, Mauro Magnani

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Recombinant bacterial cocaine esterase (CocE) represents a potential protein therapeutic for cocaine use disorder treatment. Unfortunately, the native enzyme was highly unstable and the corresponding mutagenized derivatives, RBP-8000 and E196-301, although improving in vitro thermo-stability and in vivo half-life, were a partial solution to the problem. For cocaine use disorder treatment, an efficient cocaine-metabolizing enzyme with a longer residence time in circulation would be needed. We investigated in vitro the possibility of developing red blood cells (RBCs) loaded with RBP-8000 and E196-301 as a biocompatible system to metabolize cocaine for a longer period of time. RBP 8000 stability within human …


Suspected Malignant Hyperthermia And The Application Of A Multidisciplinary Response, Laura Ebbitt, Eric Johnson, Brooke Herndon, Kristina Karrick, Aric Johnson Sep 2020

Suspected Malignant Hyperthermia And The Application Of A Multidisciplinary Response, Laura Ebbitt, Eric Johnson, Brooke Herndon, Kristina Karrick, Aric Johnson

Pharmacy Practice and Science Faculty Publications

Purpose: Malignant hyperthermia (MH) is a critical and potentially life-threatening emergency associated with inhaled anesthetic and depolarizing neuromuscular blocker administration. This is a single center’s response to MH. Summary: When signs of MH are observed, a page for “anesthesia STAT-MH crisis” is called, triggering a multidisciplinary response, including the deployment of a Malignant Hyperthermia Cart. The MH cart and the delegation of duties allows nurses, physicians and pharmacists to quickly understand their role in the stabilization, transition and recovery of a suspected MH patient. Conclusion: This case highlights the importance of multi-disciplinary involvement in these rare, but potentially fatal, cases.


Everything Is Science: A Free City-Wide Science Festival, Jarrod W. Creameans, Michelle G. Pitts, Olivia White, Kellen M. Greenwell, Kristie Colón, Sylvie Garneau-Tsodikova, Vincent J. Venditto Sep 2020

Everything Is Science: A Free City-Wide Science Festival, Jarrod W. Creameans, Michelle G. Pitts, Olivia White, Kellen M. Greenwell, Kristie Colón, Sylvie Garneau-Tsodikova, Vincent J. Venditto

Pharmaceutical Sciences Faculty Publications

A week-long, city-wide science festival called Everything is Science (EiS) was developed to educate the community in an informal manner. The festival serves as a platform for presenters from diverse professions to give engaging talks (without PowerPoint slides) to the public, free of charge, in restaurants and bars around town. Over 350 people attended the events over 5 days with 33 presenters. Surveys completed by attendees and session coordinators indicate strong support for this festival. Altogether, the EiS festival serves as a no-cost method to engage with the community and improve science literacy with potential for adoption in other cities.


Afatinib For The Treatment Of Egfr Mutation-Positive Nsclc: A Review Of Clinical Findings, R. Donald Harvey, Val R. Adams, Tyler Beardslee, Patrick Medina Sep 2020

Afatinib For The Treatment Of Egfr Mutation-Positive Nsclc: A Review Of Clinical Findings, R. Donald Harvey, Val R. Adams, Tyler Beardslee, Patrick Medina

Pharmacy Practice and Science Faculty Publications

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors represent the standard of care in patients with EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC). The availability of several EGFR tyrosine kinase inhibitors approved for use in the first-line or later settings in NSCLC warrants an in-depth understanding of the pharmacological properties of, and clinical data supporting, these agents. The second-generation, irreversible ErbB-family blocker, afatinib, has been extensively studied in the context of EGFRm+ NSCLC. Results from the LUX-Lung 3 and 6 studies showed that afatinib was more active and better tolerated than chemotherapy in patients with tumors …


Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel Sep 2020

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …


Methods For Using Nhanes For Exposure Estimates, Heather R. Campbell, Robert A. Lodder Sep 2020

Methods For Using Nhanes For Exposure Estimates, Heather R. Campbell, Robert A. Lodder

Pharmaceutical Sciences Faculty Publications

The National Health and Nutrition Examination Survey (NHANES) is a scheme of studies with the objective of measuring the health and nutritional status of adults and children in the United States. The survey is unique in that it has a clinical component (NCT00005154), and combines interviews and physical examinations into its data sets. NHANES is an important program of the National Center for Health Statistics (NCHS). NCHS is a unit of the Centers for Disease Control and Prevention (CDC) and has the responsibility for producing vital and health statistics for the United States. Data from the NHANES studies …


Hypusination Of Eif5a Regulates Cytoplasmic Tdp-43 Aggregation And Accumulation In A Stress-Induced Cellular Model, Shayna Smeltzer, Zainuddin Quadri, Abraian Miller, Frank Zamudio, Jordan Hunter, Nicholas J.F. Stewart, Sheba Saji, Daniel C. Lee, Dale Chaput, Maj-Linda B. Selenica Aug 2020

Hypusination Of Eif5a Regulates Cytoplasmic Tdp-43 Aggregation And Accumulation In A Stress-Induced Cellular Model, Shayna Smeltzer, Zainuddin Quadri, Abraian Miller, Frank Zamudio, Jordan Hunter, Nicholas J.F. Stewart, Sheba Saji, Daniel C. Lee, Dale Chaput, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

TAR DNA-binding protein 43 (TDP-43) is a nuclear RNA/DNA binding protein involved in mRNA metabolism. Aberrant mislocalization to the cytoplasm and formation of phosphorylated/aggregated TDP-43 inclusions remains the hallmark pathology in a spectrum of neurodegenerative diseases, including frontotemporal disorders and Alzheimer's disease. Eukaryotic Translation Initiation Factor 5A undergoes a unique post-translation modification of lysine to hypusine (K50), which determines eIF5A binding partners. We used a sodium arsenite-induced cellular stress model to investigate the role of hypusinated eIF5A (eIF5AHypK50) in governing TDP-43 cytoplasmic mislocalization and accumulation in stress granule. Our proteomics and functional data provide evidence that eIF5A interacts …


Egfr Testing And Erlotinib Use In Non-Small Cell Lung Cancer Patients In Kentucky, Kara L. Larson, Bin Huang, Quan Chen, Thomas C. Tucker, Marissa Schuh, Susanne M. Arnold, Jill M. Kolesar Aug 2020

Egfr Testing And Erlotinib Use In Non-Small Cell Lung Cancer Patients In Kentucky, Kara L. Larson, Bin Huang, Quan Chen, Thomas C. Tucker, Marissa Schuh, Susanne M. Arnold, Jill M. Kolesar

Markey Cancer Center Faculty Publications

This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from …


Method And System For Terpene Production Platforms In Yeast, Joseph Chappell, Xun Zhuang, Shuiqin Wu Aug 2020

Method And System For Terpene Production Platforms In Yeast, Joseph Chappell, Xun Zhuang, Shuiqin Wu

Pharmaceutical Sciences Faculty Patents

A method is provided for producing modified mutant yeast and the resulting yeast that can be used as a platform for terpene production. The method includes chemical mutagenesis to effect ergosterol dependent growth in yeast. Subsequently, these yeast are subjected to an erg9 knockout mutation to thereby produce ergosterol dependent growth/ erg9 knockout mutation yeast cell lines. The resulting yeast are well suited for use in the production of terpenes.


Expanding Pharmacotherapy Data Collection, Analysis, And Implementation In Eras® Programs—The Methodology Of An Exploratory Feasibility Study, Eric Johnson, Richard Parrish Ii, Gregg Nelson, Kevin Elias, Brian Kramer, Marian Gaviola Aug 2020

Expanding Pharmacotherapy Data Collection, Analysis, And Implementation In Eras® Programs—The Methodology Of An Exploratory Feasibility Study, Eric Johnson, Richard Parrish Ii, Gregg Nelson, Kevin Elias, Brian Kramer, Marian Gaviola

Pharmacy Practice and Science Faculty Publications

Surgical organizations dedicated to the improvement of patient outcomes have led to a worldwide paradigm shift in perioperative patient care. Since 2012, the Enhanced Recovery After Surgery (ERAS®) Society has published guidelines pertaining to perioperative care in numerous disciplines including elective colorectal and gynecologic/oncology surgery patients. The ERAS® and ERAS-USA® Societies use standardized methodology for collecting and assessing various surgical parameters in real-time during the operative process. These multi-disciplinary groups have constructed a bundled framework of perioperative care that entails 22 specific components of clinical interventions, which are logged in a central database, allowing a system …


Nanoceria Distribution And Effects Are Mouse-Strain Dependent, Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham Aug 2020

Nanoceria Distribution And Effects Are Mouse-Strain Dependent, Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO2 nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more …


Application Of Enzymes In Regioselective And Stereoselective Organic Reactions, Ruipu Mu, Zhaoshuai Wang, Max C. Wamsley, Colbee N. Duke, Payton H. Lii, Sarah E. Epley, London C. Todd, Patty J. Roberts Jul 2020

Application Of Enzymes In Regioselective And Stereoselective Organic Reactions, Ruipu Mu, Zhaoshuai Wang, Max C. Wamsley, Colbee N. Duke, Payton H. Lii, Sarah E. Epley, London C. Todd, Patty J. Roberts

Pharmaceutical Sciences Faculty Publications

Nowadays, biocatalysts have received much more attention in chemistry regarding their potential to enable high efficiency, high yield, and eco-friendly processes for a myriad of applications. Nature’s vast repository of catalysts has inspired synthetic chemists. Furthermore, the revolutionary technologies in bioengineering have provided the fast discovery and evolution of enzymes that empower chemical synthesis. This article attempts to deliver a comprehensive overview of the last two decades of investigation into enzymatic reactions and highlights the effective performance progress of bio-enzymes exploited in organic synthesis. Based on the types of enzymatic reactions and enzyme commission (E.C.) numbers, the enzymes discussed in …