Pharmacology Commons^™

Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern

The University of Louisville Journal of Respiratory Infections

Background: Response to the COVID-19 pandemic has required innovative approaches to vaccination, including methods to rapidly and safely immunize communities. A major challenge to such a response involved access to untapped healthcare worker resources. The Louisville, Kentucky, response involved the use of a large volunteer workforce to supplement local public health employees in planning and implementing a large-scale drive-through vaccination event. The objective of this manuscript was to outline processes involved in training a mass immunization workforce and implementating a large-scale COVID-19 community vaccination.

Approach: Competency-based and standardized training was provided for every volunteer before working their shift. Volunteers worked …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Breadth Of Vaccinated Cancer Patient Humoral Response To Sars-Cov-2 Spike Protein And Rbd Variants, Julia Corman, Joey Breckenridge Jr., Adrienne M. Bushau-Sprinkle, Krystal T. Hamorsky, Joshua L. Fuqua

Posters-at-the-Capitol

SARS-CoV-2, the virus responsible for the COVID-19 of which several variants have emerged, such as the B.1.351 SARS-CoV-2 variant. The Receptor Binding Domain (RBD), located within the Spike protein is an immunogenic epitope for potent neutralizing antibodies. Current mRNA vaccines encode for the Spike protein, allowing the body to build antigen-specific antibodies. Assays measuring protective antibodies are essential to manage the COVID-19 pandemic and can be used as a platform for variant screening. RBD-foldon 2.2 is a novel antigen produced by fusing RBD with the trimerization domain Fibritin from Bacteriophage T4. Its amino acid sequence is based on the original …

Wastewater-Based Estimation Of Substances Discharged At The Rest Areas Along The State Highways In Kentucky, Katherine E. Gray, Eugene Shin, Tyler Whitt, Andrew Windhorst, Houston Hampton, Chris Delcher, Bikram Subedi

Posters-at-the-Capitol

The availability of licit and illicit stimulants and its adverse consequences on public health has emerged as a major drug threat to communities in the United States. Despite several drug-involved traffic incidents along the interstate highways, this report represents the first comprehensive and quantitative report of drugs discharged at the rest areas along the interstate highways. In this National Institute of Justice-funded study, the amount of several discharged drugs focusing on stimulants but also including opioids and prescription antipsychotics are being measured in raw wastewater collected from five rest areas and a truck servicing facility using a state-of-the-art mass …

Development Of A Ph-Sensitive Probe For In Vivo Cerenkov Imaging Of The Tumor Microenvironment, Andrea Estefania Rodríguez-Ríos

Publicly Accessible Penn Dissertations

Acidity in the tumor microenvironment (TME) is related to invasion, metastasis, and chemotherapeutic resistance, all of which are contributors to poor prognoses in cancer patients. In this thesis, we propose the application of Cerenkov radiation as a tool for imaging pH in vivo through the measurement of Selective Bandwidth Quenching (SBQ) and Cerenkov Radiation Energy Transfer (CRET) in triple negative human breast cancer models MDA-MB-231 and 4175-Luc+. To test the hypothesis that SBQ and CRET signals could provide measurements of TME pH in vivo, a Cerenkov-active molecule, NFbD, was conjugated and chelated with 68Ga. Cerenkov imaging was performed with NFbD-Ga …

Genetic Ablation Of Kir2.1 Channels And Its Effects On Micturition In Conscious Mice, Ryan Thomas Shields

Graduate College Dissertations and Theses

Detrusor muscle overactivity in the bladder wall is the hallmark symptom of overactive bladder syndrome and the principal target of therapy that seeks to reduce incontinence and urinary urgency. However, these interventions typically fail to alleviate long-term detrusor overactivity and simply mask the underlying pathology while also potentially introducing undesirable side effects that disrupt quality of life. One alternative mechanism driving of overactive bladder is attributed to ischemia within the bladder, which is subject to enormous swings in pressure and tension on its vasculature restricting blood flow. This observation, coupled with the fact that healthy vascular tissue within the bladder …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Modulating Ketamine’S Locomotor Activating And Reinforcing Effects Through Drug Combinations, Tegshjargal Baasansukh

Theses and Dissertations

Major Depressive Disorder (MDD) affects approximately 280 million people worldwide. The standard of care for pharmacological treatment of MDD has been monoaminergic antidepressants (MAA). However, MAAs have serious clinical limitations including a relatively slow onset of action and up to 40% of patients failing to respond and being diagnosed as “treatment resistant”. Ketamine, an N-methyl-D-aspartate antagonist, was originally approved for use as an injectable anesthetic. In addition, ketamine has been shown to rapidly improve depressive symptoms in patients with treatment resistant depression. In 2019, (S)-ketamine was approved as a nasal spray (Spravato®) for patients with MDD and treatment-resistant depression in …

Mechanisms And Treatment Of Pain-Depressed Behavior In Male And Female Mice, Clare M. Diester

Theses and Dissertations

One of the largest discrepancies between preclinical and clinical assessment of pain and analgesia is the type of behavioral endpoint used. Although most preclinical research has historically focused on drug effectiveness to block reflexive withdrawal behaviors stimulated by a noxious stimulus, increasing evidence shows that drug-induced restoration of pain-depressed behaviors provides increased clinical translation with decreased susceptibility to false-positives. Accordingly, the first portion of this dissertation designed a behavioral battery that featured pain-depressed behaviors as well as more conventional pain-stimulated behaviors for testing candidate analgesics in male and female mice. The main findings are as follows. (1) Intraperitoneal injection of …

Aging, A Pathological Factor In Neurological Injury, Aruvi Vijikumar

Graduate Theses, Dissertations, and Problem Reports

One of the main reasons for CNS drugs to fail in clinical development is not considering age as a risk factor while studying chronic age-related neurological/neurodegenerative diseases in preclinical studies. We first set out to gain a comprehensive understanding of the impact of age on various aspects (anatomical, immunological, and biochemical) in rodents that play a key role in determining the onset, progression, and evolution of disease severity. With advancing age, the vascular structure and function are compromised which is hypothesized to accelerate cognitive decline. The initial step toward developing novel therapeutics is to characterize the age-related vascular modifications. Utilizing …

Characterizing And Quantifying The Redox Behavior Of Cytokine Hmgb1 In Drug-Induced Liver Injury Via High Resolution Mass Spectrometry, Ross Pirnie

Publicly Accessible Penn Dissertations

High mobility group box 1 (HMGB1) is a protein that is released in several pathological contexts, including acetaminophen (APAP) overdose, and modulates the subsequent immune response to tissue damage. Oxidation of HMGB1 potentially regulates its interactions with the immune system but there have been a number of contradictory studies on the redox behavior of HMGB1 and what proteoforms of HMGB1 are present in oxidative pathology. Therefore, a stable isotope dilution two-dimensional nano-ultrahigh-performance liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry (2D-nano-UHPLC-PRM/HRMS) method was developed along with a hepatocarcinoma cell model of APAP overdose to allow for characterization of HMGB1 redox behavior …

Exploring The Mechanisms Of Pkg1-Α Activation By Synthetic Peptides, Connor Cronin

Graduate College Dissertations and Theses

Cyclic GMP-dependent protein kinases (PKG’s) are essential signaling macromolecules which play a pivotal role in vascular physiology and smooth muscle tone regulation. As principle downstream effectors of the secondary messenger cyclic 3’, 5’-guanosine-monophosphate (cGMP), PKG isoforms are expressed in high levels in all types of smooth muscle cells. The broad range of cellular functions effected by PKG include platelet aggregation, hypertrophy, apoptosis, neuronal plasticity, gene expression, differentiation, vasorelaxation, vascular remodeling, calcium homeostasis, and cardiac function. Recently, a newly characterized helical switch domain within the alpha isoform of PKG (PKG1-α) has led to the development of S1.1, a novel cGMP-independent peptide …

The Benefits Of Astaxanthin To Improve Pain Relief In Patients With Painful Diabetic Neuropathy: An Open-Label, Randomized Controlled Trial, Rizaldy Taslim Pinzon, Mary Rose Angelina Budi Harsana

Pharmaceutical Sciences and Research

Treatment of diabetic neuropathy is still carried out by providing symptomatic therapy, which only improves ± 50% of the total symptoms felt by patients, but does not tackle the underlying causes of the disease. Astaxanthin is a potent antioxidant, anti-inflammatory, and anti-diabetic carotenoid that could be an additional treatment option. We aimed to measure the effectiveness of administering astaxanthin as an additional therapy to improve the impact of pain and discomfort experienced daily by diabetes mellitus patients with painful diabetic neuropathy. We conducted a randomized experimental study with an open label design of 36 patients who had been diagnosed with …

“Data Architecture For Pharmaceutical Product Development At Alkermes”, Peter Couture, Damon Warnock, Marcus O'Mahony

Level 3

This paper describes how Alkermes built a data architecture for efficient management of non-GXP and R&D data. Using a ‘Create’, ‘Store’, Describe’ ‘Access’ stepwise model, the ingredients to making the journey a success are described.

Acknowledgment Of Reviewers

Journal of Food and Drug Analysis

No abstract provided.

Molecular Cartography Of Residue Pesticides On Grape Surface In 3d By Ambient Ionization Tandem Mass Spectrometry, Hung Su, Tiao-Lai Huang, Cheng-Ting Chi, Yi-Tzu Cho, Chi-Wei Lee, Jingyueh Jeng, Jentaie Shiea

Journal of Food and Drug Analysis

Thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS) was used to characterize the residual pesticides that were collected from the surface of a grape with metallic sampling probes. Fungicides, insecticides, and miticides were detected, where results were validated by simple solvent extraction followed by gas chromatography tandem mass spectrometry and liquid chromatography tandem mass spectrometry analyses. To explore the distribution of pesticide residues on grape surfaces, 149 locations of a grape surface were collected and followed by TD-ESI/MS/MS analysis. The molecular cartography was then generated from analysis of residual pesticides on the grape surface in 3D.

Variations In Bovine Milk Oligosaccharides After Calving Using P-Aminobenzoic Ethyl Ester Closed-Ring Labeling And Negative Ion Electrospray Lc/Ms/Ms, Han-Ju Chien, Yi-Chun Ma, Yi-Feng Zheng, Cheng-Yu Kuo, Wei-Chen Wang, Guor-Rong Her, Chien-Chen Lai

Journal of Food and Drug Analysis

A strategy was proposed to analyze bovine milk oligosaccharides using p-aminobenzoic ethyl ester (ABEE) closed-ring labeling and C18 capillary liquid chromatography negative ion electrospray tandem mass spectrometry. Linkage specific fragment ions were used to identify oligosaccharide isomers. By constructing the mass chromatograms using linkage specific fragment ions, isomers were differentiated based on m/z values as well as temporal separation provided by liquid chromatography. In addition to disialyllactose and the single isomer lacto-N-neohexaose, four pairs of linkage isomers including 3’/6’-sialyllactose (3’/6’-SL), 3’/6’-sialyllactosamine (3’/6’-SLN), 3’/6’-sialylgalactosyl-lactose (3’/6’-SGL), and lacto-N-tetraose/lacto-N-neotetraose (LNT/LNnT) in bovine milk were investigated. Variations of bovine milk oligosaccharides in a …

Analysis Of Heterocyclic Aromatic Amines Using Selective Extraction By Magnetic Molecularly Imprinted Polymers Coupled With Liquid Chromatography – Mass Spectrometry, Shih-Ci Jhu, Jing-Ying Wang, Hsueh-Ting Wang, Sung-Fang Chen

Journal of Food and Drug Analysis

Heterocyclic aromatic amines (HCAs) are highly carcinogenic and mutagenic chemicals. This study reports on the development of magnetic molecularly imprinted polymers (MMIPs) for the purification and quantification of HCAs. A novel magnetic molecularly imprinted polymer was successfully prepared using a surface molecular imprinting method using functionalized Fe particles as the magnetic cores. 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) was used as a molecular template; methacrylic acid (MAA), ethylene glycol dimethyl acrylate (EGDMA), 2, 2′-Azobis (2-methylpropionitrile) were used as the functional monomer, crosslinker, and initiator, respectively. The use of the template/functional monomer/crosslinking agent at a ratio of 1:4:20 resulted in a product with better adsorption …

The Impact Of The Rare Disease And Orphan Drug Act In Taiwan, Ning-Chun Hsiang, Weng-Foung Huang, Churn-Shiouh Gau, Teng-Wen Tsai, Lin-Chau Chang

Journal of Food and Drug Analysis

The Rare Disease and Orphan Drug Act (the Act) was enacted in 2000 in Taiwan for the facilitation of the research, development, and accessibility of orphan drugs and special nutritional foods; for the prevention and early diagnosis of rare diseases; and for providing intensive care for patients with rare diseases. The aim was to investigate the impact of the Act on the availability and use of orphan drugs in Taiwan in the hope of identifying the remaining challenges and possible solutions to assist future policy making, which may be applicable in other countries as well. The information and statistics for …

Determination Of Quetiapine And Its Metabolites In Plasma By Field-Enhanced Sample Stacking, Tai-Ling Liu, Li-Shan Fang, Jing-Ru Liou, Jia-Shan Dai, Yen-Ling Chen

Journal of Food and Drug Analysis

Quetiapine is an atypical antipsychotic drug that can be used to treat mental disorders, including schizophrenia, bipolar disorder and Alzheimer's disease. Quetiapine is mainly converted into the active metabolites of norquetiapine and 7-hydroxyquetiapine by the liver enzymes CYP3A4 and CYP2D6. In this study, liquid-liquid extraction (LLE) was used as a sample pretreatment method to eliminate interferences in plasma. tert-Butyl methyl ether was chosen as the extraction solvent. Field-enhanced sample injection (FESS), an online preconcentration technique, was used to analyze quetiapine and its metabolites norquetiapine and 7-hydroxyquetiapine in plasma. The optimal separation condition was 120 mM phosphate (pH 4.0) containing …