Pharmacy and Pharmaceutical Sciences Commons^™

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …

Mithramycin And Analogs For Overcoming Cisplatin Resistance In Ovarian Cancer, David Schweer, J. Robert Mccorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, …

The Inhibition Of Cdk8/19 Mediator Kinases Prevents The Development Of Resistance To Egfr-Targeting Drugs, Amanda C. Sharko, Chang-Uk Lim, Martina S.J. Mcdermott, Chuck Hennes, Kingsavanh P. Philavong, Tiffanie Aiken, Victor V. Tatarskiy, Igor Roninson Ph. D., Eugenia Broude

Faculty Publications

Drug resistance is the main obstacle to achieving cures with both conventional and targeted anticancer drugs. The emergence of acquired drug resistance is initially mediated by non-genetic transcriptional changes, which occur at a much higher frequency than mutations and may involve population-scale transcriptomic adaptation. CDK8/19 kinases, through association with transcriptional Mediator complex, regulate transcriptional reprogramming by co-operating with different signal-responsive transcription factors. Here we tested if CDK8/19 inhibition could prevent adaptation to drugs acting on epidermal growth factor receptor (EGFR/ERBB1/HER1). The development of resistance was analyzed following long-term exposure of BT474 and SKBR3 breast cancer cells to EGFR-targeting small molecules …

Bioactive Ether Lipids: Primordial Modulators Of Cellular Signaling, N. Rangholia, T. M. Leisner, S. P. Holly

Pharmaceutical Sciences

No abstract provided.

Obstetrician-Gynecologist Perceptions And Utilization Of Prescription Drug Monitoring Programs: A Survey Study, Amie Goodin, Jungjun Bae, Chris Delcher, Joshua Brown, Dikea Roussos-Ross

Pharmacy Practice and Science Faculty Publications

Query of Prescription Drug Monitoring Programs (PDMPs) is recommended before prescribing opioids by the US Centers for Disease Control and Prevention, to inform clinical practice and aid diversion prevention. Many states mandate prescriber PDMP use; however, little is known about PDMP perception of utility and use among Obstetricians-Gynecologists (OB/GYN), who are the primary provider for most women during pregnancy.

This study examined OB/GYN perceptions and utilization of their state PDMP.

Survey items were developed by expert consensus. A voluntary anonymous survey was emailed to a random sample of 5000 OB/GYNs (adjusted participants n = 1470, minus unread/refusals). Responses were stratified …

Dopamine D2 Long Receptors Are Critical For Caveolae-Mediated Α-Synuclein Uptake In Cultured Dopaminergic Neurons, Ichiro Kawahata, Tomoki Sekimori, Haoyang Wang, Yanyan Wang, Toshikuni Sasaoka, Luc Bousset, Ronald Melki, Tomohiro Mizobata, Yasushi Kawata, Kohji Fukunaga

Pharmacy Faculty Publications and Presentations

Abstract: α-synuclein accumulation into dopaminergic neurons is a pathological hallmark of Parkinson's disease. We previously demonstrated that fatty acid-binding protein 3 (FABP3) is critical for α-synuclein uptake and propagation to accumulate in dopaminergic neurons. FABP3 is abundant in dopaminergic neurons and interacts with dopamine D2 receptors, specifically the long type (D2L). Here, we investigated the importance of dopamine D2L receptors in the uptake of α-synuclein monomers and their fibrils. We employed mesencephalic neurons derived from dopamine D2L --/--, dopamine D2 receptor null (D2 null), FABP3--/--, and wild type C57BL6 mice, and analyzed the uptake ability of fluorescence-conjugated α-synuclein monomers and …

Pharmacist-Led Programs To Increase Statin Prescribing: A Narrative Review Of The Literature, Mary Elkomos, Raha Jahromi, Michael S. Kelly

Pharmacy Faculty Articles and Research

Statins are lipid-lowing medications shown to reduce cardiovascular events and are recommended for specific patient populations at elevated risk of atherosclerotic cardiovascular disease (ASCVD). Despite the demonstrated efficacy of statins for reducing ASCVD risk, and guidance on which populations should receive statin therapy, a substantial portion of eligible patients are not prescribed statin therapy. Pharmacists have attempted to increase the number of eligible patients receiving appropriate statin therapy through a variety of interventions and across several clinical settings. In this article, we highlight multiple studies evaluating the effectiveness of pharmacist-led interventions to improve statin use. A total of seven studies …

Differential Modulation Of Sk Channel Subtypes By Phosphorylation, Young-Woo Nam, Dezhi Kong, Dong Wang, Razan Orfali, Rinzhin T. Sherpa, Jennifer Totonchy, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated K⁺ (SK) channels are voltage-independent and are activated by Ca²⁺ binding to the calmodulin constitutively associated with the channels. Both the pore-forming subunits and the associated calmodulin are subject to phosphorylation. Here, we investigated the modulation of different SK channel subtypes by phosphorylation, using the cultured endothelial cells as a tool. We report that casein kinase 2 (CK2) negatively modulates the apparent Ca²⁺ sensitivity of SK1 and IK channel subtypes by more than 5-fold, whereas the apparent Ca²⁺ sensitivity of the SK3 and SK2 subtypes is only reduced by ∼2-fold, when heterologously …

Comparing Long-Term Value Creation After Biotech And Non-Biotech Ipos, 1997–2016, Ekaterina Galkina Cleary, Laura M. Mcnamee, Skyler De Boer, Jeremy Holden, Liam Fitzgerald, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

We compared the financial performance of 319 BIOTECH companies focused on developing therapeutics with IPOs from 1997–2016, to that of paired, non-biotech CONTROL companies with concurrent IPO dates. BIOTECH companies had a distinctly different financial structure with high R&D expense, little revenue, and negative profits (losses), but a similar duration of listing on public markets and frequency of acquisitions. Through 2016, BIOTECH and CONTROL companies had equivalent growth in market cap and shareholder value (> $100 billion), but BIOTECH companies had lower net value creation ($93 billion vs $411 billion). Both cohorts exhibited a high-risk/high reward pattern of return, with …

Mutyh As An Emerging Predictive Biomarker In Ovarian Cancer, Megan L. Hutchcraft, Holly H. Gallion, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog (MUTYH) are best known for MUTYH associated polyposis and colorectal cancer, it plays a role in the development of ovarian cancer. In this review, we discuss the function of the MUTYH gene, mutation epidemiology, and its mechanism for carcinogenesis. We additionally examine its emerging role in the development of ovarian cancer and how it may be used as a predictive and targetable biomarker. MUTYH mutations may confer the risk of ovarian …

Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. Mccormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe

Pharmacotherapy and Outcomes Science Publications

Aims: Platelet rich plasma (PRP) has been used in tissue repair to treat numerous inflammatory pathophysiologies. Recent studies have elucidated that the bioactive lipid fraction of PRP significantly contributes towards the resolution of inflammation. There has been great interest in how therapeutics could modulate the PRP lipidome to formulate a more pro-resolving matrix. Many of the pathways used to produce either pro-resolving or pro-inflammatory lipids are shared between ω-3 and ω-6 polyunsaturated fatty acids (PUFA). Here, we explored the separate and interacting effects acute exogenous ω-3 PUFA supplementation and aspirin had on the lipidome of PRP within 6 hours.

Methods: …

Assessing Real-World Spot Urine Sodium Values During Continuous Intravenous Infusion Of Loop Diuretics, Rachel Propst, Michael Akers

Pharmacy Posters

• The use of spot urine sodium (UNa)>60 mmol/L as an objective measure to guide diuretic therapy in patients receiving bolus intravenous loop diuretics has been associated with increased weight loss and decreased length of stay.
• There is limited published data evaluating UNa use in patients receiving continuous intravenous loop diuretic infusions.

Design And Synthesis Of Non-Xanthone Structural Analogs Of Α-Mangostin, Maryam Foroozmehr

Theses and Dissertations

α-Mangostin belongs to a class of polyphenolic compounds called xanthones. The potential pharmacological effects such as anti-bacterial and anti-cancer effects of α-mangostin have made it an important natural product for medicinal chemistry evaluation. During this thesis research, we have designed and synthesized a series of non-xanthone analogs of α-mangostin for medicinal chemistry evaluation. A commercially available starting material, methyl-4-methoxysalicylate was used to synthesize these non-xanthone analogs. The analogs were designed as more flexible derivatives compared to the tricyclic motif within α-mangostin yet retain the hydroxybenzoate scaffold. Through a one-pot chemical synthesis, with relatively high yield (70%), we prepared eight different …

A Timecourse Based Dermatotoxicity Evaluation Of Mechlorethamine On Damage And Repair Related Protein Expression In The Mouse Ear Vesicant Model, Ganming Mao

Theses and Dissertations

Mechlorethamine (HN2) is a type of nitrogen mustard alkylating agent that has been widely applied as an anticancer drug. HN2 is an analog of the corrosive reagent sulfur mustard, which is highly reactive with skin and organisms exposed to HN2 develop significant skin irritation, edema, erythema, and disruption of the dermal-epidermal junction (DEJ). These pathological affects lead to tissue damage, activate wound repair mechanisms and, if unresolved, result in necrosis. The purpose of the present study was to evaluate the time-dependent effects of HN2 on the expression of three different proteins using immunohistochemistry (IHC) and previously prepared and preserved formalin-fixed …

In Vitro And In Silico Approaches To Evaluate The Pharmacokinetics And Pharmacodynamics Of Combination Antibiotic Therapy Against Drug-Resistant Bacteria, Sharmistha Das

Selected Full-Text Dissertations 2020-

This thesis focuses on combating antibacterial resistance by developing novel in vitro and in silico techniques. In vitro techniques such as in vitro pharmacodynamic (IVPD) modeling are powerful tools for investigating pharmacokinetic and pharmacodynamic response of antibiotics against bacteria. The standard IVPD model in the literature works for simulating monotherapy and combination therapy of drugs having similar half live. But it does not work for combination therapy of drugs having different half live. The method present in the literature for combination therapy of drugs with different half live was described by Blaser. By utilizing Blaser’s method, it was observed that …

Multivariate Pharmametric Approach As A Solution To The Challenges Associated With In-Situ Uv Fiber-Optic Dissolution Testing, Rushaben Maulik Sardhara

Selected Full-Text Dissertations 2020-

The advancement and automation in analytical techniques is a current thrust of the pharmaceutical industry. It has been over 30 years since unconventional semi or fully automatic methods have begun to be developed to achieve the measurement in-situ in the dissolution test apparatus. The current study focuses on the fiber optic dissolution system (FODS), its challenges, and solutions to the challenges. The inaccuracy in dissolution profile predictions due to some limitations associated with the FODS makes it difficult to adopt this advanced automated technology for various purposes. The traditional dissolution methods are still widely used even though they are time-consuming …

Ex Vivo Dermis Microdialysis: A Tool For Bioequivalence Testing Of Topical Dermatological Drug Product (Demonstration Of Proof Of Concept And Testing), Mohammad Asif Ali

Selected Full-Text Dissertations 2020-

Clinical response to most topical dermatological drug products (TDDP) depends on the availability of the drug in the dermis. Dermal Microdialysis (dMD) is a sampling technique that permits measuring the concentration of a drug over time, in vivo, directly into the target tissue, the dermis. The pharmacokinetic parameters obtained from such studies may help to optimize the development of TDDP and potentially can be applied to the assessment of TDDP bioequivalence. However, these studies require several hours or even days of continuous sampling that makes it often stressful and unpractical for human subjects as well as animals. The goal of …

Understanding Of The Drug-Drug Co-Crystallized Solid Structure – Mechanical Properties And Improved Tableting Performance Of High Dose Metformin Hci To Optimize The Tablet Size, Jayshil Akhilkumar Bhatt

Selected Full-Text Dissertations 2020-

Crystal engineering has been widely explored to design and develop crystalline forms of drugs to address issues related to solubility, permeability, stability, bioavailability, and other properties without impacting the therapeutic efficacy of the drug. In this exploration, we aim to address the existing limitation of metformin HCl (MET) using the cocrystallization technique, an effective tool of crystal engineering. MET, an FDA-approved anti-hyperglycemic drug, is one of the most widely prescribed treatments for type II diabetes mellitus. MET is known to suffer from several limitations due to physicochemical properties and poor mechanical and structural properties, which influence the tableting performance of …

Investigation Of Dermal Bioavailability And Bioequivalence Of Topical Dermatological Drug Products Via Microdialysis In Rabbits, Sharareh Iran Senemar

Selected Full-Text Dissertations 2020-

There is no standard technique to measure skin pharmacokinetics (PK) and therefore to evaluate bioequivalence (BE) for topical dermatological drug products (TDDPs). Generic companies are required to conduct costly clinical endpoint studies to evaluate BE. For this reason, regulatory agencies are looking for more efficient methods to measure the drug bioavailability of TDDPs. It is about 40 years since microdialysis was developed as a tool to study tissue biochemistry in animals, specifically, neurotransmitter release in the rodent brain, and 30 years since it was applied to study skin PK. However, improvements in the dermal microdialysis (dMD) technique are required to …

Splenic Artery Pseudo-Aneurysm Secondary To Necrotizing Pancreatitis – A Rare Lethal Complication., Vinay Raj Dr, Divya Vishwanatha Kini Dr

Radiology Teaching Files

CLINICAL HISTORY:

A 35-year-old male patient presented with history of massive hemoptysis associated with pain abdomen and breathlessness since the past 3 days. Patient had no prior co-morbidities; however was a chronic alcoholic and smoker since the past 15 years. No hospital admissions in the past