Medicine and Health Sciences Commons^™

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 …

Statin Treatment In Specific Patient Groups: Role For Improved Cardiovascular Risk Markers, Alyssa White, Hillary R. Mishcon, John L. Redwanski, Ronald D. Hills Jr

Pharmaceutical Sciences Faculty Publications

Ample evidence supports the use of statin therapy for secondary prevention in patients with a history of atherosclerotic cardiovascular disease (ASCVD), but evidence is wanting in the case of primary prevention, low-risk individuals, and elderly adults 65+. Statins are effective in lowering low-density lipoprotein (LDL), which has long been a target for treatment decisions. We discuss the weakening dependence between cholesterol levels and mortality as a function of age and highlight recent findings on lipoprotein subfractions and other superior markers of ASCVD risk. The efficacy of statins is compared for distinct subsets of patients based on age, diabetes, ASCVD, and …

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

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 …

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 …

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.

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

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 …

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

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 …

Evaluation Of Biased And Balanced Salvinorin A Analogs In Preclinical Models Of Pain, Kelly F. Paton, Andrew Biggerstaff, Sophia Kaska, Rachel S. Crowley, Anne C. La Flamme, Thomas E. Prisinzano, Bronwyn M. Kivell

Pharmaceutical Sciences Faculty Publications

In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential. Salvinorin A (SalA) is a potent and selective KOPr agonist, however, clinical utility is limited by the short duration of action and aversive side effects. Biasing KOPr signaling toward G-protein activation has been highlighted as a key cellular mechanism to reduce the side effects of KOPr agonists. The present study investigated KOPr signaling bias and the acute antinociceptive effects and side effects of two novel analogs of SalA, 16-Bromo SalA and 16-Ethynyl SalA. 16-Bromo …

Population Data-Driven Formulation Of A Covid-19 Therapeutic, Heather R. Campbell, Regan P. Cecil, Robert A. Lodder

Pharmaceutical Sciences Faculty Publications

This study is designed to utilize computer modeling of the US population through the ongoing CDC NHANES trial to reduce the need for preclinical formulation and toxicology studies of an Ebola antiviral (BSN389) being repurposed for COVID-19, and to thereby speed the candidate therapeutic to the clinic. BSN389 has poor solubility in water and that limits its bioavailability. BCD greatly increases the solubility of BSN389 and results in high bioavailability of BSN389 in animal studies. The goal of this study is to determine the current daily exposure of the population to beta cyclodextrin (BCD), and then keep the amount of …