Pharmacy and Pharmaceutical Sciences Commons^™

Selective C1 Lesioning Slightly Decreases Angiotensin Ii Type I Receptor Expression In The Rat Rostral Ventrolateral Medulla (Rvlm)., Erick A Bourassa, Kristen A Stedenfeld, Alan F Sved, Robert Charles Speth

Faculty Articles

Cardiovascular homeostasis is regulated in large part by the rostral ventrolateral medulla (RVLM) in mammals. Projections from the RVLM to the intermediolateral column of the thoracolumbar spinal cord innervate preganglionic neurons of the sympathetic nervous system causing elevation of blood pressure and heart rate. A large proportion, but not all, of the neurons in the RVLM contain the enzymes necessary for the production of epinephrine and are identified as the C1 cell group. Angiotensin II (Ang II) activates the RVLM acting upon AT1 receptors. To assess the proportion of AT1 receptors that are located on C1 neurons in the rat …

Mechanisms Of Activation Of Nucleus Accumbens Neurons By Cocaine Via Sigma-1 Receptor-Inositol 1,4,5-Trisphosphate-Transient Receptor Potential Canonical Channel Pathways., Jeffrey L. Barr, Elena Deliu, Gabriela Cristina Brailoiu, Pingwei Zhao, Guang Yan, Mary E. Abood, Ellen M. Unterwald, Eugen Brailoiu

College of Pharmacy Faculty Papers

Cocaine promotes addictive behavior primarily by blocking the dopamine transporter, thus increasing dopamine transmission in the nucleus accumbens (nAcc); however, additional mechanisms are continually emerging. Sigma-1 receptors (σ1Rs) are known targets for cocaine, yet the mechanisms underlying σ1R-mediated effects of cocaine are incompletely understood. The present study examined direct effects of cocaine on dissociated nAcc neurons expressing phosphatidylinositol-linked D1 receptors. Endoplasmic reticulum-located σ1Rs and inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) were targeted using intracellular microinjection. IP3 microinjection robustly elevated intracellular Ca(2+) concentration, [Ca(2+)]i. While cocaine alone was devoid of an effect, the IP3-induced response was σ1R-dependently enhanced by cocaine co-injection. Likewise, …

Identification Of Novel Genes That Regulate Androgen Receptor Signaling And Growth Of Androgen-Deprived Prostate Cancer Cells, Elina Levina, Hao Ji, Mengqiang Chen, Mirza Baig, David Oliver, Patrice Ohouo, Chang-Uk Lim, Garry Schools, Steven Carmack, Ye Ding, Eugenia Broude, Igor Roninson, Ralph Buttyan, Michael Shtutman

Faculty Publications

Prostate cancer progression to castration refractory disease is associated with anomalous transcriptional activity of the androgen receptor (AR) in an androgen-depleted milieu. To identify novel gene products whose downregulation transactivates AR in prostate cancer cells, we performed a screen of enzymatically-generated shRNA lenti-libraries selecting for transduced LNCaP cells with elevated expression of a fluorescent reporter gene under the control of an AR-responsive promoter. The shRNAs present in selected populations were analyzed using high-throughput sequencing to identify target genes. Highly enriched gene targets were then validated with siRNAs against selected genes, testing first for increased expression of luciferase from an AR-responsive …

Evaluation Of A Pharmacist-Led Medication Assessment Used To Identify Prevalence Of And Associations With Polypharmacy And Potentially Inappropriate Medication Use Among Ambulatory Senior Adults With Cancer., Ginah Nightingale, Emily Hajjar, Kristine Swartz, Jocelyn Andrel-Sendecki, Andrew Chapman

College of Pharmacy Faculty Papers

PURPOSE: The use of multiple and/or inappropriate medications in seniors is a significant public health problem, and cancer treatment escalates its prevalence and complexity. Existing studies are limited by patient self-report and medical record extraction compared with a pharmacist-led comprehensive medication assessment.

PATIENTS AND METHODS: We retrospectively examined medication use in ambulatory senior adults with cancer to determine the prevalence of polypharmacy (PP) and potentially inappropriate medication (PIM) use and associated factors. PP was defined as concurrent use of five or more and less than 10 medications, and excessive polypharmacy (EPP) was defined as 10 or more medications. PIMs were …

Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation In Calyx-Bearing Vestibular Afferents, J. Chris Holt, Kevin Kewin, Paivi M. Jordan, Peter Cameron, Marcin Klapczynski, J. Michael Mcintosh, Peter A. Crooks, Linda P. Dwoskin, Anna Lysakowski

Pharmaceutical Sciences Faculty Publications

Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from α9α10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton …

Stratification Of The Impact Of Inappropriate Empirical Antimicrobial Therapy For Gram-Negative Bloodstream Infections By Predicted Prognosis, Sarah E. Cain, Joseph Kohn, P. Brandon Bookstaver, Helmut Albrecht, Majdi N. Al-Hasan

Faculty Publications

The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (<5, 5 to 9, and ≥10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31; P = 0.02) and BSIMRS of ≥10 (aHR, 4.99; 95% CI, 1.09 to 22.87; P = 0.04) but not in those with BSIMRS of <5 (aHR, 3.34; 95% CI, 0.17 to 22.77; P = 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of <5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of <5) at initial presentation.