Chemical and Pharmacologic Phenomena Commons^™

Prophylactic Intravenous Prehydration With Sodium Bicarbonate Or Sodium Chloride In The Prevention Of Contrast Induced Acute Kidney Injury, Briana Lockett, Caroline Dong

Physician Assistant Capstones, 2020-current

Introduction: Iodinated contrast media is a crucial component in the diagnostic work up of many life-threatening illnesses. However, it has been reported to cause acute kidney injury after administration, especially in patients with pre-existing renal disease. Several prophylactic treatments have been studied in hopes of minimizing these adverse events. The current standard of care in this patient population is prophylactic intravenous volume administration with either sodium chloride or sodium bicarbonate. Objective: The goal of this literature review is to determine if prophylactic intravenous volume administration with either saline or sodium bicarbonate prior to contrast administration decreases the incidence of contrast …

Spinal Metastases And The Evolving Role Of Molecular Targeted Therapy, Chemotherapy, And Immunotherapy, Elena I Fomchenko, James C Bayley, Christopher Alvarez-Breckenridge, Laurence D Rhines, Claudio E Tatsui

Faculty, Staff and Student Publications

Metastatic involvement of the spine is a common complication of systemic cancer progression. Surgery and external beam radiotherapy are palliative treatment modalities aiming to preserve neurological function, control pain and maintain functional status. More recently, with development of image guidance and stereotactic delivery of high doses of conformal radiation, local tumor control has improved; however recurrent or radiation refractory disease remains a significant clinical problem with limited treatment options. This manuscript represents a narrative overview of novel targeted molecular therapies, chemotherapies, and immunotherapy treatments for patients with breast, lung, melanoma, renal cell, prostate, and thyroid cancers, which resulted in improved …

Impact Of Alcohol On Bone Health In People Living With Hiv: Integrating Clinical Data From Serum Bone Markers With Morphometric Analysis In A Non-Human Primate Model, Alexandra Denys, Allison Norman, Daniel S. Perrien, Larry J. Suva, Liz Simon, Lee S. Mcdaniel, Tekeda Ferguson, Kim Pedersen, David Welsh, Patricia E. Molina, Martin J.J. Ronis

School of Medicine Faculty Publications

People living with HIV (PLWH) represent a vulnerable population to adverse musculoskeletal outcomes due to HIV infection, antiretroviral therapy (ART), and at-risk alcohol use. Developing measures to prevent skeletal degeneration in this group requires a grasp of the relationship between alcohol use and low bone mass in both the PLWH population and its constituents as defined by sex, age, and race. We examined the association of alcohol use with serum biochemical markers of bone health in a diverse cohort of PLWH enrolled in the New Orleans Alcohol Use in HIV (NOAH) study. To explore the effects of alcohol on bone …

Functional Determination Of Calcium-Binding Sites Required For The Activation Of Inositol 1,4,5-Trisphosphate Receptors, Vikas Arige, Lara E Terry, Larry E Wagner, Sundeep Malik, Mariah R Baker, Guizhen Fan, Suresh K Joseph, Irina I Serysheva, David I Yule

Faculty, Staff and Student Publications

Inositol 1,4,5-trisphosphate receptors (IP3Rs) initiate a diverse array of physiological responses by carefully orchestrating intracellular calcium (Ca2+) signals in response to various external cues. Notably, IP3R channel activity is determined by several obligatory factors, including IP3, Ca2+, and ATP. The critical basic amino acid residues in the N-terminal IP3-binding core (IBC) region that facilitate IP3 binding are well characterized. In contrast, the residues conferring regulation by Ca2+ have yet to be ascertained. Using comparative structural analysis of Ca2+-binding sites identified in two main families of intracellular Ca2+-release channels, ryanodine receptors (RyRs) and IP3Rs, we identified putative acidic residues coordinating Ca2+ …

Associations Between Cannabis, Psychosis, And Schizophrenia In Adolescents, Lauren Moment

Academic Leadership Journal in Student Research

The effects of cannabis use on the brain, mind, and body have been studied for decades. The developing brain, particularly the adolescent and young adult brain, undergoes critical development that makes it especially susceptible to the effects of cannabis use. Among the adverse effects of cannabis use in adolescence and young adulthood, psychosis and psychotic disorders (e.g., schizophrenia) have been examined. The association of cannabis use with schizophrenia was first elucidated in a Swedish study of army conscripts. Specifically, conscripts reported their cannabis use exposure and were followed longitudinally to assess the emergence of schizophrenia. The authors found that those …

Visualizing Depressive Symptom Improvement: Implementing The 17-Item Hamilton Depression Rating Scale, Briana Raterman

Dissertations

Visualizing Depressive Symptom Improvement: Implementing the 17-Item Hamilton Depression Rating Scale

Abstract

Problem

Depression, a mental health diagnosis, has affected about 18.5% of adults (Villarroel & Terlizzi, 2020). Ketamine, a medication initially used as an anesthetic, has improved depressive symptoms in individuals struggling with treatment-resistant depression.

Method

This quality improvement (QI) project used the 17-item Hamilton Depression Rating Scale questionnaire to assess depressive symptom changes in patients receiving intramuscular ketamine for treatment-resistant depression. The questionnaire was administered to patients pre-and post-intramuscular ketamine administration. The data was collected on injections one, three, and six on each participant’s set schedule of injections …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

Channelopathy Of Small- And Intermediate-Conductance Ca2+-Activated K+ Channels, Young-Woo Nam, Miles Downey, Mohammad Asikur Rahman, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca²⁺-activated K⁺ (K_Ca2.x/K_Ca3.1 also called SK/IK) channels are gated exclusively by intracellular Ca²⁺. The Ca²⁺ binding protein calmodulin confers sub-micromolar Ca²⁺ sensitivity to the channel-calmodulin complex. The calmodulin C-lobe is constitutively associated with the proximal C-terminus of the channel. Interactions between calmodulin N-lobe and the channel S4-S5 linker are Ca²⁺-dependent, which subsequently trigger conformational changes in the channel pore and open the gate. KCNN genes encode four subtypes, including KCNN1 for K_Ca2.1 (SK1), KCNN2 for K_Ca2.2 (SK2), KCNN3 for K …

Riluzole For Pediatric Patients With Treatment-Refractory Obsessive-Compulsive Disorder, Maheen Mohammad, Stuti Parikh

Rowan-Virtua Research Day

Obsessive-compulsive disorder (OCD) occurs in about 1-3% of the pediatric population, but many do not respond to standard therapies. Riluzole, a glutamate antagonist, has shown to be an effective treatment for refractory OCD in adults, however few trials have been conducted to show the effectiveness of Riluzole in children to treat refractory OCD. The study investigates the potential use of riluzole in children to treat refractory OCD.

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

Development And Characterization Of Anti-Galectin-9 Antibodies That Protect T Cells From Galectin-9-Induced Cell Death, Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung

Faculty, Staff and Student Publications

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two …

Late-Stage Chemoenzymatic Installation Of Hydroxy-Bearing Allyl Moiety On The Indole Ring Of Tryptophan-Containing Peptides, Nagaraju Mupparapu, Lauren Brewster, Katrina F. Ostrom, Sherif I. Elshahawi

Pharmacy Faculty Articles and Research

The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification and leads to changes in their biological properties. Here, the synthesis of two hydroxy-bearing allyl pyrophosphates is described. A chemoenzymatic method is demonstrated which uses a promiscuous indole prenyltransferase enzyme to install a dual reactive hydroxy-bearing allyl moiety directly on the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.

Channelopathy-Causing Mutations In The S45A/S45B And Ha/Hb Helices Of KCa2.3 And KCa3.1 Channels Alter Their Apparent Ca2+ Sensitivity, Razan Orfali, Young-Woo Nam, Hai Minh Nguyen, Mohammad Asikur Rahman, Grace Yang, Meng Cui, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca²⁺-activated potassium (K_Ca2.x and K_Ca3.1, also called SK and IK) channels are activated exclusively by a Ca²⁺-calmodulin gating mechanism. Wild-type K_Ca2.3 channels have a Ca²⁺ EC₅₀ value of ∼0.3 μM, while the apparent Ca²⁺ sensitivity of wild-type K_Ca3.1 channels is ∼0.27 μM. Heterozygous genetic mutations of K_Ca2.3 channels have been associated with Zimmermann-Laband syndrome and idiopathic noncirrhotic portal hypertension, while K_Ca3.1 channel mutations were reported in hereditary xerocytosis patients. K_Ca2.3_S436C and K_Ca2.3_V450L channels with …