Medical Pharmacology Commons^™

Triamcinolone With Vitamin D Synergistic Efficacy In Psoriasis, Steven Repas, Jeffrey B. Travers

Medical Student Research Symposium Abstracts and Posters

Psoriasis is one of the most common skin conditions in the United States affecting more than 8 million people. High amounts of vitamin D has been shown to be effective in treatment of psoriasis. It also has a well-documented safety profile at the doses and duration that will be used during this study. Triamcinolone and other topical corticosteroids are considered a first line treatment for mild to moderate psoriasis with a well-documented safety profile. Individually both of these medications have shown effectiveness in the management and treatment of mild to moderate psoriasis. This study is designed to test whether a …

The Crosstalk Between Insulin Resistance, Systemic Inflammation, Redox Imbalance And The Thyroid In Subjects With Obesity, Nicoleta Răcătăianu, Nicoleta Valentina Leach, Sorana D. Bolboacă, Maria Loredana Soran, Mirela Flonta, Ana Valea, Andrada-Luciana Lazăr, Cristina Ghervan

Journal of Mind and Medical Sciences

We aimed at assessing the interaction between visceral adipose tissue (VAT), insulin resistance (IR), circulating levels of monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) and the thyroid parameters in obese subjects. Methods. Obese subjects without thyroid pathologies or diseases associated with systemic inflammation and OS were recruited. Insulinemia, visceral fat thickness, metabolic and thyroid parameters were assayed. Circulating levels of MCP-1 and MDA were used to quantify inflammation and OS. Results. A number of 160 obese subjects were included. The MCP-1 level increased with the degree of obesity and HOMA-IR. MCP 1 was positively associated with antithyroperoxidase antibody (TPOab) levels …

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …

Methamphetamine Associated Cardiomyopathy In Pregnancy: The Distinctions And The Implications, Ashan Hatharasinghe, Hossein Akhondi

HCA Healthcare Journal of Medicine

Introduction

Methamphetamine associated cardiomyopathy (MAC) and peripartum cardiomyopathy (PPCM) are both rare obstetric conditions. Literature regarding methamphetamine associated cardiomyopathy in the obstetric population is limited, and it can be difficult to make the distinction between the two given the similarities in clinical presentation. However similar, there are significant distinctions in the pathophysiology of these two that can help clinicians with the management process.

Clinical Findings and Outcomes

This case involves a 35-year-old Hispanic G6P5005 at 37 weeks gestation presenting with acute respiratory failure secondary to acute decompensated heart failure with reduced ejection fraction and superimposed preeclampsia leading to urgent cesarean …

Correspondence Between Perceived Pubertal Development And Hormone Levels In 9-10 Year-Olds From The Adolescent Brain Cognitive Development Study., Megan M Herting, Kristina A Uban, Marybel Robledo Gonzalez, Fiona C Baker, Eric C Kan, Wesley K Thompson, Douglas A Granger, Matthew D Albaugh, Andrey P Anokhin, Kara S Bagot, Marie T Banich, Deanna M Barch, Arielle Baskin-Sommers, Florence J Breslin, B J Casey, Bader Chaarani, Linda Chang, Duncan B Clark, Christine C Cloak, R Todd Constable, Linda B Cottler, Rada K Dagher, Mirella Dapretto, Anthony S Dick, Nico Dosenbach, Gayathri J Dowling, Julie A Dumas, Sarah Edwards, Thomas Ernst, Damien A Fair, Sarah W Feldstein-Ewing, Edward G Freedman, Bernard F Fuemmeler, Hugh Garavan, Dylan G Gee, Jay N Giedd, Paul E A Glaser, Aimee Goldstone, Kevin M Gray, Samuel W Hawes, Andrew C Heath, Mary M Heitzeg, John K Hewitt, Charles J Heyser, Elizabeth A Hoffman, Rebekah S Huber, Marilyn A. Huestis, Luke W Hyde, M Alejandra Infante, Masha Y Ivanova, Joanna Jacobus, Terry L Jernigan, Nicole R Karcher, Angela R Laird, Kimberly H Leblanc, Krista Lisdahl, Monica Luciana, Beatriz Luna, Hermine H Maes, Andrew T Marshall, Michael J Mason, Erin C Mcglade, Amanda S Morris, Bonnie J Nagel, Gretchen N Neigh, Clare E Palmer, Martin P Paulus, Alexandra S Potter, Leon I Puttler, Nishadi Rajapakse, Kristina Rapuano, Gloria Reeves, Perry F Renshaw, Claudiu Schirda, Kenneth J Sher, Chandni Sheth, Paul D Shilling, Lindsay M Squeglia, Matthew T Sutherland, Susan F Tapert, Rachel L Tomko, Deborah Yurgelun-Todd, Natasha E Wade, Susan R B Weiss, Robert A Zucker, Elizabeth R Sowell

Institute of Emerging Health Professions Faculty Papers

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.

Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study—a multi-site sample of 9–10 year-olds (n = 11,875)—and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal …

Macrophage-Derived Thrombospondin 1 Promotes Obesity-Associated Non-Alcoholic Fatty Liver Disease, Taesik Gwag, Raja Gopal Reddy Mooli, Dong Li, Sangderk Lee, Eun Young Lee, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Background

Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. We previously showed that TSP1 has an important role in obesity-associated metabolic complications, including inflammation, insulin resistance, cardiovascular, and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD or NASH) remains largely unknown; thus, we aimed to determine its role.

Methods

High-fat diet or AMLN (amylin liver NASH) diet-induced obese and insulin-resistant NAFLD/NASH mouse models were utilised, in addition to tissue-specific Tsp1-knockout mice, to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development.

Results

Liver TSP1 levels were increased in experimental obese …

Targeting Parp-1 With Metronomic Therapy Modulates Mdsc Suppressive Function And Enhances Anti-Pd-1 Immunotherapy In Colon Cancer, Mohamed A. Ghonim, Salome V. Ibba, Abdelmetalab F. Tarhuni, Youssef Errami, Hanh H. Luu, Matthew J. Dean, Ali H. El-Bahrawy, Dorota Wyczechowska, Ilyes A. Benslimane, Luis Del Valle, Amir A. Al-Khami, Augusto C. Ochoa, A Hamid Boulares

School of Graduate Studies Faculty Publications

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) are effective against BRCA-mutated cancers at/near maximum tolerated doses by trapping PARP-1 on damaged chromatin, benefitting only small patient proportions. The benefits of targeting non-DNA repair aspects of PARP with metronomic doses remain unexplored. METHODS: Colon epithelial cells or mouse or human bone marrow (BM)-derived-myeloid-derived suppressor cells (MDSCs) were stimulated to assess the effect of partial PARP-1 inhibition on inflammatory gene expression or immune suppression. Mice treated with azoxymethane/four dextran-sulfate-sodium cycles or mice bred into PARP-1 or treated with olaparib were used to examine the role of PARP-1 in colitis-induced or spontaneous colon …

The Association Of Circulating Amylin With Β-Amyloid In Familial Alzheimer's Disease, Han Gia Ly, Nirmal Verma, Savita Sharma, Deepak Kotiya, Sanda Despa, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Donna M. Wilcock, Larry B. Goldstein, Rita Guerreiro, José Brás, Angela J. Hanson, Suzanne Craft, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Alzheimer’S Disease Exome Sequencing Group, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Introduction

This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods

Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats.

Results

Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected …

Efficacy And Safety Of Once-Daily Vibegron For Treatment Of Overactive Bladder In Patients Aged ≥65 And ≥75 Years: Subpopulation Analysis From The Empowur Randomized, International, Phase Iii Study, Susann Varano, David Staskin, Jeffrey Frankel, Denise Shortino, Rachel Jankowich, Paul N. Mudd

Physician Associate Studies Faculty Publications

Background

Overactive bladder (OAB) is common among older adults. The efficacy and safety of vibegron for the treatment of OAB were demonstrated in the international, phase III EMPOWUR trial. This subpopulation analysis from EMPOWUR assessed the efficacy and safety of vibegron in patients aged ≥ 65 and ≥ 75 years.

Methods

In EMPOWUR, patients with OAB were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, once daily for 12 weeks. Coprimary efficacy endpoints were change from baseline at week 12 in average daily number of micturitions and urge urinary incontinence (UUI) …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

The Efficacy Of In Vitro Fertilization In Treating Infertility Due To Anovulatory Pcos In Comparison To Ovulation Induction Via Letrozole, Amanda Salay

Capstone Showcase

Abstract:

Introduction: Polycystic Ovarian Syndrome (PCOS) is an endocrine disorder found in women of reproductive age that often causes infertility. The first-line treatment for infertility in anovulatory PCOS patients is ovulation induction. In vitro fertilization (IVF) is a third line treatment often used as a last resort. PCOS patients have higher failure risks of first- and second-line medications. Therefore, this review analyzes if adverse pregnancy outcomes (O) are reduced more with IVF (I) versus using letrozole for ovulation induction (C) in women aged 20-30 struggling with infertility due to anovulatory PCOS (P).

Methods: A literature search on Pubmed and EBSCOhost …

Potential Perioperative Complications Due To Difference In Timing Of Systemic Heparinization During Ruptured Aneurysm Coiling, Rouzbeh Kotaki, Ameer E. Hassan, Wondwossen G. Tekle

MEDI 9331 Scholarly Activities Clinical Years

Potential Perioperative Complications Due To Differences in Timing Of Systemic Heparin Distribution During Ruptured Aneurysm Coiling

Introduction:

In general, systematic heparin anticoagulation is standard in regards to neurovascular intervention. When coiling ruptured aneurysms, many neurointerventionalists have their own protocol as to timing of systemic heparinization. There is ample research and literature reviewing the frequency of perioperative events, predictors and outcomes, as well as the efficacy in the use of anticoagulants and/or antiplatelets before, during, and after neurovascular procedures to prevent adverse outcomes. However, there currently exists a dearth of research in regards to timing of distribution of heparin intraoperatively and …

Deep Brain Stimulation Of The Subcallosal Cingulate Gyrus In The Treatment Of Treatment Resistant Depression, Megan Caravas, Melanie Sov

Physician Assistant Capstones, 2020-current

Objective: a systematic review to determine the efficacy of deep brain stimulation (DBS) targeting the subcallosal cingulate gyrus (SCG) for the treatment of treatment resistant depression (TRD). Methods: PubMed database was utilized in a search for clinical randomized control trials that were completed after the year 2000, using the terms deep brain stimulation, treatment resistant depression, and subcallosal cingulate gyrus. Results: Three clinical trials were chosen based on specific inclusion criteria as noted in the PRISMA flow chart (Chart 1). The results of the three articles showed various discrepancies. Two of the three studies demonstrated some statistical significance in reduction …

Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in …

Research Amidst The Pandemic, Howard Burris

HCA Healthcare Journal of Medicine

Cancer patients need access to promising investigational therapies, available only through clinical trials, and the emergence of COVID-19 and the resulting pandemic became an emerging threat to fulfilling that need. Many academic medical centers were pausing their clinical research programs, diverting their resources and sheltering their teams. Sarah Cannon, the Cancer Institute of HCA Healthcare, made the decision to stay safe, but stay the course.

Tackle Epithelial-Mesenchymal Transition With Epigenetic Drugs In Cancer, Bo Dong, Zhaoping Qiu, Yadi Wu

Pharmacology and Nutritional Sciences Faculty Publications

Epithelial-mesenchymal Transition (EMT) is a de-differentiation process in which epithelial cells lose their epithelial properties to acquire mesenchymal features. EMT is essential for embryogenesis and wound healing but is aberrantly activated in pathological conditions like fibrosis and cancer. Tumor-associated EMT contributes to cancer cell initiation, invasion, metastasis, drug resistance and recurrence. This dynamic and reversible event is governed by EMT-transcription factors (EMT-TFs) with epigenetic complexes. In this review, we discuss recent advances regarding the mechanisms that modulate EMT in the context of epigenetic regulation, with emphasis on epigenetic drugs, such as DNA demethylating reagents, inhibitors of histone modifiers and non-coding …

FacebookʼS Latest Attempt To Address Vaccine Misinformation — And Why ItʼS Not Enough, Ana Santos Rutschman

All Faculty Scholarship

On October 13, 2020 Facebook announced the adoption of a series of measures to promote vaccine trust “while prohibiting ads with misinformation that could harm public health efforts.” In the post written by Kang-Xing Jin (head of health) and Rob Leathern (director of product management), the company explained that the new measures were designed with an emphasis on encouraging widespread use of this yearʼs flu vaccine, as well as in anticipation of potential COVID-19 vaccines becoming available in the near future.

The changes focus mainly on the establishment of a multiprong informational campaign about the seasonal flu vaccine, which includes …

Vitamin D Levels Affect Survival In A Bcr-Abl Acute Lymphoblastic Leukemia Mouse Model But Do Not Cause Vitamin-Drug Interactions, Kavya Annu

Theses and Dissertations (ETD)

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of vitamin D (VD3) status on systemic exposure and efficacy of chemotherapeutic agents that are CYP3A substrates. We employed VD3 sufficient and deficient mice to perform pharmacokinetics (PK) and anti-leukemic efficacy studies.

First, using hCYP3A4 transgenic mouse model we evaluated the intestinal, hepatic and renal expression …

Combating Acquired Resistance To Mapk Inhibitors In Melanoma By Targeting Abl1/2-Mediated Reactivation Of Mek/Erk/Myc Signaling, Rakshamani Tripathi, Zulong Liu, Aditi Jain, Anastasia Lyon, Christina Meeks, Dana Richards, Jinpeng Liu, Daheng He, Chi Wang, Marika Nespi, Andrey Rymar, Peng Wang, Melissa Wilson, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2nd generation …

Clinical Approach To A Request For Phentermine-Topiramate In A Young Woman With A History Of High-Risk Eating Behavior, Erin Spencer

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising Safer DL, Adler S, Dalai SS, et al. A randomized, placebo-controlled crossover trial of phentermine-topiramate ER in patients with binge-eating disorder and bulimia nervosa. Int J Eat Disord. 2019;(September):1-12. https://doi.org/10.1002/eat.23192 to inform the clinical decision of whether or not to prescribe phentermine-topiramate to an overweight 27-year-old woman who endorses risky eating behaviors.

Cyclosporine Shows Benefit As Compared To Methotrexate For Treatment Of Pediatric Atopic Dermatitis Refractory To Topical Medications When Rapidity Of Clinical Response Is Of Key Importance To The Patient, Connor R. Buechler, Steven Daveluy Md

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. European Journal of Pediatrics. 2012;172(3):351-356. https://doi.org10.1007/s00431-012-1893-3 for a pediatric patient with severe atopic dermatitis.

Ace2 Mouse Models: A Toolbox For Cardiovascular And Pulmonary Research, Hongpeng Jia, Xinping Yue, Eric Lazartigues

School of Medicine Faculty Publications

Angiotensin-converting enzyme 2 (ACE2) has been identified as the host entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic. ACE2 is a regulatory enzyme of the renin-angiotensin system and has protective functions in many cardiovascular, pulmonary and metabolic diseases. This review summarizes available murine models with systemic or organ-specific deletion of ACE2, or with overexpression of murine or human ACE2. The purpose of this review is to provide researchers with the genetic tools available for further understanding of ACE2 biology and for the investigation of ACE2 in the pathogenesis and treatment of COVID-19.

Mesencephalic Astrocyte-Derived Neurotrophic Factor (Manf) Regulates Neurite Outgrowth Through The Activation Of Akt/Mtor And Erk/Mtor Signaling Pathways, Wen Wen, Yongchao Wang, Hui Li, Hong Xu, Mei Xu, Jacqueline A. Frank, Murong Ma, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Neurite outgrowth is essential for brain development and the recovery of brain injury and neurodegenerative diseases. In this study, we examined the role of the neurotrophic factor MANF in regulating neurite outgrowth. We generated MANF knockout (KO) neuro2a (N2a) cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and demonstrated that MANF KO N2a cells failed to grow neurites in response to RA stimulation. Using MANF siRNA, this finding was confirmed in human SH-SY5Y neuronal cell line. Nevertheless, MANF overexpression by adenovirus transduction or addition of MANF into culture media facilitated the growth of longer neurites in RA-treated N2a …

A Novel Methodology To Identify The Primary Topics Contained Within The Covid-19 Research Corpus, Allen Crane, Brock Freidrich, William Fehlman, Igor Frolow, Daniel W. Engels

SMU Data Science Review

In this paper, we present a novel framework and system for the identification of primary research topics from within a corpus of related publications, the classification of individual publications according to these topics, and the results of the application of our framework and system to the COVID-19 Open Research Dataset (CORD-19). CORD-19 is a corpus of published peer reviewed and pre-peer reviewed articles related to the coronavirus that causes COVID-19. Using machine learning techniques, such as Non-negative Matrix Factorization for Natural Language Processing and a Bayesian classifier, we developed a novel framework and system that automatically extracts sparse and meaningful …

Folic Acid Supplementation In Patients With Elevated Homocysteine Levels, Alan D. Kaye, George M. Jeha, Alex D. Pham, Mitchell C. Fuller, Zachary I. Lerner, Gerald T. Sibley, Elyse M. Cornett, Ivan Urits, Omar Viswanath, Christopher G. Kevil

School of Medicine Faculty Publications

Introduction: Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5–5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease. Methods: A literature review of …