Medicine and Health Sciences Commons^™

The Concise Guide To Pharmacology 2021/22: Catalytic Receptors, Stephen Ph Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A Peters, Emma L Veale, Jane F Armstrong, Elena Faccenda, Simon D Harding, Adam J Pawson, Christopher Southan, Jamie A Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C Burnett, Richard W Farndale, Andreas Friebe, John Garthwaite, Adrian J Hobbs, Gavin E Jarvis, Michaela Kuhn, David Macewan, Tom P Monie, Andreas Papapetropoulos, Lincoln R Potter, Harald H H W Schmidt, Csaba Szabo, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will …

Level Of Utilization And Provider-Related Barriers To The Use Of Hydroxyurea In The Treatment Of Sickle Cell Disease Patients In Jos, North-Central Nigeria, Akinyemi O.D. Ofakunrin, Edache S. Okpe, Tolulope O. Afolaranmi, Rasaq Olaosebikan, Patience U. Kanhu, Kehinde Adekola, Nantok Dami, Atiene S. Sagay

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: Hydroxyurea is underutilized by sickle cell health-care providers in Nigeria despite available evidence of its effectiveness in reducing the manifestations and complications of sickle cell disease (SCD).

Objectives: To assess the level of utilization and provider-related barriers to the use of hydroxyurea in SCD therapy in Jos, Nigeria.

Methods: A cross-sectional study conducted among 132 medical doctors providing care for SCD patients. Data on so- cio-demographics, utilization and barriers to hydroxyurea use were obtained. The barriers were fed cumulatively into the logistic regression model as predictors of utilization.

Results: Of the 132 care providers, 88 (67%) had been in …

Longitudinal Evaluation Of Azithromycin And Cytokine Concentrations In Amniotic Fluid Following One-Time Oral Dosing In Pregnancy., Rupsa C. Boelig, Edwin Lam, Ankit Rochani, Gagan Kaushal, Amanda Roman, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

To utilize noninvasive collection of amniotic fluid in the setting of preterm premature rupture of membranes (PPROMs) to report the time concentration profile of azithromycin in amniotic fluid over 7 days from a single dose, and evaluate the correlation between azithromycin concentration and inflammatory markers in amniotic fluid. Prospective cohort study of five pregnant patients admitted with PPROMs and treated with a single 1 g oral azithromycin dose. Amniotic fluid was collected from pads and used to quantify azithromycin concentration as well as TNFa, IL-1a, IL-1b, IL-6, IL-8, and IL-10 concentrations. Primary outcome was time/concentration profile of azithromycin in amniotic …

Retinoids As Chemo-Preventive And Molecular-Targeted Anti-Cancer Therapies., Victoria O. Hunsu, Caroline O.B. Facey, Jeremy Z. Fields, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Retinoic acid (RA) agents possess anti‐tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms. The identification of mutations in retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. For example, chromosomal translocation involving RARA occurs in acute promyelocytic leukemia (APL), and all‐trans …

Seeking Similarities Rather Than Differences With Adults To Aid In Therapeutic Advancement For Children., Mara L. Becker, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

No abstract provided.

Emerging Targets For The Diagnosis Of Parkinson's Disease: Examination Of Systemic Biomarkers., Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Parkinson's disease (PD) is a highly prevalent and irreversible neurodegenerative disorder that is typically diagnosed in an advanced stage. Currently, there are no approved biomarkers that reliably identify PD patients before they have undergone extensive neuronal damage, eliminating the opportunity for future disease-modifying therapies to intervene in disease progression. This unmet need for diagnostic and therapeutic biomarkers has fueled PD research for decades, but these efforts have not yet yielded actionable results. Recently, studies exploring mechanisms underlying PD progression have offered insights into multisystemic contributions to pathology, challenging the classic perspective of PD as a disease isolated to the brain. …

Review Article: Diagnosis, Management And Patient Perspectives Of The Spectrum Of Constipation Disorders., Amol Sharma, Satish S C Rao, Kimberly Kearns, Kimberly D Orleck, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Chronic constipation is a common, heterogeneous disorder with multiple symptoms and pathophysiological mechanisms. Patients are often referred to a gastroenterology provider after laxatives fail. However, there is limited knowledge of the spectrum and management of constipation disorders.

AIM: To discuss the latest understanding of the spectrum of constipation disorders, tools for identifying a pathophysiologic-based diagnosis in the specialist setting, treatment options and the patient's perspective of constipation.

METHODS: Literature searches were conducted using PubMed for constipation diagnostic criteria, diagnostic tools and approved treatments. The authors provided insight from their own practices.

RESULTS: Clinical assessment, stool diaries and Rome IV …

A Randomized Trial To Improve Adherence To Follow-Up Eye Examinations Among People With Glaucoma, Benjamin E Leiby, Sarah E. Hegarty, Tingting Zhan, Jonathan S Myers, L Jay Katz, Julia A Haller, Michael Waisbourd, Christine Burns, Meskerem Divers, Jeanne Molineaux, Jeffrey Henderer, Charles Brodowski, Lisa A Hark

Department of Pharmacology and Experimental Therapeutics Faculty Papers

INTRODUCTION: Appointment nonadherence is common among people with glaucoma, making it difficult for eye care providers to monitor glaucoma progression. Our objective was to determine whether the use of patient navigators, in conjunction with social worker support, could increase adherence to recommended follow-up eye appointments.

METHODS: A randomized, controlled trial evaluated the effectiveness of an intervention that used patient navigators and social workers to improve patient adherence to follow-up eye care compared with usual care. Participants with glaucoma and other eye diseases (N = 344) were identified at primary care clinics in community settings through telemedicine screening of imaging and …

Choline-Sigma-1r As An Additional Mechanism For Potentiation Of Orexin By Cocaine, Jeffrey Barr, Pingwei Zhao, G Cristina Brailoiu, Eugen Brailoiu

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Orexin A, an endogenous peptide involved in several functions including reward, acts via activation of orexin receptors OX₁ and OX₂, Gq-coupled GPCRs. We examined the effect of a selective OX₁ agonist, OXA (17-33) on cytosolic calcium concentration, [Ca²⁺ ]_i, in neurons of nucleus accumbens, an important area in the reward circuit. OXA (17-33) increased [Ca²⁺ ]_i in a dose-dependent manner; the effect was prevented by SB-334867, a selective OX₁ receptors antagonist. In Ca²⁺-free saline, the OXA (17-33)-induced increase in [Ca²⁺ ]_i was not affected by pretreatment …

Correlations Between Coffee Consumption And Metabolic Phenotypes, Plasma Folate, And Vitamin B12: Nhanes 2003 To 2006., Pratibha V Nerurkar, Krupa Gandhi, John J Chen

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Metabolic syndrome (MetS) is prevalent not only among the overweight and obese but also normal weight individuals, and the phenotype is referred to as a metabolically unhealthy phenotype (MUHP). Besides normal weight individuals, overweight/obese individuals are also protected from MetS, and the phenotype is known as a metabolically healthy phenotype (MHP). Epidemiological studies indicate that coffee and micronutrients such as plasma folate or vitamin B12 (vit. B12) are inversely associated with MetS. However, correlations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 remain unknown. Our objective was to investigate the correlation between coffee consumption, metabolic phenotypes, plasma folate, …

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 …

The Role Of Mirnas, Mirna Clusters, And Isomirs In Development Of Cancer Stem Cell Populations In Colorectal Cancer., Victoria A Stark, Caroline O B Facey, Vignesh Viswanathan, Bruce M Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) duringdevelopment and altered expression can cause developmental defects and/or disease. Indeed,aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has beenlinked to many cancers. Mounting evidence also indicates a role for miRNAs in the developmentof the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current researchon miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentiallyexpressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genesto influence CSC phenotype. Accordingly, we discuss …