Chemicals and Drugs Commons^™

Differential Cortical Monoamines Release During Exercise In Rats Chronically Implanted With Microdialysis Probes, Christine G. Gerin

Research Symposium

Physical exercise is known to positively influence mood, to reduce anxiety and to improve reaction to stress. Cerebral monoaminergic systems are thought to underly the neurochemical influence of exercise on mood and behavior. We hypothesized that beneficial effects of exercise can be shown by variations of neurotransmitters release in the cerebral cortex. We aimed at demonstrating that there is a temporal relationship between release of plasma and cerebral monoamines (A, NA, 5-HT, DA) and spontaneous running exercise in rats. Ten Spague Dawley rats (250 g) were chronically implanted (for up to 39 days) with a left common carotid cannula and …

Circulating Endocannabinoids And N-Acylethanolamines In Individuals With Cannabis Use Disorder-Preliminary Findings, Nadia Boachie, Erin Gaudette, Richard P. Bazinet, Lin Lin, Rachel F. Tyndale, Esmaeil Mansouri, Marilyn A. Huestis, Junchao Tong, Bernard Le Foll, Stephen J. Kish, Tony P. George, Isabelle Boileau

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain.

METHODS: Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography-mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which …

Exploring Conformational Landscapes And Cryptic Binding Pockets In Distinct Functional States Of The Sars-Cov-2 Omicron Ba.1 And Ba.2 Trimers: Mutation-Induced Modulation Of Protein Dynamics And Network-Guided Prediction Of Variant-Specific Allosteric Binding Sites, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

A significant body of experimental structures of SARS-CoV-2 spike trimers for the BA.1 and BA.2 variants revealed a considerable plasticity of the spike protein and the emergence of druggable binding pockets. Understanding the interplay of conformational dynamics changes induced by the Omicron variants and the identification of cryptic dynamic binding pockets in the S protein is of paramount importance as exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In the current study, we explore conformational landscapes and characterize the universe of binding pockets in multiple open and closed functional spike states of the BA.1 and BA.2 Omicron …

Oral Dosages Of The Nsaid Aspirin Decreased The Growth Rate Of Species Found In The Human Gut Microbiome Including Akkermansia Muciniphila, Bacteroides Fragilis, Clostridium Sordellii, And Clostridium Difficile, Wyatt H. Greenbaum, Garrett J. Greenbaum, Anna Spiezio

PANDION: The Osprey Journal of Research and Ideas

Over past few decades, new insight has been revealed in the scientific community about the importance of the human gut microbiome relating to general health. It is known that imbalances in the species that reside in the human gut can cause organism-wide problems in humans. When prescribing or injecting oral medications, the thought of the downstream effects on the gut microbiome are not always considered. By exposing known healthy members of the gut; Akkermansia muciniphila, Bacteroides fragilis, Clostridium sordellii, and Clostridium difficile to the Aspirin, this study attempted to provide insight into the effects of the drug on bacterial growth. …

Editorial: Sex Differences In The Neurobiology Of Drug Relapse Vulnerability, Daniel F Manvich, Jessica A Loweth, Wendy J Lynch, Jayme R Mcreynolds

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

No abstract provided.

Protein S Antibody As An Adjunct Therapy For Hemophilia B, Hope P. Wilson, Aliyah Pierre, Ashley L. Paysse, Narender Kumar, Brian C. Cooley, Pratyadipta Rudra, Adrianne W. Dorsey, Diana Polania-Villanueva, Sabyasachi Chatterjee, Maissaa Janbain, Maria C. Velez, Rinku Majumder

School of Medicine Faculty Publications

ABSTRACT: Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (< 1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.

All-Cause And Opioid-Related Mortality Compared Between Traumatic Spinal Cord Injury And The Us General Population, Jaden Whitehead, Beatrice Ugiliweneza

The Cardinal Edge

Individuals with spinal cord injury (SCI) are susceptible to the misuse of opioids due to the introduction of these substances for pain management. There are very few studies examining the relationship between unintentional deaths caused by opioid usage following spinal cord injury. The objective of this study was to evaluate the trend of opioid-related mortality of individuals with spinal cord injury (SCI) over the years and compare these findings to the mortality rates due to opioid misuse in the general population. In this study, we used data provided by the National Spinal Cord Injury Model Systems (NSCIMS) for SCI 1999-2016 …

Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in …

Association Between Number Of Vasopressors And Mortality In Covid-19 Patients, Michael Sunnaa, Mina Kerolos, Max Ruge, Ahmad Gill, Jeanne M. Du-Fay-De-Lavallaz, Perry Robin, Joanne Michelle Dumlao Gomez, Kim Williams, Anupama Rao, Annabelle Santos Volgman, Karolina Marinescu, Tisha Marie Suboc

COVID-19 Papers, Posters, and Presentations

Study objective

Study the clinical outcomes associated with the number of concomitant vasopressors used in critically ill COVID-19 patients.

Design

A single-center retrospective cohort study was conducted on patients admitted with COVID-19 to the intensive care unit (ICU) between March and October 2020.

Setting

Rush University Medical Center, United States.

Participants

Adult patients at least 18 years old with COVID-19 with continuous infusion of any vasopressors were included.

Main outcome measures

60-day mortality in COVID-19 patients by the number of concurrent vasopressors received.

Results

A total of 637 patients met our inclusion criteria, of whom 338 (53.1 %) required the …

Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu

School of Medicine Faculty Publications

Background: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease. Methods: Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. …

Development Of A Sensitive Microplate Assay For Characterizing Rna Methyltransferase Activity: Implications For Epitranscriptomics And Drug Development, Isaiah K. Mensah, Allison B. Norvil, Ming He, Emma Lendy, Nicole Hjortland, Hern Tan, Richard T. Pomerantz, Andrew Mesecar, Humaira Gowher

Department of Biochemistry and Molecular Biology Faculty Papers

RNA methylation is a ubiquitous post-transcriptional modification found in diverse RNA classes and is a critical regulator of gene expression. In this study, we used Zika virus RNA methyltransferase (MTase) to develop a highly sensitive microplate assay that uses a biotinylated RNA substrate and radiolabeled AdoMet coenzyme. The assay is fast, highly reproducible, exhibits linear progress-curve kinetics under multiple turnover conditions, has high sensitivity in competitive inhibition assays, and significantly lower background levels compared with the currently used method. Using our newly developed microplate assay, we observed no significant difference in the catalytic constants of the full-length nonstructural protein 5 …

Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal

The Undergraduate Research Journal

Diadema savignyi spine extract in an experimental setup using L929 cell line in vitro. The cell metabolic activity of L929 cells is tested through an MTT assay. The sea urchin spine extract is applied to the cells in two concentrations: 100 μg/ml (136% viability) and 200 μg/ml (95% viability). The bioactive components of the sea urchin spine are identified via GC-MS, and the antioxidant and anti-inflammatory activities are evaluated using catalase assay (CAT), glutathione (GSH), and nitric oxide (NO) tests. Results show that the GC-MS identified bioactive components including the anti-inflammatory and anti-irritant bisabolol oxide and the pro-inflammatory oleic acid. …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …

Effect Of Caffeine In Pattern Memory And Reaction Time Test Among College Students, William T. Clark, Micheal Lawson, Garrett Garnto, Evan Smith, Kelly Massey

International Undergraduate Journal of Health Sciences

Caffeine is commonly used by college students to aid in staying alert throughout the day. The purpose of this study was to determine the effects of caffeine on visual memory and reaction time performance on college students aged 18-25 years old. The Human Benchmark (https://humanbenchmark.com) Visual Memory (VM) and Reaction Time (RT) tests were used to assess participant’s baseline scores and scores 15min post treatment. Five male (19.0y ± 1.26) and four female (20.3y ± 0.43) college students volunteered to be participants in a three-week long cross-over, counterbalanced study. Blood pressure (BP) and heart rate (HR) were assessed before each …

Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa

Pharmacy

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and …

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan

School of Medicine Faculty Publications

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …

The Noloco Strategy For Essential Hypertension, F. Matthew Mihelic Md

Faculty Publications

Ninety-nine percent of all “essential” hypertension can be controlled by using the NoLoCo strategy, without causing any significant side-effects and without an increase in insulin resistance. NoLoCo stands for Norvasc (amlodipine), Lozol (indapamide), and Cozaar (losartan), but the medicines are considered and used in reverse order.

Environmental Isolate Developing Antibiotic Resistance By Complementation, Mary Ridgeway, Ashley Fink, David Mitchell

Biology Faculty Publications

Antibiotic resistance is a growing concern within the scientific community. With few new antibiotics being introduced and an increasing number of resistant microbes, routine bacterial infections are becoming more difficult to treat in clinics and hospitals. The purpose of this study is to compare the ability of two environmental isolates – Staphylococcus aureus (S. aureus) and Exiguobacterium undae (E. undae) to grow in solutions of increasing concentrations of tetracycline and ciprofloxacin. After the bacteria showed grow in the solutions, antibiotic susceptibility was tested by examining zones of inhibition on Trypticase Soy Agar (TSA) plates. Our results …

Nanodiscs: A Novel Approach To The Study Of The Methionine Abc Transporter System, Michael T. Winslow

Master's Theses

Membrane transporter proteins play the vital role of moving compounds in and out of the cell and are essential for all living organisms. ATP Binding Cassette (ABC) family transporters function both as importers and exporters in prokaryotes. MetNI is an E. coli Type I ABC transporter responsible for the uptake of methionine into the cytosol from the cell periplasmic space through the cell membrane to maintain intracellular methionine pools. ABC transporters, like other membrane proteins, are most often mechanistically and structurally studied in vitro, solubilized by detergents. However, detergent micelles may affect the conformational changes of membrane proteins relative to …

Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec

School of Medicine Faculty Publications

Background: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. …