Pharmacology Commons^™

Pediatric Beta Blocker Therapy: A Comprehensive Review Of Development And Genetic Variation To Guide Precision-Based Therapy In Children, Adolescents, And Young Adults., Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Beta adrenergic receptor antagonists, known as beta blockers, are one of the most prescribed medications in both pediatric and adult cardiology. Unfortunately, most of these agents utilized in the pediatric clinical setting are prescribed off-label. Despite regulatory efforts aimed at increasing pediatric drug labeling, a majority of pediatric cardiovascular drug agents continue to lack pediatric-specific data to inform precision dosing for children, adolescents, and young adults. Adding to this complexity is the contribution of development (ontogeny) and genetic variation towards the variability in drug disposition and response. In the absence of current prospective trials, the purpose of this comprehensive review …

The Effect Of Caffeine On Bee Behavior: A Progressive Ratio Study, Kayle Cohen, Becky Hansis-O'Neill, Aimee Dunlap Dr

Undergraduate Research Symposium

This presentation focuses on the effect of caffeine on bee behavior using behavioral pharmacology methodologies. Researchers trained bumblebees to drink out of artificial flowers, then administered sucrose nectar or caffeinated sucrose nectar during a schedule of progressive and fixed ratios. The finding suggests that caffeine did increase the number of rewards during the fixed ratio, but not in the progressive ratio. However, research is still ongoing as bees continue to be tested..

Photoluminescence Switching In Quantum Dots Connected With Fluorinated And Hydrogenated Photochromic Molecules, Ephraiem S. Sarabamoun, Jonathan M. Bietsch, Pramod Aryal, Amelia G. Reid, Maurice Curran, Grayson Johnson, Esther H. R. Tsai, Charles W. Machan, Guijun Wang, Joshua J. Choi

Chemistry & Biochemistry Faculty Publications

We investigate switching of photoluminescence (PL) from PbS quantum dots (QDs) crosslinked with two different types of photochromic diarylethene molecules, 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (1H) and 4,4'-(1-perfluorocyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (2F). Our results show that the QDs crosslinked with the hydrogenated molecule (1H) exhibit a greater amount of switching in photoluminescence intensity compared to QDs crosslinked with the fluorinated molecule (2F). With a combination of differential pulse voltammetry and density functional theory, we attribute the different amount of PL switching to the different energy levels between 1H and 2F molecules which result in different potential barrier …

Kinome Profiling Identifies Mark3 And Stk10 As Potential Therapeutic Targets In Uveal Melanoma, Usman Baqai, Alison M. Kurimchak, Isabella Trachtenberg, Timothy J. Purwin, Jelan I. Haj, Anna Han, Kristine Luo, Nikole Fandino Pachon, Angela Jeon, Vivian Chua, Michael A. Davies, J Silvio Gutkind, Jeffrey L. Benovic, James S. Duncan, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Most uveal melanoma cases harbor activating mutations in either GNAQ or GNA11. Despite activation of the mitogen-activated protein kinase (MAPK) signaling pathway downstream of Gαq/11, there are no effective targeted kinase therapies for metastatic uveal melanoma. The human genome encodes numerous understudied kinases, also called the "dark kinome". Identifying additional kinases regulated by Gαq/11 may uncover novel therapeutic targets for uveal melanoma. In this study, we treated GNAQ-mutant uveal melanoma cell lines with a Gαq/11 inhibitor, YM-254890, and conducted a kinase signaling proteomic screen using multiplexed-kinase inhibitors followed by mass spectrometry. We observed downregulated expression and/or activity of 22 kinases. …

Enteroendocrine Cell Regulation Of The Gut-Brain Axis, Joshua Barton, Annie Londregan, Tyler Alexander, Ariana Entezari, Manuel Covarrubias, Scott Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Enteroendocrine cells (EECs) are an essential interface between the gut and brain that communicate signals about nutrients, pain, and even information from our microbiome. EECs are hormone-producing cells expressed throughout the gastrointestinal epithelium and have been leveraged by pharmaceuticals like semaglutide (Ozempic, Wegovy), terzepatide (Mounjaro), and retatrutide (Phase 2) for diabetes and weight control, and linaclotide (Linzess) to treat irritable bowel syndrome (IBS) and visceral pain. This review focuses on role of intestinal EECs to communicate signals from the gut lumen to the brain. Canonically, EECs communicate information about the intestinal environment through a variety of hormones, dividing EECs into …

Self-Administered Intranasal Etripamil Using A Symptom-Prompted, Repeat-Dose Regimen For Atrioventricular-Nodal-Dependent Supraventricular Tachycardia (Rapid): A Multicentre, Randomised Trial, Bruce S Stambler, A John Camm, Marco Alings, Paul Dorian, Hein Heidbuchel, Jaco Houtgraaf, Peter R. Kowey, Jose L Merino, Blandine Mondésert, Jonathan P Piccini, Sean D Pokorney, Philip T Sager, Atul Verma, J Marcus Wharton, David B Bharucha, Francis Plat, Silvia Shardonofsky, Michael Chen, James E Ip

Department of Medicine Faculty Papers

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min.

METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes …

Neurological-Type Wilson Disease: Epidemiology, Clinical Manifestations, Diagnosis, And Management, Nathaniel Kipker, Kaitlyn Alessi, Marko Bojkovic, Inderbir Padda, Mayur S. Parmar

HPD Articles

Wilson disease (WD) is a complex metabolic disorder caused by disruptions to copper regulation within the body, leading to an unregulated accumulation of copper within various tissues. A less understood organ affected by the collection of copper is the brain, which further leads to the generation of oxygen-free radicals and resultant demyelination. Healthcare providers must keep the neurological form of WD in their list of differentials when patients present with diverse neurological manifestations. The initial step to diagnosis will be to distinguish the characteristic disease presentation with a thorough history and physical and neurological examination. A high clinical disease suspicion …

Abaloparatide, Miis Akel, Mayur Parmar

HPD Articles

No abstract provided.

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

Bazedoxifene, Parth M. Raina, Mayur Parmar

HPD Articles

No abstract provided.

Romosozumab, Kristina Krupa, Mayur Parmar, Linda F. Delo

HPD Articles

No abstract provided.

Dataset For Manuscript: Comparing Performance Of Spectral Image Analysis Approaches For Detection Of Cellular Signals In Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy, Silas J. Leavesley

BioImaging and BioSystems Research

The dataset contains raw and processed hyperspectral timelapse image data that are described in the manuscript:

Parker, M., Annamdevula, N. S., Pleshinger, D., Ijaz, Z., Jalkh, J., Penn, R., Deshpande, D., Rich, T. C. & Leavesley, S. J. Comparing Performance of Spectral Image Analysis Approaches for Detection of Cellular Signals in Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy. Bioengineering 10, 642 (2023).

Mitoq Alleviates Hippocampal Damage After Cerebral Ischemia: The Potential Role Of Sirt6 In Regulating Mitochondrial Dysfunction And Neuroinflammation, Ayman A. Ibrahim, Sherif S. Abdel Mageed Dr, Marwa M. Safar Prof.Dr, Mohammed F. El-Yamany Prof.Dr., Mamdouh A. Oraby Dr.

Pharmacy

Aims: Mitochondrial perturbations are the major culprit of the inflammatory response during the initial phase of cerebral ischemia. The present study explored the neuroprotective effect of the mitochondrial-targeted antioxidant, Mitoquinol (MitoQ), against hippocampal neuronal loss in an experimental model of brain ischemia/ reperfusion (I/R) injury. Main methods: Rats were subjected to common carotid artery occlusion for 45 min, followed by reperfusion for 24 h. MitoQ (2 mg/kg; i.p daily) was administered for 7 successive days prior to the induction of brain ischemia. Key findings: I/R rats exhibited hippocampal damage evidenced by aggravated mitochondrial oxidative stress, thereby enhancing mtROS and oxidized …

Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov

Bioelectrics Publications

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two …

Developmental Pharmacokinetics Of Indomethacin In Preterm Neonates: Severely Decreased Drug Clearance In The First Week Of Life., Wojciech Krzyzanski, Bradley Stockard, Andrea Gaedigk, Allison Scott, Whitney M. Nolte, Kim T. Gibson, J Steven Leeder, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently …

A Case Of Transverse Myelitis Secondary To Covid-19 Infection, Rahul Borra, Neal T. Patel, Raheel Shaikh, Mayur S. Parmar, Sujatha Borra

HPD Articles

Infection with COVID-19 (SARS-CoV-2) is associated with a variety of generalized and specific symptoms, including neurological complications of both the peripheral and central nervous systems. In this case report, we present the case of a previously healthy 55-year-old woman who was diagnosed with transverse myelitis following a previous infection with COVID-19. MRI showed progressive demyelination of the cervical and thoracic spinal cord, and cerebrospinal fluid (CSF) showed increased levels of protein and red blood cells and no markers of infection, including negative polymerase chain reaction (PCR) for COVID-19 antibodies. The patient was treated with a course of methylprednisolone, multiple treatments …

Poststroke Seizure And Epilepsy: A Review Of Incidence, Risk Factors, Diagnosis, Pathophysiology, And Pharmacological Therapies, Joseph Phan, Mario Ramos, Theodore Soares, Mayur S. Parmar

HPD Articles

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase …

Seasonal Affective Disorder Treatment: Light Therapy Versus Ssri Therapy, Gabriella M. Hinde, Hannah Dyer, Ash Werner, Michaela Cisowski

Non-Thesis Student Work

To determine the effect of pharmacological and nonpharmacological treatments for seasonal depression in college students, we asked the following evidence-based PICO question: In college students (ages 18-25) with seasonal affective disorder (SAD), how does SSRI (Selective Serotonin Reuptake Inhibitor) therapy compared to light therapy affect seasonal depression syndrome? Seasonal affective disorder is synonymously used with the terminology seasonal depression due to the clinical manifestations that encompass depression, such as low energy, feelings of sadness, emptiness, or hopelessness. SAD begins in the fall months and peaks in the winter months due to a decrease in Vitamin D and ultraviolet (UV) ray …

Effects Of Covid-19 On Pregnant Women And Newborns: A Review, Bhavesh M. Patel, Deepesh Khanna, Siya Khanna, Vera Hapshy, Pragya Khanna, Payal Kahar, Mayur S. Parmar

HPD Articles

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus originated in Wuhan, China, and spread all over the world, causing the worst pandemic of the century. The disease has a broad continuum of clinical presentations, from mild to life-threatening. The virus is highly contagious and transmittable to humans. Emerging evidence of its effects on pregnant women and newborns is inconsistent and ever-evolving. Therefore, the objective of this review is to compile the scientific literature on the effects of SARS-CoV-2 coronavirus on pregnancy, pregnant women, and newborns. Data were obtained by several authors using PubMed, MEDLINE, Google Scholar, and Web …

Pharmacological Interventions For The Treatment And Control Of Shivering In Adult Patients Undergoing Elective Surgery Under Regional Anaesthesia: A Systematic Review And Meta-Analysis, Malika Hameed, Naureen Akber Ali, Khalid Ahsan, Mohsin Nazir

Department of Anaesthesia

Intraoperative shivering is quite common after regional anaesthesia, which not only increases the total body oxygen requirement but also causes discomfort to the patients. The aim of this systematic review is to determine the effectiveness of pharmacological agents administered intra-operatively for treating shivering in adult patients who are undergoing elective surgery under regional (i.e., central neuraxial) anaesthesia so that an optimal choice of an agent can be recommended for clinical application. A literature search was carried out using PubMed, Cochrane Library, CINAHL databases, and hand searches to identify relevant studies. After literature screening and information extraction, a systematic review was …

A Review Of Covid-19 In Relation To Metabolic Syndrome: Obesity, Hypertension, Diabetes, And Dyslipidemia, Elias Makhoul, Joseph L. Aklinski, Jesse Miller, Cara Leonard, Sean Backer, Payal Kahar, Mayur S. Parmar, Deepesh Khanna

HPD Articles

Although severe cases and mortality of coronavirus disease 2019 (COVID-19) are proportionally infrequent, these cases are strongly linked to patients with conditions of metabolic syndrome (obesity, hypertension, diabetes, and dyslipidemia). However, the pathophysiology of COVID-19 in relation to metabolic syndrome is not well understood. Thus, the goal of this secondary literature review was to examine the relationship between severe acute respiratory syndrome (SARS-CoV-2) infection and the individual conditions of metabolic syndrome. The objective of this secondary literature review was achieved by examining primary studies, case studies, and other secondary studies, to obtain a comprehensive perspective of theories and observations of …

Generation Of A More Immunogenic Fh Vlp Platform To Support Covid-19 Vaccine Development, Jewel E. Voyer, Xinyuan Chen Phd.

Senior Honors Projects

The SARS-CoV-2 based pandemic has seen almost a million deaths in just the United States according to the CDC. This number is due to the increase of variants of COVID-19, therefore calling a demand in vaccine production. Vaccine adjuvants and carriers have been studied to increase the immunogenicity and safety of a variety of immunizations. Flagellin fused Hepatitis B core (FH) virus like particles (VLP) has been studied to have beneficial effects of TLR5, IL6 levels, and lack of body temperature rise in murine study. The FH platform also provides an improvement from its predecessors FljB alone which is a …

Regaining Effort-Based Food Motivation: The Drug Methylphenidate Reverses The Depressive Effects Of Tetrabenazine In Female Rats, Deanna Pietrorazio

Honors Scholar Theses

Tetrabenazine (TBZ), a vesicular monoamine transporter type 2 (VMAT-2) inhibitor, depletes dopamine and induces motivational deficits and other depressive symptoms in humans. Methylphenidate (MPH) is a dopamine transport blocker that is used to enhance motivational function. Previous studies have shown that in male rats, TBZ induces a shift in effort-related choice such that a low-effort bias is induced. In male rats this occurs at a dose range of 0.75-1.0 mg/kg TBZ, and this effect is reversible with co-administration of MPH. Recent studies have shown that females need a higher dose of TBZ (2.0 mg/kg) to show the low-effort bias. The …

Buprenorphine Effects On Anxiety-Like Behavior In B6 Mice, Megan K. Thibert

Select or Award-Winning Individual Scholarship

Buprenorphine, a semi-synthetic opioid prescribed for the treatment of opioid use disorder (OUD), has been suggested as a potential pharmacological treatment for anxiety. Some preclinical and clinical studies provide support for the anxiolytic effects of buprenorphine, but research in this area is scarce, and findings to date have been mixed. The present study was designed to test the hypothesis that buprenorphine alters anxiety-like behavior in C57BL/IJ (B6) mice measured using the elevated zero maze (EZM). Adult, male mice (n=10) were given subcutaneous injections of saline (control) and three doses of buprenorphine (0.3, 1, and 10 mg/kg). One hour following injection, …

The Efficacy And Safety Of Roxadustat For The Treatment Of Anemia In Non-Dialysis Dependent Chronic Kidney Disease Patients: An Updated Systematic Review And Meta-Analysis Of Randomized Clinical Trials, Basel Abdelazeem, Joseph Shehata, Kirellos Said Abbas, Nahla Ahmed El-Shahat, Bilal Malik, Pramod Savarapu, Mostafa Eltobgy, Arvind Kunadi

School of Medicine Faculty Publications

Background Roxadustat (ROX) is a new medication for anemia as a complication of chronic kidney disease (CKD). Our meta-analysis aims to evaluate the efficacy and safety of ROX, especially on the cardiovascular risks, for anemia in NDD-CKD patients. Methods Electronic databases were searched systematically from inception to July 2021 to look for randomized control trials (RCTs) that evaluated ROX NDD-CKD patients. Hemoglobin level and iron utilization parameters, including ferritin, serum iron, transferrin saturation (TSAT), total iron-binding capacity (TIBC), transferrin, and hepcidin were analyzed for efficacy. Pooled risk ratios (RRs) and standardized mean differences (SMDs) were calculated and presented with their …

Body Mass Index (Bmi): A Screening Tool Analysis, Deepesh Khanna, Cadynce Peltzer, Payal Kahar, Mayur S. Parmar

HPD Articles

Body mass index (BMI), a measurement based on a person's height and weight, allows the classification of individuals into categories such as obese or overweight. With these classifications, we can assess risk for hypertension, diabetes, cancer, hypercholesterolemia, and other chronic diseases. Furthermore, childhood BMI serves as a prediction method for health and disease later in life. Along with BMI, researchers also study waist circumference and waist-to-hip ratio in correlation with the above-mentioned chronic illnesses. This brief review explores the associations between body mass index, waist circumference, and the waist-hip ratio as measurements and their capability as predictors for persistent conditions …

Small Interfering Rna (Sirna)-Based Therapy, Inderbir S. Padda, Arun U. Mahtani, Mayur S. Parmar

HPD Articles

No abstract provided.

Golimumab, Inderbir S. Padda, Rajat Bhatt, Mayur S. Parmar

HPD Articles

No abstract provided.

Sodium-Glucose Transport Protein 2 (Sglt2) Inhibitors, Inderbir S. Padda, Arun U. Mahtani, Mayur S. Parmar

HPD Articles

No abstract provided.

Poststroke Seizure And Epilepsy: A Review Of Incidence, Risk Factors, Diagnosis, Pathophysiology, And Pharmacological Therapies, Joseph Phan, Mario Ramos, Theodore Soares, Mayur S. Parmar

HPD Articles

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.