Medical Pharmacology Commons^™

The Effect Of Β-Caryophyllene On Isoproterenol-Induced Myocardial Infarction, Farah M. Jamal Laham

Theses

Cannabinoid type 2 receptors (CB2), a key member of the endocannabinoid system have recently emerged as a crucial therapeutic target for cardiovascular diseases (CVDs). Downregulation of CB2 receptors has been witnessed in various cancers, neurological and cardiovascular disorders. Thus, the activation of CB2 receptors may protect against ISO-induced myocardial infarction (MI) in rats. The present study investigates the cardioprotective effect of a selective cannabinoid type 2 receptor agonist β-caryophyllene (BCP), a dietary phytocannabinoid, and a natural bicyclic sesquiterpene against isoproterenol (ISO)-induced MI in rats. Male albino Wistar rats were pre-and co-treated with β-caryophyllene (50 mg/kg, orally) twice daily for 10 …

Neuroligin-1 Is Altered In The Hippocampus Of Alzheimer's Disease Patients And Mouse Models, And Modulates The Toxicity Of Amyloid-Beta Oligomers, Julien Dufort-Gervais, Chloé Provost, Laurence Charbonneau, Christopher M. Norris, Frédéric Calon, Valérie Mongrain, Jonathan Brouillette

Pharmacology and Nutritional Sciences Faculty Publications

Synapse loss occurs early and correlates with cognitive decline in Alzheimer’s disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (Aβo), but the exact synaptic components targeted by Aβo remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in the process of neurodegeneration in the hippocampus, and specifically by Aβo, and that it can modulate Aβo toxicity. We found that hippocampal NLGN1 was decreased in patients with AD in comparison to patients with mild cognitive impairment and control subjects. Female 3xTg-AD mice also showed a decreased NLGN1 level …

Adverse Aftereffects Of Methotrexate As Chemotherapy On Cognitive Deficits In Rat Models, Jubin Kang

Senior Honors Theses

Patients with acute lymphoblastic leukemia have a high five-year survival rate thanks to methotrexate (MTX). However, cognitive side effects are reported, characterized as chemo brain. The study investigated if impulsiveness is part of the aberrant cognitive functions after being exposed to MTX in the early stage of physical development. Adolescent rats were injected with either phosphate-buffered saline (PBS) or MTX. The novel object recognition (NOR) task was conducted a month after the injections to measure the memory deficits. The discounting task was performed after the rats completed training on a fixed-ratio one schedule for both levers. The NOR test showed …

Modulator Therapy For Cystic Fibrosis: An Exploration Of Current Research, Jessalyn Rombocos

Senior Honors Theses

Developing a drug therapy that addresses the root cause of cystic fibrosis (CF) by increasing CFTR protein levels has long been a research challenge. After genetic therapy failed because a suitable delivery system could not be found, researchers began searching for small organic molecules that could act as chaperones for CFTR. These molecules, known as modulators, allowed CFTR to be assembled correctly and function similarly to wild type CFTR. Since 2012, four modulator drugs have been developed, tested, and approved by the FDA. In October 2019, Trikafta was approved as the first triple-combination modulator drug and has completely revolutionized CF …

Biological Sex Influences Susceptibility To Acinetobacter Baumannii Pneumonia In Mice, Sílvia Pires, Adeline Peignier, Jeremy Seto, Davida S. Smyth, Dane Parker

Publications and Research

Acinetobacter baumannii (A. baumannii) is an extremely versatile multidrug-resistant pathogen with a very high mortality rate; therefore, it has become crucial to understand the host response during its infection. Given the importance of mice for modeling infection and their role in preclinical drug development, equal emphasis should be placed on the use of both sexes. Through our studies using a murine model of acute pneumonia with A. baumannii, we observed that female mice were more susceptible to infection. Likewise, treatment of male mice with estradiol increased their susceptibility to infection. Analysis of the airway compartment revealed enhanced inflammation and reduced …

Integrated Multimodal Genomic Analyses Reveal Novel Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukemia, Robert J. Autry

Theses and Dissertations (ETD)

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Much has been discovered in recent decades regarding ALL biology, and the outcome of patients with ALL has vastly improved, especially in pediatric ALL patients. Despite very promising overall cure rates, patients who relapse have a greatly decreased prognosis with survival rates ranging from 30-60%. These numbers stand to improve even further with new targeted therapies that seek to improve or maintain cure rates while reducing treatment related toxicities which affect patients both acutely and chronically. Glucocorticoids (GCs) are essential components of modern chemotherapeutic intervention for ALL. Resistance to glucocorticoids …

H-Discrete Fractional Model Of Tumor Growth And Anticancer Effects Of Mono And Combination Therapies, Kamala Dadashova

Masters Theses & Specialist Projects

In this thesis, we focus on h–discrete and h–discrete fractional representation of a pharmacokinetics-pharmacodynamics (PK-PD) model which describes tumor growth considering time on hNa, where h>0. First, we introduce some definitions, lemmas and theorems on both h–discrete and h–discrete fractional calculus in the preliminary section. In Chapter 3, we work on the PD model with delay by exam ining nabla h–discrete equations and nabla h–discrete fractional equations as well as variation of constants formulas, accordingly. We introduce our model and solve it using theorems we proved in the last section of the indicated chapter. When we do simulation for …

Renal Safety And Racial Disparity In Patients On Antiviral Treatment For Chronic Hepatitis B, Matthew Miller, Sindhuri Benjaram, Raya Kutaimy, Paul Naylor, Elizabeth May, Murray Ehrinpreis, Milton Mutchnick

Medical Student Research Symposium

Background:

Many African Americans (AA) are chronically infected with Hepatitis B (HBV). While antiviral therapy is highly effective, clinical trials suggest a treatment-related decline in kidney function is possible. Given that chronic HBV predominately affects Asians worldwide, most studies have contained few AA patients. We evaluated these treatment-related kidney function changes in our predominately AA patient population.

Methods:

From 225 HBV patients, we identified 42 patients who were not co-infected with HIV or HCV, had a recent visit, and at least one earlier visit (before Jan 2017). If on treatment with antivirals it must have been for at least 2 …

Vancomycin In Peritoneal Dialysis: Clinical Pharmacology Considerations In Therapy., Edwin Lam, Yi Ting Kayla Lien, Walter K. Kraft, Beth Piraino, Valvanera Vozmediano, Stephan Schmidt, Jingjing Zhang

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Intraperitoneal vancomycin is the first-line therapy in the management of peritoneal dialysis (PD)-related peritonitis. However, due to the paucity of data, vancomycin dosing for peritonitis in patients on automated peritoneal dialysis (APD) is empiric and based on clinical experience rather than evidence. Studies in continuous ambulatory peritoneal dialysis (CAPD) patients have been used to provide guidelines for dosing and are often extrapolated for APD use, but it is unclear whether this is appropriate. This review summarizes the available pharmacokinetic data used to inform optimal dosing in patients on CAPD or APD. The determinants of vancomycin disposition and pharmacodynamic effects are …

Plasmodium Falciparum Resistance To A Lead Benzoxaborole Due To Blocked Compound Activation And Altered Ubiquitination Or Sumoylation., Kirthana M. V. Sindhe, Wesley Wu, Jenny Legac, Yong-Kang Zhang, Eric E. Easom, Roland A. Cooper, Jacob J. Plattner, Yvonne R. Freund, Joseph L. Derisi, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

New antimalarial drugs are needed. The benzoxaborole AN13762 showed excellent activity against cultured Plasmodium falciparum, against fresh Ugandan P. falciparum isolates, and in murine malaria models. To gain mechanistic insights, we selected in vitro for P. falciparum isolates resistant to AN13762. In all of 11 independent selections with 100 to 200 nM AN13762, the 50% inhibitory concentration (IC50) increased from 18-118 nM to 180-890 nM, and whole-genome sequencing of resistant parasites demonstrated mutations in prodrug activation and resistance esterase (PfPARE). The introduction of PfPARE mutations led to a similar level of resistance, and recombinant PfPARE hydrolyzed AN13762 to the benzoxaborole …

Hypercholesterolemia Accelerates Both The Initiation And Progression Of Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Jing Liu, Hisashi Sawada, Deborah A. Howatt, Jessica J. Moorleghen, Olga A. Vsevolozhskaya, Alan Daugherty, Hong S. Lu

Pharmacology and Nutritional Sciences Faculty Publications

Objective: This study determined whether hypercholesterolemia would contribute to both the initiation and progression of angiotensin (Ang)II-induced abdominal aortic aneurysms (AAAs) in mice.

Methods and Results: To determine whether hypercholesterolemia accelerates the initiation of AAAs, male low-density lipoprotein (LDL) receptor -/- mice were either fed one week of Western diet prior to starting AngII infusion or initiated Western diet one week after starting AngII infusion. During the first week of AngII infusion, mice fed normal diet had less luminal expansion of the suprarenal aorta compared to those initiated Western diet after the first week of AngII infusion. The two groups …

Generation Of In-Frame Gene Deletion Mutants In Pseudomonas Aeruginosa And Testing For Virulence Attenuation In A Simple Mouse Model Of Infection, Meagan E. Valentine, Brandon D. Kirby, Hongwei D. Yu

Biomedical Sciences

Microorganisms are genetically versatile and diverse and have become a major source of many commercial products and biopharmaceuticals. Though some of these products are naturally produced by the organisms, other products require genetic engineering of the organism to increase the yields of production. Avirulent strains of Escherichia coli have traditionally been the preferred bacterial species for producing biopharmaceuticals; however, some products are difficult for E. coli to produce. Thus, avirulent strains of other bacterial species could provide useful alternatives for production of some commercial products. Pseudomonas eruginosa is a common and well-studied Gram-negative bacterium that could provide a suitable alternative …

A Phantom Of The Past: Withdrawal From Meprobamate Presenting With Focal Seizures., Thomas M. Zink, John E. Erickson

Journal of Maine Medical Center

Introduction: Meprobamate (Miltown, Equinil) is a sedative-hypnotic medication that first gained popularity as an anxiolytic and later as a muscle relaxant. It is a major metabolite of the more commonly used muscle relaxant carisoprodol (Soma). In vitro and electroencephalogram studies demonstrated that meprobamate modulates gama-aminobutyric acid (GABA) receptors, similar to barbiturates. Withdrawal from meprobamate manifests in symptoms ranging from mild anxiety to severe autonomic instability and death. Meprobamate is rarely prescribed, but is still given to a small subset of elderly patients.

Clinical findings: In this case of meprobamate withdrawal, the patient initially displayed altered mental status and recurrent seizures …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Manipulation Of Ar-V7 In Castrate Resistant Prostate Cancer, Sean Simpson

Capstone Showcase

Abstract

Introduction: Prostate cancer is the leading cancer affecting men of all races in the United States, and the second leading cause of cancer death in men. If caught early, many have had success in combating the disease, but if the cancer metastasizes, the 5-year survival rate drops to only 30%. Current treatment options heavily involve hormone therapy, radiation therapy, chemotherapy, and surgery. While these treatments can be effective for early stage prostate cancer, they can fall short in preventing the spread of the cancer to other parts of the body. This review analyzes a new potential way of preventing …

The Efficacy Of Ketamine In Adult Patients With Obsessive Compulsive Disorder With Symptoms Refractory To Standard Of Care Treatment., Brooke Thornton

Capstone Showcase

First line pharmacologic treatments for adult patients with Obsessive Compulsive Disorder (OCD) involve selective serotonin/norepinephrine reuptake inhibitors (SSRI/SNRIs). These drug classes often fail to deliver timely relief of symptoms as well as maintain longevity of symptom recurrence. This research analyzed the use of ketamine in adult patients suffering with OCD for the purposes of more efficacious management of symptoms. Although ketamine demonstrated a timelier relief of symptoms in some small clinical studies, its effects were ultimately unable to be sustained long term. Additionally, a wide range of adverse effects including dissociation, and rebound symptoms were observed. As a result, large …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Ketamine Vs Placebo For Depression, Austin Strosser

Capstone Showcase

Depression is a disease that effects millions of patients and has a variety of symptoms. It is primarily defined by depressed mood and anhedonia. The first line treatment for depression is SSRI medications. These medications have several side effects and are not effective for a large number of patients. Therefore, this study was done to review ketamine as a new treatment option for depression and see how it compares to a placebo.

Alkalinizing Agents: A Review Of Prescription, Over-The-Counter, And Medical Food Supplements., Karen L. Stern, Noah Canvasser, Michael Borofsky, Vanessa M. Gleason, Guido Kamphuis, Marawan M. El Tayeb, Ryan Hsi, Kymora B. Scotland

Jefferson Hospital Staff Papers and Presentations

Introduction

Kidney stones affect 1 in every 11 people in the United States each year. There is a significant high recurrence rate without a stone prevention protocol. Alkali citrate is beneficial in decreasing stone recurrence, but due to the cost and gastrointestinal side effects there is a low adherence rate. This study aims to serve as a review of some of the most commonly used alkalizing over‐ the‐ counter supplements that are advertised to prevent and treat kidney stones.

Methods

Data was gathered by a comprehensive online literature search and company inquiries for kidney stone prevention supplements. An additional informal …

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee

Theses and Dissertations

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Although standard treatments such as androgen deprivation therapies (ADT) and antiandrogens have increased survival for many patients, most men placed on these therapies will develop castration-resistant disease (CRPC). Previous studies have shown that these treatments have limited cytotoxicity and instead promote cell growth arrest. Our current work demonstrates that prostate tumor cells grown in the absence of androgens by using charcoal-stripped serum undergo senescence-mediated or senescent-like growth arrest, based on the cellular expression of senescence-associated-beta-galactosidase (SA-β-Gal). Our studies further suggest that this senescence is transient and …