Cardiovascular Diseases Commons^™

Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

"Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There are already ATMPs under …

Impact Of Contemporary Low Dose Aspirin Use And Cardiovascular Disease, Pratik Sharma, Ramona Stone

Public Health Sciences Student Work

No abstract provided.

Diuretic And Natriuretic Activity Of Faah Inhibition In The Renal Medulla: A Proposed Role Of Palmitoylethanolamide And Its Regulation By Renal Medullary Interstitial Cells, Sara Dempsey

Theses and Dissertations

Hypertension is a critical public health issue worldwide, and in the United States, it is the leading cause of heart disease, stroke, and kidney failure, contributing to more than 1,100 deaths per day. It is proposed that the renal medulla combats increased blood pressure by releasing a neutral lipid from the lipid droplets of medullary interstitial cells, termed medullipin, which induces diuresis- natriuresis and vasodepression. The renal medulla is enriched with fatty acid lipid ethanolamides including the endocannabinoid anandamide (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA), along with their primary hydrolyzing enzyme fatty acid amide hydrolase (FAAH). Our lab is investigating …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Psychological Well-Being And Restorative Biological Processes: Hdl-C In Older English Adults, Jackie Soo, Laura D. Kubzansky, Ying Chen, Emily S. Zevon, Julia K. Boehm

Psychology Faculty Articles and Research

Rationale

Psychological well-being is associated with better cardiovascular health, but the underlying mechanisms are unclear.

Objective

This study investigates one possible mechanism by examining psychological well-being's prospective association with lipid levels, focusing on high-density lipoprotein cholesterol (HDL-C).

Methods

Participants were 4757 healthy men and women ages ≥50 from the English Longitudinal Study of Ageing with clinical data from three times, three to five years apart. Psychological well-being was assessed at baseline using the Control, Autonomy, Satisfaction, and Pleasure scale; HDL-C, triglycerides, and total cholesterol were assayed from blood samples. Descriptive statistics and linear mixed models were used to examine associations …

Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake

Honors Scholar Theses

Peripheral artery disease is one of the most prevalent cardiovascular diseases in the United States and worldwide. It is estimated that over 8 million people in the United States are affected with peripheral artery disease, and up to 40% of people over 80 years old may have some degree of the disease. Peripheral artery disease can increase one’s chances for having other cardiovascular co-morbidities such as coronary artery disease, among others. Current interventional strategies are endovascular treatments such as transluminal angioplasty and stenting, or in more advanced cases peripheral artery bypass grafting. Medical interventions focus on managing symptoms and treating …

Cost-Effectiveness Of Alternative Anticoagulation Strategies For Postoperative Management Of Total Knee Arthroplasty Patients, Savannah R. Smith, Jeffrey Katz, Elena Losina

GW Research Days 2016 - 2020

Background: Anticoagulation is essential for deep vein thrombosis (DVT) and pulmonary embolism (PE) prevention following total knee arthroplasty (TKA). Some research has suggested that longer duration anticoagulation can substantially reduce the risks of DVT and PE; however, in the absence of definitive recommendations, physicians are left weighing the risks of DVT and PE against those of anticoagulation, including gastrointestinal (GI) and central nervous system (CNS) hemorrhage and increased likelihood of prosthetic joint infection (PJI). We conducted a cost-effectiveness analysis to evaluate the benefits and risks of 14- and 35-day therapy with the most commonly prescribed anticoagulants post-TKA.

Background: Anticoagulation is …

Acute Hepatic Failure And Oral Amiodarone, Hani Alhamoud, Sivateja Mandava, Talal Alzahrani

GW Research Days 2016 - 2020

Introduction:

Amiodarone is associated with serious complications such as lung toxicity, thyroid dysfunction, and QT-prolongation. Further, hepatic failure from the intravenous (IV) formulation of amiodarone is described in numerous case reports and case series. Although there are reports of elevated liver enzymes from the oral formulation of amiodarone, to our knowledge, none have definitively identified a case of acute hepatic failure from the oral formulation alone. In this case, we report an instance of acute hepatic failure after increasing the oral amiodarone dosage as well as rapid recovery following cessation of the medication.

Case report:

A 61-year-old male with a …

5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala

Theses and Dissertations

5-HT_2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens …

Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and …

Rationale And Design Of The Children's Oncology Group (Cog) Study Alte1621: A Randomized, Placebo-Controlled Trial To Determine If Low-Dose Carvedilol Can Prevent Anthracycline-Related Left Ventricular Remodeling In Childhood Cancer Survivors At High Risk For Developing Heart Failure., Saro H. Armenian, Melissa M. Hudson, Ming Hui Chen, Steven D. Colan, Lanie Lindenfeld, George Mills, Aida Siyahian, Sarah Gelehrter, Ha Dang, Wendy Hein, Daniel M M. Green, Leslie L. Robison, F Lennie Wong, Pamela S. Douglas, Smita Bhatia

Manuscripts, Articles, Book Chapters and Other Papers

Background: Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy …

Epigenetics Of Lipid Phenotypes, Sergi Sayols-Baixeras, Marguerite R. Irvin, Donna K. Arnett, Roberto Elosua, Stella W. Aslibekyan

Epidemiology and Environmental Health Faculty Publications

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay …

Pediatric Statin Administration: Navigating A Frontier With Limited Data., Jonathan B. Wagner, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

Increasingly, children and adolescents with dyslipidemia qualify for pharmacologic intervention. As they are for adults, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are the mainstay of pediatric dyslipidemia treatment when lifestyle modifications have failed. Despite the overall success of these drugs, the magnitude of variability in dose-exposure-response profiles contributes to adverse events and treatment failure. In children, the cause of treatment failures remains unclear. This review describes the updated guidelines for screening and management of pediatric dyslipidemia and statin disposition pathway to assist the provider in recognizing scenarios where alterations in dosage may be warranted to meet patients' specific needs.

Drug-Induced Nutrient Depletion, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

The Effects Of Smoking On The Calcification Of The Aortic Valve, Brittany Pendergraft

Biological Sciences Undergraduate Honors Theses

Calcific Aortic Valve Disease is responsible for approximately 28,000 deaths annually and the complete mechanism is not completely understood. The disease is known to be effected by an inflammatory response, osteogenic response and an oxidative stress response that leads to thickening and mineralization of the aortic valve. Originally, this disease was thought to be brought on by age and deterioration of the valve but these rapid stress responses when the valve is disrupted by biochemical and mechanical stress has led to its classification as an active disease. Smoking has been shown to have many of the same effects experienced by …

Is The High Frequency Of Postoperative Atrial Fibrillation After Cardiac And Lung Surgeries Related To Hypomagnesemia And Releases Of Ceramides And Platelet-Activating Factor?, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Aimin Zhang, Wenyan Li, Bella T. Altura

Touro College of Osteopathic Medicine (Middletown) Publications and Research

The authors discuss the possible role of hypomagnesemia, ceramides and platelet-activating factor in the incidence of postoperative atrial fibrillation after cardiac and lung surgeries.

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Effects Of Moderate Intake Of Alcohol On Coronary Heart Disease, Eli Derdik

The Science Journal of the Lander College of Arts and Sciences

The french paradox is caused by an inconsistency with scientific experimentation: The French have a very high intake of saturated fat and cholesterol, which is associated with coronary heart disease, yet they have un-commensurately low levels of deaths due to this disease. It has been proposed that alcohol, as a part of the French diet, is the factor that helps decrease the risk of heart disease in the French population by 20-30%. Research has been gathered from many medical journals to create a larger and more accurate perspective to determine if alcohol has any effect on coronary heart disease. Experiments …

Essentials Of Herb-Drug Interactions In The Elderly With Cardiovascular Disease, Sulaiman Sultan, Maria Viqar, Rabaiya Ali, A. Jamil Tajik, Arshad Jahangir

Journal of Patient-Centered Research and Reviews

As the number of individuals, particularly the elderly, using herbal products with prescription drugs continues to grow, the risk for adverse interactions increases but remains poorly recognized. The true incidence and nature of adverse herb reactions or herb-drug interactions remains unknown since no postmarketing surveillance mechanism exists. Adverse events are greatly underreported, and information regarding safety mainly comes from case reports and suboptimally conducted studies in a limited number of healthy young volunteers or patients with limited comorbidities. Therefore, convincing evidence for the safety of herbal products in the elderly is lacking, and the true magnitude of problems that herb-drug …

Novel Oral Anticoagulants For Stroke Prophylaxis And Venous Thromboembolism Prevention And Treatment, Laith G. Alsayegh

Journal of Patient-Centered Research and Reviews

Novel oral anticoagulants (NOACs) are becoming popular management options for stroke prophylaxis in nonvalvular atrial fibrillation as well as deep vein thrombosis and pulmonary embolism treatment and prophylaxis. NOACs have similar efficacy to warfarin along with noninferior safety profiles. Patient comorbidities, size, renal and hepatic function, and concomitant drug regimen play a role in which NOAC a physician may choose.

Effects Of Heat Stress On Arterial Compliance In Smokers: A Pilot Study, Erin Dougherty

Health, Human Performance and Recreation Undergraduate Honors Theses

Arterial compliance (i.e., arterial elasticity) is a major contributor to the pathophysiology of cardiovascular disease (CVD) and has been recognized as an independent risk factor for CVD. Smokers have poor arterial compliance compared to non-smokers. In non-smokers, passive heat stress has been shown to acutely improve arterial compliance. It is unknown how passive heat stress affects arterial compliance in smokers. The purpose of this pilot study was to test the hypothesis that passive heat stress improves arterial compliance in smokers to a greater extent than non-smokers. This pilot study involved 2 male smokers and 2 male non-smokers, ages 18-21. Smokers …

Accidental Phosphine Gas Poisoning With Fatal Myocardial Dysfunction In Two Families, Saleem Akhtar, Arshalooz Rehman, Surraya Bano, Anwarul Haque

Department of Emergency Medicine

ABSTRACT Aluminum phosphide is commonly used as a rodenticide and insecticide and is one of the most fatal poisons. The active ingredient is Phosphine gas which inhibits cytochrome oxidase and cellular oxygen utilization. The clinical symptoms are due to multiorgan involvement including cardiac toxicity which is the most common cause of mortality. Severity of clinical manifestations depends upon the amount of the gas to which a person is exposed. There is no specific antidote available. High index of suspicion and early aggressive treatment is the key to success. We report 2 cases of aluminum phosphide toxicity in 2 families due …

Mdivi-1, A Mitochondrial Division Inhibitor, Exerts Cardioprotective Effects In Myocardial Ischemia/Reperfusion (Mi/R) When Given At Reperfusion, Devon P. Stutzman

PCOM Biomedical Studies Student Scholarship

Acute myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Accompanying MI is myocardial ischemia/reperfusion (MI/R) injury, which results in cardiac contractile dysfunction and additional myocardial cell death. MI/R injury is initiated in part by mitochondrial-derived reactive oxygen species due to mitochondrial membrane potential collapse and uncoupling of the electron transport chain, which may be due to mitochondrial fission in MI/R. Mitochondrial fission is in turn associated with shortening/fragmentation of mitochondria, decreased ATP production, and is thought to promote cardiac contractile dysfunction and post-reperfused cardiomyocyte loss, leading to increased infarct size. Therefore, inhibiting mitochondrial fission may be …

Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant

Theses and Dissertations

Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …

Effect Of Sweeteners On The Renin-Angiotensin System In Rats, Jacob Ball

Journal of Undergraduate Research at Minnesota State University, Mankato

Normal abundant dietary sugars such as fructose and sucrose can contribute to hypertension and other health issues. To avoid these health complications, many individuals use artificial sweeteners. An equivalent intake of some artificial sweeteners also can lead to hypertension. However, Stevia, a sweetener that is isolated from a Paraguayan plant, was shown in relevant literature to decrease blood pressure in both rat specimens and humans. The general purpose of this research project was to study the effect of Stevia, saccharin, and sucrose on the expression of two key components of the renin-angiotensin- aldosterone system (RAAS): prorenin receptor (PRR) and angiotensin …

Endothelial And Smooth Muscle-Dependent Vascular Reactivity In Immature Arterialized Collateral Capillaries, Caitlin Koeroghlian

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) occurs due to the build up of atherosclerotic plaque and reduces blood flow to cause chronic ischemia. Patients with PAOD may experience intermittent claudication, or the pain in limb skeletal muscles due to a decease in blood flow. Collateral arteries can act as a natural bypass and improve blood flow to hypoxic tissue by creating an alternate route for blood to flow, but not all patients with PAOD have pre-existing collateral networks. Animal studies indicate that tissues without pre-existing collateral networks can form de novo collaterals from capillaries following occlusion of a feed artery. Unfortunately, …

Childhood Obesity And Familial Hypercholesterolemia: Genetic Diseases That Contribute To Cardiovascular Disease, Alyssa Caudle

Senior Honors Theses

Childhood obesity occurs as the result of an imbalance between caloric intake and energy expenditure. Genetic risk factors for obesity have become an area of research due to its permanency. Mutated genes such as Fat Mass and Obesity Associated (FTO), Leptin (LEP), Leptin Receptor (LEPR), Melanocortin 4 Receptor (MC4R), Adiponectin C1Q and Collagen Domain Containing (ADIPOQ), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1), and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) all contribute to the development of childhood obesity. In the presence of high cholesterol caused by obesity, the genetic condition known as familial hypercholesterolemia is exacerbated. Familial hypercholesterolemia is caused by a …

Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper

School of Medical Diagnostics & Translational Sciences Publications

Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary …

Cardiac Troponin Assessment Following Atrial Fibrillation Ablation: Implications For Chest Pain Evaluation, Jason C. Rubenstein, Jason T. Jacobson, Jeffrey J. Goldberger, Rod Passman, Alan H. Kadish, Michael H. Kim

Office of the President Publications and Research

Background: The range of elevation of troponin I (tI) that is within expected limits from left atrial radiofrequency ablation for atrial fibrillation (AF) is not well described, though such information may be of clinical value.

Objectives: Identify the expected range of tI values post-atrial fibrillation (AF) ablation.

Methods: 31 patients undergoing AF ablation had a single tI level drawn the day following the procedure. Clinical variables were also collected, such as ablation type and radiofrequency (RF) time.

Results: Paroxysmal AF was present in 23 patients, and 8 had chronic AF. The average RF time was 2627.8 …