Chemicals and Drugs Commons^™

Pharmacists’ Role In The Management Of Patients Receiving Dual Or Triple Antithrombotic Therapy, Laura Neubauer, Radhan Gopalani, Kristen De Almeida

All Publications

Purpose: Patients on dual and triple antithrombotic therapy present the therapeutic dilemma of mitigating bleed risk while sustaining antithrombotic efficacy. Lack of literature and variability in existing published guidance potentiates inconsistent management of these patients. Furthermore, suboptimal dosing of direct oral anticoagulants is relatively common. One study reported as high as 43% of patients receive higher and 13% receive lower than clinically indicated doses. These findings were associated with a significantly increased risk of major bleeding and incidence of stroke, thus highlighting the importance of selecting an ideal regimen. The purpose of this project is to highlight pharmacists’ role in …

A Computational Analysis Of Selective Metabolism Of Bupropion By Cytochrome P450 2b6, Alyssa Santos

Honors Scholar Theses

Bupropion is an antidepressant and smoking cessation aid that is extensively metabolized by cytochrome P450 (CYP) 2B6. It is a highly lipophilic chiral drug that undergoes stereoselective metabolism with preference for the (S)-enantiomer. Despite chemical reasons for why bupropion can be metabolized by other CYP isozymes, clinically, bupropion is preferentially metabolized by CYP2B6, and at certain concentrations, CYP2E1, CYP2C19, and CYP3A4. A computational analysis with simulated molecular docking was performed using two different scoring algorithms to analyze the specific amino acid interactions between bupropion and various CYP isozymes. Trials were run using one stereoisomer of bupropion (R …

Vertical Transmission Of Zika Virus In An Opossum Model, Dionn Carlo Silva

Theses and Dissertations

This study will identify Brazilian ZIKV infection in the offsprings of mated, inoculated Monodelphis domestica females. Unlike non-human primates (NHP) and transgenic mice, M. domestica provides an opportunity to study ZIKV infection in a novel animal model possibly useful for in-utero studies. M. domestica has also been used in cancer and dietary research with varying degrees of success. ZIKV infection will be identified using antibody staining and in situ hybridization. The expected result of this study is that ZIKV will be identified in various tissues and reveal that ZIKV is transmitted vertically in this animal model. The significance of this …

System For Hiv-1 Treatment To The Brain, Caroline Rose Garcia

Theses and Dissertations

While HIV-1 treatment has been revolutionized by combination antiretroviral therapy in the past two decades, HIV-1 remains persistent in organs that don’t allow easy penetration of anti-HIV drugs (e.g., brain) and cause persistent HIV-1 infections and inflammation. Researchers have turned towards nanotechnology-based drug carriers to combat this challenge, such as nanodiscoidal bicelles (ND) and liposomes. Bicelles entrap the drug in their interior hydrophobic core until metabolized by the body, and the payload can be released at the desired location in a controlled, long-lasting dosage. This study investigated the toxicity and extended-release of an anti-HIV drug-loaded within ND and liposomes for …

Inoculation Of Juvenile Monodelphis Domestica With Zika Virus Using Various Routes Of Infection, Juan Garcia Jr.

Theses and Dissertations

Monodelphis domestica is a small marsupial from South America that has been previously been used in human metabolism research. However, their suitability as models for Zika virus (ZIKV) research, is currently unknown. Preliminary studies have shown M. domestica susceptible to ZIKV through the intracerebral route. We utilized immunohistochemistry, and analyzation of serological responses to show that juvenile Monodelphis domestica can be infected with ZIKV by using various routes of infection that include subcutaneous, intraperitoneal, and intramuscular. ELISAs performed on sera confirmed that juveniles injected with ZIKV by all three routes generated anti-ZIKV antibodies. Additionally, ZIKV nonstructural protein 1 was detected …

Unlocking Knowledge To Benefit The Patient : How Connecting Km And Qrm Can Strengthen Science And Risk-Based Decision Making, Martin J. Lipa

Doctoral

This thesis explored knowledge management effectiveness in the pharmaceutical sector and included an examination of the critical relationship between knowledge management (KM) and quality risk management (QRM) as the dual enablers of an effective pharmaceutical quality system. The primary research objectives were to improve understanding and effectiveness of the interdependency between KM and QRM and to improve knowledge management across the pharmaceutical product lifecycle, starting with a focus on knowledge transfer during technology transfer. The thesis explored how improved KM across the product lifecycle coupled with thoughtful and intentional connectivity between KM and QRM as defined by this study could …

Optimizing Empiric Vancomycin Use In Febrile Neutropenia Patients, Nicole Tadros, Erika Dittmar, Radhan Gopalani

All Publications

Introduction: Febrile neutropenia (FN) is a complication of chemotherapy resulting in a temperature 100.4⁰F or greater plus an absolute neutrophil count (ANC) below 500 cells/mm³ or an ANC below 1000 cells/mm³ and expected to decrease below 500 cells/mm³ within 48 hours. Timely administration of broad-spectrum antimicrobial therapy is a cornerstone for the initial management of FN. However, prolonged empiric antimicrobial treatment can lead to resistance and toxicity. National guidelines and published literature do not support vancomycin as a routine part of empiric antimicrobial regimens in FN; it is only recommended in patients with specific clinical indications. This …

Evaluation Of Antiplatelet-Related Bleeding Events In A Community Hospital, Frank C. Moreno Exposito, Heidi Clarke, Erika Dittmar

All Publications

Background:Bleeding rate among patients who take high-dose aspirin is approximately 1.92% with an expected 2-3 fold increase after a second antiplatelet is added. Similarly, the addition of an anticoagulant to single or dual antiplatelet therapy results in increased bleeding rates of approximately 13.9% and 15.7% respectively. The concomitant use of antiplatelets and anticoagulants has become a common practice due to the high incidence of clinical conditions for which these agents are used. Hence, reversal of antithrombotic agents is often needed during major bleeding events or invasive procedures. However, the use of antiplatelet reversal is still under-utilized, and its efficacy …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza

Graduate Theses and Dissertations

The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …

Hydrogen Peroxide Colitis: The Accidental Enema, Ramin Karimi, Ashish Sharma, Kevin Tran, Sebastian Montgomery

HCA Healthcare Journal of Medicine

Chemical colitis is defined as inflammation of the large intestine or colon as a result of exposure from a harsh chemical through an enema or other procedure. In this case, the chemical is hydrogen peroxide, which is commonly used as an antiseptic for minor abrasions. Hydrogen peroxide enemas were once popular for difficult to treat constipation. However, resultant colitis and proctitis limited its use. When administered rectally in a high enough concentration, intense abdominal pain and transient bloody diarrhea can occur, with the majority of affected patients making a full recovery with supportive management. Here we discuss a case of …

The Effect Of Chronic Alcohol Consumption On Exercise-Induced Muscle Damage In Young Men, Emma Hamilton, Grant Hilliard

Honors Theses

PURPOSE: To investigate the effects of chronic alcohol consumption on exercise-induced muscle damage of the knee extensors in young men. METHODS: Twenty-one males (age 21.9 ± 1.1 yr; weight 183.4 ± 27.6 lbs; height 174.0 ± 13.1 cm) performed 100 maximal eccentric contractions at 30°/sec of the knee extensors using their non-dominant leg. The isometric and isokinetic muscle strengths (60°/sec and 180°/sec) were measured pre-exercise and immediately, 24 h, 48 h, 72 h, 96 h, and 120 h post-exercise. Muscle soreness and plasma creatine kinase (CK) activity were measured pre-exercise and 24 h, 48 h, 72 h, 96 h, and …

Bibliometric Analysis Of Emerging Technologies In The Field Of Computer Science Helping In Ovarian Cancer Research, Sonali Kothari Dr., Anvita Gupta, Muskaan Agrawal Agrawal, Kajal Jaggi, Adhiraj Dev Goswami, Ketan Kotecha, M. Karthikeyan Dr., Vijayshri Khedkar

Library Philosophy and Practice (e-journal)

This study is carried out to provide an analysis of the literature available at the intersection of ovarian cancer and computing. A comprehensive search was conducted using Scopus database for English-language peer-reviewed articles. The study administers chronological, domain clustering and text analysis of the articles under consideration to provide high-level concept map composed of specific words and the connections between them.

The Effects Of Progesterone Induced Blocking Factor And 17-Hydroxyprogesterone Caproate On The Pathophysiology Of Preeclampsia, Kyleigh M. Comley

Honors Theses

Preeclampsia (PE) is responsible for about 20% of the 13 million preterm births each year worldwide, including 100,000 cases annually in the United States. Despite being a leading cause of maternal and perinatal morbidity, the mechanisms of pathogenesis are still largely unknown. PE is progesterone deficient state characterized by hypertension, chronic immune activation, endothelial dysfunction and severe forms can lead to seizures. Treatment of seizures includes the administration of magnesium sulfate (MgSO4) though not all PE patients are responsive, and it does not decrease PE-associated hypertension. To resolve these conditions, PE patients are delivered early thereby making PE the leading …

Synthesis Of Novel Long Chain Unsaturated Fatty Acid Analogs Of Capsaicin, Eli Bettiga

Honors Theses

A number of key studies have shown that the natural product capsaicin displays in vitro and in vivo antitumor effects against a variety of cancers, however, both the analgesic and cancer-related therapeutic potential of capsaicin have been limited by its unpleasant pungent side effects and modest potency. N-acyl vanillylamides (N-AVAMs) are a unique class of compounds that are simple side chain modified capsaicin derivatives. Limited structure-activity relationship (SAR) studies of N-AVAMs demonstrated that substitution of the capsaicin side-chain with longer unsaturated fatty acid groups results in non-pungent analogs with improved anti-invasive activity relative to capsaicin. In an effort to ultimately …

Drug Repurposing And Dosage Form Development Of Anti-Covid-19, Kevin Kwok

Pharmaceutical Sciences and Research

The COVID-19 pandemic has been occurring approximately for more than 1 year. This pandemic has been a health issue that hits all countries in the world caused by the transmission of SARS-CoV-2 virus from one individual to another. The symptoms showed from the infected are fever, shortness of breath, dry cough, headache, and sore throat, among others. The SARS-CoV-2 virus is transmitted through sneezing, coughing, talking, and touching infected objects. Along with this transmission, the SARS-CoV-2 virus will continue to mutate. This mutation becomes an obstacle as well as a challenge to find drugs that can overcome the SARS-CoV-2 virus …

Use Of Antisense Oligonucleotides To Target Notch2 In Mouse Chondrocytes, Gabrielle Viviana Lanza

Honors Scholar Theses

NOTCH2 is a transmembrane receptor that is part of the Notch receptor family, known for controlling cell differentiation and function. Notch receptors play a crucial role in skeletal development and bone homeostasis. Hajdu Cheney Syndrome (HCS) is a rare monogenic disorder affecting the skeleton caused by a gain-of-function mutation in NOTCH2. Antisense oligonucleotides (ASO) are sequence-specific single-stranded nucleic acids that bind to target mRNA and initiate mRNA degradation. While previous work has explored the role of Notch2 ASOs in osteoblasts and osteoclasts, this paper explores the role of Notch2 and Notch2 ASOs in cells of cartilage tissue. The effect of …

Suppression Of Human Coronavirus 229e Infection In Lung Fibroblast Cells Via Rna Interference, Hamidreza Montazeri Aliabadi, Jennifer Totonchy, Parvin Mahdipoor, Keykavous Parang, Hasan Uludağ

Pharmacy Faculty Articles and Research

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will …

Ciliary Extracellular Vesicles Are Distinct From The Cytosolic Extracellular Vesicles, Ashraf M. Mohieldin, Rajasekharreddy Pala, Richard Beuttler, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Extracellular vesicles (EVs) are cell‐derived membrane vesicles that are released into the extracellular space. EVs encapsulate key proteins and mediate intercellular signalling pathways. Recently, primary cilia have been shown to release EVs under fluid‐shear flow, but many proteins encapsulated in these vesicles have never been identified. Primary cilia are ubiquitous mechanosensory organelles that protrude from the apical surface of almost all human cells. Primary cilia also serve as compartments for signalling pathways, and their defects have been associated with a wide range of human genetic diseases called ciliopathies. To better understand the mechanism of ciliopathies, it is imperative to know …

Thyroid Hormone Synthesis Continues Despite Biallelic Thyroglobulin Mutation With Cell Death, Xiaohan Zhang, Aaron P. Kellogg, Cintia E. Citterio, Hao Zhang, Dennis Larkin, Yoshiaki Morishita, Héctor M. Targovnik, Viviana A. Balbi, Peter Arvan

Pharmacy Faculty Articles and Research

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe …