Chemicals and Drugs Commons^™

Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw

Electronic Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to PM_2.5 is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD is less clear. Overall, this work aimed to examine the effect of pollutants with lesser documented effects on cardiovascular disease using a multi-pronged approach to exposure assessment. The three aims were to examine the relationship between county-level toxic chemical releases and CVD mortality in the contiguous United States between 2002 and 2012, to assess the relationship between individual-level VOC metabolites and vascular function, and to build multipollutant …

Heterocyclic Amines And Arylamine N-Acetyltransferase 2 Polymorphism In Pathogenesis Of Insulin Resistance., Kennedy M. Walls

Electronic Theses and Dissertations

Heterocyclic amines (HCAs) are formed when cooking meats at high temperatures or for long periods of time, and their major metabolic pathway includes hepatic N‑hydroxylation by CYP1A2 followed by O-acetylation by N-acetyltransferase 2 (NAT2). NAT2 is a highly polymorphic gene involved in metabolism of drugs and xenobiotics, and its single nucleotide polymorphisms (SNPs) produce phenotypes characterized as slow, intermediate, or rapid acetylator. Recent studies have documented associations between HCAs and insulin resistance and between certain NAT2 phenotypes and insulin resistance. In this study, we demonstrated that NAT2 activity and exposure to certain HCAs may alter cellular glucose …

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 …

The Effects Of Steroid Use In Sports, Jake Page

Emerging Writers

This article highlights the main points around the argument that professional sports organizations should increase rules and regulations against the use of steroids. This is done by referencing numerous trustworthy sources along with providing personal insight on how certain points affect the sports community and beyond. The main points can be summed up that steroids have a negative effect due to the huge scandals involved along with the health effects of steroid usage.

Headache And Its Association With Adhd/Add And Stimulant Medication, Claire Nitzsche

Honors Scholar Theses

Years of research has shown that headache (in terms of frequency, duration, and severity) is perpetuated by dysregulation of lifestyle behaviors such as sleep habits, eating habits, level of stress, physical activity etc. Our project aims to explore the potential combined and independent impacts that having ADHD/ADD and taking stimulant drugs have on disrupting one’s lifestyle and examine whether dysregulated lifestyle behaviors contribute to one’s headache experience. No research has investigated how both ADHD/ADD and stimulant drug use effect headache experience. In this cross-sectional study, 177 UConn undergraduate students completed a 10-minute survey regarding lifestyle behaviors and headache experience. Participants …

The Effects Of Dexmedetomidine On Preventing/Decreasing Severity Of Delirium When Given To Surgical Intensive Care Unit Patients: A Systematic Review Of Randomized Control Trials, Lindsey Hettish

The Eleanor Mann School of Nursing Undergraduate Honors Theses

The purpose of this systematic review was to integrate research evidence from studies published from 2010 to 2020 on the relationship between administration of dexmedetomidine and severity/prevalence of postprocedural delirium in patients in the surgical intensive care unit. In this review, clinical trial studies were recovered by searching the MEDLINE Complete and PubMed databases and utilizing MeSH terminology search. The MeSH terms utilized to search for applicable articles on PubMed included: “intensive care units” or “critical care” or “critical care nursing”, and “delirium”, “dexmedetomidine”, and “surgical procedures, operative”. On MEDLINE Complete, the search terms utilized were “ICU or intensive care …

Identification And Characterization Of Butyrate-Producing Species In The Human Gut Microbiome, Grace Maline

Theses/Capstones/Creative Projects

Inflammatory Bowel Diseases (IBD) including ulcerative colitis, indeterminate colitis, and Crohn’s disease are increasingly common conditions that places a high physical and financial burden on individuals and global healthcare systems. Though many treatments exist for these conditions, their unpredictable nature and causation make them difficult to manage across the variety of IBD patients. Additionally, many of these treatments come with undesirable side effects or modes of delivery. Therefore, it is worthwhile to explore the use of Short Chain Fatty Acids (SCFAs) such as butyrate whose affects in the human gut include decreased inflammation and decreased risk of colorectal cancer. As …

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 …

Optimization Of Albumin 5% Use In A Community Hospital, Robyn Feldman, Stephanie Palma, Erika Dittmar, Heidi Clarke

All Publications

Background: The debate surrounding the use of crystalloids versus colloids remains a source of controversy due to limited and conflicting evidence. Emerging data favors the use of crystalloids over colloids in addition to cost benefits. Baptist Hospital of Miami (BHM) has evidence-based guidance for albumin 5%, but it is unclear the degree of appropriate usage. The purpose of this study is to assess the prescribing practices of albumin 5% at BHM and optimize appropriate use through pharmacy driven interventions.

Methodology: A single-center, IRB-reviewed, bi-phasic study was conducted within a community hospital. In phase I, a retrospective chart review of patients …

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 …

The Effects Of Timing And Long-Term Estrogen Deficiency On Cardiac Fibrosis Following Chronic Sympathetic Stimulation, Samuel Wisecarver

Undergraduate Honors Theses

Evidence in animal studies show that estrogen in women is cardioprotective, but discrepancies remain between clinical and animal studies regarding progression of cardiovascular disease after menopause. Cardiac fibrosis, the build-up of type I and III collagen fibers, is a staple of cardiac remodeling. The goal of this study was to examine the effects of long-term estrogen loss in the heart; this study includes two time points (1-month and 5-month) post-ovariectomy. Mice were randomly selected for 4 treatment groups: SHAM, Ovariectomy (OVX), Isoproterenol (ISO) (a β-adrenergic agonist used to mimic chronic sympathetic stimulation) and OVX+ISO. Mice were infused with either Saline …

The Impact Of Prolonged Estrogen Deficiency On Cardiac Hypertrophy Following Chronic Sympathetic Stimulation, Isabelle Krueger

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of death for both men and women in developed countries. Compared to age-matched males, premenopausal women experience lower rates of CVD but this increases after menopause. A central feature in CVD is changes in sympathetic regulation leading to pathological changes such as cardiac hypertrophy characterized by changes in cardiomyocyte size due to overcompensation of the muscle following injury. The goal of this research is to study the effect of prolonged estrogen loss on cardiac hypertrophy following chronic sympathetic stimulation. Female mice were ovariectomized at 10 weeks of age and treated with Isoproterenol to …

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 …

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 …

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Angelina Sorensen, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

Opioids such as morphine are important pain-relieving drugs but also carry a risk of harmful side effects including addiction. Morphine is active in both healthy and inflamed tissue, however, decreasing the pKa of the biochemically-active amine group can promote selective binding in the more acidic conditions of inflamed tissue and reduce harmful side effects associated with opioids. Herein, we explore the impact of fluorination on the pKa of fluoromorphine derivatives to identify which will bind selectively in inflamed tissue. Theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔGaq" …

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 …

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 …