Chemicals and Drugs Commons^™

Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

"Alzheimer’s disease (AD) is the sixth leading cause of death in the United States with approximately 5.8 million Americans currently living with AD. Due to the lack of a disease modifying treatment for AD and the aging baby boomer generation, this number is projected to grow to 13.8 million by 2050 (Gaugler et al., 2019). Amyloid-beta (Aβ) plaque accumulation, one of the major pathological hallmarks of AD, can begin > 20 years before clinical symptoms of AD. By the time AD is clinically diagnosed, neuronal loss and neuropathological lesions (Aβ plaques and tau tangles) have already occurred in many brain regions …

Proteomic Identification Reveals The Role Of Ciliary Extracellular‐Like Vesicle In Cardiovascular Function, Ashraf M. Mohieldin, Rajasekharreddy Pala, Rinzhin T. Sherpa, Madhawi Alanazi, Ashwaq Alanazi, Kiumars Shamloo, Amir Ahsan, Wissam A. Aboualaiwi, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are shown to have membrane swelling, also known as ciliary bulbs. However, the role of these structures and their physiological relevance remains unknown. Here, it is reported that a ciliary bulb has extracellular vesicle (EV)‐like characteristics. The ciliary extracellular‐like vesicle (cELV) has a unique dynamic movement and can be released by mechanical fluid force. To better identify the cELV, differential multidimensional proteomic analyses are performed on the cELV. A database of 172 cELV proteins is generated, and all that examined are confirmed to be in the cELV. Repressing the expression of these proteins in vitro and in vivo …

Risk Of Acute Kidney Injury In Patients Receiving Vancomycin And Piperacillin-Tazobactam Compared To Vancomycin And Cefepime, Viktoria Andonova

All Publications

No abstract provided.

Comparative Antiviral Activity Of Remdesivir And Anti-Hiv Nucleoside Analogs Against Human Coronavirus 229e (Hcov-229e), Keykavous Parang, Naglaa Salem El-Sayed, Assad J. Kazeminy, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. …

Determining The Link Between Advanced Glycation Endproducts (Ages), Feeding, And Metabolism, Lauren Wimer

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Reactive a-dicarbonyls (a-DC’s), such as methylglyoxal (MGO), are unavoidable metabolites generated during glycolysis that accumulate with age and have been linked with chronic age-related metabolic diseases such as Diabetes Mellitus. Diabetes Mellitus is generally characterized by peripheral neuropathy and sustained hyperglycemia. Chronic hyperglycemia leads to an increase in glycolysis and a downstream increase in reactive a-DC’s. The human body has a natural method of detoxifying these a-DC’s. Glycolytic cells have enzymes which can detoxify a-DC’s, but if overwhelmed, a-DC’s can accumulate and react non-enzymatically with proteins, lipids and DNA to yield a group of molecules called advanced glycation end-products (AGEs). …

Swimming Pool Environment And Respiratory Health Issues Experienced By Masters Swimmers: Results From A Literature Review And Survey Of United States Masters Swimming Clubs, Jody C. Gan, Julia Snegg, William Harder

International Journal of Aquatic Research and Education

After three members of a Masters adult swim club died of lung cancer, both a literature review and survey were conducted with representatives from 746 United States Masters Swimming clubs to explore a possible relationship between swimming and cancers of the respiratory tract. Six other clubs reported known cancers of the respiratory tract among club members, but none of the other 740 clubs reported a similar cluster of lung cancer. More clubs reported cases of chronic respiratory infections and widespread complaints about air quality. While no studies exploring a relationship between swimming and lung cancer could be found in the …

Assessing The Effect Of Chronic Dopamine Receptor 2 Blockade As A Potential Model Of Secondary Negative Symptoms In Rats Using The Fr5/Chow Feeding Choice Task, Cyrene Nicholas

Honors Scholar Theses

Haloperidol, a dopamine (DA) D2 receptor antagonist, is an antipsychotic drug which is commonly used to treat schizophrenia and other psychiatric disorders. These disorders are often characterized by elevated striatal dopamine, which is speculated to have a role in producing positive symptoms such as hallucinations, delusions, and paranoia, as well as symptoms related to motivational salience and reward prediction. Individuals with schizophrenia also exhibit negative symptoms, such as amotivation, anergia, fatigue, and apathy among others. While some negative symptoms of schizophrenia are inherent to the pathophysiology, other negative symptoms are hypothesized to be partially induced by chronic exposure to antipsychotic …

Proteoglycan-4 Regulates Fibroblast To Myofibroblast Transition And Expression Of Fibrotic Genes In The Synovium, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Holly Richendrfer, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo.

Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or …

The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell

Honors Theses

Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …

Hailey-Hailey Disease Successfully Treated With Low-Dose Naltrexone, John Moesch, Richard Miller

West Florida Division GME Research Day 2020

Hailey-Hailey disease (HHD) is an uncommon autosomal dominant disorder resulting from a mutation in the ATP2C1 gene resulting in dysfunction of the Golgi apparatus calcium-associated ATPase, thus interfering with intercellular calcium signaling.

HHD presents clinically as flaccid blisters and erosions in intertriginous areas, especially the axillae and groin.

The major histologic finding is acantholysis throughout the spinous layer of the epidermis, commonly referred to as a “dilapidated brick wall” appearance.

The initial lesions and associated symptoms usually develop during the second or third decade of life.

Complications of HHD include infections (bacterial, fungal, and viral), and malignant transformation (cutaneous squamous …

Ctrp3 And Alcoholic Liver Disease In Female Mice, Callie Root

Undergraduate Honors Theses

C1q TNF Related Protein 3 (CTRP3), is a cytokine that is primarily secreted from adipose tissue, which classifies it as an adipokine. Our previous research has shown that CTRP3 prevents alcoholic fatty liver disease (ALD) in male mice. However, even when accounting for confounding factors such as absolute and relative alcohol intake, females are more sensitive to the effects of consumption compared to male mice. Therefore, the goal of this project was to determine whether CTRP3 prevented ALD in female mice. Methods: Female wild type (WT) and female CTRP3 transgenic over expressing (Tg) mice were fed an ethanol containing liquid …

The Effects Of Zoledronate And Sleep Deprivation On The Distal Femur Trabecular Thickness Of Ovariectomized Rats: Application Of Different Statistical Methods, Erin Nolte

Student Scholar Symposium Abstracts and Posters

Osteoporosis is a disease that causes the degradation of bone, leading to an increased risk of fracture. 1 in 3 women over the age of 50 will be affected by Osteoporosis. This study aims to understand how bone is affected by sleep deprivation in estrogen-deficient rats, and how Zoledronate might negate the inimical effects of sleep deprivation on bone. As bone mineral density (BMD) is a crude evaluation of the architectural changes seen in Osteoporosis, trabecular thickness may serve as a better single evaluation of bone health. 31 Wistar female rats were ovariectomized and separated into 4 random groups. The …

Evaluation Of Clinical Outcomes Of 4-Factor Prothrombin Complex Concentrate Versus Andexanet Alfa In The Treatment Of Intracerebral Hemorrhage, Eduardo Guizan Corrales, Radhan Gopalani, Heidi Clarke, Jonatha Kline, Felipe De Los Rios La Rosa, Thomas Wolfel

All Publications

Purpose: Oral anticoagulants account for up to 20% of intracerebral hemorrhages (ICH) with one-year mortality estimated as high as 54%. Several studies have examined the use of 4-Factor prothrombin complex concentrate (4F-PCC) and andexanet alfa in the treatment of factor Xa associated ICH. High cost burden, lack of clinical outcomes, and risk of thromboembolic events continues to be a major dilemma behind product selection at many healthcare systems. The purpose of this project is to compare clinical outcomes between 4F-PCC and andexanet alfa in the management of patients with ICH secondary to apixaban and rivaroxaban at Baptist Hospital of Miami …

Calcitonin Prescribing Criteria For The Management Of Hypercalcemia In A Community Hospital, Jessica Hernandez, Radhan Gopalani, Heidi Clarke, Joyce Lee, Alyssa Donadio

All Publications

Purpose/Background: Hypercalcemia is a clinical condition in which serum calcium levels exceed the upper limit of normal (>10.5 mg/dL). The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy, however, it can also be caused by vitamin D intoxication, endocrine disorders, and immobilization due to an increase in bone resorption. First-line treatment of hypercalcemia includes hydration with intravenous (IV) normal saline and IV bisphosphonates. Calcitonin (Miacalcin®) is a synthetic hormone with a rapid onset of action and used intramuscularly (IM) or subcutaneously (SQ) as a second-line treatment in the management of hypercalcemia, specifically in severe and in symptomatic …

A Systematic Search And Review On The Efficacy, Safety, And Cost-Effectiveness Of Utilizing Lactobacillus Probiotics In Concurrence With Prescribing Antibiotics To Reduce Clostridium Difficile Infection Rates In Hospitalized Patients, Laura Sheehan

Nursing Masters Papers

Incidence of Clostridium difficile infection, (CDI) in patients receiving antibiotics is significant. In 2017, there were approximately 223,900 cases of CDI in hospitalized patients alone (Center for Disease Control [CDC], 2017). Despite enhanced infection control measures, CDI rates remain prevalent and are associated with increased costs to healthcare. An integrative literature review and synthesis was performed. Studies were analyzed to delineate if Lactobacillus containing probiotics, when administered concurrently with high risk antibiotics, decrease CDI rates for patients in the inpatient hospital setting. Additional analysis of probiotic safety and a cost versus benefit analysis was researched. The purpose of the review …

Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston

Senior Honors Theses

The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …

A Closer Look At Muscle Breakdown: An Overview Of The Causes, Complications, And Diagnostics Of Rhabdomyolysis, Jamie Holchin

Senior Honors Theses

Rhabdomyolysis is the rapid breakdown of myocytes in skeletal muscle. This condition can be triggered by a variety of things including crush injury, drugs, prolonged exercise, and venom. Although the causes can vary, the general pathophysiology of rhabdomyolysis is similar. Increased intracellular calcium ion levels instigate the breakdown of cellular and certain organelle membranes of muscle cells. Reactive oxygen species form, ATP is depleted, and the sarcoplasmic reticulum, which regulates muscle contraction, is also damaged. Necrosis ensues, leading to toxic intracellular components spreading throughout the body. Rhabdomyolysis can then lead to several complications including acute renal injury and heart arrhythmias, …

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 …

Validation Of A Lysis Buffer Containing 4 M Guanidinium Thiocyanate (Gitc)/ Triton X-100 For Extraction Of Sars-Cov-2 Rna For Covid-19 Testing: Comparison Of Formulated Lysis Buffers Containing 4 To 6 M Gitc, Roche External Lysis Buffer And Qiagen Rtl Lysis Buffer, Martina F. Scallan, Catherine Dempsey, John Mcsharry, Isabelle O'Callaghan, Paula M. O'Connor, Conor P. Horgan, Edel Durack, Paul D. Cotter, Sarah Hudson, Humphrey A. Moynihan, Brigid Lucey

Dept. of Biological Sciences Preprints

The COVID-19 pandemic has resulted in increased need for diagnostic testing using reverse transcriptase real-time PCR (RT-PCR). An exponential increase in demand has resulted in a shortage of numerous reagents in particular those associated with the lysis buffer required to extract the viral RNA. Herein, we describe a rapid collective effort by hospital laboratory scientists, academic researchers and the biopharma industry to generate a validated lysis buffer. We have formulated a 4M Guanidinium thiocyanate (GITC)/ Triton X-100 Lysis buffer which provides comparable results with the recommended reagents. This buffer will ease the burden on hospital labs in their heroic efforts …

Cd44 Receptor Mediates Urate Crystal Phagocytosis By Macrophages And Regulates Inflammation In A Murine Peritoneal Model Of Acute Gout, Emira Bousoik, Marwa Qadri, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is a chronic arthritis caused by the deposition of poorly soluble monosodium urate monohydrate (MSU) crystals in peripheral joints. Resident macrophages initiate inflammation in response to MSU mediated by NF-κB nuclear translocation and NLRP3 inflammasome activation. We investigated the role of CD44, a transmembrane receptor, in mediating MSU phagocytosis by macrophages. We used an antibody that sheds the extracellular domain (ECD) of CD44 to study the role of the receptor and its associated protein phosphatase 2A (PP2A) in macrophage activation. We also studied the significance of CD44 in mediating MSU inflammation in-vivo. Cd44^−/− BMDMs showed reduced MSU …

Dementia: Types, What They Are And How They Differ, Jessica N. Schnetzer

Honors Thesis

Dementia: types, what they are and how they differ centers on the known and unknown complexities of dementia. Dementia is a very complex cognitive disease that consumes the brain, an organ of which we know very little about. Even so, this common disorder is actively being researched and is the topic of special interest of this thesis research. Described are Alzheimer’s disease, Creutzfeldt-Jakob disease, Frontotemporal dementia, Huntington’s disease, Korsakoff’s syndrome, Lewy body dementia, Parkinson’s dementia, and Vascular dementia, focusing on what they are, their specific risks, diagnosis, treatment, and their differing progressions. Guidance of this study provided by thesis director …

Diabetes Debunked: What You Need To Know, Maggie Hutson

Honors Program: Senior Projects (Public)

The goal of this Honors creative project is to encourage health literacy in populations who are curious about Type 2 Diabetes or have Type 2 Diabetes. From personal experience, I have seen noncompliance in diabetics and wondered why since it is a serious, progressive disease. After researching, I found that some diabetics do not understand the scope of their disease, especially since many of the dangerous complications that arise from Type 2 Diabetes do not present until later in the disease when it is too late. For my senior project, I decided to write an educational paper as a supplement …

Pectin-Tannic Acid Nano-Complexes Promote The Delivery And Bioactivity Of Drugs In Pancreatic Cancer Cells, Sumeet S. Chauhan, Advait B. Shetty, Elham Hatami, Pallabita Chowdhury, Murali M. Yallapu

School of Medicine Publications

Pancreatic cancer (PanCa) is a lethal disease. Conventional chemotherapies for PanCa offer severe systemic toxicities. Thus, the development of a successful nanomedicine-based therapeutic regimen with augmented therapeutic efficacy is highly sought. Naturally occurring pectin and modified pectin-based drug delivery systems exhibit remarkable self-targeting ability via galactose residues to various cancer cells. Herein, we developed and used an innovative approach of highly stable nanocomplexes based on modified pectin and tannic acid (MPT-NCs). The nanocomplex formation was enabled by strong intermolecular interactions between pectin and tannic acid under very mild conditions. These nanocomplexes were characterized by particle size and morphology (DLS, TEM, …

Chrysin‐Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity Against Staphylococcus Aureus, Busi Siddhardha, Uday Pandey, K. Kaviyarasu, Rajasekharreddy Pala, Asad Syed, Ali K. Bahkali, Abdallah M. Elgorban

Pharmacy Faculty Articles and Research

The application of nanotechnology in medicine is gaining popularity due to its ability to increase the bioavailability and biosorption of numerous drugs. Chrysin, a flavone constituent of Orocylumineicum vent is well‐reported for its biological properties. However, its therapeutic potential has not been fully exploited due to its poor solubility and bioavailability. In the present study, chrysin was encapsulated into chitosan nanoparticles using TPP as a linker. The nanoparticles were characterized and investigated for their anti‐biofilm activity against Staphylococcus aureus. At sub‐Minimum Inhibitory Concentration, the nanoparticles exhibited enhanced anti‐biofilm efficacy against S. aureus as compared to its bulk counterparts, chrysin …

Synthesis And Preliminary Ex Vivo Testing Of Sirna Targeting Tcrb: A Proposed Therapy For The Treatment Of Autoimmunity, Nicholas J. Magazine

LSU Doctoral Dissertations

Abstract

Background:

As of 2018, the United States National Institutes of Health estimate that over half a billion people worldwide are affected by autoimmune disorders. Though these conditions are prevalent, treatment options remain relatively poor, relying primarily on various forms of immunosuppression which carry potentially severe side effects and often lose effectiveness overtime. Given this, new forms of therapy are needed. We propose small-interfering RNA (siRNA) for hypervariable regions of the T-cell receptor β-chain gene (TCRb) as a highly targeted, novel means of therapy for the treatment of autoimmune disorders.

Objectives:

To develop methods to produce siRNA targeting …

The Nuclear Legacy In Appalachia, Michele Morrone, Harold Perkins

Journal of Appalachian Health

Nestled in the rolling hills of Appalachia Ohio is a reminder of the role that the region played in winning the Cold War. For more than 40 years in rural Pike County, the 3,700-acre Portsmouth Gaseous Diffusion Plant (PORTS), or the “A-Plant” as the locals refer to it, enriched uranium for use in nuclear weapons. While the facility produced nuclear fuel for national security, it simultaneously exposed plant workers to chemicals and radiation and discharged pollution into the surrounding community. The A-Plant is now being demolished and the site repurposed. However, the site continues to affect the community as, for …

Hsp90 Inhibitors For Ipf/Covid-19, Ruben Manuel Luciano Colunga Biancatelli, Pavel A. Solopov, John Catravas

Bioelectrics Publications

Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

Determining The Antibacterial Activity And Mode Of Action Of Tirandamycin, Hailey Bouchard

CMC Senior Theses

Tirandamycin is a small molecule natural product that has been isolated from various species of marine and terrestrial Streptomyces. The natural product has shown antibacterial activity against an array of Gram-positive and Gram-negative bacteria, showing promise as a pharmaceutical drug. Tirandamycin has 14 known derivatives, many of which have been created synthetically. Some of its derivatives are particularly potent against the high-risk bacteria vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae and Escherichia coli. However, the antibacterial potency of these derivatives has not been tested systematically leading to the possibility of discovering more potent …