Medical Pharmacology Commons^™

Modulation Of Tlr4/Nf-Κb, Nrf2/Ho-1 And Pi3k/Akt Signaling By Cilostazol Mitigates Lipopolysaccharide-Induced Septic Acute Kidney Injury, Ahmed F. Mohamed Dr., Helmy Said Dr, Hala F. Zaki, Marwa M. Safar Prof. Dr.

Pharmacy

Aim: Cilostazol was investigated as a protective agent against lipopolysaccharide (LPS)-associated acute kidney damage in mice. Methods: Cilostazol (50 mg/kg/day; p.o.) administered for 7 consecutive days before a single LPS dose (2 mg/kg; i.p.). Results: Cilostazol hampered serum creatinine, cystatin C, and renal kidney injury molecule-1 and neutrophil gelatinase associated lipocalin; repressed toll-like receptor 4 and MyD88 transcription, as well as nuclear factor-kappa B p65, interleukin-1b, and malondialdehyde content; and boosted Nrf2 mRNA expression, hemeoxygenase-1 activity, and reduced glutathione content. This was synchronous with an upregulation of p-phosphoinositide 3-kinase and p-Akt expressions. Conclusion: Collectively, cilostazol prevented LPS renal injury, which …

The Effect Of An Educational Handout On Knowledge, Awareness And Attitudes Of Pre-Exposure Prophylaxis (Prep) Among Participants At A Needle And Syringe Exchange Site, Mckenzie Buckel

DNP Projects

Background: In 2018, the total number of HIV cases in the United States was 1.2 million. Almost 186,500 of these cases were attributed to intravenous drug use. With the adherence to pre-exposure prophylaxis (PrEP) there is approximately a 49% decrease in the rates of HIV among people who inject drugs and the most significant barrier to PrEP among this population is a lack of awareness and knowledge.

Objective: The purpose of this study was to determine participants’ of a needle and syringe exchange site knowledge, awareness and attitudes of PrEP after reviewing an educational handout about PrEP.

Methods: A quasi …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Endothelial Activation Impairs The Function Of Small Extracellular Vesicles, Nicolas Herrera-Zelada, Úrsula Zúñiga-Cuevas, Andrés Ramírez-Reyes, Ignacio Norambuena-Soto, Leslye Venegas-Zamora, Mayarling F Troncoso, Alejandra Hernández, Gina Sánchez, Zully Pedrozo, Sergio Lavandero, Jaime A Riquelme

Faculty, Staff and Student Publications

Small extracellular vesicles are nanosized vesicles (30-200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-reduce in vitro ischemia/reperfusion (I/R) injury in cardiomyocytes, but whether a pro-inflammatory state of the endothelium impairs the functionality of these SEVs remains to be elucidated. To test this, human umbilical vein endothelial cells cells were treated with TNF-α 10 ng/mL and the expression of the pro-inflammatory parameters VCAM-1, ICAM-1 and eNOS were determined by Western blot. SEVs were …

Storage Stability Of Atheroglitatide, An Echogenic Liposomal Formulation Of Pioglitazone Targeted To Advanced Atheroma With A Fibrin-Binding Peptide, Khalid Alghamdi, Zeyad Alehaideb, Ashok Kumar, Hamad Al-Eidi, Sahar S Alghamdi, Rasha Suliman, Rizwan Ali, Feras Almourfi, Saleh M Alghamdi, Mohamed Boudjelal, Sabine Matou-Nasri

Faculty, Staff and Student Publications

There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In this study, traditional medicinal plant extracts were tested for cultured human melanocyte proliferation, migration, and melanogenesis using MTT, scratch wound-healing assays, transmission electron microscopy, immunofluorescence staining, and Western blot technology. Of the methanolic extracts, Lycium shawii L. (L. shawii) extract increased melanocyte proliferation at low concentrations and modulated melanocyte migration. At the lowest tested concentration (i.e., 7.8 μg/mL), the L. shawii …

Factors Associated With Improved Outcome Of Inhaled Corticosteroid Use In Covid-19: A Single Institutional Study, A. Manfra, Claire Chen, Kavita Batra, Kyaw Min Tun, Mutsumi Kioka

Department of Internal Medicine Faculty Research

Asthmatics seem less prone to adverse outcomes in coronavirus disease 2019 (COVID-19) and some data shows that inhaled corticosteroids (ICS) are protective. We gathered data on anecdotal ICS and outcomes of patients hospitalized with COVID-19, given there is literature supporting ICS may reduce risk of severe infection. In addition, we fill gaps in current literature evaluating Charlson Comorbidity Index (CCI) as a risk assessment tool for COVID-19. This was a single-center, retrospective study designed and conducted to identify factors associated intubation and inpatient mortality. A multivariate logistic regression model was fit to generate adjusted odds ratios (OR). Intubation was associated …

The Safety And Efficacy Of Pravastatin In The Treatment Of Preeclampsia, Miranda Shelly, Tara Riley

Physician Assistant Capstones, 2020-current

Objective: Assess the efficacy of pravastatin in the prevention or treatment of preeclampsia in women who are at risk. Design: Systematic literature review. Methods: A search was performed using Pubmed utilizing the terms preeclampsia and pravastatin. The results were limited to studies that were double blind and placebo controlled and that occurred in the last 5 years. Results: None of the studies found statistical significance in the rate of preeclampsia between the experimental and control groups. Only one study found statistically significant differences in fetal birth weight and age at delivery. The other two studies found no differences between groups …

Prophylactic Intravenous Prehydration With Sodium Bicarbonate Or Sodium Chloride In The Prevention Of Contrast Induced Acute Kidney Injury, Briana Lockett, Caroline Dong

Physician Assistant Capstones, 2020-current

Introduction: Iodinated contrast media is a crucial component in the diagnostic work up of many life-threatening illnesses. However, it has been reported to cause acute kidney injury after administration, especially in patients with pre-existing renal disease. Several prophylactic treatments have been studied in hopes of minimizing these adverse events. The current standard of care in this patient population is prophylactic intravenous volume administration with either sodium chloride or sodium bicarbonate. Objective: The goal of this literature review is to determine if prophylactic intravenous volume administration with either saline or sodium bicarbonate prior to contrast administration decreases the incidence of contrast …

Cystic Fibrosis Transmembrane Conductance Regulator Modulation May Improve Intestinal Inflammation In Adults With Cystic Fibrosis, Lauren G. Culver

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Ooi CY, Syed SA, Rossi L, Garg M, Needham B, Avolio J, Young K, Surette MG, Gonska T. Impact of CFTR modulation with Ivacaftor on Gut Microbiota and Intestinal Inflammation. Sci Rep. 2018 Dec 13;8(1):17834. https://doi.org/10.1038/s41598-018-36364-6

for a patient with cystic fibrosis experiencing small bowel obstruction.

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …

The Nogo Receptor Ngr2, A Novel Αvβ3 Integrin Effector, Induces Neuroendocrine Differentiation In Prostate Cancer, Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey-Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter Mccue, Andrew V. Kossenkov, Yanqing Wang, David W. Goodrich, Sheng-Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, …

A Reactivation Of Ocular Toxoplasmosis During Pregnancy, Brett Garee Od, Ms, Sarah Dieter Od, Pete Liette Od

Optometric Clinical Practice

Background: Toxoplasma gondii is a parasite estimated to affect over 500 million people worldwide. The feline is the definitive host for the parasite and infection may be acquired or congenital via maternal transmission. Humans may acquire the infection by ingestion of raw or undercooked meats and vegetables, contaminated water, or exposure to infected cat feces. The infection is often benign, self-limiting, and asymptomatic for humans, but potentially life threatening to infants or the immunocompromised patient.

Case Report: A 22 year-old Caucasian female, pregnant at 12 weeks gestation, presented to the optometry service with acute symptoms of hazy vision …

Effect Of Cell Cycle On Cell Surface Expression Of Voltage-Gated Sodium Channels And Na+,K+-Atpase, Samantha Edenfield, Abigail M. Sims, Constance Porretta, Harry J. Gould, Dennis Paul

School of Graduate Studies Faculty Publications

Voltage-gated sodium channels (VGSCs) are the target for many therapies. Variation in membrane potential occurs throughout the cell cycle, yet little attention has been devoted to the role of VGSCs and Na+,K+-ATPases. We hypothesized that in addition to doubling DNA and cell membrane in anticipation of cell division, there should be a doubling of VGSCs and Na+,K+-ATPase compared to non-dividing cells. We tested this hypothesis in eight immortalized cell lines by correlating immunocytofluorescent labeling of VGSCs or Na+,K+-ATPase with propidium iodide or DAPI fluorescence using flow cytometry and imaging. Cell surface expression of VGSCs during phases S through M was …

Ctpathway: A Crosstalk-Based Pathway Enrichment Analysis Method For Cancer Research, Haizhou Liu, Mengqin Yuan, Ramkrishna Mitra, Xu Zhou, Min Long, Wanyue Lei, Shunheng Zhou, Yu-E Huang, Fei Hou, Christine M. Eischen, Wei Jiang

Department of Cancer Biology Faculty Papers

Background: Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated.

Methods: To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with >440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in …

Lysine Methyltransferase Nsd1 And Cancers: Any Role In Melanoma?, Imène Krossa, Thomas Strub, Andrew E Aplin, Robert Ballotti, Corine Bertolotto

Department of Cancer Biology Faculty Papers

Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of NSD1 in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or …

Diverging Effects Of Adolescent Ethanol Exposure On Tripartite Synaptic Development Across Prefrontal Cortex Subregions, Christopher Douglas Walker, Hannah Gray Sexton, Jentre Hyde, Brittani Greene, Mary-Louise Risher

Biomedical Sciences

Adolescence is a developmental period that encompasses, but is not limited to, puberty and continues into early adulthood. During this period, maturation and refinement are observed across brain regions such as the prefrontal cortex (PFC), which is critical for cognitive function. Adolescence is also a time when excessive alcohol consumption in the form of binge drinking peaks, increasing the risk of long-term cognitive deficits and the risk of developing an alcohol use disorder later in life. Animal models have revealed that adolescent ethanol (EtOH) exposure results in protracted disruption of neuronal function and performance on PFC-dependent tasks that require higher-order …

Novel Drugs Approved In 2021-2022, Michael Do, Bona Shin, Elaina Lioudis, Emaleigh Munn

Transformative Medicine

This article provides an abbreviated overview of the newly Federal Drug Administration (FDA)approved novel drugs of 2021-2022 with their respective approved indication(s). The FDA serves as the governing body that regularly evaluates and approves medications that will eventually be introduced to the market for routine use. These medications include both drugs that are the same or related to previously approved products (e.g., Extended indications of priorly approved medications) and novel drugs. By definition, a novel drug is an innovative product which serves to improve quality care in patient populations with unmet or advanced medical needs to overall advance patient care …

The Effects Of Cannabidiol On Aqueous Humor Outflow And Trabecular Meshwork Cell Signaling., Alyssa S. Aebersold, Zhao-Hui Song

Faculty and Staff Scholarship

Intraocular pressure (IOP) is regulated primarily through aqueous humor production by ciliary body and drainage through uveoscleral and trabecular meshwork (TM) tissues. The goal of this study was to measure the effect of non-psychotropic cannabidiol (CBD) on aqueous humor outflow through TM and assess the effect of CBD on the TM cell signaling pathways that are important for regulating outflow. Perfused porcine eye anterior segment explants were used to investigate the effects of CBD on aqueous humor outflow. Cultured porcine TM cells were used to study the effects of CBD on TM cell contractility, myosin light chain (MLC) and myosin …