Medicine and Health Sciences Commons^™

Chemical Synthesis And Evaluation Of Azotochelin Analogs As Anticancer Agents And Their Ability To Reverse Anticancer Drug Resistance, Nishant Karadkhelkar

Theses and Dissertations

Cancer has been plaguing the humanity for several decades. In the meanwhile, multi-drug resistance (MDR) is causing abatement of effective therapeutic drugs, necessitating discovery of new class of anticancer agents. Natural products have been proved to be a promising source of structurally new anticancer agents. A specific class of bacterial secondary metabolites, named siderophores have been explored as potential anticancer agents. Enterobactin is one of the most studied siderophores as a potential anticancer agent. Azotochelin is a structurally similar but structurally simpler siderophore compared to enterobactin. Our research project focused on the evaluation of the structure activity relationship assessment of …

Understanding The Healthcare Experiences And Needs Of African Immigrants In The United States: A Scoping Review, Ogbonnaya I. Omenk, Dennis P. Watson, Hugh C. Hendrie

Scholarship and Professional Work – COPHS

Background: Africans immigrants in the United States are the least-studied immigrant group, despite the research and policy efforts to address health disparities within immigrant communities. Although their healthcare experiences and needs are unique, they are often included in the “black” category, along with other phenotypically-similar groups. This process makes utilizing research data to make critical healthcare decisions specifically targeting African immigrants, difficult. The purpose of this Scoping Review was to examine extant information about African immigrant health in the U.S., in order to develop lines of inquiry using the identified knowledge-gaps.

Methods: Literature published in the English language between 1980 …

College Of Pharmacy 2020, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Bill Gatton College Of Pharmacy Viewbook - 2020, Bill Gatton College Of Pharmacy, East Tennessee State University

Bill Gatton College of Pharmacy Miscellaneous Publications

No abstract provided.

Postnatal Catch-Up Growth Leads To Higher P66shc And Mitochondrial Dysfunction., Shelby Oke, Gurjeev Sohi, Daniel Barry Hardy

Physiology and Pharmacology Publications

Epidemiological data suggest an inverse relationship between birth weight and long-term metabolic deficits, which is exacerbated by postnatal catch-up growth. We have previously demonstrated that rat offspring subject to maternal protein restriction (MPR) followed by catch-up growth exhibit impaired hepatic function and ER stress. Given that mitochondrial dysfunction is associated with various metabolic pathologies, we hypothesized that altered expression of p66Shc, a gatekeeper of oxidative stress and mitochondrial function, contributes to the hepatic defects observed in MPR offspring. To test this hypothesis, pregnant Wistar rats were fed a control (20% protein) diet or an isocaloric low protein (8%; LP) diet …

Quantification Of Joint Blood Flow By Dynamic Contrast-Enhanced Near-Infrared Spectroscopy: Application To Monitoring Disease Activity In A Rat Model Of Rheumatoid Arthritis, Seva Ioussoufovitch, Laura B. Morrison, Lise Desjardins, Jennifer A. Hadway, Keith St Lawrence, Ting Yim Lee, Frank Beier, Mamadou Diop

Physiology and Pharmacology Publications

No abstract provided.

Nanopore-Based Metagenomic Comparison Of Airway Colonizers Between Cystic Fibrosis Patients And Healthy Individuals, Anita Samadabadi

Honors Undergraduate Theses

Cystic fibrosis (CF) is an autosomal recessive genetic disorder involving a mutation in the CF transmembrane conductance regulator protein (CFTR), which causes dysfunctional transport of chloride ions across cell membranes. CF affects multiple body systems and a few of its symptoms include chronic cough, difficulty breathing, obstructive airway disease, bacterial pulmonary infections, maldigestion, malabsorption, pancreatitis, and male infertility. Until recently, treatment options have been limited to alleviating symptoms, but a new classification of drugs, CFTR modulators, provide an opportunity to slow the progression of the disease and improve clinical outcomes. The effect of CFTR modulators may be attributed to the …

Interaction Of Aβ42 With Membranes Triggers The Self-Assembly Into Oligomers, Siddhartha Banerjee, Mohtadin Hashemi, Karen Zagorski, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The self-assembly of amyloid β (Aβ) proteins into oligomers is the major pathogenic event leading to Alzheimer's disease (AD). Typical in vitro experiments require high protein concentrations, whereas the physiological concentration of Aβ is in the picomolar to low nanomolar range. This complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here, we demonstrate that Aβ42 self-assembles into aggregates on membrane bilayers at low nanomolar concentrations - a pathway in which the membrane plays the role of a catalyst. Additionally, physiological ionic conditions (150 mM NaCl) significantly enhance on-membrane aggregation, leading to the rapid …

Paroxetine Is Pro-Inflammatory In Human Brain Microvascular Endothelial Cells, Syeda Hashimi, Sulay Patel, Omar Hassan, Bukola Odeniyi

Graduate Research Posters

BACKGROUND: Paroxetine is an antidepressant that is widely used. However, Paroxetine possesses anticholinergic properties which may contribute to cognitive decline in older adults. Surprisingly, the mechanisms of the cognitive decline of anticholinergic drugs in older adults remains elusive. A hypothesis is that a loss of cholinergic signaling is pro-inflammatory in the brain. We designed experiments to determine if Paroxetine is pro-inflammatory in Normal Human Brain Microvascular Endothelial Cells (NHBMECs).

METHOD: NHBMECs were grown at 5% CO2, 37C and 95% relative humidity until 90% confluent. NHBMECs were treated with the RNA free water as control, Paroxetine as 1.67x 10 4 mM/mol, …

Local Lung Targeting Of Tumor Associated Macrophages Combined With Cytoreductive Therapy Decrease Tumor Burden In A Secondary Lung Cancer Model, Sulaiman Alhudaithi, Hanming Zhang, Rashed Almuqbil, Wei Du, Fatemah Sunbul, Paula Bos, Sandro Da Rocha

Graduate Research Posters

Backgrounds. The efficacy of a locally administered small molecule colony stimulating factor 1 receptor inhibitor (CSF-1Ri), PLX3397, alone or in combination with cytoreductive therapy (paclitaxel) in reducing the tumor burden of an in vivo model of secondary lung cancer was investigated in this work. Local administration of immunotherapy to the lungs may enhance lung biodistribution of such therapies and reduce potential unwanted off-target toxicity. In addition, combination of such therapy with low dose standard of care chemotherapy may offer improved anti-tumor effects.

Methods. Murine breast cancer cells (4T1, known to be highly metastasized to the lungs) were transduced to …

Dendrimer Conjugation Enhances Tumor Penetration And Cell Kill Of Doxorubicin In 3d Coculture Lung Cancer Models, Rashed Almuqbil, Rodrigo S. Heyder, Elizabeth R. Bielski, Mikhail Durymanov, Joshua J. Reineke, Sandro R. P. Da Rocha

Graduate Research Posters

Background: Doxorubicin (DOX) is a potent chemotherapeutic widely used for solid tumors (1). Despite high efficacy in 2D cell culture, DOX efficacy does not translate to in vivo lung cancer models (2). Major side effects such as cardiotoxicity may be alleviated with nano-based drug delivery systems (nanoDDS). However, tumor penetration of DOX and DOX-nanoDDS is largely unknown and is an additional barrier to effective clinical therapy (3). Here we describe a nanoDDS capable of enhancing the penetration of DOX.

Methods: DOX was conjugated to generation 4 poly(amido-amine) dendrimers through (GFLG) tumor- liable bond. G4SA-GFLG-DOX was synthesized/characterized. spheroids were formed of …

Development Of An R Script For Simple Lipidomic And Metabolomic Data Analysis, Suad Alshammari, Joshua M. Morriss, Daniel Contaifer, Dayanjan S. Wijesinghe, Monther Alsultan

Graduate Research Posters

Background: Metabolomic and lipidomic studies generate vast quantities of data that are often analysed in a closed software environment with little to no access to the underlying algorithms. As a result, data processed via different software pipelines yield different results thus leading to a widespread problem of low reproducibility within these fields. To address this problem, we are developing LipidAnalyst; an R based lipidomics software pipeline. As a part of this project, we are creating a simple statistical analysis and graphing module in R to generate accurate, reproducible, high-resolution figures.

Methods: R scripts were developed under version 3.5.3 with the …

A Pre-Transplant Blood-Based Lipid Signature For Prediction Of Antibody-Mediated Rejection In Kidney Transplant Patients, Monther Al Sultan, Daniel Contaifer Jr., Joshua Morriss, Suad Alshammari, Jeffrey Stern, Sindhura Bobba, Pamela Kimball, Anne King, Dhiren Kumar, Marlon Levy, Gaurav Gupta, Dayanjan Wijesinghe

Graduate Research Posters

Purpose. The aim of this study is to demonstrate the potential of the pre-transplant lipidome to predict post-transplant antibody-mediated rejection (AMR) in kidney transplant patients.

Methods. Patients were selected from a prospective observational cohort of a single-center adult kidney transplant center in the United States. The study included 16 kidney transplant patients who develop AMR within 2 years post-transplant and 29 stable control (SC) kidney transplant patients who did not develop AMR at any time within the post-transplant follow up. Selection of group differences on the day of transplant was determined by t-test analysis. Stepwise forward method was used to …

Molecular Predictors Of Anakinra Treatment Success In Heart Failure Patients With Reduced Ejection Fraction, Joshua Morriss, Daniel Contaifer Jr, Leo F. Buckley, George Wohlford, Monther Alsultan, Suad Alshammari, Asanga D. Ranasinghe, Salvatore Carbone, Justin M. Canada, Cory Trankle, Elvin T. Price, Antonio Abbate, Benjamin W. Van Tassell, Dayanjan S. Wijesinghe

Graduate Research Posters

Background. Kineret (Anakinra) is an interleukin-1 antagonist that is under investigation for its novel clinical application treating patients that have heart failure with reduced (<50%) ejection fraction (HFrEF). A prior study from our group indicated that Anakinra may restore heart function by addressing dysregulations in HFrEF metabolic pathways. Herein, we attempt to elicit Anakinra’s effects on both metabolome and lipidome.

Methods. Lipids and metabolites that had previously been quantified by mass spectrometry (MS) from patients (n=49) who had ≥2 mg/L of high-sensitivity C-reactive protein (hs-CRP) were mTIC normalized and transformed. We conducted a stepwise Linear Discriminant Analysis (r- LDA) to test Anakinra (2 and 12 weeks) vs placebo for separation from combined baseline. Metabolic pathway analysis was performed with Fisher’s exact test algorithm for detection of over-represented and enriched analytes. Univariate analysis (one tailed t-test …

Afm Probing Of Amyloid-Beta 42 Dimers And Trimers, Sibaprasad Maity, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Elucidating the molecular mechanisms in the development of such a devastating neurodegenerative disorder as Alzheimer's disease (AD) is currently one of the major challenges of molecular medicine. Evidence strongly suggests that the development of AD is due to the accumulation of amyloid β (Aβ) oligomers; therefore, understanding the molecular mechanisms defining the conversion of physiologically important monomers of Aβ proteins into neurotoxic oligomeric species is the key for the development of treatments and preventions of AD. However, these oligomers are unstable and unavailable for structural, physical, and chemical studies. We have recently developed a novel flexible nano array (FNA)-oligomer scaffold …

Exogenous Flupirtine As Potential Treatment For Cln3 Disease, Katia Maalouf, Joelle Makoukji, Sara Saab, Nadine J. Makhoul, Angelica V. Carmona, Nihar Kinarivala, Noël Ghanem, Paul C. Trippier, Rose-Mary Boustany

Journal Articles: Pharmaceutical Sciences

CLN3 disease is a fatal neurodegenerative disorder affecting children. Hallmarks include brain atrophy, accelerated neuronal apoptosis, and ceramide elevation. Treatment regimens are supportive, highlighting the importance of novel, disease-modifying drugs. Flupirtine and its new allyl carbamate derivative (compound 6) confer neuroprotective effects in CLN3-deficient cells. This study lays the groundwork for investigating beneficial effects in Cln3^Δex7/8 mice. WT/Cln3^Δex7/8 mice received flupirtine/compound 6/vehicle for 14 weeks. Short-term effect of flupirtine or compound 6 was tested using a battery of behavioral testing. For flupirtine, gene expression profiles, astrogliosis, and neuronal cell counts were determined. Flupirtine improved neurobehavioral parameters in …

Exploring Healthcare Services Utilization And Medication Adherence Of The Arab Descent Americans In South Florida, Haifa Abdulrahman Fadil

Student Theses, Dissertations and Capstones

Research into health outcomes of Arab-descent Americans (ADAs) is sparse. ADAs identify as “White,” instead of in a separate census category, contributing to their underrepresentation in the census and the limited amount of research on their health outcomes. In the current U.S. sociopolitical climate, better understandings are needed of the impact of discrimination and Arabic culture, including level of health literacy, on ADAs’ general health and health outcomes. This study employed mixed methods to explore the impact of health literacy level and perceived discrimination on HSU and medication adherence for ADAs in South Florida. In its qualitative phase, a convenience …

Chronic Liver Disease, Medha Singhal, Rajendra Prasad, Suresh Babu, Manthappa M

Digital Journal of Clinical Medicine

No abstract provided.

A Case Of Tetanus With Classical Presentations, Maaz Khan, Dr. Bhanukumar M

Digital Journal of Clinical Medicine

No abstract provided.

Airway Management In Case Of Granulomatosis With Polyangiitis, Dr. Pranay Penmetsa, Dr. Subramanian R

Digital Journal of Clinical Medicine

No abstract provided.

Multiple Sclerosis With Depression, Dr. Siri Gangadkar, Dr. Megha Tandure, Dr. Kishor M

Digital Journal of Clinical Medicine

No abstract provided.

Suicide Attempt In Relation To Covid-19 Crisis, Dr. Sreelakshmi Rajeev, Dr. Pranahith Reddy, Ms. Chinmayi K., Dr. Kishor M

Digital Journal of Clinical Medicine

No abstract provided.

A Rare Cause Of Hyponatremia, Dr. Tamanna Gupta, Dr. Pratibha Pereira

Digital Journal of Clinical Medicine

No abstract provided.

A Case Of Pancreatic Pseudocyst Following Acute Pancreatitis, Dr Hitha Suresh, Dr Madhu C P

Digital Journal of Clinical Medicine

No abstract provided.

Collagen Xii Is A Regulator Of Corneal Stroma Structure And Function, Mei Sun, Nabeel Zafrullah, Floriane Devaux, Chinda Hemmavanh, Sheila Adams, Noel M. Ziebarth, Manuel Koch, David E. Birk, Edgar M. Espana

Molecular Pharmacology & Physiology Faculty Publications

Purpose: The aim of this study was to determine the roles of collagen XII in the regulation of stromal hierarchical organization, keratocyte organization, and corneal mechanics.

Methods: The temporal and spatial expression of collagen XII at postnatal days 4, 10, 30, 90, and 150 were evaluated in wild-type (WT) mice. The role of collagen XII in hierarchical organization was analyzed by measuring fibril diameter and density, as well as stromal lamellar structure, within ultrastructural micrographs obtained from WT and collagen XII-deficient mice (Col12a1–/–). Keratocyte morphology and networks were assessed using actin staining with phalloidin and in vivo confocal …

Effects Of An Exogenous Ketone Supplement On Five‐Kilometer Running Performance, Philip J. Prins, Andrew P. Koutnik, Dominic P. D’Agostino, Christopher Q. Rogers, Jacob F. Seibert, Jillian A. Breckenridge, Daniel S. Jackson, Edward J. Ryan, Jeffrey D. Buxton, Dana L. Ault

Molecular Pharmacology & Physiology Faculty Publications

Numerous oral ketone supplements are marketed with the claim that they will rapidly induce ketosis and improve exercise performance. The purpose of this study was to assess exercise performance time and related physiological, metabolic and perceptual responses of recreational endurance runners after ingestion of a commercially available oral ketone supplement. Recreational endurance runners (n = 10; age: 20.8 ± 1.0 years; body mass: 68.9 ± 5.6 kg; height: 175.6 ± 4.9 cm) participated in a double-blind, crossover, repeated-measures study where they were randomized to 300 mg.kg-1 body weight of an oral β-hydroxybutyrate-salt + Medium Chain Triglyceride (βHB-salt+MCT) ketone supplement or …

Ketone Bodies Attenuate Wasting In Models Of Atrophy, Andrew P. Koutnik, Angela M. Poff, Nathan P. Ward, Janine M. Deblasi, Maricel A. Soliven, Matthew A. Romero, Paul A. Roberson, Carl D. Fox, Michael D. Roberts, Dominic P. D'Agostino

Molecular Pharmacology & Physiology Faculty Publications

Background: Cancer Anorexia Cachexia Syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer-related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therapeutic treatments.

Methods: A novel model of systemic metastasis was evaluated for the comprehensive CACS (metastasis, skeletal muscle and adipose tissue wasting, inflammation, anorexia, anemia, elevated protein breakdown, hypoalbuminemia, and metabolic derangement) in both males and females. Ex vivo skeletal muscle analysis was utilized to determine ubiquitin proteasome degradation pathway activation. …

Anticancer Activity Of Cepharanthine On Non-Small Cell Lung Cancer Cells, Yaowaluck Detpichai

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cepharanthine (CEP) is a biscoclaurine alkaloid, isolated from the roots of Stephania cepharanthine Hayata that possesses potent anticancer properties against several types of cancer such as hepatocellular carcinoma, colorectal cancer, leukemia and ovarian cancer. However, there is still limited information regarding to its effects on non-small cell lung cancer cells. Therefore, the objectives of the present study were to determine the cytotoxicity of CEP and its underlying mechanisms in non-small cell lung cancer cells expressing wild-type p53 and EGFR (A549) and non-small cell lung cancer cells expressing mutant p53 and EGFR (H1975). The results indicated that CEP significantly inhibited the …

Profiling Transcription And Retrotransposition Of Mouse L1 Subfamilies, Lingqi Kong

Electronic Theses and Dissertations

Transposable elements, also called jumping genes, comprise almost 45% of the human genome. In contrast, only 1% of the human genome is protein-coding sequences. The function and advantages of maintaining such massive copies of transposable elements in the human genome are still unclear. Long interspersed element 1 (L1), the most substantial group and the only active autonomous transposable element in the human genome, has revealed its unique roles in many diseases. The insertional mutagenesis induced by L1 retrotransposition events could threaten human genomic stability and generate unexpected mutations. L1 overexpression has been documented in both somatic and germline cells and, …

Anaphylaxis Diagnosis And Management In The Emergency Department Of A Tertiary Hospital In The Philippines, Michelle Joy De Vera, Iris Conela Tagaro

Ateneo School of Medicine and Public Health Publications

Background:
In the Emergency Department (ED), diagnosis and management of anaphylaxis are challenging with at least 50% of anaphylaxis episodes misdiagnosed when the diagnostic criteria of current guidelines are not used.

Objective:
Objective of our study was to assess anaphylaxis diagnosis and management in patients presenting to the ED.

Methods:
Retrospective chart review conducted on patients presenting to The Medical City Hospital ED, the Philippines from 2013–2015 was done. Cases were identified based on International Statistical Classification of Diseases, 10th revision coding for either anaphylaxis or other allergic related diagnosis. Cases fitting the definition of anaphylaxis as identified by the …