Chemicals and Drugs Commons^™

Targeted Next-Generation Sequencing Of Congenital Hypothyroidism-Causative Genes Reveals Unexpected Thyroglobulin Gene Variants In Patients With Iodide Transport Defect, Carlos Eduardo Bernal Barquero, Romina Celeste Geysels, Virginie Jacques, Gerardo Hérnan Carro, Mariano Martín, Victoria Peyret, María Celeste Abregú, Patricia Papendieck, Ana María Masini-Repiso, Frédérique Savagner, Ana Elena Chiesa, Cintia E. Citterio, Juan Pablo Nicola

Pharmacy Faculty Articles and Research

Congenital iodide transport defect is an uncommon autosomal recessive disorder caused by loss-of-function variants in the sodium iodide symporter (NIS)-coding SLC5A5 gene and leading to dyshormonogenic congenital hypothyroidism. Here, we conducted a targeted next-generation sequencing assessment of congenital hypothyroidism-causative genes in a cohort of nine unrelated pediatric patients suspected of having a congenital iodide transport defect based on the absence of 99mTc-pertechnetate accumulation in a eutopic thyroid gland. Although, unexpectedly, we could not detect pathogenic SLC5A5 gene variants, we identified two novel compound heterozygous TG gene variants (p.Q29* and c.177-2A>C), three novel heterozygous TG gene variants (p.F1542Vfs*20, p.Y2563C, and …

Clinical Characteristics And Implications Of Bradycardia In Covid‐19 Patients Treated With Remdesivir: A Single‐Center Retrospective Cohort Study, Ariyon Schreiber, Justin S. Bauzon, Kavita Batra, Salman Mohammed, Kevin Lee, Nazanin Houshmand, Uyen Pham, Celica Cosme, Kim Inciong, Omar Al‑Taweel, Keaton Nasser, Jibran Rana, Chris Sossou, Ariel Go, Dalia Hawwass, Jimmy Diep, Chowdhury H. Ahsan

School of Medicine Faculty Research

Background and Objectives: Remdesivir is an antiviral drug used to treat coronavirus disease 2019 (COVID-19) with a relatively obscure cardiac efect profle. Previous studies have reported bradycardia associated with remdesivir, but few have examined its clinical characteristics. The objective of this study was to investigate remdesivir associated bradycardia and its associated clinical characteristics and outcomes. Methods: This is a single-institution retrospective study that investigated bradycardia in 600 patients who received remdesivir for treatment of COVID-19. A total of 375 patients were included in the study after screening for other known causes of bradycardia (atrioventricular [AV] nodal blockers). All patients were …

Neuropilin-2 In Advanced Prostate Cancer And Its Targeting With Novel Small Molecule Inhibitors, Ridwan Islam

Theses & Dissertations

Despite the development of new therapies, clinical management of advanced metastatic castrationresistant prostate cancer (mCRPC) still remains challenging owing to the emergence of therapy resistance. Resistance to the therapies is driven by both AR and non-AR pathways. Non-AR pathway is characterized by a lineage switch that leads to the development of neuroendocrine-like (NE-like) prostate cancer (PCa), which has a fulminant clinical course due to the lack of effective treatment strategy. Therefore, novel molecular targets need to be identified to develop effective therapeutic regimen to improve the outcomes in advanced PCa patients including NE-like PCa. Recent investigation on advanced PCa patients …

The Kinetics And Cellular Imaging Of Multi-Color Fluorescent And Chemiluminescent Compounds, Bo Li

Chemistry Theses and Dissertations

A three-dimensional display is a useful method which can provide spatially accurate representations of high-resolution images with a 360^° view. Therefore, it has potential to be applied widely in the medical area, entertainment industry and for military applications. According to the first-generation 3D digital light photoactivatable dye display (3D Light PAD), N-phenyl spirolactam rhodamine B was used as photoactivatable compound that could be switched from non-fluorescent to fluorescent using ultraviolet light. However, the detailed mechanism, how other rhodamine derivatives would perform in 3D Light PAD, and what other factors in this system could improve the imaging quality remained unclear. …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Development Of A New Affinity Membrane For Rapidly Purifying Non-Antibody Proteins, Friendship Edioma

All Theses

This thesis project describes the modification and evaluation of a new affinity membrane for rapid chromatographic purification of non-antibody proteins. The affinity membrane utilizes Im7/CL7 coupling technology developed by Dr. Vassylyev's lab at the University of Alabama Birmingham (UAB), licensed by TriAltus Bioscience. The behavior of the membrane was evaluated using purified CL7-tagged Cas9 as my model protein for static and dynamic binding capacity analysis.

Chapter one provides an overview on biopharmaceutical drug production process development. I discuss how protein drugs are produced, isolated, and purified from the cell supernatant after upstream phases are completed. Despite increasing demands for biologics, …

Identification And Quantitation Of Unspecified Impurities Discovered In Novel Oral Irinotecan By Lc-Ms/Ms And Uhplc, Laura B. Miller

Forensic Science Master's Projects

Irinotecan is a cancer medication approved for medical use in the United States in 1996. It is currently administered via intravenous injection. However, intravenous dosing has disadvantages such as requirement of administration by a trained professional in a medical facility, possible severe adverse effects, pain at the injection site, and possible hemolysis if injected too rapidly. Previously oral administration was not feasible because the p-glycoprotein (p-GP) on the cell membrane of stomach cells acts as a defense mechanism against harmful substances by pumping the irinotecan back into the intestinal lumen for excretion. With the discovery of the p-GP inhibitor encequidar …

Protein-Protein Interaction Prediction From Language Of Biological Coding, Nayan Howladar

LSU New Orleans Theses and Dissertations

Protein-protein interactions in a cell are essential to the characterization and performance of various fundamental biological processes. Due to the tedious, resource-expensive, and time-consuming experimental processes, computational techniques to solve protein pair interaction difficulties have emerged as an active research area in bioinformatics. This research seeks to develop an innovative machine learning-based technique that predicts the interaction of a protein pair based on carefully selected input features and exploits information-rich evolutionary information. We developed a protein-protein interaction predictor, PPILS, that leverages the evolutionary knowledge from the protein language model. We examined several distinct neural network architectures: CNN+LSTM, Transformer, Encoder-Decoder, and …

Role Of Type 4 Phosphodiesterases In Thermoregulation And Salivation In Mice, Abigail Grace Boyd

Graduate Theses and Dissertations (2019 - present)

Type 4 cAMP phosphodiesterases (PDE4s) comprise a family of four isoenzymes, PDE4A to D, that hydrolyze and inactivate the second messenger cAMP. Non/PAN selective PDE4 inhibitors, which inhibit all four subtypes simultaneously, produce many promising therapeutic benefits, such as anti-inflammatory or cognition- and memory-enhancing effects. However, unwanted side effects, principally, nausea, diarrhea, and emesis, have long hampered their clinical and commercial success. Targeting individual PDE4 subtypes has been proposed for developing drugs with an improved safety profile, but which PDE4 subtype(s) is/are actually responsible for nausea and emesis remains ill defined. In mice treated with PAN-selective inhibitors, there is substantial …

Radioluminescence Based Biochemical Sensing And Imaging Strategies To Measure Local Drug Release And Ph, Gretchen B. Schober

All Dissertations

In this dissertation we describe methods for measuring infection relevant biochemical analytes using radioluminescent and ultrasound luminescent materials. Films and nanoparticles fabricated with europium doped gadolinium oxysulfide (Gd₂O₂S:Eu³⁺) are used to quantitatively measure radiolabeled pharmaceutical concentration, specifically tritium labeled vancomycin (³H-vancomycin). Europium and dysprosium doped strontium aluminate is used to fabricate an ultrasound modulated, pH sensing film. These methods are indicated for theranostic evaluation of implant associated infection. Bacterial biofilms are inherently resistant to traditional antibiotic treatment and can coat biomedical implants. These biofilm related infections are difficult or impossible to eradicate …

Hla Pharmacogenetic Markers Of Drug Hypersensitivity From The Perspective Of The Populations Of The Greater Middle East, Hend Chaker Masmoudi, Nariman Afify, Halima Alnaqbi, Zainab Alhalwachi, Guan Kwang Tay, Habiba Alsafar

Research outputs 2022 to 2026

Specific HLA associations with drug hypersensitivity may vary between geographic regions and ethnic groups. There are little to no data related to HLA-drug hypersensitivity on populations who reside in the Greater Middle East (GME), a vast region spanning from Morocco in the west to Pakistan in the east. In this review, the authors intended to summarize the significant HLA alleles associated with hypersensitive drug reactions induced by different drugs, as have been found in different populations, and to summarize the prevalence of these alleles in the specific and diverse populations of the GME. For example, HLA-B * 57:01 allele prevalence, …

Statins: Masked Anti-Epileptic Warriors, Govinda Khatri, Priya Kotak, Ayush Kumar, Mohammad Mehedi Hasan

Medical College Documents

No abstract provided.

Sar Study Of Niclosamide Derivatives In The Human Glioblastoma U-87 Mg Cells, Shizue Mito, Benxu Cheng, Benjamin A. Garcia, Daniela Gonzalez, Xin Yee Ooi, Tess C. Ruiz, Francisco Xavier Elisarraras, Andrew Tsin, Sue Anne Chew, Marco A. Arriaga

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Glioblastoma is a lethal malignant brain tumor, and the development of efficient chemotherapeutic agents remains an urgent need. Niclosamide, an anthelmintic drug, which has been used to treat tapeworm infections more than 50 years, has recently attracted renewed attention due to its evident anticancer activities. It has been shown that niclosamide induces cytotoxicity in human glioblastoma U-87 MG cells corresponding with increased protein ubiquitination, ER stress, and autophagy. Furthermore, niclosamide showed down regulation of multiple pro-survival signaling pathways including Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and STAT3, which further caused reduction of U87-MG cell viability. However, the molecular mechanisms of niclosimide and its …

Development Of A Decellularized Hydrogel Composite And Its Application In A Novel Model Of Disc-Associated Low Back Pain In Female Sprague Dawley Rats, David Lillyman

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant pathology associated with chronic low back pain is degeneration of intervertebral discs in the lumbar spine. During degeneration, nerves can sprout into the intervertebral disc tissue and be chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to screen therapeutics and study pathomechanisms of pain.

While many research teams have created animal models of disc degeneration, the translation of these platforms …

Treatment Of Tardive Dyskinesia With High Dose Vitamin B6 Associated With Depression, Marjorie Mccoy, Adam Schindzielorz, Suzanne Holroyd

Marshall Journal of Medicine

Tardive dyskinesia (TD) is a movement disorder associated with dopamine receptor blocking medications. Recommended treatments for TD include discontinuing the causative agent, adding vesicular monoamine transporter 2 (VMAT2) inhibitors, or adding vitamin B6. We present a 66-year-old Caucasian male with bipolar I disorder who developed TD while on lithium and quetiapine having been euthymic on this regimen for three years. He was initially treated with 1200 mg B6 daily. This failed to improve his TD and was associated with a depressive episode. He switched to valbenazine 40 mg daily which improved his TD and concurrently his mood, but months later …

Synthesis Of Triaminopyrimidine Derivatives For Inhibition Of Inflammatory Caspases, Marianna C. Haddad, Caitlin Karver

DePaul Discoveries

Caspases are cysteine-dependent aspartic proteases whose functions are connected to different mechanisms of cell death and inflammation. As caspase-1 plays a significant role in the immune response, its activity has been of interest as a target for inhibitor development as its inhibition will reduce the levels of pro-inflammatory cytokines in inflammatory diseases, thus minimizing the symptoms that arise and serving as a possible therapeutic approach. Prior work discovered a family of potent inhibitors of caspase-1 with a common triaminopyrimidine scaffold. To further explore structure-activity relationship profiles of potential inhibitors of caspase-1, two different syntheses were attempted to create two new …

In-Silico Analysis Of Interacting Pathways Through Kim-1 Protein Interaction In Diabetic Nephropathy, Fatima Abid, Z Rubab, Syeda Sadia Fatima, A Qureshi, Arfa Azhar, A Jafri

Department of Biological & Biomedical Sciences

Background: Human Kidney Injury Molecule-1, also known as HAVCR-1 (Hepatitis A virus cellular receptor 1), belongs to the cell-surface protein of immunoglobulin superfamily involved in the phagocytosis by acting as scavenger receptor epithelial cells. The study focused on pinpointing the mechanisms and genes that interact with KIM-1.
Methods: This in-silico study was done from March 2019 to December 2019. The Enrichment and protein-protein interaction (PPI) network carefully choose proteins. In addition, the diagramed gene data sets were accomplished using FunRich version 3.1.3. It was done to unveil the proteins that may affect the regulation of HAVCR1 or may be regulated …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …

A Changing Epidemic And The Rise Of Opioid-Stimulant Co-Use, Saeed Ahmed, Zouina Sarfraz, Azza Sarfraz

Department of Paediatrics and Child Health

No abstract provided.

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

Influence Of Paclitaxel Nanomedicine On The Pancreatic Tumor Immune Components, Godwin Peasah-Darkwah

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortalities in the U.S due to ineffective therapeutic options. Pancreatic tumors are highly desmoplastic and inhibit efficient uptake of therapeutic payloads. Paclitaxel (PTX) has been tested in PanCa therapy with marginally better clinical outcomes, but remain limited by its poor hemocompatibility, biodistribution and intracellular accumulation in tumor cells. Thus, we synthesized a next generation nanoparticle system for PTX to improve its pharmacokinetics and pharmacodynamics (PKPD) in treating PanCa. We also examined ability of the nano formulation to potentiate gemcitabine (GEM) activity in combating chemoresistance in the pancreatic tumor microenvironment …

Emicizumab-Kxwh: A Critical Review, Kiera O'Leary

International Undergraduate Journal of Health Sciences

The first descriptions of haemophilia A were reported in the second century AD, with the first modern description by John Conrad Otto in 1803. Historically, the natural history of haemophilia A was associated with very high rates morbidity and mortality, often following trivial accidents. Although treatment options for haemophilia A have been revolutionised in recent decades, haemophilia A remains a hereditary disease of concern and factor replacement products remain the mainstay of treatment.

As such, patients with haemophilia can carry huge burdens, particularly when a complication such as a FVIII inhibitor is present. A recently approved novel therapeutic, Emicizumab-kxwh, has …

Multidrug Resistance In Cancer: Understanding Molecular Mechanisms, Immunoprevention And Therapeutic Approaches, Talha Bin Emran, Asif Shahriar, Aar Rafi Mahmud, Tanjilur Rahman, Mehedy Hasan Abir, Mohd Faijanur-Rob Siddiquee, Hossain Ahmed, Nova Rahman, Firzan Nainu, Elly Wahyudin

School of Medicine Publications

Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as …

17Β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation Of Mesenteric Arteries In Ovariectomized Uc Davis Type 2 Diabetes Mellitus Rats In Prediabetic State, Md Rahatullah Razan, Farjana Akther, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

We recently reported sex differences in mesenteric arterial function of the UC Davis type-2 diabetes mellitus (UCD-T2DM) rats as early as the prediabetic state. We reported that mesenteric arteries (MA) from prediabetic male rats exhibited a greater impairment compared to that in prediabetic females. However, when females became diabetic, they exhibited a greater vascular dysfunction than males. Thus, the aim of this study was to investigate whether the female sex hormone, estrogen preserves mesenteric arterial vasorelaxation in UCD-T2DM female rats at an early prediabetic state. Age-matched female Sprague Dawley and prediabetic (PD) UCD-T2DM rats were ovariectomized (OVX) and subcutaneously implanted …

Biowill - Characterising Willow Bark Bio-Actives For Skin Therapies, Arnold Marisa

ORBioM (Open Research BioSciences Meeting)

Willow bark is considered as a disposable by-product when processing willow for biomass. Willow (Salix) is known to contain high value bioactive compounds which include salicin and its derivatives, and other phytochemicals of interest such as polyphenols and flavonoids. The plant is historically known as the primary source of salicylates to which the well-known drug aspirin is derived from. The work forms part of the Interreg project BioWILL, which is focused on integrated “Zero Waste” biorefinery utilising all fractions of willow feedstock for the production of biochemicals and renewable energy. This project aims to investigate the crude and …

Thromboelastography Profiles Of Hemophilia A Patients On Emicizumab, Daniel J. Vanzweden, Meera Chitlur, Charity J. Stadler

Medical Student Research Symposium

Emicizumab is a new monoclonal antibody developed to dtreat people with Hemophilia A, especially those with antibodies. However, breakthrough bleeding can still occur in patients taking Emicizumab. TEG is a global coagulation assay which measures coagulability through viscosity. This study describes the use of tissue factor activated TEG in measuring bleeding profiles in patients taking Emicizumab. The goal of this prospective study is to determine if TEG can be used, which variables of TEG might be useful, and how much more useful it is than the current standard, aPtt. Findings include a 25% increased R time and 24% increased K …

Sex Differences In Locomotor Activity And Behavioral Sensitization In Rats Administered Fentanyl, Jessica J. Lee, Nareen Sadik, Cameron Davidson Phd, Majd Yahya, Josie Zdun, Shane Perrine Phd

Medical Student Research Symposium

Opioid overdoses have continued to increase, and women have experienced a greater rate of increase than males. Preclinical studies demonstrate marked sex differences in addiction-related behaviors, with females being more vulnerable due to a potential role of estradiol. We sought to understand how the estrous cycle, as a proxy measure of estradiol, influences sex differences in the sensitizing effects of fentanyl. In this ongoing study, we used male and female rats to investigate potential sex effects of fentanyl (20µg/kg subcutaneously) administration for 14 days and a forced abstinence period of 13 days on behavioral sensitization via locomotor activity (LMA) following …

Developing An Accurate Empirical Correlation For Predicting Anti-Cancer Drugs’ Dissolution In Supercritical Carbon Dioxide, Fardad Faress, Amin Yari, Fereshteh Rajabi Kouchi, Ava Safari Nezhad, Alireza Hadizadeh, Leili Sharif Bakhtiar, Yousef Naserzadeh, Niloufar Mahmoudi

International Business and Entrepreneurship Faculty Publications

This study introduces a universal correlation based on the modified version of the Arrhenius equation to estimate the solubility of anti-cancer drugs in supercritical carbon dioxide (CO2). A combination of an Arrhenius-shape term and a departure function was proposed to estimate the solubility of anti-cancer drugs in supercritical CO2. This modified Arrhenius correlation predicts the solubility of anti-cancer drugs in supercritical CO2 from pressure, temperature, and carbon dioxide density. The pre-exponential of the Arrhenius linearly relates to the temperature and carbon dioxide density, and its exponential term is an inverse function of pressure. Moreover, the departure function linearly correlates with …

Synthesis Of Curcumin Derivatives: Increasing Compound Stability, Chloe Wilke

Undergraduate Research Symposium

Curcumin (C₂₁H₂₀O₆), the main active component in the spice Turmeric, has many recognized health benefits ranging from anti-inflammatory agents to the suppression of the proliferation of tumors. Curcumin has been used worldwide as an antiseptic and treatment for inflammatory conditions, arthritis, and sepsis. This water-insoluble molecule is unstable and degrades quickly upon entering the body. In order to preserve the beneficial structure of curcumin before it is broken down by the digestive system, carbohydrates are attached to alter the compound, increasing polarity and solubility. This topic was researched by analyzing multiple journal articles and …