Chemicals and Drugs Commons^™

Application Of Artificial Intelligence And Machine Learning In Chemistry, Niraj Verma

Chemistry Theses and Dissertations

In the last four years, I have been exposed to various topics in scientific research under the supervision of Dr. Kraka in the CATCO group. Numerous involved chemistry projects were undertaken to gain an understanding of the basic laws of nature involving vibrational spectroscopy, molecular acidity, and catalysts based on transition metals for halogen chemistry. The insights from computational chemistry were then applied to model and predict various complicated problems in chemistry via artificial intelligence. With the help of classical artificial intelligence, the non-covalent interactions governing the properties of proteins and water properties were analyzed. Significant improvements were made in …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

Modulation Of Antibacterial Activity And Cytotoxicity In Amphipathic Cyclic Peptide [R4w4] Using Histidine Substitution, Ryan Stueber

Pharmaceutical Sciences (MS) Theses

Antibiotics have been the gold standard frontline defense against bacterial infections for decades. At the same time, these infecting bacteria have continued to evolve to resist developed antibiotics in an almost endless cycle. As such, we aim to take an alternative approach utilizing antimicrobial peptides (AMPs) as a means to end this cycle. [R4W4] is among known AMPs that demonstrated antimicrobial activity against methicillin-resistant staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 2.67 μg/mL. This peptide had notably effective antimicrobial activity, especially relative to linear (R4W4). However, it displayed a concerning level of cytotoxicity; eliciting a human embryonic …

July / August 2021, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy.

Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton

Graduate Theses/Dissertations

Diethylene glycol monoethyl ether (DEGEE) is a promising solvent component in topical cream formulations due to its superior solubilizing abilities with certain active pharmaceutical ingredients. One of the goals of this study is to characterize the effects of pH on the physical and chemical stabilities of topical cream formulations containing particularly high concentrations of DEGEE by characterizing a full topical pH profile of 3.5 – 9.0. The second goal is to evaluate the presence, amount, and characteristics of lyotropic liquid crystals (LLCs), molecularly structured in a lamellar phase, in a model cream emulsion utilizing polarized light microscopy (PLM). The presence …

Milk Exosomes: Nature's Abundant Nanoplatform For Theranostic Applications, Benilde Adriano, Nycol Cotto, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles. Exosomes have proven to be excellent nanocarriers for carrying lipids, proteins, mRNAs, non-coding RNAs, and DNAs, and disseminating long-distance intercellular communications in various biological processes. Among various cell-line or biological fluid derived exosomes, milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications. To be an effective delivery carrier for their clinical translation, exosomes must inbuilt loading, release, targeting, and imaging/tracking characteristics. Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the …

Targeting Plasma Membrane Phosphatidylserine Content To Inhibit Oncogenic Kras Function, Walaa E. Kattan

Dissertations and Theses (Open Access)

The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). We therefore investigated whether reducing PM PtdSer content is sufficient to abrogate KRAS oncogenesis. Oxysterol-related binding proteins ORP5 and ORP8 exchange PtdSer synthesized in the ER for phosphatidylinositol-4-phosphate (PI4P) synthesized in the PM. We show that depletion of ORP5 or ORP8 reduced PM PtdSer levels, resulting in extensive mislocalization of KRAS from the PM. Concordantly, ORP5 or ORP8 depletion …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Exploration Of Patient Variables And Characteristics Best Suited For Medical Marijuana Treatment For Anxiety And Depressive Disorders, Corey Gazoo

Dissertations

Individuals with posttraumatic stress, anxiety and depressive disorders are currently being prescribed medical marijuana as a treatment in many states across the United States. However, marijuana is still considered a schedule one narcotic by the Drug Enforcement Administration and federal government, which provides several barriers and challenges to conduct research such as approval from the U.S. Food and Drug Administration and following guidelines from the National Institute on Drug Abuse issued by the DEA. Additionally, individuals prescribed medical marijuana for mental health disorders are not always thoroughly instructed on the type of medical marijuana, the dosage, and how frequently to …

Suppression Of Dc-Sign And Gh Reveals Complex, Subset-Specific Mechanisms For Kshv Entry In Primary B Lymphocytes, Nancy Palmerin, Farizeh Aalam, Romina Nabiee, Murali Muniraju, Javier Gordon Ogembo, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of multiple cancers in immunocompromised patients including two lymphoproliferative disorders associated with KSHV infection of B lymphocytes. Despite many years of research into the pathogenesis of KSHV associated diseases, basic questions related to KSHV molecular virology remain unresolved. One such unresolved question is the cellular receptors and viral glycoproteins needed for KSHV entry into primary B lymphocytes. In this study, we assess the contributions of KSHV glycoprotein H (gH) and the cellular receptor DC-SIGN to KSHV infection in tonsil-derived B lymphocytes. Our results show that (1) neither KSHV-gH nor DC-SIGN are essential …

Toward The Total Synthesis Of Dragonamide E And Its Potential Medicinal Application Against Leishmaniasis, Nathaniel M. Smith

Chemistry Theses

Leishmaniasis is one of the world’s most neglected tropical diseases, with hundreds of thousands of cases occurring worldwide annually. The disease originates from being infected by protozoa of the Leishmania genus, which are parasites that destroy mammalian cells as part of their life cycle. Currently utilized treatment strategies for leishmaniasis have many disadvantages, warranting the search for a new leishmaniasis treatment.

Cyanobacteria have been discovered to synthesize a wide variety of cytotoxic chemicals as part of their own defense mechanism. One strain of cyanobacteria, Lyngbya majuscula, produces several families of compounds, one of which is known as the “dragonamides”. …

Dimeric Allostery Mechanism Of The Plant Circadian Clock Photoreceptor Zeitlupe, Francesco Trozzi, Feng Wang, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

In Arabidopsis thaliana, the Light-Oxygen-Voltage (LOV) domain containing protein ZEITLUPE (ZTL) integrates light quality, intensity, and duration into regulation of the circadian clock. Recent structural and biochemical studies of ZTL indicate that the protein diverges from other members of the LOV superfamily in its allosteric mechanism, and that the divergent allosteric mechanism hinges upon conservation of two signaling residues G46 and V48 that alter dynamic motions of a Gln residue implicated in signal transduction in all LOV proteins. Here, we delineate the allosteric mechanism of ZTL via an integrated computational approach that employs atomistic simulations of wild type and …

Complexation Of Glycoalkaloid Α- Tomatine With Sterols And Its Potential Application As An Anti-Cancer Drug, Bishal Nepal

Dissertations

Glycoalkaloids (GAs) are secondary metabolites found mostly in higher plant species and some marine invertebrates. They are known to form complexes with 3β-hydroxy sterols such as cholesterol causing membrane disruption. So far the visual evidence showcasing the complexes formed between glycoalkaloids and sterols has been mainly restricted to some earlier studies using Brewster angle microscopy. This study aimed to develop a method for topographic and morphological analysis of sterol-glycoalkaloid complexes. Langmuir-Blodgett (LB) transfer of monolayers comprising of glycoalkaloid tomatine, sterols, and lipids in varying molar ratios onto mica followed by AFM examination was performed. The AFM method used required minimal …

Optimization Of Mechanical Properties At The Infarct Border Zone, Kaushik Sunder

LSU Master's Theses

A myocardial infarction (MI) occurs every 39 seconds in the United States. As of 2016, an estimated 550,000 new and 200,000 recurrent episodes of myocardial infarction (MI) occur each year in the United States was. Infarction is often distinguished by a considerable decrease in wall thickness and an increase in heart size or left ventricular volume. This behavior happens when there is a prolonged lack of blood flow, usually due to damage or clotting, which causes cardiomyocytes to die (CMs). The development of non-contractile infarct scarring is the primary pathophysiology of MI. While the infarct scar prevents myocardial rupture during …

Exposure To Endocrine Disrupting Chemicals (Edcs) And Cardiometabolic Indices During Pregnancy: The Home Study, Ann M. Vuong, Joseph M. Braun, Andreas Sjödin, Antonia M. Calafat, Kimberly Yolton, Bruce P. Lanphear, Aimin Chen

School of Public Health Faculty Research

Background: Toxicology studies have identified pregnancy as a window of susceptibility for endocrine disrupting chemicals (EDCs) and cardiometabolic indices in women. No study in humans, however, has examined EDC mixtures and cardiometabolic indices during pregnancy. Methods: We used the Health Outcomes and Measures of the Environment (HOME) Study to examine whether bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFAS), and phthalates are associated with blood pressure, glucose, and lipids in 388 pregnant women. We measured PBDEs and PFAS in serum at 16 weeks gestation, while BPA and phthalate metabolites were quantified in urine at 16 and …

Transversus Abdominis Plane Block: A Scoping Review, Liam Maher, Leanne Orians, Gabrielle Pappas, Lanny Coker Dnsc, Crna

Doctor of Nursing Practice Projects

The purpose of this project is to provide an overview of the literature on the analgesic effects of transverse abdominal plane (TAP) block and its effectiveness in reducing opioid consumption.

Intraoperative Dexmedetomidine For Reduction Of Postoperative Delirium In The Elderly: A Scoping Review, Gregory B. Harris Bsn, Rn, Srna, Brooke N. Hatchell Bsn, Rn, Srna, Davelin D. Woodard Bsn, Rn, Srna, Dwayne Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Background/Purpose: Post-operative delirium leads to significant morbidity in elderly patients, yet there is no regimen to prevent POD. Opioid use in the elderly surgical population is of the most significant risk factors for developing POD. The purpose of this scoping review is to recognize that Dexmedetomidine mitigates cognitive dysfunction secondary to acute pain and the use of narcotic analgesia by decreasing the amount of norepinephrine (an excitatory neurotransmitter) released during times of stress. This mechanism of action also provides analgesia through decreased perception and modulation of pain.

Methods: The authors developed eligibility criteria for inclusion of articles and performed a …

Lipoprotein-Induced Increases In Cholesterol And 7-Ketocholesterol Result In Opposite Molecular-Scale Biophysical Effects On Membrane Structure, Manuela A.A. Ayee, Irena Levitan

Faculty Work Comprehensive List

Under hypercholesterolemic conditions, exposure of cells to lipoproteins results in a subtle membrane increase in the levels of cholesterol and 7-ketocholesterol, as compared to normal conditions. The effect of these physiologically relevant concentration increases on multicomponent bilayer membranes was investigated using coarse-grained molecular dynamics simulations. Significant changes in the structural and dynamic properties of the bilayer membranes resulted from these subtle increases in sterol levels, with both sterol species inducing decreases in the lateral area and inhibiting lateral diffusion to varying extents. Cholesterol and 7-ketocholesterol, however, exhibited opposite effects on lipid packing and orientation. The results from this study indicate …

Pain Control: Opioid Vs. Nonopioid Analgesia During The Immediate Postoperative Period, Shamsie M. Lumpkin Bsn, Srna, Isaac W. Parrish Bsn, Srna, Austin S. Terrell Bsn, Srna, Dwayne S. Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Background Opioid analgesia has become the mainstay for acute pain management in the postoperative setting. However, the use of opioid medications comes with significant risks and side effects. Due to increasing numbers of prescriptions to those with chronic pain, opioid medications have become more expensive while becoming less effective due to the buildup of patient tolerance. The idea of opioid-free analgesic techniques has rarely been breached in many hospitals. Emerging research has shown that opioid-sparing approaches have resulted in lower reported pain scores across the board, as well as significant cost reductions to hospitals and insurance agencies. In addition to …