Chemicals and Drugs Commons^™

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. …

A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …

July 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

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

High-Density Lipoprotein Inhibits Serum Amyloid A-Mediated Reactive Oxygen Species Generation And Nlrp3 Inflammasome Activation, Preetha Shridas, Maria C. De Beer, Nancy R. Webb

Internal Medicine Faculty Publications

Serum amyloid A (SAA) is a high-density apolipoprotein whose plasma levels can increase more than 1000-fold during a severe acute-phase inflammatory response and are more modestly elevated in chronic inflammation. SAA is thought to play important roles in innate immunity, but its biological activities have not been completely delineated. We previously reported that SAA deficiency protects mice from developing abdominal aortic aneurysms (AAAs) induced by chronic angiotensin II (AngII) infusion. Here, we report that SAA is required for AngII-induced increases in interleukin-1β (IL-1β), a potent proinflammatory cytokine that is tightly controlled by the Nod-like receptor protein 3 (NLRP3) inflammasome and …

Transcriptomics Of Learning, Pablo Iturralde

Theses

Learning is a basic and important component of behavior yet we have very little empirical information about the interaction between mechanisms of learning and evolution. In our work, we are testing hypotheses about the neurogenetic mechanisms through which animal learning abilities evolve. We are able to test this directly by using experimentally evolved populations of flies, which differ in learning ability. These populations were previously evolved within the lab by creating worlds with different patterns of change following theoretically predicted effects on which enhanced learning will evolve. How has evolution acted to modulate genes and gene expression in the brain …

Kisspeptin Modulates Luteinizing Hormone Release And Ovarian Follicular Dynamics In Pre-Pubertal And Adult Murrah Buffaloes, Vishalkumar Pottapenjera, Srinivasa R. Rajanala, Chandrasekhar Reddy, Arunakumari Gangineni, Kiran Avula, Sandeep K. Bejjanki, Sriravali Sathagopam, Surabhi Kesharwani, Sathya Velmurugan

Pharmacology and Nutritional Sciences Faculty Publications

Kisspeptin is a neuropeptide that governs the reproductive axis upstream to GnRH. We wanted to study whether kisspeptin modulates plasma LH and FSH levels and ovarian follicular dynamics in buffaloes and whether kisspeptin can be used for fixed time artificial insemination (FTAI). We carried out these studies in comparison with buserelin, a potent GnRH agonist. Kisspeptin dose-dependently increased plasma LH levels. However, the kisspeptin-induced increase in LH was short-lived as the peak reached in 15–30 min returned to basal values by 1–2 h. The kisspeptin-induced increase in LH level was less compared to buserelin-induced increase in LH level which sustained …

Photochemical Investigation Of High-Valent Metal-Oxo Intermediates Containing Corrole And Light-Harvesting Porphyrin Ligands, Jonathan Malone

Masters Theses & Specialist Projects

In enzymatic and synthetic catalytic oxidations, high-valent iron-oxo intermediates play a vital role as the active oxidant. In this regard, many synthetic metal catalysts are designed as biomimetic models to resemble the active site of Cytochrome P450 enzymes (P450) which are the predominant oxidation catalysts in nature. Vitamin B12 cofactors, with a corrole-like structure corrin, are also utilized in some of the more difficult reactions in nature such as rearrangement and reductase reactions.

In this work, application of the promising photochemical method to corrolecontaining ligands systems showed much success in the generation of manganese(V)-oxo corrole intermediates using two electron-deficient corrole …

Endocannabinoid Metabolome Of Human Breast Milk, Adriana V. Gaitan Espinoza

LSU Doctoral Dissertations

Human breast milk (HBM) is an extremely complex yet fascinating biofluid tailored to meet an infant’s nutritional requirements for development. Amongst the nutrients present in HBM, the long-chain polyunsaturated fatty acids (LCPUFAs) are of high importance due to the pivotal role they play in infant cognitive and visual development, and growth. In addition, the LCPUFAs are precursors to endocannabinoids (EC) which are endogenous lipid mediators. EC exert metabolic responses including appetite and food intake regulation, and they have been identified to play a role in establishing the suckling response of the newborn that is needed to nurse. Thus, we aimed …

The Effect Of The Oxytocin Hormone In Cocaine Addicted Rats Suffering From Abstinence Syndrome, Juan Padilla

The International Student Science Fair 2018

Rehabilitation from a history of drug abuse is a very difficult and life changing process. Abstinence syndrome forces the rehabilitating patient to go through anxiety like symptoms. The Oxytocin hormone has been believed to be a potential facilitator in the rehabilitation process. This hormone is very present during interactions of affection (hugs) and birth, it foments trust while it associates to a feeling of calmness. Oxytocin would theoretically be a calming agent to the anxiety like symptoms such as craving. The experiment aimed to test the calming effects of the hormone, consisted of a five-day systemic cocaine injections treatment schedule …

Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0–15% cytotoxicity at 5–100 μM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected to help with the permeation of the …

Super‐Resolution Imaging Of Amyloid Structures Over Extended Times By Using Transient Binding Of Single Thioflavin T Molecules, Kevin Spehar, Tianben Ding, Yuanzi Sun, Niraja Kedia, Jin Lu, George R. Nahass, Matthew D. Lew, Jan Bieschke

Electrical & Systems Engineering Publications and Presentations

Oligomeric amyloid structures are crucial therapeutic targets in Alzheimer's and other amyloid diseases. However, these oligomers are too small to be resolved by standard light microscopy. We have developed a simple and versatile tool to image amyloid structures by using thioflavin T without the need for covalent labeling or immunostaining. The dynamic binding of single dye molecules generates photon bursts that are used for fluorophore localization on a nanometer scale. Thus, photobleaching cannot degrade image quality, allowing for extended observation times. Super‐resolution transient amyloid binding microscopy promises to directly image native amyloid by using standard probes and record amyloid dynamics …

Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine, Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos. Herein, a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug, emtricitabine. Two new decapeptides, with linear and cyclic natures, both containing alternate tryptophan and histidine residues, were synthesized using Fmoc/tBu solid-phase chemistry. The peptides were characterized and purified by using matrix-assisted laser desorption/ionization (MALDI) spectroscopy and high-performance liquid chromatography (HPLC), respectively. These peptides did not show significant toxicity up …

The Effect Of The Oxytocin Hormone In Cocaine Addicted Rats Suffering From Abstinence Syndrome, Juan Padilla

The International Student Science Fair 2018

This study aimed to understand the effects of oxytocin in cocaine-addicted rats to prove its ability to help recovering drug addicts overcome the extreme anxiety and craving that makes them relapse during their rehabilitation.

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …

June 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

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

Microgel Core/Shell Architectures As Targeted Agents For Fibrinolysis, Purva Kodlekere, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We demonstrate the utility of microgel core/shell structures conjugated to fibrin-specific peptides as fibrinolytic agents. Poly(N-isopropylmethacrylamide) (pNIPMAm) based microgels conjugated to the peptide GPRPFPAC (GPRP) were observed to bring about fibrin clot erosion, merely through exploitation of the dynamic nature of the clots. These results suggest the potential utility of peptide–microgel hybrids in clot disruption and clotting modulation.

Anti-Tumor Activity Of Phenoxybenzamine And Its Inhibition Of Histone Deacetylases, Mario A. Inchiosa

NYMC Faculty Publications

The principal finding from this study was the recognition that the α-adrenergic antagonist, phenoxybenzamine, possesses histone deacetylase inhibitory activity. Phenoxybenzamine is approved by the United States Food and Drug Administration for the treatment of hypertensive crises associated with tumors of the adrenal medulla, pheochromocytomas. It has several "off label" indications relative to its capacity to relax vascular smooth muscle and smooth muscle of the urogenital tract. The drug also has a long history of apparent efficacy in ameliorating, and perhaps reversing, the severe symptoms of neuropathic pain syndromes. Our interest in this feature of the drug relates to the fact …

Codon Usage Revisited: Lack Of Correlation Between Codon Usage And The Number Of Trna Genes In Enterobacteria, Joaquín Rojas, Gabriel Castillo, Lorenzo Eugenio Leiva, Sara Elgamal, Omar Orellana, Michael Ibba, Assaf Katz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

It is widely believed that if a high number of genes are found for any tRNA in a rapidly replicating bacteria, then the cytoplasmic levels of that tRNA will be high and an open reading frame containing a higher frequency of the complementary codon will be translated faster. This idea is based on correlations between the number of tRNA genes, tRNA concentration and the frequency of codon usage observed in a limited number of strains as well as from the fact that artificially changing the number of tRNA genes alters translation efficiency and consequently the amount of properly folded protein …

Optimization Of The Split-Spinach Aptamer For Monitoring Contiguous Rna Nanoparticle Assembly, Jack M. O'Hara

Honors Projects

The emerging field of RNA nanotechnology takes advantage of the RNA’s ability to self-assemble into exquisite structures. As nanoparticle design continues to advance and move into increasingly complex biological systems, tools to monitor their assembly and location will be of great importance. Here, a split-aptamer system is used to monitor assembly of a six-membered nanoring based on fluorescence feedback of a fluorophore. First, the split-aptamer is designed into two of the six pieces of the ring. Through mutation and deletion, we optimize the fluorescence feedback established when a six membered nanoparticle assembles, compared to partial assembly. We demonstrate that with …

Zolpidem Facilitated Sexual Assaults: A Hair Method Validation, Danielle N. Chasworth

Student Theses

A liquid chromatography tandem mass spectrometry (LC-MSMS) method was developed and validated to detect for the presence of zolpidem in human hair samples. Zolpidem is a sedative hypnotic whose adverse effects make it a common drug found in drug facilitated crimes (DFC). It is important to be able to detect and quantitate the drug after a long period of time due to the victim’s delayed reporting of the crime. Hair’s long window of detection makes it a useful matrix for DFC investigations. The linear range of the assay was targeted at 2 pg/mg to 1,000 pg/mg and experiments designed to …

Preparation Of Supramolecular Amphiphilic Cyclodextrin Bilayer Vesicles For Pharmaceutical Applications, Kate E. Frischkorn

Master's Theses

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological …

Characterization Of Nanodiamondbased Anti-Hiv Drug Delivery To The Brain, Upal Roy, Vadym Drozd, Andriy Durygin, Jesse Rodriguez, Paul Barber, Venkata Atluri, Xiaohua Liu, Thomas G. Voss, Surendra Saxena, Madhavan Nair

Health & Biomedical Sciences Faculty Publications

Human Immunodefciency Virus Type 1 (HIV-1) remains one of the leading causes of death worldwide. Present combination antiretroviral therapy has substantially improved HIV-1 related pathology. However, delivery of therapeutic agents to the HIV reservoir organ like Central nervous system (CNS) remains a major challenge primarily due to the inefective transmigration of drugs through Blood Brain Barrier (BBB). The recent advent of nanomedicine-based drug delivery has stimulated the development of innovative systems for drug delivery. In this regard, particular focus has been given to nanodiamond due to its natural biocompatibility and non-toxic nature–making it a more efcient drug carrier than other …

Modeling Pharmaceutical Inhibition Of Glucose-Stimulated Renin-Angiotensin System In Kidneys, Ashlee N. Ford Versypt, Minu R. Pilvankar, Hui Ling Yong

Biology and Medicine Through Mathematics Conference

No abstract provided.

30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman

Celebration of Learning

There are no controlled studies of acetaminophen toxicity in horses. The objective was to test the hypotheses that oral acetaminophen administered at a dosage 25% higher than that sometimes used in horses would result in measurable hepatic toxicity as seen in humans and other species. Six healthy adult horses were administered 25 mg/kg acetaminophen powder in corn syrup twice daily for 30 days. Three other horses served as negative controls receiving only corn syrup. Jugular venous blood samples were obtained on days 7 and 1 before treatment; on treatment days 1, 2, 5, 8, 12, 15, 19, 22, 26 and …

Visualizing Mutation-Specific Differences In The Trafficking-Deficient Phenotype Of Kv11.1 Proteins Linked To Long Qt Syndrome Type 2, Allison R. Hall, Corey L. Anderson, Jennifer L. Smith, Tooraj Mirshahi, Samy-Claude Elayi, Craig T. January, Brian P. Delisle

Physiology Faculty Publications

KCNH2 encodes the Kv11.1 α-subunit that underlies the rapidly activating delayed-rectifier K⁺ current in the heart. Loss-of-function KCNH2 mutations cause long QT syndrome type 2 (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channel protein to the cell surface membrane. Several trafficking-deficient LQT2 mutations (e.g., G601S) generate Kv11.1 proteins that are sequestered in a microtubule-dependent quality control (QC) compartment in the transitional endoplasmic reticulum (ER). We tested the hypothesis that the QC mechanisms that regulate LQT2-linked Kv11.1 protein trafficking are mutation-specific. Confocal imaging analyses of HEK293 cells stably expressing the trafficking-deficient LQT2 mutation F805C showed that, …

A Modified Method Of High Molecular Weight Adsorbable Organic Chlorine Measurement In Saline Water: Dialysis Pretreatment, Jiajian Liu, Li Ling, Yi Li, Chao Wang, Chii Shang

Faculty of Science & Technology (THEi)

Adsorbable organic halogen is a mean to quantify total organic halogen, which is an important toxicity indicator in disinfection byproduct studies. However, quantification of low concentrations of adsorbable organic chlorine (AOCl) formation in seawater chlorination using the USEPAMethod 9020Bwas found inaccurate due to the presence of high concentrations of chloride. In this study, a dialysis-based pretreatment techniquewas proposed, optimized and adopted to eliminate the interference of chloride in quantifying low concentrations of AOCl inseawater. A volumetric ratio of dialysis samples to continuous-flow deionized water at 1:1200 was found sufficient to remove over 99% of chloride. As a result, chloride to …

Music As A Catalyst For Altered States Of Consciousness And Peak Experiences In The Treatment Of Depression, Anxiety, And Ptsd, Paul Battles

Expressive Therapies Capstone Theses

Abstract This paper investigates the therapeutic uses of altered states of consciousness (ASC) and peak experiences (PE) for the treatment of depression, anxiety, and post-traumatic stress disorder (PTSD), and the ways in which music can be used to facilitate or enhance these experiences. ASC’s and PE’s can help uncover hidden or repressed unconscious material and potentially change the way an individual views and interacts with his or her world. In cases of people suffering from depression, anxiety, and post-traumatic stress disorder (PTSD), these emotional, cognitive, and perceptual changes have been shown to have sometimes profound and long- lasting therapeutic effects, …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Site-Selective Modification Of Peptides And Proteins Via Organocatalyzed Henry Reaction, Zilma Pereira Muneeswaran

Seton Hall University Dissertations and Theses (ETDs)

In this research, peptides and protein containing serine on the N-terminus underwent site-selective modification following organocatalyzed bioconjugation that offered an additional functional group. It was shown that transforming the N-terminus serine to an aldehyde allowed site-specific bioconjugation to occur by utilizing the well-known Henry reaction. This method also grants a safer pathway for bioconjugation utilizing “green-chemistry” and biocompatible conditions. Amino acids and amino acid derived organocatalysts were utilized in the Henry reaction resulting in yields of up to 86 % conversion. Promising preliminary results were achieved in this research using peptides and myoglobin as the bioconjugation targets. Further investigation to …

In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian

Veterinary Science Faculty Publications

Background

The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the …