Medicine and Health Sciences Commons^™

Glucocorticoids Rapidly Activate Camp Production Via GΑs To Initiate Non-Genomic Signaling That Contributes To One-Third Of Their Canonical Genomic Effects, Francisco J. Nuñez, Timothy B. Johnstone, Maia L. Corpuz, Austin G. Kazarian, Nicole N. Mohajer, Omar Tliba, Reynold A. Pannettieri Jr., Cynthia J. Koziol-White, Moom Roosan, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Glucocorticoids are widely used for the suppression of inflammation, but evidence is growing that they can have rapid, non-genomic actions that have been unappreciated. Diverse cell signaling effects have been reported for glucocorticoids, leading us to hypothesize that glucocorticoids alone can swiftly increase the 3′,5′-cyclic adenosine monophosphate (cAMP) production. We found that prednisone, fluticasone, budesonide, and progesterone each increased cAMP levels within 3 minutes without phosphodiesterase inhibitors by measuring real-time cAMP dynamics using the cAMP difference detector in situ assay in a variety of immortalized cell lines and primary human airway smooth muscle (HASM) cells. A membrane- impermeable glucocorticoid showed …

Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect. …

Alanyl-Trna Synthetase Quality Control Prevents Global Dysregulation Of The Escherichia Coli Proteome, Paul Kelly, Nicholas Backes, Kyle Mohler, Christopher Buser, Arundhati Kavoor, Jesse Rinehart, Gregory Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mechanisms have evolved to prevent errors in replication, transcription, and translation of genetic material, with translational errors occurring most frequently. Errors in protein synthesis can occur at two steps, during tRNA aminoacylation and ribosome decoding. Recent advances in protein mass spectrometry have indicated that previous reports of translational errors have potentially underestimated the frequency of these events, but also that the majority of translational errors occur during ribosomal decoding, suggesting that aminoacylation errors are evolutionarily less tolerated. Despite that interpretation, there is evidence that some aminoacylation errors may be regulated, and thus provide a benefit to the cell, while others …

Chlorhexidine Gluconate Vs Povidone-Iodine In The Prevention Of Clean-Contaminated Surgical Site Infections, Erin Layne, Abigail Stone

Physician Assistant Capstones, 2016 to 2019

Abstract

Background:

A patient’s skin is the major source of pathogens that can cause post-operative complications such as surgical site infections (SSIs). Optimization of pre-operative skin antisepsis is obtained with chlorhexidine gluconate (CG) and povidone-iodine (PI). These two solutions are the most widely used antiseptics for pre-operative purposes.

Objective:

Among surgical patients greater than 18 years of age undergoing clean-contaminated surgery, which antiseptic, iodophors or chlorhexidine gluconate, is more effective at reducing postoperative surgical site infections?

Methods:

A search was done in PubMed utilizing the terms chlorhexidine, infection control, iodophors, and surgical site infection. The limits applied included randomized …

The Use Of Probiotics To Prevent Ventilator-Associated Pneumonia In Adults, Michael Roper, Paige Douthett

Physician Assistant Capstones, 2016 to 2019

Objective: To assess the efficacy and safety of preventing the acquisition of ventilator- associated pneumonia with the use of probiotic supplementation, as compared to a placebo, among hospitalized adult men and women receiving more than 24 hours of mechanical ventilation. Design: Systematic Literature Review. Methods: Systematic searches were conducted through PubMed and Scopus using the search terms “ventilator”, “probiotics”, and “prevention”. Records were excluded from the analysis if they were published before 2015, full text was not available, studies other than randomized control trial or cohort studies, and if the study population was less than 18 years old. Results: Of …

Subanesthetic Iv Ketamine Reduces Acute Suicidal Ideation In Patients With Mood Disorders, Kimberly Jenko, Jack Anzilotti

Physician Assistant Capstones, 2016 to 2019

Background. Depression and suicide are common in the United States and present a significant problem in the healthcare landscape. Currently, there are few options that can rapidly reduce suicidal ideation in patients with depression. Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to reduce acute suicidality in patients with depression. Previous studies have a reduction of suicidal ideation compared to saline placebo, but few studies have shown a significant effect compared to a similar psychoactive drug such as midazolam.

Method. A search of PubMed and PsychNET was performed in September 2018 using the terms “ketamine,” “suicide,” …

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Optical Detection Of The Structural Properties Of Tumor Tissue Generated By Xenografting Of Drug-Sensitive And Drug-Resistant Cancer Cells Using Partial Wave Spectroscopy (Pws), Prakash A. Adhikari, Prashanth K.B. Nagesh, Fatemah Alharthi, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu, Prabhakar Pradhan

School of Medicine Publications and Presentations

A mesoscopic physics-based optical imaging technique, partial wave spectroscopy (PWS), has been used for the detection of cancer by probing nanoscale structural alterations in cells/tissue. The development of drug-resistant cancer cells/tissues during chemotherapy is a major challenge in cancer treatment. In this paper, using a mouse model and PWS, the structural properties of tumor tissue grown in 3D structures by xenografting drug-resistant and drug-sensitive human prostate cancer cells having 2D structures, are studied. The results show that the 3D xenografted tissues maintain a similar hierarchy of the degree of structural disorder properties as that of the 2D original drug-sensitive and …

Full Recovery From Cocaine-Induced Toxic Leukoencephalopathy: Emphasizing The Role Of Neuroinflammation And Brain Edema, Edward C. Mader Jr., Alexander B. Ramos, Roberto A. Cruz, Lionel A. Branch

School of Medicine Publications and Presentations

Toxic leukoencephalopathy (TL) is characterized by white matter disease on magnetic resonance imaging (MRI) and evidence of exposure to a neurotoxic agent. We describe a case of cocaine-induced TL in which extensive white matter disease did not preclude full recovery. A 57-year-old man with substance abuse disorder presented with a 5-day history of strange behavior. On admission, he was alert but had difficulty concentrating, psychomotor retardation, and diffuse hyperreflexia. Brain MRI revealed confluent subcortical white matter hyperintensities with restricted diffusion in some but not in other areas. Electroencephalography (EEG) showed mild diffuse slowing. Blood tests were normal except for mild …

Evaluating Antipsychotic Prescribing In The Intensive Care Unit And Across The Continuum Of Care, Michael Pasqualicchio, Heidi Clarke

All Publications

Purpose/Background: The 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS) recommend against both typical and atypical antipsychotic use for delirium in critically ill patients. This recommendation is based on evidence showing that these medications are not associated with shorter durations of delirium, mechanical ventilation, intensive care unit (ICU) length of stay, or reduced mortality. There are many long term complications associated with the use of antipsychotics including QTc prolongation, extrapyramidal symptoms, metabolic abnormalities, and anticholinergic effects. Regardless, antipsychotics remain the most common medication used …

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …

Budesonide Enhances Agonist-Induced Bronchodilation In Human Small Airways By Increasing Camp Production In Airway Smooth Muscle, Cynthia J. Koziol-White, Timothy B. Johnstone, Maia L. Corpuz, Gaoyuan Cao, Sarah Orfanos, Vishal Parikh, Brian Deeney, Omar Tliba, Rennolds S. Ostrom, Ian Dainty, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

The non-genomic mechanisms by which glucocorticoids modulate β₂ agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E₂ (PGE₂), cholera toxin (CTX) or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE₂, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation …

November 2019, Randy Curry, Cindy Brooks

RURAL ROCKS

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

Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study Of Plasmodium Falciparum Hsp70s, Arnold Amusengeri, Lindy Astl, Kevin Lobb, Gennady M. Verkhivker, Özlem Tastan Bishop

Mathematics, Physics, and Computer Science Faculty Articles and Research

Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malaria cases. To prevent catastrophic results, we need to find non-conventional approaches. Allosteric drug targeting sites and modulators might be a new hope for malarial treatments. Heat shock proteins (HSPs) are potential malarial drug targets and have complex allosteric control mechanisms. Yet, studies on designing allosteric modulators against them are limited. Here, we identified allosteric …

How Oxygen Availability Affects The Antimicrobial Efficacy Of Host Defense Peptides: Lessons Learned From Studying The Copper-Binding Peptides Piscidins 1 And 3, Adenrele Oludiran, David S. Courson, Malia D. Stuart, Anwar R. Radwan, John C. Putsma, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we …

Gemcitabine Combination Nano Therapies For Pancreatic Cancer, Kamalika Samanta, Saini Setua, Sonam Kumari, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications and Presentations

Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely …

Incidence Of Aspirin Effect In An Anticipated Aspirin Negative Elderly Population, Emily Gullette, Heather Rhodes Md, Brant Clatterbuck Md, Nayda Parisio Poldiak, Christoph Kaufmann

General Surgery

No abstract provided.

Doxycycline-Induced Acute Pancreatitis: A Likely Source Rarely Seen, Paul Hoffman Do, Wilco Civil Sr, Jung Yoon Do, Gurjeet Kang Do, Christopher Lozano Orpiano Do, Michael Quinn Do, Joseph Staffetti Md, Dilip Ghanekar Md, Lakshminarasimhan Venu Md, Lily N. Jones Do, Ji Kwon Do, Shaival Thakore Md

Gastroenterology

No abstract provided.

October 2019, Randy Curry, Cindy Brooks

RURAL ROCKS

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

Leaving Ligand Effects On Reactivity And Solubility Of Monofunctional Platinum(Ii) Anticancer Complexes, Heidi Linn Hruska Millay

Masters Theses & Specialist Projects

Monofunctional platinum(II) complexes, such as phenanthriplatin and pyriplatin, have notably different characteristics from the bifunctional anticancer complexes, such as cisplatin and oxaliplatin, which have detrimental toxicities and resistance associated with them. The unique properties of the monofunctional complexes may be exploited to target cancer cells without producing the toxic side effects associated with the current FDA-approved platinum-based anticancer drugs. To advance the understanding of these monofunctional platinum(II) complexes, this study replaced the chloride leaving ligand with an acetate group, which should increase solubility and alter the rate of reactivity with key amino acid and nucleotide targets. Phenanthriplatin and pyriplatin compounds …

Synthesis Of Bis(Imino)Pyridine Iron(Ii) Complexes And Development Of Bis(Imino)Pyridine Iron(Ii) Catalyzed Carbene Transfer Reactions, Ban Wang

Masters Theses & Specialist Projects

Metal catalysis of symmetric and asymmetric carbene transfer reactions has been widely applied in natural product synthesis and material science over years. Metal carbene can be easily generated from the extrusion of nitrogen under the catalysis of metal complexes to further undergo various organic reactions, O/N/C-H insertions, cycloadditions, and ylide formations. Currently, the dominant effective catalysts for carbene reactions are built with expensive precious metal, for example, rhodium, ruthenium, palladium, gold. Notably, the effective reactivity and enantioselectivity of the dirhodium(II) catalysts are researched and established over the decades. However, the use of precious metal catalysts is the major source of …

Dormant Pathogenic Cd4(+) T Cells Are Prevalent In The Peripheral Repertoire Of Healthy Mice, Anna Cebula, Michal Kuczma, Edyta Szurek, Maciej Pietrzak, Natasha Savage, Wessam R. Elhefnawy, Grzegorz Rempala, Piotr Kraj, Leszek Ignatowicz

Computer Science Faculty Publications

Thymic central tolerance eliminates most immature T cells with autoreactive T cell receptors (TCR) that recognize self MHC/peptide complexes. Regardless, an unknown number of autoreactive CD4+Foxp3⁻ T cells escape negative selection and in the periphery require continuous suppression by CD4+Foxp3⁺ regulatory cells (Tregs). Here, we compare immune repertoires of Treg-deficient and Treg-sufficient mice to find Tregs continuously constraining one-third of mature CD4⁺Foxp3⁻ cells from converting to pathogenic effectors in healthy mice. These dormant pathogenic clones frequently express TCRs activatable by ubiquitous autoantigens presented by class II MHCs on conventional dendritic cells, including selfpeptides that select …

Interaction Of A Platinum Triamine Complex Having A Seven-Membered Chelate Ring With N-Acetyl-Lmethionine And Guanosine 5'-Monophosphate, Jae Ko

Masters Theses & Specialist Projects

In the 1960s, Rosenberg and his colleagues confirmed the anti-cancer activity of cisplatin. Although cisplatin was capable of killing testicular cancer cells there were also serious side effects. It was necessary to find alternate ways of overcoming side effects, and soon many researchers have discovered novel platinum compounds that show similar reactivity. Recently, replacing one chloride group to a heterocyclic amine group showed significant cytotoxicity with a different binding activity than cisplatin. Previously in our lab, [Pt(Me5dien)(NO3)]+ and [Pt(Et2dien)Cl]+ have been synthesized and reacted with NAcetyl- L-methionine (N-AcMet) and Guanosine 5’-monophosphate (5’-GMP) showed unusual reactivity. Unlike most previously studied platinum …

Effects Of Dabigatran In Mouse Models Of Aging And Cerebral Amyloid Angiopathy, Neethu Michael, Mher Mahoney Grigoryan, Kelley Kilday, Rachita K. Sumbria, Vitaly Vasilevko, Joanne Van Ryn, David H. Cribbs, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants. We analyzed whether the anticoagulant dabigatran produces cerebral microhemorrhage (the pathological substrate of MRI-demonstrable cerebral microbleeds) or intracerebral hemorrhage in aged mice with and without hemorrhage-predisposing angiopathy. We studied aged (22 months old) Tg2576 (a model of CAA) and wild-type (WT) littermate mice. Mice received either dabigatran etexilate (DE) …

The Fitness Landscape Of The African Salmonella Typhimurium St313 Strain D23580 Reveals Unique Properties Of The Pbt1 Plasmid, Rocío Canals, Roy R. Chaudhuri, Rebecca E. Steiner, Siân V. Owen, Natalia Quinones-Olvera, Melita A. Gordon, Michael Baym, Michael Ibba, Jay C. D. Hinton

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We have used a transposon insertion sequencing (TIS) approach to establish the fitness landscape of the African Salmonella enterica serovar Typhimurium ST313 strain D23580, to complement our previous comparative genomic and functional transcriptomic studies. We used a genome-wide transposon library with insertions every 10 nucleotides to identify genes required for survival and growth in vitro and during infection of murine macrophages. The analysis revealed genomic regions important for fitness under two in vitro growth conditions. Overall, 724 coding genes were required for optimal growth in LB medium, and 851 coding genes were required for growth in SPI-2-inducing minimal medium. These …

September 2019, Randy Curry, Cindy Brooks

RURAL ROCKS

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

A Population Pharmacokinetic Model For Simvastatin And Its Metabolites In Children And Adolescents., Kayode Ogungbenro, Jonathan B. Wagner, Susan M. Abdel-Rahman, J Steven Leeder, Aleksandra Galetin

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Poor adherence to dietary/behaviour modifications as interventions for hypercholesterolemia in paediatric patients often necessitates the initiation of statin therapy. The aim of this study was to develop a joint population pharmacokinetic model for simvastatin and four metabolites in children and adolescents to investigate sources of variability in simvastatin acid exposure in this patient population, in addition to SLCO1B1 genotype status.

METHODS: Plasma concentrations of simvastatin and its four metabolites, demographic and polymorphism data for OATP1B1 and CYP3A5 were analysed utilising a population pharmacokinetic modelling approach from an existing single oral dose (10 mg < 17 years and 20 mg ≥ 18 years) pharmacokinetic dataset of 32 children and adolescents.

RESULTS: The population PK model included …

Rare Degs1 Variant Significantly Alters De Novo Ceramide Synthesis Pathway, Nicholas B. Blackburn, Laura F. Michael, Peter J. Meikle, Juan M. Peralta, Marian Mosior, Scott Mcahren, Hai H. Bui, Melissa A. Bellinger, Corey Giles, Satish Kumar, Ana C. Leandro, Marcio Almeida, Jacquelyn M. Weir, Michael C. Mahaney, Thomas D. Dyer, Laura Almasy, John L. Vandeberg, Sarah Williams-Blangero, David C. Glahn, Ravindranath Duggirala, Mark Kowala, John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

The de novo ceramide synthesis pathway is essential to human biology and health but genetic influences remain unexplored. The core function of this pathway is the generation of biologically active ceramide from its precursor, dihydroceramide. Dihydroceramides have diverse, often protective, biological roles; conversely, increased ceramide levels are biomarkers of complex disease. To explore the genetics of the ceramide synthesis pathway, we searched for deleterious nonsynonymous variants in the genomes of 1,020 Mexican Americans from extended pedigrees. We identified a Hispanic ancestry−specific rare functional variant, L175Q, in DEGS1, a key enzyme in the pathway that converts dihydroceramide to ceramide. This amino …

Association Of Fish Oil And Physical Activity On Mobility Disability In Older Adults, Anoop T. Balachandran

Publications and Research

Purpose: This study aimed to examine whether long-term fish oil (FO) supplementation is associated with a lower risk of mobility disability and enhances benefits of physical activity (PA). Methods: A total of 1635 sedentary adults age 70 to 89 yr from the Lifestyle Interventions and Independence for Elders single-blinded randomized,multicenter clinical trial, which compared a structured PA program to a health education program. Primary outcome was incident major mobility disability (MMD), defined by loss of ability to walk 400 m, measured every 6 months for an average of 2.6 yr. Secondary outcomes included persistent mobility disability, Short Physical Performance Battery, …