Chemicals and Drugs Commons^™

Rosiglitazone Treatment Of Type 2 Diabetic Db/Db Mice Attenuates Urinary Albumin And Angiotensin Converting Enzyme 2 Excretion, Harshita Chodavarapu, Nadja Grobe, Hari Krishna Somineni, Esam Said Busah Salem, Malav Navinchandra Madhu, Khalid M. Elased

Pharmacology and Toxicology Faculty Publications

Alterations within the renal renin angiotensin system play a pivotal role in the development and progression of cardiovascular and renal disease. Angiotensin converting enzyme 2 (ACE2) is highly expressed in renal tubules and has been shown to be renoprotective in diabetes. The protease, a disintegrin and metalloprotease (ADAM) 17, is involved in the ectodomain shedding of several transmembrane proteins including ACE2. Renal ACE2 and ADAM17 were significantly increased in db/db mice compared to controls. We investigated the effect of the insulin sensitizer, rosiglitazone, on albuminuria, renal ADAM17 protein expression and ACE2 shedding in db/db diabetic mice. …

Design, Synthesis And Evaluation Of Antimicrobial Activity Of N-Terminal Modified Leucocin A Analogues, Krishna Chaitanya Bodapati, Rania Soudy, Hashem Etayash, Michael Stiles, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Class IIa bacteriocins are potent antimicrobial peptides produced by lactic acid bacteria to destroy competing microorganisms. The N-terminal domain of these peptides consists of a conserved YGNGV sequence and a disulphide bond. The YGNGV motif is essential for activity, whereas, the two cysteines involved in the disulphide bond can be replaced with hydrophobic residues. The C-terminal region has variable sequences, and folds into a conserved amphipathic α-helical structure. To elucidate the structure–activity relationship in the N-terminal domain of these peptides, three analogues (1–3) of a class IIa bacteriocin, Leucocin A (LeuA), were designed and synthesized by …

Divergent Protein Motifs Direct Ef-P Mediated Translational Regulation In Salmonella And Escherichia Coli, Steven J. Hersch, Mengchi Wang, S. Betty Zou, Kyung-Mee Moon, Leonard J. Foster, Michael Ibba, William Wiley Navarre

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is a universally conserved bacterial translation factor homologous to eukaryotic/archaeal initiation factor 5A. In Salmonella, deletion of the efp gene results in pleiotropic phenotypes, including increased susceptibility to numerous cellular stressors. Only a limited number of proteins are affected by the loss of EF-P, and it has recently been determined that EF-P plays a critical role in rescuing ribosomes stalled at PPP and PPG peptide sequences. Here we present an unbiased in vivo investigation of the specific targets of EF-P by employing stable isotope labeling of amino acids in cell culture (SILAC) to compare the …

Testosterone, Cardiovascular, Men, Trial, Lin Xu, Guy Freeman, Benjamin J. Cowling, Mary Schooling

Publications and Research

Background
Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease.

Methods
A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, …

Resveratrol Effects On Breast Cancer, Shelby Young

Undergraduate Research Conference

Resveratrol (RES) is a polyphenolic compound found in 72 different plant species. Grape skins, red wine, berries, pomegranates, soybeans and peanuts are excellent sources. RES is more bioavailable in whole food form than supplemental.

Combatting Dental Anxiety In Patients, Gretchen Osdoba

Natural Science Student Work

Dental Anxiety is a highly debilitating condition that can keep people away from the dentist and from receiving critical care. This can lead to serious medical conditions that could have easily been prevented through proper dental care. The purpose of this paper is to describe the nature of dental fear and the different treatment options available. I will focus on helpful traits of dentists and the use of psychological treatments, nitrous oxide, anti-anxiety medications, and general anesthesia to reduce this fear. I will also discuss a comparison of a psychological treatment and an anti-anxiety medication as short-term and long-term treatment …

Norepinephrine Involvement In The Intermittent Swim Stress-Induced Deficit In Spatial Learning And Memory, Emily Elgert

Honors Theses and Capstones

Learning and memory impairments are often caused by stress disorders including depression. The present study investigated the involvement of norepinephrine in the swim stress-induced deficits of spatial learning and memory. Exposure to intermittent swim stress (ISS) followed by learning and memory tests in the Morris water maze (MWM) were used to investigate this relationship. The ISS paradigm consists of intermittent exposure to cold water, producing stress responses in rats. Reboxetine, a norepinephrine selective reuptake inhibitor (NSRI), was employed to investigate whether this compound reverses the ISS-induced deficit. In other words, rats exposed to the ISS, were hypothesized to experience impaired …

Explaining The Supreme Court's Interest In Patent Law, Timothy R. Holbrook

IP Theory

No abstract provided.

Differential Effects Of Micrornas On Glioblastoma Growth And Migration, Duane Jeansonne, Marco Pacifici, Adam Lassak, Krzysztof Reiss, Giuseppe Russo, Jovanny Zabaleta, Francesca Peruzzi

School of Medicine Faculty Publications

Glioblastoma multiforme is characterized by rapid proliferation, aggressive metastatic potential, and resistance to radio- and chemotherapy. The matricellular protein CYR61 regulates cellular proliferation and migration and is highly expressed in Glioblastomas. MicroRNAs are 22-nucleotides long RNAs that regulate gene expression post-transcriptionally. Here, we utilized the LN229 glioblastoma cell line and found that CYR61 is a target of miR-136, miR-155, and miR-634. Over-expression of miR-136 and miR-634 miRNAs negatively affected proliferation, but not migration, while expression of miR-155 reduced migration but did not affect the proliferation of LN229 cells. Investigation of the molecular mechanisms affected by expression of miR-634 revealed an …

Nitric Oxide And Its Metabolites In The Critical Phase Of Illness: Rapid Biomarkers In The Making, Asad Mian, Mayank Aranke, Nathan S. Bryan

Department of Emergency Medicine

The potential of nitric oxide (NO) as a rapid assay biomarker, one that could provide a quantum leap in acute care, remains largely untapped. NO plays a crucial role as bronchodilator, vasodilator and inflammatory mediator. The main objective of this review is to demonstrate how NO is a molecule of heavy interest in various acute disease states along the emergency department and critical care spectrum: respiratory infections, central nervous system infections, asthma, acute kidney injury, sepsis, septic shock, and myocardial ischemia, to name just a few. We discuss how NO and its oxidative metabolites, nitrite and nitrate, are readily detectable …

Is Brain-Derived Neurotrophic Factor A Possible Mechanism Underlying Risperidone Sensitization In Adolescent Rats?, Qing Shu, Gang Hu, Ming Li

Department of Psychology: Faculty Publications

Risperidone is one of the most widely used atypical antipsychotic drugs and is approved for the treatment of mental disorders (eg. schizophrenia, autism) in children and adolescents. The present study investigated the repeated treatment effect of risperidone and associated neurotropic mechanism in the phencyclidine (PCP)-induced hyperlocomotion model in adolescent rats. We examined whether repeated risperidone treatment would cause a sensitized inhibition of PCP-induced hyperlocomotion in adolescent rats, and whether such a sensitization effect was mediated by risperidone-induced alterations in Brain-Derived Neurotrophic Factor (BDNF), an important biomarker which plays a role in neuropathology of schizophrenia and action of antipsychotic medications. Male …

The Effect Of Statins On Testosterone In Men And Women, A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Mary Schooling, Shiu Lun Au Yeung, Guy Freeman, Benjamin J. Cowling

Publications and Research

Background
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates morethan other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statinsunexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would beexpected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins’ pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.

Methods
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, …

Inhibition Of Cholinergic Signaling Causes Apoptosis In Human Bronchioalveolar Carcinoma, Jamie K. Lau, Kathleen C. Brown, Brent A. Thornhill, Clayton M. Crabtree, Aaron M. Dom, Theodore R. Witte, W. Elaine Hardman, Christopher A. Mcnees, Cody A. Stover, A. Betts Carpenter, Haitao Luo, Yi C. Chen, Brandon S. Shiflett, Piyali Dasgupta

Biochemistry and Microbiology

Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BAC) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChR). In this study, we show that human BACs produce acetylcholine (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3), and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs, and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by α7-, α3β2-, and β3-nAChRs, ChAT and VAChT pathways. We observed that …

Challenges In Testing Genetically Modified Crops For Potential Increases In Endogenous Allergen Expression For Safety, Rakhi Panda, H. Ariyarathna, Plaimein Amnuaycheewa, Afua O. Tetteh, S. N. Pramod, Steve Taylor, B. K. Ballmer-Weber, Richard E. Goodman

Department of Food Science and Technology: Faculty Publications

Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for …

Dimethyl Sulfoxide (Dmso) Exacerbates Cisplatin-Induced Sensory Hair Cell Death In Zebrafish (Danio Rerio), Phillip M. Uribe, Melissa A. Mueller, Julia S. Gleichman, Matthew D. Kramer, Qi Wang, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger, Douglas A. Cotanche, Jonathan I. Matsui

Chemistry Faculty Publications and Presentations

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells …

Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion

STAR Program Research Presentations

Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.

Atrazine And Nitrate In Public Drinking Water Supplies And Non-Hodgkin Lymphoma In Nebraska, Usa, Martha G. Rhoades, Jane L. Meza, Cheryl L. Beseler, Patrick J. Shea, Andy Kahle, Julie M. Vose, Kent M. Eskridge, Roy F. Spalding

School of Natural Resources: Faculty Publications

A secondary analysis of 1999–2002 Nebraska case-control data was conducted to assess the risk of non-Hodgkin lymphoma (NHL) associated with exposure to nitrate- and atrazine-contaminated drinking water. Water chemistry data were collected and weighted by well contribution and proximity of residence to water supply, followed by logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI). We found no association between NHL risk and exposure to drinking water containing atrazine or nitrate alone. Risk associated with the interaction of nitrate and atrazine in drinking water was elevated (OR, 2.5; CI, 1.0–6.2). Risk of indolent B-cell lymphoma was higher …

Interactions Between Estradiol, Bdnf And Dendritic Spines In Promoting Memory., V. Luine, M. Frankfurt

Journal Articles

Several lines of evidence have converged to indicate that memory formation involves plasticity of dendritic spines in the medial prefrontal cortex (PFC) and the hippocampus. Memory varies with estrogen levels throughout the lifespan of the female. Generally, increased levels of estrogen are related to greater dendritic spine density on pyramidal cells in the PFC and the hippocampus and to improved memory function. Brain-derived neurotrophic factor (BDNF) is a growth factor which increases dendritic spines and enhances memory function. Estrogens increase BDNF levels in the PFC and the hippocampus. In the present review we provide evidence that estradiol and BDNF may …

Ribosomally Synthesized And Post-Translationally Modified Peptide Natural Products: Overview And Recommendations For A Universal Nomenclature, P. G. Arnison, M. J. Bibb, G. Bierbaum, A. A. Bowers, T. S. Bugni, G. Bulaj, J. A. Camarero, D. J. Campopiano, J. M. Willey, W. A. Van Der Donk, +55 Additional Authors

Journal Articles

This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.

Parallel Changes In Intracellular Water Volume And Ph Induced By Nh3/Nh4+ Exposure In Single Neuroblastoma Cells, Victor M. Blanco, Martín S. Márquez, Francisco J. Alvarez-Leefmans

Pharmacology and Toxicology Faculty Publications

BACKGROUND:

Increased blood levels of ammonia (NH3) and ammonium (NH4(+)), i.e. hyperammonemia, leads to cellular brain edema in humans with acute liver failure. The pathophysiology of this edema is poorly understood. This is partly due to incomplete understanding of the osmotic effects of the pair NH3/NH4(+) at the cellular and molecular levels. Cell exposure to solutions containing NH3/NH4(+) elicits changes in intracellular pH (pHi), which can in turn affect cell water volume (CWV) by activating transport mechanisms that produce net gain or loss of solutes and water. The occurrence of CWV changes caused by NH3/NH4(+) has long been suspected, but …