Chemicals and Drugs Commons^™

New-Onset Diabetes Mellitus With Exposure To Ledipasvir And Sofosbuvir., Resmi Premji, Nira Roopnarinesingh, Nazia Qazi, Eric S. Nylen

Medicine Faculty Publications

The combination therapy of ledipasvir/sofosbuvir was approved by the Food and Drug Administration in 2014 for the treatment of chronic hepatitis C. Although hyperglycemia is not well known to occur with its use, we present 2 cases of new-onset diabetes mellitus and a review of the literature suggesting an adverse event association. In the first patient with HIV, we postulate that ledipasvir/sofosbuvir increased the levels of tenofovir and thereby potentiated hyperglycemia. In the second case of a patient with prediabetes, ledipasvir/sofosbuvir appeared to increase insulin resistance. A literature review further supported an association of hyperglycemia and the use of ledipasvir/sofosbuvir. …

Intra-Individual Consistency In Endocrine Profiles Across Successive Pregnancies, Molly Fox, Curt A. Sandman, Elyssia Poggi Davis, Laura M. Glynn

Psychology Faculty Articles and Research

Context: It is yet unknown how similar women’s hormone levels are during successive pregnancies, and very little is known about the degree to which siblings experience similar prenatal environments. Given the importance of understanding how women’s reproductive life-histories exert cumulative effects on health via hormone exposure, and the importance of understanding how fetal programming via endocrine signaling affects sibling trait concordance, here we address this important lacuna in the literature.

Objective: To investigate how consistent are women’s hormone profiles across two successive pregnancies.

Design and Main Outcome Measures: This longitudinal, prospective study followed a cohort of 28 …

The Controversy Of Vaccinations, Nicholas G. Aboreden

The Kabod

Recently vaccination has become a controversial topic. There is a growing number of people who believe that vaccines carry great health risks to patients and therefore refuse to be vaccinated or to vaccinate their children. This ill-informed view of immunizations is beginning to cause serious problems in the United States as growing numbers of disease cases are being seen. A closer look into the science of vaccines and the benefits they have brought, clearly show that not only do vaccines carry very little risk to patients, but they are responsible for the eradication and reduction of multiple debilitating diseases.

Elongation Factor-P At The Crossroads Of The Host-Endosymbiont Interface, Andrei Rajkovic, Anne Witzky, William Navarre, Andrew J. Darwin, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. In both cases EF-P receives a post-translational modification, critical for its function, on a highly conserved residue that protrudes into the peptidyl-transfer center of the ribosome. EPMSs are comprised of a gene(s) that synthesizes the precursor molecule …

Formaldehyde From E-Cigarettes - It's Not As Simple As Some Suggest, James F. Pankow, Robert M. Strongin, David H. Peyton

Chemistry Faculty Publications and Presentations

The Authors address critics of a previously published letter to the Editor in The New England Journal of Medicine, pertaining to hidden formaldehyde in E-Cigarette aerosols and the need for future testing of their safety.

Tnf-Α-Induced Micrornas Control Dystrophin Expression In Becker Muscular Dystrophy., Alyson A. Fiorillo, Christopher R. Heier, James S. Novak, Christopher B. Tully, Kristy J. Brown, Kitipong Uaesoontrachoon, Maria C. Vila, Peter P. Ngheim, Luca Bello, Joe N. Kornegay, Corrado Angelini, Terence A. Partridge, Kanneboyina Nagaraju, Eric P. Hoffman

Genomics and Precision Medicine Faculty Publications

The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45–47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low …

Magic Bullet, Karen Haydock

The Transdisciplinary STEAM+ Journal

Two of the most powerful types of corporations in the world today are those that produce pharmaceuticals and weapons. While the corporations are concerned with increasing their profits, we wonder if their products have any magical powers.

[India ink on rag paper]

This poster explores the military-industrial complex. The weapons industry profits through imperialism. The pharmaceutical industry profits through by taking advantage of people’s illnesses.

The poster has multiple interpretations, hopefully encouraging the viewer to participate by asking relevant questions, such as:

“What is that person drinking?”

”Are they pills or bombs?”

“Medicines cure us - how can a pill …

Lipopolysaccharide Induced Map Kinase Activation In Raw 264.7 Cells Attenuated By Cerium Oxide Nanoparticles, Vellaisamy Selvaraj, Niraj Nepa, Steven Rogers, Nandini D.P.K. Manne, Ravi K. Arvapalli, Kevin M. Rice, Shinichi Asano, Erin Fankenhanel, J. Y. Ma, Tolou Shokuhfar, Mani Maheshwari, Eric R. Blough

Pharmaceutical Science and Research

High mortality rates are associated with the life threatening disease of sepsis. Improvements in septic patient survivability have failed to materialize with currently available treatments. This article represents data regarding a study published in biomaterials (Vellaisamy et al., Biomaterials, 2015, in press). with the purpose of evaluating whether severe sepsis mortality and associated hepatic dysfunction induced by lipopolysaccharide (LPS) can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the method and processing of raw data related to our study publish in Biomaterials and Data in Brief (Vellaisamy et al., …

Acidic And Basic Destruction Of Tissues, Cydney Eaton

University Honors Program

A coroner’s case I had learned about involved a man attempting to dispose of a body with acid. Shortly after exposure, the man was apprehended and the body was located. Upon investigation, police force determined the acid used to be hydrochloric acid, however, exact concentration remains unknown (Kohr, 2010). This led to the question of which easily accessible acid works best to degrade tissue. To answer this, an experiment was conducted involving pig feet and various concentrations of common acids and a single strong base. The feet were submerged in the solutions overnight and mass percent lost or gained was …

Application Of Ichip To Grow “Uncultivable” Microorganisms And Its Impact On Antibiotic Discovery, Rinzhin T. Sherpa, Caretta J. Reese, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Purpose. Antibiotics have revolutionized modern medicine, allowing significant progress in healthcare and improvement in life expectancy. Development of antibiotic resistance by pathogenic bacteria is a natural phenomenon; however, the rate of antibiotic resistance emergence is increasing at an alarming rate, due to indiscriminate use of antibiotics in healthcare, agriculture and even everyday products. Traditionally, antibiotic discovery has been conducted by screening extracts of microorganisms for antimicrobial activity. However, this conventional source has been over-used to such an extent that it poses the risk of “running out” of new antibiotics. Aiming to increase access to a greater diversity of microorganisms, …

Novel Oral Anticoagulants For Stroke Prophylaxis And Venous Thromboembolism Prevention And Treatment, Laith G. Alsayegh

Journal of Patient-Centered Research and Reviews

Novel oral anticoagulants (NOACs) are becoming popular management options for stroke prophylaxis in nonvalvular atrial fibrillation as well as deep vein thrombosis and pulmonary embolism treatment and prophylaxis. NOACs have similar efficacy to warfarin along with noninferior safety profiles. Patient comorbidities, size, renal and hepatic function, and concomitant drug regimen play a role in which NOAC a physician may choose.

An Insight Into The Role Of Vitamins Other Than Vitamin D On Bone, Robert E. Salazar, Jameela Banu

Health & Biomedical Sciences Faculty Publications

Vitamins are essential micronutrients for normal development. Great emphasis has been placed on vitamin D for bone development and maintenance. However, other vitamins also influence bone health. While some of them are more beneficial to bone and increase bone mass by increasing bone formation, calcium deposition and stimulate osteoblastogenesis, higher concentrations of others have deleterious effects causing fragile bones and increasing the risk of fractures. Knowledge about the effects of these vitamins will help in better maintenance of bone. This review focuses on the information available on vitamins A,B,C,E and K on bone health. Existing information supports vitamin C and …

Investigation Of Stilbenoids As Potential Therapeutic Agents For Rotavirus Gastroenteritis, Judith M. Ball, Fabricio Medina-Bolivar, Katelyn D. Defrates, Emily Hambleton, Megan E. Hurlburt, Lingling Fang, Tianhong Yang, Luis Nopo-Olazabal, Richard L. Atwill, Pooj Ghai, Rebecca D. Parr

Faculty Publications

Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced …

Electrochemical Characterization Of Protein Adsorption Onto Yngrt-Au And Vlgxe-Au Surfaces, Hanna Trzeciakiewicz, Jose Esteves-Villanueva, Rania Soudy, Kamaljit Kaur, Sanela Martic-Milne

Pharmacy Faculty Articles and Research

The adsorption of the proteins CD13, mucin and bovine serum albumin on VLGXE-Au and YNGRT-Au interfaces was monitored by electrochemical impedance spectroscopy in the presence of [Fe(CN)6]3−/4−. The hydrophobicity of the Au surface was tailored using specific peptides, blocking agents and diluents. The combination of blocking agents (ethanolamine or n-butylamine) and diluents (hexanethiol or 2-mercaptoethanol) was used to prepare various peptide-modified Au surfaces. Protein adsorption onto the peptide-Au surfaces modified with the combination of n-butylamine and hexanethiol produced a dramatic decrease in the charge transfer resistance, Rct, for all three proteins. In contrast, polar peptide-surfaces induced a minimal change in …

Fluorescein Dye For Exploring Anti-Cancer Drug Dissolution Kinetics, Connor Davis, Tonglei Li, Wei Gao

The Summer Undergraduate Research Fellowship (SURF) Symposium

Nanocrystalline formulations of anti-tumor drugs have been shown to improve desirable characteristics as well as increase the efficacy of delivery. However, the improvements seen are not strong enough to eradicate tumors and there exists a need to better understand how the drug particles move about and release in the body. The use of fluorophores incorporated into substrates allows for highly sensitive and resolute imaging in the body without the need for radioisotopes. This research aims to utilize quenching characteristics of fluorescein in order to provide pharmacokinetic information to aid in the improvement of nanoparticulate delivery formulations. Nanocrystal formulations of paclitaxel …

Bio-Inspired Composite Hydrogels For Osteochondral Regenerative Engineering, Grant N. Gellert, Liangju Kuang, Chunhui Jiang, Nur P. Damayanti, Joseph Irudayaraj, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Treatment of osteochondral defects encompassing injury or degeneration to both the articular cartilage as well as the underlying subchondral bone presents a significant medical challenge. Current treatment options including autografts and allografts suffer from limited availability and risk of immunogenicity, respectively. The long term goal of this work is to develop an integrated scaffold system for treatment of osteochondral defects via in situ regeneration of bone, cartilage and the bone-cartilage interface. Hydrogels composed of polymer networks swollen in water provide an attractive biomaterial platform for regeneration of cartilage. In the present study, we have developed a novel composite hydrogel consisting …

Development Of A Scalable Synthesis Of Hp-Β-Cd Pluronic Polyrotaxanes, Joseph L. Skulsky, Elizabeth A. Slepko, Bradley P. Loren, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

Polyrotaxanes are polymers that have macrocycles threaded onto them, analogous to beads threaded onto a string. These materials are used for a variety of different biomedical applications.^1-3 The Thompson group has been developing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) polyrotaxanes as therapeutics for the treatment of Niemann-Pick Type C (NPC) disease. NPC is a debilitating genetic disorder where cholesterol accumulates in the lysosomes of cells.⁴ Developing a scalable process is crucial for the advancement of these materials as NPC therapeutics. The goal of this project is to optimize the only protocol for the synthesis of HP-β-CD/Pluronic polyrotaxanes in order to develop a …

Efficacy Of Galactose And Adalimumab In Patients With Resistant Focal Segmental Glomerulosclerosis: Report Of The Font Clinical Trial Group., Howard Trachtman, Suzanne Vento, Emily Herreshoff, Milena Radeva, Jennifer Gassman, Daniel T. Stein, Virginia J. Savin, Mukut Sharma, Jochen Reiser, Changli Wei, Michael Somers, Tarak Srivastava, Debbie S. Gipson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with resistant focal segmental glomerulosclerosis (FSGS) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease. In the absence of curative treatment, current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS) Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was designed to assess the efficacy of adalimumab and galactose compared to standard medical therapy which was comprised of lisinopril, losartan, and atorvastatin.

METHODS: Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative …

Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides, Miao Zhang, Xuan-Yu Meng, Ji-Fang Zhang, Meng Cui, Diomedes E. Logothetis

Pharmacy Faculty Articles and Research

Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins.

Regulated Phosphorylation Of The K-Cl Cotransporter Kcc3 Is A Molecular Switch Of Intracellular Potassium Content And Cell Volume Homeostasis, Norma C. Adragna, Nagendra B. Ravilla, Peter K. Lauf, Gulnaz Begum, Arjun R. Khanna, Dandan Sun, Kristopher K. Kahle

Pharmacology and Toxicology Faculty Publications

The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K+ and Cl− efflux via activation of K+ channels, volume-regulated anion channels (VRACs), and the K+-Cl− cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the …

Editorial: Phosphoinositides And Their Phosphatases: Linking Electrical And Chemical Signals In Biological Processes, Susy C. Kohout, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

No abstract provided.

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

Molecular Determinants Underlying Binding Specificities Of The Abl Kinase Inhibitors: Combining Alanine Scanning Of Binding Hot Spots With Network Analysis Of Residue Interactions And Coevolution, Amanda Tse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown …

Characterization Of The Role That Alternative Ribonucleotide Reductases Play In Restoring Replication In The Presence Of Hydroxyurea In Escherichia Coli, Michael Sadek

PSU McNair Scholars Online Journal

DNA replication is essential for cells to grow and divide. Ribonucleotide reductase is an essential enzyme that is responsible for the formation of deoxyribonucleotides that are used in DNA synthesis during replication. Hydroxyurea is a chemotherapeutic agent that is thought to work by specifically inhibiting the ribonuceotide reductase to prevent replication. However, recent studies in E. coli have shown that following an initial period of inhibition, DNA synthesis then recovers in the presence of hydroxyurea, suggesting that the mode of death and cellular response to hydroxyurea is more complex than originally proposed. The E.coli genome encodes three ribonucleotide reductases that …

Cyclic Rhamnosylated Elongation Factor P Establishes Antibiotic Resistance In Pseudomonas Aeruginosa, Andrei Rajkovic, Sarah Erickson, Anne Witzky, Owen E. Branson, Jin Seo, Philip R. Gafken, Michael A. Frietas, Julian P. Whitelegge, Kym F. Faull, William Wiley Navarre, Andrew J. Darwin, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is a ubiquitous bacterial protein that is required for the synthesis of poly-proline motifs during translation. In Escherichia coli and Salmonella enterica, the posttranslational β-lysylation of Lys34 by the PoxA protein is critical for EF-P activity. PoxA is absent from many bacterial species such as Pseudomonas aeruginosa, prompting a search for alternative EF-P posttranslation modification pathways. Structural analyses of P. aeruginosa EF-P revealed the attachment of a single cyclic rhamnose moiety to an Arg residue at a position equivalent to that at which β-Lys is attached to E. coli EF-P. Analysis of the genomes …

Effects Of Pringle Maneuver And Partial Hepatectomy On The Pharmacokinetics And Blood–Brain Barrier Permeability Of Sodium Fluorescein In Rats, Mohammad K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia–reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood–brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial …

The Effects Of Arginine Vasopressin On Maternal Behavior And Aggression In Peromyscus Californicus Mothers, Nathaniel Ng

Honors Projects

Research studies since the 1950s have shown that a chemical within the brain called arginine vasopressin (AVP) is associated with the modulation of many different social behaviors in mammals. Some of these behaviors are related to parenting, such as parental care initiation, aggression, social recognition, depression and anxiety. Understanding the physiology behind AVP regulation could allow for the creation of new therapies for treating human social disorders, such as using an AVP receptor antagonist to attenuate anxiety. This project examines how neural injections of AVP and an AVP receptor antagonist affect both maternal care and aggression in female Peromyscus californicus …

Orexin Receptor Activation Generates Gamma Band Input To Cholinergic And Serotonergic Arousal System Neurons And Drives An Intrinsic Ca(2+)-Dependent Resonance In Ldt And Ppt Cholinergic Neurons, Masaru Ishibashi, Iryna Gumenchuk, Bryan Kang, Catherine Steger, Elizabeth Lynn, Nancy Molina, Leonard M. Eisenberg, Christopher S. Leonard

NYMC Faculty Publications

A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz) - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT) and pedunculopontine (PPT) tegmental neurons and serotonergic dorsal raphe (DR) neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca(2+)-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal …

Evolutionary Convergence Of The Caffeine Biosynthetic Pathway In Chocolate Followed Duplication Of A Constrained Ancestral Enzyme, Andrew J. O'Donnell

Masters Theses

Caffeine biosynthesis is widely distributed in flowering plants and requires three consecutive methylation steps of xanthine alkaloids. Genes that have previously been reported to participate in the multi-step pathway in Coffea sp. (coffee) and Camellia sinensis (tea) encode members of the SABATH family of methyltransferases. Two genes highly expressed in fruits of Theobroma cacao (cacao) are orthologous to the caffeine genes in tea and appear to have diversified following gene duplication. Biochemical characterization of the enzymes (XMTs) encoded by these genes strongly suggest an unprecedented major pathway to theobromine, a precursor to caffeine. These findings imply that caffeine biosynthesis evolved …

Instituting Patient-Self Test Meters In Adults On Warfarin In A Cardiology Practice, Melvyn Grace Manzano Rabanal

Doctor of Nursing Practice Final Manuscripts

Background: Warfarin is the oral anticoagulant that is most commonly used to control and prevent thromboembolic disorders. It requires meticulous testing and dosing adjustments to attain therapeutic international normalized ratio (INR) levels. Patient self-testing (PST) is associated with a reduced risk of all-cause mortality and lower rates of thromboembolism and bleeding. PST meters offers convenience and promotes self-initiative of care.

Purpose: The purpose of the project is to evaluate the effectiveness of INR PST in adult patients diagnosed with atrial fibrillation, deep vein thrombosis, and mechanical heart valve on warfarin therapy in a Cardiology practice compared to traditional …