Chemicals and Drugs Commons^™

Nanoparticle Elasticity Directs Tumor Uptake, Peng Guo, Daxing Liu, Kriti Subramanyam, Biran Wang, Jiang Yang, Jing Huang, Debra T. Auguste, Marsha A. Moses

Publications and Research

To date, the role of elasticity in drug delivery remains elusive due to the inability to measure microscale mechanics and alter rheology without affecting chemistry. Herein, we describe the in vitro cellular uptake and in vivo tumor uptake of nanolipogels (NLGs). NLGs are composed of identical lipid bilayers encapsulating an alginate core, with tunable elasticity. The elasticity of NLGs was evaluated by atomic force microscopy, which demonstrated that they exhibit Young’s moduli ranging from 45 ± 9 to 19,000 ± 5 kPa. Neoplastic and non-neoplastic cells exhibited significantly greater uptake of soft NLGs (Young’s modulus13.8 MPa). In an orthotopic breast …

Component Tree Analysis Of Cystovirus Φ6 Nucleocapsid Cryo-Em Single Particle Reconstructions, Lucas Oliveira, Ze Ye, Al Katz, Alexandra Alimova, Hui Wei, Gabor T. Herman, Paul Gottlieb

Publications and Research

The 3-dimensional structure of the nucleocapsid (NC) of bacteriophage φ6 is described utilizing component tree analysis, a topological and geometric image descriptor. The component trees are derived from density maps of cryo-electron microscopy single particle reconstructions. Analysis determines position and occupancy of structure elements responsible for RNA packaging and transcription. Occupancy of the hexameric nucleotide triphosphorylase (P4) and RNA polymerase (P2) are found to be essentially complete in the NC. The P8 protein lattice likely fixes P4 and P2 in place during maturation. We propose that the viral procapsid (PC) is a dynamic structural intermediate where the P4 and P2 …

Antagonistic Actions Of Juvenile Hormone And 20-Hydroxyecdysone Within The Ring Gland Determine Developmental Transitions In Drosophila, Suning Liu, Kang Li, Yue Gao, Xi Liu, Weiting Chen, Wei Ge, Qili Feng, Subba Reddy Palli, Sheng Li

Entomology Faculty Publications

In both vertebrates and insects, developmental transition from the juvenile stage to adulthood is regulated by steroid hormones. In insects, the steroid hormone, 20-hydroxyecdysone (20E), elicits metamorphosis, thus promoting this transition, while the sesquiterpenoid juvenile hormone (JH) antagonizes 20E signaling to prevent precocious metamorphosis during the larval stages. However, not much is known about the mechanisms involved in cross-talk between these two hormones. In this study, we discovered that in the ring gland (RG) of Drosophila larvae, JH and 20E control each other’s biosynthesis. JH induces expression of a Krüppel-like transcription factor gene Kr-h1 in the prothoracic gland (PG), a …

Randomized Trial To Reduce Air Particle Levels In Homes Of Smokers And Children, Suzanne C. Hughes, John Belletierre, Benjamin Nguyen, Sandy Liles, Neil E. Klepeis, Penelope J.E. Quintana, Vincent Berardi, Saori Obayashi, Savannah Bradley, C. Richard Hofstetter, Melbourne F. Hovell

Psychology Faculty Articles and Research

Introduction

Exposure to fine particulate matter in the home from sources such as smoking, cooking, and cleaning may put residents, especially children, at risk for detrimental health effects. A randomized clinical trial was conducted from 2011 to 2016 to determine whether real-time feedback in the home plus brief coaching of parents or guardians could reduce fine particle levels in homes with smokers and children.

Design

A randomized trial with two groups—intervention and control.

Setting/participants

A total of 298 participants from predominantly low-income households with an adult smoker and a child aged <14 years. Participants were recruited during 2012–2015 from multiple sources in San Diego, mainly Women, Infants and Children Program sites.

Intervention

The multicomponent intervention consisted of continuous lights and …

Sptransformer Proteins From The Purple Sea Urchin Opsonize Bacteria, Augment Phagocytosis, And Retard Bacterial Growth, H. Y. Chou, C. Lun, L. C. Smith

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The purple sea urchin, Strongylocentrotus purpuratus, has a complex and robust immune system that is mediated by a number of multi-gene families including the SpTransformer (SpTrf) gene family (formerly Sp185/333). In response to immune challenge from bacteria and various pathogen-associated molecular patterns, the SpTrf genes are up-regulated in sea urchin phagocytes and express a diverse array of SpTrf proteins. We show here that SpTrf proteins from coelomocytes and isolated by nickel affinity (cNi-SpTrf) bind to Gram-positive and Gram-negative bacteria and to Baker’s yeast, Saccharomyces cerevisiae, with saturable kinetics and specificity. cNi-SpTrf opsonization of the marine bacteria, Vibrio diazotrophicus, augments phagocytosis, …

Parent Perspectives On Health And Functioning Of School-Aged Adolescents With Disabilities, Gavin Colquit Edd, Cape, Cscs, Ashley D. Walker Phd, Ches, Moya L. Alfonso Phd, Msph, Maria Olivas Mph, Bethrand Ugwu Mph, Theophile Dipita Dr, Ph

United States Food and Drug Administration: Publications

BACKGROUND: Youth living with disabilities are at risk of experiencing poor health outcomes. Coordinated school health programs have an opportunity to help youth with disabilities and their families through health education, health services, and community engagement. The World Health Organization developed the International Classification of Functioning, Disability, and Health (ICF) as a framework to analyze factors related to health conditions. We used the ICF to examine parental perceptions of health and function among students with disabilities living in rural and urban areas.

METHODS: We surveyed parents (N = 71) using the parent-report versions of the Pediatric Outcomes Data Collection Instrument …

Mental Health Problems And Onset Of Tobacco Use Among 12- To 24-Year-Olds In The Path Study, Victoria R. Green Mhs, Kevin P. Conway Phd, Ches, Marushka L. Silveira Bds, Mph, Phd, Karin A. Kasza Ma, Amy Cohn Phd, K. Michael Cummings Phd, Mph, Cassandra A. Stanton Phd, Priscilla Callahan-Lyon Md, Wendy Slavit Mph, Ches, James D. Sargent Md, Nahla Hilmi Mph, Raymond S. Niaura Phd, Chad J. Reissig Phd, Elizabeth Lambert Ma, Izabella Zandberg Phd, Mary F. Brunette Md, Susanne E. Tanski Md, Nicolette Borek Phd, Andrew J. Hyland Phd, Wilson M. Compton Md, Mpe

United States Food and Drug Administration: Publications

Objective: To examine whether mental health problems predict incident use of 12 different tobacco products in a nationally representative sample of youth and young adults.

Method: This study analyzed Wave (W) 1 and W2 data from 10,533 12- to 24-year-old W1 never tobacco users in the Population Assessment of Tobacco and Health (PATH) Study. Self-reported lifetime internalizing and externalizing symptoms were assessed at W1. Past 12-month use of cigarettes, electronic nicotine delivery systems (ENDS), traditional cigars, cigarillos, filtered cigars, pipe, hookah, snus pouches, other smokeless tobacco, bidis and kreteks (youth only), and dissolvable tobacco was assessed at W2.

Results:In multivariable …

Etiology Of Teen Dating Violence Among Adolescent Children Of Alcoholics, Jennifer A. Livingston, Rina D. Eiden, Jared Lessard, Meghan Casey, James Henrie, Kenneth E. Leonard

United States Food and Drug Administration: Publications

Family processes in early life have been impli- cated in adolescent involvement in teen dating violence, yet the developmental pathways through which this occurs are not well understood. In this study, etiological pathways from parental psychopathology and marital conflict in infancy to involvement in dating violence in late adoles- cence were examined in a sample of children at high-risk due to parental alcohol problems. Families (N = 227) recruited when the child was 12 months of age were assessed at 12-, 24-, 36-months, kindergarten, 6th, 8th, and 12th grades. Slightly more than half of the children were female (51%) and …

Prevalence Of Adhd In Publicly Insured Adults, Yanmin Zhu, Wie Liu, Yan Li, Xi Wang, Almut G. Winterstein

United States Food and Drug Administration: Publications

Objective: To estimate the prevalence of adult ADHD diagnosis and treatment in U.S. Medicaid beneficiaries. Method: Using outpatient, inpatient, and pharmacy billing records for patients eligible for Medicaid fee-for-service benefits within 29 states from 1999 to 2010, we estimated the annual prevalence of ADHD diagnosis and treatment. Results: The prevalence of ADHD diagnosis increased from 2.20 per 1,000 patients in 1999 to 10.57 in 2010. Likewise, prevalence of ADHD treatment increased from 1.95 per 1,000 patients in 1999 to 13.16 in 2010. Between 40% and 65%, patients had ADHD drug prescription fills 6 months after ADHD diagnosis, whereas 45% to …

The Acute Effects Of Alpha-Gpc On Hand Grip Strength, Jump Height, Power Output, Mood, And Reaction-Time In Recreationally Trained, College-Aged Individuals, Josey Lucas Cruse

Online Theses and Dissertations

Introduction: While alpha-GPC has received recent praise as a mental and physical performance enhancement supplement, very limited research on this topic exist, and no current studies examine alpha-GPC in collegiate-aged trained individuals. This study hopes to bridge the gap in the current research literature on the topic of alpha-GPC ingestion in young healthy adults in the cognitive and anaerobic paradigms, potentially shedding new light on the theoretical synergistic effect of caffeine and alpha-GPC.

Purpose: To investigate and identify the acute effects of alpha-GPC ingestion on performance testing (hand-grip strength, jump height, force kinetics, rate of force development) & reaction time …

The Safety And Efficacy Of Creatine Supplementation In The General Public, Cody Baxter

Physician Assistant Scholarly Project Posters

The purpose of this study was to determine whether supplementation with creatine monohydrate is efficacious beyond the realm of its most popular use, which is in athletics. This study investigated the safety of creatine supplementation in the general population. References were collected through a review of PubMed and Scopus databases. Initial keywords searched were creatine supplementation and creatine safety. Where possible, trials with human subjects were utilized. Studies focused on creatine’s effects in athletes or weightlifting parameters were eliminated. Topics were further narrowed down by conditions with the most amount of research and medical concerns recognized as common to primary …

Co-Occurrence Of Tobacco Product Use, Substance Use, And Mental Health Problems Among Youth: Findings From Wave 1 (2013–2014) Of The Population Assessment Of Tobacco And Health (Path) Study, Kevin P. Conway, Victoria R. Green, Karin A. Kasza, Marushka L. Silveira, Nicolette Borek, Heather L. Kimmel, James D. Sargent, Cassandra A. Stanton, Elizabeth Lambert, Nahla Hilmi, Chad J. Reissig, Kia J. Jackson, Susanne E. Tanski, David Maklan, Andrew J. Hyland, Wilson M. Compton

United States Food and Drug Administration: Publications

Introduction: Cigarette use is associated with substance use and mental health problems among youth, but as- sociations are unknown for non-cigarette tobacco product use, as well as the increasingly common poly-tobacco use.

Methods: The current study examined co-occurrence of substance use and mental health problems across tobacco products among 13,617 youth aged 12–17 years from Wave 1 (2013–2014) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. Participants self-reported ever cigarette, e-cigar- ette, smokeless tobacco, traditional cigar, cigarillo, filtered cigar, hookah, and other tobacco product use; al- cohol, marijuana, and other drugs; and lifetime substance use, internalizing …

Trends And Economic Drivers For United States Naloxone Pricing, January T 2006 To February 2017, Matthew Rosenberg, Grace Chai, Shekhar Mehta, Andreas Schick

United States Food and Drug Administration: Publications

Anecdotal evidence indicates that naloxone prices have risen in recent years, but limited research has examined the magnitude of these increases and potential causes. We contribute nationally representative evidence to help answer each of these questions, including wholesale pricing data from a proprietary drug sales database span- ning January 2006 to February 2017. We find that all formulations of naloxone increased in price since 2006 except for Narcan Nasal Spray. These cumulative increases totaled 2281% for the 0.4 MG single-dose products, 244% for the 2 MG single-dose products, 3797% for the 4 MG multi-dose products, and 469% for the 0.4 …

Toxicology Of Engineered Nanoparticles: Focus On Poly(Amidoamine) Dendrimers, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne

Articles

Engineered nanomaterials are increasingly being developed for paints, sunscreens, cosmetics, industrial lubricants, tyres, semiconductor devices, and also for biomedical applications such as in diagnostics, therapeutics, and contrast agents. As a result, nanomaterials are being manufactured, transported, and used in larger and larger quantities, and potential impacts on environmental and human health have been raised. Poly(amidoamine) (PAMAM) dendrimers are specifically suitable for biomedical applications. They are well-defined nanoscale molecules which contain a 2-carbon ethylenediamine core and primary amine groups at the surface. The systematically variable structural architecture and the large internal free volume make these dendrimers an attractive option for drug …

Effects Of Clinical Pathway Implementation On Antibiotic Prescriptions For Pediatric Community-Acquired Pneumonia., Daniele Donà, Silvia Zingarella, Andrea Gastaldi, Rebecca Lundin, Giorgio Perilongo, Anna Chiara Frigo, Rana F Hamdy, Theoklis Zaoutis, Liviana Da Dalt, Carlo Giaquinto

Pediatrics Faculty Publications

BACKGROUND: Italian pediatric antimicrobial prescription rates are among the highest in Europe. As a first step in an Antimicrobial Stewardship Program, we implemented a Clinical Pathway (CP) for Community Acquired Pneumonia with the aim of decreasing overall prescription of antibiotics, especially broad-spectrum.

MATERIALS AND METHODS: The CP was implemented on 10/01/2015. We collected antibiotic prescribing and outcomes data from children aged 3 months-15 years diagnosed with CAP from 10/15/2014 to 04/15/2015 (pre-intervention period) and from 10/15/2015 to 04/15/2016 (post-intervention period). We assessed antibiotic prescription differences pre- and post-CP, including rates, breadth of spectrum, and duration of therapy. We also compared …

The Effects Of Hormone Replacement Therapy (Hrt) On Surgically Postmenopausal Women: A Review Of The Literature, Leslie M. Hertweck

Honors Undergraduate Theses

The primary purpose of this research was to examine the effects of HRT in women with acute estrogen deficiency from surgically induced menopause. The secondary purpose was to evaluate how HRT improves symptoms of acute estrogen deficiency and quality of life (QOL) in women using hormone supplementation. Peer reviewed articles published from 2000 to 2017 that were written in the English language with a focus on the use of HRT in women with acute estrogen deficiency after surgical menopause were evaluated for relevance. Evidence suggests the primary reason for decreased use of HRT is the associated risks outweighing the benefits; …

The Effects Of Emerging Technology On Healthcare And The Difficulties Of Integration, Skyler J. Pavlish-Carpenter

Honors Undergraduate Theses

Background: Disruptive technology describes technology that is significantly more advanced than previous iterations, such as: 3D printing, genetic manipulation, stem cell research, innovative surgical procedures, and computer-based charting software. These technologies often require extensive overhauls to implement into older systems and must overcome many difficult financial and societal complications before they can be widely used. In a field like healthcare that makes frequent advancements, these difficulties can mean that the technology will not be utilized to its full potential or implemented at all.

Objective: To determine the inhibiting factors that prevent disruptive technology from being implemented in conventional healthcare.

Methods: …

Design And Evaluation Of Gemini Surfactant-Based Lipoplexes Modified With Cell-Binding Peptide For Targeted Gene Therapy, Waleed Mohammed-Saeid, Rania Soudy, Richa Tikoo, Kamaljit Kaur, Ronald E. Verrall, Ildiko Badea

Pharmacy Faculty Articles and Research

Purpose Achieving successful gene therapy requires delivery of a gene vector specifically to the targeted tissue with efficient expression and a good safety profile. The objective of this work was to develop, characterize and determine if a novel gemini surfactant-based lipoplex systems, modified with a cancer-targeting peptide p18-4, could serve this role. Methods The targeting peptide p18-4 was either chemically coupled to a gemini surfactant backbone or physically co-formulated with the lipoplexes. The influence of targeting ligand and formulation strategies on essential physicochemical properties of the lipoplexes was evaluated by dynamic light scattering and small angle X-ray scattering techniques. In …

A Ninja Initiative At Children's Mercy, Richard Ogden, Bradley A. Warady, Vimal Chadha, Wendy Hoebing

Posters

No abstract provided.

Sustainability And Outcomes Of A Standardized Aminoglycoside Induced Ototoxicity Monitoring Algorithm, Claire Elson, Christopher M. Oermann, Michelle Weltman, Ellen Meier

Posters

No abstract provided.

The Role Of Ceramide In Neutrophil Elastase Induced Inflammation In The Lungs, Sophia Karandashova

Theses and Dissertations

Alterations to sphingolipid metabolism are associated with increased pulmonary inflammation, but the impact of inflammatory mediators, such as neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. NE is a protease associated CF lung disease progression, and can be found in up to micromolar concentrations in patient airways. While sphingolipids have been investigated in the context of CF, the focus has been on loss of cystic fibrosis transmembrane conductance regulator (CFTR) function. Here, we present a novel observation: oropharyngeal aspiration of NE increases airway ceramides in mice. Using a previously characterized mouse model of NE-induced inflammation, we demonstrate that NE …

Implementing A Public Health Perspective In Fda Drug Regulation, Patricia J. Zettler, Margaret Foster Riley, Aaron S. Kesselheim

Faculty Publications By Year

There is, without question, a public health crisis in the United States arising from both illicit and prescription opioid misuse, addiction, and overdose. The Food and Drug Administration (FDA) is one regulator with an important role to play in minimizing the harms associated with prescription opioids, while also ensuring that prescription opioids are available for the evidence-based management of pain. One question, however, is to what extent the agency can consider in its decisions to approve opioids and keep existing ones on the market the provider and patient behaviors contributing to the epidemic. This is, in part, because FDA’s approval …

Communicating Nutrition Information At The Point Of Purchase: An Eye‐Tracking Study Of Shoppers At Two Grocery Stores In The United States, Mike Bartels, Katherin Tillack, Chung‐Tung Jordan Lin

United States Food and Drug Administration: Publications

Providing nutrition information at the point of purchase is one approach that can be used to help consumers adopt and maintain a healthy diet. Previous research has examined consumer self‐reported notice and use of the information as well as how the design of the information affects its attention and use in a laboratory environ‐ ment using eye‐tracking methodology. This study advances the literature by applying eye‐tracking methodology to explore consumer visual and choice behavior in a real shopping environment, and by recognizing that nutrition information competes with other visual stimuli in the store and consumers are vulnerable to a “limited …

Hyperthermia As A Cancer Treatment- From Theory To Practice, Graham Fullerton

CMC Senior Theses

Using iron super-paramagnetic and ferromagnetic nanoparticles composed of Fe₃O₄ molecules, scientists analyze the effectiveness and practicality of this new treatment theory, hyperthermia. The problems of magnetic particle density, isothermal barriers/cellular cooling thresholds, and nanoparticle specific targeting are addressed in this review.

Iron magnetic nanoparticles were chosen due to their relatively low biological reactivates and lack of subsequent cellular toxicity. However, there are significant heating problems associated with these magnetic nanoparticles due to their relative size and short thermal time constants or thermal half-lives. Effectively, these aforementioned issues create a phenomenon where cancerous cells, surrounded by unheated healthy …

A Purification And In Vitro Activity Assay For A (P)Ppgpp Synthetase From Clostridium Difficile, Astha Pokhrel, Asia Poudel, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

Kinase and pyrophosphokinase enzymes transfer the gamma phosphate or the beta-gamma pyrophosphate moiety from nucleotide triphosphate precursors to substrates to create phosphorylated products. The use of γ-³²-P labeled NTP precursors allows simultaneous monitoring of substrate utilization and product formation by radiography. Thin layer chromatography (TLC) on cellulose plates allows rapid separation and sensitive quantification of substrate and product. We present a method for utilizing the thin-layer chromatography to assay the pyrophosphokinase activity of a purified (p)ppGpp synthetase. This method has previously been used to characterize the activity of cyclic nucleotide and dinucleotide synthetases and is broadly suitable for …

Population Pharmacokinetic/Pharmacodynamic Modeling Of Depot Testosterone Cypionate In Healthy Male Subjects, Youwei Bi, Paul J. Perry, Michael Ellerby, Daryl J. Murry

Faculty Publications & Research of the TUC College of Pharmacy

A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate (TC). Thirty-one healthy men were randomized into a dose group of 100, 250, or 500 mg/wk and received 14 weekly injections of TC. A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize testosterone concentrations and link exposure to change in luteinizing hormone and spermatogenesis following long-term TC administration. A linear one-compartment model best described the concentration-time profile of total testosterone. The population mean estimates for testosterone were 2.6 kL/day for clearance and 14.4 kL for volume of distribution. Weight, albumin, and their changes from baseline were …

The Efficacy And Safety Of Creatine Supplementation In The General Population, Cody Baxter

Physician Assistant Scholarly Project Papers

The purpose of this study was to determine whether supplementation with creatine monohydrate is efficacious beyond the realm of its most popular use, which is in athletics. This study investigated the safety of creatine supplementation in the general population. References were collected through a review of PubMed and Scopus databases. Initial keywords searched were creatine supplementation and creatine safety. Where possible, trials with human subjects were utilized. Studies focused on creatine’s effects in athletes or weightlifting parameters were eliminated. Topics were further narrowed down by conditions with the most amount of research and medical concerns recognized as common to primary …

Cannabinoid Therapy In Chronic Pain Management, Breanna Joy Privratsky,

Physician Assistant Scholarly Project Papers

In 1996, the state of California was the first in the union to allow for the use of medical marijuana. Since then, 28 more states have enacted similar laws (National Conference of State Legislatures, [NCSL], 2017). With the ever-growing opiate problem that has now been classified as an epidemic by the Centers for Disease Control and Prevention, medical marijuana could be a viable alternative to this problem. As of 2014, the CDC reported opioid deaths were up 369%, which is more than 91 deaths per day from overdose (Centers for Disease Control, [CDC], 2017). The purpose of this study is …

Development Of Polyvinylpyrrolidone/Paclitaxel Self-Assemblies For Breast Cancer, Pallabita Chowdhury, Prashanth K.B. Nagesh, Sheema Khan, Bilal B. Hafeez, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self-assembly (PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an …

Testing Cr(Ii)-Btc For Ammonia Adsorption Capabilities: A Research Proposal, Tyler Hemingway

Undergraduate Honors Theses

Excerpt from Purpose and Hypothesis

The purpose of this thesis is to determine the ability of a particular metal-organic framework (MOF), Cr(II)-BTC, to adsorb ammonia (NH₃) gas. This particular MOF was chosen for this study due to the Cr having open metal sites, which are generally suitable locations for ammonia adsorption as seen in other MOFs.^1,2,3 This study will be done by testing Cr(II)-BTC’s ability to adsorb as well as another MOFs ability to adsorb ammonia. From this data, the ability of Cr(II)-BTC to adsorb ammonia repeatedly and under dry or humid conditions will also be determined. …