Chemicals and Drugs Commons^™

Rapid Testing Of Food Matrices For Bacillus Cereus Enterotoxins, Sandra M. Tallent, Jennifer M. Hait, Ann M. Knolhoff, Reginald W. Bennett, Thomas S. Hammack, Timothy R. Croley

United States Food and Drug Administration: Publications

Nine different food products frequently associated with Bacillus cereus outbreaks were chosen as representative matrices to be evaluated with end-point polymerase chain reaction (PCR), enzyme linked immunosorbent assay, lateral flow device and mass spectrometry for detection of enterotoxins associated with human illness. Testing was performed on food portions inoculated with a bacterial strain and incubated at 30C for either 5 h or 24 h. A screening end-point multiplex PCR targeting enterotoxin genes including the emetic toxin and three diarrheal toxins, hemolytic hemolysin BL (Hbl), nonhemoltyic enterotoxin (Nhe), and cytolysin K. Commercially available kits were used to determine the presence/absence of …

Antiemetic Use Among Pregnant Women In The United States: The Escalating Use Of Ondansetron, Lockwood G. Taylor, Steven T. Bird, Leyla Sahin, Melissa S. Tassinari, Patty Greene, Marsha E. Reichman, Susan E. Andrade, Katherine Haffenreffer, Sengwee Toh

United States Food and Drug Administration: Publications

Purpose To examine ondansetron use in pregnancy in the context of other antiemetic use among a large insured United States population of women delivering live births.

Methods We assessed ondansetron and other antiemetic use among pregnant women delivering live births between 2001 and 2015 in 15 data partners contributing data to the Mini-Sentinel Distributed Database. We identified live birth pregnancies using a validated algorithm, and all forms of ondansetron and other available antiemetics were identified using National Drug Codes or procedure codes. We assessed the prevalence of antiemetic use by trimester, calendar year, and formulation.

Results In over 2.3 million …

Food Safety Traceability, Yimin Wei, Boli Guo, Hongyan Liu, Shuai Wei, Jianrong Zhang

United States Food and Drug Administration: Publications

With globalized economics, it is becoming more frequent to trade food across country and regional borders, which leads to expanding and spreading of all kinds of food safety incidents and hazards. Mad cow disease, foot and mouth disease, avian flu and other zoonotic diseases pose a grave threat to food safety and human health, causing serious economic losses for food industries and causing social panic at the same time. In order to reduce the losses caused by such serious zoonotic diseases, as well as to ensure food safety, many countries have started to implement food safety traceability systems. The European …

Quality By Design: Process Trajectory Development For A Dynamic Pharmaceutical Coprecipitation Process Based On An Integrated Real‐Time Process Monitoring Strategy, Huiquan Wu, Mansoor A. Khan

United States Food and Drug Administration: Publications

Increasing prevalence of poorly water‐soluble drugs in pharmaceutical development provides notable risks of new products demonstrating low and erratic bioavailability. This dissolution‐limited bioavailability may have consequences for safety and efficacy, particularly for drugs delivered by the oral route of administration. Several novel drug delivery technologies have been developed to improve drug solubility, dissolution rates, and bioavailability. Among those are solid dispersion, nanotechnology, supercritical fluid technology, lipid‐based technology, and crystal engineering. Although these strategies are available for enhancing the bioavailability of drugs with low aqueous solubility, the success of these approaches is not yet guaranteed and is greatly dependent on the …

The Impact Of The Boxed Warning On The Duration Of Use For Depot Medroxprogesterone Acetate, Efe Eworuke, Joo-Yeon Lee, Lisa Soule, Vaishali Popat, David G. Moeny

United States Food and Drug Administration: Publications

Objective The objective of this study was to examine the impact of the Food and Drug Administration’s boxed warning on the utilization of depot medroxyprogesterone (DMPA).

Methods From the IMS Lifelink data (2001–2009), we identified DMPA and oral combined hormonal contraceptive (CHC) users without a prescription claim 6 months before and after the first and last claim. Episodes were defined as all contiguous claims with no more than 90- day DMPA or 30-day CHC between claims. Days’ supply (CHC) and 90-day duration (DMPA) was used to determine episodes. We used interrupted time series to evaluate changes in the mean episode …

Modeling And Statistical Issues Related To Salmonella In Low Water Activity Foods, Sofia M. Santillana Farakos, Michelle Danyluk, Donald Schaffner, Régis Pouillot, Linda J. Harris, Bradley P. Marks

United States Food and Drug Administration: Publications

The presence and survival of Salmonella in low water activity (a_w) foods continues to pose a challenge for the food industry. Peer‐reviewed literature data on prevalence and levels of contamination of Salmonella in low water activity foods in the United States are limited. Available published data include those on: Salmonella contamination on nuts and peanuts (Calhoun et al., 2013), almonds (Danyluk et al., 2007; Bansal et al., 2010), pecans (Brar, Strawn, and Danyluk, 2016), and walnuts (Davidson et al., 2015); prevalence and levels of Salmonella on spices (Van Doren et al., 2013); as …

Disparities In Hypertension And Cardiovascular Disease In Blacks: The Critical Role Of Medication Adherence, Keith C. Ferdinand, Kapil Yadav, Samar A. Nasser, Helene D. Clayton-Jeter, John Lewin, Dennis R. Cryer, Fortunato Fred Senatore

United States Food and Drug Administration: Publications

Blacks are two to three times as likely as whites to die of preventable heart disease and stroke. Declines in mortality from heart disease have not eliminated racial disparities. Control and effective treatment of hypertension, a leading cause of cardiovascular disease, among blacks is less than in whites and remains a challenge. One of the driving forces behind this racial/ethnic disparity is medication nonadherence whose cause is embedded in social determinants. Eight practical approaches to addressing medication adherence with the potential to attenuate disparities were identified and include: (1) patient engagement strategies, (2) consumer-directed health care, (3) patient portals, (4) …

Current Practices In Corrosion, Surface Characterization, And Nickel Leach Testing Of Cardiovascular Metallic Implants, Srinidhi Nagaraja, Matthew Di Prima, David Saylor, Erica Takai

United States Food and Drug Administration: Publications

In an effort to better understand current test practices and improve nonclinical testing of cardiovascular metallic implants, the Food and Drug Administration (FDA) held a public workshop on Cardiovascular Metallic Implants: corrosion, surface characterization, and nickel leaching. The following topics were discussed: (1) methods used for corrosion assessments, surface characterization techniques, and nickel leach testing of metallic cardiovascular implant devices, (2) the limitations of each of these in vitro tests in predicting in vivo performance, (3) the need, utility, and circumstances when each test should be considered, and (4) the potential testing paradigms, including acceptance criteria for each test. In …

High Throughput Quantification Of Apolipoproteins A-I And B-100 By Isotope Dilution Ms Targeting Fast Trypsin Releasable Peptides Without Reduction And Alkylation, Bryan A. Parks, David M. Schieltz, Michael L. Andrews, Michael S. Gardner, John C. Rees, Christopher A. Toth, Jeffrey I. Jones, Lisa G. Mcwilliams, Zsuzsanna Kuklenyik, James L. Pirkle, John R. Barr

United States Food and Drug Administration: Publications

Purpose: Apolipoprotein A-I (ApoA-I) and apolipoprotein B-100 (ApoB-100) are amphipathic proteins that are strong predictors of cardiovascular disease risk. The traceable calibration of apolipoprotein assays is a persistent challenge, especially for ApoB-100, which cannot be solubilized in purified form.

Experimental design: A simultaneous quantitation method for ApoA-I and ApoB-100 was developed using tryptic digestion without predigestion reduction and alkylation, followed by LC separation coupled with isotope dilution MS analysis. The accuracy of the method was assured by selecting structurally exposed signature peptides, optimal choice of detergent, protein: enzyme ratio, and incubation time. Peptide calibrators were value assigned by isobaric tagging …

Exploration Of Bioactive Compounds Of Ginger As A Folk Remedy For Migraines, Nathan Vorbes Aleger

Honors Undergraduate Theses

Ginger (Zingiber Officinale) has been used in Asia for centuries to treat various ailments. Ginger has been reported to alleviate migraine pain via four bioactive compounds that can reduce nitric oxide synthase (NOS) resulting in the inhibition of nitric oxide (NO). The inhibition of nitric oxide results in the vasoconstriction of the intracranial blood vessels alleviating migraine pain. It is hypothesized that ginger has structural similarities to vasoconstrictor drugs causing similar receptor interactions. A review of the bioactive compounds in ginger and popular vasoconstrictor drugs was done to determine structural similarities. The results of this study show that …

Microbial Ecology Of Fresh Vegetables, J. Zheng, A. De Jesus, S. Sahu, A. E. Hayford, Y. Luo, A. R. Datta, E. W. Brown, R. Bell

United States Food and Drug Administration: Publications

The total consumption of fresh and processed vegetables has exceeded 123 kg per capita in the United States and 118 kg per capita in the European Union (http://www.helgilibrary.com/ indicators/index/vegetable‐consumption‐percapita) in 2009. Changes in lifestyles and consumption trends have prompted the sustained growth of fresh‐cut or minimally processed vegetables that are fresh and ready‐to‐eat (RTE). In 2011, for example, total US fresh‐cut produce sales through both food service and retail channels were estimated to surpass $27 billion (Cook et al., 2012).

Risk Of Gastrointestinal Bleeding Among Dabigatran Users – A Self Controlled Case Series Analysis, Wenze Tang, Hsien-Yen Chang, Meijia Zhou, Sonal Singh

Epidemiology Faculty Publications

This article aims to evaluate the real world risk of gastrointestinal bleeding among users naïve to dabigatran. We adopted a self-controlled case series design. We sampled 1215 eligible adult participants who were continuous insured users between July 1, 2010 and March 31, 2012 with use of dabigatran and at least one gastrointestinal bleeding episode. We used a conditional Poisson regression to estimate incidence rate ratios. The population consisted of 64.69% of male and 60.25% patients equal to or greater than age 65 at start of observation. After adjustment for time-variant confounders, the incidence rate of gastrointestinal bleeding was similar during …

Combating Antibiotic Resistance: A Policy Roadmap To Reduce Use Of Medically Important Antibiotics In Livestock, Expert Commission On Addressing The Contribution Of Livestock To The Antibiotic Resistance Crisis 2017

Antibiotic Resistance Action Center (ARAC)

No abstract provided.

“Whatever It Takes To Beat Parkinson’S”: A Controversial Approach For Symptom Relief, Sondra M. Deskins

WRIT: Journal of First-Year Writing

It is known that there is no cure for Parkinson's disease. So, physicians who treat Parkinson's patients must decide what is the best treatment option for the patients symptoms to improve their quality of life. Currently, there are pharmaceutical options for treatment, but they include adverse side effects. What if there were a way to treat patients for the side effects as well as improve the patient's symptoms? The recent commotion around the legalization of marijuana, both recreational and medicinal, has caused interest among patients and physicians. One must decide if the benefits of using marijuana as a form of …

Steroids: A Growing Dilemma In Athletics, Seara Ontiveros

Nebraska College Preparatory Academy: Senior Capstone Projects

A comprehensive and straight forward description of what exactly steroids are and what they do to the body is described by Gary Wadler, a health major at the New York University School of Medicine, he comments: “When the receptor sites in their bodies, which don’t have much testosterone in them, suddenly are presented with a lot of testosterone, they get activated…The unbalance of hormones increases the red blood cell formations... They’ll get more muscular, more defined. They’ll lose some fat, and increase their lean body mass, [they’ll] get stronger”. Although anabolic steroids and other hormones are consumed by many athletes …

Unmasking Of Myoclonus By Lacosamide In Generalized Epilepsy, Daniel Birnbaum, Mohamad Z. Koubeissi

Neurology Faculty Publications

Lacosamide is a new-generation antiseizure medication that is approved for use as an adjunctive treatment and monotherapy in focal epilepsy. Its use in generalized epilepsy, however, has not been adequately evaluated in controlled trials. We report a 67-year-old woman who experienced new-onset myoclonic seizures after initiation of lacosamide. We presume that she had an undiagnosed generalized epilepsy syndrome, likely juvenile myoclonic epilepsy. Myoclonic seizures were not reported before introducing lacosamide and completely resolved after lacosamide was discontinued. This suggests that lacosamide may have the potential to worsen myoclonus, similar to what has been reported with another sodium channel agent, lamotrigine, …

Antibiotic Resistance And Diagnostic Tests: What You Need To Know, Antibiotic Resistance Action Center (Arac)

Antibiotic Resistance Action Center (ARAC)

No abstract provided.

Can A Layer Of Antimicrobial Agents Be Placed Around Breast Implants To Prevent Staph Infections From Occurring?, Valerie L. Tran

UROP Posters

The most common infection that occurs after breast augmentation is a staph infection. Currently, there are only three ways to treat this type of infection, all of which treat the breast implant after the infection has developed. The first option is to treat the infection with an oral antibiotic. If this doesn’t completely rid the infection, then intravenous antibiotics are used. If this too doesn’t remove the infection, then surgery will be performed to remove the breast implant and a new implant will be inserted. Although, these options have a low mortality rate, the success rate of completely getting rid …

Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen

Chemistry Faculty Publications

Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2- AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or basecatalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate …

Synthesis Of A 1,2,4-Substituted Imidazole For A Fragment-Based Drug Discovery Library, Tyler Lafferty

Honors Program Theses

The field of medicinal chemistry requires efficient, novel drug development processes to sustain and advance the landscape of current pharmaceutical agents. To this end, fragment-based drug discovery (FBDD) is a methodology that aims to provide a balanced approach to the hit detection and lead optimization stage in the identification of small molecule agents (fragments). These small, low-molecular weight (mw<300 amu) molecules are employed in various biochemical assays to identify leads against a biological target. One challenge in FBDD is the synthesis of novel fragments containing heterocycles with a selective synthetic handle, a functional group designed to allow further modification. Heterocyclic fragments that allow for straightforward synthesis and modification are underrepresented in fragment libraries and offer the intriguing opportunity for rapid diversification into a fragment library from single, heterocyclic parent fragment. The imidazole is a heterocycle that presents a unique synthetic challenge for organic chemists, as current imidazole syntheses do not allow for regioselective synthesis of a 1,2,4-substitued imidazole. The research herein describes the approaches taken towards the challenge of synthesizing the 1,2,4-substituted imidazole parent fragment containing a hydrophilic moiety, synthetic handle, and phenyl ring derivative.

Substituent Strength Vs Reactivity: A Study Of 1,3,4-Oxadiazoles And Electron Donating Groups, Katlynn Merringer

Undergraduate Honors Thesis Projects

This investigation focused on determining if there was a relationship between electron donating group substituent strength and resulting percent yield values of the 1,3,4-oxadiazole product. The data obtained from this investigation aimed to help chemists better understand the reactivity of the 1,3,4-oxadiazole because of its importance in the realm of drug design and development. In order to accomplish this, electron donating groups with varying pKa values were placed on the 1,3,4-oxadiazole and the resulting percent yields were analyzed for possible trends. The substituents used represented both resonance donating and inductively donating groups and were placed in both ortho and para …

Synthesis Of Oxadeazoles With Electron Withdrawing Groups And The Analysis Of Product Yield With Bond Length, Elizabeth Ann Hall Peters

Undergraduate Honors Thesis Projects

2,5-disubstituted 1,3,4-oxadiazoles are a class of organic compound that are widely used and successful in pharmaceutical chemistry because they demonstrate strong biological activity. They are part of a larger class of compound called heterocycles, which make up most pharmaceutical drugs today. When synthesizing the compounds, higher yield means higher reactivity of the compound, and this is important for pharmaceuticals that need to have a strong biological activity. Per past studies, electron withdrawing groups on the compound allow higher, product yields. Along with electron withdrawing group addition, the bond length from electron withdrawing group and its corresponding carbon is analyzed to …

Uvb Induces Mvp Release In A Paf Dependent Manner In Skin-Dervied Epithelial Cell Line, Langni Liu, Katherine E. Fahy, Christine M. Rapp, Eric J. Romer, Christina E. Borchers, Ji C. Bihl, Jeffrey B. Travers

Pharmacology and Toxicology Faculty Publications

Ultraviolet-B (UVB) irradiation of the skin can result in both acute inflammation and systemic immunosuppression. These effects are mediated by the release of bioactive molecules (e.g. cytokines and lipids) from resident skin epithelial and immune cells. Our lab has previously determined that UVB exposure stimulates the production of an inflammatory phospholipid activator, platelet-activating factor (PAF) and its oxidized analogs, which are involved in mediating the UVB responses. Due to the fact that UVB radiation is absorbed by the epidermis but causes systemic effects, we are interested in examining the PAF-mediated mechanisms of systemic intercellular communication. Microvesicle particles (MVP) are small …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

Actionable Patient Safety Solution (Apss) #3d: Pediatric Adverse Drug Events, Ron Jordan, Jerika Lam, Nathaniel Sims, Anne Lyren, Coco Yang

Pharmacy Faculty Articles and Research

This report presents a plan of action for introducing a "program to reduce the incidence of pediatric adverse drug events (pADEs) and harm ... [that] combine[s] leadership strategies, software (healthcare IT), hardware (drug compounding systems, drug delivery technology, and physiological monitoring systems), and most importantly people (changes in clinical practice, protocols and education)" to protect pediatric patients.

Antibiotic Overuse: The History, Consequences, And Possible Solutions, Brooke A. Bost

Senior Honors Theses

Antibiotic overuse has become alarmingly accepted in the developed world. This overuse is leading to drug resistance in microbes, resulting in bacterial infections that are impossible to treat. Steps must be taken to reverse the damage that has already been done and prevent further resistance from developing. This thesis will examine the context and societal situations that led to this acceptance of antibiotic overuse and misuse seen in both health care professionals and the public, the biochemical and genetic pathways that allow a microbe to develop drug resistance, the various methods that have been suggested by experts to prevent and …

Infusion Of Essentail Oils In Agarose Gels To Create Antimicrobial Surfaces, Simran Guron

Honors College Theses

The current use of antibiotics is very excessive in multiple settings, from treating patients to being present in cleaning products. This overuse of antibiotics is resulting in multiple consequences, ranging from having a negative impact on human health to breeding antibiotic-resistant strains of microorganisms. Antimicrobial surfaces are useful today to aid in sterilization, especially in the medical setting. This would help prevent the spread of infection of microorganisms in these settings. In our research, agarose acts as the antimicrobial surface and essential oils would act as the solution incorporated into the surface that has the antimicrobial properties. Agarose is a …

Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker

All Master's Theses

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …

The Indirect Consequences Of Expanded Off-Label Promotion, Patricia J. Zettler

Faculty Publications By Year

The U.S. Food and Drug Administration’s (FDA) policies have been a battleground for litigation about First Amendment protections for commercial speech. In the last five years, the FDA’s position that “off-label” promotion of approved prescription drugs—when a manufacturer promotes a drug for a use for which the FDA has not approved it—leads to violations of the Federal Food, Drug, and Cosmetic Act has been subject to successful legal challenges. Although the merits of these off-label promotion decisions are well traversed in the literature, this Article explores the potential indirect consequences of recently-recognized protections for off-label promotion. This Article demonstrates that—as …

Enhanced Potency Of Bivalent Small Molecule Gp41 Inhibitors, Vladimir Sofiyev, Hardeep Kaur, Beth A. Snyder, Priscilla A. Hogan, Roger G. Ptak, Peter Hwang, Miriam Gochin

Faculty Publications & Research of the TUC College of Osteopathic Medicine

Low molecular weight peptidomimetic inhibitors with hydrophobic pocket binding properties and moderate fusion inhibitory activity against HIV-1 gp41-mediated cell fusion were elaborated by increasing the available surface area for interacting with the heptad repeat-1 (HR1) coiled coil on gp41. Two types of modifications were tested: 1) increasing the overall hydrophobicity of the molecules with an extension that could interact in the HR1 groove, and 2) forming symmetrical dimers with two peptidomimetic motifs that could potentially interact simultaneously in two hydrophobic pockets on the HR1 trimer. The latter approach was more successful, yielding 40–60 times improved potency against HIV fusion over …