Pharmacy and Pharmaceutical Sciences Commons^™

The Impact Of Concomitant Empiric Cefepime On Patient Outcomes Of Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections Treated With Vancomycin, Evan J. Zasowski, Trang D. Trinh, Safana M. Atwan, Marina Merzlyakova, Abdalhamid M. Langf, Sahil Bhatia, Michael J. Rybak

Faculty Publications & Research of the TUC College of Pharmacy

Background: Data suggest that vancomycin + β-lactam combinations improve clearance of methicillin-resistant Staphylococcus aureus(MRSA) bloodstream infections (BSIs). However, it is unclear which specific β-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin.

Methods: Retrospective cohort study of adults with MRSA BSI from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between …

Novel Flexible Heteroarotinoid, Sl-1-39, Inhibits Her2-Positive Breast Cancer Cell Proliferation By Promoting Lysosomal Degradation Of Her2., Hongye Zou, Mary B. Sevigny, Shengquan Liu, David T. Madden, Maggie C. Louie

Faculty Publications & Research of the TUC College of Pharmacy

SL-1-39 [1-(4-chloro-3-methylphenyl)-3-(4-nitrophenyl)thiourea] is a new flexible heteroarotinoid (Flex-Het) analog derived from the parental compound, SHetA2, previously shown to inhibit cell growth across multiple cancer types. The current study aims to determine growth inhibitory effects of SL-1-39 across the different subtypes of breast cancer cells and delineate its molecular mechanism. Our results demonstrate that while SL-1-39 blocks cell proliferation of all breast cancer subtypes tested, it has the highest efficacy against HER2+ breast cancer cells. Molecular analyses suggest that SL-1-39 prevents S phase progression of HER2+ breast cancer cells (SKBR3 and MDA-MB-453), which is consistent with reduced expression of key cell-cycle …

Cyclodextrin As A Drug Carrier Increasing Drug Solubility, Malka Silberberg

The Science Journal of the Lander College of Arts and Sciences

The development of a new drug requires research and evaluation before the drug is approved to enter the market. One of the factors determining the efficacy of a drug is the aqueous solubility of the drug. A current problem in today’s pharmaceutical industry is the low aqueous solubility of many useful drugs. A drug with a low aqueous solubility will not readily be absorbed by the body. The low aqueous solubility of a drug is often due to the drug’s hydrophobic character. Drug enhancement methods are necessary to avoid the obstacle of drug insolubility and many methods have been developed. …

Benzylideneoxymorphone: A New Lead For Development Of Bifunctional Mu/Delta Opioid Receptor Ligands, Jason R. Healy, Padmavani Bezawada, Nicholas W. Griggs, Andrea L. Devereaux, Rae Reiko Matsumoto, John R. Traynor, Christopher W. Cunningham

Faculty Publications & Research of the TUC College of Pharmacy

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.

A Single Dose Tmv-Ha Vaccine Protects Mice From H5n1 Influenza Challenge, Jyothi K. Mallajosyula, Trushar Jeevan, Rachel Chikwamba, Richard J. Webby, Alison A. Mccormick

Faculty Publications & Research of the TUC College of Pharmacy

Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant Hemagglutinin (HA) subunit protein are often of low potency, requiring repeated boosting to generate a sustained immune response. Previously, we demonstrated improved immunogenicity of a plant-made H1 Hemagglutinin (HA) vaccine by chemical conjugation to the surface of the Tobacco Mosaic Virus (TMV) which is non infectious in mammals. Antigen coated TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier for subunit protein vaccines. In this work, we …

In Planta Production Of Flock House Virus Transencapsidated Rna And Its Potential Use As A Vaccine, Yiyang Zhou, Payal D. Maharaj, Jyothi K. Mallajosyula, Alison A. Mccormick, Christopher M. Kearney

Faculty Publications & Research of the TUC College of Pharmacy

We have developed a transencapsidated vaccine delivery system based on the insect virus, Flock House virus (FHV). FHV is attractive due to its small genome size, simple organization, and non-pathogenic characteristics. With the insertion of a Tobacco mosaic virus (TMV) origin of assembly (Oa), the independently replicating FHV RNA1 can be transencapsidated by TMV coat protein. In this study we demonstrated that the Oa adapted FHV RNA1 transencapsidation process can take place in planta, by using a bipartite plant expression vector system, where TMV coat protein is expressed by another plant virus vector, Foxtail mosaic virus (FoMV). Dual infection in …

Development Of A Multivalent Subunit Vaccine Against Tularemia Using Tobacco Mosaic Virus (Tmv) Based Delivery System, Sukalyani Banik, Ahd Ahmed Mansour, Ragavan Varadharajan Suresh, Sherri Wykoff-Clary, Meenakshi Malik, Alison A. Mccormick, Chandra Shekhar Bakshi

Faculty Publications & Research of the TUC College of Pharmacy

Francisella tularensisis a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated …

Nanoparticle Encapsidation Of Flock House Virus By Auto Assembly Of Tobacco Mosaic Virus Coat Protein, Payal D. Maharaj, Jyothi K. Mallajosyula, Gloria Lee, Phillip Thi, Yiyang Zhou, Christopher M. Kearney, Alison A. Mccormick

Faculty Publications & Research of the TUC College of Pharmacy

Tobacco Mosaic virus (TMV) coat protein is well known for its ability to self-assemble into supramolecular nanoparticles, either as protein discs or as rods originating from the ~300 bp genomic RNA origin-of-assembly (OA). We have utilized TMV self-assembly characteristics to create a novel Flock House virus (FHV) RNA nanoparticle. FHV encodes a viral polymerase supporting autonomous replication of the FHV genome, which makes it an attractive candidate for viral transgene expression studies and targeted RNA delivery into host cells. However, FHV viral genome size is strictly limited by native FHV capsid. To determine if this packaging restriction could be eliminated, …