Pharmacy and Pharmaceutical Sciences Commons^™

In Vitro Analysis Of Nanoparticulate Hydroxyapatite/Chitosan Composites As Potential Drug Delivery Platforms For The Sustained Release Of Antibiotics In The Treatment Of Osteomyelitis, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Nanoparticulate composites of hydroxyapatite (HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one—HAp. Embedment of 5–10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, …

Cxcr7 Expression Disrupts Endothelial Cell Homeostasis And Causes Ligand-Dependent Invasion, Jennifer Totonchy, Lisa Clepper, Kevin G. Phillips, Owen J. T. Mccarty, Ashlee V. Moses

Pharmacy Faculty Articles and Research

The homeostatic function of endothelial cells (EC ) is critical for a number of physiological processes including vascular integrity, immunity, and wound healing. Indeed, vascular abnormalities resulting from EC dysfunction contribute to the development and spread of malignancies. The alternative SDF-1/CXCL12 receptor CXCR7 is frequently and specifically highly expressed in tumor-associated vessels. In this study, we investigate whether CXCR7 contributes to vascular dysfunction by specifically examining the effect of CXCR7 expression on EC barrier function and motility. We demonstrate that CXCR7 expression in EC results in redistribution of CD31/PECAM-1 and loss of contact inhibition. Moreover, CXCR7+ EC are deficient in …

Female Rats Are More Susceptible To Central Nervous System Oxygen Toxicity Than Male Rats, Heather E. Held, Raffaele Pilla, Geoffrey E. Ciarlone, Carol S. Landon, Jay B. Dean

Molecular Pharmacology & Physiology Faculty Publications

Tonic–clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) …

Synthesis Of 4-Aryl-6-Indolylpyridine-3-Carbonitriles And Evaluation Of Their Antiproliferative Activity, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Magda Goda El-Meligy, Ahmed Kamel El-Ziaty, Zenat Adeeb Nagib, Keykavous Parang

Pharmacy Faculty Articles and Research

A novel class of 6-indolypyridine-3-carbonitrile derivatives were synthesized and evaluated for antiproliferative activities to establish structure–activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, ethyl cyanoacetate, and ammonium acetate in the presence of piperidine as a catalyst, using a microwave irradiation method or a traditional thermal method. This was followed by chlorination for compounds 13a–e and subsequent nucleophilic substitution of the chlorine group by ethylenediamine at C2 position of the pyridine ring. The antiproliferative activity of these new nicotinonitriles was evaluated against human ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7), and cervix adenocarcinoma (HeLa) cells. …

Implementation Of A Pharmacy-Based Adult Vaccine Benefit: Recommendations For A Commercial Health Plan Benefit, Jeffery A. Goad, Kelly J. Ko, Rolin L. Wade, Hsing-Ting Yu, Ross M. Miller, Bruce Sherman

Pharmacy Faculty Articles and Research

BACKGROUND: Although vaccination rates in children exceed 90% in the United States, adults are vaccinated at far lower rates. In order to address this issue, additional community immunizers are needed, and pharmacists are in an ideal position to fill this void.

OBJECTIVES: To explore issues and barriers related to implementation of a pharmacy-based adult vaccine benefit and develop recommendations supporting a pathway for benefit expansion.

METHODS: A literature review on the current environment surrounding pharmacy-based adult vaccinations and structured interviews were conducted to inform an expert panel meeting using a modified Delphi process (pre/post survey). The goal …

Facile, Regio-And Diastereoselective Synthesis Of Spiro-Pyrrolidine And Pyrrolizine Derivatives And Evaluation Of Their Antiproliferative Activities, Abdulrahman I. Almansour, Raju Suresh Kumar, Farzana Beevi, Amir Nasrolahi Shirazi, Hasnah Osman, Rusli Ismail, Tan Soo Chen, Brian Sullivan, Kellen Mccaffrey, Alaa Nahhas, Keykavous Parang, Mohamed Ashraf Ali

Pharmacy Faculty Articles and Research

A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene] tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 M) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-alpha-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds …

Synthesis And Evaluation Of Antiproliferative Activity Of Substituted N-(9-Oxo-9h-Xanthen-4-Yl)Benzenesulfonamides, Somayeh Motavallizadeh, Asal Fallah-Tafti, Saeedeh Maleki, Amir Nasrolahi Shirazi, Mahboobeh Pordeli, Maliheh Safavi, Sussan Kabudanian Ardestani, Shaaban Asd, Rakesh Tiwari, Donghoon Oh, Abbas Shafiee, Alireza Foroumadi, Keykavous Parang, Tahmineh Akbarzadeh

Pharmacy Faculty Articles and Research

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDAMB- 468) cells. Structure-activity relationship studies revealed …

Effects Of Hepatic Ischemia-Reperfusion Injury On The P-Glycoprotein Activity At The Liver Canalicular Membrane And Blood-Brain Barrier Determined By In Vivo Administration Of Rhodamine 123 In Rats, M. K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Purpose To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood-brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker.

Methods Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis.

Results P-gp protein …

Bipolar Disorder: A Pharmacotherapy Management Overview, Huong Le, Tina Pham, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE activity has been developed to educate pharmacists on bipolar disorder and its management using non-pharmacologic and pharmacologic therapies.

An International Validation Study Of Two Achievement Goal Measures On Pharmacy Education Context, Saleh Alrakaf, Ahmed Abdelmageed, Mary Kiersma, Sion A. Coulman, Dai N. John, June Tordoff, Claire Anderson, Ayman M. Noreddin, Erica Sainsbury, Grenville Rose, Lorraine Smith

Pharmacy Faculty Articles and Research

Background: Achievement goal theory helps us understand what motivates students to participate in educational activities. However, measuring achievement goals in a precise manner is problematic. Elliot and McGregor’s Achievement Goal Questionnaire (AGQ) and Elliot and Murayama’s revised Achievement Goal Questionnaire (AGQ-R) are widely used to assess students’ achievement goals. Both instruments were developed and validated using undergraduate psychology students in the USA.

Methods: In this study, our aims were to first of all, assess the construct validity of both questionnaires using a cohort of Australian pharmacy students and, subsequently, to test the generalizability and replicability of these tools …

Non-Raft Ac2 Defines A Camp Signaling Compartment That Selectively Regulates Il-6 Expression In Airway Smooth Muscle Cells, Amy S. Bogard, Anna V. Birg, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclase (AC) isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions. Most cell types express multiple AC isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses in human bronchial smooth muscle cells (BSMC). Overexpression of AC2, AC3, or AC6 had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes. These data show that different AC isoforms can differentially regulate gene expression. Most notable, overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production by BSMC was …

An Analysis Of The Cause, Effect & Control Of Hyperlipidemia From A Nursing Perspective, Melissa Rodgers

Theses and Dissertations

Two of the top four causes of death worldwide, heart disease and stroke, are related to hyperlipidemia, elevated cholesterol levels; these two illnesses account for approximately seventeen million deaths each year (World Health Organization, 2014). In order to combat the prevalence of these illnesses, the National Cholesterol Educational Panel has issued guidelines regarding cholesterol management. Extensive research has been published concerning cholesterol management. However, a gap remains between evidenced-based practice and community awareness of this phenomenon. This manuscript compiles research from peer reviewed nursing journals and acclaimed government and national organizations to express the cause, effect, and control of hyperlipidemia …

Modulation Of Cns Neurotransmitter Levels And Associated Behaviors In Organic Anion Transporter 1 (Slc22a6) And Organic Anion Transporter 3 (Slc22a8) Knockout Mice, Christine Farthing

Theses and Dissertations

According to the World Health Organization, mental disorders represent the leading cause of disability in the US generating ~58 billion dollars in medical costs annually. Additionally, among the US population, ~40 million adults suffer from an anxiety disorder and ~14 million suffer from a major depressive disorder. The association between the persistence of these neurobehavioral conditions and central nervous system (CNS) levels of biogenic amines and metabolites has been studied for half a century. Further, a number of drugs interfering with neurotransmission/metabolism are used clinically for treatment of these disorders. Recently, some members of the solute carrier (SLC) superfamily, the …

Quantitative Mass Spectrometric Investigations Of Protein Biomarkers: Serum Thymidine Kinase 1 And Human Osteopontin, Morse Faria

Theses and Dissertations

Mass spectrometry is being increasingly used in biomarker research mainly due to its ability to achieve high selectivity coupled with high sensitivity. This dissertation focuses on quantitative mass spectrometric investigations of two protein biomarkers i.e. serum thymidine kinase 1 (TK1) and human osteopontin (OPN).

First part of this research was focused on developing a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for measuring the activity of TK1 in serum by monitoring the conversion of a TK1 specific exogenous substrate, 3’-deoxy-3’-fluorothymidine (FLT), to its mono-phosphorylated form 3’-deoxy-3’-fluorothymidine monophosphate (FLT-MP). A method to quantify FLT-MP on LC-MS/MS was developed and …

Solubility Enhancement And Precipitation Inhibition Of Poorly Water Soluble Compounds Utilizing Hot Melt Extrusion Technology, Jiannan Lu

Electronic Theses and Dissertations

Soluplus® (SOL), a graft amorphous copolymer, composed of polyethylene glycol, vinyl acetate and vinylcaprolactam in a ratio of 13: 30: 57, was utilized to prepare solid dispersions containing felodipine (FEL) or ketoconazole (KTZ) using hot-melt extrusion technology. The melting point depression approach was utilized to determine the miscibility and solubility of the model compounds within Soluplus® , of which felodipine demonstrated higher solubility when compared to ketoconazole (14% vs 4.3% w/w) at room temperature (298K). Moreover, the solubility parameters of FEL, KTZ and SOL were calculated as 21.76, 26.51 and 21.64, respectively.

Polarized light microscopy, Fourier transform infrared spectroscopy (FT-IR), …

Antibiotic Lock Therapy: Review Of Technique And Logistical Challenges, Julie Ann Justo, P Brandon Bookstaver

Faculty Publications

Antibiotic lock therapy (ALT) for the prevention and treatment of catheter-related bloodstream infections is a simple strategy in theory, yet its real-world application may be delayed or avoided due to technical questions and/or logistical challenges. This review focuses on these latter aspects of ALT, including preparation information for a variety of antibiotic lock solutions (ie, aminoglycosides, beta-lactams, fluoroquinolones, folate antagonists, glycopeptides, glycylcyclines, lipopeptides, oxazolidinones, polymyxins, and tetracyclines) and common clinical issues surrounding ALT administration. Detailed data regarding concentrations, additives, stability/compatibility, and dwell times are summarized. Logistical challenges such as lock preparation procedures, use of additives (eg, heparin, citrate, or ethylenediaminetetraacetic …

Pharmacy Law Brief: Implications Of Being A Specialist, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Sceletium Tortuosum And Mesembrine: A Potential Alternative Treatment For Depression, Rebecca Schell

Scripps Senior Theses

Major depressive disorder affects people’s productivity and ability to function in everyday life. The disorder can be attributed to neurochemical imbalances of various neurotransmitters including but not limited to serotonin, dopamine, and norepinephrine. Conventional pharmacological treatments have focused primarily on these three neurotransmitters, and have been shown to be effective in alleviating most of the major symptoms of depression. Although these treatments are effective with most patients, they are known to have adverse side effects, causing patients to seek alternative treatments. Sceletium tortuosum, a succulent plant found in the Cape region of South Africa, has been shown to have …

The Effect Of Damaged Bases On The End Joining Of Dna Double Strand Break Ends, Duaa Bafail

Theses and Dissertations

DNA double strand breaks (DSBs ) are extremely toxic to cells because they can lead to genomic rearrangements and even cell death. Two main pathways can repair DSBs: the homologous recombination repair (HRR) pathway and the non-homologous end-joining (NHEJ) pathway. NHEJ is the primary repair pathway in mammalian cells. HRR repairs single strand breaks (SSBs) or DSBs, mostly during late S phase and G2 phase of the cell cycle, by using an undamaged copy of the DNA sequence, and is therefore largely error-free, while the NHEJ pathway repairs DSBs without the requirement for sequence homology, may be error-free or error-prone, …

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, …