Pharmacy and Pharmaceutical Sciences Commons^™

The Role Of Megalin In The Transport Of Aminoglycosides Across Human Placenta, Amal Akour

Theses and Dissertations

Background: Intra-amniotic infections (IAIs) are common complications of labor and delivery. If inadequately treated, these infections can lead to significant morbidity and mortality in the mother and the fetus. Intrapartum aminoglycoside (AG) administration is recommended for the management of IAIs. AGs are known to cross the placenta and achieve bactericidal concentrations in fetal serum. However, the highest and most persistent fetal levels are achieved in renal tissue. So, the fetus may be vulnerable to the nephrotoxic effects of AGs. Megalin, a 600 kDaendocytic receptor, is responsible for the uptake of AGs into renal proximal tubular epithelial cells. This receptor is …

Proliferation Of Genetically Modified Human Cells On Electrospun Nanofiber Scaffolds., Mandula Borjigin, Bryan Strouse, Rohina A. Niamat, Pawel Bialk, Chris Eskridge, Jingwei Xie, Eric B. Kmiec

Journal Articles: Pharmaceutical Sciences

Gene editing is a process by which single base mutations can be corrected, in the context of the chromosome, using single-stranded oligodeoxynucleotides (ssODNs). The survival and proliferation of the corrected cells bearing modified genes, however, are impeded by a phenomenon known as reduced proliferation phenotype (RPP); this is a barrier to practical implementation. To overcome the RPP problem, we utilized nanofiber scaffolds as templates on which modified cells were allowed to recover, grow, and expand after gene editing. Here, we present evidence that some HCT116-19, bearing an integrated, mutated enhanced green fluorescent protein (eGFP) gene and corrected by gene editing, …

Heart Failure Transition Of Care Program: The Pharmacist’S Role In Reducing Readmissions, Joseph Favatella, Pharmd Candidate 2013, Joanne Heil, Pharmd, Bcps

College of Pharmacy Faculty Papers

Presented at: ASHP Mid-Year Clinical Meeting in Las Vegas.

Introduction & Background

Current Trends¹

•Approximately 19.6% of Medicare patients are readmitted to the hospital within 30 days

•These readmissions accounted for $15 billion of Medicare spending in 2009

Changes Coming

•As part of the Affordable Care Act, Medicare will not be reimbursing hospitals for patients readmitted within 30 days of discharge

•Hospitals have already begun improving discharge protocols to provide a greater continuity of care and minimize the financial loss of future readmissions

A Model²

•Boston University Medical Center's Re-Engineered Discharge (RED) was the first program to improve …

The Use Of Glucarpidase In An Open-Label Treatment Protocol As Adjunctive Treatment For A Patient With Delayed Methotrexate Elimination, Cheryl A. Abbas, Pharmd, Anne Marie Valorie-Oberle, Bs, Pharmd, Bcop

College of Pharmacy Faculty Papers

Presented at: ASHP Clinical MidYear Meeting in Las Vegas.

Background

Methotrexate (MTX)

• Cytotoxic agent that competitively inhibits dihydrofolate reductase (DHFR), the intracellular enzyme responsible for converting folic acid to reduced folate inhibitors, necessary for DNA synthesis
• Used since 1948 in the treatment of various malignancies and as a disease-modifying agent in rheumatoid arthritis and psoriasis
• High-dose mexthotrexate (HDMTX) began in 1960s solely or in combination with other chemotherapeutic agents

Methotrexate Toxicity

• Almost exclusively cleared through the kidneys
  • Precipitation of drug occurs in the renal tubules
  • Prolonged elevations of systemic MTX concentrations results in potential serious toxicity
• Increased use of HDMTX …

Maine Prevalence Of Pharmacy Robberies, John Redwanski, Diana Nguyen

Pharmacy Practice Faculty Posters

Poster presentation: The increased incidence of drug abuse in the state of Maine has correlated with the prevalence of pharmacy robberies. A 1400 percent increase of pharmacy robberies within the past 3 years has caught the attention of law enforcement and government. Maine’s attorney general commissioned the drug abuse task force to properly control this pharmacy epidemic.

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …

Limited Sampling Estimates Of Epigallocatechin Gallate Exposures In Cirrhotic And Noncirrhotic Patients With Hepatitis C After Single Oral Doses Of Green Tea Extract., Dina Halegoua-De Marzio, Walter K. Kraft, Constantine Daskalakis, Xie Ying, Roy L Hawke, Victor J. Navarro

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant, and antifibrotic properties that may have therapeutic potential for the treatment of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect EGCG disposition and augment its reported dose-dependent hepatotoxic potential.

OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.

METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled. Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis, and 3 were noncirrhotic. After a single oral dose of green tea extract 400 …

Nanotherapies For Treating Prostate Cancer, Michael Danquah

Theses and Dissertations (ETD)

Current prostate cancer treatment remains ineffective primarily due to ineffectual therapeutic strategies and numerous tumor-associated physiological barriers which hinder efficacy of anticancer agents. Therefore, the focus of this study was to investigate a new combination therapy approach for treating prostate cancer and develop polymeric nanocarriers to facilitate anticancer drug and nucleic acid delivery.

It was hypothesized that simultaneously targeting androgen-androgen receptor (AR) and X-linked inhibitor of apoptosis protein (XIAP) signaling pathways would be effective in treating prostate cancer. The effect of bicalutamide (antiandrogen) and embelin (XIAP inhibitor) on the growth of prostate cancer cells in vitro and in vivo was …

Effect Of Compression Force On Agglomeration Of Micronized Active Pharmaceutical Ingredients: Techniques To Prevent Api Agglomeration During Compression, Suresh Potharaju

Theses and Dissertations (ETD)

Micronization is one of the common processes for size reduction to increase surface area of poorly soluble Active Pharmaceutical Ingredient’s (API). This size reduction improves the dissolution rate and permeability thereby increasing the bioavailability for hydrophobic API’s.

Tablets and capsules are the most marketed and easy to manufacture solid dosage forms. During manufacturing of tablets, high compression forces are applied uniaxially on the powder bed to get a coherent consolidated compact with good tensile strength. So, diluents are required to mix with API’s and compress into tablets. When this mixture is compressed into tablets, there is a possibility of agglomeration …

High Resolution Mass Spectrometry (Hrms) Based Investigation Of Small Molecule, Bioactive Secondary Metabolites As Probes In The Examination Of Bacterial Resistance And Virulence, Jerrod Stephen Scarborough

Theses and Dissertations (ETD)

The widespread availability of antimicrobial chemotherapeutics over the last half of the twentieth century has offered dramatic increases in life expectancy. Unfortunately, many pathogenic agents are exhibiting ever increasing resistance to many frontline antibiotics. New chemotherapeutic agents are urgently needed to combat this threat; this work seeks to illustrate applications in which mass spectrometric techniques may be applied to the investigation of novel, small molecule chemotherapeutics for the treatment of bacterial infections. Chapter 1 contains an introduction to mass spectrometry, as well as an overview of relevant chromatographic techniques. Chapter 2 introduces the bacterium F tularensis and M ulcerans and …

New Applications Of Mass Spectrometry For Drug And Lipid Analysis, Elizabeth Lauren Emerson

Graduate Theses and Dissertations

Mass spectrometry is an important tool used in many different disciplines and settings that include forensics, drug discovery, environmental analysis, and proteomics. Gas chromatography - mass spectrometry (GC-MS) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI - TOF MS) are two of the most important instruments used for analysis of compounds. Chapters 1 and 2 of this discussion use GC-MS for the investigation of synthetic cannabinoids in `K2' incense products and the detection of metabolites in urine samples from individuals suspected of consuming these mixtures. Analytical standards were synthesized and used for identification and confirmation of structures. Detection of …

Costs And Use Of Oral Anti-Cancer Medications Among Senior Medicare Part D Beneficiaries, Nantana Kaisaeng

Theses and Dissertations

Oral cancer drugs are branded and expensive medications that generally do not have generics available. The restrictions of the Medicare Part D program, including the coverage gap and high cost-sharing, and the high cost of oral chemotherapy may lead to patients’ non-adherence to medication. Few studies have examined the cost and utilization of oral anti-cancer medications. This study will be the first to examine the costs associated with the use of oral anti-cancer medications and the impact of cost-sharing and type of prescription drug subsidy on medication discontinuation in the Medicare Part D elderly population. Objectives: To determine the usage …

Pharmacokinetics And Brain Uptake In The Rhesus Monkey Of A Fusion Protein Of Arylsulfatase A And A Monoclonal Antibody Against The Human Insulin Receptor, Ruben J. Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Rachita K. Sumbria, William M. Pardridge

Pharmacy Faculty Articles and Research

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, …

Anti-Cocaine Compositions And Treatment, Donald W. Landry, Joanne Macdonald, Shi-Xiang Deng, Chang-Guo Zhan, Daquan Gao, James H. Woods, Roger K. Sunahara, Diwahar L. Narasimhan, Victor Yang, Mei-Chuan Holden Ko, John J. Tesmer, Tien-Yi Lee, Young Min Kwon

Pharmaceutical Sciences Faculty Patents

Embodiments of the invention disclosed herein generally relate to anti-cocaine therapeutics. Specifically, some embodiments of the invention relate to highly efficient, thermostable, and long-lasting cocaine esterase (CocE) mutants that can protect against the toxic and reinforcing effects of cocaine in subjects. Provided herein are mutant CocE polypeptides displaying thermostable esterase activity. Also provided are methods of treating cocaine-induced conditions in a subject in need via administration of mutant CocE as well as methods for high-throughput screening of candidate esterase polypeptides.

Cyclooxygenase-2 Inhibition Attenuates Abdominal Aortic Aneurysm Progression In Hyperlipidemic Mice, Sarbani Ghoshal, Charles D Loftin

Pharmaceutical Sciences Faculty Publications

Abdominal aortic aneurysms (AAAs) are a chronic inflammatory disease that increase the risk of life-threatening aortic rupture. In humans, AAAs have been characterized by increased expression of cyclooxygenase-2 and the inactivation of COX-2 prior to disease initiation reduces AAA incidence in a mouse model of the disease. The current study examined the effectiveness of selective cyclooxygenase-2 (COX-2) inhibition on reducing AAA progression when administered after the initiation of AAA formation. AAAs were induced in hyperlipidemic apolipoprotein E-deficient mice by chronic angiotensin II (AngII) infusion and the effect of treatment with the COX-2 inhibitor celecoxib was examined when initiated at different …

Plk1 Phosphorylation Of Orc2 And Hbo1 Contributes To Gemcitabine Resistance In Pancreatic Cancer, Bing Song, X Shawn Liu, Steven J. Rice, Shihuan Kuang, Bennett D. Elzey, Stephen F. Konieczny, Timoty L. Ratliff, Tony R. Hazbun, Elena G. Chiorean, Xiaoqi Liu

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Although gemcitabine is the standard chemotherapeutic drug for treatment of pancreatic cancer, almost all patients eventually develop resistance to this agent. Previous studies identified Polo-like kinase 1 (Plk1) as the mediator of gemcitabine resistance, but the molecular mechanism remains unknown. In this study, we show that Plk1 phosphorylation of Orc2 and Hbo1 mediates the resistance to gemcitabine. We show that the level of Plk1 expression positively correlates with gemcitabine resistance, both in pancreatic cancer cells and xenograft tumors. Overexpression of Plk1 increases gemcitabine resistance, while inhibition of Plk1 sensitizes pancreatic cancer cells to gemcitabine treatment. To validate our findings, we …

A New Approach To Dried Blood Spot Analysis For Newborn Screening Using High Resolution Liquid Chromatography Tandem Mass Spectrometry, John H. Miller Iv

Theses and Dissertations

The primary purpose of newborn screening is to quickly identify children that are at risk of having a specific disorder in order to start treatment, prevent early death and reduce the chances of permanent physical or mental damage. The current and widely accepted approach used for identification of metabolism disorders involves a flow injection analysis with mass spectrometry detection of acylcarnitines and amino acids. Although this approach is widely accepted and has shown to be sufficient for identification of multiple metabolism disorders the method is not fully quantitative and results often have to be confirmed by second-tier tests. The primary …

Environews #2, Nov. 10, 2012, Richard Philp

Data and Test Instruments

This issue of Environews covers the astounding infant health problems associated with the residue of radioactivity from depleted uranium artillery shells used in Iraq, the importance of marine microbes to ocean productivity and carbon fixing, and the weakening of environmental protection by the government of Canada through changes to protective legislation.

Reviewing The American University Law Review On Extraterritoriality: A Critical Response To Viki Economides, Note, Tianrui Group Co. V. Itc: The Dubious Status Of Extraterritoriality And The Domestic Industry Requirement Requirement Of Section 337(Link), Jonathan Stroud

Scholarly Articles in Law Reviews & Journals

Recently, the Federal Circuit upheld the Commission’s decision to exclude goods based on a trade secret violation that largely happened abroad. The American University Law Review critiqued that decision on two grounds: First, that a presumption against extraterritorial application of U.S. law applied; and second, that licensing alone could not establish a domestic industry. The American University Law Review's critique remains incomplete, however, as the Federal Circuit correctly decided the case for at least two reasons. first, the Federal Circuit correctly applied the “extraterritorial presumption” canon of construction; and second, the recent Federal Circuit decision in InterDigital Communications LLC v. …

Indole Compounds And Their Use As Radiation Sensitizing Agents And Chemotherapeutic Agents, Peter A. Crooks, Thirupathi R. Yerramreddy, Narsimha Reddy Penthala, Michael L. Freeman, Sekhar R. Konjeti

Pharmaceutical Sciences Faculty Patents

Indole derivatives that are useful in the treatment of cancer as a chemotherapeutic agent or radiosensitizing agent.