Pharmacy and Pharmaceutical Sciences Commons^™

Ancestral Dependence On Breast Stemness And Nucleotide Excision Repair In Breast Cancer Stem Cells In Novel Human Model Systems, Omar Ibrahim

Student Theses, Dissertations and Capstones

Precocious puberty, measured by thelarche or menarche, is a well-established breast cancer risk factor. Using a unique and patented tissue engineering system we established cell lines from 48 primary cultures of normal breast tissue from reduction mammoplasties and used them as an in vitro model of thelarche, quantifying episphere formation and ductal differentiation. Differential ductal formation was observed based on ancestry. In light of African American (AA) precocious thelarche both in vivo and as we observed in vitro, we hypothesized that AA women would exhibit an increased proportion of breast stem cells, with greater potency for differentiation. Five AA cell …

Mechanistic Study Of P23-Mediated Aryl Hydrocarbon Receptor Expression, Beverly Pappas

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which is involved in diverse biological functions ranging from cancer metastasis to immune regulation. This receptor forms a cytoplasmic complex with Hsp90, p23, and XAP2. We have previously reported that down-regulation of p23 triggers degradation of the AHR protein, uncovering a potentially dynamic event which controls the cellular AHR levels without ligand treatment. Here we investigate the underlying mechanisms for this p23 effect using wild-type HeLa and the p23 knockdown HeLa cells. Reduction of the Hsp90 and XAP2 contents, however, did not affect the AHR protein levels, implying that this …

Measuring Knowledge And Attitudes Regarding The Use Of Pharmacogenetic Testing Among Patients And Prescribers: Diffusion Of Innovation Theory, Suhaib Mohammad Muflih

Student Theses, Dissertations and Capstones

Background: Healthcare providers play a key role in patient care. Their knowledge and attitudes may play a critical role in the incorporation of pharmacogenetic (PGx) testing into routine practice. The knowledge and attitudes of patients are also equally important in determining the rate of diffusion and the adoption of PGx testing. This study aims to test Rogers’s diffusion of innovation theory to identify and evaluate the influence of knowledge, attitudes, and sociodemographic characteristics of patients and physicians on the adoption of PGx testing in current clinical settings. Method: A cross-sectional, descriptive survey design was implemented. The sample consisted of patients …

The Development Of Preclinical Strategies For Facilitation Of Lead Candidate Selection, Christopher Dale Kulczar

Open Access Dissertations

Chapter 1 details a background of techniques used for modeling the blood-brain barrier (BBB). The BBB represents a diffusive barrier to both paracellular and transcellular movement of many compounds in and out of the brain. The main rate- limiting barriers of the BBB include exclusive tight junctions that prevent the movement of hydrophilic molecules through intercellular gaps, and efflux proteins in the membrane which pump many hydrophobic molecules back into the blood. In addition, the BBB contains metabolizing enzymes, including Cytochrome P450s. This barrier acts to protect the vulnerable tissues of the brain from harmful xenobiotics, but also can serve …

Innovative Novel Immunotherapies For The Treatment Of Glioblastoma Multiforme, Salma Salem

Open Access Theses

Glioblastoma Multiforme GBM is a very aggressive type of malignant brain tumors that affects peoples’ lives. The diffusive, infiltrative, and metastatic behaviour of GBM is the major reason for the disease recurrence. The morphological and immunohistological characteristics of Central Nervous System (CNS) tumors including GBM are heterogeneous. GBM is either primary (de novo) or secondary to low-grade astrocytomas.

Current treatment options include surgery, radiotherapy, and temozolomide chemotherapy have not achieved any improvement in success rates over the past decades. The survival time reached by GBM patients was approximately 12 months only after being treated with radiotherapy alone without temozolomide. However, …

Design, Optimization, And Characterization Of Novel Polymer-Based Formulations For Controlled Release Of Drugs, Mario Alberto Cano Vega

Open Access Theses

Pharmaceutical products are a key aspect of treatment and prevention of disease. For example, dibenzazepine (DBZ) is a drug that has proved to be useful for the treatment of obesity while progesterone is a common drug for hormonal replacement therapy in women. However, administration of these drugs by conventional dosage forms offers little control over the drug distribution and concentration in the body and often result in unintended adverse consequences on other cells/tissues.

Recent advances in nanotechnology and polymer science have enabled the design and development of controlled release systems that would allow spatiotemporal delivery of drugs with improved efficacy. …

Modeling Picking On Pharmaceutical Tablets, Shrikant Swaminathan

Open Access Dissertations

Tablets are the most popular solid dosage form in the pharmaceutical industry because they are cheap to manufacture, chemically and mechanically stable and easy to transport and fairly easy to control dosage. Pharmaceutical tableting operations have been around for decades however the process is still not well understood. One of the common problems faced during the production of pharmaceutical tablets by powder compaction is sticking of powder to the punch face, This is known as 'sticking'. A more specialized case of sticking is picking when the powder is pulled away form the compact in the vicinity of debossed features. In …

Nanoformulation For Anticancer Drug Delivery: Enhanced Pharmacokinetics And Circulation, Gaurav Parekh

Doctoral Dissertations

In this study, we have explored the application of the Layer-by-Layer (LbL) assembly technique for improving injectable drug delivery systems of low soluble anticancer drugs (e.g. Camptothecin (CPT), Paclitaxel (PTX) or Doxorubicin (DOX)). For this study, a polyelectrolyte shell encapsulates different types of drug nanocores (e.g. soft core, nanomicelle or solid lipid nanocores).The low soluble drugs tend to crystallize and precipitate in an aqueous medium. This is the reason they cannot be injected and may have low concentrations and low circulation time in the blood. Even though these drugs when present in the cancer microenvironment have high anti-tumor inhibition, the …

Predicting Aqueous Solubility Of Pharmaceutical Agents By Solid Dispersion Prepared By Solvent Evaporation Method, Karthik Reddy Patlolla

University of the Pacific Theses and Dissertations

Solubility of active pharmaceutical agents is a crucial process that determines drug absorption and ultimately its bioavailability. Many of the new therapeutically beneficial compounds discovered are lipophilic requiring various solubility enhancement strategies to improve their solubility. Among these strategies, solubility enhancement using solid dispersions is a leading method. To obtain a desirable increase in the solubility of a poorly-soluble compound, a good understanding of the molecular descriptors influencing the enhancement of solubility is essential. Therefore, the major research objective was to determine the descriptors which significantly influence the solubility enhancement by solid dispersions. After enhancing the solubility of selected poorly-soluble …

The Impact Of An Omega-3 Enriched Diet On Hyperactivity And Biochemistry In An Animal Model For Attention-Deficit/Hyperactivity Disorder, Nadine M. Hammoud

Open Access Theses

Attention-deficit/hyperactivity disorder (ADHD) is the most diagnosed behavioral disorder in children. It affects around 5% of children worldwide and 11% of children in the United States, with rates increasing. Pharmaceutical treatments, such as amphetamines and methylphenidates, are not effective for everyone and are known to have unwanted side effects. While the etiology of the disorder is not yet fully understood, there are clear genetic and environmental components. Nutritional insufficiencies have recently become a popular environmental risk factor under investigation. Essential fatty acids (EFA), omega-3 polyunsaturated fatty acids (PUFA) in particular, are needed for proper brain development and function. Our lab …

Pharmacist Collaborative Drug Therapy Management In U.S. Hospitals, Pragya Mishra

Open Access Theses

The objectives for this study were to 1) assess the current extent, scope and perceptions of CDTM in U.S. hospitals, 2) determine the associations between hospital characteristics, pharmacy director characteristics, and perceptions of CDTM, 3) investigate hospitals' short-term and long-term plans regarding CDTM, and 4) identify pharmacy directors' views about the major facilitators and barriers for CDTM in hospitals.

A self-administered written survey was mailed to a national random sample of hospitals stratified by state. Pharmacy directors indicated whether any pharmacists were engaged in CDTM, what CDTM activities were permitted, and in what treatment categories CDTM was permitted. Demographic data …

Prediction Of The Stress At The Inlet Of The Nip Region In A Roll Compactor, Timothy Patterson

Open Access Theses

The stress at the inlet nip region of a roll compactor (i.e., feeder outlet stress) is a necessary input parameter for existing powder roll compaction models; however the nip region inlet stress is poorly understood and difficult to directly measure. The inability to specify the nip region inlet stress on a roll compactor limits comparisons between powder roll compaction models and experimental results. Therefore, this thesis investigates the application of a solid plug model to a powder feed screw of a roll compactor in order to predict the stress at the inlet nip region.

The feeder outlet stress predictions of …

Risk Attitudes And Characteristics Of Student Pharmacists Across Cohorts, Kristin Rose Villa

Open Access Theses

In unstable environments, adaptation is a prerequisite for survival of organizations or groups. The Affordable Care Act has created a changing environment for health care providers. Unfortunately for Pharmacy, innovation within our profession has languished, leaving pharmacists in a precarious position. Many have noted the stagnation of the profession; in fact it has been a recurring theme in the commentary over the last five decades. The dialogue has focused on the externalities that represent barriers to the profession's evolution, including the direction change should take and the legal or organizational issues that inhibit change and innovation. Little attention has been …

Controlling Protein Release Using Biodegradable Microparticles, Benjamin Patrick Kline

Open Access Theses

Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety …

Patient Perceptions Of Physicians And Medication Adherence Among Medicare Part D Beneficiaries, Lori Marquinne Ward

Open Access Dissertations

Ward, Lori Marquinne. Ph.D., Purdue University, December, 2013. Patient Perceptions of Physicians and Medication Adherence Among Medicare Part D Beneficiaries. Major Professor: Joseph Thomas III.

An observational database analysis using Medicare Current Beneficiary Survey data was conducted to examine patient perceptions of physicians and associations with adherence to antihypertensive medication among Medicare beneficiaries enrolled in Medicare Part D. The study sample included beneficiaries if they were 65 years or older, dwelling in the community, had a diagnosis of hypertension in 2007, were enrolled in Medicare Part D all 12 months in 2008, and had Medicare Part D claims for antihypertensive …

Design, Development, And Characterization Of Novel Antimicrobial Peptides For Pharmaceutical Applications, Yazan H. Akkam

Graduate Theses and Dissertations

Candida species are the fourth leading cause of nosocomial infection. The increased incidence of drug-resistant Candida species has emphasized the need for new antifungal drugs. Histatin 5 is a naturally occurring human salivary antifungal peptide and the first line of defense against infections of the oral cavity. This research has focused on understanding the activity of histatin 5, and subsequently designing novel peptides that may serve as models for the further development of therapeutics to treat fungal infection.

This objective has been achieved in three steps: studying the structural requirement of histatin 5 involved in antifungal activity, the identification of …

Low Soluble Drug Encapsulation Based On Architecture Of Layer-By-Layer Assembly For Longer Circulation Time And Targeted Therapy, Pravin Pattekari

Doctoral Dissertations

A combined effect of sonication and layer-by-layer assembly (LbL) enhances the solubility of many poorly soluble inorganic and organic materials by forming stable particles with ca. 200 nm size and up to 90 wt% of loading. The entire method is reproducible, easy-to-handle, and flexible for varying surface properties according to the application of the materials. The method develops good colloidal stability of materials in buffers and maintains architecture for future improvement. A top-down approach, with a combined effect of sonication and LbL assembly, ruptures the material and allows adsorption of oppositely charged polyelectrolytes simultaneously. Thus, the approach is applicable for …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Off-Label Prescribing: Pediatrician Beliefs And Experience, Elizabeth G. Evola

Seton Hall University Dissertations and Theses (ETDs)

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Polyamine And Acetylpolyamine Levels During Phenylhydrazine-Induced Erythropoiesis In Mouse Spleen, Othman A. Alshabanah

University of the Pacific Theses and Dissertations

The phenylhydrazine-induced erythropoietic mouse spleen is used as a model system to demonstrate the relationship between tissue growth and polyamine metabolism. Phenylhydrazine produced significant changes in spleen weights, hematocrits and reticulocyte counts in Swiss-Webster mice. The average spleen weight went up from a control of 155 mg to 875 mg at 96 hours after phenylhydrazine administration, while a 49% reduction in the value of hematocrit was observed at 72 hours. Reticulocyte counts in peripheral blood went from 0.8 to 58% at 168 hours after treatment with phenylhydrazine. Phenylhydrazine at a dose of 40 mg/kg produced significant increases in the levels …

Design And Evaluation Of Theophylline Monitoring For Home Health Care Patients, May Naim Mikhail

University of the Pacific Theses and Dissertations

The purpose of this study was to design, evaluate, and determine the cost benefit of a pharmacokinetic service for home-based patients. Four randomly selected patient populations were used in evaluating the service for six months. The experimental group consisted of 17 patients who were under the care of family practice physicians in private practice and who received pharmacokinetic consultation and monitoring by a pharmacist as a home health care service. The retrospective control consisted of the same 17 patients of the experimental group whose past medical history for a period of six months was used. The concurrent control consisted of …

Investigation Of Physicochemical And Formulation Parameters For Transdermal Delivery Of Isoproterenol Hc1, Rajesh Arvindkumar Patel

University of the Pacific Theses and Dissertations

Effects of solubility, partition coefficient, pH and selected adjuvants (propylene glycol and Azone) on the percutaneous penetration of isoproterenol HC1 in vitro have been investigated using human cadaver skin. Preliminary stability studies demonstrated that isoproterenol HC1 was very stable (less than 1% decomposition) for 24 hours at 22(DEGREES) (+OR-) 0.5(DEGREES) in the pH range 1 to 7 in the following solvents: water, normal saline, propylene glycol and a series of propylene glycol-water mixtures (10,20,40 and 60% v/v). The rate of decomposition of the drug in aqueous solutions increased with pH beyond pH 8. In normal saline, the decomposition was significant …

Opioid Receptor Effects Of Two Aminotetralin Derivatives In Guinea Pig Ileum Longitudinal Muscle And Mouse Vas Deferens Preparations, Francisca Fatima Matos

University of the Pacific Theses and Dissertations

Two substituted analogs of 3-amino-2,2-dimethyltetralin, namely 3-dimethylamino-7-hydroxy-2,2-dimethyl-1-tetralone HBr (J) and 3-dimethylamino-7-hydroxy-2,2-dimethyl-1-tetralol (MRSAL) were evaluated for opioid agonist and antagonist activity using the electrically-stimulated guinea pig ileum longitudinal muscle and mouse vas deferens preparations. The effects of these compounds in these tissues were compared to those induced by several opioid prototype agonists at mu, kappa and delta sites (normorphine, dihydromorphine, ethylketocyclazocine, U-50,488H, beta -endorphin, dynorphin 1-13, leu-enkephalin and DADLE) and one opioid antagonist (naloxone). The results of these experiments demonstrated that compound J inhibited contractions in a concentration-dependent manner as an opioid agonist and its effects were antagonized by naloxone in …

The Effect Of Selected Adjuvants On The In Vitro Percutaneous Penetration Of Benzocaine, See-Yan Lam

University of the Pacific Theses and Dissertations

This research project was designed to test whether the in vitro percutaneous penetration of benzocaine through human cadaver skin could be enhanced by dimethyl sulfoxide (DMSO), urea, polyoxyethylene (20) isohexadecyl ether and 1-dodecylazacycloheptan-2-one (Azone) in propylene glycol/water systems. Solubility and partitioning of benzocaine in propylene glycol/water systems was investigated. The adjuvant effects were studied in a 60/40 (V/V) propylene glycol/water co-solvent system. The well known drug penetration enhancer dimethyl sulfoxide did not enhance the penetration of benzocaine at any concentration level of DMSO under the conditions of the experiment. This lack of enhancement effect was probably due to increased solubility …

Investigation Of Lanolin Alcohol As A Film-Forming Delivery System: In Vitro Kinetics Of Triamcinolone Acetonide Release And Skin Penetration., Balasubramanian Venkataraman Iyer

University of the Pacific Theses and Dissertations

The nonpolymeric high molecular weight substances such as lanolin alcohol, stearyl alcohol, and cetyl alcohol have been investigated for their film-forming potential. Furthermore, the application of this potential in the design of topical drug-delivery systems has also been explored. The utilization of such film-forming systems may offer certain unique advantages not associated with the polymeric systems.

Stearyl alcohol and cetyl alcohol do not form films of acceptable integrity. Lanolin alcohol forms thin films capable of being isolated. Inclusion of appropriate amounts of ethyl cellulose and propylene glycol or hexadecyl alcohol in lanolin alcohol was found to improve the integrity, hardness …

A Method Of Detecting Viral Contamination In Parenteral Solutions., Joseph Alexander Woelfel

University of the Pacific Theses and Dissertations

The presence of contaminants in parenteral solutions is a constant nemesis against which pharmaceutical manufacturers, as well as medical, pharmacy , and nursing practitioners mus t vigilantly struggle to provide quality health care. At each level in the parenteral drug delivery system, contamination is possible before the patient actually receives the infusion. The implementation of better practices and procedures continues in the quest of contaminant-free parenterals, nevertheless, the literature is replete with articles documenting contamination of parenteral medication.

Foreign body particulate matter has been found sequestered in the lungs of patients who have received intravenous therapy. The entrapment of foreign …

The Biochemistry Of Vascular Smooth Muscle In The Spontaneously Hypertensive Rat, John Edward Taylor

University of the Pacific Theses and Dissertations

Cyclic adenosine 3’,5’-monophosphate (cAMP) was first described as the mediator of the glycogenolytic effect of epinephrine and glucagon in the liver almost two decades ago. It has since been found that cAMP may mediate the effects of a number of hormones and neurohormones, and this observation has led to the development of the second messenger hypothesis of hormone action. According to the second messenger theory, the hormone or first messenger brings information to the cell, whereas, the second messenger (cAMP) transfers this information into intracellular events. More recent evidence has described the existence of an additional second messenger, cyclic guanosine …

A Pharmacologic Investigation Of The Antiinflammatory Activity Of Cryogenine, Donald Saadia Kosersky

University of the Pacific Theses and Dissertations

This study was conducted in an attempt to define the anti inflammatory efficacy of cryogenine, the major alkaloid of Heimia salicifolia Link and Otto. The anti inflammatory effects produced by cryogenine, phenylbutazone, indomethacin, mefenamic acid, paramethasone, hydrocortisone and 6-mercaptopurine were compared considering the sequential changes in various motameters during the course of adjuvant-induced polyarthritis in rats. Polyarthritis was induced by the subplantar injection of a suspension of heat-killed Mycobacterium butyricus in mineral oil into the right hind paw of Sprague-Dawley rats. The manifestations of the diseases were monitored in terms of hind paw swelling, subjective appearance of secondary lesions, impairment …

The Development Of An Oral Inhalation Dosage Form Antinauseant, Kit Michael Mills

University of the Pacific Theses and Dissertations

It would seem appropriate that studies be conducted on the development of an oral inhalation dosage form antinauseant. The present project will consist of developing and testing a series of aerosol formulations to determine their feasibility in antinauseant therapy. In vitro pressure, valve release, spray pattern, particle size, and aging studies will be performed. The present work will also include an in vivo evaluation of promising formulations.

Antibradykinin Evaluation Of Cryogenine And Selected Other Agents, Ralph William Trottier Jr.

University of the Pacific Theses and Dissertations

One intent of this study was to detect and to define any antibradykinin capacity that cryogenine may have using both in vivo and in vitro pharmacological models. The activity of cryogenine in these tests was compared to a variety of clinically-proven anti-inflammatory compounds as well as to other agents known to possess anti-inflammatory activity in certain experimentally-induced inflammations. Cryogenine is an unusual anti-inflammatory agent since it is an alkaloid - all of the commonly used anti-inflammatories (aspirin, phenylbutazone, indomethacin, etc.) are organic acids.