Pharmacy and Pharmaceutical Sciences Commons^™

An Analysis Of Psychologist Postdoctoral Psychopharmacology Training Materials For Critiques Of Neurobiological Hypotheses Of Depression's Etiology, Critical Analyses Of The Dsm's Rigor, And For Consumer/Survivor/Ex-Patient Content., Chris William Nicholas Rowe

Antioch University Dissertations & Theses

There is widespread agreement that neurobiology plays a role in psychological distress and that psychiatric diagnosis and associated psychopharmacological interventions can be helpful. However, there are also unresolved issues surrounding the limits of empirical support for current diagnostic criteria, shortcomings in neurobiological explanations of psychopathology, and unanswered questions about the mechanism, safety, and efficacy of psychiatric medications. This has implications for treatment errors which can precipitate negative socio-economic and health consequences, particularly for vulnerable groups like the Consumer/Survivor/Ex-Patient (c/s/x) population. It is for these reasons that the training psychologists receive to prescribe should, in addition to integrating the critiques of …

Novel Spoxazomicins Derived From Streptomyces Sp. Rm-14−6 Attenuate Ethanol Induced Cytotoxicity In Vitro, Meredith A. Saunders

Theses and Dissertations--Psychology

An estimated 13.9% of Americans currently meet criteria for an alcohol use disorder. Ultimately, chronic alcohol use may result in neurological deficits, with up to 85% of alcoholics exhibiting signs of cognitive decline. However, biochemical and behavioral factors contributing to this decline have remained elusive. Our ongoing research program encompasses a multi-tiered screening of a natural product library and validation process to provide novel information about mechanisms underlying these deficits and to identify novel chemical scaffolds to be exploited in the development of pharmacological treatments for alcohol use disorders in a rodent organotypic hippocampal slice culture mode. Experiment 1 sought …

High-Throughput Sequencing-Based Approaches For The Identification And Development Of Molecular Targets For Cancer Therapy, David Joel Oliver

Theses and Dissertations

Effective cancer treatment depends on the development of therapeutics that efficiently eliminate the disease without significant reduction to quality of life. Targeted therapeutics achieve these goals, but their long-term efficacy is limited by the ability of cancers to become resistant to these therapies over time. The identification of new therapeutic targets is crucial for the future of cancer treatment. In this work we present functional identification and characterization of novel targets for cancer therapy.

Loss-of-function screens are a well-founded approach for the functional identification of new therapeutic targets, and, in combination with high-throughput sequencing technology, can now be performed at …

Roles Of Nitric Oxide On Epithelial To Mesenchymal Transition And Cancer Stem Cell Phenotypes In Anoikis-Resistant Lung Cancer Cells, Phattrakorn Powan

Chulalongkorn University Theses and Dissertations (Chula ETD)

The interconversion between epithelial and mesenchymal is proposed to be a key machinery responsible for metastasis-related deaths. Likewise, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. The gaseous biological mediator nitric oxide (NO) is also reported to mediate metastasis. However, the linkage between the three events and their control mechanisms under detachment condition are unclear. Since an increase of E-cadherin was frequently found in mesenchymal to epithelial transition (MET) process, we used anoikis resistance H460 lung cancer cells (AR_H460) and a 3D tumor spheroid assay and other CSC-indicating assays to investigate the role …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Design And Structure-Activity Relationship Of Small Molecule C-Terminal Binding Protein (Ctbp) Inhibitors And Investigation Of The Scope Of Palladium Multi-Walled Carbon Nanotubes (Pd-Mwcnt) Catalyst In C–H Activation Reactions, Sudha Korwar

Theses and Dissertations

C-terminal binding proteins (CtBPs) are transcriptional co-repressors involved in developmental processes, and also implicated in a number of breast, ovarian, colon cancers, and resistance against cancer chemotherapy. CtBP is a validated novel potential anti-cancer target. In this project we sought to develop potent and selective small-molecule inhibitors of CtBP. Using a combination of classical medicinal chemistry and modern computational approaches, we designed a potent inhibitor HIPP (hydroxyimino-3-phenylpropanoic acid) that showed an IC₅₀ of 0.24 μM against recombinant CtBP. Further elucidation of the structure-activity relationship (SAR) of HIPP led to the design of more potent inhibitors 3-Cl HIPP (CtBP IC …

Sulfated Dehydropolymer Of Caffeic Acid For Repair Of Lung Damage And Emphysema, Tien M. Truong

Theses and Dissertations

The complex pathobiologic mechanisms of emphysema are not fully understood, leaving this deadly disease without effective pharmacotherapy for a cure. This project hypothesized that the sulfated dehydropolymer of caffeic acid (CDSO3) exhibits Fe²⁺ chelation-based hypoxia inducible factor-1a (HIF-1a) up-regulatory protective activities against in vitro emphysematous cell death and for in vivo reversal of emphysema induced with SU5416, a vascular endothelial growth factor blocker.

Using in vitro chromogenic competitive inhibition assays, CDSO3 was shown to chelate Fe²⁺ (IC₅₀ of 23 µM), but not Fe³⁺ ions. The trypan blue exclusion and lactate

dehydrogenase assays were then employed to …

Quantitative Analysis Of 5-Chloro-2-Methoxy-N-[2-(4-Sulfamoylphenyl)Ethyl]Benzamide (Glyburide Analogue, Ga) In Mouse Plasma And Whole Blood Using A Micro-Extraction And Liquid Chromatography-Tandem Mass Spectrometry, Ankit Zalavadia

Theses and Dissertations

Pharmacokinetic evaluation of 5-chloro-2-methoxy-N-[2-(4- sulfamoylphenyl)ethyl]benzamide in mouse plasma demanded for a suitable bioanalytical method. No reported bioanalytical method exists to-date that can quantify concentration of this compound in any biological matrix. The purpose of this study was 1) to develop and validate a new bioanalytical method using a micro-extraction and LC-MS/MS to quantify the target analyte in mouse plasma and 2) to partially validate the method in whole blood. A bioanalytical method was developed and validated in both matrices for a linear concentration range of 2-1000 ng/ml. For both matrices, the reverse predicted concentration of calibration standards (-8.95% to 12.16% …

Resource Utilization And Costs Associated With Off-Label Use Of Atypical Antipsychotics In An Adult Population, Della Varghese

Theses and Dissertations

Introduction: Atypical Antipsychotics (AAPs) are approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar disorder. AAPs are commonly used off-label to treat depression, post-traumatic stress disorder and neuropsychiatric symptoms in dementia due to lack of alternative treatment options and treatment resistance. Concerns for off-label use arise since AAPs increase the risk of cardiovascular events and death. The objectives were 1) describe patterns of RU and costs among off-label AAPs users in a nationally representative population 2) identify prevalence of off-label use in the Medicare population 3) compare RU and costs between off-label AAPs …

Curcumin/Melatonin Hybrids As Neuroprotective Agents For Alzheimer's Disease, John Saathoff

Theses and Dissertations

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, affecting ~5.2 million Americans. Current FDA approved medications provide mainly symptomatic relief and there are no agents available to delay or cure this disease. Multiple factors such as amyloid-β aggregates, dyshomeostasis of biometals, oxidative stress, and neuroinflammation have been implicated in the development of AD. Even though significant advances have been made in understanding the mechanisms leading to AD, the exact etiology still remains elusive. Given AD’s multifactorial nature, a multifunctional strategy of small molecule design would help to identify novel chemical templates. Recently our lab …

Exploring The Concept Of Human Oct3 Inhibitors As A Novel Class Of Antidepressants, Kavita A. Iyer

Theses and Dissertations

The Dukat laboratory developed 2-amino-6-chloro-3,4-dihydroquinazoline (A6CDQ) as a 5-HT₃ receptor ligand. A6CDQ and one of its positional isomers, the 7-chloro analog A7CDQ, produced antidepressant-like effects in the mouse tail suspension test (TST). We investigated and systematically ruled out a solely 5-HT₃ receptor or hSERT mediated mechanism of antidepressant-like effect for both A6CDQ and A7CDQ.

The role of organic cation transporter 3 (OCT3) as an alternative mechanism in the regulation of neurotransmitters including serotonin (5-HT) and the therapeutic potential of targeting hOCT3 to achieve antidepressant effects has been established. By virtue of possessing protonatable nitrogen atoms, 2-aminodihyroquinazolines could potentially …

Initiation And Retention In Couples Outpatient Treatment For Parents With Drug And Alcohol Use Disorders, Abbly L. Braitman, Michelle L. Kelley

Psychology Faculty Publications

The focus of the current study was to identity mental health, relationship factors, substance use related problems, and individual factors as predictors of couples-based substance abuse treatment initiation and attendance. Heterosexual couples with children that met study criteria were invited to attend 12 sessions of outpatient behavioral couples therapy. Men were more likely to initiate treatment if they had a higher income, had greater relationship satisfaction, were initiating treatment for alcohol use disorder only, were younger when they first suspected a problem, and had higher depression but lower hostility or phobic anxiety. Men attended more treatment sessions if they reported …

Effects Of Hiv And Drugs Of Abuse On The Blood-Brain Barrier, Gopika Hari

UROP Posters

Despite effective systemic therapy, HIV-1 infection within the brain results in neuronal degradation and neurocognitive dysfunction. This neurocognitive dysfunction is worsened in the setting of opiate abuse. The central nervous system (CNS) is protected by the blood-brain barrier (BBB), a selective barrier regulating the passage of substances from peripheral circulation into the CNS. The BBB is composed of microvascular endothelial cells encased by basal lamina, pericytes, and perivascular astrocyte endfeet. Intracellular junctional complexes comprising of adherens and tight junctions are located between the endothelial cells and form tight barrier, preventing traffic of compounds between cells (paracellular flux). Clinical and in …

The Pharmaceutical Industry's Effect On Rheumatologists' Patterns Of Care, Frank Bailey

Walden Dissertations and Doctoral Studies

Drug makers have developed numerous techniques to influence treatment choices. Almost no information exists regarding the pharmaceutical industry's influence on rheumatologists and how these pressures could affect patient care. This phenomenological research, conducted within the framework of social exchange theory, explored the lived experiences of rheumatologists regarding their interactions with agents of the pharmaceutical industry. A researcher-designed interview protocol was used to gather feedback from 10 rheumatologists regarding how interactions with agents of the pharmaceutical industry made them feel. Using horizonalization, meaningful statements made by rheumatologists were condensed into specific themes and patterns, which provided a composite summary of their …

The Impact Of The Sentinel Initiative And Faers Surveillance System On Consumer Safety, Sonia Batra

Walden Dissertations and Doctoral Studies

The U.S. Food and Drug Administration (FDA) uses the FDA Adverse Event Reporting System (FAERS) to monitor adverse events resulting from pharmaceutical drug use. However, this system has limitations such as not allowing real-time data collection. To address these limitations, the FDA launched the Sentinel Initiative in 2008. This comparative case study was conducted to describe perceptions of investigating the efficacy of the Sentinel Initiative compared with the FAERS. The study was based on the theory of preemption as it emphasized the need for efficient means for providing unquestionable proof that consumers suffered adverse drug effects. The sample included interivews …

Perspectives On Transdermal Electroporation, Kevin B. Ita

Faculty Publications & Research of the TUC College of Pharmacy

Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary …

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 …

The Influence Of Solid Microneedles On The Transdermal Delivery Of Selected Antiepileptic Drugs, Julia Nguyen, Kevin B. Ita, Matthew J. Morra, Inna E. Popova

Faculty Publications & Research of the TUC College of Pharmacy

The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm²/h) compared to passive delivery (12.83 ± 6.30 µg/cm …

Motivations And Predictors Of Cheating In Pharmacy School, Eric J. Ip, Kathy Nguyen, Bijal M. Shah, Shadi Doroudgar, Monica K. Bidwal

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To assess the prevalence, methods, and motivations for didactic cheating among pharmacy students and to determine predictive factors for cheating in pharmacy colleges and schools.

Methods. A 45-item cross-sectional survey was conducted at all four doctor of pharmacy programs in Northern California. For data analysis, t test, Fisher exact test, and logistic regression were used.

Results. Overall, 11.8% of students admitted to cheating in pharmacy school. Primary motivations for cheating included fear of failure, procrastination, and stress. In multivariate analysis, the only predictor for cheating in pharmacy school was a history of cheating in undergraduate studies.

Conclusion. Cheating occurs …

Obesity Management: Clinical Review And Update Of The Pharmacologic Treatment Options, Raymond A. Plodkowski, Megan E. Mcgarvey, Keith Reisinger-Kindle, Bradley Kramer, Erik Nelson, Jennifer Lee, Quang T. Nguyen

College of Osteopathic Medicine (TUN) Publications and Research

The toolbox of medications available for medical weight management is more robust than ever and includes a wide variety of mechanisms of actions and options for patients.

Treatment Of Pasireotide Lar-Associated Hyperglycemia In A Patient With Acromegaly, Cheryl Rosenfeld

Touro College of Osteopathic Medicine (Middletown) Publications and Research

Objective: Hyperglycemia was noted in pasireotide long-acting release (PAS LAR}-treated patients with acromegaly during clinical trials. We describe a clinical approach to hyperglycemia in a patient with acromegaly and diabetes mellitus type 2 (DM2) during PAS LAR initiation and treatment.

Methods: Clinical response to PAS LAR, including self­ monitored blood glucose (SMBG) levels, HbA1c, IGF-1, and adverse effects, was reported. Case Presentation: A 44-year-old male was referred for consultation in 2007 owing to uncontrolled DM2 despite maximum metformin (MET) dose. Testing led to a biochemical diagnosis of acromegaly. An 8-mm pituitary adenoma was seen on MRI. Transsphenoidal pituitary adenoma …

Anode Catalysts For The Direct Ethanol Fuel Cell, Daryl Fox

Doctoral

The anodic reaction of the Direct Ethanol Fuel Cell has been studied with various catalysts such as electrodeposited platinum, palladium, nickel and gold electrodes. The mechanism of bimetallic catalysts was used to reduce the platinum content needed for ethanol oxidation. The effects of increased temperature, ethanol concentration, electrolyte pH and scan rate have been examined. The impact of different carbon surfaces such as carbon ink, carbon paper and commonly used Vulcan XC72 have also been analysed in order to determine the optimum conditions for the EOR in a fuel cell.

Electrochemical methods were used to analyse catalyst performance such as …