Medicine and Health Sciences Commons^™

The Association Between Depression, Anxiety And Clinical Outcomes For Type 2 Diabetes Mellitus, Elham Heidari

Electronic Theses and Dissertations

Objective: To evaluate the impact of depression and/or anxiety on clinical outcomes of diabetes, including glycosylated hemoglobin (HgA1c), blood glucose, blood pressure, total cholesterol, weight and LDL among patients with incident type 2 diabetes mellitus (T2DM).

Method: A retrospective cohort study utilizing electronic medical record (EMR) data from a primary care physician (PCP) group practice was conducted to identify patients newly diagnosed with T2DM with at least 6 months pre-diagnosis and 12 months post-diagnosis of EMR data using International Classification of Disease 9th edition Clinical Modification (ICD-9-CM) coding. The presence of comorbid depression and anxiety was identified to identify four …

Community Pharmacists And Substance Use Disorders: Attitudes, Knowledge And Practices, Deepika Rao

Electronic Theses and Dissertations

Background: Substance use disorder (SUD) is a serious health concern affecting a large proportion of the US population. Community pharmacists are well-positioned to prevent, screen, and provide appropriate treatment for SUD. Stigma towards these patients and SUD results in reduced quality of care as well as poor treatment outcomes. It is imperative that pharmacists have the appropriate knowledge of and attitude towards prevention, harm reduction and treatment to develop therapeutic relationships and improve their delivery of pharmacy services

Objective: To assess knowledge, practices (with an emphasis upon screening), stigma and general attitudes of community pharmacists towards SUD and evaluate the …

Using An In Vitro-In Vivo Correlation For The ‘Bioequivalence By Design’ Development Of An Immediate Release Carbamazepine Product, Douglas Steinbach

Electronic Theses and Dissertations

The quality of a drug product may be characterized by the consistency with which its indicated clinical effect, and safety profile, is experienced by the patient. The concept that such quality should be built into a product is at the core of the United States Food and Drug Administration’s (FDA) quality by design (QbD) initiative. This vision for pharmaceutical product development emphasizes the risk-based identification of critical quality attributes (CQA) which summarize a product’s performance, the efficient refinement of critical product/process parameters (CPP) that can affect such attributes, and the systematic development of CPP limits, which assure appropriate performance of …

Synthesis Of Novel 6-Substituted And 5-Substituted Pyrrolo[2,3-D] Pyrimidine Antifolates As Targeted Anticancer Therapies, Xinxin Li

Electronic Theses and Dissertations

The dissertation will give an introduction, background and current research progress in the areas of antifolates and chemotherapy of anticancer. The design and synthesis of classical 6- substituted pyrrolo[2,3-d]pyrimidines and 5-substituted pyrrolo[2,3-d]pyrimidines as potential antifolates have been described. The design variations include: methylated thiophene regioisomers, fluorinated phenyl regioisomers, thionyl regioisomers on the side chain of pyrrolo[2,3-d]pyrimidines. As a part of this study, a series of new compounds have been synthesized and characterized. Of these, ten final compounds were submitted for biological evaluation.

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

The Influence Of Age, Gender, And Thiol Repletion In An In Vivo Model Of Lewy Body Disorders, Daniel Mason

Electronic Theses and Dissertations

Lewy body disorders are a family of neurological brain disorders associated with olfactory, motor, and cognitive deficits and are collectively defined as α-synucleinopathies, as they are characterized by hallmark “Lewy bodies” composed of aggregated, fibrillar α-synuclein. It is not certain but often posited that fibrillar α-synuclein seeds the progressive, self-propagating spread of Lewy pathology through neuroanatomical circuitry. Furthermore, the site of disease induction is still debated. In Aim I, we developed a novel protocol for generating reproducible and robust α-synucleinopathy in the limbic temporal lobe following infusions of preformed α-synuclein iv fibrils into the mouse olfactory bulb, which is frequently …

Influence Of Bilberry-Derived Anthocyanidins On Key Regulators Of Colorectal Cancer Development., Ashley M. Mudd

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths within the United States. A variety of factors including exposure to environmental carcinogens, such as benzo[a]pyrene (B[a]P), dysbiosis of the gut microbiome and hereditary influences, including APC mutations, have been shown to lead to an increased risk of developing colorectal cancer. Given the recent alarming rise in cases of colorectal cancer diagnosed in individuals under the age of 40, further insight into developing novel and effective prevention and treatment strategies are warranted. The family of plant pigments known as the anthocyanins has been identified with …

Effects Of Natural Antioxidants On Motor And Cognitive Deficits In An Animal Model Of Aging And Obesity And Dopaminergic-Like Sh-Sy5y Cell Line, Sneha Potdar

Electronic Theses and Dissertations

Aging is a universal phenomenon. One of the greatest challenges faced by the elderly population is to sustain a healthy standard of living. Advancing age is associated with increased motor and cognitive deficits. Loss of balance, falls, hip fractures, and poor memory all contribute to a decline in the quality of life of the aging population. While ongoing research is making advances to find therapeutic interventions for neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases, there is a pressing need to address deficits associated with normal aging.

Increase in oxidative stress and a decline of antioxidant mechanisms with aging have been …

Self-Assembling Bioaffinity Hydrogels For Localized Antibody Delivery, Wen Liu

Electronic Theses and Dissertations

The scope of illnesses that are being treated using monoclonal antibodies (mAbs) has been expanding from cancers to autoimmune diseases due to their high specificity to their molecular target. Because many of the new mAbs are aimed to modulate the immune system, an emerging concern is that patients with chronic illnesses are subjected to immune-related Adverse Events (irAEs). Loss of immunological tolerance to self-antigens or increased susceptibility to infections have been documented in some mAb treatments. Localized sustained release of mAb at disease sites might mitigate the risk of such toxicities. Antibody drugs are formulated typically for parenteral delivery because …

A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp

Electronic Theses and Dissertations

Cisplatin is a potent chemotherapeutic used for the treatment of many solid cancers, including testicular, ovarian, and lung cancer. Cisplatin causes many adverse side effects, of which nephrotoxicity leading to acute kidney injury is dose-limiting. Approximately 30% of patients will develop nephrotoxicity with cisplatin, and will either have their next dose of cisplatin lowered, skipped, or be switched to a less nephrotoxic chemotherapeutic altogether. These outcomes are not ideal when trying to treat cancer. Previously, it was believed that patients could recover from cisplatin-induced acute kidney injury with little to no lasting effects, but recent longitudinal studies have shown this …

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years …

The Association Between Medication Adherence In Mental Illness And Substance Use Disorder Relapse In Patients With Dual Diagnosis, Tyler Dunn

Electronic Theses and Dissertations

Objectives: The aims of the study were to (1) identify personal, social, and clinical history for patients with substance use disorder (SUD) and mental illness, (2) measure agreeance between patient self-report versus facility record history for mental illness, substance abuse, and psychotropic medication, (3) investigate the specific role of medication adherence and barriers to use for psychotropic medications upon SUD relapse, and (4) assess follow-up changes in mental illness severity and medication adherence in dual diagnosis patients enrolled in a substance abuse rehabilitation program.

Methods: The pilot study utilized a mixed methodology. Inclusion criteria included male patients at least 18 …

Extraction And Purification Of (E)-Resveratrol From The Bark Of Maine's Native Spruces, Panduka S. Piyaratne

Electronic Theses and Dissertations

Resveratrol is a plant secondary metabolite which protects plants from pathogenic invasions and acts as a remedial agent against injury, stress, and tissue damage by UV radiation. With its characteristic stilbene structure, resveratrol adopts (E) and (Z) isomeric forms. However, the (E) isomer is the most biologically active and abundant form of resveratrol in nature.

(E)- Resveratrol confers a variety of benefits to human health and well-being. Besides its antioxidant activity, the role of (E)-resveratrol as an anti-inflammatory, anti-aging, cardioprotection, and anticancer agent has been a widely explored research interest. …

Synthesis Of Novel 5-Substituted Pyrrolo[2,3-D]Pyrimidine Antifolates As Selective And Potent Anti-Tumor Agents, Mohammad Karim

Electronic Theses and Dissertations

In last few decades many folate analogs have been discovered and several compounds are successfully being used as anticancer agents. Methotrexate (MTX), pemetrexed (PMX), raltitrexed (RTX): are a few examples of classical antifolates that are currently in clinical use. Although these compounds are widely used, all of them show dose limiting toxicity due to their non-specific transport into normal cells as well as malignant cells. Currently, clinically used classical antifolates suffer from this disadvantage because there is no way to selectively transport them into malignant cells. Currently available antifolates are transported via reduced folate career (RFC) as well as Folate …

Designing A Calibration Set In Spectral Space For Efficient Development Of An Nir Method For Tablet Analysis, Md Anik Alam

Electronic Theses and Dissertations

Designing a calibration set is the first step in developing a spectroscopic calibration method for quantitative analysis of pharmaceutical tablets. This step is critical because successful model development depends on the suitability of the calibration data. For spectroscopic-based methods, traditional concentration based techniques for designing calibration sets are prone to have redundant information while simultaneously lacking necessary information for a successful calibration model. The traditional method also follows the same design approach for different spectroscopic techniques and different formulations, thereby lacks the optimizing capability to be technique and formulation specific.

A method for designing a calibration set in the Near …

The Combined Neuropharmacology And Toxicology Of Major 'Bath Salts' Constituents Mdpv, Mephedrone, And Methylone, Serena Allen

Electronic Theses and Dissertations

The synthetic cathinones, 3,4- methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4- methylenedioxymethcathinone (methylone), gained worldwide notoriety as the psychoactive components of ‘bath salts;’ a marketing term used to circumvent federal drug laws and permit their legal sale. Previous studies have shown that these drugs share pharmacological characteristics with cocaine and the amphetamines, however, descriptions of their neurotoxic properties are limited. Moreover, while forensic analysis has revealed that the most frequently abused bath salts ‘brands’ contain binary and ternary mixtures of MDPV, mephedrone, and methylone, the majority of preclinical research has focused on explicating the individual effects of these drugs. Therefore, the …

Functionality And Role Of Different Fatty Alcohols In Topical O/W Cream Formulation, Supriya Bhide

Electronic Theses and Dissertations

Fatty alcohols are excipients that are abundantly used in various pharmaceutical formulations. The objective of the present study was to evaluate the impact of incorporating different fatty alcohols on microstructural and formulation characteristics of topical o/w clotrimazole cream formulation. The formulations containing different fatty alcohols as Kolliwax® CSA 50 (CSA 50), Kolliwax® CSA 70 (CSA 70), Kolliwax® MA (MA), Kolliwax® CA (CA), Kolliwax® SA (SA) were prepared by selecting suitable RPM and homogenization time. The M.P. of API and fatty alcohols were determined using DSC technique. The prepared cream formulations were evaluated for their phase separation. The various tests like …

Preparation And Evaluation Of Valacyclovir Hydrochloride Ocular Inserts By Hot Melt Extrusion Technique, Gauri Shadambikar

Electronic Theses and Dissertations

The objective of the current study was to investigate the processability of Hot Melt Extrusion to formulate Ocular Inserts of Valacyclovir Hydrochloride and Evaluate its drug release in vitro and in vivo. Valacyclovir is the prodrug of Acyclovir, which is used in treatment of ocular keratitis and HSV infections. The bioavailability of the prodrug is better than the acyclovir and it is proved to permeate extensively through the corneal barrier. The polymer of choice was Klucel® Pharm MF and JF grades for the study. To optimize the formulation, different physical mixtures of the polymers and plasticizers (PEG 400 and Propylene …

Predictors Of Dental Opioid Analgesic Prescribing, Opioid Use And Dental Emergency Department Visits In The Mississippi Medicaid Population, Chukwuebuka Dibie

Electronic Theses and Dissertations

OBJECTIVES: The objectives of this study were: (1) to determine prevalence of opioid analgesics prescribing for non-ED dental related visits in the Mississippi Medicaid population, (2) to assess predictors of receiving opioid analgesics following non-ED dental related events among Mississippi Medicaid beneficiaries, and (3) to determine prevalence of opioid analgesic prescribing for dental related emergency departments (ED) visits in the Mississippi Medicaid population. METHODS: A retrospective, cross-sectional, observational database analysis using Mississippi Medicaid administrative claims data from January 1, 2015 to December 31, 2016. Beneficiaries with dental related visits were included in this study. Descriptive statistics were utilized to assess …

Fluorinated Organic Molecules For Medicinal Applications, Munia Sowaileh

Electronic Theses and Dissertations

The significant applications of fluorinated molecules in the pharmaceutical, agrochemical, and material sciences make them attractive synthetic targets. Difluoromethylation methods are of exceptional value and a limited number of techniques are available to perform that transformation. The primary method for introducing CF2 groups is through the use of difluoroenolates. Difluoroenolates can be generated from α-keto pentafluoro gem -diols under mild conditions. The process involves the cleavage of carbon-carbon bond and the release of trifluoroacetate. The release of trifluoroacetate is a versatile method to generate fluorinated molecules. We explored the utility of this method in generating various fluorinated moieties including α,α-difluoroketones, …

Novel Application Of Twin Screw Extruder On Production Of Diverse Formulations, Xingyou Ye

Electronic Theses and Dissertations

Twin-screw extruder has attracted considerable attention in the pharmaceutical industry as an alternative processing instrument due to its advantages compared to other conventional equipment, such as economical processing, small footprint, reduced in-process times, solvent-free and continuous processing. These superiorities have led to the application of twin-screw extruder to produce numerous dosage forms, including pellets, tablets and films. Many other formulations production can also be beneficial from the introduction of twin-screw extruder to the process. Nanocrystal formulations are promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods …

Crystalline Salt Formation Of An Acidic Drug Indomethacin Using Hot Melt Extrusion Technology, Mustafa Bookwala

Electronic Theses and Dissertations

Although salt formation is the most ubiquitous and effective method of increasing the solubility and dissolution rates of acidic and basic drugs, it consumes large quantities of organic solvents and is a batch process. Herein, we show that the dissolution rate of indomethacin (a poorly water-soluble drug) can be increased by using hot melt extrusion of a 1:1 (mol/mol) indomethacin:tromethamine mixture to form a highly crystalline salt, the physicochemical properties of which are investigated in detail. Specifically, pH–solubility studies demonstrated that this salt exhibited a maximal solubility of 19.34 mg/mL (>1000 times that of pure indomethacin) at pH 8.19. …

Development And Characterization Of Fluocinolone Acetonide Loaded Nanosized Lipid Carriers For Ocular Delivery Via Subconjunctival Route: Synergistic Effect Of Vitamin A Palmitate, Bhavik Soneta

Electronic Theses and Dissertations

Though nanotechnology which exploits the use of nanoparticles for therapeutic application have embarked as an emerging tool for drug delivery applications, the delivery of therapeutic molecules into deep ocular compartments has always been a challenging task. In this regard, the main objective of our current investigation was to develop and evaluate the fluocinolone acetonide (FA) loaded nanostructure lipid carrier (FA-NLC) in situ gel for improved ocular bioavailability by subconjunctival injection. FA, a corticosteroid administered for inhibiting the ocular inflammation either as intravitreal injection or as intravitreal implants. The FA-NLCs were developed by using vitamin A palmitate as one of the …

Synthetic Investigation Of Natural Products Causing Dopaminergic Neurodegeneration, Michael John Cunningham

Electronic Theses and Dissertations

The terrestrial organisms Streptomyces venezuelae and Rhaponticum repens produce toxic secondary metabolites that likely function as chemical deterrents. The polyketide SV-6 from S. venezuelae and the sesquiterpene lactone repin from R. repens both produce dose-dependent and selective degeneration of dopaminergic neurons. These molecules represent two possible tools that can be used to explore chemotoxic induction of Parkinson’s disease. In the case of SV-6, a newly isolated metabolite, total synthesis was undertaken to confirm its structure and biological activity. The natural product was produced from methacrolein and Roche ester starting materials that were elaborated to their respective fragments, a vinyl iodide …

Preparation And Evaluation Of Cefuroxime Axetil Gastro-Retentive Floating Drug Delivery System For Improved Delivery Via Hot-Melt Extrusion Technology, Rahul Madhukar Lalge

Electronic Theses and Dissertations

Purpose: The objective of the present study was to develop lipid-based gastro-retentive floating drug delivery system of amorphous Cefuroxime Axetil (CA) to minimize the enzymatic degradation in the gastro intestinal tract utilizing hot-melt extrusion technology for improved absorption.

Methods: Preliminary studies were performed to select the appropriate lipids. Selected ratios of CA and lipids were extruded using a twin screw hot-melt extruder. Extrudates obtained were milled to obtain floating granules and were further evaluated for drug content, floating strength and micromeritic properties. In vitro drug release studies were performed in 900 mL of simulated gastric fluid (without enzyme) of pH …

The Role Of Brand Name Fluency: A Pharmaceutical Marketing Perspective, David Wamble

Electronic Theses and Dissertations

Background: consumers are exposed to thousands of advertisements, most all of which are designed to promote a particular brand and accompanying brand name. The selection of a brand name is a critical strategic decision and is an important means to building brand equity. The importance of branding elements, specifically brand names, has led pharmaceutical manufacturers to become more creative and open the possibilities of language in brand name development. Given the complexities associated with brand name development in the U.S. pharmaceutical industry and the trends observed in recent pharmaceutical brand names, advancing the understanding of how brand name selection can …

Polymer Based Delivery Of Doxycycline Hyclate For The Prevention Of Peri-Implant Mucositis Infection, Sagar Deepak Sawant

Electronic Theses and Dissertations

Peri-implant mucositis is a silent inflammatory condition that is destructive in nature affecting only the soft tissues in the vicinity of dental implants. The current line of treatment includes the use of systemic antibiotics, mechanical debridement using LASER decontamination, the use of mouthwash or oral rinsing with chlorhexidine, maintenance and improvement of oral hygiene, mechanical debridement with or without systemic antibiotic treatment, mechanical debridement with or without the use of local drug delivery systems. However, these treatments do not solve the problem of implant rejection as peri-mucositis progresses to per-implantitis which causes severe bone loss and ultimately leading to implant …

A Novel Acetaminophen Soft-Chew Formulation Produced Via Hot Melt Extrusion With Inline Near-Infrared Monitoring As A Process Analytical Technology Tool, Pengchong Xu

Electronic Theses and Dissertations

People suffer dysphagia when swallowing hard tablets and capsules. Gelatin based soft chewable tablets was used as an alternative and novel drug delivery format to overcome dysphagia. But conventional method of producing gelatin based soft chewable tablets has many potential issues. The objective of this study is using glycerol and hot-melt extrusion technique to address potential issues and optimizing the formulation. Gelatin (15%), acetaminophen (30%), saccharin (1.5%), xylitol (6.5%), sodium chloride (2%) and six different ratios of water (45-0%) and glycerol (0-45%) were used in seven formulations. The extrusion process temperature of formulation 1-6 and formulation 7 were 90 ëšc …

Synthesis And Characterization Of Redox-Sensitive Polymer And Prodrug For Targeted Drug Delivery, Chang-Hee Whang

Electronic Theses and Dissertations

Systemic administration of chemotherapeutics is associated with various side effects deriving from accumulation in off-target sites and acute toxicity of the drugs. In the past decade, engineering targeted drug delivery platforms arose as a novel paradigm to overcome such obstacles and ultimately achieve advanced forms of chemotherapy. This thesis reports successful syntheses of l-RSP, a redox-sensitive self-immolative polymer, and DNS-SN38, thiol-sensitive SN-38 prodrug, as potential candidates for targeted drug delivery platforms. By covalently conjugating a redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), a novel self-immolative monomer was obtained. Polymerization of the respective monomer …

Topical Formulation For Stimulating Sweat Secretion As An Alternative To Iontophoresis, Tasnim Fatima

Electronic Theses and Dissertations

Sweat test or pilocarpine iontophoresis test is the existing method for diagnosis of cystic fibrosis that is recommended to perform at 48 hours after birth. However, the current method is painful, with several side effects such as full thickness skin burn, skin rash, erythema etc. Therefore, the purpose of this study is to develop a pilocarpine topical formulation which can stimulate sweat secretion when applied on skin without iontophoresis. Several formulations with Transcutol®, polyethylene glycol 400 (PEG 400), Polyethylene glycol 200 (PEG 200), menthol and salicylic acid (SA) each at varying concentrations were screened as penetration enhancers. In vitro penetration …