Medicine and Health Sciences Commons^™

Therapeutic Gene Delivery To Human Pancreatic Islets For Treatment Of Diabetes And The Effect Of Tfo On Liver Fibrosis Induced By Bile Duct Ligation, Ravikiran Panakanti

Theses and Dissertations (ETD)

Ex vivo gene transfer can improve the outcome of islet transplantation for treating Type I diabetes. Earlier we have shown co‑expression of human vascular endothelial growth factor (hVEGF) and human interleukin‑1 receptor antagonist (hI‑1Ra) after transfection of plasmid DNA encoding these two genes. Due to poor transfection efficiency of plasmid DNA and the better known islet transduction efficiency of adenoviral (Adv) vectors, in this study, we constructed Adv‑hVEGF‑hIL‑1Ra by cloning hVEGF and hIL‑1Ra coding sequences and polyA signal under separate cytomegalovirus (CMV) promoters in Adenoquick plasmid (Ad 13.1). There was dose and time dependent expression of these genes after transduction …

Development And Evaluation Of Therapeutics In The Setting Of Radiation Injury, Karin Emmons Thompson

Theses and Dissertations (ETD)

The possibility of an incident involving radiation exposure is at the forefront of public attention in the current global environment. With a greater number of entities possessing nuclear weapons and increased demand for nuclear power, the concern for uncontained exposure to radiation is increasing. In light of these developments, the need for treatments that may be easily stored and administered to large numbers of people who have been exposed to high doses of total body irradiation (TBI) is more urgent than ever before.

Our goal was to identify and develop novel, drug-like small molecules that would exhibit radiomitigating activity for …

Design Of Lipid And Polymeric Carriers For Nucleic Acid Delivery, Lin Zhu

Theses and Dissertations (ETD)

The objectives of the study were to investigate and develop lipid and polymeric carriers for nucleic acid delivery. These included: i) to develop novel cationic lipids for plasmid, oligonucleotide, and siRNA delivery; ii) to develop a novel polymeric delivery system, polyethylene glycol (PEG) based bio–conjugate, for oligonucleotide delivery; iii) to develop a novel bio–conjugate delivery system for siRNA delivery.

In Chapter 2, we discussed the barriers and strategies of nucleic acid delivery, as well as summarized the commonly used lipids, polymers, and the corresponding carriers in terms of their characteristics, applications, advantages and limitations.

Cationic lipids are most commonly used …

Patients’ Knowledge And Attitudes Toward Psychiatric Medication On Admission To An Inpatient Behavioral Health Unit, Krina H. Patel Pharmad, Edward R. Norris Md, Fapa, Fapm, Julia R. Correll Ba, Laurence P. Karper Md, Mary Ellen O'Connell Rn, Msn, Mba, Michael Kaufmann Md

Department of Psychiatry

No abstract provided.

Concurrent Validation Of The Dash And The Quickdash In Comparison To Neck-Specific Scales In Patients With Neck Pain, Saurabh Mehta, Joy Macdermid, Lisa Carlesso, Colleen Mcphee

Physical Therapy Faculty Research

Study Design. Concurrent validity study.

Objective. To examine the validity of the Disabilities of Arm, Shoulder, and Hand (DASH) and the QuickDASH in patients with neck pain in comparison with the Neck Disability Index (NDI), the Cervical Spine Outcome Questionnaire (CSOQ), and the Visual Analogue Scale (VAS) for pain. To examine the agreement between the DASH and the QuickDASH and assess whether the QuickDASH can be used instead of full DASH in patients with neck pain.

Summary of Background Data. NDI is commonly used for measuring neck-related disability in patients with neck pain; but it does not offer to assess …

Nanosized Hydroxyapatite And Other Calcium Phosphates: Chemistry Of Formation And Application As Drug And Gene Delivery Agents, Vuk Uskoković, Dragan Uskoković

Pharmacy Faculty Articles and Research

The first part of this review looks at the fundamental properties of hydroxyapatite (HAP), the basic mineral constituent of mammalian hard tissues, including the physicochemical features that govern its formation by precipitation. A special emphasis is placed on the analysis of qualities of different methods of synthesis and of the phase transformations intrinsic to the formation of HAP following precipitation from aqueous solutions. This serves as an introduction to the second part and the main subject of this review, which relates to the discourse regarding the prospects of fabrication of ultrafine, nanosized particles based on calcium phosphate carriers with various …

At₁ Angiotensin Ii Receptor And Novel Non-At₁, Non-At₂ Angiotensin Ii/Iii Binding Site In Brainstem Cardiovascular Regulatory Centers Of The Spontaneously Hypertensive Rat, Erick A. Bourassa, Xiefan Fang, Xia Li, Alan F. Sved, Robert C. Speth

HPD Articles

Spontaneously hypertensive rats (SHR) have an activated brain angiotensin system that contributes to the elevation of blood pressure in this animal model. Physiological and pharmacological studies suggest that hyperactivation of brain AT₁ angiotensin receptors is a major pathophysiological factor. Consistent with these observations, radioligand binding studies indicate widespread up-regulation of brain angiotensin receptors in SHR. One key brainstem site in which AT₁ receptor stimulation appears to contribute to the elevated blood pressure in SHR is the rostral ventrolateral medulla (RVLM). However, no quantitative comparison of AT₁ receptor binding in the RVLM has been made in SHR versus normotensive rats. A …

Dna Synapsis Through Transient Tetramerization Triggers Cleavage By Ecl18ki Restriction Enzyme., Mindaugas Zaremba, Amelia Owsicka, Gintautas Tamulaitis, Giedrius Sasnauskas, Luda S. Shlyakhtenko, Alexander Y. Lushnikov, Yuri L. Lyubchenko, Niels Laurens, Bram Van Den Broek, Gijs J.L. Wuite, Virginijus Siksnys

Journal Articles: Pharmaceutical Sciences

To cut DNA at their target sites, restriction enzymes assemble into different oligomeric structures. The Ecl18kI endonuclease in the crystal is arranged as a tetramer made of two dimers each bound to a DNA copy. However, free in solution Ecl18kI is a dimer. To find out whether the Ecl18kI dimer or tetramer represents the functionally important assembly, we generated mutants aimed at disrupting the putative dimer-dimer interface and analysed the functional properties of Ecl18kI and mutant variants. We show by atomic force microscopy that on two-site DNA, Ecl18kI loops out an intervening DNA fragment and forms a tetramer. Using the …

An In Vitro Model For Pelger-Huët Anomaly, Ada L. Olins, Aurélie Ernst, Monika Zwerger, Harald Hermann, Donald E. Olins

Pharmaceutical Sciences Faculty Publications

The principal human blood granulocyte (neutrophil) possesses a lobulated and deformable nucleus, important to facilitate rapid egress from blood vessels as these cells migrate to sites of bacterial or fungal infection. This unusual nuclear shape is a product of elevated levels of an integral membrane protein of the nuclear envelope lamin B receptor (LBR) and of decreased amounts of lamin A/C. In humans, a genetic deficiency of LBR produces Pelger-Huët anomaly, resulting in blood neutrophils that exhibit hypolobulated nuclei with redistributed heterochromatin. Structural changes in nuclear architecture occur during granulopoiesis within bone marrow. The exact mechanisms of this nuclear shape …

Diagnosing Conflict-Of-Interest Disorder, Lisa Cosgrove

Counseling, School Psychology & Sport Faculty Publication Series

In June 2010, the Association of American Medical Colleges issued the third and final portion of its conflict-of-interest policy initiatives. The task force on “Conflicts of Interest in Clinical Care” did not mince words when it described the impetus for these initiatives: “It is imperative that the possibility or perception of [financial conflict of interest] be advertently examined and appropriately evaluated to ensure that academic medicine in all of its missions is fundamentally dedicated to the welfare of patients and the improvement of public health.”

This report is especially timely because of recent questions raised by investigative journalists and policy …

Psychiatric Taxonomy, Psychopharmacology And Big Pharma, Lisa Cosgrove

Counseling, School Psychology & Sport Faculty Publication Series

Clinicians practicing today need to be aware of the ways in which the current industry-dominated climate may undermine the integrity of the scientific process and, thus, may compromise patient care. In the mental health field, corporate sponsorship bias can affect psychiatric taxonomy and clinical Practice Guidelines (CPG). Financial conflicts of interest (FCOI) can occur when there are financial associations between researchers, authors, or panel members developing psychiatric diagnostic and treatment guidelines, and the pharmaceutical industry, or when randomized clinical trials (RCTs) are industry funded. Therefore, clinicians need to be especially vigilant about the informed consent process when patients are prescribed …

Preliminary Studies Into Dna Binding Capabilities Of Ruthenium Nitro Nitrosyl As Anti-Tumor Pro-Drugs, Natasha Hansson

Seton Hall University Dissertations and Theses (ETDs)

The complex [Ru(bpy)z(NO)(N02)](PF6)2 was investigated as a potential anti­ tumor drug option. The nitrosyl group was displaced by reaction with azide ion in acetone to yield the solvento complex in situ. The products isolated from addition of a solution or slurry of guanine, adenine, cytosine or thiamine to the resulting [Ru(bpy)(N02)(acetone)t were investigated by electronic absorption spectroscopy, infra­ 1 red spectroscopy, H NMR spectroscopy and cyclic voltammetry. The results of the studies showed that guanine, adenine and thiamine form adducts with Ru(bpy)z(N02)(acetone)t. However, each base forms a unique complex as shown by electronic spectroscopy. Guanine is the strongest field ligand, …

Plant Phenolics: Extraction, Analysis And Their Antioxidant And Anticancer Properties, Jin Dai, Russell J. Mumper

Pharmaceutical Sciences Faculty Publications

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro …

Agmatine And Agmatine Analogs In The Treatment Of Epilepsy, Seizure, And Electroconvulsive Disorders, Peter A. Crooks, Aimee K. Bence, David R. Worthen

Pharmaceutical Sciences Faculty Patents

Pharmaceutical preparations containing of agmatine, congeners, analogs or derivatives thereof for use in preventing or treating epilepsy, seizures and other electroconvulsive disorders are provided. Embodiments include administering an effective amount of agmatine, an agmatine analog or a pharmaceutically acceptable salt thereof to a human subject in need of treatment or prevention of epilepsy, seizure or other electroconvulsive disorder to treat, reduce, or prevent the disorder in the subject.

Tabor Dry Goods Store - Hartford, Kentucky (Mss 339), Manuscripts & Folklife Archives

Manuscript Collection Finding Aids

Finding aid only for Manuscripts Collection 339. Day books, account books, and invoice books of Pardon Winfield Tabor's dry goods store in Hartford, Ohio County, Kentucky. Includes some druggists' prescription forms and farm records of his son, Earl P. Tabor.

Failure To Ubiquitinate C-Met Leads To Hyperactivation Of Mtor Signaling In A Mouse Model Of Autosomal Dominant Polycystic Kidney Disease, Shan Qin, Mary Taglienti, Surya M. Nauli, Leah Contrino, Ayumi Takakura, Jing Zhou, Jordan A. Kreidberg

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder that is caused by mutations at two loci, polycystin 1 (PKD1) and polycystin 2 (PKD2). It is characterized by the formation of multiple cysts in the kidneys that can lead to chronic renal failure. Previous studies have suggested a role for hyperactivation of mammalian target of rapamycin (mTOR) in cystogenesis, but the etiology of mTOR hyperactivation has not been fully elucidated. In this report we have shown that mTOR is hyperactivated. in Pkd1-null mouse cells due to failure of the HGF receptor c-Met to be properly ubiquitinated and subsequently …

Educational Innovations: Categories Of Bulletin Board Postings Designed To Increase Awareness Of Contemporary Pharmaceutical Policy Issues, Jacob T. Painter, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

OBJECTIVE: The goal of this project was to categorize and classify bulletin board postings pertaining to pharmaceutical policy from both the professional and lay press.

METHODS: Bulletin board postings were used to supplement in-class discussion to keep students, faculty and staff up-to-date on emerging trends. A bulletin board located in the main classroom area of the College of Pharmacy Building where students would pass by on the way to class and congregate during break periods was used to display articles from various sources concerning topics related to pharmaceutical policy. Information is presented about the primary subject matters addressed …

Utilization Patterns And Economic Impact Of Iv Iron And Erythropoiesis Stimulating Agents In Chronic Kidney Disease Patients: A Multi-Hospital Study, Avani Joshi

Theses and Dissertations

Background: Chronic kidney disease (CKD) affects approximately 20 million Americans and is the cause of significant morbidity and mortality. Anemia, common in CKD, develops early in the disease process. It contributes to increased risk of cardiovascular disease, hospitalization, mortality, and diminishes health-related quality of life. Intravenous iron and Erythropoiesis Stimulating Agents (ESAs) are recommended for anemia management in CKD. The utilization patterns of IV iron and ESA, and their impact on hospital costs and length of stay merits investigation. Objectives: There were five general objectives of this investigation. The rate and extent of utilization of IV iron in anemic CKD …

Ph-Sensitive Mucoadhesive Film-Forming Gels And Wax-Film Composites Suitable For Topical And Mucosal Delivery Of Molecules, Russell J. Mumper, Michael Jay

Pharmaceutical Sciences Faculty Patents

The present invention relates to pH-sensitive mucoadhesive film-forming gels and wax-film composites suitable for topical and mucosal delivery of molecules of interest, namely active pharmaceuticals. The gels comprise a pharmaceutically acceptable pH-sensitive polymer that responds to a lowering of pH by precipitating into films when in contact with the skin or mucosal surface. The films also comprise an adhesive polymer that allows the film to remain in contact with the tissue for an extended period of time. The wax-film composites comprise a bi-layer film having both the said pH-sensitive mucoadhesive layer to promote strong adherence to the skin and mucosal …

Gilvocarcin Gene Cluster, Recombinant Production And Use Thereof, Jürgen Rohr, Carsten Fischer

Pharmaceutical Sciences Faculty Patents

A nucleic acid molecule encoding the gilvocarcin V gene cluster and subunits thereof. Recombinant vectors and host cells comprising a nucleic acid compound encoding the gilvocarcin V gene cluster or subunits thereof. Host cells comprising recombinant vectors encoding the gilvocarcin polyketide synthase and gilvocarcin post-PKS modifying enzymes from Streptomyces griseoflavus can be used to produce gilvocarcin and functional gilvocarcin mutants, analogs and derivatives thereof with application as antibiotics, anticancer agents, immunosuppressants, antivirals, and neuroprotective agents.

Materials For Pharmaceutical Dosage Forms: Molecular Pharmaceutics And Controlled Release Drug Delivery Aspects, Heidi M. Mansour, Minji Sohn, Abeer Al-Ghananeem, Patrick P. Deluca

Pharmaceutical Sciences Faculty Publications

Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

Identification Of Thioaptamer Ligand Against E-Selectin: Potential Application For Inflamed Vasculature Targeting., Aman P Mann, Anoma Somasunderam, René Nieves-Alicea, Xin Li, Austin Hu, Anil K Sood, Mauro Ferrari, David G Gorenstein, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA) against E-selectin (ESTA-1) by employing a two-step selection strategy: a recombinant protein-based …

Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani

Department of Biological & Biomedical Sciences

Background: The objective of present study was to provide the pharmacological basis for the medicinal use of Morinda citrifolia Linn in dyslipidemia using the aqueous-ethanolic extracts of its fruits (Mc.Cr.F), leaves (Mc.Cr.L) and roots (Mc.Cr.R). Results: Mc.Cr.F, Mc.Cr.L and Mc.Cr.R showed antidyslipidemic effects in both triton (WR-1339) and high fat diet-induced dyslipidemic rat models to variable extents. All three extracts caused reduction in total cholesterol and triglyceride levels in triton-induced dyslipidemia. In high fat diet-induced dyslipidemia all these extracts caused significant reduction in total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), atherogenic index and TC/HDL ratio. Mc.Cr.R extract also caused increase …

Development And Applications Of The Hint Forcefield In Prediction Of Antibiotic Efflux And Virtual Screening For Antivirals, Aurijit Sarkar

Theses and Dissertations

This work was aimed at developing novel tools that utilize HINT, an empirical forcefield capable of quantitating both hydrophobic and hydrophilic (hydropathic) interactions, for implementation in theoretical biology and drug discovery/design. The role of hydrophobicity in determination of macromolecular structure and formation of complexes in biological molecules is undeniable and has been the subject of research across several decades. Hydrophobicity is introduced, with a review of its history and contemporary theories. This is followed by a description of various methods that quantify this all-pervading phenomenon and their use in protein folding and contemporary drug design projects – including a detailed …

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou

Natural Sciences and Mathematics | Faculty Scholarship

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …

Synthesis Of A Water Soluble Resveratrol Derivative As A Potential Anti-Cancer Drug., Augustine Essel

Electronic Theses and Dissertations

Research on development of water soluble anti-cancer drugs is one of the great challenges of modern medicinal chemistry. Resveratrol (Res) is one of the many phytoalexins producing stilbenoids present in several medicinal plants, grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, and anti-oxidant properties. Water solubility and bioavailability are some of the setbacks of this interesting compound. In view of this, effort has been made to synthesize amino acid derivative of resveratrol to improve its bioavailability and solubility in water. Methyl 4-{-[(1E)-2-(3, 5-dihydroxyphenyl)-ethenyl] - phenoxy} butyrate (7), a novel ester intermediate, has been synthesized …

A Bayesian Approach To Dose-Response Assessment And Drug-Drug Interaction Analysis: Application To In Vitro Studies, Violeta G. Hennessey

Dissertations and Theses (Open Access)

The considerable search for synergistic agents in cancer research is motivated by the therapeutic benefits achieved by combining anti-cancer agents. Synergistic agents make it possible to reduce dosage while maintaining or enhancing a desired effect. Other favorable outcomes of synergistic agents include reduction in toxicity and minimizing or delaying drug resistance. Dose-response assessment and drug-drug interaction analysis play an important part in the drug discovery process, however analysis are often poorly done. This dissertation is an effort to notably improve dose-response assessment and drug-drug interaction analysis.

The most commonly used method in published analysis is the Median-Effect Principle/Combination Index method …

Investigation And Optimization Of A Solvent / Anti-Solvent Crystallization Process For The Production Of Inhalation Particles, Swati Agrawal

Theses and Dissertations

Dry powder inhalers (DPIs) are commonly used to deliver drugs to the lungs. The drug particles used in these DPIs should possess a number of key properties. These include an aerodynamic particle size < 5μm and particle crystallinity for long term formulation stability. The conventionally used micronization technique to produce inhalation particles offers limited opportunities to control and optimize the particle characteristics. It is also known to induce crystalline disorder in the particles leading to formulation instability. Hence, this research project investigates and optimizes a solvent/anti-solvent crystallization process capable of directly yielding inhalation particles using albuterol sulfate (AS) as a model drug. Further, the feasibility of the process to produce combination particles of AS and ipratropium bromide monohydrate (IB) in predictable proportions and in a size suitable for inhalation is also investigated. The solvent / anti-solvent systems employed were water / ethyl acetate (EA) and water / isopropanol (IPA). Investigation and optimization of the crystallization variables with the water / EA system revealed that particle crystallinity was significantly influenced by an interaction between the drug solution / anti-solvent ratio (Ra ratio), stirring speed and crystal maturation time. Inducing a temperature difference between the drug solution and anti-solvent (Tdrug solution > Tanti-solvent) resulted in smaller particles being formed at a positive temperature difference of 65°C. IPA was shown to be the optimum anti-solvent for producing AS particles (IPA-AS) in a size range suitable for inhalation. In vitro aerosol performance of these IPA-AS particles was found to be superior compared to the conventionally used micronized particles when aerosolized from the Novolizer®. The solvent / anti-solvent systems investigated and optimized …

Research News: 2010, No. 1, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants, publications, technology transfer, special announcements

Insights Into The Catalytic Mechanism Of Retro-Aldol Cleavage Of Β-Hydroxy Amino Acids By Escherichia Coli L-Threonine Aldolase, Remsh Soumya Govinda

Theses and Dissertations

With over 140 vitamin B6 (Pyridoxal 5’-phosphate, PLP) dependent enzymes, serving vital roles in various transamination, decarboxylation, retro-aldol cleavage and synthesis pathways these enzymes constitute the most versatile catalytic systems in nature. Enzymes of this group have an inherent reaction as well as substrate specificity. A single co-factor namely, PLP is used by specific enzymes of this group to serve distinct roles during the catalytic reaction. An ordered evolutionary adaptation in these enzymes has led to specialization achieved by each enzyme for catalyzing specific reactions. L-Threonine aldolase (L-TA) is one such PLP- dependent enzyme that catalyzes the retro-aldol cleavage of …