Medicine and Health Sciences Commons^™

Discovery Of Quinic Acid Derivatives As Oral Anti-Inflammatory Agents, Kui Zeng

Theses and Dissertations (ETD)

Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. Cat’s claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB). Herein, we described the synthesis and biological testing of novel QA derivatives. Inhibition of NF-κB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-κB response element. A549- NF-κB cells were stimulated with TNF-α (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at …

Library Synthesis Of Anticancer And Antibacterial Agents Via Azide Chemistry, Jianjun Zhang

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Various anticancer and antibacterial agents have been synthesized via azide chemistry by taking advantage of carbohydrate. Starting from the synthesis of 14 glycosyl azides, a library of carbohydrate-oxazolidinone conjugates and a library of carbohydrate-cyclopamine conjugates with biological interests were synthesized based on a highly efficient "click reaction" assisted by sonication. Some of the conjugates have improved solubility and enhanced anticancer activity.

A library of neomycin B derivatives with various modifications at the 5" position has been synthesized. Two leads exhibit prominent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Antibacterial activities were measured when combined with other …

Hedgehog/Gli Supports Androgen Signaling In Androgen Deprived And Androgen Independent Prostate Cancer Cells, Mengqian Chen, Michael A. Feuerstein, Elina Levina, Prateek S. Baghel, Richard D. Carkner, Matthew J. Tanner, Michael Shtutman, Francis Vacherot, Stéphane Terry, Alexandre De La Taille, Ralph Buttyan

Faculty Publications

Background: Castration resistant prostate cancer (CRPC) develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR) despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh) signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk …

Prophylactic And Therapeutic Efficacy Of Avian Antibodies Against Influenza Virus H5n1 And H1n1 In Mice, Huan H. Nguyen, Terrence M. Tumpey, Hae-Jung Park, Young-Ho Byun, Linh D. Tran, Van D. Nguyen, Paul E. Kilgore, Cecil Czerkinsky, Jacqueline M. Katz, Baik Lin Seong, Jae Min Song, Young Bong Kim, Hoa T. Do, Tung Nguyen, Cam V. Nguyen

Department of Pharmacy Practice

Background: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs) have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY) found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian …

Methods And Compositions For Optimizing Blood And Tissue Stability Of Camptothecin And Other Albumin-Binding Therapeutic Compounds, Thomas G. Burke, Daniel C. Carter

Pharmaceutical Sciences Faculty Patents

The present invention provides methods and formulations for optimizing the anti-cancer and anti-HIV activities of a camptothecin drug, including camptothecin and its related analogs including 9-aminocamptothecin and 9-nitrocamptothecin. The invention involves methodologies and formulations that limit human serum albumin-mediated reduction of the anti-cancer and anti-HIV effects of the camptothecins, and the methods and formulations provide combination therapies in which binding of the camptothecin agent to human serum albumin can be modulated by the administration of a competing agent that also binds human serum albumin. Reduced camptothecin drug binding to human serum albumin can result in elevated camptothecin free drug levels …

Resolution Of Clinical Signs Of Ventilator-Associated Pneumonia In Trauma Patients, Kathryn A. Connor, Joseph M. Swanson, Bradley A. Boucher, G. Christopher Wood

Pharmacy Faculty/Staff Publications

Objectives: The ATS/IDSA Ventilator-Associated Pneumonia (VAP) guidelines suggest that clinical improvement of VAP should be apparent within 3–6 days. This study evaluated resolution of clinical signs of VAP in trauma patients after diagnosis.

Methods: Critically injured adults admitted to the trauma intensive care unit (ICU) from June 1, 2006, to December 31, 2007, and subsequently given a diagnosis of VAP were retrospectively assessed. Clinical signs, including derangements of maximum temperature (Tmax), white blood cell (WBC) count, and PaO2/FiO2, were evaluated on days 1–16 after VAP diagnosis. Data are presented as mean ± SD unless otherwise stated. Clinical parameters after VAP …

Patient Centered Care Approach To Adherence With Cardiovascular Medications: Self-Determination Theory Integration, David S. Li

Health Services Research Dissertations

Problem statement. Behavioral intervention is used to improve adherence with medication in patients with cardiovascular diseases (CVD), but the effect was not sustainable. Patient-centered care (PCC) as a consumer movement has gained acceptance, but it lacks a theoretical framework. Self-determination theory (SDT) may provide an alternative to improve patients' adherence to chronic cardiovascular medication, as well as a theoretical framework for PCC. Both approaches to CVD management have not been evaluated.

Methods. The study was a quasi-experimental pretest posttest comparison design with consecutive sampling of a hospitalized cardiac patient population. Sixty patients each for the usual care (UC) …

Virus-Triggered Ubiquitination Of Traf3/6 By Ciap1/2 Is Essential For Induction Of Interferon- &Beta (Ifn-&Beta) And Cellular Antiviral Response, Ai-Ping Mao, Shu Li, Bo Zhong, Ying Li, Jie Yan, Qi Li, Chengwen Teng Pharm.D.. Ph.D, Hong-Bing Shu

Faculty Publications

Viral infection causes activation of transcription factors NF-κB and IRF3, which collaborate to induce type I interferons (IFNs) and cellular antiviral response. Here we show that knockdown of the E3 ubiquitin ligases cIAP1 and cIAP2 markedly inhibited virus-triggered activation of IRF3 and NF-κB as well as IFN-β induction. Knockdown of cIAP1 and cIAP2 also inhibited cytoplasmic dsRNA-triggered cellular antiviral response. Endogenous coimmunoprecipitation experiments indicated that viral infection caused recruitment of cIAP1 and cIAP2 to TRAF3, TRAF6, and VISA. Furthermore, we demonstrated that cIAP1- and cIAP2-mediated virus-triggered ubiquitination of TRAF3 and TRAF6. These findings suggest that virus-triggered ubiquitination of TRAF3 and …

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

To view this abstract, please download this patent.

Pharmaceutical Philanthropic Shell Games, Lisa Cosgrove, Harold J. Bursztajn

Counseling, School Psychology & Sport Faculty Publication Series

In response to increasing public distrust and congressional concerns regarding pharmaceutical company influence on medical research and education, professional organizations have taken steps to phase out or regulate industry-sponsored educational support. A related problem is industry funding of philanthropic organizations, such as patient advocacy groups. Thus, when the office of Sen Charles Grassley (R-Iowa) recently reported that the National Alliance for the Mentally Ill received substantial pharmaceutical funding, there was concern among the membership’s psychiatric patients and their families.

Computational Pharmacology: Simulating Circuits Of The Brain For Drug Development, Patrick D. Roberts

Systems Science Friday Noon Seminar Series

The pharmaceutical industry is approaching unsustainable research costs to develop new drug therapies for mental disease because of the high failure rate in clinical trials. These failures are due to limitations of pre-clinical studies in animal models that fail to predict the efficacy of new drugs in human subjects. The gap between pre-clinical trials and clinical trials is particularly difficult in complex mental diseases such as schizophrenia because of the complex dynamics of the brain and the multiple chemical pathways that drugs can affect.

However, many biological mechanisms associated with schizophrenia are now understood, and computational power and methods have …

Countervailing Power In Wholesale Pharmaceuticals, Sara F. Ellison, Christopher M. Snyder

Dartmouth Scholarship

Using data on wholesale prices for antibiotics sold to U.S. drugstores, we test the growing theoretical literature on ‘countervailing power’ (a term for the ability of large buyers to extract discounts from suppliers). Large drugstores receive a modest discount for antibiotics produced by competing suppliers but no discount for antibiotics produced by monopolists. These findings support theories suggesting that supplier competition is a prerequisite for countervailing power. As further evidence for the importance of supplier competition, we find that hospitals receive substantial discounts relative to drugstores, attributed to hospitals' greater ability to induce supplier competition through restrictive formularies.

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …

Brain-Selective Overexpression Of Human Angiotensin-Converting Enzyme Type 2 Attenuates Neurogenic Hypertension, Yumei Feng, Huijing Xia, Yanhui Cai, Carmen M. Halabi, Lenice K. Becker, Robson A. Santos, Robert C. Speth, Curt D. Sigmund, Eric Lazartigues

HPD Articles

RATIONALE: Angiotensin converting enzyme type 2 (ACE2) is a new member of the brain renin-angiotensin system, that might be activated by an overactive renin-angiotensin system. OBJECTIVE: To clarify the role of central ACE2 using a new transgenic mouse model with human (h)ACE2 under the control of a synapsin promoter, allowing neuron-targeted expression in the central nervous system. METHODS AND RESULTS: Syn-hACE2 (SA) transgenic mice exhibit high hACE2 protein expression and activity throughout the brain. Baseline hemodynamic parameters (telemetry), autonomic function, and spontaneous baroreflex sensitivity (SBRS) were not significantly different between SA mice and nontransgenic littermates. Brain-targeted ACE2 overexpression attenuated the …

Evaluation Of Enteral Feeding Success In Head Injured Patients Placed In Pentobarbital Induced Comas, Jane M. Gervasio, Jonathan Egel, Joshua Mcgehee, Gabriel Drew Stillabower, Nicole Ponton, Lawrence Bortenschlager, Timothy Pohlman

Scholarship and Professional Work – COPHS

Abstract of Distinction from Clinical Nutrition Week, Las Vegas, NV, February 8-10, 2010.

A Comparison Of Efficacy Of Heparin 0.5 Unit/Ml Versus Heparin 1 Unit/Ml In Parenteral Nutrition Administrated In The Neonatal Population, Jane M. Gervasio, Meredith Mckinney, Iftekar Kalsekar, Elaina Szeszycki

Scholarship and Professional Work – COPHS

Abstract from Clinical Nutrition Week, Las Vegas, NV, February 8-10, 2010.

Stability Of Extemporaneously Prepared Rufinamide Oral Suspensions, David Hutchinson, Yayin Liou, Robert Best, Fang Zhao

Pharmacy Faculty/Staff Publications

Background:

Rufinamide is an oral antiepileptic drug indicated for adjunctive therapy in treating generalized seizures associated with Lennox-Gastaut syndrome. Currently, rufinanide is available as 200-mg and 400-mg tablets. A liquid dosage form does not exist at the present time. Lack of a suspension formulation may present an administration problem for many children and adults who are unable to swallow tablets. The availability of a liquid dosage form will provide an easy and accurate way to measure and administer the medication.

Objective:

To determine the stability of both sugar-containing and sugar-free rufinamide suspensions over a 90-day period.

Methods:

A suspension of …

Antidepressant Stimulation Of Cdp-Diacylglycerol Synthesis Does Not Require Monoamine Reuptake Inhibition, Marwa A. Aboukhatwa, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

Background: Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of …

Methods To Impair Hematologic Cancer Progenitor Cells And Compounds Related Thereto, Craig Jordan

Pharmaceutical Sciences Faculty Patents

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3Rα or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful …

Antispasmodic And Vasodilator Activities Of Morinda Citrifolia Root Extract Are Mediated Through Blockade Of Voltage Dependent Calcium Channels, Anwarul Hassan Gilani, Saf-Ur-Rehman Mandukhail, Javeid Iqbal, Masoom Yasinzai, Nauman Aziz, Aslam Khan, Najeeb-Ur-Rehman

Department of Biological & Biomedical Sciences

Background: Morinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders. Methods: Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract …

Epoxyketone-Based Immunoproteasome Inhibitors, Kyung Bo Kim, Yik Khuan Ho

Pharmaceutical Sciences Faculty Patents

An efficient new route for the preparation of dihydroeponemycin, an active eponemycin derivative, is provided, which includes the synthesis of the intermediate compound, a hydroxymethyl-substituted enone. In addition, a method is provided for synthesizing inhibitors, which includes PI′-modified analogues. These analogues selectively bind to a major immunoproteasome catalytic subunit LMP2 and inactivate its proteolytic activity in a method of treating diseases, including myeloma and other cancers, Huntington's disease and Alzheimer's disease.

The Impact Of Formal Nursing Education And Nursing Experience On Medication Errors Made By Nurses In The Hospital Setting, Shellie M. Bumgarner

Nursing Theses and Capstone Projects

The occurrence of medication errors is a problem that is common to health care systems worldwide. There has been countless research performed to try to determine the cause of medication errors. It has been found that shifts worked, pharmacy involvement, miscommunication and multiple other elements contribute to the occurrence of medication errors. The primary person involved in medication administration is the nurse. This study was performed at a Western North Carolina hospital examining recorded medication errors from January 1, 2007 through December 31, 2007. Using a retrospective, descriptive, correlation design (n=293), the study determined that a significant correlation exists between …

Mass Spectrometric Analyses Of Organophosphate Insecticide Oxon Protein Adducts, Charles M. Thompson, John M. Prins, Kathleen M. George

Biomedical and Pharmaceutical Sciences Faculty Publications

OBJECTIVE: Organophosphate (OP) insecticides continue to be used to control insect pests. Acute and chronic exposures to OP insecticides have been documented-to cause adverse health effects, but few OP-adducted proteins have been correlated with these illnesses at the molecular level. Our aim was to review the literature covering the current state of the art in mass spectrometry (MS) used to identify OP protein biomarkers. DATA SOURCES AND EXTRACTION: We identified general and specific research reports related to OP insecticides, OP toxicity, OP structure, and protein MS by searching PubMed and Chemical Abstracts for articles published before December 2008. DATA SYNTHESIS: …

Lamin B Receptor, Ada L. Olins, Gale Rhodes, David B. Mark Welch, Monika Zwerger, Donald E. Olins

Pharmaceutical Sciences Faculty Publications

Lamin B Receptor (LBR) is an integral membrane protein of the interphase nuclear envelope (NE). The N-terminal end resides in the nucleoplasm, binding to lamin B and heterochromatin, with the interactions disrupted during mitosis. The C-terminal end resides within the inner nuclear membrane, retreating with the ER away from condensing chromosomes during mitotic NE breakdown. Some of these properties are interpretable in terms of our current structural knowledge of LBR, but many of the structural features remain unknown. LBR apparently has an evolutionary history which brought together at least two ancient conserved structural domains (i.e. Tudor and sterol reductase). This …

Trends In International Compulsory Licensing Of Pharmaceuticals Since The Institution Of The Trade-Related Aspects Of Intellectual Property Protection (Trips) Agreement, Reed F. Beall

Electronic Theses and Dissertations

The Trade-related Aspects of Intellectual Property Rights (TRIPS) Agreement went into effect for World Trade Organization (WTO) members in 1995. The agreement defines minimum standards of patent protection that must eventually be observed by all signatories. TRIPS includes "compulsory licensing", a policy that allows for states under certain conditions to permit the use of a patented innovation without the consent of the patent holder. This paper considers instances of compulsory licenses (CLs) aimed to increase access to pharmaceuticals during urgent public health scenarios. The WTO maintains no registry of CLs; therefore, this research is an effort to catalog as many …

Evaluating The Duration Of Post-Operative Cefuroxime Prophylaxis On Infectious Outcomes In Pediatric Cardiovascular Surgery Patients., Chad A. Knoderer, Michelle D. Berg, Andrea H. Webster, Elaine G. Cox

Scholarship and Professional Work – COPHS

Abstract of poster presented at: Pediatric Academic Societies Annual Meeting; May 2010; Vancouver, British Columbia.

Pharmaceutical Crops: An Overview, Shiyou Li, Wei Yuan, Peiying Yang, Mikhail Antoun, Michael Balick, Gordon Cragg

Faculty Publications

Pharmaceutical crops is an ambiguous term used by biologists and chemists for different categories of plants. We define pharmaceutical crops as those cultivated species that are used for extraction or preparation of therapeutic substances such as active pharmaceutical ingredients (APIs), excipients used in pharmaceutical formulations, vaccines and antibodies, as well as other therapeutic proteins. Based on the type of pharmaceutical product, these crops can be classified into three distinct yet sometimes overlapping categories: crops for the production of small therapeutic molecules (STMs), large therapeutic molecules (LMTs), or standard therapeutic extracts (STEs). This review briefly discusses the relationships of pharmaceutical crops …

An Overview Of Genus Aesculus L.: Ethnobotany, Phytochemistry, And Pharmacological Activities, Shiyou Li, Xiao-Yuan Lian, Zhizhen Zhang

Faculty Publications

The genus Aesculus L. (Hippocastanaceae) has 12 species distributed in eastern Asia, eastern and western North America, and Europe. In Europe and the United States, A. hippocastanum has been used for the treatment of chronic venous insufficiency, hemorrhoids, and postoperative edema. In China, A. chinensis var. chinense has been used as a stomachic and analgesic in the treatment of distention and pain in the chest and the abdomen, malaria, dysentery, and heart disease. The objective of this paper is to review the ethnobotany, phytochemistry, and pharmacological properties of the genus Aesculus. To date, more than 210 compounds have been isolated …

Forming Bodies And Reforming Healthcare: The Co-Construction Of Information Technologies And Bodies Through The Imperative For Self Care, Scout Calvert

University of Nebraska-Lincoln Libraries: Faculty Publications

Care work and technological work are markedly striated by sex; the sites where they overlap are few. What happens when the labor of care meets up with information technologies? It makes good methodological sense to look at largely feminized environments that are also increasingly technological. Gender, Health, and Information Technology in Context, edited and with contributions by Ellen Balka, Eileen Green, and Flis Henwood, is a welcome contribution to the body of evidence about the socio-technical co-construction of technology, health, and gender. The volume houses nine studies, bookended by an astute introduction and conclusion by the editors. Each study …

Pharmaceutical Counterfeiting And The Rfid Technology Intervention, Alberto Coustasse, Cody Arvidson, Phil Rutsohn

Management Faculty Research

Both nationally and internationally, pharmaceutical counterfeiting has become a problem that is threatening economic stability and public health. The purpose of the present research study review was to analyze the scope and severity of pharmaceutical counterfeiting and to establish if the implantation of the Radio Frequency Identification Device (RFID) model can more efficiently be used within the pharmaceutical supply chain to reduce the problem counterfeit drugs impose on public health and international economic stability. Results indicated that implementing the RFID model for tracking drugs at the item level in the pharmaceutical supply chain has potential to alleviate the scope of …