Medicine and Health Sciences Commons^™

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 …

Complement Factor H-Related Proteins Cfhr2 And Cfhr5 Represent Novel Ligands For The Infection-Associated Crasp Proteins Of Borrelia Burgdorferi, Corinna Siegel, Teresia Hallström, Christine Skerka, Hannes Eberhardt, Barbara Uzonyi, Tobias Beckhaus, Michael Karas, Reinhard Wallich, Brian Stevenson, Peter F. Zipfel, Peter Kraiczy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: One virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASP) which interact with complement regulator factor H (CFH) and factor H-like protein 1 (FHL1) or factor H-related protein 1 (CFHR1). In the present study we elucidate the role of the infection-associated CRASP-3 and CRASP-5 protein to serve as ligands for additional complement regulatory proteins as well as for complement resistance of B. burgdorferi.

METHODOLOGY/PRINCIPAL FINDINGS: To elucidate whether CRASP-5 and CRASP-3 interact with various human proteins, both borrelial proteins …

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.

Compositions And Methods For Inhibiting Drusen Complement Components C3a And C5a For The Treatment Of Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Activated C3 (C3a) and its receptor (C3aR) and activated C5 (C5a) and its receptor (C5aR) have been shown to induce vascular endothelial growth factor (VEGF) expression in vitro and in vivo. Compositions and methods for inhibiting C3a, C3aR, C5a and C5aR for the treatment and/or prevention of neovascular disease are provided. Also provided are Novel therapeutic targets and diagnostic markers for choroidal neovascularization.

Composition And Methods For Treating Yersinia Pestis Infection, Susan C. Straley, Brian S. Murphy, Stanislav Forman, Christine R. Wulff, Robert D. Perry, Tanya Myers-Morales

Microbiology, Immunology and Molecular Genetics Faculty Patents

Compositions and methods for treating a Yersinia pestis (Y. pestis) infection are provided. Compositions and methods of for inducing an immune response in a subject are provided. Composition can include a YadC polypeptide.

Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, And Upar Expression Of Prostate Cancer Cells, Kalvin J. Gregory, Bing Zhao, Diane R. Bielenberg, Sami Dridi, Jason Wu, Weihua Jiang, Bin Huang, Steven Pirie-Shepherd, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors.

METHODS AND FINDINGS: In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry …

The Us Preventive Service Taskforce And The Guide To Clinical Preventive Services., F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Route Of Administration For Illicit Prescription Opioids: A Comparison Of Rural And Urban Drug Users, April M. Young, Jennifer R. Havens, Carl G. Leukefeld

Behavioral Science Faculty Publications

BACKGROUND: Nonmedical prescription opioid use has emerged as a major public health concern in recent years, particularly in rural Appalachia. Little is known about the routes of administration (ROA) involved in nonmedical prescription opioid use among rural and urban drug users. The purpose of this study was to describe rural-urban differences in ROA for nonmedical prescription opioid use.

METHODS: A purposive sample of 212 prescription drug users was recruited from a rural Appalachian county (n = 101) and a major metropolitan area (n = 111) in Kentucky. Consenting participants were given an interviewer-administered questionnaire examining sociodemographics, psychiatric disorders, and self-reported …

High-Intensity Mechanical Therapy For Loss Of Knee Extension For Worker's Compensation And Non-Compensation Patients, Amanda L. Dempsey, Thomas P. Branch, Timothy Mills, Robert M. Karsch

Orthopaedic Surgery and Sports Medicine Faculty Publications

BACKGROUND: Knee flexion contractures have been associated with increased pain and a reduced ability to perform activities of daily living. Contractures can be treated either surgically or conservatively, but these treatment options may not be as successful with worker's compensation patients. The purposes of retrospective review were to 1) determine the efficacy of using adjunctive high-intensity stretch (HIS) mechanical therapy to treat flexion contractures, and 2) compare the results between groups of worker's compensation and non-compensation patients.

METHODS: Fifty-six patients (19 women, 37 men, age = 51.5 ± 17.0 years) with flexion contractures were treated with HIS mechanical therapy as …

Community Health Assesments, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Insulin Degrading Enzyme Assays For Treatment Of Alzheimer's Disease, Louis B. Hersh

Molecular and Cellular Biochemistry Faculty Patents

Estrogen has been shown to increase the expression and activity of amyloid peptide inactivating enzymes in the brain. Peptides have been shown to increase the activity of an amyloid peptide inactivating enzyme. Methods of identifying compounds for, and methods of treating patients with, Alzheimer's Disease is disclosed.

Public Health Services And Systems Research: Data For Research, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Rafinesque And Transylvania’S First Botanical Garden, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Five Early American Botanists: Works And Opinions Of Rafinesque, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

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 …

Service Technician Working Alone Dies After Being Assaulted, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Other

One late fall evening in 2009, a 53 year-old male technician was working alone at a repair shop. At approximately 9:45 PM, the technician returned to the shop with his dinner from a nearby fast-food establishment. He spread his dinner on the work bench and began eating when apparently he was attacked from behind. His attacker used a knife and cut the technician’s carotid artery and jugular vein on the left side of his neck. The attacker fled, and the technician used a cell phone to call 911, emergency medical services (EMS). When EMS arrived, they found the technician dead …

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 …

The Mir-15/107 Group Of Microrna Genes: Evolutionary Biology, Cellular Functions, And Roles In Human Diseases, John R. Finnerty, Wang-Xia Wang, Sébastien S. Hébert, Bernard R. Wilfred, Guogen Mao, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

The miR-15/107 group of microRNA (miRNA) gene is increasingly appreciated to serve key functions in humans. These miRNAs regulate gene expression involved in cell division, metabolism, stress response, and angiogenesis in vertebrate species. The miR-15/107 group has also been implicated in human cancers, cardiovascular disease and neurodegenerative disease, including Alzheimer's disease. Here we provide an overview of the following: (1) the evolution of miR-15/107 group member genes; (2) the expression levels of miRNAs in mammalian tissues; (3) evidence for overlapping gene-regulatory functions by different miRNAs; (4) the normal biochemical pathways regulated by miR-15/107 group miRNAs; and (5) the roles played …

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.

Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication Via Interaction With Ddx3x, Chaomin Sun, Cara T. Pager, Guangxiang Luo, Peter Sarnow, Jamie H. D. Cate

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16-36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent …

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.

Sialic Acid Transport And Catabolism Are Cooperatively Regulated By Siar And Crp In Nontypeable Haemophilus Influenzae, Jason W. Johnston, Haider Shamsulddin, Anne-Frances Miller, Michael A. Apicella

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: The transport and catabolism of sialic acid, a critical virulence factor for nontypeable Haemophilus influenzae, is regulated by two transcription factors, SiaR and CRP.

RESULTS: Using a mutagenesis approach, glucosamine-6-phosphate (GlcN-6P) was identified as a co-activator for SiaR. Evidence for the cooperative regulation of both the sialic acid catabolic and transport operons suggested that cooperativity between SiaR and CRP is required for regulation. cAMP was unable to influence the expression of the catabolic operon in the absence of SiaR but was able to induce catabolic operon expression when both SiaR and GlcN-6P were present. Alteration of helical phasing supported …

Deficient Liver Biosynthesis Of Docosahexaenoic Acid Correlates With Cognitive Impairment In Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Nicole C. Berchtold, Vinh Q. Nguyen, Daniel L. Gillen, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P = 0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P = 0.005) and mid-frontal cortex (P = 0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's …

Public Health Systems And Services Research: Bridging The Practice-Research Gap., F. Douglas Scutchfield, Cynthia D. Lamberth

Preventive Medicine and Environmental Health Faculty Publications

Public health practitioners understand the principles of evidence-based practice

and the science that should drive their efforts to improve the community’s

health through the implementation of science-driven public health programs.

However, the translation of research to practice still has numerous barriers.

This commentary provides suggestions to strengthen the link between research

and practice.

Hiv-1 Reactivation Induced By The Periodontal Pathogens Fusobacterium Nucleatum And Porphyromonas Gingivalis Involves Toll-Like Receptor 2 And 9 Activation In Monocytes/Macrophages, Octavio A. Gonzalez, Mengtao Li, Jeffrey L. Ebersole, Chifu B. Huang

Center for Oral Health Research Faculty Publications

Although oral coinfections (e.g., periodontal disease) are highly prevalent in human immunodeficiency virus type 1-positive (HIV-1⁺) patients and appear to positively correlate with viral load levels, the potential for oral bacteria to induce HIV-1 reactivation in latently infected cells has received little attention. We showed that HIV-1 long terminal repeat (LTR) promoter activation can be induced by periodontopathogens in monocytes/macrophages; nevertheless, the mechanisms involved in this response remain undetermined. Since Toll-like receptor 2 (TLR2), TLR4, and TLR9 activation have been involved in HIV-1 recrudescence, we sought to determine the role of these TLRs in HIV-1 reactivation induced by …

Insulin Resistance In African-American And Caucasian Women: Differences In Lipotoxicity, Adipokines, And Gene Expression In Adipose Tissue And Muscle, Latasha M. Smith, Aiwei Yao-Borengasser, Tasha Starks, Mark Tripputi, Philip A. Kern, Neda Rasouli

Clinical and Translational Science Faculty Publications

Objectives: We tested whether African-American (AA) women are different from Caucasian women in regard to lipotoxicity, adipokines, and gene expression in adipose tissue and muscle.

Design: Insulin sensitivity (S_I), plasma adipocytokine levels, intramyocellular lipid (IMCL), and the expression of candidate genes in adipose tissue and muscle were measured in AA and Caucasian women.

Setting: This study was performed in an ambulatory general clinical research center.

Subjects: Subjects were healthy, nondiabetic AA and Caucasian women.

Interventions: There were no interventions.

Main Outcome Measures: Comparison of S_I, IMCL, plasma adiponectin, and the expression of candidate genes regulating adipogenesis, …

Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4⁺ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals …

Bpab, A Novel Protein Encoded By The Lyme Disease Spirochete's Cp32 Prophages, Binds To Erp Operator 2 Dna, Logan H. Burns, Claire A. Adams, Sean P. Riley, Brandon L. Jutras, Amy Bowman, Alicia M. Chenail, Anne E. Cooley, Laura A. Haselhorst, Alisha M. Moore, Kelly Babb, Michael G. Fried, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi produces Erp outer surface proteins throughout mammalian infection, but represses their synthesis during colonization of vector ticks. A DNA region 5′ of the start of erp transcription, Operator 2, was previously shown to be essential for regulation of expression. We now report identification and characterization of a novel erp Operator 2-binding protein, which we named BpaB. erp operons are located on episomal cp32 prophages, and a single bacterium may contain as many as 10 different cp32s. Each cp32 family member encodes a unique BpaB protein, yet the three tested cp32-encoded BpaB alleles all bound to the same DNA …

Training For Equipment Maintenance And Repair, Sam Powdrill, Ismael Cordero, V Srinivasan

Health and Clinical Sciences Faculty Publications

In order to ensure the that equipment functions well, both equipment users and the equipment maintenance and repair team must be trained. Users must be trained in basic care and maintenance of equipment, and the equipment team must be trained to undertake repairs and more complex maintenance tasks.

Identification Of A Unique Core Domain Of Par-4 Sufficient For Selective Apoptosis Induction In Cancer Cells, Vivek M. Rangnekar

Radiation Medicine Faculty Patents

The present invention relates to Par-4 mutants which cause apoptosis in cancer cells which are sensitive to Par-4 and also induce apoptosis in cancer cells which are resistant to Par-4. The present invention also relates to methods of using the Par-4 mutant to treat certain cancers, as well as to kits, vectors, and polypeptides for same.