Medicine and Health Sciences Commons^™

Permeable, Water Soluble, Non-Irritating Prodrugs Of Chemotherapeutic Agents With Oxaalkanoic Acids, Peter A. Crooks, Tadeusz Cynkowski, Grazyna Cynkowska, Hong Guo, Paul Ashton

Pharmaceutical Sciences Faculty Patents

The present invention relates to the field of prodrugs of chemotherapeutic agents and method of use thereof.

Differential Neuromuscular Training Effects On Acl Injury Risk Factors In"High-Risk" Versus "Low-Risk" Athletes, Gregory D. Myer, Kevin R. Ford, Jensen L. Brent, Timothy E. Hewett

Kinesiology and Health Promotion Faculty Publications

BACKGROUND: Neuromuscular training may reduce risk factors that contribute to ACL injury incidence in female athletes. Multi-component, ACL injury prevention training programs can be time and labor intensive, which may ultimately limit training program utilization or compliance. The purpose of this study was to determine the effect of neuromuscular training on those classified as "high-risk" compared to those classified as "low-risk." The hypothesis was that high-risk athletes would decrease knee abduction moments while low-risk and control athletes would not show measurable changes.

METHODS: Eighteen high school female athletes participated in neuromuscular training 3x/week over a 7-week period. Knee kinematics and …

Long Haul Trucker Dies After Striking An Embankment At The End Of An Interstate Highway Off-Ramp, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

In the fall of year 2005, at 12:40 AM, a 47-year-old male semi-truck driver began his delivery route hauling a refrigerated trailer loaded with 23,000 pounds of produce. His first delivery was approximately 265 miles away. After two hours and twenty minutes, he exited the interstate 23 miles from the start of his route. At the end of the exit ramp he attempted to turn right onto a 4-lane highway. He missed the turn and drove straight across the highway through a guardrail; the truck became airborne, and crashed into an embankment exploding into flames. An unidentified motorist driving behind …

Efficacy Of The De Novo-Derived Antimicrobial Peptide Wlbu2 Against Oral Bacteria, Karen F. Novak, William J. Diamond, Sreenatha S. Kirakodu, Rebecca Peyyala, Kimberly W. Anderson, Ronald C. Montelaro, Timothy A. Mietzner

Center for Oral Health Research Faculty Publications

The efficacy of a novel synthetic antimicrobial peptide (WLBU2) was evaluated against three oral microorganisms (grown planktonically): Streptococcus gordonii, Fusobacterium nucleatum, and Porphyromonas gingivalis. WLBU2 killed all three species, with F. nucleatum being the most susceptible. WLBU2 also reduced the bacterial burden of S. gordonii and F. nucleatum biofilms.

Expansion Of The Calcium Hypothesis Of Brain Aging And Alzheimer's Disease: Minding The Store, Olivier Thibault, John C. Gant, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. …

Development Of A Decision Support Tool To Facilitate Primary Care Management Of Patients With Abnormal Liver Function Tests Without Clinically Apparent Liver Disease [Hta03/38/02]. Abnormal Liver Function Investigations Evaluation (Alfie), Peter T. Donnan, David Mclernon, Douglas Steinke, Stephen Ryder, Paul Roderick, Frank M. Sullivan, William Rosenberg, John F. Dillon

Pharmacy Practice and Science Faculty Publications

BACKGROUND: Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs.

METHODS/DESIGN: …

Bridging The Critical Chasm Between Service And Research: The Cancer Information Service’S Collaboratory, Linda Squiers, Nigel Bush, Robin C. Vanderpool, Ludmila Cofta-Woerpel, Cecilia Fabrizio

Health, Behavior & Society Faculty Publications

As a collaboratory for cancer communication and education research, the National Cancer Institute's (NCIs) Cancer Information Service (CIS) is in an ideal position to bridge the critical chasm that exists between service and research. This article describes the CIS' current research program as well as the CIS Research Agenda launched in 2005. The CIS' progress in developing and supporting recently funded studies that address this agenda is detailed. The unique resources and opportunities available to researchers, public health practitioners, health care providers, and community-based organizations interested in developing collaborative cancer communication and cancer education studies with the CIS are identified …

Chronic Disease Prevention In Adolescence, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

The Health Implications Of Violence Against Women: Untangling The Complexities Of Acute And Chronic Effects: Part One, Carol E. Jordan

Office for Policy Studies on Violence Against Women Publications

No abstract provided.

Adrb2 Arg16gly Polymorphism, Lung Function, And Mortality: Results From The Atherosclerosis Risk In Communities Study, Jill M. Ferdinands, David M. Mannino, Marta L. Gwinn, Molly S. Bray

Internal Medicine Faculty Publications

BACKGROUND: Growing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy. We sought to examine the association of beta-agonist use and the Arg16Gly polymorphism with lung function and mortality among participants in the Atherosclerosis Risk in Communities study.

METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped study participants and analyzed the association of the Arg16Gly polymorphism and beta-agonist use with lung function at baseline and clinical examination three years later and with all-cause mortality during 10 years of follow-up. Lung function was characterized by percent-predicted forced expiratory volume in 1 …

Sociodemographic Characteristics And Diabetes Predict Invalid Self-Reported Non-Smoking In A Population-Based Study Of U.S. Adults, Monica A. Fisher, George W. Taylor, Brent J. Shelton, Sara M. Debanne

Markey Cancer Center Faculty Publications

BACKGROUND: Nearly all studies reporting smoking status collect self-reported data. The objective of this study was to assess sociodemographic characteristics and selected, common smoking-related diseases as predictors of invalid reporting of non-smoking. Valid self-reported smoking may be related to the degree to which smoking is a behavior that is not tolerated by the smoker's social group.

METHODS: True smoking was defined as having serum cotinine of 15+ng/ml. 1483 "true" smokers 45+ years of age with self-reported smoking and serum cotinine data from the Mobile Examination Center were identified in the third National Health and Nutrition Examination Survey. Invalid non-smoking was …

Phase I And Phase Ii Ocular Metabolic Activities And The Role Of Metabolism In Ophthalmic Prodrug And Codrug Design And Delivery, Abeer M. Al-Ghananeem, Peter A. Crooks

Pharmaceutical Sciences Faculty Publications

While the mammalian eye is seldom considered an organ of drug metabolism, the capacity for biotransformation is present. Compared to the liver, the metabolic capabilities of the eye are minuscule; however, phase I and phase II metabolic activities have been detected in various ocular structures. The careful consideration of ocular tissue metabolic processes within the eye has important implications for controlling the detoxification of therapeutic agents and for providing the potential for site-specific bio-activation of certain drug molecules, thus enabling significant improvements in drug efficacy and the minimization of side-effect from either local or systemic drug delivery to the eye. …

Fatal Aerial Lift Injuries, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Motor Vehicle

To prevent injuries while working in aerial lifts:

• A “pre-job safety plan” should be developed for each job site and reviewed prior to each day on the job site.
• Mechanical checks should be performed on all equipment at each job site prior to each use.
• There should be communication between the worker in the elevated lift and ground control crew.
• Ensure that appropriate fall protection equipment is available and correctly used when working from elevations.
• Employees should work within job qualifications and job limits.

Avoiding Bias In The Annualized Rate Of Changed Of Fev1, David M. Mannino, Matthew M. Reichert, Kourtney J. Davis

David M. Mannino

No abstract provided.

Adrb2 Arg16gly Polymorphism, Lung Function, And Mortality: Results From The Atherosclerosis Risk In Community Study, Jill M. Ferdinands, David M. Mannino, Marta L. Gwinn, Molly S. Bray

David M. Mannino

Background

Growing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy. We sought to examine the association of beta-agonist use and the Arg16Gly polymorphism with lung function and mortality among participants in the Atherosclerosis Risk in Communities study.

Methodology and Principal Findings

We genotyped study participants and analyzed the association of the Arg16Gly polymorphism and beta-agonist use with lung function at baseline and clinical examination three years later and with all-cause mortality during 10 years of follow-up. Lung function was characterized by percent-predicted forced expiratory volume in 1 …

Teenage Pregnancy: Impact Of The Integral Attention Given To The Pregnant Teenager And Adolescent Mother As A Protective Factor For Repeat Pregnancy, Maria José Carvalho Sant'anna, Kepler Alencar Mendes Carvalho, Amanda Melhado, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

The purpose of this study was to evaluate the impact of the integral attention to the health of pregnant adolescents and adolescent mothers, having follow-up from the Integral Support Program for the Pregnant Teen (ISPPT), with the intention to determine quality of life and prevent repeat pregnancy. A prospective study comprised 85 adolescents attended by the ISPPT between January 2002 and June 2006 who participated in meetings during pregnancy with a multidisciplinary team that provided orientation concerning family planning, self-esteem, pregnancy prevention, motivation to continue education and/or work, and evaluate the postpartum mother-child relationship. The following were analyzed: education level, …

Improving Student Dentist Competencies And Perception Of Difficulty In Delivering Care To Children With Developmental Disabilities Using A Virtual Patient Module, Harold L. Kleinert, Carla Sanders, John Mink, David A. Nash, Jeff Johnson, Sara Boyd, Sandra Challman

Human Development Institute Faculty Publications

An interactive, multimedia, virtual patient module was designed and developed on compact disc (CD-ROM) to address the need for student dentists to increase their competence and decrease their perception of difficulty in caring for children with developmental disabilities. A development team consisting of pediatric dentistry faculty members, parents of children with developmental disabilities, an individual with a developmental disability, and educational specialists developed an interactive virtual patient case. The case involved a ten-year-old child with Down syndrome presenting with a painful tooth. Student dentists were required to make decisions regarding proper interactions with the child, as well as appropriate clinical …

Human Visfatin Expression: Relationship To Insulin Sensitivity, Intramyocellular Lipids, And Inflammation, Vijayalakshmi Varma, Aiwei Yao-Borengasser, Neda Rasouli, Angela M. Bodles, Bounleut Phanavanh, Mi-Jeong Lee, Tasha Starks, Leslie M. Kern, Horace J. Spencer Iii, Robert E. Mcgehee Jr., Susan K. Fried, Philip A. Kern

Clinical and Translational Science Faculty Publications

Context: Visfatin (VF) is a recently described adipokine preferentially secreted by visceral adipose tissue (VAT) with insulin mimetic properties.

Objective: The aim of this study was to examine the association of VF with insulin sensitivity, intramyocellular lipids (IMCL), and inflammation in humans.

Design and Patients: VF mRNA was examined in paired samples of VAT and abdominal sc adipose tissue (SAT) obtained from subjects undergoing surgery. Plasma VF and VF mRNA was also examined in SAT and muscle tissue, obtained by biopsy from well-characterized subjects with normal or impaired glucose tolerance, with a wide range in body mass index (BMI) and …

The Effect Of Cpg-Odn On Antigen Presenting Cells Of The Foal, M. Julia B.F. Flaminio, Alexandre S. Borges, Daryl V. Nydam, David W. Horohov, Rolf Hecker, Mary Beth Matychak

Veterinary Science Faculty Publications

BACKGROUND: Cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) has been used successfully to induce immune responses against viral and intracellular organisms in mammals. The main objective of this study was to test the effect of CpG-ODN on antigen presenting cells of young foals.

METHODS: Peripheral blood monocytes of foals (n = 7) were isolated in the first day of life and monthly thereafter up to 3 months of life. Adult horse (n = 7) monocytes were isolated and tested once for comparison. Isolated monocytes were stimulated with IL-4 and GM-CSF (to obtain dendritic cells, DC) or not stimulated (to obtain macrophages). Macrophages and DCs …

Human Health Risk Assessment For Aluminium, Aluminium Oxide, And Aluminium Hydroxide, Daniel Krewski, Robert A. Yokel, Evert Nieboer, David Borchelt, Joshua Cohen, Jean Harry, Sam Kacew, Joan Lindsay, Amal M. Mahfouz, Virginie Rondeau

Pharmaceutical Sciences Faculty Publications

A compendium is provided of aluminium compounds used in industrial settings, and as pharmaceuticals, food additives, cosmetics and as other household products. Most aluminium compounds are solids exhibiting high melting points. The solubility of aluminium salts is governed by pH, because the aluminium(III)-cation (Al³⁺) has a strong affinity for the hydroxide ion, which promotes precipitation. Like Mg²⁺ and Ca²⁺ ions, Al³⁺ in most situations seeks out complexing agents with oxygen-atom donor sites such as carboxylate and phosphate groups, including in biological systems. Aluminium oxides, hydroxides and oxyhydroxides occur in numerous crystallographic forms, which exhibit different …

Public Health Performance, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

The Association Of Lung Cancer Mortality With Income And Education In Kentucky Counties, David A. Gross

Center of Excellence in Rural Health Presentations

Lung cancer, the primary cause of cancer death in the United States, is particularly problematic in Kentucky, which has the nation’s highest rate of adult smokers. In fact, each Kentucky county exceeds the national rate for per capita lung cancer deaths. This project analyzes the relationships between lung cancer deaths, high school graduation rates, per capita personal income and adult smoking – and whether statistically significant differences exist among the variables between Kentucky’s Appalachian and non-Appalachian counties.

Public Health Performance, F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

Xenobiotic Transporters In Lactating Mammary Epithelial Cells: Predictions For Drug Accumulation In Breast Milk, Philip Earle Empey

Theses and Dissertations--Pharmacy

Recent literature has established that breast cancer resistance protein (ABCG2) is upregulated during lactation and is responsible for the greater than predicted accumulation of many drugs in breast milk. The objectives of this project were (1) to investigate the role of this transporter in the reported apically-directed nitrofurantoin flux in the CIT3 cell culture model of lactation, (2) to develop a mathematical model for drug transfer into breast milk to relate initial flux rates, steady-state concentrations, efflux ratios, and in vivo milk to serum ratios (M/S) and (3) to identify xenobiotic transporters that are highly expressed, and therefore potentially important …

Molecular Mechanisms Of Olfactory Neurodegeneration, Radhika Anand Vaishnav

University of Kentucky Doctoral Dissertations

Olfactory sensory decline has been associated with normal aging as well as neurodegenerative disorders, yet the underlying mechanisms are unclear. The overall aim of this dissertation was to investigate the fundamental molecular and cellular mechanisms associated with olfactory neurodegeneration. This investigation uses an integrative approach, combining proteomics and gene expression analyses with cellular and tissuelevel characterization. Using these approaches, two model systems were investigated: 1) normally aging C57BL/6 mice of ages 1.5-, 6- and 20-months; and 2) a mouse model of elevated endogenous oxidative stress-associated neurodegeneration, namely, the Harlequin mutant mouse. The first specific aim was to test the hypothesis …

Tracing The Origin Of The Recent Rise In Neuropathogenic Ehv-1, Kathryn Laura Smith

University of Kentucky Master's Theses

Equine herpesvirus type-1(EHV-1) is a complex virus known for inducing various forms of disease in horses. In recent years, the number of cases of neurological disease caused by this virus has increased. While there are a number of possible sources for this recent surge, this project set out to determine if a genotypic shift in the latent population of the virus in favor of the neuropathogenic form of EHV-1 is the basis for the recent increase in frequency of EHV-1 neurologic disease. To ascertain if such a shift has in fact occurred, 450 EHV-1 isolates were obtained from fetal tissues …

Replication Fork Regression In Vitro By The Werner Syndrome Protein (Wrn): Holliday Junction Formation, The Effect Of Leading Arm Structure And A Potential Role For Wrn Exonuclease Activity, Amrita Machwe, Liren Xiao, Robert G Lloyd, Edward Bolt, David K. Orren

Toxicology and Cancer Biology Faculty Publications

The premature aging and cancer-prone disease Werner syndrome stems from loss of WRN protein function. WRN deficiency causes replication abnormalities, sensitivity to certain genotoxic agents, genomic instability and early replicative senescence in primary fibroblasts. As a RecQ helicase family member, WRN is a DNA-dependent ATPase and unwinding enzyme, but also possesses strand annealing and exonuclease activities. RecQ helicases are postulated to participate in pathways responding to replication blockage, pathways possibly initiated by fork regression. In this study, a series of model replication fork substrates were used to examine the fork regression capability of WRN. Our results demonstrate that WRN catalyzes …

Identification And Characterization Of Ogg1 Mutations In Patients With Alzheimer's Disease, Guogen Mao, Xiaoyu Pan, Beibei Zhu, Yanbin Zhang, Fenghua Yuan, Jian Huang, Mark A. Lovell, Maxwell P. Lee, William R. Markesbery, Guo-Min Li, Liya Gu

Toxicology and Cancer Biology Faculty Publications

Patients with Alzheimer's disease (AD) exhibit higher levels of 8-oxo-guanine (8-oxoG) DNA lesions in their brain, suggesting a reduced or defective 8-oxoG repair. To test this hypothesis, this study investigated 14 AD patients and 10 age-matched controls for mutations of the major 8-oxoG removal gene OGG1. Whereas no alterations were detected in any control samples, four AD patients exhibited mutations in OGG1, two carried a common single base (C₇₉₆) deletion that alters the carboxyl terminal sequence of OGG1, and the other two had nucleotide alterations leading to single amino acid substitutions. In vitro biochemical assays revealed …

Senate Bill (Sb) 172: Governance Of Nutrition In Kentucky Public Schools: Implementation Analysis Final Report, Bill Brumbach

MPA/MPP/MPFM Capstone Projects

This report is intended to evaluate the implementation of Senate Bill (SB) 172 in Kentucky's public schools. This law requires that all schools in Kentucky implement strict nutrition standards that apply to all foods sold during the school day. This report highlights the different methods used by selected schools in implementing the requirements in SB 172. In performing my analysis, I traveled to different schools in central and southeastern Kentucky to assess how these select schools were meeting the requirements of the law. Site visits allowed me to discuss implementation strategies with school administrators and aided in my understanding of …

Evaluating If The Built Environment Has A Substantial Effect On Obesity In Fayette County, Kentucky, Will Warren

MPA/MPP/MPFM Capstone Projects

Background:

Obesity is a major health issue in the United States and Fayette County. As Fayette County has become increasingly obese, it too has had an issue of sprawl within its urban service area and beyond. Relationships between obesity and aspects of the built environment are continuing to be studied.

Objective:

To evaluate the impact certain factors may have on the body mass index of Fayette County residents, in particular whether urban sprawl has an overriding impact on the weight of residents.

Methods:

The study area used was Fayette County, which was broken down into its fourteen zip code areas …