Medicine and Health Sciences Commons^™

Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr^-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …

Social Factors Affecting Treatment Of Cervical Cancer: Ethical Issues And Policy Implications, Shannon N. Westin, Dan Bustillos, Jacalyn B. Gano, Margaret M. Fields, Ann L. Coker, Charlotte C. Sun, Lois M. Ramondetta

CRVAW Faculty Journal Articles

Health care in the United States has become a privilege rather than a right. Patients who have the greatest need are the ones most likely to be denied this privilege. Despite recent advances in disease detection and treatment, many patients do not receive even the bare minimum of care. The high complexity of the health care system in the setting of patients with low levels of health literacy significantly affects the ability to seek and receive treatment in a timely fashion. In addition, lack of insurance, transportation, and social support further complicate access to care. To truly provide a standard …

Finding Order In Complexity: A Typology Of Local Public Health Delivery Systems, Glen P. Mays, F. Douglas Scutchfield, Michelyn Bhandari, Sharla A. Smith

Health Management and Policy Reports

Public health decision-makers and researchers currently lack an evidence-based framework for describing, classifying, and comparing public health delivery systems based on their organizational components, operational characteristics, and division of responsibility. Related typologies developed in the health services sector have proven extremely valuable for policy and administrative decision-making as well as for ongoing research. Performance assessment, quality improvement, and accreditation activities are now blossoming in public health—adding urgency to the need for classification and comparison frameworks. This brief describes a newly-developed empirical typology for local public health systems and highlights its policy and managerial applications.

Application Of Prodrugs To Inflammatory Diseases Of The Gut, Helieh S. Oz, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Oral delivery is the most common and preferred route of drug administration although the digestive tract exhibits several obstacles to drug delivery including motility and intraluminal pH profiles. The gut milieu represents the largest mucosal surface exposed to microorganisms with 10^10-12 colony forming bacteria/g of colonic content. Approximately, one third of fecal dry matter is made of bacteria/ bacterial components. Indeed, the normal gut microbiota is responsible for healthy digestion of dietary fibers (polysaccharides) and fermentation of short chain fatty acids such as acetate and butyrate that provide carbon sources (fuel) for these bacteria. Inflammatory bowel disease (IBD) results …

Method For Treating A Viral Infection Related Or A Chemical Toxin Related Hepatic Injury With Deltorphin D, Peter R. Oeltgen, Paul D. Bishop, Craig J. Mcclain, Shirish Barve

Pathology and Laboratory Medicine Faculty Patents

A method of modulating cytokine mediated hepatic injury by administering compound-D SEQ ID NO:1 to a mammal. A concentration of the compound in the range of about 0.5 mg/kg to about 20 mg/kg in a physiologically acceptable formulation blocks a cytokine cascade. A therapeutic method of modulating cytokine mediated acute inflammatory, trauma induced and toxin induced hepatic injury, particularly via tumor necrosis factor modulation, is thus disclosed.

Primers And Probe To Identify Mycobacterium Tuberculosis Complex, Subodh M. Lele, Manjiri S. Lele, Nada H. Khattar

Pathology and Laboratory Medicine Faculty Patents

Methods and nucleic acids for rapid, reliable and sensitive detection of Mycobacterium tuberculosis (MTB) complex pathogen in a biological sample. Oligonucleotides are provided which amplify MTB DNA and which are useful in carrying out real time PCR of DNA obtained from formalin-fixed and paraffin-embedded tissue samples.

Male Semi-Truck Driver Killed In Rollover Crash On County Road, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

Early in the morning during the winter of 2005, a 31-year-old male semi-truck driver died when the semi-tractor trailer he was driving left the roadway and rolled over into a ditch. He had just picked up a load of raw lumber from a lumber yard and pulled out of the gate onto a county road and driven about a mile when the incident occurred. His destination was a lumber mill approximately 150 miles away. He was driving on a straight stretch of the road when the right tires left the pavement and dropped onto the sloped grassy area next to …

Coal Truck Driver Fatally Injured In Collision With Another Coal Tractor-Trailer, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

During the winter of 2008, a 39 –year-old tractor-trailer driver died after striking the right rear of a coal tractor-trailer with his vehicle, then veering into an embankment, rolling over and catching fire. The driver of a coal tractor-trailer (Truck 1) and the decedent driver of a second coal tractor-trailer (Truck 2) had descended a hill in the lane next to one another on a four-lane undivided highway. Truck 1 stopped at a traffic light at an intersection at the bottom of a hill while Truck 2 approached the intersection from behind in the left lane. The light turned green …

Thrombospondin-1 Is An Adipokine Associated With Obesity, Adipose Inflammation, And Insulin Resistance, Vijayalakshmi Varma, Aiwei Yao-Borengasser, Angela M. Bodles, Neda Rasouli, Bounleut Phanavanh, Greg T. Nolen, Emily M. Kern, Radhakrishnan Nagarajan, Horace J. Spencer, Mi-Jeong Lee, Susan K. Fried, Charlotte A. Peterson, Philip A. Kern

Clinical and Translational Science Faculty Publications

OBJECTIVE-We examined the relationship between the expression of thrombospondin (TSP)1, an antiangiogenic factor and regulator of transforming growth factor-β activity, obesity, adipose inflammation, and insulin resistance.

RESEARCH DESIGN AND METHODS-TSP1 gene expression was quantified in subcutaneous adipose tissue (SAT) of 86 nondiabetic subjects covering a wide range of BMI and insulin sensitivity, from visceral adipose (VAT) and SAT from 14 surgical patients and from 38 subjects with impaired glucose tolerance randomized to receive either pioglitazone or metformin for 10 weeks. An adipocyte culture system was also used to assess the effects of pioglitazone and coculture with macrophages on …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Hispanic Carpenter Dies After Falling From Homemade Platform, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Falls

In the Spring of 2007, a 32-year-old Hispanic male carpenter (decedent) died when he fell from a homemade platform (extended approximately seven feet in the air) after it detached from a telehandler (forklift). The decedent and two other carpenters were framing a new construction, single-family residence located on a hillside which was rough and steep. The three carpenters were framing the wall at the rear corner of the house which was high because of the sloping terrain. To reach the area, the crew decided to use a homemade platform as a makeshift scaffold. A fourth worker operated a rough-terrain forklift …

Dump Truck Driver Dies After Being Entangled In Power-Take-Off Drive Shaft, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

During the fall of 2006, a 25-year-old male company dump truck driver (decedent) died when he became entangled in the drive shaft of the power-take-off pump (PTO) underneath a dump truck. He and four other dump truck drivers were waiting to have their trucks filled with asphalt when one of the other drivers (Driver 1) began having difficulty with the bed of his truck raising and lowering properly. Another driver (Driver 2) attempted to assist Driver 1 with the problem, but was unsuccessful. Driver 1 decided to inform the plant manager (Owner 1) of the situation and request assistance from …

Pioglitazone Inhibition Of Lipopolysaccharide-Induced Nitric Oxide Synthase Is Associated With Altered Activity Of P38 Map Kinase And Pi3k/Akt, Bin Xing, Tao Xin, Randy Lee Hunter, Guoying Bing

Neuroscience Faculty Publications

BACKGROUND: Previous studies have suggested that peroxisome proliferator activated receptor-gamma (PPAR-gamma)-mediated neuroprotection involves inhibition of microglial activation and decreased expression and activity of inducible nitric oxide synthase (iNOS); however, the underlying molecular mechanisms have not yet been well established. In the present study we explored: (1) the effect of the PPAR-gamma agonist pioglitazone on lipopolysaccharide (LPS)-induced iNOS activity and nitric oxide (NO) generation by microglia; (2) the differential role of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun NH(2)-terminal kinase (JNK), and phosphoinositide 3-kinase (PI3K) on LPS-induced NO generation; and (3) the regulation of p38 MAPK, JNK, and PI3K by pioglitazone. …

Optimizing Qpcr For The Quantification Of Periodontal Pathogens In A Complex Plaque Biofilm, Sreenatha S. Kirakodu, M. Govindaswami, Michael John Novak, Jeffrey L. Ebersole, Karen F. Novak

Center for Oral Health Research Faculty Publications

Quantitative PCR (qPCR) has recently been used to quantify microorganisms in complex communities, including dental plaque biofilms. However, there is variability in the qPCR protocols being used. This study was designed to evaluate the validity of two of these variables with the intent of developing a more standardized qPCR protocol. The two variables evaluated were (1) the use of DNA content versus actual cell counts to estimate bacterial numbers in mixed plaque samples and (2) the effectiveness of three different universal primers versus species specific primers in amplifying specific target pathogens in these samples. Results lead to the development of …

Suicides Among Farmers In Three Southeastern States, 1990-1998, Steven R. Browning, Susan C. Westneat, Robert H. Mcknight

Epidemiology and Environmental Health Faculty Publications

Several studies have documented higher rates of suicide among farmers in comparison to other occupational groups, both in the U.S. and internationally. The purpose of this study is to describe the epidemiology of farmer suicides in three southeastern states (Kentucky, North Carolina, and South Carolina) during the nine-year period 1990-1998. Electronic death certificate data were obtained from the National Center for Health Statistics. Over the nine-year period, there were 590 deaths related to suicide (E-codes: 950-959) among farmers (occupation codes: 473, 474, 475, 477, and 479) in the states of Kentucky, North Carolina, and South Carolina. The results of this …

The Collected Works Of Hippocrates And Galen: The Greatest Physicians Of The Graeco-Roman World, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Tampons And Menstrual Hygiene Products, Shibani Kanungo, Hatim A. Omar

Obstetrics and Gynecology Faculty Publications

No abstract provided.

Micrornas (Mirnas) In Neurodegenerative Diseases, Peter T. Nelson, Wang-Xia Wang, Bernard W. Rajeev

Sanders-Brown Center on Aging Faculty Publications

Aging-related neurodegenerative diseases (NDs) are the culmination of many different genetic and environmental influences. Prior studies have shown that RNAs are pathologically altered during the inexorable course of some NDs. Recent evidence suggests that microRNAs (miRNAs) may be a contributing factor in neurodegeneration. miRNAs are brain-enriched, small (~22 nucleotides) non-coding RNAs that participate in mRNA translational regulation. Although discovered in the framework of worm development, miRNAs are now appreciated to play a dynamic role in many mammalian brain-related biochemical pathways, including neuroplasticity and stress responses. Research about miRNAs in the context of neurodegeneration is accumulating rapidly, and the goal of …

Sr-Bi Protects Against Endotoxemia In Mice Through Its Roles In Glucocorticoid Production And Hepatic Clearance, Lei Cai, Ailing Ji, Frederick C. De Beer, Lisa R. Tannock, Deneys R. Van Der Westhuyzen

Internal Medicine Faculty Publications

Septic shock results from an uncontrolled inflammatory response, mediated primarily by LPS. Cholesterol transport plays an important role in the host response to LPS, as LPS is neutralized by lipoproteins and adrenal cholesterol uptake is required for antiinflammatory glucocorticoid synthesis. In this study, we show that scavenger receptor B-I (SR-BI), an HDL receptor that mediates HDL cholesterol ester uptake into cells, is required for the normal antiinflammatory response to LPS-induced endotoxic shock. Despite elevated plasma HDL levels, SR-BI–null mice displayed an uncontrollable inflammatory cytokine response and a markedly higher lethality rate than control mice in response to LPS. In addition, …

Role Of Reactive Oxygen Species Peroxynitrite In Traumatic Spinal Cord Injury, Yiqin Xiong

University of Kentucky Doctoral Dissertations

Peroxynitrite (PN, ONOO-), formed by nitric oxide radical (^•NO) and superoxide radical (O2^•-), plays an important role in post-traumatic oxidative damage. In the early work, we determined the temporal characteristics of PN-derived oxidative damage in a rat spinal cord injury (SCI) model. Our results showed 3-nitrotyrosine (3-NT), a specific marker for PN, rapidly accumulated at early time points (1 hr, 3 hrs), after when it plateaued and the high level was sustained to 1 week post injury. The co-localization of 3-NT and lipid peroxidation derived-4-HNE observed in immunohistochemistry indicates PN is involved in lipid peroxidative as …

The Underlying Mechanism(S) Of Fasting Induced Neuroprotection After Moderate Traumatic Brain Injury, Laurie Michelle Helene Davis

University of Kentucky Doctoral Dissertations

Traumatic brain injury (TBI) is becoming a national epidemic, as it accounts for 1.5 million cases each year. This disorder affects primarily the young population and elderly. Currently, there is no treatment for TBI, which means that ~2% of the U.S. population is currently living with prolonged neurological damage and dysfunction. Recently, there have been many studies showing that TBI negatively impacts mitochondrial function. It has been proposed that in order to save the cell from destruction mitochondrial function must be preserved. The ketogenic diet, originally designed to mimic fasting physiology, is effective in treating epilepsy. Therefore, we have used …

Selective Regulation Of Cardiomyocyte Signaling By Rgl2, Leah M. Allen

University of Kentucky Doctoral Dissertations

A key cardiovascular signaling molecule involved in both physiologic and pathologic regulation of cardiomyocytes is the small molecular weight G-protein, Ras. Differential effects of Ras are mediated by multiple effector molecules, including the RalGEFs which activate Ral. Studies performed in cardiomyocytes have indicated a role for Ral in cardiac hypertrophic signaling and the RalGEF family member, Rgl2, was shown to specifically interact with Ras in the heart. Therefore, I hypothesized that Rgl2 was an important Ras effector that would regulate cardiomyocyte signaling.

To elucidate the potential importance of Rgl2 in regulating cardiomyocyte signaling, a gain-of-function approach was utilized in which …

Induction Of The Heat Shock Response To Protect Against Polyglutamine Diseases And The Role Of Protein Sumoylation In Laminopathies And Alzheimer's Disease, Yu-Qian Zhang

University of Kentucky Doctoral Dissertations

Heat shock proteins function as molecular chaperones which help protein folding and prevent protein aggregation. My study shows that celastrol, a pharmacological compound capable of up-regulating the levels of heat shock proteins, inhibits cell death and protein aggregation caused by expanded polyglutamine containing protein, and the protective effects of celastrol are dependent on heat shock factor 1. These results suggest the potential of celastrol as a therapeutic agent in the treatment of polyglutamine diseases.

Sumoylation is a protein modification which plays diverse roles in regulating the target proteins. My study shows that lamin A is a target of protein sumoylation, …

Implications For The Hsf2/Prc1 Interaction And Regulation Of Condensin By Phosphorylation During Mitosis, Lynea Alene Murphy

University of Kentucky Doctoral Dissertations

At the beginning of mitosis, chromosomes are condensed and segregated to facilitate correct alignment later in cytokinesis. Condensin is the pentameric enzyme responsible for this DNA compaction and is composed of two structural maintenance of chromosomes (SMC) subunits and three non-SMC subunits. Condensin mutations generate chromosomal abnormalities due to improper segregation, leading to genome instability and eventual malignant transformation of the cell. Cdc2 phosphorylation of the non-SMC subunits, CAP-G, CAP-D2, and CAP-H, has been demonstrated to be important for condensin supercoiling activity and function. While these subunits are thought to be phosphorylated by Cdc2, the exact sites have not yet …

Thermal Sensitivity Of Vagal Pulmonary Sensory Neurons: Role Of Transient Receptor Potential Vanilloid Channels, Dan Ni

University of Kentucky Doctoral Dissertations

Hyperthermia can occur in lungs and airways during both physiological and pathophysiological conditions. A previous study carried out in our laboratory showed that hyperthermia activates and sensitizes vagal bronchopulmonary Cfiber afferents, whether this effect is through a direct action of hyperthermia on sensory nerves is not known. This dissertation study was aimed to investigate the thermal-sensitivity of pulmonary sensory neurons, and the roles of thermalsensitive transient receptor potential vanilloid (TRPV) channels. Whole-cell patch-clamp recordings of neurons isolated from nodose/jugular ganglia were applied in the study. Results of this study showed that hyperthermia directly activates pulmonary sensory neurons, and this effect …

Nitration And Inactivation Of Manganese Superoxide Dismutase Plays A Critical Role In Metabolic Switch, Muthuswamy Anantharaman

University of Kentucky Doctoral Dissertations

Alzheimer’s disease (AD) is a multifactorial, progressive, age-related neurodegenerative disease. Oxidative stress hypothesis is most prevalent and is gaining significant support. Inspite of the progress achieved on oxidative stress related damages in AD brain; the modification occurring on the various cellular antioxidant enzymes antioxidant has not been identified. Tyrosine nitration, a marker for peroxynitrite induced oxidative damage to protein is widespread in AD brain and Manganese superoxide dismutase (MnSOD), primary mitochondrial antioxidant enzyme is prone to peroxynitrite induced nitration and inactivation. Nitration of proteins involved in energy metabolism has been demonstrated in AD brain, which may explain the altered glucose …

Reciprocal Regulation Of Par-4 And Caspase-8 In The Trail Signaling Pathway, Padhma Ranganathan

University of Kentucky Doctoral Dissertations

Par‐4 is a pro‐apoptotic tumor suppressor that is mutated, suppressed or inactivated in cancer. Par‐4 exploits components of the extrinsic pathway to cause apoptosis selectively of cancer cells. This study identified Par‐4 as an essential component of the apoptotic pathway induced by TRAIL, which selectively targets cancer cells. RNA interference‐mediated knockdown of Par‐4 rendered cancer cells unresponsive to TRAIL‐induced apoptosis. Cells with knocked‐down levels of Par‐4 were deficient in the activation of the apoptosis‐initiator caspase‐8 and the apoptosis‐effector caspase‐3 in response to TRAIL. Par‐4 was identified as a critical mediator of membrane translocation of caspase‐8 and the adapter protein FADD. …

Effect Of Chronic Airway Inflammation Induced By Allergen Sensitization On Vagal Bronchopulmonary Sensory Nerves In Rats, Guangfan Zhang

University of Kentucky Doctoral Dissertations

Airway hyperresponsivness (AHR) is one of most prominent pathophysiological features of asthma. Increasing evidence suggests that vagal bronchopulmonary afferents may be involved in the development of AHR. However, the underlying mechanisms are not clear. Therefore, the purpose of this dissertation was to investigate the effect of chronic airway inflammation induced by allergen sensitization on vagal bronchopulmonary afferents. The study was carried out in an animal model of allergic asthma. Brown-Norway rats were sensitized by intraperitoneal Ovalbumin (Ova) and exposed to aerosolized Ova 3 times/week for three weeks. Control rats received the vehicle. In vivo single-fiber recording technique was applied in …

Effects Of Fescue Herbicides Plateau® And Cimarron® On Pregnancy Maintenance In Broodmares And On Alkaloid Concentrations In Endophyte Infected Tall Fescue, Kathleen Scarlett Black

University of Kentucky Master's Theses

Ingestion of endophyte infected (E+) fescue by pregnant mares can cause significant reproductive problems. Plateau® and Cimarron® herbicides suppress fescue while leaving desired forages unharmed. To determine if these herbicides are harmful to pregnant mares, they were allowed to graze pastures treated with Plateau®, Cimarron®, or vehicle carrier. Pregnancies were monitored via ultrasonography, blood chemistry, and hematology. Of the components measured only creatinine differed among treatments over time (P=0.0003) and that increase was only significant in one of four studies.

Two additional experiments were conducted to determine the effect of the herbicides on alkaloids within E+ fescue. A greenhouse experiment …

Obesity, Hypertension, And Mental Health Evaluation In Adolescents: A Comprehensive Approach, Stefan G. Kiessling, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The global epidemic of childhood and adolescent obesity in developing and developed countries has become a major public health concern. Given the relation between obesity and hypertension as documented in several landmark studies, it is no surprise that as the prevalence of obesity has increased in the pediatric population, the rates of hypertension have also increased substantially. Hypertension is one of the most important risk factors for cardiovascular diseases and stroke; therefore, evaluation and initiation of appropriate treatment are extremely important in the pediatric population. Evaluation for secondary causes of hypertension, including renovascular, renoparenchymal, and endocrine disease is the approach …