Medicine and Health Sciences Commons^™

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay

Physiology Faculty Publications

AIMS AND HYPOTHESIS: Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.

METHODS: Gem-deficient mice were generated and their metabolic phenotype characterised by in …

Role Of Nsmase-3/Cermide Signaling In Muscle Atrophy, Zaheen Rabbani

Kaleidoscope

No abstract provided.

Hiv-1 Tat Triggers Nuclear Localization Of Zo-1 Via Rho Signaling And Camp Response Element-Binding Protein Activation, Yu Zhong, Bei Zhang, Sung Yong Eum, Michal Toborek

Neurosurgery Faculty Publications

The human immunodeficiency virus (HIV)-specific protein trans-activator of transcription (Tat) can contribute to the dysfunction of brain endothelial cells and HIV trafficking into the brain by disrupting tight junction (TJ) integrity at the blood–brain barrier (BBB) level. Specific TJ proteins, such as zonula occludens (ZO) proteins, localize not only at the cell–cell borders but are also present in the nuclei. The objective of the present study was to evaluate the mechanisms and significance of Tat-induced nuclear localization of ZO-1. Treatment of a brain endothelial cell line (hCMEC/D3 cells) with Tat resulted in a decrease in total levels of ZO-1 but …

Contraception In Adolescents, Donald E. Greydanus, Carolyn M. Lentzsch-Parcells, Hatim A. Omar

Pediatrics Faculty Publications

The age of adolescence is the time when most adolescents in the world begin to be sexually active with resultant millions of pregnancies and sexually transmitted diseases (STDs). This chapter considers methods of contraception for these adolescents, including oral contraceptives, transdermal contraception, minipills, intra-vaginal ring, injectable contraception, intrauterine devices (IUDs), barrier contraceptives, implants, and others. It is important for clinicians caring for sexually active youth to provide information regarding contraception and appropriate contraceptive prescriptions.

Sexually Transmitted Diseases (Stds), Donald E. Greydanus, Jane Seyler, Hatim A. Omar

Pediatrics Faculty Publications

High rates of unprotected sexual behavior in adolescents result in millions of cases of STDs in the world. This chapter reviews factors inducing high STD rates, specific STDs, and their management based on 2010 U.S. Centers for Disease Control and Prevention (CDC) STD guidelines. Clinicians should screen all their sexually active adolescent patients for STDs and provide preventive education as well as treatment measures.

Adolescence And Contraception, Donald E. Greydanus, Carolyn M. Lentzsch-Parcells, Hatim A. Omar, Colleen B. Dodich

Pediatrics Faculty Publications

The age of adolescence is the time when most adolescents in the world become sexually active with resultant millions of pregnancies and sexually transmitted diseases. This paper considers methods of contraception for these adolescents, including oral contraceptions, transdermal contraception, mini-pills, intravaginal ring, injectable contraception, intrauterine devices, barrier contraceptives, implants, and others. It is important for clinicians caring for sexually active youth to provide information regarding contraception and appropriate contraceptive prescriptions.

Sexually Transmitted Diseases In Adolescence, Donald E. Greydanus, Jane Seyler, Hatim A. Omar, Colleen B. Dodich

Pediatrics Faculty Publications

High rates of unprotected sexual behavior in adolescents result in millions of sexually transmitted diseases (STDs) in the world. This paper reviews factors inducing high STD rates, specific STDs, and their management based on 2010 US Centers for Disease and Prevention (CDC) STD guidelines. Clinicians should screen all their sexually active adolescent patients for STDs and provide preventive education as well as treatment measures.

Physical Activity, Sleep Patterns, And Health Outcomes In University Law Enforcement Officers, Nicole C. Koebke

Theses and Dissertations--Kinesiology and Health Promotion

Research indicates that law enforcement officers (LEOs) have a higher prevalence of developing coronary artery disease (CAD) compared to the general population. Sleep deprivation and physical inactivity have been found to be related to many risk factors for CAD. This cross-sectional study examined the health status and the relationship between sleep and physical activity outcomes versus CAD risk factors among 27 University LEOs. The subjects’ health behaviors, and CAD and metabolic syndrome risk factors were described using basic statistics. Accelerometer derived sleep and physical activity outcomes were correlated to measures of health to identify potential relationships. 33% of LEOs were …

The Cellular Nucleic Acid Binding Protein Regulates The Alzheimer’S Disease Β-Secretase Protein Bace1, Christopher J. Holler

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting the elderly population and is believed to be caused by the overproduction and accumulation of the toxic amyloid beta (Aβ) peptide in the brain. Aβ is produced by two separate enzymatic cleavage events of the larger membrane bound amyloid precursor protein, APP. The first, and rate-limiting, cleavage event is made by beta-secretase, or BACE1, and is thus an attractive therapeutic target. Our lab, as well as many others, has shown that BACE1 protein and activity are increased in late-stage sporadic AD. We have extended these findings to show that BACE1 …

Noninvasive Assessment And Modeling Of Diabetic Cardiovascular Autonomic Neuropathy, Siqi Wang

Theses and Dissertations--Biomedical Engineering

Noninvasive assessment of diabetic cardiovascular autonomic neuropathy (AN): Cardiac and vascular dysfunctions resulting from AN are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure regulation in patients with polyneuropathy, and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. Continuous 12-lead electrocardiography (ECG), blood pressure (BP), respiration, regional blood flow and bio-impedance were recorded from 12 able-bodied subjects (AB), 7 diabetics without (D0), 7 with possible (D1) and 8 with definite polyneuropathy (D2), during 10 minutes supine control, 30 minutes 70-degree head-up tilt and 5 minutes supine recovery. …

Blast-Induced Brain Injury: Influence Of Shockwave Components, Dexter V. Reneer

Theses and Dissertations--Neuroscience

Blast-induced traumatic brain injury (bTBI) has been described as the defining injury of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF). Previously, most blast injury research has focused on the effects of blast on internal, gas filled organs due to their increased susceptibility. However, due to a change in enemy tactics combined with better armor and front-line medical care, bTBI has become one of the most common injuries due to blast. Though there has been a significant amount of research characterizing the brain injury produced by blast, a sound understanding of the contribution of each component of the shockwave to the …

Behavioral Health Change In Appalachian Women With High Cardiovascular Disease Risk Report, Sarah Cole

Kaleidoscope

No abstract provided.

Functional Plasticity Of Central Trpv1 Receptors In Brainstem Dorsal Vagal Complex Circuits Of Streptozotocin-Treated Hyperglycemic Mice, Andrea Zsombok, Muthu D. Bhaskaran, Hong Gao, Andrei V. Derbenev, Bret N. Smith

Physiology Faculty Publications

Emerging data indicate that central neurons participate in diabetic processes by modulating autonomic output from neurons in the dorsal motor nucleus of the vagus (DMV). We tested the hypothesis that synaptic modulation by transient receptor potential vanilloid type 1 (TRPV1) receptors is reduced in the DMV in slices from a murine model of type 1 diabetes. The TRPV1 agonist capsaicin robustly enhanced glutamate release onto DMV neurons by acting at preterminal receptors in slices from intact mice, but failed to do so in slices from diabetic mice. TRPV1 receptor protein expression in the vagal complex was unaltered. Brief insulin preapplication …

No Significant Change In Sexual Behavior In Association With Human Papilloma Virus Vaccination In Young Girls, Wafa R.R. Al Romaih, Archana Srinivas, Said Shahtahmasebi, Hatim A. Omar

Pediatrics Faculty Publications

The first human Papilloma virus (HPV) vaccine was approved in the United States in 2006 with the potential to reduce cervical cancer and genital warts. Since then, its efficacy in preventing HPV-related cancers in both males and females has been promising. Despite CDC recommendations, opponents of the vaccine assert that vaccinating pre-adolescents and adolescents will increase their sexual activity, as well as overtly condone risky sexual behavior. We analyzed clinic data of 499 adolescents with a mean age of 16 years to explore whether vaccination led to change in sexual behavior after one year. Our results showed no statistically significant …

The Relationship Between Obesity And Skin And Soft Tissue Infections, Juliana Swiney

MPA/MPP/MPFM Capstone Projects

The Problem:

It is well known that our country is experiencing an obesity epidemic: 33.9% of all adults are obese (BMI>30) and 67% of adults are either overweight or obese (BMI>25). Obesity is a risk factor for several serious disease states such as, diabetes, stroke, hypertension, heart disease and some types of cancer. It also has a less well defined relationship with skin and soft tissue infections.

Although it is known that excessive weight increases the opportunity for harmful skin conditions, this relationship has not been as well studied. Some of the mechanisms that predispose obese people to …

Ethnic Disparities In Cervical Cancer Survival Among Texas Women, Ann L. Coker, Christopher P. Desimone, Katherine S. Eggleston, Arica L. White, Melanie Williams

CRVAW Faculty Journal Articles

Objective: The aim of this work was to determine whether minority women are more likely to die of cervical cancer. A population-based cohort study was performed using Texas Cancer Registry (TCR) data from 1998 to 2002.

Methods: A total of 5,166 women with cervical cancer were identified during 1998–2002 through the TCR. Measures of socioeconomic status (SES) and urbanization were created using census block group-level data. Multilevel logistic regression was used to calculate the odds of dying from cervical cancer by race, and Cox proportional hazards modeling was used for cervical cancer-specific survival analysis.

Results: After adjusting for age, SES, …

Hpv Vaccine Acceptance Among Latina Mothers By Hpv Status, Maureen Sanderson, Ann L. Coker, Katherine S. Eggleston, Maria E. Fernandez, Concepcion D. Arrastia, Mary Kay Fadden

CRVAW Faculty Journal Articles

Objective: We investigated whether Latina mothers who were and were not human papillomavirus (HPV) positive differed in their knowledge and acceptance of the HPV vaccine for their children.

Methods: We conducted a cross–sectional survey among women aged 18–64 years between April 2007 and April 2008. Data collectors conducted in-person interviews in community clinics with 215 HPV-negative women and 190 HPV-positive women (with respective response rates of 64% and 84%). Most (83%) HPV-positive women were recruited at dysplasia clinics. Although no HPV-negative women were recruited at dysplasia clinics, they were recruited at other low-income public and private clinics.

Results: After adjustment …

Long-Term Survival After Radical Prostatectomy Compared To Other Treatments In Older Men With Local Or Regional Prostate Cancer, Liqian Liu, Ann L. Coker, Xianglin L. Du, Janice N. Cormier, Charles E. Ford, Shenying Fang

CRVAW Faculty Journal Articles

Background

This study aimed to address long-term survival in a large population-based cohort of men with prostate cancer receiving radical prostatectomy compared to other treatments.

Methods

We studied 5,845 patients diagnosed with local/regional stage prostate cancer at age 65–74 in 1992 with comorbidity score

Results

Of 5,845 patients, 10-year all-cause survival rates were the highest for patients receiving radical prostatectomy (81.0%; 95% CI: 79.4–82.4%), followed by radical prostatectomy in combination with radiotherapy (67.6%; 62.0–72.5%), radiotherapy (60.5%; 58.3–62.6%), and were the lowest for watchful-waiting (50.7%; 47.5–53.8%). A similar pattern was found for 10-year prostate cancer-specific survivals by treatments. After adjusting for …

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 …

Transcriptional Control Of Vascular Smooth Muscle Cell Proliferation By Peroxisome Proliferator-Activated Receptor-Γ: Therapeutic Implications For Cardiovascular Diseases, Florence Gizard, Dennis Bruemmer

Internal Medicine Faculty Publications

Proliferation of vascular smooth muscle cells (SMCs) is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR) gamma is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD), used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARgamma is prominently upregulated during neointima formation …

Stress, Coping, Social Support, And Prostate Cancer Risk Among Older African American And Caucasian Men, Ann L. Coker, Maureen Sanderson, Gary L. Ellison, Mary Kay Fadden

CRVAW Faculty Journal Articles

Objectives: While psychosocial stress and high effort coping have been associated with reduced immune function, no epidemiologic study has addressed psychological stress and risk of prostate cancer. The purpose of this analysis was to investigate the association between stress, coping, social support, and risk of prostate cancer among older men (age 65–79 years). Design: Population-based case-control study in South Carolina.

Participants: Cases were 400 incident, histologically confirmed prostate cancer cases identified through the South Carolina Central Cancer Registry between 1999 and 2001 (70.6% response rate). Controls were 385 men identified through the 1999 Health Care Financing Administration Medicare beneficiary file …

Racial Disparity And Socioeconomic Status In Association With Survival In Older Men With Local/Regional Stage Prostate Cancer: Findings From A Large Community-Based Cohort, Xianglin L. Du, Shenying Fang, Ann L. Coker, Corinne Aragaki, Janice N. Cormier, Yan Xing, Beverly J. Gor, Wenyaw Chan

CRVAW Faculty Journal Articles

BACKGROUND

Few studies have examined the outcomes for Hispanic men with prostate carcinoma and incorporated socioeconomic factors in association with race/ethnicity in affecting survival, adjusting for factors on cancer stage, grade, comorbidity, and treatment.

METHODS

We studied a population-based cohort of 61,228 men diagnosed with local or regional stage prostate carcinoma at age 65 years or older between 1992 and 1999 in the 11 SEER (Surveillance, Epidemiology, and End Results) areas, identified from the SEER-Medicare linked data with up to 11 years of followup.

RESULTS

Low socioeconomic status was significantly associated with decreasing survival in all men with prostate carcinoma. …

A Case-Control Study Of Farming And Prostate Cancer In African-American And Caucasian Men, Tamra E. Meyer, Ann L. Coker, Maureen Sanderson, Elaine Symanski

CRVAW Faculty Journal Articles

Objective: To determine the risk of prostate cancer associated with farming by duration, recency and specific activities among African-Americans and Caucasians.

Methods: This population-based case–control study had information on farming-related activities for 405 incident prostate cancer cases and 392 controls matched for age, race and region in South Carolina, USA, from 1999 to 2001. Cases with histologically confirmed, primary invasive prostate cancer who were aged between 65 and 79 years were ascertained through the South Carolina Central Cancer Registry. Appropriately matched controls were identified from the Health Care Financing Administration Medicare Beneficiary File. Data were collected using computer-assisted telephone interviewing, …

Cervical Cancer Survival By Socioeconomic Status, Race/Ethnicity, And Place Of Residence In Texas, 1995–2001, Katherine S. Eggleston, Ann L. Coker, Melanie Williams, Guillermo Tortolero-Luna, Jeanne B. Martin, Susan R. Tortolero

CRVAW Faculty Journal Articles

Objective: The current study explored whether socioeconomic status (SES), race/ethnicity, and rural residence may be linked to poorer cervical cancer survival by stage at diagnosis.

Methods: Data from 7,237 cervical cancer cases reported to the Texas Cancer Registry from 1995–2001 were used to address the association by stage at diagnosis and cause of death. Zip code-level census data were used to classify residence and to develop a composite variable for SES. Multilevel Cox proportional hazards modeling was used to estimate hazard ratios

(HR) and 95% confidence intervals (CI).

Results: Late stage at diagnosis was a strong predictor …

Psychosocial Stress And Prostate Cancer: A Theoretical Model, Gary L. Ellison, Ann L. Coker, James R. Hebert, Maureen Sanderson, Charmaine D. Royal, Sally P. Weinrich

CRVAW Faculty Journal Articles

African-American men are more likely to develop and die from prostate cancer than are European-American men; yet, factors responsible for the racial disparity in incidence and mortality have not been elucidated. Socioeconomic disadvantage can lead to psychosocial stress and may be linked to negative lifestyle behaviors. Regardless of socioeconomic position, African-American men routinely experience racism-induced stress. We propose a theoretical framework for an association between psychosocial stress and prostate cancer. With the context of history and culture, we further propose that psychosocial stress may partially explain the variable incidence of prostate cancer between these diverse groups. Psychosocial stress may negatively …

Hormonal And Barrier Methods Of Contraception, Oncogenic Human Papillomaviruses, And Cervical Squamous Intraepithelial Lesion Development, Ann L. Coker, Laura C. Sanders, Sharon M. Bond, Tsilya Gerasimova, Lucia Pirisi

CRVAW Faculty Journal Articles

We assessed the influence of hormonal (oral, injectable, or levonorgestrel [Norplant, Wyeth-Ayerst, Philadelphia, PA]) and barrier methods of contraception on the risk of cervical squamous intraepithelial lesions (SIL), while adjusting for high-risk (HR) HPV infection. Subjects were women receiving family planning services through the state health department clinics from 1995 to 1998. We selected 60 cases with high-grade cervical/SIL (HSIL) and 316 with low-grade cervical/SIL (LSIL) and controls (427 women with normal cervical cytology) and analyzed cervical DNA for HR-HPV, using Hybrid Capture I (Digene; Gaithersburg, MD).When assessing ever use, duration, recency, latency, and age at first use, neither oral …

Intimate Partner Violence And Cervical Neoplasia, Ann L. Coker, Maureen Sanderson, Mary Kay Fadden, Lucia Pirisi

CRVAW Faculty Journal Articles

Intimate partner violence (IPV) is associated with a range of adverse physical health outcomes, including chronic and infectious diseases. An emerging literature suggests that partner violence and specifically sexual violence may be associated with an increased risk of cervical neoplasia. To assess the risk of preinvasive and invasive cervical cancer in a cross-sectional study of women screened for IPV by type, frequency and duration, 1152 women ages 18–65 were recruited from family practice clinics in 1997–1998. They were screened for IPV during a brief in-clinic interview, and health history and current status were assessed in a follow-up interview. Of 1152 …

Correlates And Consequences Of Early Initiation Of Sexual Intercourse, Ann L. Coker, Donna L. Richter, Robert F. Valois, Robert E. Mckeown, Carol Z. Garrison, Murray L. Vincent

CRVAW Faculty Journal Articles

This cross-sectional analysis of the 1991 CDC Youth Risk Behavior Survey explored factors associated with an early age at first sexual intercourse. Almost 18% of White males, 49% of Black males, 5% of White females and 12% of Black females were sexually active before age 13. Carrying a weapon to school, fighting, and early (< age 13) experimentation with cigarettes and alcohol were associated with early initiation of sexual activity for all four race and gender groupings. Those initiating sexual activity early had greater numbers of partners but were 50% less likely to use condoms regularly and were two-seven times more likely to have been pregnant or caused a pregnancy. Females who initiated sexual activity early were more likely to have had a sexually transmitted disease (STD). Interventions to postpone sexual activity need to be tailored to the ethnic and gender differences observed in these analyses. Interventions must begin before age 13 and should be comprehensive school-based efforts.

Patients As Subjects For Research: Ethical Dilemmas For The Primary Care Clinician-Investigator, Susan F. Slatkoff, Peter Curtis, Ann L. Coker

CRVAW Faculty Journal Articles

Background: Past studies suggested an association between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN). In 1987, University of North Carolina (UNC) Hospitals Family Practice Center clinicians were approached for a control population to study this association. Methods: One hundred fives patients attending the UNC Hospitals Neoplasia Clinic with biopsy-proven CIN 2 or 3 and 268 control patients attending the UNC Family Practice Center for a routine Papanicolaou smear were enrolled in this case-control study. Case and control patients consented to having an additional cervical specimen taken and to being interviewed. The cervical specimens were classified by the Southern blot …