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Non-Alcoholic Fatty Liver Disease: The Bile Acid-Activated Farnesoid X Receptor As An Emerging Treatment Target, Michael Fuchs

Internal Medicine Publications

Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. It may progress to liver cirrhosis and liver cancer and is poised to represent the most common indication for liver transplantation in the near future. The pathogenesis of NAFLD is multifactorial and not fully understood, but it represents an insulin resistance state characterized by a cluster of cardiovascular risk factors including obesity, dyslipidemia, hyperglycemia, and hypertension. Importantly, NAFLD also has evolved as independent risk factor for cardiovascular disease. Unfortunately thus far no established treatment does exist for NAFLD. The bile acid-activated nuclear farnesoid X receptor …

Posttransplant Metabolic Syndrome, M. Shadab Siddiqui, Richard K. Sterling

Internal Medicine Publications

Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44–58%. The main …

Inflammation, Coagulation And Cardiovascular Disease In Hiv-Infected Individuals, Daniel A. Duprez, Jacqueline Neuhaus, Lewis H. Kuller, Russell Tracy, Waldo Belloso, Stephane De Wit, Fraser Drummond, H. Clifford Lane, Bruno Ledergerber, Jens Lundgren, Daniel Nixon, Nicholas I. Paton, Ronald J. Prineas

Internal Medicine Publications

Background

The SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral suppression [VS]) as a strategy to reduce toxicities, including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors.

Methods

A blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI …

Metabolomic Profiling To Identify Predictors Of Response To Vitamin E For Non-Alcoholic Steatohepatitis (Nash), Jianfeng Cheng, Andrew Joyce, Katherine Yates, Bradley Aouizerat, Arun J. Sanyal

Internal Medicine Publications

Vitamin E was recently shown to improve hepatic histology in a randomized controlled trial of pioglitazone or vitamin E for nonalcoholic steatohepatitis (PIVENS). The current study utilized samples collected in the PIVENS trial to identify: (1) baseline metabolomic profiles that could identify who would respond to vitamin E treatment and (2) end of treatment metabolomic profiles reflective of histologic improvement. A comprehensive analysis of metabolomics profiles (n = 547) quantified by mass spectrometry was performed in vitamin E responders (n = 16), vitamin E non-responders (n = 15), and placebo responders (n = 15). At baseline, phenyl-propionic acid (Odds ratio: …

Acrolein Induces Endoplasmic Reticulum Stress And Causes Airspace Enlargement, Yoshiaki Kitaguchi, Laimute Taraseviciene-Stewart, Masayuki Hanaoka, Ramesh Natarajan, Donatas Kraskauskas, Norbert F. Voelkel

Internal Medicine Publications

Background

Given the relative abundance and toxic potential of acrolein in inhaled cigarette smoke, it is surprising how little is known about the pulmonary and systemic effects of acrolein. Here we test the hypothesis whether systemic administration of acrolein could cause endoplasmic reticulum (ER) stress, and lung cell apoptosis, leading to the enlargement of the alveolar air spaces in rats.

Methods

Acute and chronic effects of intraperitoneally administered acrolein were tested. Mean alveolar airspace area was measured by using light microscopy and imaging system software. TUNEL staining and immunohistochemistry (IHC) for active caspase 3 and Western blot analysis for active …

Copper Deficiency Induced Emphysema Is Associated With Focal Adhesion Kinase Inactivation, Shiro Mizuno, Masanori Yasuo, Harm J. Bogaard, Donatas Kraskauskas, Aysar A. Alhussini, Jose Gomez-Arroyo, Daniela Farkas, Laszlo Farkas, Norbert F. Voelkel

Internal Medicine Publications

Background

Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1α) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein cross-linking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK).

Methodology

To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the …

From Cox-2 Inhibitor Nimesulide To Potent Anti-Cancer Agent: Synthesis, In Vitro, In Vivo And Pharmacokinetic Evaluation, Bo Zhong, Xiaohan Cai, Snigdha Chennamaneni, Xin Yi, Lili Liu, John J. Pink, Afshin Dowlati, Yan Xu, Aimin Zhou, Bin Su

Chemistry Faculty Publications

Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure–function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC50s around 100 nM–200 nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC50s around 100 nM–500 nM. …

Women In Engineering; A Phenomenological Analysis Of Sociocultural Contextual Meaning Of Gender Roles, Pamela C. Charity-Leeke

ETD Archive

The twenty-first century presents many new challenges in career development and choices in the workforce for men and women. Currently, women comprise nearly half of the United States labor force. United States women are employed in various career areas, ranging from the traditional careers for women, such as education and secretarial, to their growing numbers in business, law, and medicine (U.S. Dept. of Labor, Bureau of Labor Statistics, 2010). As technology becomes the driving force of the economy, it has become essential that science, technology, engineering, and mathematics are areas that more U.S. citizens should pursue. Although engineering is a …

Characterization Of Pharmaceutical Materials By Thermal And Analytical Methods, Manik Pavan Kumar Maheswaram

ETD Archive

No abstract provided.

Biofeedback-Assisted Stress Management Training To Reverse Myocardial Remodeling In Patients With End-Stage Heart Failure, Dana Lynn Schneeberger

ETD Archive

Heart failure is a progressive disease in which the heart is no longer able to pump sufficient amounts of blood to the body. Over six million Americans currently suffer from heart failure, and although pharmacological and surgical therapies continue to improve, about 50 of people with heart failure still die within five years of diagnosis.As the human heart fails, many structural, cellular and molecular alterations occur that contribute to the decrease in heart function. It has been well-established that some of these alterations are the result of sympathetic nervous system hyperactivation, and decreasing sympathetic input with a beta blocker or …

Factors Associated With Educational Mobility;Voices Of Highly Transient Elementary Students, Rebecca Anne Vaslavsky

ETD Archive

Student mobility - students changing schools for reasons other than being promoted to the next school level - is often correlated with negative academic, social and emotional consequences (Sanderson, 2004). Reporting transient students' voices and their experiences in the early grades is crucial to providing educators and other school personnel with highly valuable qualitative data of the struggles and coping strategies of these students that they can then use to craft prevention and intervention strategies. This study describes the experiences of highly mobile, urban elementary school students and provides educational professionals with an in-depth view of mobile students' experiences. Using …

The Relationship Between Ohio Schools' Teacher Quality Indicators And Equity In Third Grade Reading Achievement, Jennifer M. Dohy

ETD Archive

The purpose of this study was to identify teacher quality variables that can predict school equity in the third grade reading passage rate at the school building level. In the present study, the operational definition of equity is the difference (or gap) in passage rates between those who may struggle academically in reading and their respective peers. Teacher quality is represented by the percentage of teachers with a Master's degree, percentage of teachers who are properly certified, average teacher attendance rates, and average years of teaching experience.A multiple linear regression model was used to determine the extent to which teacher …

The After Effects Of Colonialism In The Postmodern Era: Competing Narratives And Celebrating The Local In Michael Ondaatje's Anil's Ghost, Priyanthan A. Pillainayagam

ETD Archive

Through the utilization of Jean-Francois Lyotard's views on the Postmodern condition, this paper highlights the failure of metanarratives to accurately convince, as well as convey information and understanding in a postmodern society. This is due in part to what Lyotard believes is an increasing skepticism towards the grand totalizing nature of metanarratives and their reliance on some form of universal truth. In order to reverse the overarching effect of the metanarrative, its all-encompassing nature, and its power to legitimize illegitimate versions of institutionalized truths one must focus on what Lyotard describes as "petit recits" or "little stories". This theoretical framework …

Controlled Delivery Of Tgf-Ss1 From Plga Nanoparticles, Pratik K. Vaidya

ETD Archive

Abdominal aortic aneurysms (AAAs) typically manifest as localized wall weakening and dilation of the infrarenal aorta, which grows gradually, and ultimately leads to fatal rupture. It is caused due to overexpression of proteolytic enzymes (matrix metalloproteases or MMPs) resulting into disruption of tissue structure, especially elastic matrix, which cannot be regenerated by adult vascular cells. On account of post-operative complications associated with their surgical repair, there is a critical need for developing non-surgical strategies for slowing and even regressing AAA growth. Recent studies in our laboratory have demonstrated that 1 ng/mL of transforming growth factor-β1 (TGF-β1) enhances regenerative repair by …

Elastogenic Characterization Of Rat Bm-Msc-Derived Smcs Towards Use In Soft Tissue Engineering, Sahithya Wintrich

ETD Archive

No abstract provided.

The Role Of Verbal Aggression And Humor In Father-Son Relationships And Its Impact On Relational Satisfaction, Paul M. Palisin

ETD Archive

The purpose of this study was the examine the role of verbal aggression and humor within the father and adult son relationship. Specifically, the study investigated the relationship between verbal aggression and humor orientation and how this relationship impacted relational satisfaction within the father and son dyad. A total of 101 father and son pairs were surveyed. The Humor Orientation scale (Booth-Butterfield & Booth-Butterfield, 1991) and the Verbal Aggression Scale (Infante & Wigley, 1986) were used to measure communication traits and a modified version of Quality Marriage Index (Norton, 1983) was used to measure relational satisfaction. Generally, most of the …

Time-Of-Day Effects On Younger And Older Adult Executive Functioning, Carly E. Violand

ETD Archive

The most recent time-of-day (TOD) body of research has explored how TOD effects can influence certain cognitive domains such as semantic memory, episodic memory, processing speed, and executive functioning (Allen et al., 2008). Research by Horne and Ostberg (1976) has shown how differences in age can be associated with a preference for a certain TOD (i.e., morning or afternoon). Seventy-five percent of adults 65 years or older tend to prefer the morning, whereas fewer than 10 of younger adults tend to prefer the afternoon (Horne & Ostberg, 1976 West et al., 2002). Research by Allen and colleagues (2008) has shown …

Implementing The Dit-Achiev Model: A Carlingford Case Study, Kevin Griffin, Sheila Flanagan, Jane Fitzgerald

Other resources

No abstract provided.

Variants Located Upstream Of Chrnb4 On Chromosome 15q25.1 Are Associated With Age At Onset Of Daily Smoking And Habitual Smoking, Manav Kapoor, Jen-Chyong Wang, Sarah Bertelsen, Kathy Bucholz, John P. Budde, Anthony Hinrichs, Arpana Agrawal, Andrew Brooks, David Chorlian, Danielle Dick, Victor Hesselbrock, Tatiana Foroud, John Kramer, Sammuel Kuperman, Niklas Manz, John Numberger Jr, Bernice Porjesz, John Rice, Jay Tischfield, Xiaoling Xuei, Marc Schuckit, Haward J. Edenberg, Laura J. Bierut, Alison M. Goate

Psychiatry Publications

Several genome-wide association and candidate gene studies have linked chromosome 15q24–q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking theCHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were …

Adenovirus-36 Is Associated With Obesity In Children And Adults In Sweden As Determined By Rapid Elisa, Malin Almgren, Richard Atkinson, Jia He, Agenta Hilding, Emilia Hagman, Alicia Wolk, Anders Thorell, Claude Marcus, Erik Naslund, Claes-Goren Ostenson, Martin Schalling, Catherina Lavebratt

Pathology Publications

Background

Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals.

Principal Findings

Using …

Fracture Detection In Traumatic Pelvic Ct Images, Jie Wu, Pavani Davuluri, Kevin R. Ward, Charles Cockrell, Rosalyn H. Hargraves, Kayvan Najarian

Computer Science Publications

Fracture detection in pelvic bones is vital for patient diagnostic decisions and treatment planning in traumatic pelvic injuries. Manual detection of bone fracture from computed tomography (CT) images is very challenging due to low resolution of the images and the complex pelvic structures. Automated fracture detection from segmented bones can significantly help physicians analyze pelvic CT images and detect the severity of injuries in a very short period. This paper presents an automated hierarchical algorithm for bone fracture detection in pelvic CT scans using adaptive windowing, boundary tracing, and wavelet transform while incorporating anatomical information. Fracture detection is performed on …

An Automated Optimal Engagement And Attention Detection System Using Electrocardiogram, Ashwin Belle, Rosalyn H. Hargraves, Kayvan Najarian

Computer Science Publications

This research proposes to develop a monitoring system which uses Electrocardiograph (ECG) as a fundamental physiological signal, to analyze and predict the presence or lack of cognitive attention in individuals during a task execution. The primary focus of this study is to identify the correlation between fluctuating level of attention and its implications on the cardiac rhythm recorded in the ECG. Furthermore, Electroencephalograph (EEG) signals are also analyzed and classified for use as a benchmark for comparison with ECG analysis. Several advanced signal processing techniques have been implemented and investigated to derive multiple clandestine and informative features from both these …

Cardiorespiratory Fitness, Alcohol Intake, And Metabolic Syndrome Incidence In Men, Kerem Shuval, Carrie E. Finley, Karen G. Chartier, Bijal A. Balasubramanian, Kelley Pettee Gabriel, Carolyn E. Barlow

Social Work Publications

Purpose

To prospectively examine the independent and joint effects of alcohol consumption and cardiorespiratory fitness on the incidence of metabolic syndrome in a cohort of men.

Methods

A prospective examination of 3,411 apparently healthy men at baseline, who came to the Cooper Clinic (Dallas, Texas) for at least 2 preventive visits (1979–2010). Primary exposure variables were cardiorespiratory fitness and alcohol intake; the outcome measure was metabolic syndrome (MetS) and the components thereof. Cox proportional hazard models were computed to assess the relationship between the exposure variables and the incidence of MetS while adjusting for confounders.

Results

Over a mean follow-up …

Lipid Environment Modulates The Development Of Acute Tolerance To Ethanol In Caenorhabditis Elegans, Jill C. Bettinger, Kapo Leung, Mia H. Bolling, Andrew D. Goldsmith, Andrew G. Davies

Pharmacology and Toxicology Publications

The development of tolerance to a drug at the level of the neuron reflects a homeostatic mechanism by which neurons respond to perturbations of their function by external stimuli. Acute functional tolerance (AFT) to ethanol is a fast compensatory response that develops within a single drug session and normalizes neuronal function despite the continued presence of the drug. We performed a genetic screen to identify genes required for the development of acute functional tolerance to ethanol in the nematode C. elegans. We identified mutations affecting multiple genes in a genetic pathway known to regulate levels of triacylglycerols (TAGs) via …

Morphine Decreases Enteric Neuron Excitability Via Inhibition Of Sodium Channels, Tricia H. Smith, John R. Grider, William L. Dewey, Hamid I. Akbarali

Pharmacology and Toxicology Publications

Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a Swiss-Webster mouse myenteric neuron culture and examined their electrophysiological properties by patch-clamp techniques and determined the mechanism for morphine-induced decrease in neuronal excitability. Isolated neurons in culture were confirmed …

Otx But Not Mitf Transcription Factors Are Required For Zebrafish Retinal Pigment Epithelium Development, Brandon M. Lane, James A. Lister

Human and Molecular Genetics Publications

Otx and Mitf transcription factors have been implicated in the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific roles in the development of the RPE have not been fully defined. The role of the three Otx transcription factors (Otx1a, Otx1b, and Otx2) and two Mitf transcription factors (Mitfa and Mitfb) in the development of the zebrafish RPE was explored in these experiments. The loss of Otx activity through morpholino knockdown produced variable eye defects, ranging from delayed RPE pigmentation to severe coloboma, depending on the combination of Otx factors that were targeted. …

Genetic Dissection Of Acute Ethanol Responsive Gene Networks In Prefrontal Cortex: Functional And Mechanistic Implications, Aaron R. Wolen, Charles A. Phillips, Michael A. Langston, Alex H. Putman, Paul J. Vorster, Nathan A. Bruce, Timothy P. York, Robert W. Williams, Michael F. Miles

Human and Molecular Genetics Publications

Background

Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain) across a highly diverse family of 27 isogenic mouse strains (BXD panel) before and after treatment with ethanol.

Results

Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted …

A Duplication Cnv That Conveys Traits Reciprocal To Metabolic Syndrome And Protects Against Diet-Induced Obesity In Mice And Men, Melanie Lacaria, Pradip Saha, Lorraine Potocki, Weimin Bi, Jiong Yan, Santhosh Girirajan, Brooke Burns, Sarah H. Elsea, Katherina Walz, Lawrence Chan, James R. Lupski, Wenli Gu

Human and Molecular Genetics Publications

The functional contribution of CNV to human biology and disease pathophysiology has undergone limited exploration. Recent observations in humans indicate a tentative link between CNV and weight regulation. Smith-Magenis syndrome (SMS), manifesting obesity and hypercholesterolemia, results from a deletion CNV at 17p11.2, but is sometimes due to haploinsufficiency of a single gene, RAI1. The reciprocal duplication in 17p11.2 causes Potocki-Lupski syndrome (PTLS). We previously constructed mouse strains with a deletion,Df(11)17, or duplication, Dp(11)17, of the mouse genomic interval syntenic to the SMS/PTLS region. We demonstrate that Dp(11)17 is obesity-opposing; it conveys a highly penetrant, strain-independent phenotype …

Mineralization Potential Of Electrospun Pdo-Hydroxyapatite-Fibrinogen Blended Scaffolds, Isaac Rodriguez, Parthasarathy A. Madurantakam, Jennifer M. Mccool, Scott A. Sell, Hu Yang, Peter C. Moon, Gary L. Bowlin

Biomedical Engineering Publications

The current bone autograft procedure for cleft palate repair presents several disadvantages such as limited availability, additional invasive surgery, and donor site morbidity. The present preliminary study evaluates the mineralization potential of electrospun polydioxanone:nano-hydroxyapatite : fibrinogen (PDO : nHA : Fg) blended scaffolds in different simulated body fluids (SBF). Scaffolds were fabricated by blending PDO : nHA : Fg in the following percent by weight ratios: 100 : 0 : 0, 50 : 25 : 25, 50 : 50 : 0, 50 : 0 : 50, 0 : 0 : 100, and 0 : 50 : 50. Samples were immersed …

A Preliminary Study On The Potential Of Manuka Honey And Platelet-Rich Plasma In Wound Healing, Scott A. Sell, Patricia Wolfe, Andrew J. Spence, Isaac Rodriguez, Jennifer M. Mccool, Rebecca L. Petrella, Koyal Garg, Jeffery J. Ericksen, Gary L. Bowlin

Biomedical Engineering Publications

Aim. The purpose of this study was to determine the in vitro response of cells critical to the wound healing process in culture media supplemented with a lyophilized preparation rich in growth factors (PRGF) and Manuka honey. Materials and Methods. This study utilized cell culture media supplemented with PRGF, as well as whole Manuka honey and the medical-grade Medihoney (MH), a Manuka honey product. The response of human fibroblasts (hDF), macrophages, and endothelial cells (hPMEC) was evaluated, with respect to cell proliferation, chemotaxis, collagen matrix production, and angiogenic potential, when subjected to culture with media containing PRGF, MH, Manuka honey, …