Inside Exploration, 2016 College Scholars Program
Inside Exploration, Reagan E. Long
Chancellor’s Honors Program Projects
No abstract provided.
Tgf-Β Neutralization Enhances Angii-Induced Aortic Rupture And Aneurysm In Both Thoracic And Abdominal Regions, 2016 University of Kentucky
Tgf-Β Neutralization Enhances Angii-Induced Aortic Rupture And Aneurysm In Both Thoracic And Abdominal Regions, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Lisa A. Cassis, Alan Daugherty
Saha Cardiovascular Research Center Faculty Publications
AngII and TGF-β interact in development of thoracic and abdominal aortic diseases, although there are many facets of this interaction that have not been clearly defined. The aim of the present study was to determine the effects of TGF-β neutralization on AngII induced-aortic pathologies. Male C57BL/6J mice were administered with either a rabbit or mouse TGF-β neutralizing antibody and then infused with AngII. The rabbit TGF-β antibody modestly reduced serum TGF-β concentrations, with no significant enhancements to AngII-induced aneurysm or rupture. Administration of this rabbit TGF-β antibody in mice led to high serum titers against rabbit IgG that may have …
Almond Supplementation Reduces Serum Uric Acid In Coronary Artery Disease Patients: A Randomized Controlled Trial., 2016 Aga Khan University
Almond Supplementation Reduces Serum Uric Acid In Coronary Artery Disease Patients: A Randomized Controlled Trial., Humaira Jamshed, Anwar Gilani, Fateh Ali Tipoo Sultan, Faridah Amin, Jamshed Arslan Arslan, Sumaira Ghani, Madiha Masroor
Department of Biological & Biomedical Sciences
Objective
Elevated serum uric acid (UA), a biomarker of renal insufficiency, is also an independent prognostic marker for morbidity in coronary artery disease (CAD) and poses serious health risks. This study reports the effect of almond consumption on UA in CAD patients.
Study design
A randomized controlled clinical trial was conducted with three groups: no-intervention (NI), Pakistani almonds (PA) or American almonds (AA). Patients were recruited from the Cardiology Clinics, Aga Khan University Hospital. Two follow-ups were scheduled at week-6 and week-12. 150 patients were randomly divided in three groups (50 per group). NI was not given almonds, whereas the …
Novel Bone-Targeting Agent For Enhanced Delivery Of Vancomycin To Bone, 2016 University of Arkansas for Medical Sciences
Novel Bone-Targeting Agent For Enhanced Delivery Of Vancomycin To Bone, Zaineb A. F. Albayati, Manjula Sunkara, Suzannah M. Schmidt-Malan, Melissa J. Karau, Andrew J. Morris, James M. Steckelberg, Robin Patel, Philip J. Breen, Mark S. Smeltzer, K. Grant Taylor, Kevyn E. Merten, William M. Pierce, Peter A. Crooks
Saha Cardiovascular Research Center Faculty Publications
We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome.
Gene Expression Microarray Data From Human Microvascular Endothelial Cells Supplemented With A Low Concentration Of Niacin, 2016 Western University
Gene Expression Microarray Data From Human Microvascular Endothelial Cells Supplemented With A Low Concentration Of Niacin, Nica M. Borradaile, Jennifer M. Hughes-Large
Physiology and Pharmacology Publications
The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors [1]. Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA) values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, …
Elevated Transpulmonary Gradient And Cardiac Magnetic Resonance-Derived Right Ventricular Remodeling Predict Poor Outcomes In Sickle Cell Disease, 2016 Lung and Blood Institute
Elevated Transpulmonary Gradient And Cardiac Magnetic Resonance-Derived Right Ventricular Remodeling Predict Poor Outcomes In Sickle Cell Disease, Kim-Lien Nguyen, Xin Tian, Shoaib Alam, Alem Mehari, Steve W. Leung, Catherine Seamon, Darlene Allen, Caterina P. Minniti, Vandana Sachdev, Andrew E. Arai, Gregory J. Kato
Saha Cardiovascular Research Center Faculty Publications
No abstract provided.
The Protective Role Of Mlcp-Mediated Erm Dephosphorylation In Endotoxin-Induced Lung Injury In Vitro And In Vivo, 2016 Old Dominion University
The Protective Role Of Mlcp-Mediated Erm Dephosphorylation In Endotoxin-Induced Lung Injury In Vitro And In Vivo, Anita Kovacs-Kasa, Boris A. Gorshkov, Kyung-Mi Kim, Sanjiv Kumar, Stephen M. Black, David J. Fulton, Christiana Dimitropoulou, John D. Catravas, Alexander D. Verin
Bioelectrics Publications
The goal of this study was to investigate the role of MLC phosphatase (MLCP) in a LPS model of acute lung injury (ALI). We demonstrate that ectopic expression of a constitutively-active (C/A) MLCP regulatory subunit (MYPT1) attenuates the ability of LPS to increase endothelial (EC) permeability. Down-regulation of MYPT1 exacerbates LPS-induced expression of ICAM1 suggesting an anti-inflammatory role of MLCP. To determine whether MLCP contributes to LPS-induced ALI in vivo, we utilized a nanoparticle DNA delivery method to specifically target lung EC. Expression of a C/A MYPT1 reduced LPS-induced lung inflammation and vascular permeability. Further, increased expression of the …
Towards 3d In Vitro Models For The Study Of Cardiovascular Tissues And Disease, 2016 Technological University Dublin
Towards 3d In Vitro Models For The Study Of Cardiovascular Tissues And Disease, Claire M. Brougham, Alan J. Ryan, Carolina D. Garciarena, Steve W. Kerrigan, Fergal J. O'Brien
Articles
The field of tissue engineering is developing biomimetic biomaterial scaffolds which are showing increasing therapeutic potential for the repair of cardiovascular tissues. However, a major opportunity exists to use them as 3D in vitro models for the study of cardiovascular tissues and disease in addition to drug development and testing. These in vitro models can span the gap between 2D culture and in vivo testing thus reducing cost, time and the ethical burden of current approaches. This review outlines the progress to date and requirements for the development of ideal in vitro 3D models for blood vessels, heart valves and …
Hsp90 Inhibition Suppresses Nf-Κb Transcriptional Activation Via Sirt-2 In Human Lung Microvascular Endothelial Cells, 2016 Old Dominion University
Hsp90 Inhibition Suppresses Nf-Κb Transcriptional Activation Via Sirt-2 In Human Lung Microvascular Endothelial Cells, Gagan S. Thangjam, Charalampos Birmpas, Nektarios Barabutis, Betsy W. Gregory, Mary Ann Clemens, Joseph R. Newton, David Fulton, John D. Catravas
Bioelectrics Publications
The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a “transcriptional block,” which is reversed by either inhibition or downregulation …
Field Testing Adolescent Females For Cardiovascular Disease Risk, 2015 University of Dayton
Field Testing Adolescent Females For Cardiovascular Disease Risk, C. Brahler, Wesley Stephens, Betsy Donahoe Fillmore
C. Jayne Brahler
Over-fatness and poor cardiovascular (CV) fitness are well-documented risk factors for cardiovascular disease (CVD) in adults, but less is known about their association with disease risk in adolescents. This study aimed to determine the relationship between anthropometrics, fitness, and CVD risk.
Six anthropometric indicators of body fatness, seven measures of fitness, and seven metabolic and hemodynamic CVD risk factors were measured in a convenience sample of 28 female high school students (15-18 years of age). A tally was made of the number of factors for which each subject was outside the normal reference range (CVD risk).
Correlation analyses were completed …
Interaction Of Alu Polymorphisms And Novel Measures Of Discrimination In Association With Blood Pressure In African Americans Living In Tallahassee, 2015 University of Florida
Interaction Of Alu Polymorphisms And Novel Measures Of Discrimination In Association With Blood Pressure In African Americans Living In Tallahassee, Alexis C. Boulter, Jackyn Quinlan, Aida T. Miró-Herrans, Laurel N. Pearson, Nubiana L. Todd, Clarence C. Gravlee, Connie J. Mulligan
Human Biology Open Access Pre-Prints
African Americans are 40% more likely to be afflicted with hypertension in comparison to non-Hispanic, white Americans, resulting in a 30% higher instance of mortality due to cardiovascular disease. There is debate about the relative contributions of genetic and sociocultural risk factors to the racial disparity in hypertension.
We assayed three Alu insertion polymorphisms located in the angiotensin-1-converting enzyme (ACE), tissue plasminogen activator (PLAT), and with no-lysine kinase 1 (WNK1) genes. We also estimated West African genetic ancestry and developed novel measures of perceived discrimination to create a biocultural model of blood pressure among …
Cardiovascular Regulation And Effects Of Respiratory Motor Training In Patients With Chronic Spinal Cord Injury., 2015 University of Louisville
Cardiovascular Regulation And Effects Of Respiratory Motor Training In Patients With Chronic Spinal Cord Injury., Bonnie Legg Ditterline
Electronic Theses and Dissertations
This dissertation attempts to discover the mechanisms between cardiovascular and respiratory motor control post spinal cord injury (SCI): in normal, non-injured (NI) persons, cardiovascular regulation is dependent upon respiration, but there is nothing that suggests the mechanism for this relationship post-SCI. Thus we hoped to evaluate various aspects of cardiovascular regulation to further illustrate how this relationship is changed or unchanged by SCI. Chapter I describes the anatomy and physiology of the spine, respiratory system, and cardiovascular system in a NI person, and then describes how the function of these systems is changed by SCI. In addition, we describe therapies …
Gadolinium Free Cardiovascular Magnetic Resonance With 2-Point Cine Balanced Steady State Free Precession, 2015 University of Kentucky
Gadolinium Free Cardiovascular Magnetic Resonance With 2-Point Cine Balanced Steady State Free Precession, Tori A. Stromp, Steve W. Leung, Kristin N Andres, Linyuan Jing, Brandon K. Fornwalt, Richard Charnigo, Vincent L. Sorrell, Moriel H. Vandsburger
Saha Cardiovascular Research Center Faculty Publications
BACKGROUND: Cardiovascular magnetic resonance (CMR) of ventricular structure and function is widely performed using cine balanced steady state free precession (bSSFP) MRI. The bSSFP signal of myocardium is weighted by magnetization transfer (MT) and T1/T2-relaxation times. In edematous and fibrotic tissues, increased T2 and reduced MT lead to increased signal intensity on images acquired with high excitation flip angles. We hypothesized that acquisition of two differentially MT-weighted bSSFP images (termed 2-point bSSFP) can identify tissue that would enhance with gadolinium similar to standard of care late gadolinium enhancement (LGE).
METHODS: Cine bSSFP images (flip angles of 5° and …
Tobramycin-Treated Pseudomonas Aeruginosa Pa14 Enhances Streptococcus Constellatus 7155 Biofilm Formation In A Cystic Fibrosis Model System, 2015 Dartmouth College
Tobramycin-Treated Pseudomonas Aeruginosa Pa14 Enhances Streptococcus Constellatus 7155 Biofilm Formation In A Cystic Fibrosis Model System, Katherine E. E. Price, Amanda A. Naimie, Edward F. Griffin, Charles Bay, George A. O'Toole
Dartmouth Scholarship
Cystic fibrosis (CF) is a human genetic disorder which results in a lung environment that is highly conducive to chronic microbial infection. Over the past decade, deep-sequencing studies have demonstrated that the CF lung can harbor a highly diverse polymicrobial community. We expanded our existing in vitro model of Pseudomonas aeruginosa biofilm formation on CF-derived airway cells to include this broader set of CF airway colonizers to investigate their contributions to CF lung disease, particularly as they relate to the antibiotic response of the population. Using this system, we identified an interspecies interaction between P. aeruginosa, a bacterium associated with …
Hyperpolarized 129xe Magnetic Resonance Imaging Of Radiation-Induced Lung Injury, 2015 The University of Western Ontario
Hyperpolarized 129xe Magnetic Resonance Imaging Of Radiation-Induced Lung Injury, Ozkan Doganay
Electronic Thesis and Dissertation Repository
Lung cancer is the largest contributor to cancer-related mortality worldwide. Only 20% of stage III non-small cell lung cancer patients survive after 5-years post radiation therapy (RT). Although RT is an important treatment modality for lung cancer, it is limited by Radiation-Induced Lung Injury (RILI). RILI develops in two phases: (i) the early phase (days-weeks) referred to radiation pneumonitis (RP), and (ii) the late phase (months). There is a strong interest in early detection of RP using imaging to improve outcomes of RT for lung cancer. This thesis describes a promising approach based on 129Xe gas as a contrast …
Effects Of Adipocyte Aryl Hydrocarbon Receptor Deficiency On Pcb-Induced Disruption Of Glucose Homeostasis In Lean And Obese Mice, 2015 University of Kentucky
Effects Of Adipocyte Aryl Hydrocarbon Receptor Deficiency On Pcb-Induced Disruption Of Glucose Homeostasis In Lean And Obese Mice, Nicki A. Baker, Robin Shoemaker, Victoria English, Nika Larian, Manjula Sunkara, Andrew J. Morris, Mary Walker, Frederique Yiannikouris, Lisa A. Cassis
Saha Cardiovascular Research Center Faculty Publications
BACKGROUND: Coplanar polychlorinated biphenyls (PCBs) promote adipocyte inflammation and impair glucose homeostasis in lean mice. The diabetes-promoting effects of lipophilic PCBs have been observed only during weight loss in obese mice. The molecular mechanisms linking PCB exposures to impaired glucose metabolism are unclear.
OBJECTIVES: In this study we tested the hypothesis that coplanar PCBs act at adipocyte aryl hydrocarbon receptors (AhRs) to promote adipose inflammation and impair glucose homeostasis in lean mice and in obese mice during weight loss.
METHODS AND RESULTS: PCB-77 administration impaired glucose and insulin tolerance in LF (low fat diet)-fed control (AhRfl/fl) mice …
Lipin1 Regulates Skeletal Muscle Differentiation Through Extracellular Signal-Regulated Kinase (Erk) Activation And Cyclin D Complex-Regulated Cell Cycle Withdrawal, 2015 University of Kentucky
Lipin1 Regulates Skeletal Muscle Differentiation Through Extracellular Signal-Regulated Kinase (Erk) Activation And Cyclin D Complex-Regulated Cell Cycle Withdrawal, Weihua Jiang, Jing Zhu, Xun Zhuang, Xiping Zhang, Tao Luo, Karyn Esser, Hongmei Ren
Saha Cardiovascular Research Center Faculty Publications
Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated …
Left Ventricular Mechanical Dysfunction In Diet-Induced Obese Mice Is Exacerbated During Inotropic Stress: A Cine Dense Cardiovascular Magnetic Resonance Study, 2015 University of Kentucky
Left Ventricular Mechanical Dysfunction In Diet-Induced Obese Mice Is Exacerbated During Inotropic Stress: A Cine Dense Cardiovascular Magnetic Resonance Study, Christopher M. Haggerty, Andrea C. Mattingly, Sage P. Kramer, Cassi M. Binkley, Linyuan Jing, Jonathan D. Suever, David K. Powell, Richard J. Charnigo, Frederick H. Epstein, Brandon K. Fornwalt
Saha Cardiovascular Research Center Faculty Publications
BACKGROUND: Obesity is a risk factor for cardiovascular disease. There is evidence of impaired left ventricular (LV) function associated with obesity, which may relate to cardiovascular mortality, but some studies have reported no dysfunction. Ventricular function data are generally acquired under resting conditions, which could mask subtle differences and potentially contribute to these contradictory findings. Furthermore, abnormal ventricular mechanics (strains, strain rates, and torsion) may manifest prior to global changes in cardiac function (i.e., ejection fraction) and may therefore represent more sensitive markers of cardiovascular disease. This study evaluated LV mechanics under both resting and stress conditions with the hypothesis …
Atrial Fibrillation Promotion By Intermittent Hypoxia In The Rat, 2015 The University of Western Ontario
Atrial Fibrillation Promotion By Intermittent Hypoxia In The Rat, Sara Bober
Electronic Thesis and Dissertation Repository
Obstructive sleep apnea (OSA) is a significant risk factor for developing atrial fibrillation (AF) in clinical populations, but the underlying mechanisms are unknown. Intermittent hypoxia (IH), as elicited by nocturnal airway obstructive events in OSA patients, has been implicated as the mediator of OSA-related cardiovascular outcomes. However, the role of IH in OSA-related atrial arrhythmogenesis has not been reported. For the first time, this thesis demonstrates AF promotion in a rodent model of OSA using IH to mimic hypoxic events, and investigates the underlying vulnerable substrates of induced AF. Rats exposed to IH for 7 days had significantly enhanced AF …
The Kinetics Of Cystatin C: A Marker For Dialysis Adequacy, 2015 The University of Western Ontario
The Kinetics Of Cystatin C: A Marker For Dialysis Adequacy, Huang S. Shih-Han
Electronic Thesis and Dissertation Repository
When 90% or more of native kidney function is lost, renal replacement therapy must be initiated to sustain life. Renal transplantation is the preferred method, but availability is limited. The ideal dialysis prescription remains elusive. Small molecular weight molecules (such as urea and creatinine) have been used as markers of both kidney (native and transplant) and dialysis toxin clearance (function), but there are pitfalls in using these markers to assess total ‘renal’ dose (kidney plus dialysis). Body weight, gender and other factors also affect the concentrations of these small molecules, but not cystatin C. Furthermore, cystatin C has been shown …