Anatomy Commons^™

Informing The Pathway Of Copd Treatment (Impact) Trial: Fibrinogen Levels Predict Risk Of Moderate Or Severe Exacerbations, Dave Singh, Gerard J. Criner, Mark T. Dransfield, David M. G. Halpin, Meilan K. Han, Peter Lange, Sally Lettis, David A. Lipson, David M. Mannino, Neil Martin, Fernando J. Martinez, Bruce E. Miller, Robert Wise, Chang-Qing Zhu, David Lomas

Preventive Medicine and Environmental Health Faculty Publications

Background: Fibrinogen is the frst qualifed prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated futicasone furoate/umeclidinium/ vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacer‑ bations. This analysis used IMPACT trial data to examine the relationship between fbrinogen levels and exacerbation outcomes in patients with COPD.

Methods: 8094 patients with a fbrinogen assessment at Week 16 were included, baseline fbrinogen data were not measured. Post hoc analyses were performed by fbrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events …

Chromosome Xq23 Is Associated With Lower Atherogenic Lipid Concentrations And Favorable Cardiometabolic Indices, Pradeep Natarajan, Akhil Pampana, Sarah E. Graham, Sanni E. Ruotsalainen, James A. Perry, Paul S. De Vries, Jai G. Broome, James P. Pirruccello, Michael C. Honigberg, Krishna Aragam, Brooke Wolford, Jennifer A. Brody, Lucinda Antonacci-Fulton, Moscati Arden, Stella Aslibekyan, Themistocles L. Assimes, Christie M. Ballantyne, Lawrence F. Bielak, Joshua C. Bis, Brian E. Cade, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10⁻⁷²), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 …

Gold In Practice: Chronic Obstructive Pulmonary Disease Treatment And Management In The Primary Care Setting, Barbara P. Yawn, Matthew L. Mintz, Dennis E. Doherty

Internal Medicine Faculty Publications

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Early detection and appropriate treatment and management of COPD can lower morbidity and perhaps mortality. Clinicians in the primary care setting provide the majority of COPD care and are pivotal in the diagnosis and management of COPD. In this review, we provide an overview of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 report, with a focus on the management of COPD in the primary care setting. We discuss the pathophysiology of COPD; describe COPD risk factors, signs, and symptoms that may facilitate earlier diagnosis …

Accumbens Cholinergic Interneurons Mediate Cue-Induced Nicotine Seeking And Associated Glutamatergic Plasticity, Jonna M. Leyrer-Jackson, Michael Holter, Paula F. Overby, Jason M. Newbern, Michael D. Scofield, M. Foster Olive, Cassandra D. Gipson

Family and Community Medicine Faculty Publications

Nicotine, the primary addictive substance in tobacco, is widely abused. Relapse to cues associated with nicotine results in increased glutamate release within nucleus accumbens core (NAcore), modifying synaptic plasticity of medium spiny neurons (MSNs), which contributes to reinstatement of nicotine seeking. However, the role of cholinergic interneurons (ChIs) within the NAcore in mediating these neurobehavioral processes is unknown. ChIs represent less than 1% of the accumbens neuronal population and are activated during drug seeking and reward-predicting events. Thus, we hypothesized that ChIs may play a significant role in mediating glutamatergic plasticity that underlies nicotine-seeking behavior. Using chemogenetics in transgenic rats …

Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration, Sandeep Saxena

Theses and Dissertations--Biology

Mammalian system consists of stress-sensing molecules that regulates their cellular response against damage, injury and oncogenic stress. During vertebrate regeneration, cells responding to injury re-enter the cell cycle and proliferate to form new tissue. Cell cycle re-entry or arrest is at least partly regulated by cellular senescence which negatively impacts the proliferative pool of cells during regeneration. What remains unclear is whether cells in regenerating systems possess an increased propensity to proliferate and are refractory to signals that induce senescence. My thesis work has focused on how fibroblasts from the ear pinna differentially regulate healing in highly regenerative mammals (e.g., …

Long Qt Syndrome Type 2: Emerging Strategies For Correcting Class 2 Kcnh2 (Herg) Mutations And Identifying New Patients, Makoto Ono, Don E. Burgess, Elizabeth A. Schroder, Claude S. Elayi, Corey L. Anderson, Craig T. January, Bin Sun, Kalyan Immadisetty, Peter M. Kekenes-Huskey, Brian P. Delisle

Physiology Faculty Publications

Significant advances in our understanding of the molecular mechanisms that cause congenital long QT syndrome (LQTS) have been made. A wide variety of experimental approaches, including heterologous expression of mutant ion channel proteins and the use of inducible pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from LQTS patients offer insights into etiology and new therapeutic strategies. This review briefly discusses the major molecular mechanisms underlying LQTS type 2 (LQT2), which is caused by loss-of-function (LOF) mutations in the KCNH2 gene (also known as the human ether-à-go-go-related gene or hERG). Almost half of suspected LQT2-causing mutations are missense mutations, and functional studies …

Individualizing Patient Care During Percutaneous Coronary Intervention To Reduce Operator Risk Adjusted Bleeding Rates: A Pre/Post Interventional Study, Sarah Brown

DNP Projects

OBJECTIVE: It is well documented that the most common problems associated with diagnostic and interventional angiography are major bleeding and vascular complications. While previous research and the American College of Cardiology (ACC) recommend the use of bleeding risk stratification tools, there is little evidence related to the use of bleeding avoidance strategies in the high-risk for bleeding population. This study aims to determine if individualizing access site and anticoagulation strategies based on bleeding risk stratification would positively impact NCDR Risk-Adjusted Bleeding Rates.

METHODS: This was a single-center pilot study utilizing retrospective chart reviews with pre/post design. Data was collected on …

The Late Stage Of Copi Vesicle Fission Requires Shorter Forms Of Phosphatidic Acid And Diacylglycerol, Seung-Yeol Park, Jia-Shu Yang, Zhen Li, Pan Deng, Xiaohong Zhu, David Young, Maria Ericsson, Ruben L. H. Andringa, Adriaan J. Minnaard, Chunmei Zhu, Fei Sun, D. Branch Moody, Andrew J. Morris, Jun Fan, Victor W. Hsu

Internal Medicine Faculty Publications

Studies on vesicle formation by the Coat Protein I (COPI) complex have contributed to a basic understanding of how vesicular transport is initiated. Phosphatidic acid (PA) and diacylglycerol (DAG) have been found previously to be required for the fission stage of COPI vesicle formation. Here, we find that PA with varying lipid geometry can all promote early fission, but only PA with shortened acyl chains promotes late fission. Moreover, diacylglycerol (DAG) acts after PA in late fission, with this role of DAG also requiring shorter acyl chains. Further highlighting the importance of the short-chain lipid geometry for late fission, we …

Modulation Of Osteogenic And Myogenic Differentiation By A Phytoestrogen Formononetin Via P38mapk-Dependent Jak-Stat And Smad-1/5/8 Signaling Pathways In Mouse Myogenic Progenitor Cells, Ilavenil Soundharrajan, Da Hye Kim, Palaniselvam Kuppusamy, Ki Choon Choi

Center for Research on Environmental Disease Faculty Publications

Formononetin (FN), a typical phytoestrogen has attracted substantial attention as a novel agent because of its diverse biological activities including, osteogenic differentiation. However, the molecular mechanisms underlying osteogenic and myogenic differentiation by FN in C2C12 progenitor cells remain unknown. Therefore the objective of the current study was to investigate the action of FN on myogenic and osteogenic differentiation and its impact on signaling pathways in C2C12 cells. FN significantly increased myogenic markers such as Myogenin, myosin heavy chains, and myogenic differentiation 1 (MyoD). In addition, the expression of osteogenic specific genes alkaline phosphatase (ALP), Run-related transcription factor 2(RUNX2), and osteocalcin …

What Lies Beneath? Molecular Evolution During The Radiation Of Caecilian Amphibians, María Torres-Sánchez, David J. Gower, David Alvarez-Ponce, Christopher J. Creevey, Mark Wilkinson, Diego San Mauro

Neuroscience Faculty Publications

Background: Evolution leaves an imprint in species through genetic change. At the molecular level, evolutionary changes can be explored by studying ratios of nucleotide substitutions. The interplay among molecular evolution, derived phenotypes, and ecological ranges can provide insights into adaptive radiations. Caecilians (order Gymnophiona), probably the least known of the major lineages of vertebrates, are limbless tropical amphibians, with adults of most species burrowing in soils (fossoriality). This enigmatic order of amphibians are very distinct phenotypically from other extant amphibians and likely from the ancestor of Lissamphibia, but little to nothing is known about the molecular changes underpinning their radiation. …

Hdac Regulates Transcription At The Outset Of Axolotl Tail Regeneration, S. Randal Voss, Larissa V. Ponomareva, Varun B. Dwaraka, Kaitlin E. Pardue, Nour W. Al Haj Baddar, A. Katherine Rodgers, M. Ryan Woodcock, Qingchao Qiu, Anne Crowner, Dana Blichmann, Shivam Khatri, Jon S. Thorson

Neuroscience Faculty Publications

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited …

Local In Vivo Measures Of Muscle Lipid And Oxygen Consumption Change In Response To Combined Vitamin D Repletion And Aerobic Training In Older Adults, D. Travis Thomas, David M. Schnell, Maja Redzic, Mingjun Zhao, Hideat Abraha, Danielle Jones, Howard Brim, Guoqiang Yu

Health and Clinical Sciences Faculty Publications

Intramyocellular (IMCL), extramyocellular lipid (EMCL), and vitamin D deficiency are associated with muscle metabolic dysfunction. This study compared the change in [IMCL]:[EMCL] following the combined treatment of vitamin D and aerobic training (DAT) compared with vitamin D (D), aerobic training (AT), and control (CTL). Male and female subjects aged 60–80 years with a BMI ranging from 18.5–34.9 and vitamin D status of ≤ 32 ng/mL (25(OH)D) were recruited to randomized, prospective clinical trial double-blinded for supplement with a 2 × 2 factorial design. Cholecalciferol (Vitamin D₃) (10,000 IU × 5 days/week) or placebo was provided for 13 weeks …

Rediscovering The Axolotl As A Model For Thyroid Hormone Dependent Development, Anne Crowner, Shivam Khatri, Dana Blichmann, S. Randal Voss

Neuroscience Faculty Publications

The Mexican axolotl (Ambystoma mexicanum) is an important model organism in biomedical research. Much current attention is focused on the axolotl's amazing ability to regenerate tissues and whole organs after injury. However, not forgotten is the axolotl's equally amazing ability to thwart aspects of tissue maturation and retain juvenile morphology into the adult phase of life. Unlike close tiger salamander relatives that undergo a thyroid hormone regulated metamorphosis, the axolotl does not typically undergo a metamorphosis. Instead, the axolotl exhibits a paedomorphic mode of development that enables a completely aquatic life cycle. The evolution of paedomorphosis allowed axolotls …

Life-Long Reduction In Myomir Expression Does Not Adversely Affect Skeletal Muscle Morphology, Ivan J. Vechetti Jr., Yuan Wen, Thomas Chaillou, Kevin A. Murach, Alexander Alimov, Vandre C. Figueiredo, Maeli Dal-Pai-Silva, John J. Mccarthy

Physiology Faculty Publications

We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for ~22 months following Dicer inactivation to determine …

The Effects Of Huntingtin-Lowering: What Do We Know So Far?, William F. Kaemmerer, Richard C. Grondin

Neuroscience Faculty Publications

Therapies targeting mutant huntingtin DNA, mRNA, and protein have a chance at becoming the first disease-modifying treatments for Huntington’s disease, a fatal inherited neurodegenerative disorder for which only symptom management treatments are available today. This review focuses on evidence addressing several key questions pertinent to huntingtin-lowering, ranging from the functions of wild-type huntingtin (wtHTT) that may be disrupted by huntingtin-lowering treatments through the various ways huntingtin can be lowered, the tolerability of wtHTT-lowering in mice and primates, what has been found in the Ionis Pharmaceutical safety trial of a huntingtin-lowering therapy, and to the question of how much mutant huntingtin …

Human Skeletal Muscle Macrophages Increase Following Cycle Training And Are Associated With Adaptations That May Facilitate Growth, R. Grace Walton, Kate Kosmac, Jyothi Mula, Christopher S. Fry, Bailey D. Peck, Jason S. Groshong, Brian S. Finlin, Beibei Zhu, Philip A. Kern, Charlotte A. Peterson

Center for Muscle Biology Faculty Publications

Skeletal muscle macrophages participate in repair and regeneration following injury. However, their role in physiological adaptations to exercise is unexplored. We determined whether endurance exercise training (EET) alters macrophage content and characteristics in response to resistance exercise (RE), and whether macrophages are associated with other exercise adaptations. Subjects provided vastus lateralis biopsies before and after one bout of RE, after 12 weeks of EET (cycling), and after a final bout of RE. M2 macrophages (CD11b+/CD206+) did not increase with RE, but increased in response to EET (P < 0.01). Increases in M2 macrophages were positively correlated with fiber hypertrophy (r = 0.49) and satellite cells (r = 0.47). M2c macrophages (CD206+/CD163+) also increased following EET (P < 0.001), and were associated with fiber hypertrophy (r = 0.64). Gene expression was quantified using NanoString. Following EET, the change in M2 macrophages was positively associated with changes in HGF, IGF1, and extracellular matrix genes. EET decreased expression of IL6 (P < 0.05), C/EBPβ (P < 0.01), and MuRF (P < 0.05), and increased expression of IL-4 (P < 0.01), TNFα (P < 0.01) and the TWEAK receptor FN14 (P < 0.05). The change in FN14 gene expression was inversely associated with changes in C/EBPβ (r = −0.58) and MuRF (r = −0.46) following EET. In cultured human myotubes, siRNA inhibition of FN14 increased expression of C/EBPβ (P < 0.05) and MuRF (P < 0.05). Our data suggest that macrophages contribute to the muscle response to EET, potentially including modulation of TWEAK-FN14 signaling.

Candidemia Following Ureteric Stent Placement In A Patient With Type 2 Diabetes Treated With Canagliflozin, Rishi Raj, Jon Hendrie, Aasems Jacob, Derick Adams

Internal Medicine Faculty Publications

A 38-year-old female patient with well-controlled type 2 diabetes mellitus treated with canagliflozin underwent ureteral stent placement for obstructive renal calculi. Ten days following ureteroscopy and ureteral stenting, she developed fevers and blood cultures grew Candida glabrata (C. glabrata). The patient was successfully treated with an extended course of broad-spectrum antibiotics and antifungal agents. The clinical presentation of candidemia is indistinguishable from bacteremia resulting in delay in diagnosis and treatment. Candiduria is commonly seen in patients with type 2 diabetes, however it rarely leads to candidemia in an otherwise healthy person following a relatively simple urologic procedure. Sodium-glucose …

Validations Of Apomorphine-Induced Bold Activation Correlations In Hemiparkinsonian Rhesus Macaques, Jorge E. Quintero, Yi Ai, Anders H. Andersen, Peter A. Hardy, Richard Grondin, Zain Guduru, Don M. Gash, Greg A. Gerhardt, Zhiming Zhang

Neuroscience Faculty Publications

Identification of Parkinson's disease at the earliest possible stage of the disease may provide the best opportunity for the use of disease modifying treatments. However, diagnosing the disease during the pre-symptomatic period remains an unmet goal. To that end, we used pharmacological MRI (phMRI) to assess the function of the cortico-basal ganglia circuit in a non-human primate model of dopamine deficiency to determine the possible relationships between phMRI signals with behavioral, neurochemical, and histological measurements. Animals with unilateral treatments with the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), that expressed stable, long-term hemiparkinsonism were challenged with the dopaminergic receptor agonist, apomorphine, and structure-specific phMRI …

Neuroprotective Strategies Following Experimental Traumatic Brain Injury: Lipid Peroxidation-Derived Aldehyde Scavenging And Inhibition Of Mitochondrial Permeability Transition, Jacqueline Renee Kulbe

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) represents a significant health crisis. To date there are no FDA-approved pharmacotherapies available to prevent the neurologic deficits caused by TBI. Following TBI, dysfunctional mitochondria generate reactive oxygen and nitrogen species, initiating lipid peroxidation (LP) and the formation of LP-derived neurotoxic aldehydes, which bind mitochondrial proteins, exacerbating dysfunction and opening of the mitochondrial permeability pore (mPTP), resulting in extrusion of mitochondrial sequestered calcium into the cytosol, and initiating a downstream cascade of calpain activation, spectrin degradation, neurodegeneration and neurologic impairment.

As central mediators of the TBI secondary injury cascade, mitochondria and LP-derived neurotoxic aldehydes make promising …

A Singer’S Stress: Yoga And Meditation Techniques In The Collegiate Voice Studio, Zackery David Morris

Theses and Dissertations--Music

Often neglected in voice study is the understanding that a singer’s instrument lives in his/her body and therefore cannot be packed away like other musical objects. Yoga and mindfulness compliment the belief of a whole body instrument. Data gathered on college campuses report that stress and anxiety are on the rise, thus reinforcing the need for MBSR and yoga as beneficial and proven tools for stress relief. The current state of research in the realm of mental health in colleges merits the study of a cohesive layout of these exercises and their expected outcomes in singing as well as stress …

Patients' Perceptions And Patient-Reported Outcomes In Progressive-Fibrosing Interstitial Lung Diseases, Jeffrey J. Swigris, Kevin K. Brown, Rayid Abdulqawi, Ketan Buch, Daniel F. Dilling, Dirk Koschel, Krishna Thavarajah, Rade Tomic, Yoshikazu Inoue

Internal Medicine Faculty Publications

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be …

Manganese-Enhanced Magnetic Resonance Imaging: Overview And Central Nervous System Applications With A Focus On Neurodegeneration, Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra

Physiology Faculty Publications

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and …

Femoroacetabular Impingement As A Complication Of Acetabular Fracture Fixation, David A. Zuelzer, Christopher B. Hayes, Raymond D. Wright, Stephen T. Duncan

Orthopaedic Surgery and Sports Medicine Faculty Publications

Case

We present the case of a thirteen-year-old female who sustained a posterior wall acetabular fracture dislocation. She underwent urgent closed reduction and subsequent uncomplicated open reduction and internal fixation. Post reduction computed tomography demonstrated a concentrically reduced hip joint with no evidence of femoroacetabular impingement (FAI). She subsequently healed her fracture and returned to running activities; however, one year later presented with aching pain in her thigh. Radiographs demonstrated the development of a large osseous prominence on her anterolateral femoral neck consistent with femoroacetabular impingement. Based on these findings she was evaluated by a hip preservation specialist. She subsequently …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

Rapid And Robust Restoration Of Breathing Long After Spinal Cord Injury, Philippa M. Warren, Stephanie C. Steiger, Thomas E. Dick, Peter M. Macfarlane, Warren J. Alilain, Jerry Silver

Spinal Cord and Brain Injury Research Center Faculty Publications

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess …

Waardenburg Syndrome And Left Persistent Superior Vena Cava, Driss Raissi, Alexander Christie, Kimberly Applegate

Radiology Faculty Publications

Waardenburg syndrome (WS) is a rare genetic disorder secondary to neural crest cell developmental abnormalities. It is predominantly described as an auditory-pigmentary syndrome with diverse patient presentation, typically involving congenital sensorineural hearing loss and pigmentation abnormalities of the skin, hair, and iris. Other developmental abnormalities that may be associated with this syndrome are Hirschsprung's disease and a myriad of cardiovascular congenital defects. We present a case of a young girl with WS who found to have a persistent left superior vena cava (PLSVC) draining into the coronary sinus. The prevalence of PLSVC is increased in patients with chromosomal and genetic …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Glimepiride Administered In Chow Reversibly Impairs Glucose Tolerance In Mice, Dana M. Niedowicz, Sabire Özcan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no …

A Novel Tetracycline-Responsive Transgenic Mouse Strain For Skeletal Muscle-Specific Gene Expression, Masahiro Iwata, Davis A. Englund, Yuan Wen, Cory M. Dungan, Kevin A. Murach, Ivan J. Vechetti Jr., Christopher B. Mobley, Charlotte A. Peterson, John J. Mccarthy

Center for Muscle Biology Faculty Publications

Background: The tetracycline-responsive system (Tet-ON/OFF) has proven to be a valuable tool for manipulating gene expression in an inducible, temporal, and tissue-specific manner. The purpose of this study was to create and characterize a new transgenic mouse strain utilizing the human skeletal muscle α-actin (HSA) promoter to drive skeletal muscle-specific expression of the reverse tetracycline transactivator (rtTA) gene which we have designated as the HSA-rtTA mouse.

Methods: To confirm the HSA-rtTA mouse was capable of driving skeletal muscle-specific expression, we crossed the HSA-rtTA mouse with the tetracycline-responsive histone H2B-green fluorescent protein (H2B-GFP) transgenic mouse in order to label myonuclei.

Results: …

Editorial: Ion Channel Trafficking And Cardiac Arrhythmias, Marcel A. G. Van Der Heyden, Brian P. Delisle, Hugues Abriel

Physiology Faculty Publications

No abstract provided.