Digital Commons Network^™

Oseltamivir-Warfarin Interaction In Hypoplastic Left Heart Syndrome: Case Report And Review., Jonathan B. Wagner, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

An 8-year-old boy with hypoplastic left heart syndrome with a previous history of thrombosis within the inferior vena cava receiving stable warfarin dosing for anticoagulation was diagnosed with influenza B. He was subsequently placed on oseltamivir therapy according to the Centers for Disease Control and Prevention clinical practice guidelines. During the hospitalization, his international normalized ratio steadily increased to supratherapeutic levels and returned to baseline after discontinuation of oseltamivir therapy. This case represents a drug-drug interaction that has not been previously reported in children or adolescents. An extensive review of the pharmacokinetic and pharmacodynamic literature did not uncover a definitive …

Adolescent And Adult African Americans Have Similar Metabolic Dyslipidemia., Samuel S. Gidding, Scott W. Keith, Bonita Falkner

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: African Americans (AAs) have lower triglyceride (TG) and higher high-density lipoprotein cholesterol (HDL-C) than other ethnic groups; yet, they also have higher risk for developing diabetes mellitus despite the strong relationship of dyslipidemia with insulin resistance. No studies directly compare adolescents and adults with regard to relationships among dyslipidemia, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance. Here, we compare AA adolescents to adults with regard to the relationships of adiposity-related lipid risk markers (TG-to-HDL ratio and non-HDL-C) with body mass index (BMI), waist circumference (WC), homeostasis model of insulin resistance (HOMA), and hs-CRP.

METHODS: Two cohorts of healthy AA …

Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism In High Fat Diet-Induced Obesity, R. Grace Walton, Beibei Zhu, Resat Unal, Michael Spencer, Manjula Sunkara, Andrew J. Morris, Richard Charnigo, Wendy S. Katz, Alan Daugherty, Deborah A. Howatt, Philip A. Kern, Brian S. Finlin

Barnstable Brown Diabetes Center Faculty Publications

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization …

The Reproducibility And Absolute Values Of Echocardiographic Measurements Of Left Ventricular Size And Function In Children Are Algorithm Dependent., Renee Margossian, Shan Chen, Lynn A. Sleeper, Lloyd Y. Tani, Girish S. Shirali, Fraser Golding, Elif Seda Selamet Tierney, Karen Altmann, Michael J. Campbell, Anita Szwast, Angela Sharkey, Elizabeth Radojewski, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Several quantification algorithms for measuring left ventricular (LV) size and function are used in clinical and research settings. The aims of this study were to investigate the effects of measurement algorithm and beat averaging on the reproducibility of measurements of the left ventricle and to assess the magnitude of agreement among the algorithms in children with dilated cardiomyopathy.

METHODS: Echocardiograms were obtained in 169 children from eight clinical centers. Inter- and intrareader reproducibility was assessed on measurements of LV volumes using the biplane Simpson, modified Simpson, and 5/6 × area × length (5/6AL) algorithms. Percentage error was calculated as …

Compensatory Fetal Membrane Mechanisms Between Biglycan And Decorin In Inflammation., Luciana Batalha De Miranda De Araujo, Casie E Horgan, Abraham Aron, Renato V. Iozzo, Beatrice E Lechner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, …

Effects Of Chronic Manganese Exposure On Attention And Working Memory In Non-Human Primates., Jay S. Schneider, Charles Williams, Mark Ault, Tomás R. Guilarte

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Manganese (Mn) is essential for a variety of physiological processes, but at elevated levels, can be neurotoxic. While cognitive dysfunction has been recently appreciated to occur as a result of chronic Mn exposures, it is still unclear as to which cognitive domains are most susceptible to disruption by Mn exposure. We previously described early appearing Mn-induced changes in performance on a paired associate learning task in monkeys chronically exposed to Mn and suggested that performance of this task might be a sensitive tool for detecting cognitive dysfunction resulting from Mn exposure. As chronic Mn exposure has been suggested to be …

Transarterial Chemoembolization Is Ineffective For Neuroendocrine Tumors Metastatic To The Caudate Lobe: A Single Institution Review., Lawrence A Shirley, Megan Mcnally, Ravi Chokshi, Natalie Jones, Patrick Tassone, Gregory Guy, Hooman Khabiri, Carl Schmidt, Manisha Shah, Mark Bloomston

Oncology Articles

BACKGROUND: Caudate lobe liver metastases occur commonly in patients with neuroendocrine tumors. It is unknown, however, how these lesions respond to regional therapy and how their presence impacts outcomes. We reviewed our experience treating these lesions using transarterial chemoembolization (TACE).

METHODS: We reviewed radiographic response to TACE in 86 patients with metastatic neuroendocrine tumors to the liver. We determined the impact of caudate lesions on outcomes in comparison to the cohort of patients without caudate lesions, as well as response of caudate lesions to TACE versus lesions elsewhere in the liver.

RESULTS: Caudate lesions were identified in 45 (52%) patients. …

Multimodal Frontostriatal Connectivity Underlies Individual Differences In Self-Esteem, Robert S. Chavez, Todd F. Heatherton

Dartmouth Scholarship

A heightened sense of self-esteem is associated with a reduced risk for several types of affective and psychiatric disorders, including depression, anxiety and eating disorders. However, little is known about how brain systems integrate self-referential processing and positive evaluation to give rise to these feelings. To address this, we combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to test how frontostriatal connectivity reflects long-term trait and short-term state aspects of self-esteem. Using DTI, we found individual variability in white matter structural integrity between the medial prefrontal cortex and the ventral striatum was related to trait measures of …

Powerful Anti-Tumor And Anti-Angiogenic Activity Of A New Anti-Vascular Endothelial Growth Factor Receptor 1 Peptide In Colorectal Cancer Models, Valeria Cicatiello, Ivana Apicella, Laura Tudisco, Valeria Tarallo, Luigi Formisano, Annamaria Sandomenico, Younghee Kim, Ana Bastos-Carvalho, Augusto Orlandi, Jayakrishna Ambati, Menotti Ruvo, Roberto Bianco, Sandro De Falco

Ophthalmology and Visual Science Faculty Publications

To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit …

Multi-Level Effects Of Low Dose Rate Ionizing Radiation On Southern Toad, Anaxyrus [Bufo] Terrestris, Karolina Stark, David E. Scott, Olga Tsyusko, Daniel P. Coughlin, Thomas G. Hinton

Plant and Soil Sciences Faculty Publications

Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development -embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d^-1, resulting in total doses up to 15.8 …

Eleven Years Of Data On The Jefferson Scale Of Empathy-Medical Student Version (Jse-S): Proxy Norm Data And Tentative Cutoff Scores., Mohammadreza Hojat, Joseph S. Gonnella

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE: This study was designed to provide typical descriptive statistics, score distributions and percentile ranks of the Jefferson Scale of Empathy-Medical Student version (JSE-S) of male and female medical school matriculants to serve as proxy norm data and tentative cutoff scores.

SUBJECTS AND METHODS: The participants were 2,637 students (1,336 women and 1,301 men) who matriculated at Sidney Kimmel (formerly Jefferson) Medical College between 2002 and 2012, and completed the JSE at the beginning of medical school. Information extracted from descriptive statistics, score distributions and percentile ranks for male and female matriculants were used to develop proxy norm data and …

Plasma Tnf-Α And Soluble Tnf Receptor Levels After Doxorubicin With Or Without Co-Administration Of Mesna-A Randomized, Cross-Over Clinical Study, John Hayslip, Emily Van Meter Dressler, Heidi L. Weiss, Tammy J. Taylor, Mara D. Chambers, Teresa Noel, Sumitra Miriyala, Jeriel T. R. Keeney, Xiaojia Ren, Rukhsana Sultana, Mary Vore, D. Allan Butterfield, Daret St. Clair, Jeffrey A. Moscow

Markey Cancer Center Faculty Publications

PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines.

METHODS: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast …

Closed Head Injury In An Age-Related Alzheimer Mouse Model Leads To An Altered Neuroinflammatory Response And Persistent Cognitive Impairment, Scott J. Webster, Linda J. Van Eldik, D. Martin Watterson, Adam D. Bachstetter

Sanders-Brown Center on Aging Faculty Publications

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal …

Mechanism-Based Combination Treatment Dramatically Increases Therapeutic Efficacy In Murine Globoid Cell Leukodystrophy, Jacqueline A. Hawkins-Salsbury, Lauren Shea, Xuntian Jiang, Daniel A. Hunter, A Miguel Guzman, Adarsh S. Reddy, Elizabeth Y. Qin, Yedda Li, Steven J. Gray, Daniel S. Ory, Mark S. Sands

Open Access Publications

Globoid cell leukodystrophy (GLD, Krabbe disease) is a lysosomal storage disease (LSD) caused by a deficiency in galactocerebrosidase (GALC) activity. In the absence of GALC activity, the cytotoxic lipid, galactosylsphingosine (psychosine), accumulates in the CNS and peripheral nervous system. Oligodendrocytes and Schwann cells are particularly sensitive to psychosine, thus leading to a demyelinating phenotype. Although hematopoietic stem-cell transplantation provides modest benefit in both presymptomatic children and the murine model (Twitcher), there is no cure for GLD. In addition, GLD has been relatively refractory to virtually every experimental therapy attempted. Here, Twitcher mice were simultaneously treated with CNS-directed gene therapy, substrate …

Preempting Performance Challenges: The Effects Of Inoculation Messaging On Attacks To Task Self-Efficacy, Ben Jackson, Josh Compton, Ryan Whiddett, David R. Anthony, James A. Dimmock

Dartmouth Scholarship

Although inoculation messages have been shown to be effective for inducing resistance to counter-attitudinal attacks, researchers have devoted relatively little attention toward studying the way in which inoculation theory principles might support challenges to psychological phenomena other than attitudes (e.g., self-efficacy). Prior to completing a physical (i.e., balance) task, undergraduates (N = 127, M_age = 19.20, SD = 2.16) were randomly assigned to receive either a control or inoculation message, and reported their confidence in their ability regarding the upcoming task. During the task, a confederate provided standardized negative feedback to all participants regarding their performance, and following …

Can Shared Decision-Making Reduce Medical Malpractice Litigation? A Systematic Review, Marie-Anne Durand, Benjamin Moulton, Elizabeth Cockle, Mala Mann, Glyn Elwyn

Dartmouth Scholarship

Background: To explore the likely influence and impact of shared decision-making on medical malpractice litigation and patients’ intentions to initiate litigation.

Methods: We included all observational, interventional and qualitative studies published in all languages, which assessed the effect or likely influence of shared decision-making or shared decision-making interventions on medical malpractice litigation or on patients ’ intentions to litigate. The following databases were searched from inception until January 2014: CINAHL, Cochrane Register of Controlled Trials, Cochrane Da tabase of Systematic Reviews, EMBASE, HMIC, Lexis library, MEDLINE, NHS Economic Evaluation Database, Open SIGLE, PsycINFO and Web of Knowledge. We also hand …

Identifying Cases Of Undiagnosed, Clinically Significant Copd In Primary Care: Qualitative Insight From Patients In The Target Population, Nancy K. Leidy, Katherine Kim, Elizabeth D. Bacci, Barbara P. Yawn, David M. Mannino, Byron M. Thomashow, R. Graham Barr, Stephen I. Rennard, Julia F. Houfek, Meilan K. Han, Catherine A. Meldrum, Barry J. Make, Russ P. Bowler, Anna W. Steenrod, Lindsey T. Murray, John W. Walsh, Fernando Martinez

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations.

AIMS: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care.

METHODS: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the …

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective P38Αmapk Inhibitor That Attenuates Disease Progression In Alzheimer's Disease Mouse Models, Saktimayee M. Roy, Valerie L. Grum-Tokars, James P. Schavocky, Faisal Saeed, Agnieszka Staniszewski, Andrew F. Teich, Ottavio Arancio, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, George Minasov, Wayne F. Anderson, Jeffrey C. Pelletier, D. Martin Watterson

Spinal Cord and Brain Injury Research Center Faculty Publications

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, …

Implementing A Patient-Initiated Review System In Rheumatoid Arthritis: A Qualitative Evaluation., Sue Child, Victoria A. Goodwin, Mark G. Perry, Christian A. Gericke, Richard Byng

Peninsula Medical School

BACKGROUND: The management of Rheumatoid Arthritis (RA), a chronic relapsing condition primarily affecting joints usually entails regular hospital reviews with a specialist. These reviews can occur when the patient is well. This study forms part of a service evaluation of a system wide implementation of a patient initiated review appointment system which we have called Direct Access (DA). The aim was to explore the experiences of patients and staff of a DA system in order to understand the process of the implementation and to identify potential improvements. METHODS: Twenty-three patients with RA that had completed one year of follow-up on …

One-Step Generation Of Multiple Transgenic Mouse Lines Using An Improved Pronuclear Injection-Based Targeted Transgenesis (I-Pitt)., Masato Ohtsuka, Hiromi Miura, Keiji Mochida, Michiko Hirose, Ayumi Hasegawa, Atsuo Ogura, Ryuta Mizutani, Minoru Kimura, Ayako Isotani, Masahito Ikawa, Masahiro Sato, Channabasavaiah B. Gurumurthy

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: The pronuclear injection (PI) is the simplest and widely used method to generate transgenic (Tg) mice. Unfortunately, PI-based Tg mice show uncertain transgene expression due to random transgene insertion in the genome, usually with multiple copies. Thus, typically at least three or more Tg lines are produced by injecting over 200 zygotes and the best line/s among them are selected through laborious screening steps. Recently, we developed technologies using Cre-loxP system that allow targeted insertion of single-copy transgene into a predetermined locus through PI. We termed the method as PI-based Targeted Transgenesis (PITT). A similar method using PhiC31-attP/B system …

Myocardial Feature Tracking Reduces Observer-Dependence In Low-Dose Dobutamine Stress Cardiovascular Magnetic Resonance., Andreas Schuster, Matthias Paul, Nuno Bettencourt, Shazia T. Hussain, Geraint Morton, Shelby Kutty, Boris Bigalke, Amedeo Chiribiri, Divaka Perera, Eike Nagel, Philipp Beerbaum

Journal Articles: Cardiology

OBJECTIVES: To determine whether quantitative wall motion assessment by CMR myocardial feature tracking (CMR-FT) would reduce the impact of observer experience as compared to visual analysis in patients with ischemic cardiomyopathy (ICM).

METHODS: 15 consecutive patients with ICM referred for assessment of hibernating myocardium were studied at 3 Tesla using SSFP cine images at rest and during low dose dobutamine stress (5 and 10 μg/kg/min of dobutamine). Conventional visual, qualitative analysis was performed independently and blinded by an experienced and an inexperienced reader, followed by post-processing of the same images by CMR-FT to quantify subendocardial and subepicardial circumferential (Eccendo and …

The Human Motor System Alters Its Reaching Movement Plan For Task-Irrelevant, Positional Forces., Joshua G A Cashaback, Heather R Mcgregor, Paul L Gribble

Brain and Mind Institute Researchers' Publications

The minimum intervention principle and the uncontrolled manifold hypothesis state that our nervous system only responds to force perturbations and sensorimotor noise if they affect task success. This idea has been tested in muscle and joint coordinate frames and more recently using workspace redundancy (e.g., reaching to large targets). However, reaching studies typically involve spatial and or temporal constraints. Constrained reaches represent a small proportion of movements we perform daily and may limit the emergence of natural behavior. Using more relaxed constraints, we conducted two reaching experiments to test the hypothesis that humans respond to task-relevant forces and ignore task-irrelevant …

True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring., Debra A Benator, Angelo Elmi, Manuel D Rodriguez, Howard B Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires

Medicine Faculty Publications

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 …

Narcotic-Induced Pain, Sudeep Thapa, Jason Schairer

Gastroenterology Articles

No abstract provided.

Transcatheter Aortic Valve Implantation Despite Challenging Vascular Access, Angelo Nascimbene, Federico Azpurua, James J Livesay, R David Fish, Zvonimir Krajcer

The Texas Heart Institute Journal

We describe transcatheter aortic valve implantation in a patient who had severe peripheral artery disease. The patient's vascular condition required additional preliminary peripheral intervention to enable adequate vascular access.

A 78-year-old man with severe aortic stenosis, substantial comorbidities, and severe heart failure symptoms was referred for aortic valve replacement. The patient's 20-mm aortic annulus necessitated the use of a 23-mm Edwards Sapien valve inserted through a 22F sheath, which itself needed a vessel diameter of at least 7 mm for percutaneous delivery. The left common femoral artery was selected for valve delivery. The left iliac artery and infrarenal aorta underwent …

Regression Of Left Ventricular Mass After Implantation Of The Sutureless 3f Enable Aortic Bioprosthesis, Giovanni Concistrè, Antonio Miceli, Federica Marchi, Francesca Chiaramonti, Mattia Glauber, Marco Solinas

The Texas Heart Institute Journal

Left ventricular hypertrophy in aortic stenosis is considered a compensatory response for the maintenance of systolic function but a risk factor for cardiac morbidity and death. We investigated the degree of left ventricular mass regression after implantation of the sutureless Medtronic 3f Enable® Aortic Bioprosthesis.

We studied 19 patients who, from May 2010 through July 2011, underwent isolated aortic valve replacement with the 3f Enable bioprosthetic valve, with clinical and echocardiographic follow-up at 6 months. The mean age was 77.1 ± 5.1 years (range, 68–86 yr); 14 patients were women (73.7%); and the mean logistic EuroSCORE was 15.4% ± 11.8%. …

Effects Of Periodontal Therapy On White Blood Cell Count And Levels Of Transforming Growth Factor Beta In Serum Of Subjects With Severe Periodontitis, A. C. E. Leite, V. M. A. Carneiro, Ana Carolina Morandini, Erivan Schnaider Ramos-Junior, M. C. M. Guimarães

All Dugoni School of Dentistry Faculty Articles

This study aimed to investigate the effects of nonsurgical periodontal therapy on white blood cell (WBC) count and levels of transforming growth factor beta (TGF—β) in serum from subjects with severe periodontitis. Serum from 28 subjects with periodontitis (mean age: 34.36±6.24; 32% men) and 27 healthy controls (mean age: 33.18±6.42; 33% men) were collected prior to therapy. Blood samples were obtained from 23 subjects who completed therapy (9—12 months). A well—controlled periodontal treatment protocol was established in three stages: mechanical periodontal therapy (scaling and root planning), reinstrumentation of dental sites, and supportive periodontal therapy. Periodontal and systemic parameters such as …

Hco3(-)-Independent Ph Regulation In Astrocytes In Situ Is Dominated By V-Atpase., Daniel Bloch Hansen, Nestor Garrido-Comas, Mike Salter, Robert Fern

More Faculty of Health Research

The mechanisms of HCO3(-)-independent intracellular pH (pHi) regulation were examined in fibrous astrocytes within isolated neonatal rat optic nerve (RON) and in cultured cortical astrocytes. In agreement with previous studies, resting pHi in cultured astrocytes was 6.82 ± 0.06 and inhibition of the V-ATPase H(+) pump by Cl(-) removal or via the selective inhibitor bafilomycin had only a small effect upon resting pHi and recovery following an acid load. In contrast, resting pHi in RON astrocytes was 7.10 ± 0.04, significantly less acidic than that in cultured cells (p < 0.001), and responded to inhibition of V-ATPase with profound acidification to the 6.3-6.5 range. Fluorescent immuno-staining and immuno-gold labeling confirmed the presence V-ATPase in the cell membrane of RON astrocyte processes and somata. Using ammonia pulse recovery, pHi recovery in RON astrocyte was achieved largely via V-ATPase with sodium-proton exchange (NHE) playing a minor role. The findings indicate that astrocytes in a whole-mount preparation such as the optic nerve rely to a greater degree upon V-ATPase for HCO3(-)-independent pHi regulation than do cultured astrocytes, with important functional consequences for the regulation of pH in the CNS.

Enhanced Nmda Receptor-Mediated Modulation Of Excitatory Neurotransmission In The Dorsal Vagal Complex Of Streptozotocin-Treated, Chronically Hyperglycemic Mice, Eva C. Bach, Katalin Cs. Halmos, Bret N. Smith

Physiology Faculty Publications

A variety of metabolic disorders, including complications experienced by diabetic patients, have been linked to altered neural activity in the dorsal vagal complex. This study tested the hypothesis that augmentation of N-Methyl-D-Aspartate (NMDA) receptor-mediated responses in the vagal complex contributes to increased glutamate release in the dorsal motor nucleus of the vagus nerve (DMV) in mice with streptozotocin-induced chronic hyperglycemia (i.e., hyperglycemic mice), a model of type 1 diabetes. Antagonism of NMDA receptors with AP-5 (100 μM) suppressed sEPSC frequency in vagal motor neurons recorded in vitro, confirming that constitutively active NMDA receptors regulate glutamate release in the DMV. There …

Association Of Early Imaging For Back Pain With Clinical Outcomes In Older Adults, Jeffrey G. Jarvik, Laura S. Gold, Bryan A. Comstock, Patrick J. Heagerty, Sean D. Rundell, Judith A. Turner, Andrew L. Avins, Zoya Bauer, Brian W. Bresnahan, Janna L. Friedly, Kathryn James, Larry Kessler, Srdjan S. Nedeljkovic, David R. Nerenz, Xu Shi, Sean D. Sullivan, Leighton Chan, Jason M. Schwalb, Richard A. Deyo

Center for Health Policy and Health Services Research Articles

IMPORTANCE: In contrast to the recommendations for younger adults, many guidelines allow for older adults with back pain to undergo imaging without waiting 4 to 6 weeks. However, early imaging may precipitate interventions that do not improve outcomes.

OBJECTIVE: To compare function and pain at the 12-month follow-up visit among older adults who received early imaging with those who did not receive early imaging after a new primary care visit for back pain without radiculopathy.

DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort of 5239 patients 65 years or older with a new primary care visit for back pain (2011-2013) in 3 …