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Medical Sciences

2013

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Articles 1 - 30 of 151

Full-Text Articles in Medicine and Health Sciences

Diabetes Alters Contraction-Induced Mitogen Activated Protein Kinase Activation In The Rat Soleus And Plantaris, Anjaiah Katta, Deborah L. Preston, Sunil K. Kakarla, Shinichi Asano, Sarath Meduru, Sriram P. Mupparaju, Ellie Yokochi, Kevin M. Rice, Devashish H. Desai, Eric R. Blough Dec 2013

Diabetes Alters Contraction-Induced Mitogen Activated Protein Kinase Activation In The Rat Soleus And Plantaris, Anjaiah Katta, Deborah L. Preston, Sunil K. Kakarla, Shinichi Asano, Sarath Meduru, Sriram P. Mupparaju, Ellie Yokochi, Kevin M. Rice, Devashish H. Desai, Eric R. Blough

Deborah L Preston

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and …


Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation Of Mitogen Activated Protein Kinases In The Rat Inferior Vena Cava, Kevin M. Rice, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Deborah L. Preston, Paulette Wehner, Eric R. Blough Dec 2013

Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation Of Mitogen Activated Protein Kinases In The Rat Inferior Vena Cava, Kevin M. Rice, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Deborah L. Preston, Paulette Wehner, Eric R. Blough

Deborah L Preston

Background Diabetes mellitus is an important risk factor for increased vein graft failure after bypass surgery. However, the cellular and molecular mechanism(s) underlying vessel attrition in this population remain largely unexplored. Recent reports have suggested that the pathological remodeling of vein grafts may be mediated by mechanically-induced activation of the mitogen activated protein kinase (MAPK) signaling pathways and the MAPK-related induction of caspase-3 activity. On the basis of these findings, we hypothesized that diabetes may be associated with alterations in how veins "sense" and "respond" to altered mechanical loading. Methods Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and …


Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough Dec 2013

Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough

Deborah L Preston

The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …


Early Chronic Low-Level Lead Exposure Produces Glomerular Hypertrophy In Young C57bl/6j Mice, Christina Sobin, John Basgen Dec 2013

Early Chronic Low-Level Lead Exposure Produces Glomerular Hypertrophy In Young C57bl/6j Mice, Christina Sobin, John Basgen

Christina Sobin, Ph.D.

Early chronic lead exposure continues to pose serious health risks for children, particularly those living in lower socioeconomic environments. This study examined effects on developing glomeruli in young C57BL/6J mice exposed to low (30 ppm), higher (330 ppm) or no lead via dams’ drinking water from birth to sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19 (0.70) µg/dL] had an increase in glomerular volume but no change in podocyte number compared to control mice [0.03 (0.01) µg/dL]. Higher-level lead exposed mice [14.68 (2.74) µg/dL] had no change in either glomerular volume or podocyte number. The …


Proconvulsant Actions Of Intrahippocampal Botulinum Neurotoxin B In The Rat, Sonja Bröer, Dorota Zolkowska, Manuela Gernert, Michael A. Rogawski Nov 2013

Proconvulsant Actions Of Intrahippocampal Botulinum Neurotoxin B In The Rat, Sonja Bröer, Dorota Zolkowska, Manuela Gernert, Michael A. Rogawski

Michael A. Rogawski

Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target synaptosomal-associated protein 25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000 Unit) …


Características Sociodemográficas E Aspectos Clínicos De Pacientes Com Doença Renal Policística Do Adulto Submetidos À Hemodiálise; Sociodemographic Characteristics And Clinical Features Of Patients With Adult Polycystic Kidney Disease Undergoing Hemodialysis, Everton Alves, Luiza Tsuneto, Sueli Borelli, Renata Cadidé, Rosane De Freitas, Ângela Gravena, Sandra Pelloso, Maria Dalva Carvalho Nov 2013

Características Sociodemográficas E Aspectos Clínicos De Pacientes Com Doença Renal Policística Do Adulto Submetidos À Hemodiálise; Sociodemographic Characteristics And Clinical Features Of Patients With Adult Polycystic Kidney Disease Undergoing Hemodialysis, Everton Alves, Luiza Tsuneto, Sueli Borelli, Renata Cadidé, Rosane De Freitas, Ângela Gravena, Sandra Pelloso, Maria Dalva Carvalho

Everton Fernando Alves

Aims: To analyze the socio-demographic and clinical characteristics of patients with adult polycystic kidney disease

admitted to hemodialysis services in Northwestern Paraná state, Brazil.

Methods: This was an observational, descriptive and retrospective longitudinal study. Medical records of patients

with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the

coverage area of the 15th Regional Health Region of Paraná state where analyzed.

Results: We found that 10.3% of hemodialysis patients had polycystic kidney disease as a leading cause of stage 5 of

chronic kidney disease. The mean age of patients was 54.9±9.4 years …


Outcomes Of Peginterferon Alfa-2a And Ribavirin Combination Therapy In A Resident-Initiated, Multidisciplinary, Hepatitis C Clinic, Nicole M. Agostino Do, Erini Vasiliadis Do, K Nadeem Ahmed Md, Suzanne J. Templer Do, Edward R. Norris Md, Fapa, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Joseph L. Yozviak Do, Facp Nov 2013

Outcomes Of Peginterferon Alfa-2a And Ribavirin Combination Therapy In A Resident-Initiated, Multidisciplinary, Hepatitis C Clinic, Nicole M. Agostino Do, Erini Vasiliadis Do, K Nadeem Ahmed Md, Suzanne J. Templer Do, Edward R. Norris Md, Fapa, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Joseph L. Yozviak Do, Facp

Edward R Norris MD, FAPA, FAPM

No abstract provided.


Psychiatric Outcomes In A Resident-Run, Multidisciplinary, Hepatitis C Clinic (Poster), Nicole M. Agostino Do, Edward Norris Md, Fapm, Joseph L. Yozviak Do, Facp, Suzanne J. Templer Do, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Michael Kaufmann Md Nov 2013

Psychiatric Outcomes In A Resident-Run, Multidisciplinary, Hepatitis C Clinic (Poster), Nicole M. Agostino Do, Edward Norris Md, Fapm, Joseph L. Yozviak Do, Facp, Suzanne J. Templer Do, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Michael Kaufmann Md

Edward R Norris MD, FAPA, FAPM

No abstract provided.


Expanding Access To Care Through A Resident-Initiated Hepatitis C Clinic - An Innovative Method For Incorporating Acgme Core Competencies Into The Management Of Medically Underserved Patients, Joseph L. Yozviak Do, Facp, Suzanne J. Templer Do, Erini Vasiliadis Do, Vishal Patel Md, Nicole M. Agostino Do, K Nadeem Ahmed Md, Edward Norris Md, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph Nov 2013

Expanding Access To Care Through A Resident-Initiated Hepatitis C Clinic - An Innovative Method For Incorporating Acgme Core Competencies Into The Management Of Medically Underserved Patients, Joseph L. Yozviak Do, Facp, Suzanne J. Templer Do, Erini Vasiliadis Do, Vishal Patel Md, Nicole M. Agostino Do, K Nadeem Ahmed Md, Edward Norris Md, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph

Edward R Norris MD, FAPA, FAPM

No abstract provided.


St-Segment Elevation (Stemi) Real Time Data Feedback –A Process Of Care Initiative, Orlando E. Rivera Rn, Nainesh Patel Md, Bruce Feldman Do, Mercedes Rios-Scott Bs, David M. Richardson Md, J Patrick Kleaveland Md, David A. Cox Md, Ronald S. Freudenberger Md Oct 2013

St-Segment Elevation (Stemi) Real Time Data Feedback –A Process Of Care Initiative, Orlando E. Rivera Rn, Nainesh Patel Md, Bruce Feldman Do, Mercedes Rios-Scott Bs, David M. Richardson Md, J Patrick Kleaveland Md, David A. Cox Md, Ronald S. Freudenberger Md

Ronald S Freudenberger MD

No abstract provided.


Pre-Operative Angiotensin Converting Enzyme Inhibitors And Angiotensin Receptor Blockers On The Occurrence Of Post Operative Atrial Fibrillation After Cardiac Valve Department Of Surgery, Nasir Shariff, Matthew W. Martinez Md, Ravi V. Desai Md, Michael J. Weiss, Vadim Levin Md, Larry E. Jacobs Md, Martin E. Matsumura Md, Ronald S. Freudenberger Md Oct 2013

Pre-Operative Angiotensin Converting Enzyme Inhibitors And Angiotensin Receptor Blockers On The Occurrence Of Post Operative Atrial Fibrillation After Cardiac Valve Department Of Surgery, Nasir Shariff, Matthew W. Martinez Md, Ravi V. Desai Md, Michael J. Weiss, Vadim Levin Md, Larry E. Jacobs Md, Martin E. Matsumura Md, Ronald S. Freudenberger Md

Ronald S Freudenberger MD

No abstract provided.


The Impact Of A Mental Health-Related Diagnosis On Readmission Rates For Heart Failure, Ronald S. Freudenberger Md, Carol A. Foltz Phd, Lou Lukas Md, Donna F. Petruccelli Crnp, Hannah D. Paxton Rn, Mph, Victoria Sabella Bsn Oct 2013

The Impact Of A Mental Health-Related Diagnosis On Readmission Rates For Heart Failure, Ronald S. Freudenberger Md, Carol A. Foltz Phd, Lou Lukas Md, Donna F. Petruccelli Crnp, Hannah D. Paxton Rn, Mph, Victoria Sabella Bsn

Ronald S Freudenberger MD

No abstract provided.


Comparison Of Chronic Persistent And Post-Operative Atrial Fibrillation On Long Term Survival In Patients Undergoing Cardiac Valve Surgery, Nasir Shariff, Ravi V. Desai Md, Sherrine Eid, Michael J. Weiss, Matthew W. Martinez, Sultan M. Siddique, Ronald S. Freudenberger Md Oct 2013

Comparison Of Chronic Persistent And Post-Operative Atrial Fibrillation On Long Term Survival In Patients Undergoing Cardiac Valve Surgery, Nasir Shariff, Ravi V. Desai Md, Sherrine Eid, Michael J. Weiss, Matthew W. Martinez, Sultan M. Siddique, Ronald S. Freudenberger Md

Ronald S Freudenberger MD

No abstract provided.


Risk Factors Affecting Surgical Outcomes In Patients Undergoing Hypothermic Circulatory Arrest During Aortic Surgeries: A 10-Year Study, Bree Ann Young, James K. Wu, Martin E. Matsumura Md, Sanjay M. Mehta Md, Theodore G. Phillips Md, Michael F. Szwerc Md, Gary W. Szydlowski Md, Raymond L. Singer Md Oct 2013

Risk Factors Affecting Surgical Outcomes In Patients Undergoing Hypothermic Circulatory Arrest During Aortic Surgeries: A 10-Year Study, Bree Ann Young, James K. Wu, Martin E. Matsumura Md, Sanjay M. Mehta Md, Theodore G. Phillips Md, Michael F. Szwerc Md, Gary W. Szydlowski Md, Raymond L. Singer Md

James K. Wu, M.D.

No abstract provided.


Outcome Of Traumatic Aortic Rupture: A 14-Year Experience, Matthew Wilson, James K. Wu, Sanjay M. Mehta Md, Theodore G. Phillips Md, Raymond L. Singer Md, Michael F. Szwerc Md, Gary W. Szydlowski Md Oct 2013

Outcome Of Traumatic Aortic Rupture: A 14-Year Experience, Matthew Wilson, James K. Wu, Sanjay M. Mehta Md, Theodore G. Phillips Md, Raymond L. Singer Md, Michael F. Szwerc Md, Gary W. Szydlowski Md

James K. Wu, M.D.

No abstract provided.


Successful Long-Term Extracorporeal Cardiopulmonary Membrane Oxygenation Without Anti-Coagulation, Janissa Nair, Dorothea T. Watson Do, Rita Pechulis Md, Fccp, Nicholas M. Rini Pa-C, Tim S. Misselbeck Md, Kenneth Miller Rrt, James K. Wu Md Oct 2013

Successful Long-Term Extracorporeal Cardiopulmonary Membrane Oxygenation Without Anti-Coagulation, Janissa Nair, Dorothea T. Watson Do, Rita Pechulis Md, Fccp, Nicholas M. Rini Pa-C, Tim S. Misselbeck Md, Kenneth Miller Rrt, James K. Wu Md

James K. Wu, M.D.

No abstract provided.


Pre-Operative Angiotensin Converting Enzyme Inhibitors And Angiotensin Receptor Blockers On The Occurrence Of Post Operative Atrial Fibrillation After Cardiac Valve Department Of Surgery, Nasir Shariff, Matthew W. Martinez Md, Ravi V. Desai Md, Michael J. Weiss, Vadim Levin Md, Larry E. Jacobs Md, Martin E. Matsumura Md, Ronald S. Freudenberger Md Oct 2013

Pre-Operative Angiotensin Converting Enzyme Inhibitors And Angiotensin Receptor Blockers On The Occurrence Of Post Operative Atrial Fibrillation After Cardiac Valve Department Of Surgery, Nasir Shariff, Matthew W. Martinez Md, Ravi V. Desai Md, Michael J. Weiss, Vadim Levin Md, Larry E. Jacobs Md, Martin E. Matsumura Md, Ronald S. Freudenberger Md

Vadim A Levin MD

No abstract provided.


Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten Oct 2013

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

David D Dunigan Ph. D.

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis, …


Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel Oct 2013

Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel

Simon Laws

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) …


Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass Oct 2013

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.


Reactive Oxygen And Nitrogen Species Induce Protein And Dna Modifications Driving Arthrofibrosis Following Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck Oct 2013

Reactive Oxygen And Nitrogen Species Induce Protein And Dna Modifications Driving Arthrofibrosis Following Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck

Theresa A Freeman

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation.

RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed …


The Age Old Question, Karolina M. Zielinska-Dabkowska, Veronika Labancova Oct 2013

The Age Old Question, Karolina M. Zielinska-Dabkowska, Veronika Labancova

Dr. Karolina M. Zielinska-Dabkowska, IALD, IES, CIE, RIBA

Research about the impact of age on the perception of light quality by Dr. Karolina M. Zielinska - Dabkowska and Veronika Labancová of the University of Applied Sciences, Technology, Business and Design Wismar/ Germany.


Riptek: Best Thermogenic Fat Loss Accelerator, Lissa Coffey Sep 2013

Riptek: Best Thermogenic Fat Loss Accelerator, Lissa Coffey

LissaCoffey

QNT Riptek combines the latest European and American fat burning technologies and starts working from the first time that you take it! Riptek is most powerful fat burner that raises your metabolism naturally without the excessive use of stimulants and prevents the storage of body fat. As soon as you consume the first dose of Riptek you will feel an immediate burst of energy, along with a rise in your core body temperature as Riptek starts to promote burning body fat [...]


Elasmobranch Qpcr Reference Genes: A Case Study Of Hypoxia Preconditioned Epaulette Sharks, Kalle T. Rytkönen, Gillian M. C. Renshaw, Kevin J. Ashton, Grant Williams-Pritchard, Erica H. Leder, Mikko Nikinmaa Sep 2013

Elasmobranch Qpcr Reference Genes: A Case Study Of Hypoxia Preconditioned Epaulette Sharks, Kalle T. Rytkönen, Gillian M. C. Renshaw, Kevin J. Ashton, Grant Williams-Pritchard, Erica H. Leder, Mikko Nikinmaa

Kevin Ashton

Background: Elasmobranch fishes are an ancient group of vertebrates which have high potential as model species for research into evolutionary physiology and genomics. However, no comparative studies have established suitable reference genes for quantitative PCR (qPCR) in elasmobranchs for any physiological conditions. Oxygen availability has been a major force shaping the physiological evolution of vertebrates, especially fishes. Here we examined the suitability of 9 reference candidates from various functional categories after a single hypoxic insult or after hypoxia preconditioning in epaulette shark (Hemiscyllium ocellatum).Results: Epaulette sharks were caught and exposed to hypoxia. Tissues were collected from 10 controls, 10 individuals …


Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski Aug 2013

Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski

Michael A. Rogawski

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. Here we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully-kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-min period by convection enhanced delivery (CED). Electrographic (EEG) and behavioral …


Gucy2c Opposes Systemic Genotoxic Tumorigenesis By Regulating Akt-Dependent Intestinal Barrier Integrity, Jieru Egeria Lin, Adam Eugene Snook, Peng Li, Brian Arthur Stoecker, Gilbert Won Kim, Michael Sullivan Magee, Alex Vladimir Mejia Garcia, Michael Anthony Valentino, Terry Hyslop, Stephanie Schulz, Scott Arthur Waldman Aug 2013

Gucy2c Opposes Systemic Genotoxic Tumorigenesis By Regulating Akt-Dependent Intestinal Barrier Integrity, Jieru Egeria Lin, Adam Eugene Snook, Peng Li, Brian Arthur Stoecker, Gilbert Won Kim, Michael Sullivan Magee, Alex Vladimir Mejia Garcia, Michael Anthony Valentino, Terry Hyslop, Stephanie Schulz, Scott Arthur Waldman

Adam E Snook

The barrier separating mucosal and systemic compartments comprises epithelial cells, annealed by tight junctions, limiting permeability. GUCY2C recently emerged as an intestinal tumor suppressor coordinating AKT1-dependent crypt-villus homeostasis. Here, the contribution of GUCY2C to barrier integrity opposing colitis and systemic tumorigenesis is defined. Mice deficient in GUCY2C (Gucy2c−/−) exhibited barrier hyperpermeability associated with reduced junctional proteins. Conversely, activation of GUCY2C in mice reduced barrier permeability associated with increased junctional proteins. Further, silencing GUCY2C exacerbated, while activation reduced, chemical barrier disruption and colitis. Moreover, eliminating GUCY2C amplified, while activation reduced, systemic oxidative DNA damage. This genotoxicity was associated with increased spontaneous …


Kisspeptin Receptor Agonist (Ftm080) Increased Plasma Concentrations Of Luteinizing Hormone In Anestrous Ewes, Brian K. Whitlock, Kelly A. Chameroy, Rebecca R. Payton, Shinya Oishi, Nobutaka Fujii, Joseph A. Daniel Aug 2013

Kisspeptin Receptor Agonist (Ftm080) Increased Plasma Concentrations Of Luteinizing Hormone In Anestrous Ewes, Brian K. Whitlock, Kelly A. Chameroy, Rebecca R. Payton, Shinya Oishi, Nobutaka Fujii, Joseph A. Daniel

Brian K Whitlock, PhD, DVM, DACT

Kisspeptin (KP) and the KP receptor (Kiss1r) are integral to central regulation of the gonadotropic-axis. The demonstration that intravenous infusion of KP can stimulate gonadotropin secretion and ovulation in seasonally anestrous female sheep offers a means of manipulating the reproductive axis. However, KP may be of limited clinical use because of the short circulating half-life. Kiss1r agonists with increased half-life and similar efficacy to KP in vitro potentially may provide beneficial applications in breeding management of many species. However, many of these agonists have not been tested in vivo. This study was designed to test and compare the effects of …


Epilepsy Therapy Development: Technical And Methodologic Issues In Studies With Animal Models, Aristea S. Galanopoulou, Merab Kokaia, Jeffrey A. Loeb, Astrid Nehlig, Asla Pitkanen, Michael A. Rogawski, Kevin J. Staley, Vicky H. Whittemore, F. Edward Dudek Jul 2013

Epilepsy Therapy Development: Technical And Methodologic Issues In Studies With Animal Models, Aristea S. Galanopoulou, Merab Kokaia, Jeffrey A. Loeb, Astrid Nehlig, Asla Pitkanen, Michael A. Rogawski, Kevin J. Staley, Vicky H. Whittemore, F. Edward Dudek

Michael A. Rogawski

The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. Herein we provide a summary of the discussions and proposals of the Working Group 2 as presented in the Joint American Epilepsy Society and International League Against Epilepsy Translational Workshop in London (September 2012). We propose methodologic and reporting …


Rapid Quantitative Pharmacodynamic Imaging By A Novel Method: Theory, Simulation Testing And Proof Of Principle, Kevin J. Black, Jonathan M. Koller, Brad D. Miller Jul 2013

Rapid Quantitative Pharmacodynamic Imaging By A Novel Method: Theory, Simulation Testing And Proof Of Principle, Kevin J. Black, Jonathan M. Koller, Brad D. Miller

Kevin J. Black, MD

Pharmacological challenge imaging has mapped, but rarely quantified, the sensitivity of a biological system to a given drug. We describe a novel method called rapid quantitative pharmacodynamic imaging. This method combines pharmacokinetic-pharmacodynamic modeling, repeated small doses of a challenge drug over a short time scale, and functional imaging to rapidly provide quantitative estimates of drug sensitivity including EC50 (the concentration of drug that produces half the maximum possible effect). We first test the method with simulated data, assuming a typical sigmoidal dose-response curve and assuming imperfect imaging that includes artifactual baseline signal drift and random error. With these few assumptions, …


Towards Objectively Quantifying Sensory Hypersensitivity: A Pilot Study Of The “Ariana Effect.”, Vassilis N. Panagopoulos, Deanna J. Greene, Meghan C. Campbell, Kevin J. Black Jul 2013

Towards Objectively Quantifying Sensory Hypersensitivity: A Pilot Study Of The “Ariana Effect.”, Vassilis N. Panagopoulos, Deanna J. Greene, Meghan C. Campbell, Kevin J. Black

Kevin J. Black, MD

Background. Normally one habituates rapidly to steady, faint sensations. People with sensory hypersensitivity (SH), by contrast, continue to attend to such stimuli and find them noxious. SH is common in Tourette syndrome (TS) and autism, and methods to quantify SH may lead to better understanding of these disorders. In an attempt to objectively quantify SH severity, the authors tested whether a choice reaction time (CRT) task was a sensitive enough measure to detect significant distraction from a steady tactile stimulus, and to detect significantly greater distraction in subjects with more severe SH.

Methods. Nineteen ambulatory adult volunteers with varying scores …