Targeting The Endocannabinoid System To Reduce Inflammatory Pain, 2012 Virginia Commonwealth University
Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh
Theses and Dissertations
The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …
Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, 2012 Garvan Institute of Medical Research, University of New South Wales
Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay
Pharmacology and Toxicology Publications
Aims and Hypothesis
Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.
Methods
Gem-deficient mice were generated and their metabolic phenotype characterised by …
Acid Sphingomyelinase Gene Knockout Ameliorates Hyperhomocysteinemic Glomerular Injury In Mice Lacking Cystathionine-Β-Synthase, 2012 Virginia Commonwealth University
Acid Sphingomyelinase Gene Knockout Ameliorates Hyperhomocysteinemic Glomerular Injury In Mice Lacking Cystathionine-Β-Synthase, Krishna M. Boini, Min Xia, Justine M. Abais, Ming Xu, Cai-Xia Li, Pin-Lan Li
Pharmacology and Toxicology Publications
Acid sphingomyelinase (ASM) has been implicated in the development of hyperhomocysteinemia (hHcys)-induced glomerular oxidative stress and injury. However, it remains unknown whether genetically engineering of ASM gene produces beneficial or detrimental action on hHcys-induced glomerular injury. The present study generated and characterized the mice lacking cystathionine β-synthase (Cbs) and Asm mouse gene by cross breeding Cbs+/− and Asm+/− mice. Given that the homozygotes of Cbs−/−/Asm−/− mice could not survive for 3 weeks. Cbs+/−/Asm+/+, Cbs+/−/Asm+/− and Cbs+/−/Asm−/− as well as their Cbs wild type littermates were used to study the role of Asm−/− under a background of Cbs+/− with hHcys. HPLC …
Discovery Of Prostamide F2Α And Its Role In Inflammatory Pain And Dorsal Horn Nociceptive Neuron Hyperexcitability, 2012 Second University of Naples
Discovery Of Prostamide F2Α And Its Role In Inflammatory Pain And Dorsal Horn Nociceptive Neuron Hyperexcitability, Luisa Gatta, Fabiana Piscitelli, Catia Giordano, Serana Boccella, Aron H. Lichtman, Sebatino Maione, Vincenzo Di Marzo
Pharmacology and Toxicology Publications
It was suggested that endocannabinoids are metabolized by cyclooxygenase (COX)-2 in the spinal cord of rats with kaolin/λ-carrageenan-induced knee inflammation, and that this mechanism contributes to the analgesic effects of COX-2 inhibitors in this experimental model. We report the development of a specific method for the identification of endocannabinoid COX-2 metabolites, its application to measure the levels of these compounds in tissues, and the finding of prostamide F2α (PMF2α) in mice with knee inflammation. Whereas the levels of spinal endocannabinoids were not significantly altered by kaolin/λ-carrageenan-induced knee inflammation, those of the COX-2 metabolite of AEA, PMF2α, were strongly elevated. The …
C-Abl And Arg Drive Cancer Chemoresistance Via Activation Of Multiple Signaling Pathways, 2012 University of Kentucky
C-Abl And Arg Drive Cancer Chemoresistance Via Activation Of Multiple Signaling Pathways, Jonathan Thomas Sims
Theses and Dissertations--Pharmacology and Nutritional Sciences
Despite 35 years of clinical trials, there has been little improvement in one-year survival rates with any chemotherapeutic regimen for the treatment of metastatic melanoma due to resistance to all known agents. Regardless of advances in detection and prevention, diagnosis of metastatic disease remains a death sentence. Resistance mechanisms, including aberrant kinase signaling and drug transport pumps, indicate a need for identification of other therapeutic targets that impinge upon multiple signaling pathways. The Abl family of non-receptor tyrosine kinases (c-Abl, Arg) has been indicted as a causative force in leukemia for more than three decades; however, their role in solid …
Sterol Lipid Metabolism In Down Syndrome Revisited: Down Syndrome Is Associated With A Selective Reduction In Serum Brassicasterol Levels, 2012 University of British Columbia, Canada
Sterol Lipid Metabolism In Down Syndrome Revisited: Down Syndrome Is Associated With A Selective Reduction In Serum Brassicasterol Levels, Gavin Tansley, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, Cheryl L. Wellington
Pharmacology and Nutritional Sciences Faculty Publications
Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population's unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with …
Vascular Inflammatory Cells In Hypertension., 2012 George Washington University
Vascular Inflammatory Cells In Hypertension., David G Harrison, Paul J. Marvar, Jens M Titze
Pharmacology and Physiology Faculty Publications
Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients, and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. …
Seroprevalencia De Pestivirus De Rumiantes En Ovinos Reproductores De Una Empresa De La Sierra Central Del Perú, 2012 National University of San Marcos
Seroprevalencia De Pestivirus De Rumiantes En Ovinos Reproductores De Una Empresa De La Sierra Central Del Perú, Nathalie A. Llancares, Hermelinda G. Rivera, Mariluz Araínga, Nestor Falcon P.
Journal Articles: Pharmacology & Experimental Neuroscience
The aim of the present study was to determine the prevalence of Bovine Viral Diarrhea Virus (BVDV) and Border Disease virus (BDV) in breeding sheep from a large cooperative farm in the Central highlands of Peru. Blood samples from apparently healthy sheep of 4 years old, both sexes (female = 165; male = 165) were collected for antibodies detection against BVDV and BDV using the virus neutralization test. The 2.1 ± 1.5% (7/330) and 28.5 ± 4.9% (94/330) of breeding sheep had antibodies against BVDV and BDV respectively, with antibodies titers of 1:2 and 1:16. There was significant association between …
Interferon-Α Regulates Glutaminase 1 Promoter Through Stat1 Phosphorylation: Relevance To Hiv-1 Associated Neurocognitive Disorders., 2012 University of Nebraska Medical Center
Interferon-Α Regulates Glutaminase 1 Promoter Through Stat1 Phosphorylation: Relevance To Hiv-1 Associated Neurocognitive Disorders., Lixia Zhao, Yunlong Huang, Changhai Tian, Lynn Taylor, Norman Curthoys, Yi Wang, Hamilton Vernon, Jialin C. Zheng
Journal Articles: Pharmacology & Experimental Neuroscience
HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In …
Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, 2012 Virginia Commonwealth University
Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra
Theses and Dissertations
DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the resolution of terminally blocked DNA DSBs is the biologically relevant function of Artemis, Artemis deficient fibroblasts were stably complemented with wild type or an endonuclease deficient D165N mutant Artemis. Physiological levels of wild type (WT) Artemis completely restored DSB repair proficiency and resistance to γ-radiation, bleomycin, and neocarzinostatin. Cells expressing the D165N mutants remained as chemo/radiosensitive and as repair deficient …
Lipid Environment Modulates The Development Of Acute Tolerance To Ethanol In Caenorhabditis Elegans, 2012 Virginia Commonwealth University, University of California San Francisco
Lipid Environment Modulates The Development Of Acute Tolerance To Ethanol In Caenorhabditis Elegans, Jill C. Bettinger, Kapo Leung, Mia H. Bolling, Andrew D. Goldsmith, Andrew G. Davies
Pharmacology and Toxicology Publications
The development of tolerance to a drug at the level of the neuron reflects a homeostatic mechanism by which neurons respond to perturbations of their function by external stimuli. Acute functional tolerance (AFT) to ethanol is a fast compensatory response that develops within a single drug session and normalizes neuronal function despite the continued presence of the drug. We performed a genetic screen to identify genes required for the development of acute functional tolerance to ethanol in the nematode C. elegans. We identified mutations affecting multiple genes in a genetic pathway known to regulate levels of triacylglycerols (TAGs) via …
Morphine Decreases Enteric Neuron Excitability Via Inhibition Of Sodium Channels, 2012 Virginia Commonwealth University
Morphine Decreases Enteric Neuron Excitability Via Inhibition Of Sodium Channels, Tricia H. Smith, John R. Grider, William L. Dewey, Hamid I. Akbarali
Pharmacology and Toxicology Publications
Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a Swiss-Webster mouse myenteric neuron culture and examined their electrophysiological properties by patch-clamp techniques and determined the mechanism for morphine-induced decrease in neuronal excitability. Isolated neurons in culture were confirmed …
The Use Of Cerium Oxide And Curcumin Nanoparticles As Therapeutic Agents For The Treatment Of Ventricular Hypertrophy Following Pulmonary Arterial Hypertension, 2012 Marshall University
The Use Of Cerium Oxide And Curcumin Nanoparticles As Therapeutic Agents For The Treatment Of Ventricular Hypertrophy Following Pulmonary Arterial Hypertension, Madhukar Babu Kolli
Theses, Dissertations and Capstones
Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by inflammation, increased pulmonary vascular resistance, right ventricular failure and premature death. Monocrotaline (MCT) has been used to induce PAH in laboratory rats. Previous in vitro and in vivo work suggested that cerium oxide (CeO2)-and curcumin nanoparticles exhibit anti-inflammatory activity; however, it is unknown if these materials are effective for the treatment of PAH induced cardiac hypertrophy. To determine the efficacy of CeO2 nanoparticle treatment in preventing MCT-induced RV hypertrophy, male Sprague Dawley rats were divided into one of three groups (control, MCT, or MCT + CeO2 nanoparticle, n=6/group). …
The Fit-Hansa Demonstrates Reliability And Convergent Validity Of Functional Performance In Patients With Shoulder Disorders, 2012 McMaster University
The Fit-Hansa Demonstrates Reliability And Convergent Validity Of Functional Performance In Patients With Shoulder Disorders, Prajyot Kumta, Joy C. Macdermid, Saurabh Mehta, Paul W. Stratford
Physical Therapy Faculty Research
Study
DesignPsychometric study design.
Objectives
To assess the test-retest reliability and convergent validity of the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) in patients with shoulder disorders.
Background
Performance tests that assess functional ability of patients with shoulder disorders can provide useful information for making clinical or return-to-activity decisions. No performance-based shoulder test has yet demonstrated sufficient relevance or clinical measurement properties. The FIT-HaNSA examines upper extremity performance during repetitive tasks that emphasize shoulder reaching and static postures and, therefore, has greater relevance for assessing performance.
Methods
Thirty-six patients with shoulder disorders and 65 healthy controls were recruited for the study. …
Efficacy Of Infection Control Interventions In Reducing The Spread Of Multidrug-Resistant Organisms In The Hospital Setting, 2012 University of Richmond
Efficacy Of Infection Control Interventions In Reducing The Spread Of Multidrug-Resistant Organisms In The Hospital Setting, Joanna R. Wares, Erika M.C. D'Agata, Mary Ann Horn, Shigui Ruan, Glenn F. Webb
Department of Math & Statistics Faculty Publications
Multidrug-resistant organisms (MDRO) continue to spread in hospitals globally, but the population-level impact of recommended preventive strategies and the relative benefit of individual strategies targeting all MDRO in the hospital setting are unclear. To explore the dynamics of MDRO transmission in the hospital, we develop a model extending data from clinical individual-level studies to quantify the impact of hand hygiene, contact precautions, reducing antimicrobial exposure and screening surveillance cultures in decreasing the prevalence of MDRO colonization and infection. The effect of an ongoing increase in the influx of patients colonized with MDRO into the hospital setting is also quantified. We …
Characterization Of A Hyperthermophilic Redox Protein, Rubredoxin, As A Potential Targeted Cancer Therapeutic, 2012 Philadelphia College of Osteopathic Medicine
Characterization Of A Hyperthermophilic Redox Protein, Rubredoxin, As A Potential Targeted Cancer Therapeutic, Siri Lakshmi Chirumamilla
PCOM Biomedical Studies Student Scholarship
Cancer is an elusive neoplastic disease that claims the lives of many people around the world every year. Though treatments have become more specific to the different types of cancer, the need remains for antineoplastic drugs that target cancer cells and leave normal cells unharmed, with little to no systemic toxicity. The search for a targeted cancer therapeutic is necessary and urgent, and Pyrococcus furiosus rubredoxin might be such a tool. Rubredoxin is a small (53 amino acids), water soluble, non-heme iron electron transfer protein that contains an iron atom cofactor bound by the sulfurs of four cysteine residues, which …
Is 1.25 Mg Oral Fingolimod Effective In Reducing Relapses In Adults With Relapsing Multiple Sclerosis?, 2012 Philadelphia College of Osteopathic Medicine
Is 1.25 Mg Oral Fingolimod Effective In Reducing Relapses In Adults With Relapsing Multiple Sclerosis?, Caitlin M. Cook
PCOM Physician Assistant Studies Student Scholarship
OBJECTIVE: The objective of this systematic review is to determine whether or not is 1.25 mg oral fingolimod effective in reducing relapses in adults with relapsing multiple sclerosis.
STUDY DESIGN: Review of three English language primary studies published between 2006 and 2010.
DATA SOURCES: Randomized, double-blind, controlled clinical trials comparing daily 1.25 mg oral fingolimod to either identical placebo capsules or weekly intramuscular interferon beta-1a therapy were found using Pubmed and Cochrane Databases.
OUTCOMES MEASURED: Annualized relapse rate was assessed in all studies. Relapses were confirmed by neurologists and assessed using the Expanded Disability Status Scale (EDSS) to evaluate worsening …
Is Etanercept A Safe And Effective Treatment For Ankylosing Spondylitis?, 2012 Philadelphia College of Osteopathic Medicine
Is Etanercept A Safe And Effective Treatment For Ankylosing Spondylitis?, Robyn M. Albert
PCOM Physician Assistant Studies Student Scholarship
Objective: The objective of this selective EBM review is to determine whether or not etanercept is a safe and effective treatment for ankylosing spondylitis (AS).
Study Design: Review of three English language randomized control trials published in 2007, 2008, and 2010.
Data Sources: Two double-blind placebo-controlled randomized controlled trials and one placebo-controlled randomized control trial comparing etanercept to placebo were found using PubMed.
Outcomes Measured: Work instability was measured through the Ankylosing Spondylitis Work Instability Scale (AS-WIS) based on scores of 1-20. Quality of life was measured through the EuroQOL-5D (EQ-5D), which assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. …
Is Dabigatran Non-Inferior To Warfarin For The Prevention Of Stroke In Those With Atrial Fibrillation?, 2012 Philadelphia College of Osteopathic Medicine
Is Dabigatran Non-Inferior To Warfarin For The Prevention Of Stroke In Those With Atrial Fibrillation?, Brittany Burlakoff
PCOM Physician Assistant Studies Student Scholarship
OBJECTIVE: The objective of this systematic review is to determine whether or not dabigatran 150 mg twice daily is non-inferior to warfarin for the prevention of stroke in those with atrial fibrillation with similar rates of bleeding events.
STUDY DESIGN: Review of 3 English language primary studies. All three trials were randomized controlled trials which were blinded for those receiving dabigatran and un-blinded for those receiving warfarin.
DATA SOURCES: Articles were found using PUBMED and COCHRANE databases.
OUTCOME MEASURED: The primary outcomes of these studies were either incidence of stroke or systemic embolism and/or major bleeding events.
RESULTS:The RE-LY …
Is Methylphenidate Transdermal System (Daytrana®) Safe And Effective For Managing Attention Deficit Hyperactivity Disorder Symptoms In Children?, 2012 Philadelphia College of Osteopathic Medicine
Is Methylphenidate Transdermal System (Daytrana®) Safe And Effective For Managing Attention Deficit Hyperactivity Disorder Symptoms In Children?, Pamela Cassidy
PCOM Physician Assistant Studies Student Scholarship
OBJECTIVE: The objective of this selective EBM review is to determine whether or not methylphenidate transdermal system (Daytrana®) is safe and effective for managing attention deficit hyperactivity disorder symptoms in children.
STUDY DESIGN: A review of three English language studies published from 2006-2010. Includes two randomized, double-blind, controlled trials and one randomized, controlled crossover study.
DATA SOURCES: Randomized, placebo-controlled studies evaluating the effectiveness and safety of methylphenidate transdermal system (MTS) for managing attention deficit hyperactivity disorder (ADHD) symptoms in children were located using the PubMed, CINAHL, and Cochrane Library databases.
OUTCOMES MEASURED: The primary measures of effectiveness used were the …