Caffeine and Adenosine
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
The Adenosinergic System a Non-Dopaminergic Target in Parkinson’S Disease
springer.com Biomedicine : Neurosciences Morelli, M., Simola, N., Wardas, J. (Eds.) The Adenosinergic System A Non-Dopaminergic Target in Parkinson’s Disease Comprehensive book that discusses all the aspects of this class of drugs in relation to Parkinson's Disease Includes a review on the history of istradefylline Includes a review on urate as a biomarker and neuroprotectant Adenosine A2A receptor antagonists have shown great promise in the treatment of Parkinson's Disease and alleviation of symptoms. This bookaddresses various aspects of this class of drugs from their chemical development to their clinical use. Among the many insightful chapters contained in this book, there are three unique reviews that have not previously been published in any format: (1) a history of istradefylline, the first A2A antagonist approved for treatment of Parkinson's Disease, (2) an overview of neuroimaging studies in human death and disease and (3) a study of urate as a possible biomarker and neuroprotectant. Springer 1st ed. 2015, XII, 337 p. 41 Order online at springer.com/booksellers 1st illus., 31 illus. in color. Springer Nature Customer Service Center LLC edition 233 Spring Street New York, NY 10013 USA Printed book T: +1-800-SPRINGER NATURE Hardcover (777-4643) or 212-460-1500 [email protected] Printed book Hardcover ISBN 978-3-319-20272-3 $ 199,99 Available Discount group Professional Books (2) Product category Contributed volume Series Current Topics in Neurotoxicity Other renditions Softcover ISBN 978-3-319-37186-3 Softcover ISBN 978-3-319-20274-7 Prices and other details are subject to change without notice. -
Inhalants Booklet6/4/0712:04Ampage1 Inhalants Inhalants Booklet 6/4/07 12:04 AM Page 2
inhalants booklet6/4/0712:04AMPage1 inhalants inhalants booklet 6/4/07 12:04 AM Page 2 inhalants WHAT ARE INHALANTS? Inhalants are a range of products that are sniffed or inhaled to give the user an immediate head rush or ‘high’. These substances are easily absorbed through the lungs and carried to the brain, where they act to slow down the central nervous system. Many familiar household products are inhalants. Some of the most common are: • Glue • Aerosol spray cans • Cleaning fluids • Felt-tipped pens • Correction fluid (liquid paper) • Chrome-based paints • Paint or paint thinner • Petrol • Anaesthetics Many inhalants are classified as volatile solvents. These change rapidly from a liquid or semi-solid state to a gas when exposed to air. They include chemicals that are found in products such as deodorants, air fresheners, lighter fuels and propellant gases used in aerosols such as whipped cream dispensers. Some volatile solvents are inhaled because of the effects produced not only by the product’s main ingredient, but by the propellant gases, as in aerosols, such as hair spray. Other solvents found in aerosol products such as gold and silver spray paint are sniffed not because of the effects from propellant gases but because of the psychoactive effects caused by the specific solvents necessary to suspend these metallic paints in the spray. The sniffing of metallic paints is known as ‘chroming’. inhalants booklet 6/4/07 12:04 AM Page 3 Another category of inhalant is the nitrites. Amyl, butyl and isobutyl nitrite (collectively known as alkyl nitrites) are clear, yellow liquids which are inhaled for their intoxicating effects. -
Phosphodiesterase-5 Inhibitors and the Heart: Heart: First Published As 10.1136/Heartjnl-2017-312865 on 8 March 2018
Heart Online First, published on March 8, 2018 as 10.1136/heartjnl-2017-312865 Review Phosphodiesterase-5 inhibitors and the heart: Heart: first published as 10.1136/heartjnl-2017-312865 on 8 March 2018. Downloaded from compound cardioprotection? David Charles Hutchings, Simon George Anderson, Jessica L Caldwell, Andrew W Trafford Unit of Cardiac Physiology, ABSTRACT recently reported that PDE5i use in patients with Division of Cardiovascular Novel cardioprotective agents are needed in both type 2 diabetes (T2DM) and high cardiovascular Sciences, School of Medical risk was associated with reduced mortality.6 The Sciences, Faculty of Biology, heart failure (HF) and myocardial infarction. Increasing Medicine and Health, The evidence from cellular studies and animal models effect was stronger in patients with prior MI and University of Manchester, indicate protective effects of phosphodiesterase-5 was associated with reduced incidence of new MI, Manchester Academic Health (PDE5) inhibitors, drugs usually reserved as treatments of raising the possibility that PDE5is could prevent Science Centre, Manchester, UK erectile dysfunction and pulmonary arterial hypertension. both complications post-MI and future cardio- PDE5 inhibitors have been shown to improve vascular events. Subsequent similar findings were Correspondence to observed in a post-MI cohort showing PDE5i use Dr David Charles Hutchings, contractile function in systolic HF, regress left ventricular Institute of Cardiovascular hypertrophy, reduce myocardial infarct size and suppress was accompanied with reduced mortality and HF 7 Sciences, The University of ischaemia-induced ventricular arrhythmias. Underpinning hospitalisation. Potential for confounding in these Manchester, Manchester, M13 these actions are complex but increasingly understood observational studies is high, however, and data 9NT, UK; david. -
An Ecological Investigation of the Time Course of Hangover
AN ECOLOGICAL INVESTIGATION OF HANGOVER SEVERITY AND TIME COURSE _______________________________________ A Dissertation presented to the Faculty of the Graduate School at the University of Missouri-Columbia _______________________________________________________ In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy _____________________________________________________ by ERIN HUNT-CARTER Dr. Thomas Piasecki, Dissertation Supervisor DECEMBER 2010 The undersigned, appointed by the dean of the Graduate School, have examined the dissertation entitled AN ECOLOGICAL INVESTIGATION OF HANGOVER SEVERITY AND TIME COURSE presented by Erin E. Hunt-Carter, a candidate for the degree of doctor of philosophy, and hereby certify that, in their opinion, it is worthy of acceptance. Professor Thomas M. Piasecki Professor Wendy S. Slutske Professor Kenneth J. Sher Professor Dennis K. Miller Professor Daniel C. Vinson Thank you to my wonderful husband, Brent. I would not have completed this without your endless encouragement and kindness. Thank you to my parents, Toni and John Hunt, and my parents-in-law, Sondra and Guy Carter. Their support and many hours of babysitting were invaluable. Thank you to my sister, Meghan Hunt, for being riotously funny and supporting me through this process. Finally, I’d like to thank my children, Ian and Anna Carter, for keeping me grounded and reminding me what is truly important in life. ACKNOWLEDGEMENTS It is a pleasure to thank those who made this dissertation possible. First, I would like to express my gratitude to my doctoral advisor, Dr. Thomas Piasecki. He generously welcomed me into his lab, and enabled me to gain invaluable experience with ecological momentary assessment. I could not have completed this dissertation without his patient advice, extensive knowledge, and encouragement. -
Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels During Exposure, Short-Term, and Long-Term Withdrawal
Neuropsychopharmacology (2008) 33, 599–610 & 2008 Nature Publishing Group All rights reserved 0893-133X/08 $30.00 www.neuropsychopharmacology.org Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal ,1 1 1 1 Yael Abreu-Villac¸a* , Fernanda Nunes , Fabı´ola do E Queiroz-Gomes , Alex C Manha˜es and 1 Cla´udio C Filgueiras 1 ˆ ˆ Laborato´rio de Neurofisiologia, Departamento de Ciencias Fisiolo´gicas, Instituto de Biologia Roberto Alcantara Gomes, Centro Biome´dico, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil Smoking and consumption of alcoholic beverages are frequently associated during adolescence. This association could be explained by the cumulative behavioral effects of nicotine and ethanol, particularly those related to anxiety levels. However, despite epidemiological findings, there have been few animal studies of the basic neurobiology of the combined exposure in the adolescent brain. In the present work we assessed, through the use of the elevated plus maze, the short- and long-term anxiety effects of nicotine (NIC) and/or ethanol (ETOH) exposure during adolescence (from the 30th to the 45th postnatal day) in four groups of male and female C57BL/6 mice: (1) Concomitant NIC (nicotine free-base solution (50 mg/ml) in 2% saccharin to drink) and ETOH (ethanol solution (25%, 2 g/kg) i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) Vehicle. C57BL/6 mice were selected, in spite of the fact that they present slower ethanol metabolism, because they readily consume nicotine in the concentration used in the present study. -
Mechanisms of Action of PDE5 Inhibition in Erectile Dysfunction
International Journal of Impotence Research (2004) 16, S4–S7 & 2004 Nature Publishing Group All rights reserved 0955-9930/04 $30.00 www.nature.com/ijir Original Research Mechanisms of action of PDE5 inhibition in erectile dysfunction JD Corbin1* 1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennesse, USA A spinal reflex and the L-arginine–nitric oxide–guanylyl cyclase–cyclic guanosine monophosphate (cGMP) pathway mediate smooth muscle relaxation that results in penile erection. Nerves and endothelial cells directly release nitric oxide in the penis, where it stimulates guanylyl cyclase to produce cGMP and lowers intracellular calcium levels. This triggers relaxation of arterial and trabecular smooth muscle, leading to arterial dilatation, venous constriction, and erection. Phosphodiesterase 5 (PDE5) is the predominant phosphodiesterase in the corpus cavernosum. The catalytic site of PDE5 normally degrades cGMP, and PDE5 inhibitors such as sildenafil potentiate endogenous increases in cGMP by inhibiting its breakdown at the catalytic site. Phosphorylation of PDE5 increases its enzymatic activity as well as the affinity of its allosteric (noncatalytic/GAF domains) sites for cGMP. Binding of cGMP to the allosteric site further stimulates enzymatic activity. Thus phosphorylation of PDE5 and binding of cGMP to the noncatalytic sites mediate negative feedback regulation of the cGMP pathway. International Journal of Impotence Research (2004) 16, S4–S7. doi:10.1038/sj.ijir.3901205 Keywords: phosphodiesterase inhibitors; vasodilator agents; cyclic GMP; impotence; penile erection Introduction the tone of penile vasculature and the smooth muscle of the corpus cavernosum. In primates, including humans, the L-arginine– In recent years, a deeper understanding of the nitric oxide–guanylyl cyclase–cyclic guanosine regulation of penile smooth muscle has led to monophosphate (cGMP) pathway is the key me- greater insight into the physiology of normal erectile chanism of penile erection1–4 (Figure 1). -
Effects of Tianeptine on Onset Time of Pentylenetetrazole-Induced Seizures in Mice: Possible Role of Adenosine A1 Receptors
Neuropsychopharmacology (2007) 32, 412–416 & 2007 Nature Publishing Group All rights reserved 0893-133X/07 $30.00 www.neuropsychopharmacology.org Effects of Tianeptine on Onset Time of Pentylenetetrazole-Induced Seizures in Mice: Possible Role of Adenosine A1 Receptors ,1 1 1 Tayfun I Uzbay* , Hakan Kayir and Mert Ceyhan 1Department of Medical Pharmacology, Psychopharmacology Research Unit, Gulhane Military Medical Academy, Ankara, Turkey Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss–Webster mice (25–35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5–80 mg/kg, i.p.) or saline administration. The onset times of ‘first myoclonic jerk’ (FMJ) and ‘generalized clonic seizures’ (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10–60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. -
Caspase-1-Dependent Inflammatory Signaling in Retinal Müller Cells During the Development of Diabetic Retinopathy
CASPASE-1-DEPENDENT INFLAMMATORY SIGNALING IN RETINAL MüLLER CELLS DURING THE DEVELOPMENT OF DIABETIC RETINOPATHY by KATHERINE EILEEN TRUEBLOOD Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Dissertation Advisor: Dr. George R. Dubyak Department of Physiology and Biophysics CASE WESTERN RESERVE UNIVERSITY January 2012 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Katherine Eileen Trueblood ______________________________________________________ Doctor of Philosophy candidate for the ________________________________degree *. Dr. Corey Smith (signed)_______________________________________________ (chair of the committee) Dr. George R. Dubyak ________________________________________________ Dr. Thomas McCormick ________________________________________________ Dr. Patrick Wintrode ________________________________________________ Dr. Margaret Chandler ________________________________________________ Dr. Thomas Nosek ________________________________________________ 10/21/11 (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. ii DEDICATION I dedicate this work to my brother, Jonathan Vern Trueblood, as he embarks on his own graduate school career this year. There will be many days where you will want to give up and throw in the towel; but I promise there will be many more to come where you will be glad you didn’t. Rom. 4:18-21 Always “hope against hope!” iii TABLE -
Inhalant Abuse Pediatric Care
CLINICAL REPORT Guidance for the Clinician in Rendering Inhalant Abuse Pediatric Care Janet F. Williams, MD, Michael Storck, MD, and the Committee on Substance Abuse and Committee on Native American Child Health ABSTRACT Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet-underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeco- nomic boundaries, causing significant morbidity and mortality in school-aged and older children. This clinical report reviews key aspects of inhalant abuse, empha- sizes the need for greater awareness, and offers advice regarding the pediatrician’s role in the prevention and management of this substance abuse problem. TYPES OF CHEMICALS AND PRODUCTS ABUSED The term “inhalant” encompasses a wide range of pharmacologically diverse substances that readily vaporize. Most other substances of abuse are classified by grouping together substances that share a specific central nervous system action or perceived psychoactive effect, but inhalant substances that are abused are grouped by having a common route of drug use. Inhalant abuse, sometimes referred to as solvent or volatile substance abuse, can be better understood when the expansive list of inhalants is classified into 3 groups on the basis of what is currently known pharmacologically: group I includes volatile solvents, fuels, and anesthetics; group II includes nitrous oxide; and group III includes volatile alkyl nitrites (Table 1). This classification is also consistent with reported differences in user populations, patterns of abuse, and associated problems seen clinically.1–3 Drugs that do not www.pediatrics.org/cgi/doi/10.1542/ readily vaporize at room temperature, such as cocaine, heroin, nicotine, or alcohol, peds.2007-0470 can also be abused through inhalation, but characteristic pharmacologic properties doi:10.1542/peds.2007-0470 distinguish these substances from inhalants. -
Expectation Hangover “I Wish I’D Had This Step-By-Step Guide on How to Overcome Huge Obstacles When I Shattered Both My Wrist and My Dreams of Playing for the NFL
Praise for Expectation Hangover “I wish I’d had this step-by-step guide on how to overcome huge obstacles when I shattered both my wrist and my dreams of playing for the NFL. Don’t let your Expectation Hangover control your life — apply what is in this book!” — Lewis Howes, former pro athlete turned lifestyle entrepreneur, host of The School of Greatness podcast “Christine Hassler is the kind of true spiritual guide we all need in our corner — soulful, wise, compassionate, and practical. Her proven methods and deep personal understanding are like the best medicine ever for your heart and soul.” — Christine Arylo, self-love catalyst and author of Madly in Love with ME: The Daring Adventure of Becoming Your Own Best Friend “Christine Hassler continues to be an invaluable voice for every generation. Her insights and observations have changed and enlightened the way I look at my life and the way I raise my children.” — Michael DeLuca, film producer and Columbia Pictures president of production “Disappointment can be a big, ugly monster hiding under our beds. This book is the go-to for getting us through Expectation Hangovers with grace and shining light to cast away those ugly creatures of disappointment!” — Kathryn Budig, author of The Women’s Health Big Book of Yoga “Christine Hassler is brilliant and insightful. Finally, here is the solution for dealing with something that plagues so many, myself included. If you’re hoping to thrive in a world that seems to hand out setbacks at every oppor- tunity, this is the book for you. -
Phosphodiesterase (PDE)
Phosphodiesterase (PDE) Phosphodiesterase (PDE) is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators ofsignal transduction mediated by these second messenger molecules. www.MedChemExpress.com 1 Phosphodiesterase (PDE) Inhibitors, Activators & Modulators (+)-Medioresinol Di-O-β-D-glucopyranoside (R)-(-)-Rolipram Cat. No.: HY-N8209 ((R)-Rolipram; (-)-Rolipram) Cat. No.: HY-16900A (+)-Medioresinol Di-O-β-D-glucopyranoside is a (R)-(-)-Rolipram is the R-enantiomer of Rolipram. lignan glucoside with strong inhibitory activity Rolipram is a selective inhibitor of of 3', 5'-cyclic monophosphate (cyclic AMP) phosphodiesterases PDE4 with IC50 of 3 nM, 130 nM phosphodiesterase. and 240 nM for PDE4A, PDE4B, and PDE4D, respectively. Purity: >98% Purity: 99.91% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 10 mg, 50 mg (R)-DNMDP (S)-(+)-Rolipram Cat. No.: HY-122751 ((+)-Rolipram; (S)-Rolipram) Cat. No.: HY-B0392 (R)-DNMDP is a potent and selective cancer cell (S)-(+)-Rolipram ((+)-Rolipram) is a cyclic cytotoxic agent. (R)-DNMDP, the R-form of DNMDP, AMP(cAMP)-specific phosphodiesterase (PDE) binds PDE3A directly. -
Phosphodiesterase Type 5 Inhibitors for the Treatment of Erectile Dysfunction in Patients with Diabetes Mellitus
International Journal of Impotence Research (2002) 14, 466–471 ß 2002 Nature Publishing Group All rights reserved 0955-9930/02 $25.00 www.nature.com/ijir Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus MA Vickers1,2* and R Satyanarayana1 1Department of Surgery, Togus VA Medical Center, Togus, Maine, USA; and 2Department of Surgery, Division of Urology, University of Massachusetts Medical School, Worcester, Massachusetts, USA Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in ‘general’ and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built. International Journal of Impotence Research (2002) 14, 466–471. doi:10.1038=sj.ijir.3900910 Keywords: phosphodiesterase inhibitor; erectile dysfunction; diabetes mellitus; sildenafil; tadalafil; vardenafil Introduction (NO), vasointestinal peptide and prostacyclin, de- creases. Additionally, the endothelial cells that line the cavernosal arteries and sinusoids have a Pathophysiology of ED in diabetes decreased response to nitric oxide due to increased production of advanced glycation end-products and changes associated with insulin resistance.5,6 The Diabetes mellitus is a risk factor for erectile diabetic also experiences a decreased level of dysfunction (ED).