Saliva: a Reliable Sample Matrix in Bioanalytics

Total Page:16

File Type:pdf, Size:1020Kb

Saliva: a Reliable Sample Matrix in Bioanalytics Review For reprint orders, please contact [email protected] 9 Review Saliva: a reliable sample matrix in bioanalytics Bioanalysis Saliva is gaining increasing attention as a bioanalytical sample matrix. Mostly because Michael Gröschl of the easy and noninvasive collection, it is not only beneficial in endocrinological Celerion Switzerland AG, Allmendstrasse and behavioral science, but also in pediatrics. Saliva also has the advantage of being 32, CH-8320 Fehraltorf, Switzerland Author for correspondence: the only body fluid which can be collected even during physical exercise, for example, Tel.: +41 43 355 7619 during sportive activities, and there are physiological characteristics that make it [email protected] superior to serum/plasma or urine for specific scientific questions. This review provides an insight into the physiology of saliva formation, explaining how certain compounds enter this bodily fluid, and gives advice for collection, storage and analytical methods. Finally, it presents a number of reliable and proven applications for saliva analysis from scientific fields including endocrinology, sports medicine, forensics and immunology. First draft submitted: 17 January 2017; Accepted for publication: 2 March 2017; Published online: 15 May 2017 Keywords: bioanalytics • endocrinology • forensics • immunology • noninvasive • saliva • sports medicine Traditional biological matrices for the analysis achieved for the majority of parameters. There- of diagnostic substances, such as hormones, fore, it is still state of the art to assess saliva drugs or immunoglobulins, are serum, plasma concentrations in combination with results and urine. Although serum and plasma pro- obtained from matched plasma samples. vide information about the currently circu- This review provides possibilities of saliva lating concentration of the analyte, urine analysis in various fields of research and to provides an overview of the accumulated show potentials for diagnostics and clinical 8 excretory metabolites since the last act of uri- trials. First, information is given on physiol- nation. Over years, the analysis of saliva has ogy of the salivary glands and saliva secretion. attracted increased attention, in particular, Subsequently, the methodological aspects for among clinicians and researchers who con- sampling and measurement of saliva are dis- 2017 sider saliva as a noninvasive and stress-free cussed. Finally, the diversity of saliva analysis alternative to blood sampling. is demonstrated with examples from the fields Numerous publications have demonstrated of endocrinology, forensic chemistry, thera- the analysis of saliva to be a useful alterna- peutic drug monitoring, sports medicine, tive for determining many endocrine param- metabolic diseases, immunology, and oral eters since saliva lacks the one main problem and gastrointestinal diseases. of blood collection, which is the invasiveness of the venipuncture resulting an increased Anatomy & physiology of the response of stress hormones, namely glucocor- salivary glands ticoids [1,2] and catecholamines [3]. To date, a The major part (65%) of saliva is produced definitive interpretation of salivary concentra- by the submandibular glands. The parotid tions for daily routine purpose has not been glands contribute between 20 and 50% to part of 10.4155/bio-2017-0010 © 2017 Future Science Ltd Bioanalysis (Epub ahead of print) ISSN 1757-6180 Review Gröschl the total saliva volume, depending on stimulation [4,5]. Furthermore, saliva contains factors of the immune Only a minor fraction of 5% is secreted by the sublin- response, such as secretory IgA [12], cathelicidin [13] or gual glands. The remaining 10% derive from numer- adrenomedullin [14], controlling the microbial growth ous small glands embedded in the oral cavity [5,6]. For on the epithelia. routine applications, open-field studies or outpatient The acini are surrounded by blood capillaries that sampling, mixed saliva is the only suitable sample enable the passage of substances from the circulation material, while gland-specific collection at the exit into the salivary glands (Figure 1) [15] . of the excretory ducts with cannulas or pipettes is The concentration- or speed-limiting step of hor- extremely intricate and is only performed for specific mone transfer from blood into saliva is the passage otorhinolaryngologic investigations. This mixed saliva through the capillary wall and the membrane of the contains, to a small portion, exudate from the gingiva glandular epithelial cells. Transfer of substances from and peeled oral epithelial cells. the capillaries into the acini is driven by diverse mech- Saliva is produced in secretory end pieces of the anisms resulting in a complex fluid. These transport glands, called acini. These acini drain into the sali- mechanisms are either passive diffusion, ultrafiltration vary ducts, with small ‘striated’ ducts opening into through pores or active and energy dependent against wider intercalated and excretory ducts (Figure 1). The concentration gradients [16] . daily total volume ranges between 500 and 1500 ml, In passive diffusion, lipid-soluble materials cross the depending on water balance and stimulation [7,8]. cell membranes of capillaries and acini. The salivary con- Various enzymes like amylase and lipase, prepar- centrations of lipid-soluble, unconjugated steroids such ing food for digestion, are supplied by saliva [9–11] . as cortisol and testosterone approximate the unbound Protein-bound steroid or amine Lipophilic substances transported from blood Capillary Hydrophilic substances transported from blood Steroid after conversion Peptides produced by salivary glands Tunnel or transporter protein Acinus Glandular enzymes Acinus Striated duct Capillary Intercalated duct Expression and secretion Active transport (energy dependent) Passive diffusion Blood flow Saliva flow Figure 1. Transport mechanisms of substances into saliva. Small lipophilic compounds, such as steroids, enter the glands by passive diffusion. Hydrophilic compounds (electrolytes and many proteins) are actively transported from the circulation to the glands. Enzymatic conversion has been reported (e.g., androstenedione to testosterone by 17-hydroxysteroid oxidoreductase). Peptides are either actively transported from blood to saliva (e.g., insulin) or are produced by the glands themselves (e.g., EGF). 10.4155/bio-2017-0010 Bioanalysis (Epub ahead of print) future science group Saliva: a reliable sample matrix in bioanalytics Review plasma concentrations, while hydrophilic, conjugated Serum (IU/ml) steroids such as dehydroepiandrosterone sulfate only 50 reach 1% of the unbound plasma concentrations [17] . Saliva (IU/ml) Ultrafiltration drives the transport of small polar 40 molecules into saliva through tight junctions at the apical pole of the acini. Mazariegos et al. [18] found 30 these tight junctions in the resting rat parotid gland 20 impermeable to tracers of molecular weights >2 kDa. IU/ml An active transport mechanism clearly applies for 10 many electrolytes [19,20] and for some peptides such as insulin [21], but was also proven for some drugs [16] . 0 Borzelleca and Cherrick [22] had already investigated the presence of antibiotics in saliva in 1965. The secre- 01530456075 90 105 120 tion of penicillin and tetracycline appeared to correlate Min with the concentration in blood. Since the secretion of penicillin by the salivary glands and by the kidney was Figure 2. Curse of insulin in matched serum and saliva prevented by probenecid, an inhibitor of renal activity, (n = 8 each) after oral glucose administration. In saliva, penicillin secretion in saliva is subjected to an active the CMax is delayed by approximately 30 min, reaching transport. Zuidema and Van Ginneken [23] confirmed only lower concentrations compared with serum. this finding. Another inhibitor of renal activity, pro- benecid, showed no effect on the salivary secretion of broad antiviral activity, since hepatitis B virus remains diprophylline. These data suggested that the secretory infectious in mixed saliva [29]. mechanism in the kidney and in the salivary gland is A prerequisite for conducting pharmacokinetic not identical. studies using saliva is to avoid residues of orally admin- It is noteworthy that an active transport is not only istered drugs in the oral cavity, as shown for amphet- energy-consuming, but also time-consuming, and can amines capsuled in gelatin [30]. Usually, the problem lead to a shift in the appearance of the compound, can be solved by rinsing the mouth with water before when matched plasma and saliva samples are plotted starting the collection, but the possibility of dilution together, as indicated in Figure 2 for human insulin. effects needs to be considered [31] . The contribution of The movement of marker substances from blood crevicular fluid from the gingiva to mixed saliva can be to saliva and vice versa was investigated [24], describ- limited by avoiding tooth brushing prior to sampling ing permeability barriers in the glands that allow for and by rinsing the mouth with water prior to sam- some substances to pass readily into the saliva while pling [32,33]. To ensure robust and reproducible profiles, other substances were held back. Some pharmaceuti- circadian rhythms as well in salivary gland activity [34] cals enhance saliva secretion by dilation of the tight and production of compounds being transferred into junctions of the secretory end pieces [25], while some saliva (e.g., steroid hormones
Recommended publications
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
    [Show full text]
  • Wo 2010/075090 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 1 July 2010 (01.07.2010) WO 2010/075090 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 409/14 (2006.01) A61K 31/7028 (2006.01) kind of national protection available): AE, AG, AL, AM, C07D 409/12 (2006.01) A61P 11/06 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2009/068073 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 15 December 2009 (15.12.2009) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (26) Publication Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/122,478 15 December 2008 (15.12.2008) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): AUS- ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, PEX PHARMACEUTICALS, INC.
    [Show full text]
  • The Latin Language and Medical Terminology
    T. Titiyevska, O. Gordiyenko, A. Kulichenko THE LATIN LANGUAGE AND MEDICAL TERMINOLOGY QUIZZES AND TASKS FOR PRACTICAL SKILLS EVALUATION for the First-Year Students of the Medical Faculties with the English Medium of Instruction, Specialty 222 “General Medicine” Zaporizhzhia 2019 1 Zaporizhzhia State Medical University Department of Foreign Languages T. Titiyevska, O. Gordiyenko, A. Kulichenko THE LATIN LANGUAGE AND MEDICAL TERMINOLOGY QUIZZES AND TASKS FOR PRACTICAL SKILLS EVALUATION for the First-Year Students of the Medical Faculties with the English Medium of Instruction, Specialty 222 “General Medicine” Zaporizhzhia 2019 2 UDC 811.124:[001.4:61](076.1) T64 A manual is approved and recommended for using in learning process by the Central Methodical Commission of Zaporizhzhia State Medical University (record No. 1 from September 26, 2019). Reviewers: S. Chugin, PhD (Medicine), Associate Professor, Department of Human Anatomy, Operative Surgery and Topographic Anatomy, Zaporizhzhia State Medical University. R. Shramko, PhD (Philology), Associate Professor, Department of English and German Philology, Poltava V.G. Korolenko National Pedagogical University. Authors: T. Titiyevska, Senior Lecturer, Department of Foreign Languages, Zaporizhzhia State Medical University. O. Gordiyenko, PhD (Philology), Associate Professor, Department of Foreign Languages, Zaporizhzhia State Medical University. A. Kulichenko, PhD (Pedagogics), Associate Professor, Department of Foreign Languages, Zaporizhzhia State Medical University. Е The Latin Language and Medical Terminology. Quizzes and Tasks for Practical Skills Evaluation for the First-Year Students of the Medical Faculties with the English Medium of Instruction, specialty 222 “General Medicine” = Латинська T64 мова та медична термінологія. Зб. завд. для самост. роб. та завд. для перев. практ. навич. у студ.-іноз.
    [Show full text]
  • Comparing Retention in Xanthines Separation Between a Silica and Titania Stationary Phase in HPLC
    22 General Comparing retention in xanthines separation between a silica and titania stationary phase in HPLC Agnieszka PIWIEN Introduction The Objective of analytical chemistry is to determine chemical composi- Fig.1. Dependence of retention factor Lnk to % tions. of ACN in mobile phase in Aquasil column, Nowadays, it mostly relies on instrumental methods. Research conditions: !ow rate 200μL/min, ACN-Water (v/v) focuses on discovering new materials and chromatography principles. Columns with a silica layer are currently being used as a stationary phase in high performance liquid chromatography (HPLC). Owing to their low mechanical, thermal and pH stability the scientists are forced to investi- gate the different column supports. Therefore, the study on titanium support column was performed on the grounds of its strong Lewis acid sites probably resistant to changes of pH. The aim of these experiments was to compare the effectiveness of these two columns. Experimental methods First of all the xanthines and their derivatives were analyzed in the silica column Aquasil (50mm x 2,1mm I.D., 1,9m) in RPLC mode then in the Fig.2. Dependence of retention factor Lnk to % titanium dioxide column SachtoporeNP (100mm x 2,1mm I.D., 5m) in of water in mobile phase in Sachtopore column, HILIC mode. The Titania column was also studied under the influence of a conditions: !ow rate 200μL/min, ACN-Water mobile phase with and without a buffer solution. (v/v) All solutions were prepared using deionized water (Elga LAB WATER) and acetonitrile in a 1:1 (v/v) ratio. Uracile and naphthalene were respectively used as dead time markers, the former in the RP mode and the latter in HILIC mode (Hydrophilic interaction liquid chromatography).
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2010/0304998 A1 Sem (43) Pub
    US 20100304998A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0304998 A1 Sem (43) Pub. Date: Dec. 2, 2010 (54) CHEMICAL PROTEOMIC ASSAY FOR Related U.S. Application Data OPTIMIZING DRUG BINDING TO TARGET (60) Provisional application No. 61/217,585, filed on Jun. PROTEINS 2, 2009. (75) Inventor: Daniel S. Sem, New Berlin, WI Publication Classification (US) (51) Int. C. GOIN 33/545 (2006.01) Correspondence Address: GOIN 27/26 (2006.01) ANDRUS, SCEALES, STARKE & SAWALL, LLP C40B 30/04 (2006.01) 100 EAST WISCONSINAVENUE, SUITE 1100 (52) U.S. Cl. ............... 506/9: 436/531; 204/456; 435/7.1 MILWAUKEE, WI 53202 (US) (57) ABSTRACT (73) Assignee: MARQUETTE UNIVERSITY, Disclosed herein are methods related to drug development. Milwaukee, WI (US) The methods typically include steps whereby an existing drug is modified to obtain a derivative form or whereby an analog (21) Appl. No.: 12/792,398 of an existing drug is identified in order to obtain a new therapeutic agent that preferably has a higher efficacy and (22) Filed: Jun. 2, 2010 fewer side effects than the existing drug. Patent Application Publication Dec. 2, 2010 Sheet 1 of 22 US 2010/0304998 A1 augavpop, Patent Application Publication Dec. 2, 2010 Sheet 2 of 22 US 2010/0304998 A1 g Patent Application Publication Dec. 2, 2010 Sheet 3 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 4 of 22 US 2010/0304998 A1 tg & Patent Application Publication Dec. 2, 2010 Sheet 5 of 22 US 2010/0304998 A1 Patent Application Publication Dec.
    [Show full text]
  • 1120 Bronchodilators and Anti-Asthma Drugs
    1120 Bronchodilators and Anti-asthma Drugs Profile Preparations unchanged in the urine with an elimination half-life of about 2 Cilomilast is a phosphodiesterase type-4 inhibitor that has been Proprietary Preparations (details are given in Part 3) hours. Diprophylline is distributed into breast milk. investigated in the treatment of chronic obstructive pulmonary Arg.: Bronq-C; Clembumar; Oxibron; Austria: Spiropent; Chile: Airum; disease. Uses and Administration Asmeren; Broncotosil†; Cz.: Spiropent; Ger.: Contraspasmin†; Spiropent; Diprophylline is a theophylline derivative which is used similar- Gr.: Spiropent; Hong Kong: Clenasma†; Hung.: Spiropent; Indon.: Spiropent; Ital.: Clenasma†; Monores; Prontovent†; Spiropent; Jpn: ly to theophylline (p.1146) as a bronchodilator in reversible air- Spiropent; Mex.: Novegam; Oxyflux; Spiropent; Philipp.: Spiropent; ways obstruction. Clenbuterol Hydrochloride (BANM, rINNM) ⊗ Port.: Broncoterol; Cesbron; Spain: Spiropent†; Ventolase; Venez.: Brodi- The usual oral dose of diprophylline is up to 15 mg/kg every 6 lan; Brodilin; Buclen; Clenbunal; Risopent. Clenbutérol, chlorhydrate de; Clenbuteroli hydrochloridum; Hid- hours. It has also been given intramuscularly. Diprophylline is Multi-ingredient: Arg.: Mucosolvon Compositum; Oxibron NF; Aus- rocloruro de clenbuterol; Klenbuterol hydrochlorid; Klenbuterol- also an ingredient of preparations that have been promoted for tria: Mucospas; Ger.: Spasmo-Mucosolvan; Mex.: Ambodil-C; Balsibron- coughs. hidroklorid; Klenbuterolhydroklorid; Klenbuterolihydrokloridi;
    [Show full text]
  • Video Course Evaluation Form My Name Is
    Garden State CLE 2000 Hamilton Avenue Hamilton, New Jersey 08619 (609) 584-1924 – Phone (609) 584-1920 - Fax Video Course Evaluation Form My Name is: __________________________________________ Name of Course: ______________________________________ My Street address: _____________________________________ City: _____________________ State: _____ Zip Code: ____ Email Address: ________________________________________ Please Circle the Appropriate Answer Instructors: Poor Satisfactory Good Excellent Materials: Poor Satisfactory Good Excellent CLE Rating: Poor Satisfactory Good Excellent Required: Secret words that appeared on the screen during the seminar. 1) __________________________ 2) _______________________ 3) __________________________ 4) _______________________ What did you like most about the seminar? _____________________________________________________________ _____________________________________________________________ What criticisms, if any, do you have? _____________________________________________________________ _____________________________________________________________ I certify that I watched, in its entirety, the above-listed CLE Course. Signature ___________________________________ Date_________ In order to receive your CLE credits, please send our payment and this completed form to Garden State CLE, 2000 Hamilton Avenue, Hamilton, New Jersey, 08619. BURLINGTON COUNTY BAR ASSOCIATION --- Interpreting Your Client’s Drug Lab Results: Were They Impaired? © Chris Baxter 2020 DO LAB RESULTS MATTER IN A DUI-D? YES ➢State
    [Show full text]
  • Methylxanthines and Neurodegenerative Diseases: an Update
    nutrients Review Methylxanthines and Neurodegenerative Diseases: An Update Daniel Janitschke 1,† , Anna A. Lauer 1,†, Cornel M. Bachmann 1, Heike S. Grimm 1, Tobias Hartmann 1,2 and Marcus O. W. Grimm 1,2,* 1 Experimental Neurology, Saarland University, 66421 Homburg/Saar, Germany; [email protected] (D.J.); [email protected] (A.A.L.); [email protected] (C.M.B.); [email protected] (H.S.G.); [email protected] (T.H.) 2 Deutsches Institut für DemenzPrävention (DIDP), Saarland University, 66421 Homburg/Saar, Germany * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review Citation: Janitschke, D.; Lauer, A.A.; Bachmann, C.M.; Grimm, H.S.; we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson’s disease Hartmann, T.; Grimm, M.O.W.
    [Show full text]
  • Alphabetical Listing of ATC Drugs & Codes
    Alphabetical Listing of ATC drugs & codes. Introduction This file is an alphabetical listing of ATC codes as supplied to us in November 1999. It is supplied free as a service to those who care about good medicine use by mSupply support. To get an overview of the ATC system, use the “ATC categories.pdf” document also alvailable from www.msupply.org.nz Thanks to the WHO collaborating centre for Drug Statistics & Methodology, Norway, for supplying the raw data. I have intentionally supplied these files as PDFs so that they are not quite so easily manipulated and redistributed. I am told there is no copyright on the files, but it still seems polite to ask before using other people’s work, so please contact <[email protected]> for permission before asking us for text files. mSupply support also distributes mSupply software for inventory control, which has an inbuilt system for reporting on medicine usage using the ATC system You can download a full working version from www.msupply.org.nz Craig Drown, mSupply Support <[email protected]> April 2000 A (2-benzhydryloxyethyl)diethyl-methylammonium iodide A03AB16 0.3 g O 2-(4-chlorphenoxy)-ethanol D01AE06 4-dimethylaminophenol V03AB27 Abciximab B01AC13 25 mg P Absorbable gelatin sponge B02BC01 Acadesine C01EB13 Acamprosate V03AA03 2 g O Acarbose A10BF01 0.3 g O Acebutolol C07AB04 0.4 g O,P Acebutolol and thiazides C07BB04 Aceclidine S01EB08 Aceclidine, combinations S01EB58 Aceclofenac M01AB16 0.2 g O Acefylline piperazine R03DA09 Acemetacin M01AB11 Acenocoumarol B01AA07 5 mg O Acepromazine N05AA04
    [Show full text]
  • Comparison of Caffeine and D-Amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary
    NIH Public Access Author Manuscript J Addict Res Ther. Author manuscript; available in PMC 2014 November 18. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: J Addict Res Ther. 2014 ; 5(2): 176–. doi:10.4172/2155-6105.1000176. Comparison of Caffeine and d-amphetamine in Cocaine- Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine Scott D Lane1,*, Charles E Green1, Joy M Schmitz1, Nuvan Rathnayaka1, Wendy B Fang2, Sergi Ferré3, and F Gerard Moeller4 1Center for Neurobehavioral Research on Addictions, Department of Psychiatry & Behavioral Sciences, University of Texas Health Science Center – Houston, Houston, TX USA 2Center for Human Toxicology, University of Utah, Salt Lake City, UT, USA 3Integrative Neurobiology, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA 4Division on Addictions, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA Abstract Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2011/0142957 A1 VAN KEMPEN (43) Pub
    US 2011 O142957A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0142957 A1 VAN KEMPEN (43) Pub. Date: Jun. 16, 2011 (54) METHOD OF TREATING PARTURIENT Publication Classification PLACENTAL MAMMALS IN ORDER TO (51) Int. Cl. REDUCE MATERNAL AND/OR UTERINE A633/42 (2006.01) EXHAUSTION A633/04 (2006.01) A633/00 (2006.01) (76) Inventor: Theo VAN KEMPEN, Sint Stevens A6II 3/522 (2006.01) Woluwe (BE) A63L/35 (2006.01) (21) Appl. No.: 13/030,422 (52) U.S. Cl. ... 424/601; 424/709: 424/722: 514/263.34; 514/654 (22) Filed: Feb. 18, 2011 (57) ABSTRACT Related U.S. Application Data The present invention relates to a method of facilitating the birth process of placental mammals, especially to a method of (62) Division of application No. 12/063,830, filed on Aug. reducing delays in the birth process and, thereby, complica 4, 2008, now Pat. No. 7,893,070, filed as application tions resulting there from that may negatively affect the health No. PCT/NL2006/050201 on Aug. 14, 2006. and wellbeing of the mother and increase the incidence of stillbirths and/or neonatal mortality. According to the present (60) Provisional application No. 60/707,954, filed on Aug. invention delays in parturition that result from maternal and/ 15, 2005. or uterine exhaustion may be prevented or reduced by the administration of an effective amount of one or more psycho (30) Foreign Application Priority Data motor stimulants to the parturient mammal prior to and/or during parturition. Said psychomotor stimulant is selected Aug.
    [Show full text]