DOCSLIB.ORG

Research Article Blood Harmane Concentrations in 497 Individuals Relative to Coffee, Cigarettes, and Food Consumption on the Morning of Testing

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Research Article Blood Harmane Concentrations in 497 Individuals Relative to Coffee, Cigarettes, and Food Consumption on the Morning of Testing View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Hindawi Publishing Corporation Journal of Toxicology Volume 2011, Article ID 628151, 6 pages doi:10.1155/2011/628151 Research Article Blood Harmane Concentrations in 497 Individuals Relative to Coffee, Cigarettes, and Food Consumption on the Morning of Testing Elan D. Louis,1, 2, 3, 4 Pam Factor-Litvak,3 Marina Gerbin,1 Wendy Jiang,5 and Wei Zheng5 1 GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, Unit 198, Neurological Institute, 710 West 168th Street, New York, NY 10032-2699, USA 2 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10027-6900, USA 3 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032-3727, USA 4 Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 5 School of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, USA Correspondence should be addressed to Elan D. Louis, [email protected] Received 23 November 2010; Revised 11 February 2011; Accepted 16 February 2011 Academic Editor: Margaret James Copyright © 2011 Elan D. Louis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Harmane, a potent neurotoxin linked with several neurological disorders, is present in many foods, coffee,andcigarettes.We assessed whether morning food/coffee consumption and smoking were reflected in blood harmane concentrations (BHCs) we obtained in an epidemiologic sample (n = 497). Participants who smoked on the morning of phlebotomy had similar logBHCs to those who had not smoked (P = .57);therewasnocorrelationbetweenlogBHCsandnumberofcigarettes(P = .59). Among the coffee drinkers, there was no correlation between number of cups and logBHCs (P = .98). Participants who had eaten on the morning of phlebotomy had similar logBHCs to those who had not (P = .49); logBHCs did not correlate with the time latency between last food consumption and phlebotomy (P = .74). BHCs in this sample of ∼500 individuals did not covary with recent smoking, coffee, or food consumption, suggesting that our inability to withhold these exposures on the morning of phlebotomy was not reflected in the BHCs we measured. 1. Introduction (harmane dissolved in corn oil), blood harmane levels in rats peaked rapidly (in approximately 30 minutes) and then Harmane (1-methyl-9H-pyrido[3,4-β]indole) is a potent gradually returned to baseline within 3–5 hours [9]. neurotoxin that has been linked with several neurological Studies of harmane and its relation to neurological outcomes [1, 2]. Although it is produced endogenously outcomes (essential tremor [ET] and Parkinson’s disease) by the body, harmane is also present in many foods (esp. often involve work with frail and elderly study subjects meats but also plant-derived foods) [3]. Studies have shown for whom fasting on the morning of testing is not fea- that harmane concentrations are particularly high in certain sible, especially as many of these patients must also take commonly consumed beverages (esp. coffee) [3–6]aswell prescription medications (often accompanied with food). as cigarettes [3, 5, 7]. Coffee consumption and smoking are It is also difficult to ask smokers to refrain, and their widespread and common human behaviors. attempts to do so can transiently exacerbate their tremor, Smoking [8] and food ingestion [9] have been shown to confounding the accurate assessment of tremor severity. result in transient elevations in BHCs. After smoking, blood Given these limitations, it is important to know whether harmane levels rise rapidly and seem to return to baseline food consumption, coffee consumption, and/or smoking on within one hour, although the number of tested human the morning of phlebotomy are reflected in blood harmane volunteers has been small (n = 3) [8]. After oral dosing concentrations (BHCs). 2 Journal of Toxicology Our overarching question was whether morning [53.9%] female, chi-square = 0.00, and P = .96), years of food/coffee consumption and smoking were reflected in education (15.4 ± 3.5versus15.3 ± 3.5years,t = 0.49, and the BHCs we obtained. The specific questions we asked P = .63), and proportion who were current smokers (43 were the following. (1) Did participants who smoked on [8.7%] versus 57 [8.2%]) chi-square = 0.09, and P = .77). the morning of phlebotomy have higher BHCs than those who did not smoke? (2) Was the the number of cigarettes 2.2. Clinical Evaluation. All participants were evaluated in smoked on the morning of phlebotomy correlated with person by a trained tester. The tester administered clinical ff BHCs? (3) Did participants who consumed co ee on the questionnaires and performed a videotaped tremor exami- morning of phlebotomy have higher BHCs than those nation and phlebotomy. ff who did not? (4) Was the number of cups of co ee on the As noted above, most evaluations were home visits and, morning of phlebotomy correlated with BHCs? (5) Was therefore, were performed in the late morning, making there a correlation between the time of last food ingestion fasting BHCs impractical. ffi and BHCs? If these questions were answered a rmatively, The tester used a structured questionnaire to collect this would suggest that these exposures are important to demographic information including age in years, gender, ff consider when assessing case-control di erences in BHCs. race, years of education, current smoker (yes versus no), the If not, it would suggest that these exposures are relatively number of cigarettes smoked per day, cigarette pack years, the unimportant in this context. Using data from a large number of cigarettes smoked on the morning of phlebotomy, epidemiological study of ET, we evaluated these exposures and the number of cups of coffee consumed on the morning in approximately 500 individuals. In addition to BHCs, of phlebotomy. Several years into the study, questions were ff information on smoking, co ee consumption, and food added as to whether food was consumed on the morning intake on the morning of phlebotomy were available. of phlebotomy and the number of hours between last food consumption and the phlebotomy. Similar data on number of hours between smoking or coffee consumption and 2. Methods phlebotomy were not available. Medical comorbidity was assessed with the cumulative illness rating scale (range = 0– 2.1. Participants. All participants were enrolled between 42 (high comorbidity)) [13]. June 2000 and May 2008 in a study of the environmental The tester videotaped a tremor examination in all epidemiology of tremor at Columbia-University Medical participants [10, 12]. Each of 12 videotaped action tremor Center (CUMC). Participants consisted of ET cases and items was rated by a senior movement disorder neurologist controls. By design, ET cases were identified from several (E.D.L.) on a scale from 0 (none) to 3 (severe tremor) sources; the major ones were a computerized billing database [10–12]. of patients at the Neurological Institute of New York, CUMC, and the International Essential Tremor Foundation, whose members were mailed advertisements [2, 10]. All cases had 2.3. BHCs. At the time of the evaluation, phlebotomy was received a diagnosis of ET from their treating neurologist performed. When the evaluation was performed in the par- and lived within two-hour driving distance of CUMC in ticipant’s home, blood samples were temporarily stored on − ◦ the New York Metropolitan area. Based on a videotaped ice packs and then several hours later transferred to a 20 C tremor examination, described below, their diagnoses were freezer; if performed at CUMC, they were placed immedi- − ◦ confirmed by a senior movement disorder neurologist ately into a 20 C freezer. Blood harmane concentrations (E.D.L.) using published diagnostic criteria (moderate or were measured blinded to all clinical information with a greater amplitude action tremor during ≥3 activities or a well-established high-performance liquid chromatography head tremor in the absence of Parkinson’s disease, dystonia, method described in detail in our previous studies [2, 10, 14]. ffi or another neurological disorder) [10–12]. The intraday precision, measured as a coe cient of variation Normal control subjects were also recruited during the at 25 ng/mL, was 6.7%. The interday precision was 7.3% [14]. same time period [2, 10].Thesecontrolswereidentified Our method uses whole blood rather than plasma. Harmane using random digit telephone dialing within a defined set of is highly lipophilic, accumulating inside of blood cells, with telephone area codes in the New York Metropolitan area that published studies demonstrating low relative recovery of were represented by the ET cases. Controls were frequency harmane from plasma [9, 14]. matched to cases based on gender, race, and current age. The CUMC Internal Review Board approved of all 2.4. Statistical Analyses. Statistical analyses were performed study procedures, and signed written informed consent was in SPSS (Version 18.0). The empirical distribution of BHCs obtained from all participants upon enrollment [2, 10]. was positively skewed (one-sample Kolmogorov-Smirnov Of 698 ET cases and controls enrolled, complete data test, z = 9.37, P<.001), even after log transformation were available in 497 (71.2%). The majority of the remaining (one-sample Kolmogorov-Smirnov test, z = 2.37, P<.001). participants had refused phlebotomy or had had an unsuc- Hence, nonparametric tests (Mann Whitney U, Kruskal- cessful phlebotomy attempt. The final sample of 497 was Wallis, Spearman’s rho) were used when assessing this similar to the base sample of 698 in terms of age (mean ± variable. For smoking, pack years was assigned the value “0” standard deviation = 66.0 ± 14.4versus67.2 ± 14.2years, for nonsmokers.
Load more

Recommended publications
  • National Center for Toxicological Research
    National Center for Toxicological Research Annual Report Research Accomplishments and Plans FY 2015 – FY 2016 Page 0 of 193 Table of Contents Preface – William Slikker, Jr., Ph.D. ................................................................................... 3 NCTR Vision ......................................................................................................................... 7 NCTR Mission ...................................................................................................................... 7 NCTR Strategic Plan ............................................................................................................ 7 NCTR Organizational Structure .......................................................................................... 8 NCTR Location and Facilities .............................................................................................. 9 NCTR Advances Research Through Outreach and Collaboration ................................... 10 NCTR Global Outreach and Training Activities ............................................................... 12 Global Summit on Regulatory Science .................................................................................................12 Training Activities .................................................................................................................................14 NCTR Scientists – Leaders in the Research Community .................................................. 15 Science Advisory Board ...................................................................................................
    [Show full text]
  • TAAR1 Activation Modulates Monoaminergic Neurotransmission, Preventing Hyperdopaminergic and Hypoglutamatergic Activity
    TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity Florent G. Revela, Jean-Luc Moreaua, Raul R. Gainetdinovb, Amyaouch Bradaiac, Tatyana D. Sotnikovab, Roland Morya, Sean Durkina, Katrin Groebke Zbindend, Roger Norcrossd, Claas A. Meyere, Veit Metzlera, Sylvie Chaboza, Laurence Ozmena, Gerhard Trubea, Bruno Pouzeta, Bernhard Bettlerf, Marc G. Carong, Joseph G. Wettsteina, and Marius C. Hoenera,1 aNeuroscience Research, dDiscovery Chemistry, and eDiscovery Technologies, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland; bDepartment of Neuroscience and Brain Technologies, Italian Institute of Technology, 16163 Genoa, Italy; cNeuroservice, Domaine de Saint-Hilaire, 13593 Aix-en-Provence, France; fDepartment of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, CH-4056 Basel, Switzerland; and gDepartment of Cell Biology, Duke University Medical Center, Durham, NC 27710 Edited by Richard D. Palmiter, University of Washington, Seattle, WA, and approved March 31, 2011 (received for review February 24, 2011) The trace amine-associated receptor 1 (TAAR1), activated by en- sitive to the locomotor-stimulating effect of d-amphetamine dogenous metabolites of amino acids like the trace amines and show elevated striatal release of dopamine (DA), noradren- p-tyramine and β-phenylethylamine, has proven to be an impor- aline (NA), and serotonin [5-hydroxytryptamine (5-HT)] after a d-amphetamine challenge (10, 12). Furthermore, the spontaneous tant modulator of the dopaminergic system and is considered −/− firing rate of the VTA DA neurons is augmented in Taar1 mice, a promising target for the treatment of neuropsychiatric disorders. fi To decipher the brain functions of TAAR1, a selective TAAR1 ago- and only in WT mice does pTyr decrease this ring rate (10).
    [Show full text]
  • 'Gating' Residues Ile199 and Tyr326 in Human Monoamine Oxidase B
    The ‘gating’ residues Ile199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitor recognition Erika M. Milczek1,*, Claudia Binda2, Stefano Rovida2, Andrea Mattevi2 and Dale E. Edmondson1 1 Departments of Chemistry and Biochemistry, Emory University, Atlanta, Georgia, USA 2 Department of Genetics and Microbiology, University of Pavia, Italy Keywords The major structural difference between human monoamine oxidases A dipartite to monopartite cavity conversion; (MAO A) and B (MAO B) is that MAO A has a monopartite substrate inhibitor specificity; monoamine oxidase B; cavity of 550 A˚3 volume and MAO B contains a dipartite cavity struc- mutations of gating residues; structure of ture with volumes of 290 A˚3 (entrance cavity) and 400 A˚3 (substrate methylene blue complex cavity). Ile199 and Tyr326 side chains separate these two cavities in MAO Correspondence B. To probe the function of these gating residues, Ile199Ala and Ile199Ala- D. E. Edmondson, Department of Tyr326Ala mutant forms of MAO B were investigated. Structural data on Biochemistry, Emory University, 1510 the Ile199Ala MAO B mutant show no alterations in active site geometries Clifton Road, Atlanta, GA 30322, USA compared with wild-type enzyme while the Ile199Ala-Tyr326Ala MAO B Fax: +1 404 727 2738 mutant exhibits alterations in residues 100–103 which are part of the loop Tel: +1 404 727 5972 gating the entrance to the active site. Both mutant enzymes exhibit catalytic E-mail: [email protected] properties with increased amine KM but unaltered kcat values. The altered *Present address KM values on mutation are attributed to the influence of the cavity struc- Department of Chemistry, Princeton ture in the binding and subsequent deprotonation of the amine substrate.
    [Show full text]
  • Parkinson Disease and Other Movement Disorders
    P1: Trim: 8.375in × 10.875in Top: 0.373in Gutter: 0.664in LWBK915-57 LWW-KodaKimble-educational September 17, 2011 2:31 Parkinson Disease and Other 57 Movement Disorders Michael E. Ernst and Mildred D. Gottwald CORE PRINCIPLES CHAPTER CASES PARKINSON DISEASE 1 Parkinson disease (PD) is a chronic, progressive movement disorder resulting from Case 57-1 (Questions 1, 2) loss of dopamine from the nigrostriatal tracts in the brain, and is characterized by rigidity, bradykinesia, postural disturbances, and tremor. 2 Treatment for PD is aimed at restoring dopamine supply through one, or a Case 57-1 combination, of the following methods: exogenous dopamine in the form of a (Questions 3–18), precursor, levodopa; direct stimulation of dopamine receptors via dopamine Case 57-2 (Questions 1, 2) agonists; and inhibition of metabolic pathways responsible for degradation of levodopa. 3 Therapy for PD is usually delayed until there is a significant effect on quality of life; Case 57-1 (Questions 4, 10) generally younger patients start with dopamine agonists, whereas older patients may start with levodopa. 4 Initial therapy with dopamine agonists is associated with a lower risk of developing Case 57-1 (Questions 4, motor complications than with levodopa, but all patients will eventually require 10–15) levodopa. 5 Advanced PD is characterized by motor fluctuations including a gradual decline in Case 57-1 (Questions on time, and the development of troubling dopaminergic-induced dyskinesias. 15–18), Case 57-2 Dopamine agonists, monoamine oxidase type B (MAO-B) inhibitors, and (Question 1), Case 57-3 catechol-O-methyltransferase (COMT) inhibitors can reduce motor fluctuations; (Questions 1, 2) amantadine can improve dyskinesias.
    [Show full text]
  • Recent Applications of Capillary Electrophoresis in the Determination of Active Compounds in Medicinal Plants and Pharmaceutical Formulations
    molecules Review Recent Applications of Capillary Electrophoresis in the Determination of Active Compounds in Medicinal Plants and Pharmaceutical Formulations Marcin Gackowski 1,* , Anna Przybylska 1 , Stefan Kruszewski 2 , Marcin Koba 1 , Katarzyna M ˛adra-Gackowska 3 and Artur Bogacz 4 1 Department of Toxicology and Bromatology, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, A. Jurasza 2 Street, PL–85089 Bydgoszcz, Poland; [email protected] (A.P.); [email protected] (M.K.) 2 Biophysics Department, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Jagiello´nska13 Street, PL–85067 Bydgoszcz, Poland; [email protected] 3 Department of Geriatrics, Faculty of Health Sciences, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Skłodowskiej Curie 9 Street, PL–85094 Bydgoszcz, Poland; [email protected] 4 Department of Otolaryngology and Oncology, Faculty of Medicine, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Skłodowskiej Curie 9 Street, PL–85094 Bydgoszcz, Poland; [email protected] Citation: Gackowski, M.; Przybylska, * Correspondence: [email protected] A.; Kruszewski, S.; Koba, M.; M ˛adra-Gackowska,K.; Bogacz, A. Abstract: The present review summarizes scientific reports from between 2010 and 2019 on the use Recent Applications of Capillary of capillary electrophoresis to quantify active constituents (i.e., phenolic compounds, coumarins, Electrophoresis in the Determination protoberberines, curcuminoids, iridoid glycosides, alkaloids, triterpene acids) in medicinal plants and of Active Compounds in Medicinal herbal formulations. The present literature review is founded on PRISMA guidelines and selection Plants and Pharmaceutical criteria were formulated on the basis of PICOS (Population, Intervention, Comparison, Outcome, Formulations.
    [Show full text]
  • Β-Carboline Alkaloids and Essential Tremor: Exploring the Environmental Determinants of One of the Most Prevalent Neurological Diseases
    Review TheScientificWorldJOURNAL (2010) 10, 1783–1794 ISSN 1537-744X; DOI 10.1100/tsw.2010.159 β-Carboline Alkaloids and Essential Tremor: Exploring the Environmental Determinants of One of the Most Prevalent Neurological Diseases Elan D. Louis1,2,3,4,* and Wei Zheng5 1GH Sergievsky Center, 2Department of Neurology, 3Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York; 4Department of Epidemiology, Mailman School of Public Health, Columbia University, New York; 5School of Health Sciences, Purdue University, West Lafayette, IN E-mail: [email protected]; [email protected] Received May 24, 2010; Revised July 15, 2010; Accepted July 15, 2010; Published September 1, 2010 Essential tremor (ET) is among the most prevalent neurological diseases, yet its etiology is not well understood. Susceptibility genotypes undoubtedly underlie many ET cases, although no genes have been identified thus far. Environmental factors are also likely to contribute to the etiology of ET. Harmane (1-methyl-9H-pyrido[3,4- β]indole) is a potent, tremor-producing β-carboline alkaloid, and emerging literature has provided initial links between this neurotoxin and ET. In this report, we review this literature. Two studies, both in New York, have demonstrated higher blood harmane levels in ET cases than controls and, in one study, especially high levels in familial ET cases. Replication studies of populations outside of New York and studies of brain harmane levels in ET have yet to be undertaken. A small number of studies have explored several of the biological correlates of exposure to harmane in ET patients.
    [Show full text]
  • MALDI Mass Spectrometry Imaging for Visualizing in Situ Metabolism of Endogenous Metabolites and Dietary Phytochemicals
    Metabolites 2014, 4, 319-346; doi:10.3390/metabo4020319 OPEN ACCESS metabolites ISSN 2218-1989 www.mdpi.com/journal/metabolites/ Review MALDI Mass Spectrometry Imaging for Visualizing In Situ Metabolism of Endogenous Metabolites and Dietary Phytochemicals Yoshinori Fujimura * and Daisuke Miura * Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan * Authors to whom correspondence should be addressed; E-Mails: [email protected] (Y.F.); [email protected] (D.M.); Tel.: +81-92-642-6160 (Y.F.); +81-92-642-6091 (D.M.); Fax: +81-92-642-6285 (Y.F.); +81-92-642-6285 (D.M.). Received: 26 February 2014; in revised form: 17 April 2014 / Accepted: 4 May 2014 / Published: 5 May 2014 Abstract: Understanding the spatial distribution of bioactive small molecules is indispensable for elucidating their biological or pharmaceutical roles. Mass spectrometry imaging (MSI) enables determination of the distribution of ionizable molecules present in tissue sections of whole-body or single heterogeneous organ samples by direct ionization and detection. This emerging technique is now widely used for in situ label-free molecular imaging of endogenous or exogenous small molecules. MSI allows the simultaneous visualization of many types of molecules including a parent molecule and its metabolites. Thus, MSI has received much attention as a potential tool for pathological analysis, understanding pharmaceutical mechanisms, and biomarker discovery. On the other hand, several issues
    [Show full text]
  • EFFECTS of FLAVONOIDS and OTHER PHYTOCHEMICALS on FISH Cypla MONOOXYGENASES, EMBRYONIC and REPRODUCTIVE DEVELOPMENT
    EFFECTS OF FLAVONOIDS AND OTHER PHYTOCHEMICALS ON FISH CYPlA MONOOXYGENASES, EMBRYONIC AND REPRODUCTIVE DEVELOPMENT A Thesis Submitted to the Committee of Graduate Studies in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the Faculty of Arts and Science Trent University Peterborough. Ontario. Canada 0 Y iannis Kiparissis 200 1 Watershed Ecosystems Ph.D. Program June 2001 National Library Bibliothbque nationale du Canada Acquisitions and Acquisitions et Bibliographic Sewices services bibliographiques 395 Wellington Street 395, rue WeUington Ottawa ON KIA ON4 Ottawa ON KIAON4 Canada Canada The author has granted a non- L'auteur a accorde une Licence non exclusive licence allowing the exclusive pernettant a la National Library of Canada to Bibliotheque nationale du Canada de reproduce, loan, distr!iiute or sell reproduire, preter, distniuer ou copies of this thesis in microform, vendre des copies de cette these sous paper or electronic formats. la forme de microfiche/film, de reproduction sur papier ou sur format electronique. The author retains ownership of the L'auteur conserve la propriete du copyright in this thesis. Neither the droit d'auteur qui protege cette these. thesis nor substantial extracts &om it Ni la these ni des extraits substantiels may be printed or othenvise de celfe-ci ne doivent &re imprimes reproduced without the author's ou autrement reproduits sans son permission. autorisation. ABSTRACT Effects of Flavonoids and Other Phytochemicals on Fish CYPIA Monooxygenases, Embryonic and Reproductive Development The purpose of this study was to demonstrate that biological responses in fish such as induction of CYP1 A-dependent monooxygenases. embryonic defects.
    [Show full text]
  • Download Product Insert (PDF)
    PRODUCT INFORMATION Harmane Item No. 29613 CAS Registry No.: 486-84-0 Formal Name: 1-methyl-9H-pyrido[3,4-b]indole Synonyms: 1-Methyl-β-Carboline, NSC 54439 H MF: C H N 12 10 2 N FW: 182.2 Purity: ≥98% N UV/Vis.: λmax: 213, 234, 249, 288 nm Supplied as: A solid Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Harmane is supplied as a solid. A stock solution may be made by dissolving the harmane in the solvent of choice, which should be purged with an inert gas. Harmane is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF). The solubility of harmane in ethanol is approximately 10 mg/ml and approximately 20 mg/ml in DMSO and DMF. Harmane is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, harmane should first be dissolved in DMSO and then diluted with the aqueous buffer of choice. Harmane has a solubility of approximately 0.25 mg/ml in a 1:3 solution of DMSO:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day. Description Harmane is a β-carboline that has been found in P. harmala, as well as in cooked meats and tobacco 1-7 and has diverse biological activities. It is an inhibitor of monoamine oxidase A (MAO-A; IC50 = 0.5 µM) 3 that also inhibits MAO-B (IC50 = 5 µM).
    [Show full text]
  • Gaurtieraa 1939Redux.Pdf (9.693Mb)
    SYNTHESIS AND RESOLUTION OF PUKATEINE AND OF A CLOSELY RELATED ALKALOID. by Alec A. Gautier (Geneva) Dipl. Ing. E.T.H. Zürich. Thesis submitted for the Degree of Ph.D. University of Edinburgh. April 1939. Preface. This thesis embodies the results of synthetical work carried out in the laboratory of the Medical Chemistry Department of the University of Edinburgh during the academic years 1°37 -38 and 193M -39, under the supervision of the late Professor G. Barger, F.R.S. The author wishes to express his sincere thanks to Professor G.F. Marrian of the Medical Chemistry Department of the University of Edinburgh, for his valuable advice towards the competion of this work, and to the Moray Fund of the University of Edinburgh for a grant which has defrayed the cost of materials. Contents. Page I. THEORY OF THE ORIGIN OF ALKALOIDS.. 1 II. SYNTHESIS OF PUKATEINE. (a) Theoretical 21 (b) Experimental .. .. .. .. .. 37 III. SYNTTHESIS AND RESOLUTION OF A CLOSELY RELATED ALKALOID. (a) Theoretical . 52 (b) Experimental .. .. .. .. .. 56 References .. .. 72 -1- I. THEORY OF THE ORIGIN OF ALKALOIDS. The wide occurrence of alkaloids in the vegetable kingdom makes it reasonable to assume that they must fulfil some important function in the life of the plant. Although this matter has often been dis- cussed and investigated experimentally, it cannot be said that the solution of the problem is in sight. Heckel put forward the assumption that the alkaloids were intermediate products in the building up of protoplasm. If this is the case at all, it must be confined to a few alkaloids which are related to the protein amino- acids.
    [Show full text]
  • Hyperkinetic Movement Disorders Differential Diagnosis and Treatment
    Hyperkinetic Movement Disorders Differential diagnosis and treatment Albanese_ffirs.indd i 1/23/2012 10:47:45 AM Wiley Desktop Edition This book gives you free access to a Wiley Desktop Edition – a digital, interactive version of your book available on your PC, Mac, laptop or Apple mobile device. To access your Wiley Desktop Edition: • Find the redemption code on the inside front cover of this book and carefully scratch away the top coating of the label. • Visit “http://www.vitalsource.com/software/bookshelf/downloads” to download the Bookshelf application. • Open the Bookshelf application on your computer and register for an account. • Follow the registration process and enter your redemption code to download your digital book. • For full access instructions, visit “http://www.wiley.com/go/albanese/movement” Companion Web Site A companion site with all the videos cited in this book can be found at: www.wiley.com/go/albanese/movement Albanese_ffirs.indd ii 1/23/2012 10:47:45 AM Hyperkinetic Movement Disorders Differential diagnosis and treatment EDITED BY Alberto Albanese MD Professor of Neurology Fondazione IRCCS Istituto Neurologico Carlo Besta Università Cattolica del Sacro Cuore, Milan, Italy Joseph Jankovic MD Professor of Neurology Director, Parkinson’s Disease Center and Movement Disorders Clinic Department of Neurology Baylor College of Medicine Houston, TX, USA A John Wiley & Sons, Ltd., Publication Albanese_ffirs.indd iii 1/23/2012 10:47:45 AM This edition first published 2012, © 2012 by Blackwell Publishing Ltd Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical and Medical business to form Wiley-Blackwell.
    [Show full text]
  • Exploring the Physiological Role of Vibrio Fischeri Pepn
    EXPLORING THE PHYSIOLOGICAL ROLE OF VIBRIO FISCHERI PEPN A thesis presented to the Faculty of California Polytechnic State University, San Luis Obispo In Partial Fulfillment of the Requirements for the Degree Master of Science in Biological Sciences by Sally L. Cello April 2015 © 2015 Sally L. Cello ALL RIGHTS RESERVED ii COMMITTEE MEMBERSHIP TITLE: Exploring the physiological role of Vibrio fischeri PepN AUTHOR: Sally L. Cello DATE SUBMITTED: April 2015 COMMITTEE CHAIR: Pat Fidopiastis, Ph.D. Associate Professor of Biological Sciences COMMITTEE MEMBER: Chris Kitts, Ph.D. Department Chair of Biological Sciences Professor of Biological Sciences COMMITTEE MEMBER: Candace Winstead, Ph.D. Associate Professor of Biological Sciences iii ABSTRACT Exploring the physiological role of Vibrio fischeri PepN Sally L. Cello The primary contributor to Vibrio fischeri aminopeptidase activity is aminopeptidase N, PepN. Colonization assays revealed the pepN mutant strain to be deficient at forming dense aggregates and populating the host’s light organ compared to wildtype within the first 12 hours of colonization; however the mutant competed normally at 24 hours. To address the role of PepN in colonization initiation and establish additional phenotypes for the pepN mutant strain, stress response and other physiological assays were employed. Marked differences were found between pepN mutant and wildtype strain in response to salinity, acidity, and antibiotic tolerance. This study has provided a foundation for future work on identifying a putative role for V. fischeri PepN in regulating stress response. iv ACKNOWLEDGMENTS Thank you to my wonderful friends and family for their endless support during this journey. Thank you to Pat Fidopiastis for his guidance and quick replies! Thank you to my committee members for their words of wisdom contributing to a well-polished paper.
    [Show full text]