Silent Synapse Activation in Epilepsy
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Development of Pain-Free Methods for Analyzing 231 Multiclass Drugs and Metabolites by LC-MS/MS
Clinical, Forensic & Toxicology Article “The Big Pain”: Development of Pain-Free Methods for Analyzing 231 Multiclass Drugs and Metabolites by LC-MS/MS By Sharon Lupo As the use of prescription and nonprescription drugs grows, the need for fast, accurate, and comprehensive methods is also rapidly increasing. Historically, drug testing has focused on forensic applications such as cause of death determinations or the detection of drug use in specific populations (military, workplace, probation/parole, sports doping). However, modern drug testing has expanded well into the clinical arena with a growing list of target analytes and testing purposes. Clinicians often request the analysis of large panels of drugs and metabolites that can be used to ensure compliance with prescribed pain medication regimens and to detect abuse or diversion of medications. With prescription drug abuse reaching epidemic levels [1], demand is growing for analytical methods that can ensure accurate results for comprehensive drug lists with reasonable analysis times. LC-MS/MS is an excellent technique for this work because it offers greater sensitivity and specificity than immunoassay and—with a highly selective and retentive Raptor™ Biphenyl column—can provide definitive results for a wide range of compounds. Typically, forensic and pain management drug testing consists of an initial screening analysis, which is qualitative, quick, and requires only minimal sample preparation. Samples that test positive during screening are then subjected to a quantitative confirmatory analysis. Whereas screening assays may cover a broad list of compounds and are generally less sensitive and specific, confirmation testing provides fast, targeted analysis using chromatographic conditions that are optimized for specific panels. -
Diminished Neuronal Activity Increases Neuron–Neuron Connectivity Underlying Silent Synapse Formation and the Rapid Conversion of Silent to Functional Synapses
4040 • The Journal of Neuroscience, April 20, 2005 • 25(16):4040–4051 Cellular/Molecular Diminished Neuronal Activity Increases Neuron–Neuron Connectivity Underlying Silent Synapse Formation and the Rapid Conversion of Silent to Functional Synapses Kimiko Nakayama, Kazuyuki Kiyosue, and Takahisa Taguchi Neuronics Research Group, Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka 563- 8577, Japan Neuronal activity regulates the synaptic strength of neuronal networks. However, it is still unclear how diminished activity changes connection patterns in neuronal circuits. To address this issue, we analyzed neuronal connectivity and relevant mechanisms using hippocampal cultures in which developmental synaptogenesis had occurred. We show that diminution of network activity in mature neuronal circuit promotes reorganization of neuronal circuits via NR2B subunit-containing NMDA-type glutamate receptors (NR2B- NMDARs), which mediate silent synapse formation. Simultaneous double whole-cell recordings revealed that diminishing neuronal circuit activity for 48 h increased the number of synaptically connected neuron pairs with both silent and functional synapses. This increase was accompanied by the specific expression of NR2B-NMDARs at synaptic sites. Analysis of miniature EPSCs (mEPSCs) showed that the frequency of NMDAR-mediated, but not AMPAR-mediated, mEPSCs increased, indicating that diminished neuronal activity promotes silent synapse formation via the surface delivering NR2B-NMDARs in mature neurons. After activation of neuronal circuit by releasing from TTX blockade (referred as circuit reactivation), the frequency of AMPAR-mediated mEPSCs increased instead, and this increase was prevented by ifenprodil. The circuit reactivation also caused an increased colocalization of glutamate receptor 1-specfic and synaptic NR2B-specific puncta. -
FYCOMPA® • Severe Hepatic Impairment: Not Recommended (2.4) ® Safely and Effectively
HIGHLIGHTS OF PRESCRIBING INFORMATION mg (mild) and 4 mg (moderate) once daily at bedtime (2.4) ® These highlights do not include all the information needed to use FYCOMPA • Severe Hepatic Impairment: Not recommended (2.4) ® safely and effectively. See full prescribing information for FYCOMPA . • Severe Renal Impairment or on Hemodialysis: Not recommended (2.5) ® • Elderly: Increase dose no more frequently than every 2 weeks (2.6) FYCOMPA (perampanel) tablets, for oral use, CIII FYCOMPA® (perampanel) oral suspension, CIII ----------------------DOSAGE FORMS AND STRENGTHS----------------- Initial U.S. Approval: 2012 • Tablets: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg (3) WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS • Oral Suspension: 0.5 mg/mL (3) See full prescribing information for complete boxed warning. ----------------------------------CONTRAINDICATIONS---------------------- None (4) • Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation -----------------------WARNINGS AND PRECAUTIONS-------------------- and threats have been reported in patients taking FYCOMPA (5.1) • Suicidal Behavior and Ideation: Monitor for suicidal thoughts or • Monitor patients for these reactions as well as for changes in mood, behavior (5.2) behavior, or personality that are not typical for the patient, particularly • Neurologic Effects: Monitor for dizziness, gait disturbance, somnolence, during the titration period and at higher doses (5.1) and fatigue -
"Bouncy Gait" in Lance-Adams Syndrome with Perampanel
Open Access Case Report DOI: 10.7759/cureus.6773 Improvement of "Bouncy Gait" in Lance-Adams Syndrome with Perampanel Shen-Yang Lim 1 , Dushyanth Babu Jasti 2 , Ai Huey Tan 1 1. Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson’s & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, MYS 2. Division of Neurology, Kasturba Medical College, Manipal, IND Corresponding author: Shen-Yang Lim, [email protected] Abstract Lance-Adams syndrome (LAS) is chronic post-hypoxic myoclonus that is often associated with sudden lapses in muscle tone (negative myoclonus) in the legs, causing a disabling "bouncy gait." Given its relative rarity, there are no controlled treatment studies of LAS. The majority of cases require polypharmacy management, with an incomplete response. "Bouncy gait," in particular, is notoriously medication-refractory. Here, we report a patient with long-standing LAS who improved markedly when low-dose perampanel was added to his existing treatment regime consisting of clonazepam, levetiracetam, sodium valproate, and acetazolamide. Categories: Internal Medicine, Neurology, Physical Medicine & Rehabilitation Keywords: lance-adams syndrome, perampanel, myoclonus, negative myoclonus, bouncy gait Introduction Lance-Adams syndrome (LAS) is chronic post-hypoxic myoclonus with onset days to weeks after a hypoxic episode, when the patient has regained consciousness [1]. The myoclonus is typically multifocal, worse with action, and associated with sudden lapses in muscle tone in the legs, causing a "bouncy gait" [1]. Additional features may include cognitive impairment, seizures, dysarthria, and ataxia [1]. Given its relative rarity, there are no controlled treatment studies of LAS. The majority of cases require polypharmacy management, with an incomplete response. -
BOARD MEETING AGENDA Meeting Location: Portland State Office Building 800 NE Oregon Street, Portland, OR 97232 June 6-7, 2018 Updated 6.4.18
Oregon Board of Pharmacy BOARD MEETING AGENDA Meeting Location: Portland State Office Building 800 NE Oregon Street, Portland, OR 97232 June 6-7, 2018 Updated 6.4.18 The mission of the Oregon State Board of Pharmacy is to promote, preserve and protect the public health, safety and welfare by ensuring high standards in the practice of pharmacy and by regulating the quality, manufacture, sale and distribution of drugs. Wednesday, June 6, 2018 @ 8:30AM – Conference Rm A Thursday, June 7, 2018 @ 8:30AM – Conference Room A ≈ If special accommodations are needed for you to attend or participate in this Board Meeting, please contact Loretta Glenn at: (971) 673-0001. ≈ WEDNESDAY, JUNE 6, 2018 I. 8:30AM OPEN SESSION, Penny Reher, R.Ph, Presiding A. Roll Call B. Agenda Review and Approval Action Necessary II. Contested Case Deliberation pursuant to ORS 192.690(1) - Not Open to the Public III. EXECUTIVE SESSION – NOT OPEN TO THE PUBLIC, pursuant to ORS 676.175, ORS 192.660 (1) (2) (f) (k). A. Items for Consideration and Discussion: 1. Deliberation on Disciplinary Cases and Investigations 2. Personal Appearances 3. Deficiency Notifications 4. Case Review B. Employee Performance Review pursuant to ORS 192.660(2)(i). IV. OPEN SESSION - PUBLIC MAY ATTEND - At the conclusion of Executive Session, the Board may convene Open Session to begin some of the following scheduled agenda items - time permitting at approximately 3:30PM. V. Approve Consent Agenda* Action Necessary *Items listed under the consent agenda are considered to be routine agency matters and will be approved by a single motion of the Board without separate discussion. -
Pdf4 Complex I and the Aryl Palladium Precursor II Underwent Sequential Single Electron Abstraction from Aryl Pd(II) Complex
Design, synthesis, methodology development, and evaluation of PET imaging agents targeting cancer and CNS disorders By Gengyang Yuan B.S. in Chemical Engineering and Technology, Zhejiang University of Technology M.S. in Pharmaceutical Engineering, Zhejiang University A dissertation submitted to The Faculty of the College of Science of Northeastern University in partial fulfillment of the requirements for the degree of Doctor of Philosophy April 21, 2017 Dissertation directed by Michael P. Pollastri Associate Professor and Chair of Chemistry and Chemical Biology Co-directed by Neil Vasdev Adjunct Associate Professor of Chemsitry and Chemical Biology Associate Professor of Radiology, Massachusetts General Hospital and Harvard Medical School Dedication To my parents Zhijun and Yongmian and my wife Ran and daughter Isabella ii Acknowledgements This dissertation would not have been possible without the support, guidance and encouragement of numerous people who have helped me along the way. First and foremost, I would like to thank Northeastern University and the Department of Chemistry and Chemical Biology for supporting me to pursue my doctoral study. I would like to especially thank my current advisor Professor Michael Pollastri for helping me out when I needed it the most. I appreciate you for taking me into your group and giving me full support to finish my thesis projects. I also especially thank my co-advisor Professor Neil Vasdev for taking me into his group at Mass. General Hospital & Harvard Medical School and teaching me the PET radiochemistry and PET imaging. I could not image how I could accomplish this work without your help. I also got a lot of help from Dr. -
Introduced B.,Byhansen, 16
LB301 LB301 2021 2021 LEGISLATURE OF NEBRASKA ONE HUNDRED SEVENTH LEGISLATURE FIRST SESSION LEGISLATIVE BILL 301 Introduced by Hansen, B., 16. Read first time January 12, 2021 Committee: Judiciary 1 A BILL FOR AN ACT relating to the Uniform Controlled Substances Act; to 2 amend sections 28-401, 28-405, and 28-416, Revised Statutes 3 Cumulative Supplement, 2020; to redefine terms; to change drug 4 schedules and adopt federal drug provisions; to change a penalty 5 provision; and to repeal the original sections. 6 Be it enacted by the people of the State of Nebraska, -1- LB301 LB301 2021 2021 1 Section 1. Section 28-401, Revised Statutes Cumulative Supplement, 2 2020, is amended to read: 3 28-401 As used in the Uniform Controlled Substances Act, unless the 4 context otherwise requires: 5 (1) Administer means to directly apply a controlled substance by 6 injection, inhalation, ingestion, or any other means to the body of a 7 patient or research subject; 8 (2) Agent means an authorized person who acts on behalf of or at the 9 direction of another person but does not include a common or contract 10 carrier, public warehouse keeper, or employee of a carrier or warehouse 11 keeper; 12 (3) Administration means the Drug Enforcement Administration of the 13 United States Department of Justice; 14 (4) Controlled substance means a drug, biological, substance, or 15 immediate precursor in Schedules I through V of section 28-405. 16 Controlled substance does not include distilled spirits, wine, malt 17 beverages, tobacco, hemp, or any nonnarcotic substance if such substance 18 may, under the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. -
Activation with Glutamate/NMDA Receptor Inhibition
biomolecules Article − Amantadine Combines Astroglial System Xc Activation with Glutamate/NMDA Receptor Inhibition Tomosuke Nakano, Toshiki Hasegawa, Dai Suzuki, Eishi Motomura and Motohiro Okada * Department of Neuropsychiatry, Division of Neuroscience, Graduate School of Medicine, Mie University, Tsu 514-8507, Japan; [email protected] (T.N.); [email protected] (T.H.); [email protected] (D.S.); [email protected] (E.M.) * Correspondence: [email protected]; Tel.: +81-59-231-5018 Received: 21 April 2019; Accepted: 15 May 2019; Published: 17 May 2019 Abstract: A glutamate/NMDA receptor (NMDA-R) antagonist, amantadine (AMA) exhibits a broad spectrum of clinically important properties, including antiviral, antiparkinsonian, neuroprotective, neuro-reparative and cognitive-enhancing effects. However, both clinical and pre-clinical studies have demonstrated that noncompetitive NMDA-R antagonists induce severe schizophrenia-like cognitive deficits. Therefore, this study aims to clarify the clinical discrepancy between AMA and noncompetitive NMDA-R antagonists by comparing the effects of AMA with those of a noncompetitive NMDA-R antagonist, MK801, on rat tripartite glutamatergic synaptic transmission using microdialysis and primary cultured astrocytes. Microdialysis study demonstrated that the stimulatory effects of AMA on L-glutamate release differed from those of MK801 in the globus pallidus, entorhinal cortex and entopeduncular nucleus. The stimulatory effect of AMA on L-glutamate release was modulated by activation of cystine/glutamate antiporter (Sxc). Primary cultured astrocytes study demonstrated that AMA also enhanced glutathione synthesis via Sxc activation. Furthermore, carbon-monoxide induced damage of the astroglial glutathione synthesis system was repaired by AMA but not MK801. -
A Synthetic Likelihood Solution to the Silent Synapse Estimation Problem
bioRxiv preprint doi: https://doi.org/10.1101/781898; this version posted September 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Classification: Biological sciences (Neuroscience) Title: A synthetic likelihood solution to the silent synapse estimation problem Authors: Michael Lynna, Kevin F.H. Leea, Cary Soaresa, Richard Nauda,e & Jean-Claude Béïquea,b,c,d Affiliations: a Department of Cellular and Molecular Medicine, bCanadian Partnership for Stroke Recovery, c Centre for Neural Dynamics, d Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada K1H 8M5 eDepartment of Physics, STEM Complex, room 336, 150 Louis Pasteur Pvt., University of Ottawa, K1N 6N5, Ottawa, Canada. Corresponding author: Jean-Claude Beique University of Ottawa 451 Smyth Road, RGN 3501N Ottawa, Ontario, Canada K1H 8M5 Tel: 1-613-562-5800 ext. 4968 [email protected] Keywords: silent synapses, plasticity, statistical inference, synthetic likelihood bioRxiv preprint doi: https://doi.org/10.1101/781898; this version posted September 25, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract The proportions of AMPA-lacking silent synapses are believed to play a fundamental role in determining the plasticity potential of neural networks. It is, however, unclear whether current methods to quantify silent synapses possess adequate estimation properties. -
2021 Formulary List of Covered Prescription Drugs
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Antiepileptic Drugs in Development Pipeline: a Recent Update
eNeurologicalSci 4 (2016) 42–51 Contents lists available at ScienceDirect eNeurologicalSci journal homepage: http://ees.elsevier.com/ensci/ Review article Antiepileptic drugs in development pipeline: A recent update Harjeet Kaur, Baldeep Kumar, Bikash Medhi ⁎ Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India article info abstract Article history: Epilepsy is the most common neurological disorder which significantly affects the quality of life and poses a Received 16 September 2015 health as well as economic burden on society. Epilepsy affects approximately 70 million people in the world. Received in revised form 16 April 2016 The present article reviews the scientific rationale, brief pathophysiology of epilepsy and newer antiepileptic Accepted 15 June 2016 drugs which are presently under clinical development. We have searched the investigational drugs using the Available online 17 June 2016 key words ‘antiepileptic drugs,’‘epilepsy,’‘Phase I,’‘Phase II’ and ‘Phase III’ in American clinical trial registers Keywords: (clinicaltrials.gov), the relevant published articles using National Library of Medicine's PubMed database, compa- Seizures ny websites and supplemented results with a manual search of cross-references and conference abstracts. This Epilepsy review provides a brief description about the antiepileptic drugs which are targeting different mechanisms Drug development and the clinical development status of these drugs. Besides the presence of old as well as new AEDs, still there Neuroprotection is a need of new drugs or the modified version of old drugs in order to make affected people free of seizures. Clinical trial An optimistic approach should be used to translate the success of preclinical testing to clinical practice. -
BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available
BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] BMJ Open Pediatric drug utilization in the Western Pacific region: Australia, Japan, South Korea, Hong Kong and Taiwan Journal: BMJ Open ManuscriptFor ID peerbmjopen-2019-032426 review only Article Type: Research Date Submitted by the 27-Jun-2019 Author: Complete List of Authors: Brauer, Ruth; University College London, Research Department of Practice and Policy, School of Pharmacy Wong, Ian; University College London, Research Department of Practice and Policy, School of Pharmacy; University of Hong Kong, Centre for Safe Medication Practice and Research, Department