ATE330606T1 - Verfahren zur vorbeugung von nmda-rezeptor vermittelten neuronalen schäden - Google Patents
Verfahren zur vorbeugung von nmda-rezeptor vermittelten neuronalen schädenInfo
- Publication number
- ATE330606T1 ATE330606T1 AT93923724T AT93923724T ATE330606T1 AT E330606 T1 ATE330606 T1 AT E330606T1 AT 93923724 T AT93923724 T AT 93923724T AT 93923724 T AT93923724 T AT 93923724T AT E330606 T1 ATE330606 T1 AT E330606T1
- Authority
- AT
- Austria
- Prior art keywords
- nmda receptor
- neuronal damage
- mediated neuronal
- mammal
- preventing nmda
- Prior art date
Links
- 230000003961 neuronal insult Effects 0.000 title abstract 3
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 title 1
- 241000124008 Mammalia Species 0.000 abstract 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract 4
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 abstract 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 abstract 2
- 230000003247 decreasing effect Effects 0.000 abstract 2
- 230000001404 mediated effect Effects 0.000 abstract 2
- 230000004112 neuroprotection Effects 0.000 abstract 2
- 229960003753 nitric oxide Drugs 0.000 abstract 2
- 150000002832 nitroso derivatives Chemical class 0.000 abstract 2
- 241000894007 species Species 0.000 abstract 2
- 230000000694 effects Effects 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
- A61K38/446—Superoxide dismutase (1.15)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/295—Iron group metal compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
- A61K38/063—Glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/556—Angiotensin converting enzyme inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/949,342 US5234956A (en) | 1991-04-19 | 1992-09-22 | Method of preventing NMDA receptor complex-mediated neuronal damage |
| US08/025,028 US5455279A (en) | 1991-04-19 | 1993-03-02 | Regimen method of mediating neuronal damage using nitroglycerine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE330606T1 true ATE330606T1 (de) | 2006-07-15 |
Family
ID=26699179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT93923724T ATE330606T1 (de) | 1992-09-22 | 1993-09-22 | Verfahren zur vorbeugung von nmda-rezeptor vermittelten neuronalen schäden |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US5455279A (de) |
| EP (1) | EP0661973B1 (de) |
| AT (1) | ATE330606T1 (de) |
| AU (1) | AU5348194A (de) |
| DE (1) | DE69334035T2 (de) |
| DK (1) | DK0661973T3 (de) |
| ES (1) | ES2264122T3 (de) |
| WO (1) | WO1994006428A1 (de) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991002810A1 (en) * | 1989-08-09 | 1991-03-07 | The Children's Medical Center Corporation | Nmda oxidizing agents for protecting neurons from injury |
| US5922773A (en) * | 1992-12-04 | 1999-07-13 | The Children's Medical Center Corp. | Glaucoma treatment |
| CA2159106C (en) * | 1993-04-20 | 2009-10-06 | Lorrie P. Daggett | Human n-methyl-d-aspartate receptor subunits, nucleic acids encoding same and uses therefor |
| FR2714828B1 (fr) * | 1994-01-12 | 1996-02-02 | Rhone Poulenc Rorer Sa | Application du riluzole dans le traitement des maladies mitochondriales. |
| JPH08208511A (ja) * | 1995-01-31 | 1996-08-13 | Samu Kenkyusho:Kk | 抗運動ニューロン疾患剤 |
| RU2106864C1 (ru) | 1995-10-23 | 1998-03-20 | Николай Серафимович Зефиров | Средство для лечения болезни альцгеймера |
| US6140309A (en) * | 1996-03-12 | 2000-10-31 | University Of South Florida | Vasoactive effects and free radical generation by β-amyloid peptides |
| US5807847A (en) * | 1996-06-04 | 1998-09-15 | Queen's University At Kingston | Nitrate esters |
| US20050137191A1 (en) * | 1996-06-04 | 2005-06-23 | Thatcher Gregory R. | Nitrate esters and their use for mitigating cellular damage |
| US6310052B1 (en) | 1996-06-04 | 2001-10-30 | Queen's University At Kingston | Nitrate esters and their use for neurological conditions |
| US5872124A (en) * | 1996-07-31 | 1999-02-16 | Thomas Jefferson University | Treatment of diseases of the central nervous system using uric acid as a scavenger of peroxynitrite |
| CA2264959A1 (en) * | 1996-09-03 | 1998-03-12 | Yeda Research And Development Co. Ltd. | Central nervous system-derived immune privilege factor and uses thereof |
| US6126939A (en) * | 1996-09-03 | 2000-10-03 | Yeda Research And Development Co. Ltd. | Anti-inflammatory dipeptide and pharmaceutical composition thereof |
| WO1998043621A1 (en) * | 1997-03-31 | 1998-10-08 | The Children's Medical Center Corporation | Nitrosylation to inactivate apoptotic enzymes |
| US6057373A (en) * | 1997-05-22 | 2000-05-02 | Synchroneuron, Llc | Methods of treating tardive dyskinesia and other movement disorders using NMDA receptor antagonists |
| US5866585A (en) * | 1997-05-22 | 1999-02-02 | Synchroneuron, Llc | Methods of treating tardive dyskinesia using NMDA receptor antagonists |
| HUP0002859A2 (hu) * | 1997-07-11 | 2001-01-29 | The Johns Hopkins University School Of Medicine | A nitrogén-monoxidot kibocsátó vegyületek alkalmazása rinovírus-fertőzés által előidézett kórtünetek enyhítésére |
| US6436996B1 (en) * | 1997-09-30 | 2002-08-20 | Duke University | Modulation of nitric oxide production |
| US6294583B1 (en) | 1998-01-13 | 2001-09-25 | Synchroneuron, Llc | Methods of treating tardive dyskinesia and other movement disorders |
| US5952389A (en) * | 1998-01-13 | 1999-09-14 | Synchroneuron | Methods of treating tardive dyskinesia and other movement disorders |
| JPH11217330A (ja) * | 1998-01-30 | 1999-08-10 | Sumitomo Pharmaceut Co Ltd | 神経栄養因子分泌促進剤 |
| EP1013272A1 (de) * | 1998-12-23 | 2000-06-28 | Biomedical Primate Research Centre (BPRC) | Beeinflussung der Aktivität eines Stickoxidradikalherstellungsweges zur Behandlung von mit freien Sauerstoffradikalen verbundenen Krankheiten |
| US6482854B1 (en) | 1999-03-25 | 2002-11-19 | Massachusetts Eye And Ear Infirmary | Glaucoma treatment |
| FR2791571B1 (fr) * | 1999-04-02 | 2002-10-04 | Sod Conseils Rech Applic | Association inhibiteur(s) de no synthase et antioxydant(s) metabolique(s) |
| US6255280B1 (en) | 1999-04-08 | 2001-07-03 | University Of Kentucky Research Foundation | Protection against traumatic brain injury |
| GB9908175D0 (en) * | 1999-04-09 | 1999-06-02 | Lilly Co Eli | Method of treating neurological disorders |
| US6432434B1 (en) * | 1999-04-22 | 2002-08-13 | The United States Of America As Represented By The Secretary Of The Army | Treatment of and/or prophylaxis against brain and spinal cord injury |
| US6417227B1 (en) | 1999-04-28 | 2002-07-09 | Cg And Associates | Methods of delivery of cetyl myristoleate |
| AU5601300A (en) * | 1999-06-09 | 2000-12-28 | Department Of The Army, U.S. Government | Method and compositions for treating and preventing retinal damage |
| US6444702B1 (en) | 2000-02-22 | 2002-09-03 | Neuromolecular, Inc. | Aminoadamantane derivatives as therapeutic agents |
| US7820420B2 (en) * | 2000-08-11 | 2010-10-26 | Whitlock David R | Compositions including ammonia oxidizing bacteria to increase production of nitric oxide and nitric oxide precursors and methods of using same |
| MXPA03005130A (es) * | 2000-12-07 | 2004-12-06 | Neuromolecular Inc | Metodos para tratar trastornos neurosiquiatricos con antagonistas del receptor del nmda. |
| EP1852113A3 (de) * | 2000-12-07 | 2008-03-12 | Neuromolecular Inc. | Verfahren zur Behandlung neuropsychiatrischer Erkrankungen mit NMDA-Rezeptorantagonisten |
| US20020072512A1 (en) * | 2000-12-08 | 2002-06-13 | Metaphore Pharmaceuticals, Inc | Method of preventing and treating HIV-mediated central nervous system damage |
| US20030232739A1 (en) * | 2001-08-15 | 2003-12-18 | Pfizer Inc. | Pharmaceutical combinations comprising a NOS inhibitor and an NMDA receptor antagonist |
| US20030045449A1 (en) * | 2001-08-15 | 2003-03-06 | Pfizer, Inc. | Pharmaceutical combinations for the treatment of neurodegenerative diseases |
| EP1472021A4 (de) * | 2002-01-11 | 2008-04-16 | David R Whitlock | Ammoniak oxidierende bakterien enthaltende zusammensetzungen und verwendungsverfahren dafür |
| US20030229114A1 (en) * | 2002-04-04 | 2003-12-11 | Rosenberg Paul A. | Pyrroloquinoline quinone drugs as a neuroprotectant and methods of use thereof |
| US20050148673A1 (en) * | 2002-07-11 | 2005-07-07 | Harbut Ronald E. | Prolonged administration of NMDA antagonist and safener drug to alter neuropathic pain condition |
| US7086532B2 (en) * | 2003-07-16 | 2006-08-08 | Allergan, Inc. | Titration/compliance pack with increasing doses |
| US20070148136A1 (en) * | 2003-09-26 | 2007-06-28 | Whitlock David R | Methods of using ammonia oxidizing bacteria |
| AR046314A1 (es) | 2003-11-05 | 2005-11-30 | Merz Pharma Gmbh & Co Kgaa | Composiciones que comprenden ciclohexilaminas y aminoadamantanos |
| ES2483126T3 (es) | 2004-06-17 | 2014-08-05 | Merz Pharma Gmbh & Co. Kgaa | Formulaciones de formas de dosificación de neramexano |
| US7619007B2 (en) | 2004-11-23 | 2009-11-17 | Adamas Pharmaceuticals, Inc. | Method and composition for administering an NMDA receptor antagonist to a subject |
| JP5666087B2 (ja) | 2005-04-06 | 2015-02-12 | アダマス・ファーマシューティカルズ・インコーポレーテッド | Cns関連疾患の治療のための方法及び組成物 |
| WO2007116458A1 (ja) * | 2006-03-30 | 2007-10-18 | Tohru Hasegawa | 神経変性疾患治療薬 |
| JP5228912B2 (ja) * | 2006-09-08 | 2013-07-03 | 三菱瓦斯化学株式会社 | 高血圧改善剤 |
| EP2111858A1 (de) | 2008-04-25 | 2009-10-28 | EPFL Ecole Polytechnique Fédérale de Lausanne | Neue Behandlung für Morbus Alzheimer |
| IT1398507B1 (it) * | 2009-01-13 | 2013-03-01 | Giellepi Chemicals S P A | Composizione per il trattamento di neuropatie |
| US9023890B2 (en) * | 2009-12-02 | 2015-05-05 | The Charlotte-Mecklenburg Hospital Authority | Nitrate esters and their use for the treatment of muscle and muscle related diseases |
| NZ601635A (en) | 2010-01-27 | 2013-06-28 | Takeda Pharmaceutical | Compounds for suppressing a peripheral nerve disorder induced by an anti-cancer agent |
| US9452117B2 (en) | 2011-06-01 | 2016-09-27 | The Charlotte-Mecklenburg Hospital Authority | Nitrate esters and their use for the treatment of muscle and muscle related diseases |
| EP2948135B1 (de) | 2013-01-25 | 2019-01-02 | Case Western Reserve University | Zusammensetzungen und verfahren zur behandlung von erkrankungen mit pervasiver entwicklung |
| JP2017519486A (ja) | 2014-04-15 | 2017-07-20 | エーオーバイオーム, エルエルシー.AOBiome, LLC. | アンモニア酸化Nitrosomonas eutropha株D23 |
| US11225640B2 (en) | 2014-04-15 | 2022-01-18 | Aobiome Llc | Ammonia oxidizing bacteria for treatment of psoriasis |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3328251A (en) * | 1965-12-30 | 1967-06-27 | Du Pont | Pharmaceutical compositions and methods utilizing 2-aminoadamantane and its derivatives |
| US3391142A (en) * | 1966-02-09 | 1968-07-02 | Lilly Co Eli | Adamantyl secondary amines |
| CH603545A5 (de) * | 1972-04-20 | 1978-08-31 | Merz & Co | |
| US4064139A (en) * | 1975-04-07 | 1977-12-20 | Merck & Co., Inc. | Substituted 9,10-dihydroanthracen-9,10-imines |
| US4399141A (en) * | 1977-09-19 | 1983-08-16 | Merck & Co., Inc. | 5-Alkyl or hydroxyalkyl substituted-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imines and anticonvulsant use thereof |
| US4374838A (en) * | 1977-09-19 | 1983-02-22 | Merck & Co., Inc. | Dibenzo[a,d]cycloocten-5,12-(and 6,12)-imines |
| DE2856393C2 (de) * | 1978-12-27 | 1983-04-28 | Merz + Co GmbH & Co, 6000 Frankfurt | Arzneimittel zur Behandlung von Morbus Parkinson |
| US4513137A (en) * | 1981-04-09 | 1985-04-23 | The University Of Akron | Iodonium salts |
| US4351847A (en) * | 1981-06-26 | 1982-09-28 | Pennwalt Corporation | Antiviral alpha, alpha-dialkyl adamantylethylamines |
| GB8600783D0 (en) * | 1986-01-14 | 1986-02-19 | Merck Sharp & Dohme | N-methyl-d-aspartate receptor antagonists |
| US4736048A (en) * | 1986-06-04 | 1988-04-05 | Dow Corning Corporation | Pressure sensitive adhesive release liner and fluorosilicone compounds, compositions and method therefor |
| US4806543A (en) * | 1986-11-25 | 1989-02-21 | Board Of Trustees Of The Leland Stanford Junior University | Method and compositions for reducing neurotoxic injury |
| DE3856401D1 (de) * | 1987-01-23 | 2000-05-04 | Gen Hospital Corp | Hydralazin zur topischen Behandlung von Glaukom |
| US4898920A (en) * | 1987-10-15 | 1990-02-06 | Dow Corning Corporation | Adhesive compositions, controlled release compositions and transdermal delivery device |
| ES2059602T3 (es) * | 1989-04-14 | 1994-11-16 | Merz & Co Gmbh & Co | Uso de derivados de adamantano para la prevencion y tratamiento de isquemia cerebral. |
| WO1991002810A1 (en) * | 1989-08-09 | 1991-03-07 | The Children's Medical Center Corporation | Nmda oxidizing agents for protecting neurons from injury |
| US5521215A (en) * | 1989-11-07 | 1996-05-28 | Ramot University Authority For Applied Research And Industrial Development Ltd. | NMDA-blocking pharmaceuticals |
| US5264371A (en) * | 1989-11-22 | 1993-11-23 | Neurex Corporation | Screening method for neuroprotective compounds |
| US5559095A (en) * | 1989-11-22 | 1996-09-24 | Neurex Corporation | Delayed treatment method of reducing ischemia-related neuronal damage |
| US5091391A (en) * | 1990-08-16 | 1992-02-25 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Method of resisting neurodegenerative disorders |
| WO1992018112A1 (en) * | 1991-04-19 | 1992-10-29 | The Children's Medical Center Corporation | Method of preventing nmda receptor complex-mediated neuronal damage |
-
1993
- 1993-03-02 US US08/025,028 patent/US5455279A/en not_active Expired - Lifetime
- 1993-09-22 AT AT93923724T patent/ATE330606T1/de active
- 1993-09-22 DK DK93923724T patent/DK0661973T3/da active
- 1993-09-22 WO PCT/US1993/009019 patent/WO1994006428A1/en not_active Ceased
- 1993-09-22 DE DE69334035T patent/DE69334035T2/de not_active Expired - Lifetime
- 1993-09-22 EP EP93923724A patent/EP0661973B1/de not_active Expired - Lifetime
- 1993-09-22 ES ES93923724T patent/ES2264122T3/es not_active Expired - Lifetime
- 1993-09-22 AU AU53481/94A patent/AU5348194A/en not_active Abandoned
-
1995
- 1995-03-22 US US08/407,973 patent/US5747545A/en not_active Expired - Lifetime
- 1995-06-07 US US08/482,365 patent/US5801203A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ES2264122T3 (es) | 2006-12-16 |
| DE69334035D1 (de) | 2006-08-03 |
| EP0661973B1 (de) | 2006-06-21 |
| DK0661973T3 (da) | 2006-10-30 |
| AU5348194A (en) | 1994-04-12 |
| EP0661973A1 (de) | 1995-07-12 |
| US5747545A (en) | 1998-05-05 |
| DE69334035T2 (de) | 2006-12-28 |
| US5801203A (en) | 1998-09-01 |
| US5455279A (en) | 1995-10-03 |
| EP0661973A4 (de) | 1999-12-22 |
| WO1994006428A1 (en) | 1994-03-31 |
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