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Elucidation of spinal itch transmitters and development of antipruritic therapy

Research Project

Project/Area Number 25860428
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pain science
Research InstitutionJuntendo University

Principal Investigator

TOMINAGA Mitsutoshi  順天堂大学, 医学(系)研究科(研究院), 准教授 (50468592)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords難治性かゆみ / アトピー性皮膚炎 / 脊髄 / 神経伝達物質 / かゆみ / 脊髄後角 / 後根神経節 / 電気生理
Outline of Final Research Achievements

This study was performed to reveal mechanisms of spinal itch transmission using in vivo electrophysiological, pharmacological and behavior methods. We found that SP, GRP, and glutamate each partially contribute to histamine-independent itch, whereas histamine-evoked itch is mediated primarily by glutamate. Co-application of NK-1, GRP, and AMPA receptor antagonists may prove beneficial in treating chronic and intractable itch such as atopic dermatitis. We are currently trying to investigate antipruritic therapeutic effects in chronic itch models such as dry skin and atopic dermatitis.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (56 results)

All 2015 2014 2013 Other

All Journal Article (18 results) (of which Peer Reviewed: 13 results,  Acknowledgement Compliant: 4 results) Presentation (32 results) (of which Invited: 6 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Retinoid-related orphan receptor alpha is involved in induction of semaphorin 3A expression in normal human epidermal keratinocytes2015

    • Author(s)
      Yayoi Kamata, Mitsutoshi Tominaga, Azumi Sakaguchi, Yoshie Umehara, Osamu Negi, Hideoki Ogawa, Kenji Takamori
    • Journal Title

      J Dermatol Sci

      Volume: 印刷中 Issue: 1 Pages: 84-86

    • DOI

      10.1016/j.jdermsci.2015.03.015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mechanisms of itch in atopic dermatitis2015

    • Author(s)
      Tominaga M, Kamata Y, Umehara Y, Ko KC, Takamori K
    • Journal Title

      J Environ Dermatol Cutan Allergol

      Volume: 9 Pages: 1-11

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] かゆみのメカニズム2015

    • Author(s)
      冨永光俊、加茂敦子、鎌田弥生、高森建二
    • Journal Title

      Mebio

      Volume: 32 Pages: 29-37

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] かゆみと皮膚-セマフォリン他について-2015

    • Author(s)
      冨永光俊、高森建二
    • Journal Title

      日皮会誌「皮膚科セミナリウム」

      Volume: 125 Pages: 395-402

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Importance of the tryptophan nitration of carbonic anhydrase III for the morbidity of atopic dermatitis2014

    • Author(s)
      Hiroaki Kawasaki, Mitsutoshi Tominaga, Ayako Shigenaga, Atsuko Kamo, Yayoi Kamata, Kyoichi Iizumi, Utako Kimura, Hideoki Ogawa, Kenji Takamori, Fumiyuki Yamakura
    • Journal Title

      Free Radic Biol Med

      Volume: 73 Pages: 75-83

    • DOI

      10.1016/j.freeradbiomed.2014.04.034

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.2014

    • Author(s)
      Atsuko Kamo, Mitsutoshi Tominaga, Yayoi Kamata, Kazuyuki Kaneda, Kyi Chan Ko, Hironori Matsuda, Utako Kimura, Hideoki Ogawa, Kenji Takamori
    • Journal Title

      J Invest Dermatol

      Volume: 134 Issue: 12 Pages: 2977-2984

    • DOI

      10.1038/jid.2014.256

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of spinal bombesin-responsive neurons in non-histaminergic itch2014

    • Author(s)
      Akiyama T, Tominaga M, Takamori K, Iodi Carstens M, Carstens E
    • Journal Title

      J Neurophysiol

      Volume: 112 Issue: 9 Pages: 2283-9

    • DOI

      10.1152/jn.00409.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Itch and nerve fibers with special reference to atopic dermatitis: Therapeutic implications.2014

    • Author(s)
      Tominaga M, Takamori K
    • Journal Title

      J Dermatol

      Volume: 41 Issue: 3 Pages: 205-212

    • DOI

      10.1111/1346-8138.12317

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles of glutamate, substance P, and gastrin-releasing peptide as spinal neurotransmitters of histaminergic and nonhistaminergic itch.2014

    • Author(s)
      Akiyama T, Tominaga M, Takamori K, Carstens MI, Carstens E
    • Journal Title

      Pain

      Volume: 155 Issue: 1 Pages: 80-92

    • DOI

      10.1016/j.pain.2013.09.011

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histamine H(4) receptor antagonists ineffective against itch and skin inflammation in atopic dermatitis mouse model.2014

    • Author(s)
      Kamo A, Negi O, Tengara S, Kamata Y, Noguchi A, Ogawa H, Tominaga M, Takamori K
    • Journal Title

      J Invest Dermatol

      Volume: 134 Issue: 2 Pages: 546-548

    • DOI

      10.1038/jid.2013.351

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 加齢と皮膚の生理機能(バリア機能を中心に)2014

    • Author(s)
      冨永光俊、鎌田弥生、加茂敦子、高森建二
    • Journal Title

      アレルギー・免疫

      Volume: 21

    • Related Report
      2013 Research-status Report
  • [Journal Article] An update on peripheral mechanisms and treatments of itch.2013

    • Author(s)
      Tominaga M, Takamori K
    • Journal Title

      Biol Pharm Bull

      Volume: 36 Pages: 1241-1247

    • NAID

      130003361499

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neurotropin inhibits the increase in intraepidermal nerve density in the acetone-treated dry-skin mouse model.2013

    • Author(s)
      Kamo A, Tominaga M, Taneda K, Ogawa H, Takamori K
    • Journal Title

      Clin Exp Dermatol

      Volume: 38 Issue: 6 Pages: 665-668

    • DOI

      10.1111/ced.12100

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles for substance P and gastrin-releasing peptide as neurotransmitters released by primary afferent pruriceptors.2013

    • Author(s)
      Akiyama T, Tominaga M, Davoodi A, Nagamine M, Blansit K, Horwitz A, Carstens MI, Carstens E
    • Journal Title

      J Neurophysiol

      Volume: 109 Issue: 3 Pages: 742-748

    • DOI

      10.1152/jn.00539.2012

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] バリア機能と痒み2013

    • Author(s)
      冨永光俊、高森建二
    • Journal Title

      アレルギーの臨床

      Volume: 33 Pages: 39-43

    • Related Report
      2013 Research-status Report
  • [Journal Article] アトピー性皮膚炎のかゆみのメカニズムと新たなる治療戦略2013

    • Author(s)
      高森建二、冨永光俊
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 59 Pages: 191-197

    • Related Report
      2013 Research-status Report
  • [Journal Article] 老人性乾皮症の痒み発生機序の解明と治療法開発2013

    • Author(s)
      冨永光俊、加茂敦子、髙森建二
    • Journal Title

      加齢皮膚医学セミナー

      Volume: 8 Pages: 23-28

    • Related Report
      2013 Research-status Report
  • [Journal Article] かゆみとスキンケア2013

    • Author(s)
      根木 治、冨永光俊、高森建二
    • Journal Title

      Monthly Book Derma

      Volume: 210 Pages: 23-30

    • Related Report
      2013 Research-status Report
  • [Presentation] Epidermal nerve fibers in atopic dermatitis-updates2015

    • Author(s)
      Takamori K, Tominaga M
    • Organizer
      23rd World Congress of Dermatology
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2015-06-08 – 2015-06-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Effects of H1-antihistamines on expression of axon guidance molecules in normal human epidermal keratinocytes2015

    • Author(s)
      Kamata Y, Sakaguchi A, Umehara Y, Tominaga M, Ogawa H, Takamori K
    • Organizer
      2015 SOCIETY FOR INVESTIGATIVE DERMATOLOGY (SID) annual meeting
    • Place of Presentation
      Atlanta, Georgia, USA
    • Year and Date
      2015-05-06 – 2015-05-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] The antimicrobial peptide cathelicidin LL-37 induces semaphorin 3A production in normal human epidermal keratinocytes2015

    • Author(s)
      Umehara Y, Kamata Y, Tominaga M, Niyonsaba F, Ogawa H, Takamori K
    • Organizer
      2015 SOCIETY FOR INVESTIGATIVE DERMATOLOGY (SID)
    • Place of Presentation
      Atlanta, Georgia, USA
    • Year and Date
      2015-05-06 – 2015-05-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of spinal neurotransmitters in histaminergic and non-histaminergic itch2014

    • Author(s)
      Tominaga M, Akiyama T, Carstens MI, Carstens E, Takamori K
    • Organizer
      第39回日本研究皮膚科学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-11 – 2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Roles of granzyame A in pathology of patients with atopic dermatitis2014

    • Author(s)
      Kamata Y, Kimura U, Matsuda H, Tengara S, Iizumi K, Tominaga M, Takamori K
    • Organizer
      第39回日本研究皮膚科学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-11 – 2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of cyclosporine A in inhibitory mechanism of pruritus in atopic dermatitis2014

    • Author(s)
      Ko KC, Tominaga M, Kamata Y, Umehara Y, Takamori K
    • Organizer
      第39回日本研究皮膚科学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-11 – 2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effects of antimicrobial peptides on semaphorin 3A expression in normal human epidermal keratinocytes2014

    • Author(s)
      Umehara Y, Kamata Y, Tominaga M, Niyonsaba F, Takamori K
    • Organizer
      第39回日本研究皮膚科学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-11 – 2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Irradiation of excimer lamp induces intraepidermal nerve degeneration and inhibits itch-related behavior in a dry-skin mouse model2014

    • Author(s)
      Kamo A, Tominaga M, Kamata Y, Kaneda K, Ko KC, Matsuda H, Kimura U, Takamori K
    • Organizer
      第39回日本研究皮膚科学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-11 – 2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Spinal antinociceptive effect of gastrin releasing peptide (GRP) via GABAergic inhibitory interneurons expressing the GRP receptor (GRPR)2014

    • Author(s)
      Akiyama T, Tominaga M, Davoodi A, Nagamine M, Takamori K, Carstens MI, Carstens E
    • Organizer
      Neuroscience 2014
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 表皮内神経線維に対する紫外線療法エキシマランプ照射の影響-難治性痒み治療としての有用性の検討-2014

    • Author(s)
      加茂敦子、冨永光俊、高森建二
    • Organizer
      第13回コ・メディカル形態機能学会
    • Place of Presentation
      山形
    • Year and Date
      2014-11-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] 皮膚のかゆみの発生機序と制御-特に、アトピー性皮膚炎に関して-2014

    • Author(s)
      冨永光俊、高森建二
    • Organizer
      第7回セラミド研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Antimicrobial peptide LL-37 induces semaphorin 3A in normal human epidermal keratinocytes2014

    • Author(s)
      Umehara Y, Kamata Y, Tominnaga M, Niyonsaba F, Takamori K
    • Organizer
      第24回国際かゆみシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Antipruritic mechanisms of cyclosporine A in atopic dermatitis mouse2014

    • Author(s)
      Ko KC, Tominaga M, Kamata Y, Umehara Y, Takamori K
    • Organizer
      第24回国際かゆみシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] アトピー性皮膚炎の難治性痒み発現におけるグランザイムAの役割2014

    • Author(s)
      鎌田弥生、木村有太子、Suhandy Tengara、加茂 敦子、冨永光俊、高森建二
    • Organizer
      第19回日本病態プロテアーゼ学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-08-08 – 2014-08-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脊髄におけるかゆみの神経伝達機構の解明2014

    • Author(s)
      冨永光俊、穐山 祐、Earl Carstens、高森建二
    • Organizer
      平成26年度生理学若手研究者フォーラム
    • Place of Presentation
      東京
    • Year and Date
      2014-07-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The retinoid-related orphan receptor ROR alpha promote semaphorin 3A expression in human keratinocytes2014

    • Author(s)
      Kamata Y, Tominaga M, Umehara Y, Takamori K
    • Organizer
      2014 SOCIETY FOR INVESTIGATIVE DERMATOLOGY (SID) annual meeting
    • Place of Presentation
      Albuquerque, New Mexico, USA
    • Year and Date
      2014-05-07 – 2014-05-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 乾燥肌のかゆみに対する保湿剤の効果2014

    • Author(s)
      冨永光俊
    • Organizer
      第129回浦安皮膚臨床懇話会
    • Place of Presentation
      浦安、千葉
    • Year and Date
      2014-04-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Histamine H4 receptor antagonists exhibit insufficient anti-pruritic and anti-inflammatory effects on mite extract ointment-induced mouse model of atopic dermatitis2013

    • Author(s)
      Tominaga M, Kamo A, Negi O, Tengara S, Kamata Y, Noguchi A, Takamori K
    • Organizer
      International Investigative Dermatology (IID) 2013
    • Place of Presentation
      Edinburgh, Scotland
    • Related Report
      2013 Research-status Report
  • [Presentation] Molecular mechanisms of Sema3A gene regulation in human epidermal keratinocytes2013

    • Author(s)
      Kamata Y, Tominaga M, Kamo A, Takamori K
    • Organizer
      International Investigative Dermatology (IID) 2013
    • Place of Presentation
      Edinburgh, Scotland
    • Related Report
      2013 Research-status Report
  • [Presentation] Excimer lamp irradiation induces reduction of intraepidermal nerve fibre: implications for possible application to intractable pruritus2013

    • Author(s)
      Kamo A, Tominaga M, Kamata Y, Takamori K
    • Organizer
      International Investigative Dermatology (IID) 2013
    • Place of Presentation
      Edinburgh, Scotland
    • Related Report
      2013 Research-status Report
  • [Presentation] Histamine H4 receptor antagonists ineffective against itch and skin inflammation in atopic dermatitis mouse model2013

    • Author(s)
      Tominaga M, Kamo A, Osamu N, Tengara S, Kamata Y, Noguchi A, Takamori K
    • Organizer
      7th World Congress on Itch
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Transcriptional regulation of human semaphorin 3A gene in normal epidermal keratinocytes: implication of application to intractable itch in atopic dermatitis2013

    • Author(s)
      Kamata Y, Tominaga M, Umehara Y, Kamo A, Takamori K
    • Organizer
      7th World Congress on Itch
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Anti-pruritic effects of Neurotropin in NC/Nga mice with atopic dermatitis-like symptoms2013

    • Author(s)
      Kamo A, Tominaga M, Kamata Y, Nogchi A, Kimura U, Osamu N, Taneda K, Takamori K
    • Organizer
      7th World Congress on Itch
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Spinal neurotransmitters in histaminergic and non-histaminergic itch2013

    • Author(s)
      Akiyama T, Tominaga M, Carstens MI, Carstens E
    • Organizer
      7th World Congress on Itch
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Eximer lamp induces directly cutaneous nerve degeneration in animal models for pruritus2013

    • Author(s)
      Kamo A, Tominaga M, Kamata Y, Takamori K
    • Organizer
      22nd Congress of the European Academy of Dermatology and Venereology (EADV)
    • Place of Presentation
      Istanbul, Turkey
    • Related Report
      2013 Research-status Report
  • [Presentation] Spinal neurotransmitters in histaminergic and non-histaminergic itch2013

    • Author(s)
      Tominaga M, Akiyama T, Carstens MI, Carstens E
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] かゆみと皮膚―セマフォリン他について―2013

    • Author(s)
      冨永光俊
    • Organizer
      第112回日本皮膚科学会総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] アトピー性皮膚炎―かゆみのメカニズム―2013

    • Author(s)
      冨永光俊
    • Organizer
      第43回日本皮膚アレルギー・接触皮膚炎学会ランチョンセミナー
    • Place of Presentation
      ホテル日航金沢
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 乾燥皮膚で誘発される表皮内神経の増生に対する保湿性オリゴマーエステルD/DCの影響2013

    • Author(s)
      加茂敦子、冨永光俊、鎌田弥生、高森建二
    • Organizer
      第112回日本皮膚科学会総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 皮膚の乾燥を伴う痒みに対するノイロトロピンの有効性の検討2013

    • Author(s)
      加茂敦子、冨永光俊、鎌田弥生、野口篤、木村有太子、根木 治、種田研一、高森建二
    • Organizer
      第9回 加齢皮膚医学研究会
    • Place of Presentation
      山口大学医学部 霜仁会館
    • Related Report
      2013 Research-status Report
  • [Presentation] 6-ニトロトリプトファンはアトピー性皮膚炎患者の血漿バイオマーカーとなり得るか?2013

    • Author(s)
      飯泉恭一、冨永光俊、川崎広明、重永綾子、加茂敦子、鎌田弥生、高森建二、山倉文幸
    • Organizer
      第35回日本トリプトファン研究会
    • Place of Presentation
      京都大学杉浦ホール
    • Related Report
      2013 Research-status Report
  • [Presentation] 正常ヒト表皮角化細胞におけるセマフォリン3Aの発現制御機構2013

    • Author(s)
      鎌田弥生、冨永光俊、梅原芳恵、加茂敦子、高森建二
    • Organizer
      第23回国際かゆみシンポジウム
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Related Report
      2013 Research-status Report
  • [Book] Itch sensitization: NGF, semaphorins. Itch: Mechanisms and Treatment2014

    • Author(s)
      Tominaga M, Takamori K
    • Total Pages
      431
    • Publisher
      CRC Press, Taylor and Francis Group, LLC
    • Related Report
      2013 Research-status Report
  • [Remarks] 高森グループホームページ

    • URL

      http://www.juntendo.ac.jp/graduate/laboratory/labo/kankyo_igaku/k4_takamori.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 順天堂大学大学院医学研究科環境医学研究所高森建二グループホームページ

    • URL

      http://www.juntendo.ac.jp/graduate/laboratory/labo/kankyo_igaku/k4_takamori.html

    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] セマフォリン3A遺伝子発現増強剤、及びセマフォリン3Aタンパク産生亢進剤2015

    • Inventor(s)
      吉岡康子、鎌田弥生、冨永光俊、高森建二
    • Industrial Property Rights Holder
      吉岡康子、鎌田弥生、冨永光俊、高森建二
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-074574
    • Filing Date
      2015-03-31
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 掻痒性皮膚疾患の治療又は予防2014

    • Inventor(s)
      梅原芳恵、鎌田弥生、冨永光俊、ニヨンサバ・フランソワ、高森建二
    • Industrial Property Rights Holder
      梅原芳恵、鎌田弥生、冨永光俊、ニヨンサバ・フランソワ、高森建二
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-177778
    • Filing Date
      2014-09-02
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] セマフォリン3Aの発現調節法2013

    • Inventor(s)
      鎌田弥生、冨永光俊、高森建二
    • Industrial Property Rights Holder
      鎌田弥生、冨永光俊、高森建二
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-097100
    • Filing Date
      2013-05-02
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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