Botox injection to improve compliance in the compromised fetal bladder.

• Project/Area Number: 26861489
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Nagae Hideki 聖マリアンナ医科大学, 医学部, 助教 (90468942)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Botulin / Fetal / Surgery / Toxin / 胎児尿路閉塞 / ボツリヌス毒素 / 胎児治療 / プロテオミクス

Outline of Final Research Achievements

A recent development has been the use Botulin Toxin(BTX) to treat bladder　dysfunction. In our experiment, a vesico-amniotic (VAS) shunt in a normal fetal lamb bladder produces a thick-walled, poorly-compliant bladder. BTX improves compliance in neurogenic bladders. We tried BTX in our VAS model.
We placed non-valved VAS in 80-day gestation fetal lambs, injecting BTX (10units/kg) at 100 days at 4 sites around the shunt (Group A). They were delivered at term (145 days) and bladder volume, histology were measured.BTX injected into a compromised bladder at 100 days were able to improve a survival rate, but doesn’t improve compliance at term.

Research Products

• [Int'l Joint Research] オタゴ大学ウェリントン病院(ニュージーランド)
• [Int'l Joint Research] Otago大学(ニュージーランド)
• [Journal Article] 羊胎仔尿路閉塞モデルに発症した嚢胞腎に対するVirtual slide systemと走査電信顕微鏡を組み合わせたアプローチ (2016)
  • Author(s): 大林樹真, 田中邦英, 佐々木千鶴子, 関保二, 長江秀樹, 眞鍋周太郎, 大山慧, Kevin C. Pringle, 小池淳樹, 北川博昭
  • Journal Title: 発達腎研究会誌 Volume: 24 Pages: 6-7
  • Int'l Joint Research
• [Journal Article] Does a large abdominal wall defect affect lung growth? (2016)
  • Author(s): Juma Obayashi, Kunihide Tanaka, Junki Koike, Yasuji Seki, Hideki Nagae, Shutaro Manabe, Kei Ohyama, Jane Zuccollo, Masayuki Takagi, Kevin C. Pringle, Hiroaki Kitagawa
  • Journal Title: Journal of Pediatric Surgery Volume: 51 Issue: 12 Pages: 1972-0975
  • DOI: 10.1016/j.jpedsurg.2016.09.022
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Relational between amount of bile ducts in portal canal outcomes in biliary atresia (2016)
  • Author(s): Juma Obayashi, Kunihide Tanaka, Kei Ohyama, Shutaro Manabe, Hideki Nagae, Hideki Shima, Hideaki Sato, Shigeyuki Furuta, Munechika Wakisaka, Junki Koike, Masayuki Takagi, Hiroaki Kitagawa
  • Journal Title: Pediatric Surgery International Volume: 32 Issue: 9 Pages: 833-838
  • DOI: 10.1007/s00383-016-3941-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 羊胎仔尿路閉塞モデルにおける膀胱羊水腔シャント後の腎組織の検索 (2015)
  • Author(s): 田中邦英, 北川博昭, 小池淳樹, 眞鍋周太郎, 大山慧, 長江秀樹, 関保二, Pringle KC
  • Journal Title: 発達腎研究会誌 Volume: 23 Pages: 11-14
  • Peer Reviewed
• [Journal Article] 脳羊胎仔モデルにおける先天性尿路閉塞に対する圧調整シャントチューブを用いた治療の試み (2015)
  • Author(s): 田中邦英, 小池淳樹, 眞鍋周太郎, 大山慧, 関保二, 長江秀樹, 高木正之, Ｚｕｃｃｏｌｌｏ Ｊａｎｅ, Ｐｒｉｎｇｌｅ ＫＣ, 北川博昭
  • Journal Title: 聖マリアンナ医科大学雑誌 Volume: 43 Pages: 9-13
  • Peer Reviewed
• [Journal Article] Presure limimted vesico-amniotic shunt allows normal lung growth in a fetal lamb model of obstructive uropathy. (2015)
  • Author(s): Tanaka Kunihide, Koike Junki, Obayashi Juma, Seki Yasuji, Nagae Hideki, Manabe Shutaro, Ohyama Kei, Sasaki Chizuko, Masayuki Takagi, Jane Zuccollo, Pringle KC, Kitagawa Hiroaki
  • Journal Title: Journal of Pediatric Surgery Volume: 50 Pages: 2063-2067
  • Peer Reviewed
• [Journal Article] 病態解析のための動物モデルー何がわかったか 腹壁破裂における動物もでる作成方法とプロテオーム解析 (2014)
  • Author(s): 大山慧,佐藤利行,眞鍋周太郎,長江秀樹,關保二,Pringle KC,加藤智啓,北川博昭
  • Journal Title: 小児外科 Volume: 46 Pages: 630-634
  • Peer Reviewed
• [Journal Article] The effects of anestesia and fetal surgery on the early ovine fetus. (2014)
  • Author(s): Manabe Shutaro,Kitagawa Hiroaki,Oyama Kei,Seki Yasuji,Nagae Hideki,Takagi Masayuki,Koike Junki,Zuccollo Jane,Pringle C Kevin
  • Journal Title: Integrative Molecular Medicine Volume: 1 Pages: 76-80
  • Peer Reviewed
• [Journal Article] A peptide ptofile of amniotic fluid in a fetal lamb model of gastroschisis. (2014)
  • Author(s): Oyama Kei,Sato Toshiyuki,Tanaka Kunihide,Manabe Shutaro,Nagae Hideki,Arito Mitsumi,Iizuk Nobuko,Kojima Shigeki,Omoteyama Kazuki,Seki Yasuji, Kurokawa S Manae,Suematsu Naoya,Okamoto Kazuki,Pringle KC,Kato Tomohiro,Kitagawa Hiroaki
  • Journal Title: Integrative Molecular Medicine Volume: 1 Pages: 67-72
  • Peer Reviewed
• [Journal Article] Can a pressure-limited V-A shunt for obstructive uropathy really protect the kidney? (2014)
  • Author(s): Tanaka Kunihide,Manabe Shutaro,Oyama Kei,Seki Yasuji,Nagae Hideki,Takagi Masayuki、Ｋｏｉｋｅ Ｊｕｎｋｉ，Ｚｕｃｃｏｌｌｏ Ｊａｎｅ，Ｐｒｉｎｇｌｅ KC,Kitagawa Hiroaki
  • Journal Title: Journal of Pediatric Surgery Volume: 49 Pages: 1831-1834
  • Peer Reviewed
• [Presentation] 腹壁異常における臨床像の差異はなぜ起きるのか？－羊胎仔腹壁異常モデルを用いた検討ー (2016)
  • Author(s): 大林樹真, 関保二, 長江秀樹, 眞鍋周太郎, 大山慧, Kevin C. Pringle, 小池淳樹, 高木正之, 北川博昭
  • Organizer: 第14回日本胎児治療学会学術集会
  • Place of Presentation: 聖隷浜松病院（静岡県浜松市）
  • Year and Date: 2016-11-21
• [Presentation] Degree of Liver Fibrosis in Biliary Atresia with Ductal Plate Malformation (2016)
  • Author(s): Juma Obayashi, Kunihide Tanaka, Kei Ohyama, Shutaro Manabe, Hideki Nagae, Hideki Shima, Hideaki Sato, Shigeyuki Furuta, Kohei Kawaguchi, Munechika Wakisaka, Junki Koike, Masayuki Takagi, Hiroaki Kitagawa
  • Organizer: WOFAPS2016
  • Place of Presentation: ワシントン・アメリカ合衆国
  • Year and Date: 2016-10-09
  • Int'l Joint Research
• [Presentation] 羊胎仔を用いた糸球体構築の免疫組織学的検討 (2016)
  • Author(s): 大林樹真, 川口皓平, 田中邦英, 関保二, 長江秀樹, 眞鍋周太郎, 大山慧, Kevin C. Pringle, 小池淳樹, 高木正之, 北川博昭
  • Organizer: 第25回発達腎研究会
  • Place of Presentation: 聖路加国際大学（東京都・中央区）
  • Year and Date: 2016-08-27
• [Presentation] What causes Scoilosis in the Body stalk anomaly? (2016)
  • Author(s): Juma Obayashi, Kunihide Tanaka, Junki Koike, Yasuji Seki, Hideki Nagae, Shutaro Manabe, Kei Ohyama, Jane Zuccollo, Masayuki Takagi, Kevin C. Pringle, Hiroaki Kitagawa
  • Organizer: EUPSA2016
  • Place of Presentation: ミラノ・イタリア
  • Year and Date: 2016-06-15
  • Int'l Joint Research
• [Presentation] 羊胎仔萎縮膀胱に対する胎児期ボトックスの使用は有効か？ (2016)
  • Author(s): 長江秀樹, 大林樹真, 田中邦英, 関保二, 眞鍋周太郎, 大山慧, 小池淳樹, Kevin C. Pringle, 北川博昭
  • Organizer: 第53回日本小児外科学会学術集会
  • Place of Presentation: ヒルトン福岡シーホーク（福岡県福岡市）
  • Year and Date: 2016-05-24
• [Presentation] Does a large abdominal wall defect affect lung growth? (2016)
  • Author(s): Juma Obayashi, Kunihide Tanaka, Junki Koike, Yasuji Seki, Hideki Nagae, Shutaro Manabe, Kei Ohyama, Jane Zuccollo, Masayuki Takagi, Kevin C. Pringle, Hiroaki Kitagawa
  • Organizer: 49th Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: ハワイ・アメリカ合衆国
  • Year and Date: 2016-04-24
  • Int'l Joint Research
• [Presentation] 胎児期尿路閉塞に対する胎児治療効果ー羊を用いた胎児実験と日本の現状報告ー (2015)
  • Author(s): 北川博昭
  • Organizer: 第337回日本小児科学会神奈川県地方会
  • Place of Presentation: 神奈川県総合医療会館（神奈川県横浜市）
  • Year and Date: 2015-11-28
• [Presentation] 稀な先天性腹壁欠損症の１例 (2015)
  • Author(s): 眞鍋周太郎, 佐藤英章, 古田繁行, 相田芳夫, 北川博昭
  • Organizer: 第50回日本小児外科学会関東甲信越地方会
  • Place of Presentation: ラフレさいたま（埼玉県さいたま市）
  • Year and Date: 2015-10-10
• [Presentation] 羊胎仔尿路閉塞モデルに発症した嚢胞腎に対するVirtual slide systemと走査電子顕微鏡を組み合わせたアプローチ (2015)
  • Author(s): 大林樹真, 田中邦英, 佐々木千鶴子, 関保二, 長江秀樹, 眞鍋周太郎, 大山慧, KC Pringle, 小池淳樹, 北川博昭
  • Organizer: 第24回発達腎研究会
  • Place of Presentation: 広島医師会館（広島県広島市）
  • Year and Date: 2015-08-29
• [Presentation] 胎仔羊を用いた膀胱羊腔シャント手術後ボトックス注入時期の検討 (2015)
  • Author(s): 長江秀樹, 眞鍋周太郎, 大山慧, 田中邦英, 小池淳樹, 関保二, 高木正之, Jane Zuccollo, Kevin C Pringle, 北川博昭 2015/05/28 胎仔羊を用いた膀胱羊腔シャント手術後ボトックス注入時期の検討 第52回日本小児外科学会学術集会 福岡
  • Organizer: 第52回日本小児外科学会学術集会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-05-28
• [Presentation] 羊胎仔尿路閉塞モデルにおける圧調整シャントチューブによる治療後の肺の形態学的評価 (2015)
  • Author(s): 田中邦英, 小池淳樹, 眞鍋周太郎, 大山慧, 長江秀樹, 関保二, 高木正之, Jane Zuccollo, Kevin C Pringle, 北川博昭
  • Organizer: 第52回日本小児外科学会学術集会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-05-28
• [Presentation] Pressure limited vesico-amniotic shunt allows normal lung growth in a fetal lamb model of obstructive uropathy (2015)
  • Author(s): Tanaka Kunihide, Koike Junki, Obayashi Juma, Seki Yasuji, Nagae Hideki, Manabe Shutaro, Ohyama Kei, Sasaki Chizuko, Takagi Masayuki, Jane Zuccollo, Kevin C Pringle, Kitagawa Hiroaki
  • Organizer: 48th Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: 韓国
  • Year and Date: 2015-05-17
• [Presentation] Large gastroschisis associated with severe scoliosis and lung hypoplasia in sheep model: Is this a possible aetiology of "Limb-body wall complex?" (2014)
  • Author(s): Kitagawa Hiroaki,Kevin Pringle,Seki Yasuji,Nagae Hideki,Ooyama Kei,Manabe Shutaro,Tanaka Kunihide,Koike Junki,Takagi Masayuki,Jane Zuccollo
  • Organizer: EUPSA2014
  • Place of Presentation: Dublin(Ireland)
  • Year and Date: 2014-06-18
• [Presentation] A peptide ptofile of amniotic fluid in a fetal lamb model of gastroschisis. (2014)
  • Author(s): Ohyama Kei,Kevin C Pringle,Sato Toshiyuki,Manabe Shutaro,Nagae Hideki,Seki Yasuji,Kato Tomohiro,Kitagawa Hiroaki
  • Organizer: Paciffic Association of PediatricSurgeons 47th Annual Meeting
  • Place of Presentation: Banff(Canada)
  • Year and Date: 2014-05-25
• [Presentation] National survey of Fetal intervention for Obstructive Uropathy. Does vesico-amniotic shunt prevent fatal pulmonary hypoplasia (2014)
  • Author(s): Kitagawa Hiroaki, Usui Noriaki, Ishii Keisuke, Sago Haruhiko, Matsuoka Kentaro, Tanaka Mamoru, Tatsunami Shinobu, Hayakawa Masahiro
  • Organizer: Paciffic Association of PediatricSurgeons 47th Annual Meeting
  • Place of Presentation: Banff(Canada)
  • Year and Date: 2014-05-25
• [Presentation] Can a pressure-limited V-A shunt for obstructive uropathy really protect the kidney? (2014)
  • Author(s): Tanaka Kunihide,Manabe Shutaro,Oyama Kei,Seki Yasuji,Nagae Hideki,Takagi Masayuki、Ｋｏｉｋｅ Ｊｕｎｋｉ，Ｚｕｃｃｏｌｌｏ Ｊａｎｅ，Ｐｒｉｎｇｌｅ KC,Kitagawa Hiroaki
  • Organizer: Paciffic Association of PediatricSurgeons 47th Annual Meeting
  • Place of Presentation: Banff(Canada)
  • Year and Date: 2014-05-25
• [Presentation] 羊を用いた胎児尿路閉塞モデルの委縮膀胱に胎児期ボツリヌス注射を用いた効果 (2014)
  • Author(s): 長江秀樹,脇坂宗親,島秀樹,眞鍋周太郎,小山真理子,大山慧,田中邦英,北川博昭
  • Organizer: 第51回日本小児外科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2014-05-09
• [Presentation] 羊胎仔腹壁破裂モデル羊水ペプチドミクス解析 (2014)
  • Author(s): 大山慧,佐藤利行,田中邦英,眞鍋周太郎,長江秀樹,關保二,Jane Zuccollo,Kevin Pringle,加藤智啓,北川博昭
  • Organizer: 第51回日本小児外科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2014-05-09
• [Presentation] 羊胎仔尿路閉塞モデルの腎臓組織における空胞性変化とアクアポリン11の発現消失について (2014)
  • Author(s): 田中邦英,眞鍋周太郎,大山慧,長江秀樹,小山真理子,關保二,小池淳樹,高木正之,Jane Zuccollo,Kevin Pringle,北川博昭
  • Organizer: 第51回日本小児外科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2014-05-09
• [Presentation] 羊胎仔尿路閉塞モデルにおける胎児治療後の腎臓組織の検討 (2014)
  • Author(s): 眞鍋周太郎,田中邦英,大山慧,長江秀樹,島秀樹,關保二,小池淳樹,高木正之,Jane Zuccollo,Kevin Pringle,北川博昭
  • Organizer: 第51回日本小児外科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2014-05-09