Administration of Drugs Using Implantable Micropump.

使用植入式微泵给药。

• 批准号: 02670714
• 负责人: YAMAGUCHI Osamu
• 金额: $ 1.54万
• 依托单位: Fukushima Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670714/
• 关键词: DSD; enkephalin; GABA; bacrofen; intrathecal administration; micropump; 慢性脊髄損傷; バクロフエン; 脊髄内投与; ナロキソン

Using spinal rabbits, the contribution of enkephalinergic or GABA-minergic activity to neurogenic dysfuction of lower urinary tract was evaluated. At acute stage of spinal cord transection, enkephalinergic activity dominantly increased at the isolated lumbosacral cord, resulting in a strong supression of bladder activity. In chronic spinal rabbits with detrusor sphincter dyssynergia (DSD), GABA antagonists (picrotoxin and phacrofen) never affected the bladder and sphincter activity. This finding would indicate that DSD is further enhanced with a lack of endogenous GABA.atment of DSD by the intrathercal administration using an implanted micropump. In animals receiving 1 mug/h baclofen, DSD had been improved for 2 weeks. In 5 mug/h bacrofen infusion group, its improvement was sustained during 8 to 12 weeks. Further increase in bacrofen dose (10 mug/h) prolonged the effective period to 12 or 16 weeks. Thus, an excellent therapeutic effect of intrathecal bacrofen infusion was confirmed in chronic spinal rabbits. However, this study could not be performed in patients with DSD because of ethical problems.The intrathecal injection of GABA agonists extremely increased bladder capacity and abolished both pathologic bladder contraction and striated urethral sphincter activity in chronic spinal rabbits. Based on this result, baclofen was used for the tre

使用脊髓兔，评估了脑啡肽能或 GABA 能活性对下尿路神经源性功能障碍的影响。在脊髓横断的急性期，孤立的腰骶段脑啡肽能活性显着增加，导致膀胱活动受到强烈抑制。在患有逼尿肌括约肌协同失调 (DSD) 的慢性脊柱兔中，GABA 拮抗剂（印防己毒素和聚苯胺酸）从未影响膀胱和括约肌活动。这一发现表明，由于缺乏内源性 GABA，DSD 得到进一步增强。通过使用植入的微泵进行鞘内给药，可以进一步增强 DSD。在接受 1 杯/小时巴氯芬的动物中，DSD 改善了两周。在 5 杯/小时巴克芬输注组中，其改善持续了 8 至 12 周。进一步增加巴克芬剂量（10 杯/小时）可将有效期延长至 12 或 16 周。因此，鞘内注射巴克芬对慢性脊柱兔具有良好的治疗效果。然而，由于伦理问题，这项研究未能在 DSD 患者中进行。鞘内注射 GABA 激动剂极大地增加了慢性脊柱兔的膀胱容量，并消除了病理性膀胱收缩和横纹尿道括约肌活动。基于这一结果，巴氯芬被用于治疗

项目成果

Matsuoka,H and Yamaguchi.O: "Roles of endogenous opiates and GABA in the lower urimary tract dysfunction of spinal rabbit" Nenrourology and Vrodynamics. 11. 343-344 (1992)

Matsuoka,H 和 Yamaguchi.O：“内源性阿片类药物和 GABA 在脊髓兔下尿路功能障碍中的作用”Nenrourology 和 Vrodynamics。

H.KameoKa,Y.Fukaya,O.Yamaguchi and Y.Shiraiwa: "Enhancement of bladder activity by large dose of naloxone administration in acute spinal rabbit" Neurourology and Unodynamics. 9. 372-373 (1990)

H.KameoKa、Y.Fukaya、O.Yamaguchi 和 Y.Shiraiwa：“急性脊髓兔大剂量纳洛酮给药增强膀胱活动”神经泌尿学和 Unodynamics。