Masanori Inaba

Juntendo University, Edo, Tokyo, Japan

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Publications (7)8.29 Total impact

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    ABSTRACT: Peritoneal dialysis (PD) catheters often become severely dislocated, which may lead to malfunction. With the aim of preventing this complication, we have developed a simple method of fixing the catheter downwards in the peritoneal cavity (fixation technique), a technique that does not require a laparoscope. Sixteen patients were implanted using the conventional placement technique and 25 patients were implanted using the fixation technique. The location of the catheter tip was classified from grade 1 (downward, normal) to 5 (dislocated). The frequency of dislocation (defined as the extended time and/or decrease in volume when draining the PD solution) was measured for both the fixation technique and conventional placement technique. There was a significant difference in grade between the fixation technique (2.72 ± 1.01) and conventional technique (3.92 ± 1.31). The time until first dislocation was significantly different between the fixation technique (59.3 ± 48.1 days) and conventional technique (8.8 ± 14.6 days). The time until any dislocation was significantly different between the fixation technique (69.2 ± 41.9 days) and conventional technique (12.9 ± 13.7 days). Complications were not significantly different between the fixation technique and conventional technique. The fixation technique appears to be simple, safe, and useful for preventing severe dislocation and for lengthening the time until dislocation in PD patients.
    No preview · Article · Nov 2013 · Seminars in Dialysis
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    ABSTRACT: Marked thickening of the peritoneum and vasculopathy in the submesothelial compact zone have been reported in long-term peritoneal dialysis patients. Bone marrow (BM)-derived cell lines are considered to be useful tools for therapy of various diseases. To clarify the role of BM-derived cells in the peritoneal fibrosis (PF) model, we analyzed several lineages of cells in the peritoneum. BM cells from green fluorescent protein (GFP) transgenic mice were transplanted into naïve C57Bl/6 mice. Chlorhexidine gluconate (CG) was injected intraperitoneally to induce PF. Immunohistochemical analysis was performed with parietal peritoneum using anti-Sca-1 or -c-Kit and -GFP antibodies. Isolated BM cells were also transplanted into the CG-stimulated peritoneum. BM-derived cells from GFP transgenic mice appeared in the submesothelium from days 14 to 42. Both GFP- and stem cell marker-positive cells were observed in the submesothelium and on the surface. Isolated c-Kit-positive cells, transplanted into the peritoneal cavity, differentiated into mesothelial cells. In this study, we investigated whether or not BM-derived cells play a role in the repair of PF and immature cells have the potential of inducing repair of the peritoneum. The findings of this study suggest a new concept for therapy of PF.
    No preview · Article · May 2012 · Journal of Artificial Organs
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    ABSTRACT: Background/Purpose: Recovery from peritoneal fibrosis (PF) involves the digestion of accumulated collagens and remodeling. Matrix metalloproteinases (MMPs) may play an important role in repair. The role of MMP-13, an important component in the MMP cascade, in PF is still unclear. We examined the sequential expression of MMP synthesis during repair in a PF mouse. Methods: Forty-eight mice at 8 weeks of age were given an intraperitoneal injection of 0.1% chlorhexidine gluconate (CG) for 3 weeks. Control mice were injected with the same dosages of 15% ethanol dissolved in saline. These mice were sacrificed, and anterior abdominal walls were obtained on days 21, 28, 35, 42, 49, and 56. Gene expressions of MMP-2 and -13, tissue inhibition of metalloproteinase-1 (TIMP-1) and -2, MT1-MMP, transforming growth factor-beta 1, and collagen types I and III were analyzed by real-time polymerase chain reaction. MMP-13 enzyme activity was also measured. In immunohistological evaluation, MMP-13 expressing cells were examined. Results: Thickening of the peritoneumand marked infiltration of monocytes were induced by CG, and the alterations remained until 7 days after cessation of CG. Then tissue repair rapidly advanced. Synthesis of collagen types I and III, MMP-2, TIMP-1 and -2, and transforming growth factor-beta 1 in the injured peritoneum was significantly increased until day 28. These increments were preceded by an increase of MMP-13 synthesis and activity after cessation of CG. Some infiltrating macrophages in the thickened peritoneum showed MMP-13 expression early after cessation of CG. Conclusion: MMP-13 was synthesized by infiltrating monocytes early in the repair process in the CG-induced PF mouse. After cessation of stimulant, increase of MMP-13 synthesis may act as an inducer of an efficient degradation cascade in collagen-rich peritoneal tissue.
    No preview · Article · Apr 2012 · Hong Kong Journal of Nephrology
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    ABSTRACT: 背景: 長期腹膜透析患者では, 腹膜表面を覆う中皮細胞の脱落と細動・静脈病変, 間質の線維性肥厚を中心とする組織学的変性を認め, 腹膜透析の除水不全の一因となっている. 腎性貧血患者に投与するerythropoietin (Epo) は, 造血作用以外にも血管新生作用を有することが報告されている. 今回, クロールヘキシジングルコネート (CG) を用いた腹膜硬化モデルラットにEpoを併用することで, 組織侵襲期におけるEpoの血管新生の組織への影響について検討を行った. 方法: 24匹の8週齢のSprague-Dawleyラットを4群に分け, (1) 腹腔内にCGとEpoの投与を行ったCG+Epo群, (2) CG投与のみを行ったCG群, (3) Epo投与のみを行ったEpo群と (4) 対照群を作成した. 投与開始28日後に屠殺し, 採取した壁側腹膜を用い, hypoxia-inducible factor-1α (HIF-1α), erythropoietin receptor (EpoR), pimonidazoleの発現を免疫組織学的に検索した. HIF-1α, vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), connective tissue growth factor (CTGF) のmRNA発現をReal-time PCRで評価した. またCD34とα-smooth muscle actin (α-SMA) の蛍光二重染色を行い, 血管密度・成熟度を計測した. 結果: CG群において, 腹膜の線維性肥厚が認められ, Epoの併用で抑制された. CG+Epo群のヘマトクリットはCG群に比べ著名に上昇した. CG群の肥厚した腹膜内にHIF-1α, EpoR, pimonidazole陽性細胞が多数存在し, Epoの併用により減少した. CG群では, CG+Epo群に比べHIF-1α・VEGF・Ang-2・CTGFmRNA発現の亢進を認め, CG+Epo群と比べると, これらのmRNA発現の有意な抑制を認めた. CG群のAng-1mRNAの発現は, CG+Epo群に比べると有意に抑制されていた. CG+Epo群の血管密度と血管成熟度は, CGのそれらに比べ有意な上昇を示した. 結語: CGの投与を行った腹膜硬化モデルラットにEpoを併用することで腹膜の線維性肥厚は, 抑制された. その理由として, Epoの造血作用と成熟血管網の構築を高めることで, 虚血組織への酸素供給量が上昇したことが挙げられる. また, Epo投与は低酸素状態を改善し, HIF-1α発現抑制を介したCTGF発現を抑えたと思われた.
    No preview · Article · Jan 2011
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    ABSTRACT: 背景: 長期腹膜透析症例では, 表層を覆う中皮細胞の消失といちじるしい中皮下層の線維性肥厚, 毛細血管を含む細動静脈血管病変を中心とする組織学的変性を認め, これらの組織学的変化が透析機能低下による除水不全や細菌感染に対する防御機能低下の原因となっている. 腹膜透析の中止によって, これらの組織学的・機能的変化は改善するとの報告がある一方で, 中止後に腹膜線維化が進行し, 重大な合併症である被嚢性腹膜硬化症にいたるとする報告もみられる. hepatocyte growth factor (HGF) は, 組織修復関連因子であるとともに, 抗線維化作用を有する成長因子として知られている. 今回, われわれはクロールヘキシジンアルコールchlorhexidine gluconate (CG) を腹腔内に連続投与し作成した腹膜硬化マウスの組織修復過程を検索するとともに, この過程におけるHGFの関与を検討した. 方法: 55匹のBL/6雄マウスを2群に分け腹腔内に, 1) エタノールで溶解し, 生食で希釈した15%CG溶解液 (CG群), 2) 15%エタノール溶解液 (コントロール群) のそれぞれ0.5mlを隔日21日間注入した. 各群のマウスを投与終了時, 終了後7日, 21日, 35日目に屠殺した. 屠殺後直ちに前腹壁の腹膜を採取し, 腹膜組織のvimentin・HGF発現について免疫組織化学的に検索した. 結果: CG投与中止直後のいちじるしい血管新生を伴った間質の肥厚は, 35日後にはほぼ正常な腹膜組織に回復した. 腹膜肥厚や腹膜中皮下層への細胞浸潤は21日まではほとんど変化がなかったが, 31日では著明に改善した. 中皮下に多数のvimentin陽性細胞を認めた. 中止直後はvimentin陽性細胞が多数みられたが, 時間の経過とともに減少した. また, vimentin陽性細胞の一部にHGF陽性細胞を認め, その比率は21日目まで増加傾向を示した. 結語: CGによる腹膜障害の解除によって, 腹膜組織の修復機転が生じることが示された. この修復機転には, 間質に発現するHGFの組織修復誘導作用の関与が示唆された.
    No preview · Article · Jan 2008
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    ABSTRACT: The activity of gelatinase, matrix metalloproteinase-2, in effluent was increased in peritoneal dialysis patients with encapsulated peritoneal sclerosis (EPS) and in chlorhexidine gluconate-induced peritoneal sclerosing (PS) animal models. The objective of the present study was to investigate the effect of matrix metalloproteinase inhibitor (ONO-4817), an anticancer agent with anti-angiogenesis and anti-infiltration effects, on the development of peritoneal fibrosis in chlorhexidine gluconate-induced PS rats. Forty-five Sprague-Dawley (S-D) rats were intraperitoneally injected with saline as control (n = 15) or with chlorhexidine gluconate (CH) (1.5 ml/100 g) in the CH group (n = 15). ONO-4817 (5 mg/rat) was administered intravenously to CH rats (the ONO-4817 group, n = 15) from initiation to the end of the study. After 22 days of ONO-4817 administration, the rats were sacrificed and the parietal peritoneum was harvested. The gene expressions of transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin (alpha-SMA) and type I collagen in the peritoneum were analysed by the reverse transcription-polymerase chain reaction (RT-PCR). Peritoneal tissues were also evaluated immunohistologically. ONO-4817 significantly inhibited thickening of the submesothelial layer and accumulation of type I collagen in the peritoneum. ONO-4817 also prevented increases of the number of macrophages and blood vessels. The expressions of TGF-beta, alpha-SMA and type I collagen in the peritoneum were markedly suppressed in ONO-4817-treated rats. It appears that the administration of the MMP inhibitor ONO-4817 might be a new approach to the amelioration of PS.
    Full-text · Article · Nov 2007 · Nephrology Dialysis Transplantation
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    ABSTRACT: It is well known that injection of calcitriol (CT) or maxacalcitol (OCT) is very effective in hemodialysis patients with secondary hyperparathyroidism (2HPT). However, it is difficult to use these drugs with peritoneal dialysis (PD) patients with 2HPT because these drugs must be injected two or three times per week. The objective of the present study was to evaluate the stability of physiological activities of CT and OCT in PD bags and to determine the CT or OCT dosage for intraperitoneal (IP) administration. We added CT 1.5 microg or OCT 10 microg to Dianeal PD-2 (approximate pH = 5.0, calcium = 0.87 mmol/L; Baxter,Tokyo, Japan), Midpeliq 250 (approximate pH = 7.0, Ca = 1.0 mmol/L;Terumo Corporation, Tokyo, Japan), and Peritoliq 250 (approximate pH = 5.5, Ca = 1.0 mmol/L; Terumo Corp.). Dialysis solutions were collected from the PD bags at 0, 1, 4, 8, 12, 24, 48, and 72 hours after addition of CT and OCT. The activities of CT and OCT in the dialysis effluent were measured by radioimmunoassay. The levels of serum and effluent OCT after a single IP administration of 10 microg OCT were examined in 4 PO patients with advanced 2HPT. Although the levels of CT and OCT in PD bags made of polyvinyl resins decreased by 70% - 75% immediately after injection, levels in PD bags made of polypropylene resins decreased only slightly. The concentration of CT mixed into the acidic solution in glass containers was stable; the decreased concentration of CT in the PD solution might be due to adsorption onto polyvinyl resins. The maximum serum concentration after IP administration of 10 microg OCT was 750 pg/mL after 5 minutes, and remained at 500 pg/mL at 60 minutes. These results show good peritoneal transport of OCT but not rapid disappearance, unlike intravenous administration. If peritoneal administration of vitamin D derivatives is contemplated, it is important to select the composition of PD bag resins, type of vitamin D analog, and time lag to use when deciding the dosage of injectable vitamin D preparations, such as OCT or CT, for IP administration to PD patients. It appears that IP administration in overnight dwells might be useful for PD patients as a complementary vitamin D preparation.
    Full-text · Article · Nov 2005 · Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis