Papers by Hajimu Kurumatani
Biological & Pharmaceutical Bulletin, 1998
PubMed, Jul 1, 1991
A cardiac wall substitute made of non-woven ultrafine fibers was developed. It consists of a basa... more A cardiac wall substitute made of non-woven ultrafine fibers was developed. It consists of a basal knitted scrim with strongly entangled ultrafine polyester fibers, lined with a fine velour of entangled ultrafine fibers that provide high ravel and tear resistance, a perfect matrix for preclotting, and an anchor for cell adhesion. Six of the new patches and all control patches (a polytetrafluorethylene patch, woven Dacron patch, and glutaraldehyde-treated equine pericardium) were implanted in the right ventricular outflow tracts in 24 dogs. Animal experiments showed that the new patch was easy to handle and suture without fraying or tearing through the edge.
PubMed, Jul 1, 1990
The control of cellular responses on substrate surfaces is essential for logical surface design a... more The control of cellular responses on substrate surfaces is essential for logical surface design aiming at endothelialized, vital implant devices. In this paper, the surface property that alters cell adhesion, spreading, migration, and proliferation processes is shown to be a determinant of endothelial cell assembly or angiogenesis in vitro. This was clearly demonstrated on slightly hydrophobic cellulosic surfaces, which induced organized three-dimensional cellular assemblies of bovine thoracic endothelial cells. The results indicated that this was driven by enhanced migratory response and/or retraction or involution of two-dimensional adherent cells, in which cell-cell interaction was enforced in a time dependent fashion. The present study strongly suggests that the mechanism leading to in vitro angiogenesis is primarily due to a weak cell-substrate interaction relative to cell-cell interaction.
BMC Nephrology, Sep 19, 2014
Background: Chronic kidney disease (CKD) is public health concern even in Asian countries. TRK-10... more Background: Chronic kidney disease (CKD) is public health concern even in Asian countries. TRK-100STP, a sustained release tablet of an orally-active prostacyclin analogue, beraprost sodium, is suggested to suppress worsening of some parameters of renal filtration function, containing in slope of 1/serum creatinine (1/SCr) vs. time in a phase II clinical trial. Methods/design: We describe the design of the phase IIb/III trial of TRK-100STP, CASSIOPEIR (CRF Asian Study with Oral PGI 2 derivative for Evaluating Improvement of Renal function) conducted in approximately 160 centers in China, Hong Kong, Japan, Malaysia, Republic of Korea, Taiwan, and Thailand. A total of 750 patients (n = 250 per group) with primary glomerular disease or nephrosclerosis were planned to be enrolled. Patients were randomized into one of three treatment groups in a double-bind, placebo-controlled manner: TRK-100STP 60 μg b.i.d.; TRK-100STP 120 μg b.i.d.; or placebo. The treatment period is planned to last 2 to 4 years. The primary efficacy endpoint is the renal composite endpoint including doubling of SCr and ESRD (dialysis induction, renal transplantation, or increase in SCr to ≥6.0 mg/dL). Discussion: This trial targeting CKD patients is designed to (a) demonstrate the superiority of TRK-100STP over placebo using renal composite endpoints, (b) determine the recommended clinical dose, and (c) assess the safety of TRK-100STP in this population and setting.
Prostaglandins Leukotrienes and Essential Fatty Acids, May 1, 2009
Unilateral ureteral obstruction (UUO) is a representative model for investigating the common mech... more Unilateral ureteral obstruction (UUO) is a representative model for investigating the common mechanism of decreasing renal function in chronic renal failure. In this study, we present a new partial UUO model in adult rats and evaluated the effect of beraprost sodium (BPS: stable prostaglandin I 2 (PGI 2) analog). We could make reproductive and uniform partial UUO by ligating the left ureter together with a 0.5 mm diameter stainless steel wire with nylon thread, and withdrawing the stainless wire. One week later, the ureteral obstruction was released. After 3 weeks from the release of UUO, all animals of control group, without BPS administration, developed basophilic degeneration of tubular epithelium, tubular dilatation and interstitial fibrosis. The areas of tubular degeneration and fibrosis were significantly reduced in the BPS group, orally administered BPS 300 mg/kg twice a day from the next day of the release of obstruction, than in control group. In conclusion, we can established the adult rat partial UUO-release model and revealed that BPS can inhibit renal tubular damage and tubulointerstitial fibrosis.
Clinical Drug Investigation, Apr 28, 2021
Beraprost sodium (BPS), an orally administrable prostaglandin I2 derivative, is used for the trea... more Beraprost sodium (BPS), an orally administrable prostaglandin I2 derivative, is used for the treatment of chronic arterial occlusion and pulmonary arterial hypertension and has potential efficacy in nephropathy. Beraprost sustained release (beraprost SR) is an oral sustained-release formulation of BPS. To confirm the dose rationale reported in a multi-regional study of nephropathy patients in Asia, this open-label study evaluated ethnic differences in the pharmacokinetic profiles of BPS and its active diastereomer (BPS-314d) after beraprost SR administration among healthy Japanese, Chinese, and Korean adult males. Twelve healthy subjects in each ethnic group were enrolled. Subjects received a single oral dose of 120 μg beraprost SR under fasting conditions. The geometric mean ratio (90% confidence interval) of the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to time of the last quantifiable concentration (AUClast) of BPS was 1.12 (0.85–1.48) and 1.40 (1.05–1.86) in Chinese, and 1.18 (0.90–1.55) and 1.18 (0.89–1.58) in Korean compared to Japanese subjects. These differences were not clinically relevant. Similarly, differences in the Cmax and AUClast of BPS-314d were also small among the ethnic groups. Urinary excretion of BPS and BPS-314d was limited in all ethnic groups. Together, these findings indicate that the pharmacokinetics of beraprost SR are not affected by ethnic background. There were no clinically meaningful ethnic differences in the pharmacokinetics of BPS and BPS-314d following beraprost SR administration among Japanese, Chinese and Korean populations.
The Japanese Journal of Artificial Organs, 1990
Therapeutic Apheresis and Dialysis, Feb 21, 2021
We conducted a multicenter, randomized, double‐blind, placebo‐controlled, phase IIb/III study (CA... more We conducted a multicenter, randomized, double‐blind, placebo‐controlled, phase IIb/III study (CASSIOPEIR) using a renal composite endpoint (i.e., doubling of SCr or end‐stage renal disease) in seven Asian countries/region. CASSIOPEIR compared TRK‐100STP (120 μg and 240 μg) with placebo in patients with non‐diabetic CKD patients with primary glomerular disease or nephrosclerosis (n = 892). However, the superiority of TRK‐100STP over placebo was not observed. A prior phase II study on which the Phase IIb/III study design was based included only Japanese patients. We therefore evaluated TRK‐100STP efficacy and safety in a subgroup of Japanese patients using the CASSIOPEIR dataset. As the timing of treatment initiation is important in CKD, we conducted additional subgroup analyses based on the baseline serum creatinine (SCr) and eGFR. ITT analysis was performed in a Japanese subgroup (n = 339) in which the primary endpoint was the first occurrence of renal composite endpoint. Significant differences were observed for TRK‐100STP 240 μg vs. placebo (P = 0.0493; HR 0.69 [95% CI: 0.47, 1.00]), but no significant difference was observed between TRK‐100 120 μg and placebo (P = 0.3523; HR 0.85). More prominent improvement was observed with TRK‐100STP 240 μg vs. placebo for baseline SCr < 3.0 mg/dL (P = 0.0031; HR 0.43); SCr < 3.5 mg/dL (P = 0.0237, HR 0.59); and eGFR ≥ 10 mL/min/1.73 m2 (P = 0.0339, HR0.67), respectively. No significant changes in urinary albumin/creatinine ratio and blood pressure were observed. TRK‐100STP was generally well tolerated and most adverse drug reactions were mild or moderate in severity. In conclusion, in the Japanese subgroup of CASSIOPEIR, TRK‐100STP 240 μg/day significantly improved the renal composite endpoint compared with placebo, with greater efficacy in subjects with SCr < 3.5 or eGFR ≥ 10 mL/min/1.73 m2.
Prostaglandins & Other Lipid Mediators, Aug 1, 2014
We have previously demonstrated that renoprotective effects of a prostacyclin analog, beraprost s... more We have previously demonstrated that renoprotective effects of a prostacyclin analog, beraprost sodium, on the kidney of anti-glomerular basement membrane glomerulonephritis (GN) rats. The aim of this study is to address the renoprotection mechanism of beraprost sodium, especially in the terminal stage of GN. Beraprost sodium was orally administrated from 2 to 7 weeks after induction of GN, and renal function, morphology, protein and mRNA levels were analyzed. We found the beraprost sodium treatment suppressed the structural regression of renal microvascular network and decline of renal blood flow occurred in the kidney of GN rats. To address the mechanism of the structural maintenance, we focused on apoptosis because the increased number of apoptotic renal microvascular endothelial cells and tubular epithelial cells was observed in the kidneys of GN rats as compared with normal and beraprost sodium treated rats. Protein and mRNA analyses demonstrated that mitochondria-dependent apoptotic pathway was activated in the kidneys of GN rats, and beraprost sodium suppressed the activation by modulating the expression patterns of pro- and anti-apoptotic factors. These results suggest that inhibition of mitochondria-dependent apoptosis of renal cells in GN kidney and consequent maintenance of renal functional structures, including microvascular network might contribute to the renoprotective effect of beraprost sodium in GN.
European Journal of Pharmacology, Aug 1, 2002
Effects of beraprost sodium, a chemically stable prostacyclin analogue, on renal dysfunction in a... more Effects of beraprost sodium, a chemically stable prostacyclin analogue, on renal dysfunction in an experimental rat model of glomerulonephritis were investigated. Beraprost sodium (30, 100 and 300 microg/kg) was orally given twice daily from the late stage of nephritis in which renal dysfunction was already developed. Beraprost sodium treatment inhibited the increase in urinary protein, serum creatinine and blood urea nitrogen, and the decrease in creatinine clearance. The elevation of serum creatinine was also inhibited by predonisolone (1 mg/kg). However, captopril (25, 50 and 100 mg/kg) and dipyridamole (20 and 60 mg/kg) failed to inhibit the elevation of serum creatinine. In the beraprost sodium-treated nephritic rats, the increase in mRNA levels for monocyte chemoattractant protein-1 (MCP-1) and collagen in the kidney was inhibited. These results suggest that beraprost sodium ameliorates developed renal dysfunction and is possibly an effective agent for the treatment of human glomerulonephritis.
Journal of Veterinary Internal Medicine, Nov 13, 2017
and the KT-140 Clinical Study Group Background: Chronic kidney disease (CKD) is a common progress... more and the KT-140 Clinical Study Group Background: Chronic kidney disease (CKD) is a common progressive and irreversible disease in cats. The efficacy and safety of beraprost sodium (BPS) in cats with CKD have not been evaluated. Hypothesis/Objectives: To evaluate the efficacy and safety of BPS in the treatment of cats with CKD, as compared to placebo. Animals: Seventy-four client-owned cats with naturally occurring CKD. Methods: Double-blind, placebo-controlled, multicenter, prospective, randomized trial. The cats received BPS (55 lg/cat) or a placebo PO q12 h for 180 days. The primary endpoint was prospectively defined as a change in the serum creatinine (sCr), serum phosphorus-to-calcium ratio or urine specific gravity (USG). Results: The sCr increased significantly (P = 0.0030) in the placebo group (mean AE SD: 2.8 AE 0.7 to 3.2 AE 1.3 mg/dL) but not in the BPS group (2.4 AE 0.7 to 2.5 AE 0.7 mg/dL). The difference between the groups at day 180 was significant (0.8 mg/dL, 95% CI: 0.2 to 1.3 mg/dL, P = 0.0071). The serum phosphorus-to-calcium ratio was significantly (P = 0.0037) increased in the placebo group (0.46 AE 0.10 to 0.52 AE 0.21 mg/dL) but not in the BPS group (0.50 AE 0.08 to 0.51 AE 0.11 mg/dL). There was no significant change in the USG in either group. An adverse event judged as being treatment-related included vomiting that occurred in 1 case in the placebo group. No clinically relevant change was observed in the CBC and other blood chemistry tests. Conclusions and Clinical Importance: Beraprost sodium treatment was well tolerated and safe in cats with CKD. BPS inhibited the reduction in renal filtration function as measured by sCr increase.
Prostaglandins Leukotrienes and Essential Fatty Acids, Mar 1, 2001
Acute hemodynamic effects of beraprost sodium were tested in a canine vasoconstrictive pulmonary ... more Acute hemodynamic effects of beraprost sodium were tested in a canine vasoconstrictive pulmonary hypertension model induced by the continuous infusion of U-46619, a thromboxane A 2 mimetic.The effects of beraprost were compared with those of prostaglandin E 1 , nitroglycerin and nifedipine.Beraprost and nitroglycerin decreased pulmonary arterial pressure.On the other hand, prostaglandin E 1 and nifedipine increased pulmonary arterial pressure. All drugs except nitroglycerin increased cardiac output and decreased pulmonary vascular resistance. Beraprost was selective to pulmonary circulation, while nitroglycerin, prostaglandin E 1 , and nifedipine showed poor selectivity for the pulmonary vasculature.These results suggest that the vasodilative effect of beraprost is the most selective for the pulmonary circulation among these four vasodilators.
Japanese Journal of Pharmacology, 1997
Fisheries Science, Feb 1, 2008
Folia Pharmacologica Japonica, 2009
Journal of Bioactive and Compatible Polymers, Oct 1, 1989
ABSTRACT Heparin was immobilized onto BrCN-activated Sepharose gel us ing α,ω-diaminopoly(ethylen... more ABSTRACT Heparin was immobilized onto BrCN-activated Sepharose gel us ing α,ω-diaminopoly(ethylene oxide) (diamino PEO) with various chain lengths as a spacer. The heparin activity was measured on the basis of prolongation of activated partial thromboplastin time (APTT). The activity of immobilized heparin was observed after the amino groups at the terminal end of the spacer molecule, not used for immobilization of heparin, were blocked with formalde hyde. The flexible PEO spacer appeared to relieve the steric hindrance by the carrier to the formation of a heparin complex with cofactor AT III. The activity of immobilized heparin increased with elongation of the spacer chain and the highest activity was obtained when the chain length of the spacer was between 10 to 20. Longer spacer groups decreased the activity because the high mobil ity of the hydrated PEO chain hindered AT III access to the immobilized heparin.
Asaio Journal, Jul 1, 1993
Folia Pharmacologica Japonica, 2001
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Papers by Hajimu Kurumatani