Junya Nagai

Osaka University of Pharmaceutical Sciences

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Mikihisa Takano

Yasuda Women's University

Ryoko Yumoto

Hiroshima University

Teruo Murakami

Hiroshima International University

Shizuko Kakinuma

National Institutes for Quantum and Radiological Science and Technology

Yoshiya Shimada

National Institutes for Quantum and Radiological Science and Technology

Toshiaki Ogiu

Radiation Effects Research Foundation

Mayumi Nishimura

National Institutes for Quantum and Radiological Science and Technology

Ayumi Kubo

JEOL (Japan)

Keisuke Oda

Hiroshima International University

Toshihiko Sado

National Institutes for Quantum and Radiological Science and Technology

Cooperative Institutions

Hiroshima University

Kyoto University

Osaka University of Pharmaceutical Sciences

Kyoto University Hospital

Osaka University

Hiroshima International University

Kyoto Pharmaceutical University

National Institutes for Quantum and Radiological Science and Technology

The University of Tokyo

Kindai University

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Effect of ursodeoxycholic acid treatment on the expression and function of multidrug resistance-associated protein 2 in rat intestine

Journal of Pharmaceutical Sciences (2008)

Ryoko Yumoto Shota Hamada Kaori Okada Yuki Kato Mika Ikehata

Ursodeoxycholic acid

10.1002/jps.21628

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Citations (7)

Investigation on Estimation of Vehicle Side Slip Angle by Using Extended Kalman Filter

TRANSACTIONS OF THE JAPAN SOCIETY OF MECHANICAL ENGINEERS Series C (2013)

Junya Nagai Yasutake HARAMIISHI Yuuki Shiozawa Hiroshi MOURI

The extended Kalman filter was employed to estimate vehicle side-slip angle accurately even under the condition of low road friction and the large lateral gradient road. The direct integration method is the base structure of this estimator, and the longitudinal equation of motion was included to augment the system , and to configure the Kalman filter. For compensation of estimation value drifted by the sensor signal offset , a nonlinear map between actual yawrate and the yawrate value using in the calculation was proposed. The performance of the extended Kalman filter and the non-linear map was validated in the simulation.

Alpha beta filter

10.1299/kikaic.79.3358

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Citations (1)

Pharmacokinetic–pharmacodynamic modelling of the hypoglycaemic effect of pulsatile administration of human insulin in rats

Scientific Reports (2020)

Makoto Miyazaki Mariko Hayata Noriaki Samukawa Kazunori Iwanaga Junya Nagai

Abstract The relationship between the plasma insulin (INS) concentration–time course and plasma glucose concentration–time course during and after pulsatile INS administration to rats was characterized using a pharmacokinetic–pharmacodynamic (PK–PD) model. A total INS dose of 0.5 IU/kg was intravenously injected in 2 to 20 pulses over a 2-h period. Compared with the single bolus administration, the area under the effect-time curve (AUE) increased depending on the number of pulses, and the AUEs for more than four pulses plateaued at a significantly larger value, which was similar to that after the infusion of a total of 0.5 IU/kg of INS over 2 h. No increase in plasma INS concentration occurred after pulsatile administration. Two indirect response models primarily reflecting the receptor-binding process (IR model) or glucose transporter 4 (GLUT4) translocation (GT model) were applied to describe the PK–PD relationship after single intravenous bolus administration of INS. These models could not explain the observed data after pulsatile administration. However, the IR-GT model, which was a combination of the IR and GT models, successfully explained the effects of pulsatile administration and intravenous infusion. These results indicate that the receptor-binding process and GLUT4 translocation are responsible for the change in AUE after pulsatile administration.

Pulsatile flow

Pharmacodynamics

Bolus (digestion)

GLUT4

10.1038/s41598-020-76007-3

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Citations (4)

Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure

European Journal of Pharmacology (2000)

Zhaohui Huang Teruo Murakami Atsuko Okochi Ryoko Yumoto Junya Nagai

P-glycoprotein

Membrane glycoproteins

10.1016/s0014-2999(00)00699-3

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Citations (80)

Novel Polymyxin Derivatives Carrying Only Three Positive Charges Are Effective Antibacterial Agents

Antimicrobial Agents and Chemotherapy (2008)

Martti Vaara John Fox Günther Loidl Osmo Siikanen J. Apajalahti

ABSTRACT The lack of novel antibiotics against gram-negative bacteria has reinstated polymyxins as the drugs of last resort to treat serious infections caused by extremely multiresistant gram-negative organisms. However, polymyxins are nephrotoxic, and this feature may complicate therapy or even require its discontinuation. Like that of aminoglycosides, the nephrotoxicity of polymyxins might be related to the highly cationic nature of the molecule. Colistin and polymyxin B carry five positive charges. Here we show that novel polymyxin derivatives carrying only three positive charges are effective antibacterial agents. NAB739 has a cyclic peptide portion identical to that of polymyxin B, but in the linear portion of the peptide, it carries the threonyl- d -serinyl residue (no cationic charges) instead of the diaminobutyryl-threonyl-diaminobutyryl residue (two cationic charges). The MICs of NAB739 for 17 strains of Escherichia coli were identical, or very close, to those of polymyxin B. Furthermore, NAB739 was effective against other polymyxin-susceptible strains of Enterobacteriaceae and against Acinetobacter baumannii . At subinhibitory concentrations, it dramatically sensitized A. baumannii to low concentrations of antibiotics such as rifampin, clarithromycin, vancomycin, fusidic acid, and meropenem. NAB739 methanesulfonate was a prodrug analogous to colistin methanesulfonate. NAB740 was the most active derivative against Pseudomonas aeruginosa . NAB7061 (linear portion of the peptide, threonyl-aminobutyryl) lacked direct antibacterial activity but sensitized the targets to hydrophobic antibiotics by factors up to 2,000. The affinities of the NAB compounds for isolated rat kidney brush border membrane were significantly lower than that of polymyxin B.

Polymyxin

Colistin

Polymyxin B

Acinetobacter baumannii

Nephrotoxicity

Lipid A

10.1128/aac.00405-08

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Citations (131)

p-Aminohippurate transport in apical and basolateral membranes of the OK kidney epithelial cells.

Journal of Pharmacology and Experimental Therapeutics (1994)

Mikihisa Takano Kiyoshi HIROZANE M. OKAMURA Akira Takayama Junya Nagai

p-Aminohippurate (PAH) transport in apical and basolateral membranes of OK cells was studied to characterize each membrane process and to determine which process is important for the vectorial transport of PAH across the OK cell monolayers. PAH uptake from the basal side into OK cells was much higher than from the apical side, and was inhibited almost completely by anion transport inhibitors (probenecid and furosemide) and low temperature. On the other hand, PAH efflux from OK cells to the apical side was higher than to the basal side. The efflux across the apical membrane also was inhibited by the transport inhibitors and low temperature. The uptake of PAH across the basolateral membrane was inhibited by dicarboxylates such as alpha-ketoglutarate, and kinetic analysis showed that the inhibition was a mixed-type. These findings suggest that PAH transport in apical and basolateral membranes of OK cells is a specifically mediated process, and both processes contribute to the vectorial transport of PAH across the cell monolayers. PAH/dicarboxylate exchange may be involved in PAH transport in the basolateral membrane of OK cells.

Epithelial polarity

Apical membrane

Probenecid

Efflux

10.1016/s0022-3565(25)38901-9

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Citations (24)

ヒト肺胞上皮細胞株A549におけるインシュリン取り込みへのタバコ煙抽出物(CSE)の影響

日本薬物動態学会年会講演要旨集 (2011)

Horiuchi Taishi Keisuke Oda Junya Nagai Ryoko Yumoto Mikihisa Takano

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Enhancement Effect of Poly(amino acid)s on Insulin Uptake in Alveolar Epithelial Cells

Drug Metabolism and Pharmacokinetics (2012)

Keisuke Oda Ryoko Yumoto Junya Nagai Hirokazu Katayama Mikihisa Takano

Internalization

10.2133/dmpk.dmpk-12-rg-002

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Citations (6)

Molecular Mechanisms Underlying Renal Accumulation of Aminoglycoside Antibiotics and Mechanism‐Based Approach for Developing Nonnephrotoxic Aminoglycoside Therapy

ChemInform (2006)

Junya Nagai

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

10.1002/chin.200635295

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Citations (5)

Efflux of Intracellular α-Ketoglutarate Via p-Aminohippurate/Dicarboxylate Exchange in OK Kidney Epithelial Cells

Journal of Pharmacology and Experimental Therapeutics (1998)

Junya Nagai Ikuko Yano Yukiya Hashimoto Mikihisa Takano Ken‐ichi Inui

Efflux

10.1016/s0022-3565(24)37480-4

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Citations (0)