Kazuhiro Imai | Musashino University (original) (raw)
Papers by Kazuhiro Imai
PubMed, Aug 1, 2000
It has been a desire to develop orally effective therapeutic agents that restore the liver functi... more It has been a desire to develop orally effective therapeutic agents that restore the liver function in chronic injury. Here we demonstrated that trans-4-L-hydroxyprolyl-L-serine (JBP923) and cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485), which was previously isolated from hydrolysate of human placenta, exhibit potent antihepatitis activity after their oral administration. The increase in bilirubin concentration and activities of liver cytosolic enzymes in serum caused by alpha-naphthylisothiocyanate intoxication in rats were significantly countered both after i.v. and oral administration of these dipeptides, whereas glycyrrhizin, which has been used in the treatment of chronic hepatitis, is active only after its i.v. administration. Antihepatitis activity of dipeptides results, at least partially, from their direct effect on hepatocytes because glutamic-oxaloacetic transaminase and lactate dehydrogenase activities in the medium of hepatotoxin-exposed primary cultured hepatocytes were reduced by these compounds. When comparing the plasma concentration-time profile of JBP923 after its i.v., oral, and portal vein injection, it is suggested that JBP923 is almost completely absorbed from gastrointestinal lumen, and hepatic first-pass removal is minor. JBP923 inhibited the proton-dependent transport of glycylsarcosine in brush-border membrane vesicles, suggesting that peptide transport system(s) may recognize JBP923. Thus, these dipeptides are potent antihepatitis reagents that are still active after oral administration and may be useful for clinical applications.
Archives of Biochemistry and Biophysics, Aug 1, 2002
Analyst, 1986
Six oxalate esters of 2-nitro-4-alkoxycarbonylphenol and 2-alkoxycarbonyl-4-nitrophenol were synt... more Six oxalate esters of 2-nitro-4-alkoxycarbonylphenol and 2-alkoxycarbonyl-4-nitrophenol were synthesised for use in the peroxyoxalate chemiluminescence reactions that take place via several steps with 4-hydroxy-3-nitrobenzoic acid and 5-nitrosalicylic acid as starting ...
Progress in Neuro-psychopharmacology & Biological Psychiatry, Mar 1, 2004
![Research paper thumbnail of Determination of fluorescent cyanobenz[f]isoindole derivatives of dopamine and norepinephrine using high performance liquid chromatography with chemiluminescence detection](https://attachments.academia-assets.com/115867357/thumbnails/1.jpg)
](Biomedical Chromatography, May 1, 1990
Chromatography : journal of separation and detection sciences = クロマトグラフィー : 分離・検出科学, Oct 31, 2000
Biomedical Chromatography, May 1, 1992
A sensitive determination method for a non‐fluorescent anti‐arrhythmic drug, mexiletine, in rat p... more A sensitive determination method for a non‐fluorescent anti‐arrhythmic drug, mexiletine, in rat plasma is presented utilizing a HPLC peroxyoxalate chemiluminescence (PO‐CL) detection system. After an internal standard (4‐methylmexiletine, 4.35 pmol) and 0.1 N sodium hydroxide solution were added to 5 μL rat plasma, the solution was poured onto an Extrelut 1 column. Both mexiletine and the internal standard were eluted with diethy ether and then the eluate was evaporated to dryness. The residue was dissolved in 0.2 M borate buffer (pH 8.5) and mixed with dansyl chloride (75 nmol) in acetronitrile. After standing of 90 min at room temperature, 0.5 N HCI was added to the reaction mixture to stop the reaction and a 2/45 aliquot of the mixture was subjected to a HPLC PO‐CL detection system using bis(4‐nitro‐2(3,6,9‐trioxadecyloxycarbonyl)phenyl)oxalate (TDPO) and hydrogen peroxide. The calibration curve for mexiletine in rat plasma was linear over the range 20–100 ng/mL plasma (20.6–103 fmol/injection). The detection limit (S/N = 2) was 1.0 fmol over the whole procedure. The method was applied to the measurement of the time courses of plasma mexiletine concentration after oral administration of the drug [25 mg (115.9 μmol)/kg] to rats.
Journal of the Chemical Society, 1999
This article elucidates the relationships between the chemical structure and the fluorescence cha... more This article elucidates the relationships between the chemical structure and the fluorescence characteristics (fluorescence intensity, maximum excitation wavelength and maximum emission wavelength) of 4,7-disubstituted benzofurazan compounds with computer calculation. Our previous study using Hammett substituent constants of the substituent groups at the 4- and the 7-positions suggested that the total of electron densities on the benzofurazan skeleton and the dipole moment directed from the 4- to the 7-position might affect the fluorescence characteristics of these compounds. The sum of atomic charges on the benzofurazan skeleton, the HOMO energy and the LUMO energy were selected as parameters to reflect the total of electron densities on the benzofurazan skeleton and were obtained with the AM1 and PM3 calculations. The dipole moment directed from the 4- to the 7-position was also calculated with two hamiltonians. The LUMO energy and the dipole moment from the 4- to the 7-position obtained with the PM3 calculation is most closely related with the fluorescence characteristics. Using these parameters, the fluorescent 4,7-disubstituted benzofurazan compounds were classified into two groups, and the maximum excitation and emission wavelengths were different between these two groups. These relationships indicated that the fluorescence characteristics of 4,7-disubstituted benzofurazan compounds were determined by the total of electron densities on the benzofurazan skeleton and the dipole moment directed from the 4- to the 7-position. Furthermore, we predicted the fluorescence characteristics of four 4,7-disubstituted benzofurazan compounds based on the relationships obtained, and confirmed that the prediction agreed with the measured data.
Analyst, 1989
The effects of various factors (organic solvent, type of reservoir, temperature, water content an... more The effects of various factors (organic solvent, type of reservoir, temperature, water content and concentration of hydrogen peroxide) were investigated on the stability of a chemilumigenic reagent, bis(2,4,6-trichlorophenyl) oxalate (TCPO), for high-performance liquid chromatography. In a mixture with hydrogen peroxide, TCPO was most stable when dissolved in acetonitrile and kept in a polyethylene bottle or a high quality glass (borosilicate glass free from metals) flask. The stability of TCPO was also increased by lowering the temperature, the water content and the concentration of hydrogen peroxide in the chemilumigenic reagent solution. Under these conditions, TCPO can be used in a mixed acetonitrile solution with hydrogen peroxide for HPLC-chemiluminescence detection.
Biomedical Chromatography, 2005
Elsevier eBooks, 1989
Publisher Summary This chapter describes an attempt to separate a proper peptide fragment by mean... more Publisher Summary This chapter describes an attempt to separate a proper peptide fragment by means of chemical reactivity of the residual substituent of amino acids with newly synthesized fluorogenic reagents. The chapter describes a sensitive amino-acid-analyzer-employed chemiluminescent technology and an efficient method for peptide analysis with two-dimentional phase separation. It also discusses a simple method for purification of tryptophan- or methionine-containing peptides. In a study described in the chapter, 2-carboxy-1-hydroxy-4-naphthylmethyl-dimethylsulfonium chloride, which is a fluorogenic Koshland-type reagent (FKR) with chelating ability, was synthesized. Lysozyme and carboxymethylated lysozyme were used as model proteins. The experiments presented in the chapter reveal the selective isolation of half-cystine containing peptides by means of the specific reactivity and fluorogenic properties of 4-(aminosulfonyl)-7-fluoro-2,l,3-benzoxadiazole(ABD-F). The reagent may be useful as one of the preferable differentiation reagents in thiol groups in a protein structure.
Analytical Biochemistry, Jul 1, 2004
Analytica Chimica Acta, Oct 1, 1991
Abstract A facile and sensitive method for the determination of the fluorescent drugs dipyridamol... more Abstract A facile and sensitive method for the determination of the fluorescent drugs dipyridamole (coronary vasodilator) and benzydamine hydrochloride (anti-inflammatory) in rat plasma is presented. The method consists of the addition of an internal standard (DNS-...
Chemical & Pharmaceutical Bulletin, 1968
PubMed, Aug 1, 2000
It has been a desire to develop orally effective therapeutic agents that restore the liver functi... more It has been a desire to develop orally effective therapeutic agents that restore the liver function in chronic injury. Here we demonstrated that trans-4-L-hydroxyprolyl-L-serine (JBP923) and cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485), which was previously isolated from hydrolysate of human placenta, exhibit potent antihepatitis activity after their oral administration. The increase in bilirubin concentration and activities of liver cytosolic enzymes in serum caused by alpha-naphthylisothiocyanate intoxication in rats were significantly countered both after i.v. and oral administration of these dipeptides, whereas glycyrrhizin, which has been used in the treatment of chronic hepatitis, is active only after its i.v. administration. Antihepatitis activity of dipeptides results, at least partially, from their direct effect on hepatocytes because glutamic-oxaloacetic transaminase and lactate dehydrogenase activities in the medium of hepatotoxin-exposed primary cultured hepatocytes were reduced by these compounds. When comparing the plasma concentration-time profile of JBP923 after its i.v., oral, and portal vein injection, it is suggested that JBP923 is almost completely absorbed from gastrointestinal lumen, and hepatic first-pass removal is minor. JBP923 inhibited the proton-dependent transport of glycylsarcosine in brush-border membrane vesicles, suggesting that peptide transport system(s) may recognize JBP923. Thus, these dipeptides are potent antihepatitis reagents that are still active after oral administration and may be useful for clinical applications.
Archives of Biochemistry and Biophysics, Aug 1, 2002
Analyst, 1986
Six oxalate esters of 2-nitro-4-alkoxycarbonylphenol and 2-alkoxycarbonyl-4-nitrophenol were synt... more Six oxalate esters of 2-nitro-4-alkoxycarbonylphenol and 2-alkoxycarbonyl-4-nitrophenol were synthesised for use in the peroxyoxalate chemiluminescence reactions that take place via several steps with 4-hydroxy-3-nitrobenzoic acid and 5-nitrosalicylic acid as starting ...
Progress in Neuro-psychopharmacology & Biological Psychiatry, Mar 1, 2004
Biomedical Chromatography, May 1, 1990
Chromatography : journal of separation and detection sciences = クロマトグラフィー : 分離・検出科学, Oct 31, 2000
Biomedical Chromatography, May 1, 1992
A sensitive determination method for a non‐fluorescent anti‐arrhythmic drug, mexiletine, in rat p... more A sensitive determination method for a non‐fluorescent anti‐arrhythmic drug, mexiletine, in rat plasma is presented utilizing a HPLC peroxyoxalate chemiluminescence (PO‐CL) detection system. After an internal standard (4‐methylmexiletine, 4.35 pmol) and 0.1 N sodium hydroxide solution were added to 5 μL rat plasma, the solution was poured onto an Extrelut 1 column. Both mexiletine and the internal standard were eluted with diethy ether and then the eluate was evaporated to dryness. The residue was dissolved in 0.2 M borate buffer (pH 8.5) and mixed with dansyl chloride (75 nmol) in acetronitrile. After standing of 90 min at room temperature, 0.5 N HCI was added to the reaction mixture to stop the reaction and a 2/45 aliquot of the mixture was subjected to a HPLC PO‐CL detection system using bis(4‐nitro‐2(3,6,9‐trioxadecyloxycarbonyl)phenyl)oxalate (TDPO) and hydrogen peroxide. The calibration curve for mexiletine in rat plasma was linear over the range 20–100 ng/mL plasma (20.6–103 fmol/injection). The detection limit (S/N = 2) was 1.0 fmol over the whole procedure. The method was applied to the measurement of the time courses of plasma mexiletine concentration after oral administration of the drug [25 mg (115.9 μmol)/kg] to rats.
Journal of the Chemical Society, 1999
This article elucidates the relationships between the chemical structure and the fluorescence cha... more This article elucidates the relationships between the chemical structure and the fluorescence characteristics (fluorescence intensity, maximum excitation wavelength and maximum emission wavelength) of 4,7-disubstituted benzofurazan compounds with computer calculation. Our previous study using Hammett substituent constants of the substituent groups at the 4- and the 7-positions suggested that the total of electron densities on the benzofurazan skeleton and the dipole moment directed from the 4- to the 7-position might affect the fluorescence characteristics of these compounds. The sum of atomic charges on the benzofurazan skeleton, the HOMO energy and the LUMO energy were selected as parameters to reflect the total of electron densities on the benzofurazan skeleton and were obtained with the AM1 and PM3 calculations. The dipole moment directed from the 4- to the 7-position was also calculated with two hamiltonians. The LUMO energy and the dipole moment from the 4- to the 7-position obtained with the PM3 calculation is most closely related with the fluorescence characteristics. Using these parameters, the fluorescent 4,7-disubstituted benzofurazan compounds were classified into two groups, and the maximum excitation and emission wavelengths were different between these two groups. These relationships indicated that the fluorescence characteristics of 4,7-disubstituted benzofurazan compounds were determined by the total of electron densities on the benzofurazan skeleton and the dipole moment directed from the 4- to the 7-position. Furthermore, we predicted the fluorescence characteristics of four 4,7-disubstituted benzofurazan compounds based on the relationships obtained, and confirmed that the prediction agreed with the measured data.
Analyst, 1989
The effects of various factors (organic solvent, type of reservoir, temperature, water content an... more The effects of various factors (organic solvent, type of reservoir, temperature, water content and concentration of hydrogen peroxide) were investigated on the stability of a chemilumigenic reagent, bis(2,4,6-trichlorophenyl) oxalate (TCPO), for high-performance liquid chromatography. In a mixture with hydrogen peroxide, TCPO was most stable when dissolved in acetonitrile and kept in a polyethylene bottle or a high quality glass (borosilicate glass free from metals) flask. The stability of TCPO was also increased by lowering the temperature, the water content and the concentration of hydrogen peroxide in the chemilumigenic reagent solution. Under these conditions, TCPO can be used in a mixed acetonitrile solution with hydrogen peroxide for HPLC-chemiluminescence detection.
Biomedical Chromatography, 2005
Elsevier eBooks, 1989
Publisher Summary This chapter describes an attempt to separate a proper peptide fragment by mean... more Publisher Summary This chapter describes an attempt to separate a proper peptide fragment by means of chemical reactivity of the residual substituent of amino acids with newly synthesized fluorogenic reagents. The chapter describes a sensitive amino-acid-analyzer-employed chemiluminescent technology and an efficient method for peptide analysis with two-dimentional phase separation. It also discusses a simple method for purification of tryptophan- or methionine-containing peptides. In a study described in the chapter, 2-carboxy-1-hydroxy-4-naphthylmethyl-dimethylsulfonium chloride, which is a fluorogenic Koshland-type reagent (FKR) with chelating ability, was synthesized. Lysozyme and carboxymethylated lysozyme were used as model proteins. The experiments presented in the chapter reveal the selective isolation of half-cystine containing peptides by means of the specific reactivity and fluorogenic properties of 4-(aminosulfonyl)-7-fluoro-2,l,3-benzoxadiazole(ABD-F). The reagent may be useful as one of the preferable differentiation reagents in thiol groups in a protein structure.
Analytical Biochemistry, Jul 1, 2004
Analytica Chimica Acta, Oct 1, 1991
Abstract A facile and sensitive method for the determination of the fluorescent drugs dipyridamol... more Abstract A facile and sensitive method for the determination of the fluorescent drugs dipyridamole (coronary vasodilator) and benzydamine hydrochloride (anti-inflammatory) in rat plasma is presented. The method consists of the addition of an internal standard (DNS-...
Chemical & Pharmaceutical Bulletin, 1968