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YAKUGAKU ZASSHI, 120(9), 721-731, 2000
Analyses of trace biologically essential or toxic ionic compounds found in the environment are very important. However, the lack of sensitivity and interference caused by coexisting components are often serious problems. To determine trace levels of metal ions without the above problems, new preconcentration and analytical methods have been developed. Firstly, three methods for the selective preconcentration of metal ions are shown below: 1) 3-Chloropyridazine-6-carbohydrazide was immobilized on glass beads supports to be used as a column packing material. Multi-metal ions were concentrated on the column and eluted selectively with several buffers and hydrochloric acid. The eluate was analyzed off-line by flame atomized-atomic absorption spectrometry (AAS). This method was able to determine sub-ppb levels of cupper- and cadmium-ions in environmental samples. 2) Salicylideneamino-2-thiophenol was immobilized on the supports. Aluminum ion was concentrated selectively on the column and eluted with nitric acid. The eluate was analyzed off-line by flameless-AAS or on-line by flow injection analysis using pyrocatechol violet for a post-column colorimetric reagent. These methods were able to determine ppb-ppt levels of aluminum in environmental samples and were suitable for its state-analysis. 3) Bathocuproinesulfonic acid was immobilized on the supports. Copper ion was concentrated selectively on the column and eluted with nitric acid. The eluate was analyzed on-line by flow injection analysis using bathocuproinesulfonic acid. This method was able to determine sub-ppb levels of copper in environmental samples. On the other hand, to analyze simultaneously trace metal ions and anions, capillary electrophoresis was performed using ethylenediaminetetraacetic acid as an electrolyte component. Simultaneous determination of several ions in mineral waters was achieved by the system.
Key words--trace enrichment; aluminum ion; copper ion; flow injection analysis; atomic absorption spectrometry; capillary electrophoresis
YAKUGAKU ZASSHI, 120(9),733-747, 2000
Our recent studies on asymmetric synthesis with the assistance of organometal catalysts stereocontrolled by organosulfur functionality involved in reaction substrates or ligands are reviewed. The studies focused on asymmetric synthesis viachiral π-allylmetal complexes derived from (S)-proline allyl ester, olefinic cyclopropanes, chiral 2-alkynyl sulfinates, and chiral new ligands, and also focused on asymmetric cycloaddition reactions with chiral sulfoxides and sulfinates, such as intramolecular ene, metallo-type ene, and hetero Diels-Alder reactions. Participation of organosulfur functionality in organometal-catalyzed asymmetric reactions was unveiled on the basis of the stereochemical outcomes obtained.
Key words--asymmetric synthesis; organosulfur chemistry; transition metal; chiral sulfoxide; chiral sulfinate; organometal chemistry
YAKUGAKU ZASSHI, 120(9),749-765, 2000
Clonal micropropagation on various medicinal plants was set up resulting in the regenerated plants which possessed a homogeneous quality. The ratio of hapten to bovine serum albumin (BSA) in an antigen conjugate was determined by matrix-assisted laser desorption/ionization of mass spectrometry. A hybridoma secreting monoclonal antibody (MAb) was produced by fusing splenocytes immunized with an antigene-BSA conjugate with mouse myeloma cells. Competitive enzyme-linked immunosorbent assay (ELISA) using MAb was set up as a high sensitive, specific and reproducible qualitative method. A method of determination for ginsenosides by using a unique western blotting was established. Immunoaffinity column chromatography using an anti-ginsenoside Rb1MAb has made possible a single-step separation of ginsenoside Rb1 from a crude ginseng extract. Single chain Fv gene of anti-forskolin MAb was prepared from mRNA of hybridoma secreting anti-forskolin MAb and cloned. Gene was constructed into a pET-28a(+) vector producing a scFv protein. Modeling of forskolin and scFV was investigated. THCA synthase was purified from the homogenate of Cannabis sativa leaves on successive column chromatographies. THCA synthase was confirmed to be homogeneity having 75kDa. To obtain the corresponding cDNA clone of THCA synthase, a set of degenerate promers was constructed based on N-terinal and internal amino acide sequences of THCA synthase. The 5´ and 3´ ends of cDNA were amplified by RACE. A full sequencing has been determined to be corded a polypeptide having 545 amino acid residues. The cDNA clone was expressed in yeast system via PUC19 vector resulting in THCA synthase activity.
Key words--monoclonal antibody; biosynthetic enzyme; molecular cloning; micropropagation; western blotting; immunoaffinity column
YAKUGAKU ZASSHI, 120(9),767-778, 2000
We developed and evaluated a local area network system to make drug information papers. Because pharmacists should explain drug information both orally and using papers to patients in response to their understanding and characteristics of their diseases. The merit of this system is as follows: pharmacists can use it without any education for its operation; most data can be inputted by selection from the lists and automatic reference; the data are adjustable for individuals; different contents are available for different wards; multiple users can access the same data file. Input data in this system are available for making explanation papers on the medical examination of outpatients, and making a plan for pharmaceutical care and guidance services. This system is also available in other hospitals, and on the internet. First, we surveyed the time required for preparing drug information papers. Making a hand written paper for typical patient takes 395 sec. for manuscript, 160 sec. with the system using text data only, and 178 sec. with the system using text and picture data. Next, we surveyed 27 patients' views on the addition of drug pictures to drug information papers, and with the result that 19 patients thought it very good. Last, we surveyed 13 ward pharmacists about their usage of this system. We found that 8 pharmacists used frequently this system, and 3 pharmacists used the same file in the same hours at the maximum.
Key words--computer system; drug information paper; ward pharmacist; local area network system
YAKUGAKU ZASSHI, 120(9),779-785, 2000
We previously reported a HPLC identification method for Astragali Radix and its fluid extract using calycosin as a marker substance. However, it took about 40 min for one run using gradient elution. Therefore, we alternatively employed capillary electrophoresis (CE) for the analysis of calycosin in those materials. As a result, calycosin was clearly separated from the other components in Astragali Radix and its fluid extract by micellar electrokinetic chromatography (MEKC) mode with sodium dodecyl sulfate (SDS) within 5 min. Then we determined the content of calycosin in a drinkable preparation. Validation for the developed method was also performed in accordance with the ICH guideline.
Key words--Astragali Radix; calycosin; micellar electrokinetic chromatography (MEKC); natural medicine; analytical procedure validation
YAKUGAKU ZASSHI, 120(9),787-794, 2000
The present study examines the effects of thiabendazole (TBZ), its metabolites, 5-hydroxythiabendazole (5-OH TBZ) and 2-acetylbenzimidazole (ABI), and structural related compounds, thiazoles and thioamides on glutathione (GSH) concentration and GSH-related enzymes in the livers of ICR 11 week-old female mice. GSH concentration in liver and kidney of mice given orally TBZ 0.65 mol/kg (TBZ group) increased significantly compared with control mice from 24 h to 48 h after administration of TBZ. Even in mice to which TBZ at 0.175 mol/kg was administered in combination with L-buthionine sulfoximine (BSO) 4 mmol/kg (i.p.) (BSO-TBZ group), kidney GSH showed significant increase compared with BSO-control mice 48 h after the administration of TBZ. γ-Glutamylcysteine synthetase (γ-GCS) activity in the livers of the TBZ group markedly increased at 48 h and that of BSO-TBZ group increased from 24 h to 48 h. γ-GCS in mice liver is thus enhanced by TBZ regardless of BSO administration. Hepatic glutathione peroxidase activity of the TBZ group did not change in response to cumene hydroperoxide assubstrate. That of BSO-treated mice decreased by TBZ-coadministration and significant differences was noted between BSO-control and BSO-TBZ groups from 1 h to 48 h later. Hepatic glutathione S-transferase (GST) activity toward 1,2-dichloro-4-nitrobenzene (DCNB) was significantly elevated 24 h after administrations of TBZ in TBZ and BSO-TBZ groups. GST activity toward 1,2-epoxy-3-(p-nitrophenoxy) propane of TBZ group increased from 0.5 h to 24 h. Hepatic GST activity toward DCNB and 1-chloro-2,4-dinitrobenzene did not change by administration of 0.65 mol/kg 5-OH TBZ or ABI but increased by administrations of 0.33 mol/kg of thiazole, 4-methylthiazole, 4,5-dimethylthiazole or 2,4-dimethylthiazole. Increase in GSH concentration and GST activity in mice liver by TBZ administration may be considered to provide protection from TBZ or its active metabolites.
Key words--thiabendazole; glutathione; mice liver; glutathione S-transferase; thiazole
YAKUGAKU ZASSHI, 120(9),795-799, 2000
Recently, a case of patients with allergic contact dermatitis caused by the poly (vinyl chloride) (PVC) seat, containing 10,10´-oxybis-10H-phenoxarsine (OBPA), of a chair was reported. OBPA was developed as an antimicrobial for plastics such as PVC and polyurethane, and it has been widely used in artificial leather for the seats of chairs and sofas. To identify causative chemicals for allergic contact dermatitis, a combination of patch testing in the patients and chemical analysis of causative products is valuable. However, no analytical method and data of OBPA in commercial products was reported. In this study, a method for the determination of OBPA in the artificial leather (PVC base) was developed. OBPA was extracted from PVC samples with methanol. The extract was loaded on an aluminum oxide column, and washed with diethyl ether:hexane, and eluted with ethanol:hexane. The eluate was evaporated, dissolved in methanol and injected to a HPLC equipped an ODS column and an UV detector (detection wavelength 300 nm). OBPA standard crystal was isolated from commercial agents containing OBPA. The calibration curve for OBPA was linear in the range of 0.1--100μg/ml. The minimum detection and determination concentrations of OBPA in samples were 0.07 and 0.25μg/g. By this method, eight PVC sheets for the seat of a chair were analyzed. In two PVC sheets, 52.7 and 84.9μg/g of OBPA were detected. In the PVC product that caused contact dermatitis, OBPA was not found.
Key words--10,10´-oxybis-10H-phenoxarsine; OBPA; antimicrobial; determination; poly(vinyl chloride); HPLC
YAKUGAKU ZASSHI, 120(9),801-805, 2000
Adenosine A1-receptor antagonists have been previously shown to possess protective effects in several nephrotoxic models of acute renal failure. To investigate the mechanism of protective effects of adenosine A1-receptor antagonists, we determined effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a selective adenosine A1-receptor antagonist, on the accumulation of gentamicin (GM) into proximal renal tubules in rats. GM was intravenously administered at a dose of 10mg/kg in anesthetized rats. KW-3902 (0.1mg/kg) or its vehicle was given as a bolus injection 6 min before the GM injection. Administration of GM and KW-3902 did not affect the systemic blood pressure, heart rate, renal blood flow and glomerular filtration rate. KW-3902 did not affect the plasma concentration of GM. GM was accumulated in the proximal tubules 4 h after the GM injection. Treatment with KW-3902 significantly decreased the accumulation of GM into the proximal tubules. These results suggest that endogenous adenosine may accelerate the uptake of GM at the proximal tubules, and that the renoprotective effects of the adenosine A1-receptor antagonist may result from inhibiting this action of endogenous adenosine, leading to the suppression of intrarenal accumulation of GM.
Key words--KW-3902, adenosine A1-receptor antagonist, gentamicin, acute renal failure
YAKUGAKU ZASSHI, 120(9),807-811, 2000
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicinea and Department of Cardiovascular Medicine, Graduate School of Medicine,b Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
We showed a digoxin-itraconazole interaction in three patients in whom digoxin serum concentrations were increased. Their electrocardiograms revealed arrhythmias such as ventricular premature contraction, atrioventricular block, and ST depression. The elimination half-life of digoxin in case 3 patient who continued itraconazole therapy was 8.4 days, which was estimated by nonlinear least squares method from the serum concentrations of digoxin versus time curve. In order to evaluate the influence of itraconazole on pharmacokinetic parameters of digoxin, we estimated digoxin clearance by the Bayesian method using the population pharmacokinetic parameters in Japanese patients. During the concomitant use of itraconazole and digoxin, the digoxin clearance in all patients decreased to 50.5±8.8% (mean ±S.D.) of the clearance without itraconazole. When digoxin and itraconazole are used concomitantly, careful monitoring of digoxin serum concentrations is necessary. Based on our results of digoxin clearance evaluation, the dose of digoxin should be reduced to 50% of original dose after itraconazole is started, and digoxin serum concentration might be controlled at the same level before the concomitant use.
Key words--digoxin, itraconazole, interaction, digoxin clearance
YAKUGAKU ZASSHI, 120(9),813-816, 2000
New guidelines for the clinical use of blood preparations intended to promote more rational use were issued by the Japanese Ministry of Health and Welfare in June 1999. The purpose of this article is to clarify the current situation in the use of albumin (Alb) preparations during surgery and to design a plan to promote the rational use of these products at Yamaguchi University Hospital. Of the patients administered Alb preparations during surgery in our hospital over the 6 month period from January 1 to June 30, 1999, 158 were selected based on prescription records of plasma component preparations. Most of the patients (63%) were 60 years old or over. The total amount of Alb administered to the patients was 6150 g. Those patients, whose postoperative serum Alb concentration was lower than 3, 3 to 3.5, 3.5 to 4, and more than 4 g/dl, numbered 60, 45, 21, and 23, respectively. The total amount of Alb overdosed to the patients, whose postoperative Alb concentration was more than 3 g/dl, was 2282 g (37% of the administered Alb). The overdosed patients mainly belonged to the Cardiovascular Surgery Division and were treated with a pump-oxygenator during surgery. Three bottles (37.5 g) of concentrated Alb had usually been used to prime the perfusate. These results indicate that it is possible to cut back on Alb by reconsidering the criteria for its administration.
Key words--guideline; rational use; Alb preparation; surgical operation; Ministry of Health and Welfare