巻号一覧
37 巻, 2 号
選択された号の論文の73件中1～50を表示しています
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藤原 靖弘, 岡本 正夫1989 年 37 巻 2 号 p. 267-274
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーStereochemistry of 8, 9-dimethoxycarbonyldibenzo[2, 3 : 5, 6]bycyclo[5.2.0]nonan-4-ones (2a, 3a, 4a, and 5a) and 8, 9-dimethoxycarbonyl-4-hydroxydibenzo[2, 3 : 5, 6]tricyclo[5.2.0.04.8]nonanes (6a and 7a) was studied by chemical and spectrometrical means.Intramolecular acid anhydride formation reactions of isomeric cis-dicarboxylic acids (3c, 5c, 6c, and 4c) afforded the anhydrides (3d, 5d, 6d, and 5d), respectively. Interconversion between 2a and 3a and between 4a and 5a at higher temperature by thermal reaction resulted in equilibria of 2a and 3a (3 : 2) and of 4a and 5a (20 : 1).Detailed 13C and 1H assignments (3a, 4a, 5a, 6a, and 7a), and stereostructural assignments (3a, 4a, and 5a) were made by using nuclear magnetic resonance (NMR) techniques such as 1H-{1H} and 13C-{1H}NMR, 13C/1H chemical shift-correlated NMR, and 1H-1H and <13>C-{1H} nuclear Overhauser effect (NOE) measurements. Moreover, a possible mechanism of interconversion between 4a and 5a is discussed.抄録全体を表示PDF形式でダウンロード (1112K) -
斉藤 博満, 松島 日出夫, 白木 千尋, 平田 正1989 年 37 巻 2 号 p. 275-279
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリー7-Azido-1, 2-dehydro-1-carbacephem 13 was efficiently synthesized by employing ketene-imine cycloaddition, intramolecular Horner-Emmons reaction and elimination of a phenylsulfoxide group or an ammonium group. 7-Acylamino 1, 2-dehydro-1-carbacephems, 18 and 19, were obtained from 13. Infrared absorption frequencies of the β-lactam carbonyl in 1, 2-dehydro-1-carbacephem compounds thus prepared are equal to or higher than those of the corresponding 1-carbacephem compounds. However, 18 and 19 exhibited very poor antibacterial activity.抄録全体を表示PDF形式でダウンロード (766K) -
岩崎 源司, 木村 理恵子, 沼尾 長徳, 近藤 聖1989 年 37 巻 2 号 p. 280-283
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe diastereoselective synthesis of a series of potent angiotensin converting enzyme (ACE) inhibitors is described. The optically active intermediate, N-carbamyl (R)-2-amino-4-phenylbutyric acid (2) leading to (R)-2-halogeno or (R)-2-hydroxy-4-phenylbutyric acid was prepared by asymmetric hydrolysis of DL-5-phenethylhydantoin (1) by microbial hydantoinase. The halogenoester was subjected to SN2 reaction with L-amino acid derivatives to afford N-substituted amino acids, which were easily converted to ACE inhibitors or intermediates by deprotection.抄録全体を表示PDF形式でダウンロード (757K) -
板谷 泰助, 水谷 朱見, 竹田 資子, 塩山 智栄子1989 年 37 巻 2 号 p. 284-291
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーAcid- or base-catalyzed acylation of 1-benzylwye (7) provided the 7-substituted derivatives 9, 10, and 11 in poor yields. Although the reactions of lithiated 7 with electrophiles gave the 2-substituted derivatives 14, 15, 17, 20, 21, and 22, lithiation of 1-benzyl-7-bromo-2-chlorowye (23) followed by treatment with Me2CHCH2CHO (13) successfully introduced a side chain at the 7-position to afford 1-benzyl-2-chloro-7-(1-hydroxy-3-methylbutyl)wye (24).Cyclization of 1-benzyl-3-methylguanine (5) with 3-bromo-2-butanone followed by catalytic hydrogenolysis afforded 7-methylwye (2b), the hypermodified base isolated from archaebacterial transfer ribonucleic acids. A more efficient route for the synthesis of 2b has been developed via a series of reactions : the Vilsmeier-Haack reaction of 7, reduction with NaBH4, and catalytic hydrogenolysis over Pd-C.抄録全体を表示PDF形式でダウンロード (1364K) -
渡辺 三明, 伊達 睦廣, 古川 淳1989 年 37 巻 2 号 p. 292-297
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーA total synthesis of the anticoccidial antibiotic WS-5995A was achieved by regioselective condensation of N, N-diethyl-o-toluamide anions into bomophthalic anhydrides as a key reaction.抄録全体を表示PDF形式でダウンロード (1177K) -
松田 彰, 渡辺 一之, 宮坂 貞, 上田 亨1989 年 37 巻 2 号 p. 298-303
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe synthesis of a new carbon-bridged cyclopurine nucleoside, 2'-deoxy-8, 2'-methanoguanosine (25), which is fixed in a high-anti torsional angle region, was accomplished. 2-Acetamido-6-ethoxy-8-methanesulfonyl-9-(3, 5-di-O-acetyl-2-O-tosyl-1-β-D-ribofuranosyl)purine (18) was cyclized with carbanions of malonic esters, followed by sequential deblocking and decarboxylation to afford 25. The ultraviolet spectra of 25 in neutral solution revealed two separated bands corresponding to their B1u and B2u transitions, which was rather similar to the case of its O6-ethyl derivative (22), but quite different from the previously reported 8, 2'-methanoguanosine (26), a ribosyl counterpart of 25. The circular dichroism spectra of these cyclonucleosides are also discussed.抄録全体を表示PDF形式でダウンロード (1021K) -
尾崎 裕, 金 相元1989 年 37 巻 2 号 p. 304-307
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリー1, 2, 4-Benzenetriols were synthesized via 4, 4-bis(ethylthio)-1, 3-cyclohexanediones which were prepared by means of two types of Michael-Claisen condensation starting from methyl bis(ethylthio)acetate or 1, 1-bis(ethylthio)-2-propanone.抄録全体を表示PDF形式でダウンロード (673K) -
Giovanni BOCCARDI, Piergiorgio MEZZANZANICA, Umberto GUZZI, Giordano L ...1989 年 37 巻 2 号 p. 308-310
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe photochemical reaction of dextromethorphan 1, a widely used anti-tussive drug, in hydrochloric acid and in the presence of iron(III) salts leads to the 10β-hydroxyderivative 3 as a major product in addition to the 10-ketoderivative 2. The product composition of this reaction is strongly dependent on the experimental conditions and the effects of solvents are presented.抄録全体を表示PDF形式でダウンロード (572K) -
邵 春杰, 笠井 良次, 徐 景達, 田中 治1989 年 37 巻 2 号 p. 311-314
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーFour new triterpenois saponins named kalopanax-saponins C (4), D (5), E (6) and F (7) were isolated from the roots of Kalopanax septemlobus (THUNB.) KOIDZ. together with three known saponins, kalopanax-saponins A (1) and B (2), and chikusetsusaponin IV (3). On the basis of chemical and spectral data, the structures of these new saponins were elucidated to be as follows : (4), 3-O-α-rhamnopyranosyl-(1→2)-[β-glucopyranosyl-(1→3)]-α-arabinopyranosyl hederagenin 28-O-α-rhamnopyranosyl-(1→4)-β-glucopyranosyl-(1→6)-β-glucopyranosyl ester; (5), 3-O-α-rhamno-pyranosyl-(1→2)-[β-glucopyranosyl-(1→3)]-α-arabinopyranosyl oleanolic acid 28-O-α-rhamnopyranosyl-(1→4)-β-glucopyranosyl-(1→6)-β-glucopyranosyl ester; (6), 3-O-β-glucopyranosyl-(1→3)-β-glucuronopyranosyl oleanolic acid; (7), 3-O-α-arabinopyranosyl-(1→2)-[β-glucopyranosyl-(1→3)]β-glucuronopyranosyl oleanolic acid 28-O-β-glucopyranosyl ester.抄録全体を表示PDF形式でダウンロード (614K) -
小笠 剛裕, 斉藤 博満, 橋本 幸生, 佐藤 清, 平田 正1989 年 37 巻 2 号 p. 315-321
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリー3-H-1-Carbacephem nuclei with or without a 2α- or 2β-methyl group were prepared via 2+2 cycloaddition followed by intramolecular Horner-Emmons cyclization.Optically active 3-H-1-carbacephem compounds were efficiently prepared by employing a penicillin acylase-producing microorganism in two ways. That is, the 7-phenylacetamide of a racemic carbacephem nucleus was hydrolyzed enantioselectively with the enzyme to afford the optically pure nucleus, which was then acylated to give antimicrobial compounds. Alternatively, a racemic carbacephem nucleus was directly and enantioselectively phenylglycylated with the enzyme, 3-H-1-Carbacephem nuclei appeared to be better substrates for penicillin acylase than penam or cephem nuclei of natural origin.3-H-1-Carbacephem compounds showed potent antimicrobial activity; compound 32a exhibited activity comparable to that of ceftizoxime, a cephem analog with the same acyl group. It is of interest that the 3-H-1-carbacephem compound turned out to have more potent antimicrobial activity than its 3-substituted methyl analog.抄録全体を表示PDF形式でダウンロード (1168K) -
内多 稔, 小松 真, 森田 清司, 神辺 敏実, 中川 量之1989 年 37 巻 2 号 p. 322-326
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーA series of tetrazole alkanamides was synthesized and tested for antiulcer activity against acetic acid-induced gastric ulcer in rats. These compounds were prepared by the reaction of tetrazole alkanoic acids and various amines by the mixed anhydride method or acid chloride method. Among them, 3-[(1-ethyl-5-tetrazolyl)methylthio]propionamide (IIn) was found to have the most potent activity. The structure-activity relationships are discussed.抄録全体を表示PDF形式でダウンロード (783K) -
萩下 山治, 瀬野 薫1989 年 37 巻 2 号 p. 327-335
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーFour stereoisomers of 7-oxabicyclo[2.2.1]heptane derivatives with the benzenesulfonylamino group, 11, 14, 23 and 33, were synthesized and their sodium salts were examined in vitro for inhibitory activity against aggregation of rabbit platelet-ric plasma and of rat washed platelets. The trans-isomer 23 exhibited high potency but showed a partial agonistic effect. Compound 11 did not show a partial agonistic effect, though it was a less active inhibitor. The following trans compounds were synthesized and their IC50 values were measured : homologated trans-isomers with one methylene chain (47 and 53), an olefin derivative (58), and optically active derivatives ((-)-11 and (+)-23).抄録全体を表示PDF形式でダウンロード (1488K) -
Chung K. CHU, Jasenka MATULIC-ADAMIC, Jai-Tung HUANG, Ting-Chao CHOU, ...1989 年 37 巻 2 号 p. 336-339
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーSeven purine nucleosides containing the 2'-deoxy-2'-fluoro-β-D-arabinofuranosyl moiety were synthesized and tested for their antitumor activity. Direct condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (1) with N6-benzoyladenine in CH2Cl2 followed by saponification of the product afforded the adenine nucleoside (1, 2'-F-ara-A). Deamination of I with NaNO2 in HOAc gave the hypoxanthine analogue (II, 2'-F-ara-H). The 6-thiopurine nucleoside (III, 2'-F-ara-6MP) was prepared by condensation of 1 with 6-chloropurine by the mercury procedure followed by thiourea treatment and saponification of the product. Methylation of III gave the 6-SCH3 analogue (IV). Raney Ni desulfurization of III afforded the unsubstituted purine nucleoside (V, 2'-F-ara-P). Condensation of 1 with 2-acetamido-6-chloropurine by the silyl procedure afforded the protected 2-acetamido-6-chloropurine nucleoside which served as the precursor for both the guanine and 6-thioguanine nucleosides (VI, 2'-F-ara-G and VII, 2'-F-ara-TG, respectively). Thus, alkaline hydrolysis of the precursor gave VI. Thiourea treatment prior to alkaline hydrolysis gave VII. The new nucleoside, 2'-F-ara-G (VI) is found to be selectively toxic to human T-cell leukemia CCRF-CEM.抄録全体を表示PDF形式でダウンロード (721K) -
田中 隆, 森元 聡, 野中 源一郎, 西岡 五夫, 横澤 隆子, 鄭 海泳, 大浦 彦吉1989 年 37 巻 2 号 p. 340-344
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe active components which exhibit the improving effect on uremic symptoms have been isolated from Salviae miltriorrhizae Radix and characterized as magnesium lithospermate (1) and ammonium-potassium lithospermate (2). The stereostructure of lithospermic acid, which had remained unclarified, was also determined on the basis of chemical and spectroscopic data.抄録全体を表示PDF形式でダウンロード (773K) -
市川 和雄, 木下 武司, 三川 潮1989 年 37 巻 2 号 p. 345-348
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーHot aqueous extracts of 134 Chinese crude drugs were subjected to screening for inhibitory activity on K+ contracture of guinea pig taenia coli, and significant activity was observed in 17 crude drugs. Chemical investigations of two crude drugs, Kakko and Ubai, which originate from Pogostemon cablin and Prunus mume, respectively, were undertaken, and patchouli alcohol (I) and 5-(hydroxymethyl)-2-furaldehyde (II) were identified as their active principles, respectively.抄録全体を表示PDF形式でダウンロード (777K) -
福山 愛保, 児玉 三明, 三浦 巖, 金城 順英, 木戸 勝, 森 英雄, 中山 康夫, 高橋 真行1989 年 37 巻 2 号 p. 349-353
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーEckol (1), a novel phlorotannin with a dibenzo-1, 4-dioxin skeleton, has been isolated from the brown alga Ecklonia kurome OKAMURA as a potent and specifif and specific anti-plasmin inhibitor. Its structure has been elucidated based on the spectral data, in particular, by means of negative nuclear Overhauser effect (NOE), and finally established as 1-(3, 5-dihydroxyphenoxy)-2, 4, 7, 9-tetrahydroxydibenzo-1, 4-dioxin by X-ray analysis. Some partially methoxylated derivatives of eckol wre prepared by methylation with diazomethane and also by selective demethylation of eckol permethylate (1b) to establish the structural requirements for inhibitory activities on α2-macroglobulin and α2-plasmin inhibitor, the main plasmin inhibitors in plasma.抄録全体を表示PDF形式でダウンロード (985K) -
下村 裕子, 指田 豊, 小川 一紀1989 年 37 巻 2 号 p. 354-357
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーBy reinvestigation of the aerial parts of Ajuga nipponensis, four new bitter neo-clerodanes, ajugamarins C1, B2, B3 and D1, and a known diterpene, ajugarin-I, have been isolated. The structures of these diterpenes were elucidated on the basis of spectral data and chemical correlations.抄録全体を表示PDF形式でダウンロード (698K) -
今井 藤生, 木下 武司, 三川 潮1989 年 37 巻 2 号 p. 358-362
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーTwo new coumarins, paniculin (II) and coumurrin (V), were isolated from the leaves of Murraya paniculata (L.) JACK (Rutaceae), and their structures were elucidated on the basis of spectroscopic data. Another coumarin, named murpaniculol (III), was isolated for the first time as a natural product. Twelve other coumarins and two flavones of chemotaxonomical significance were also identified.抄録全体を表示PDF形式でダウンロード (864K) -
三井 直樹, 野呂 忠敬, 黒柳 正典, 宮瀬 敏男, 梅原 薫, 上野 明1989 年 37 巻 2 号 p. 363-366
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThree strong alkaloidal monoamine oxidase (MAO) inhibitors, quinine (1), cinchonicinol ([1S, 3'R, 4'R]-3-(3-ethenyl-4-piperidinyl)-1-(4-quinolinyl)-1-propanol) (2) and cinchonaminone ([3'R, 4'S]-2-[2-(3-ethenyl-4-piperidinyl)-acetyl]-1H-indole-3-ethanol) (3), were isolated from Cinchonae Cortex (Cinchona succirubra PAV., Rubiaceae). The structures of 2 and 3 were elucidated on the bases of spectral data and chemical evidence, and 3 is a new alkaloid.The inhibitory effects on MAO of 1, 2, 3 and related alkaloids were assayed. The type of inhibition by 1 with respect to benzylamine as a substrate was competitive.抄録全体を表示PDF形式でダウンロード (728K) -
丸中 照義, 松島 英司, 南 慶典, 東 龍太郎, 吉田 健一郎, 梅野 幸彦1989 年 37 巻 2 号 p. 367-372
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーCefodizime sodium (CDZM, THR-221) is a new semi-synthetic cephalosporin. The acidic degradation of cefodizime and structural elucidation of the degradation products were investigated. In acidic solution, cefodizime was converted to the anti-form of cefodizime [THR-221-A] and the Δ3-cephem form [THR-221-B]. In another degradation pathway, cefodizime was degraded to desacetyl cefotaxime [THR-221-I] and mercaptothiazole [THR-221-IV]. THR-221-I was further changed to desacetyl cefotaxime lactone [THR-221-IIa] and its anti-form [THR-221-IIb], two isomers of deslactam desacetyl cefotaxime lactone [THR-221-III and -III'], deslactam descarboxy desacetyl cefotaxime lactone [THR-221-IVa] and its anti-form [THR-221-IVb] and methoxyimino-aminothiazolyl aldehyde [THR-221-V].Based on the structural elucidation, the acidic degradation pathways of cefodizime were determined.抄録全体を表示PDF形式でダウンロード (993K) -
高館 明, 八ケ代 一郎, 入倉 充, 藤野 博之, 合屋 周次郎1989 年 37 巻 2 号 p. 373-376
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリー3-(7-Methoxycoumarin-3-carbonyl)- and 3-(7-dimethylaminocoumarin-3-carbonyl)-2-oxazolones (IIa and IIb) were synthesized as fluorescent labeling reagents for high-performance liquid chromatography (HPLC). Treatment of 7-methoxy- and 7-dimethylaminocoumarin-3-carboxylic acids (Ia and Ib) with diphenyl 2-oxo-3-oxazolinylphosphonate in the presence of triethylamine in dichloromethane gave IIa and IIb in 45% and 26% yields, respectively. Compounds IIa and IIb reacted with primary and secondary amines at room temperature in chloroform to give the corresponding fluorescent 7-methoxy- and 7-dimethylamino-3-carboxamides (IIIa-i and IVa-i). A mixture of primary amines was labeled with IIa and chromatographed on a reversed-phase HPLC column (mobile phase : methanol-water) with a fluorescence detector. The detection limit of a test compound, benzylamine, was 19 fmol/100 μl by the use of IIa.抄録全体を表示PDF形式でダウンロード (719K) -
田嶋 敏男, 川上 宇良雄, 原田 みち子, 今井 雅裕, 佐藤 信勝, 中川 照眞, 田中 久1989 年 37 巻 2 号 p. 377-381
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe precipitate, deposited in a 2% alkaline aqueous solution (pH 7.5-8.5) of glutaraldehyde (GA) used for chemosterilization of medical instruments, was characterized by means of thermogravimetry, pyrolysis gas chromatography, chemical ionization mass spectrometry and high-performance liquid chromatography. It was found that the precipitation could be attributed to the polymerization reaction based on aldol condensation involving both GA monomer and trioxane-type GA oligomers. The polymers produced had an average molecular weight higher than those obtained from GA alone. The relation between the turbidity of GA solution and the molecular of the polymer indicated that the precipitates included polymer with a molecular weight exceedings approximately 12000.抄録全体を表示PDF形式でダウンロード (861K) -
田端 滋, 田中 健太郎1989 年 37 巻 2 号 p. 382-387
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe mechanism of Fe transport across the rat duodenal membrane from an Fe(II)-oligosaccharide complex (designated B1-c) produced in wine by yeast and showing high hematopoietic activity in rats was examined. The Fe uptake from B1-c by brush border membrane (BBM) vesicles isolated from the rat intestine was based mainly on the Fe binding to membarne components which were suggested to be inside the vesicles. Evidence that Fe was transported into the vesicles by a special transport system other than simple diffusion was obtained by observing saturation kinetics under conditions of isotope exchange, and temperature and pH dependence. This Fe uptake was not inhibited by any metal ions tested, including inorganic Fe(II), and the BBM vesicles from the duodenum had a higher Fe uptake than those from the other parts of the small intestine. Furthermore, the BBM vesicles isolated from rats with Fe deficiency showed a significantly increased Fe uptake. The Km value for B1-c uptake was 0.16mM, lower than the values for FeSO4 and ferrous ascorbate. These results suggest that a special transport system selective for B1-c may be present on the mucosal membrane. B1-c was taken up by the BBM vesicles in the form of Fe-oligosaccharide complex. From the preloaded vesicles, B1-c was released temperature- and pH-dependently. The fractionation of the intestinal mucosa used in in situ and in vitro absorption experiments suggests that the Fe transport across the BBM by a special transport process is the initial step of the intestinal absorption of Fe from B1-c and that Fe is transferred into a soluble fraction of the mucosal cells in the form of a complex with oligosaccharide.抄録全体を表示PDF形式でダウンロード (965K) -
山口 正義, 森 聖一, 祐田 泰延1989 年 37 巻 2 号 p. 388-390
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on glucose-6-phosphatase in the microsomes of rat liver was investigated. Addition of Ca2+ up to 2.5 μM to the enzyme reaction mixture caused a significant increase of glucose-6-phosphatase activity in hepatic microsomes, while Ni2+, Zn2+, Cd2+, Cu2+, Mn2+ and Co2+ (20 μM) did not have an appreciable effect. Vanadate (V5+) markedly inhibited the enzyme activity; a significant inhibitory effect was seen at 10 μM V5+. The Ca2+-induced increase of glucose-6-phosphatase activity was reversed by the presence of regucalsin; the effect was complete at 1.0 μM of the protein. Regucalcium had no effect on the basal activity of the enzyme. Meanwhile, the inhibitory effect of V5+ (10-100 μM) on glucose-6-phosphatase was not appreciably blocked by the presence of regucalcin (up to 2.0 μM). The present data suggest that hepatic microsomal glucose-6-phosphatase is uniquely regulated by Ca2+ and V5+, of various metals, and that the Ca2+ effect is reversed by regucalcin. The present study supports the view that regucalcin plays an important role as a regulatory protein in liver cell function related to Ca2+.抄録全体を表示PDF形式でダウンロード (560K) -
安孫子 敬, 関野 宏1989 年 37 巻 2 号 p. 391-396
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリー[Glu34]human splenin (hSP) was synthesized in a conventional manner by assembling ten peptide fragments followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole (molar ration, 1 : 1) in trifluoroacetic acid in the presence of m-cresol and dimethylselenide. Finally, the deprotected peptide was incubated with dithiothreitol to reduce sulfoxide on the methionine side chain. Incubation of peripheral lymphocytes isolated from uremic patients with the synthetic [Glu<34>]hSP showed an enhancing effect on the reduced B-lymphocytes, but synthetic human thymopoietin (hTP) had no effect under the same conditions.抄録全体を表示PDF形式でダウンロード (1002K) -
川島 博人, 都丸 淳之, 山本 一夫, 辻 勉, 大沢 利昭1989 年 37 巻 2 号 p. 397-403
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーTwo monoclonal antibodies against human platelet membrane glycoprotein IIIa (GPIIIa) were obatined. One monoclonal antibody, designated as 1B1, was found to inhibit both collagen-induced platelet aggregation and release eractions. This antibody also inhibited the binding of 125I-labeled collagen to human platelets. On the other hand, the other antibody, designated as B10, had no effect on platelet activation induced by a number of physiological stimulants including collagen. Direct binding studies involving 125I-labeled 1B1 or B10 demonstrated that the binding sites for these antibodies on unstimulated platelets have dissociation constants of 4.2 and 14.0 nM, respectively. The binding of 125I-labeled 1B1 or B10 to platelets was not inhibited by the other antibody. Purified 1B1 and B10 were covalently coupled to Affi-Gel and then proteolytic fragments of GPIIIa were applied to the Affi-Gel immunoadsorbent columns. Of the several proteolytic fragments, the 56 kilodaltons (kDa) fragment obtained on digestion with V8 protease bound to both of the columns. The 69 and 55 kDa fragments obtained with BrCN bound to only the 1B1 Affi-Gel column, while the 63 kDa fragment obtained with chymotrypsin only bound to the B10-Affi-Gel column. Based on the partial amino acid sequences of these fragments and the amino acid sequence of GPIIIa (C. A. Fitzgerald, B. Steiner, S. C. Rall, Jr., S. Lo and D. R. Phillips, J. Biol. Chem., 262, 3936(1987)), the epitopes for 1B1 and B10 were concluded to be located at amino acids 335 to 582 and 206 to 335, respectively. These results indicate that a certain epitope of GPIIIa or the GPIIb/IIIa complex on the platelet cell surface constitutes a receptor for collagen, and that the epitope for 1B1 is located near or in the collagen-binding site of GPIIIa. Thus, the collagen binding site is located near the transmembrane portion of GPIIIIa, namely, amino acid residues 335 to 582. Furthermore, the 1B1 antibody was found to induce the aggregation of washed platelets, suggesting that GPIIIa is directly involved in the activation of platelets.抄録全体を表示PDF形式でダウンロード (1313K) -
荒木 富士子, 中村 弘子, 野島 直人, 九十九 賢一, 坂本 俊治1989 年 37 巻 2 号 p. 404-406
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe stability of recombinant human epidermal growth factor (hEGF) in various solutions was examined. hEGF degraded spontaneously and temperature-dependently to several degradation products in phosphate buffered saline or in 0.1 N acetic acid. The enzymatic degradation was observed in human serum or in pepsin/HCl solution. The structure and biological activities of these compounds were examined. The results suggest that the Asp11 and Trp50 residues are important for the receptor binding.抄録全体を表示PDF形式でダウンロード (511K) -
森田 全, 岩本 義久, 清水 忠順, 増澤 俊幸, 柳原 保武1989 年 37 巻 2 号 p. 407-409
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe mutagenicity (Trp+ reversion) of procarcinogens such as N-nitrosodimethylamine, 3, 4-benzpyrene and 2-acetylaminofluorene has been detected with the permeable mutant of yeast, Saccharomyces cerevisiae C658-K42. The original strain C658, however, showed a positive response only to N-nitrosodimethylamine with S9 mix. The permeable mutant C658-K42 was employed for mutagenicity tests on 12 carcinogens which had been reported to be non-mutagenic in Salmonella/microsome tests. It was found that phenobarbital, thiourea, 1, 2-dimethylhydrazine and 4-aminoantipyrine were mutagenic in the presence of S9 mix, Benzene, o-toluidine and thioacetamide were weakly mutagenic. Negative results were obtained for diethylstilbestrol, safrole, acetamide, urethane and ethionine at the concentrations used. Caprolactam did not show any mutagenic effect on C658-K42 at concentrations up to 20 mg/ml. Sodium azide, which is unlikely to be carcinogenic but is strongly mutagenic in the Ames test, showed a very weak mutagenic effect on C658-K42.抄録全体を表示PDF形式でダウンロード (570K) -
鈴木 巖, 橋本 幸一, 及川 昭蔵, 佐藤 吉朗, 大沢 真澄, 宿前 利郎1989 年 37 巻 2 号 p. 410-413
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe effects of the β-1, 3-glucan, LELFD, obtained from liquid-cultured mycelium of Grifola frondosa, on the growth of syngenetic tumors and immune responses in mice were examined. In Meth A or IMC solid tumor systems, LELFD administered intraperitoneally (i.p.) or intralesionally (i.l.) exhibited significant antitumor effects. However, the growth of L1210 and P388 leukemias was unaffected by the injection of LELFD.The injection of LELFD i.p. enhanced the activities of natural killer cells and macrophages in mice. LELFD also enhanced the antibody response when it was injected i.p. with sheep red blood cells into mice. Furthermore, it was found that LELFD could activate the alternative complement pathway.抄録全体を表示PDF形式でダウンロード (613K) -
増澤 俊幸, 関口 智彦, 清水 忠順, 岩本 義久, 森田 全, 三渕 一二, 柳原 保武1989 年 37 巻 2 号 p. 414-417
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーNine cell lines producing monoclonal antibodies (MAbs) against Leptospira interrogans serovar canicola strain Moulton were established by the cell fusion technique. The immonological reactivity of these MAbs with various kinds of serogroups, serovars and strains were examined by microscopic agglutination test (MAT) and enzyme-linked immunosorbent assay (ELISA). MAbs W1-W3 derived from mice, which were immunized with whole cells of the strain Moulton, reacted with the serogroups Canicola, Icterohaemorrhagiae and Pyrogenes. On the other hand, MAbs A1-A6 derived from mice immunized with the outer envelope (OE) fraction, which showed a potent protective activity and was extracted with ammonium hydroxide from the strain Moulton, reacted specifically with the serogroup Canicola alone in MAT. A difference in antigenic structure between subserogroup A (canicola subgroup) and subserogroups B (schiieffneri subgroup) of the serogroup Canicola was demonstrated by MAT using the MAbs. All the MAbs clearly agglutinated serovars of subserogroup A except for serovars kamituga, jonsis and bindjei, but did not react with any serovars of subserogroup B. These findings suggest that MAb highly specific to each serovar is readily available by OE immunization and is useful for the classification of Leptospira.抄録全体を表示PDF形式でダウンロード (688K) -
井川 猛, 米谷 芳枝, 町田 良治, 永井 恒司1989 年 37 巻 2 号 p. 418-421
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe utility of the absorption promoters, sodium glycocholate (GC-Na), ethylenediamine dihydrochloride (EDTA-2Na), sodium caprylate (Cap-Na) and sodium salicylate (Sal-Na), in the intranasal administration of human fibroblast interferon-β (HuIFN-β) in rabbits was investigated. The optimal amount of added EDTA-2Na, Cap-Na and Sal-Na with respect to HuIFN-β was examined for nasal absorption in the powder dosage form. Formulations of HuIFN-β with GC-Na showed greatly enhanced intranasal HuIFN-β absorption, as compared to the other absorption promoters. The results of a stability study on HuIFN-β in homogenates of nasal mucosa suggested that GC-Na behaved as a hydrolysis inhibitor in the nasal mucosa and maintained the activity of HuIFN-β.抄録全体を表示PDF形式でダウンロード (605K) -
阿曽 幸男, 林 譲, 吉岡 澄江, 武田 寧, 喜多 康浩, 西村 善文, 荒田 洋治1989 年 37 巻 2 号 p. 422-424
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーEpimerization and hydrolysis of etoposide and its analogues involving aglycons were examined in alkaline aqueous solution. The trans-lactone compounds such as etoposide were epimerized to the cis-lactone compounds such as picroetoposide, but not hydrolyzed to trans-hydroxy acid derivatives. The cis-lactone compounds were susceptible to the hydrolysis of the lactone ring. The epimerization was accelerated by the presence of the sugar substituent at position 4 and of the methoxy group at position 4'. The epimerization was also affected by the configuration of the hydroxyl group at position 4. The hydrolysis rate of the cis-lactone was decreased by the sugar substituent at position 4, and increased by the methoxy group at position 4'. The configuration of the hydroxyl group at position 4 had no effect. The nuclear magnetic resonance data suggest that the structure of etoposide is more strained and less than that of the aglycon. The acceleration of the epimerization by the sugar substituent may be ascribed to the decrease in the stability of the trans-lactone by glycosidation. The decrease of hydrolysis rate owing to glycosidation may be explained in terms of the steric handrance of the bulky sugar substituent.抄録全体を表示PDF形式でダウンロード (586K) -
川島 嘉明, 丹羽 敏幸, 半田 哲郎, 竹内 洋文, 岩本 太郎, 伊藤 洋治1989 年 37 巻 2 号 p. 425-429
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーProlonged-release spherical micro-matrices of ibuprofen with acrylic polymer (Eudragit[○!R] RS) were prepared using a novel emulsion-solvent diffusion metho. It was found by examining cross sections of the spherical matrix before and after dissolution tests with a scanning electron microscope and a porosimeter that the resultant micro-matrix had a sponge-like internal structure. The spherical matrices were successfully recovered with a relatively high concentration of the drug in ethanol (0.4-0.6g/ml) and over a wide range of temperatures (5-35°C). The size of the spherical matrix could be easily controlled by varying the agitation speed of the system and the concentration of emulsifier added to the aqueous medium. The drug release rate from the spherical matrix decreased with increasing concentration of polymer formulated due to the reduced diffusion path and increased tortuosity in the matrix. Spherical matrices with ibuprofen : Eudragit[○!R] RS=3 : 1 improved the bioavailability of the drug and prolonged the drug action in beagle dogs.抄録全体を表示PDF形式でダウンロード (947K) -
小木曽 太郎, 伊藤 吉将, 岩城 正宏, 中西 克子, 斉藤 寛子1989 年 37 巻 2 号 p. 430-434
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe phospholipid organization, lipid fiuidity and spectrin degradation were measured in human erythrocytes oxidized with phenylhydrazine, and the contribution of these structural alterations to the penetration of perazine and promethazine into the membrane was estimated. It was found that exposure of erythrocytes to phenylhydrazine (0.2-0.4mg/ml) produced a 35-40% decrease in the amount of spectrin, with resultant gross morphological changes to the echinocyte conformation. The phosphatidylethanolamine content in the treated erythrocytes was greatly lowered compared with that in the untreated cells. Treatment with phenylhydrazine (0.05-0.2mg/ml) dramatically diminished the lipid fluidity of the membrane, as estimated by electron spin resonance (ESR) spectrometry, and the ESR study revealed increased restriction of the molecular motion of the hydrophobic core in the treated membrane. These results suggest a drastic alteration of the erythrocyte membrane structure. The amount of drugs which penetrated into the treated erythrocytes increased markedly with increasing phenylhydrazine concentration, suggesting enhanced membrane permeability and facilitated localization of the drugs in the hydrphobic regions due to the structural changes and partial disturbance of the lipid organization.抄録全体を表示PDF形式でダウンロード (1131K) -
仲井 由宣, 山本 恵司, 泉川 智1989 年 37 巻 2 号 p. 435-438
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe physicochemical properties of drug molecules in a mixture with controlled-pore glass (CPG) were studied by using differential scanning calorimetry (DSC) and powder X-ray diffraction. The DSC data indicated the presence of three states of benzoic acid in the CPG mixtures below 500 A^^° CPG pore diamter. The proportions of the three states of benzoic acid in the CPG mixture varied with the content of benzoic acid and also with the pore diamter of CPG. The amount of crystalline fraction in the mixture increased with increasing pore diameter of CPG. When benzoic acid was mixed with different pore diameters of CPG (CPG120 and CPG1000), it was found that benzoic aicd molecules preferentially interacted with CPG of small pore diameter.抄録全体を表示PDF形式でダウンロード (603K) -
木村 聰城郎, 福井 栄司, 勘解由 昭, 黒原 春美, 黒崎 勇二, 中山 太二, 森田 豊, 渋沢 孝一, 大沢 重光, 武田 [ヨシ] ...1989 年 37 巻 2 号 p. 439-441
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーIn order to evalutate oral dosage forms of d-α-tocopherol acetate (VEA), d-α-tocopherol (VE) concentration in the plasma was examined following oral administration of three VEA preparations; lecithin-dispersed aqueous preparation, polysorbate 80 (PS-80)-solubiized aqueous solution and soybean oil solution. The lecithin-dispersed preparation gave the highest Cmax and the largest AUC0-24h, while Tmax was delayed. In the thoracic duct fistula rat, no increase in VE plasma concentration was observed after intraduodenal administration of lecithin-dispersed VEA preparation, while VE appeared in the thoracic lymph, indicating that VE is absorbed from the lecithin-dispersed preparation via the lymphatic route. The delayed Tmax and prolonged VE plasma concentration obtained with the lecitin-dispersed preparation in comparison with PS-80-solubilized aqueous solution could be explained by the different route of absorption.抄録全体を表示PDF形式でダウンロード (589K) -
小木曽 太郎, 伊藤 吉将, 岩城 正宏, 山本 裕子1989 年 37 巻 2 号 p. 442-445
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe percutaneous (p.c.) absorption of clonazepam (CZP), an antiepileptic drug, was investigated in rabbits. CZP was efficiently absorbed from a gel ointment (0.5% CZP, 1g, 9cm2) with Azone[○!R] and therapeutic plasma concentrations were maintained for 27h. The bioavailability of CZP from the gel ointment was 47.2±3.1%, which was significantly larger than that (3.3±0.5%) after the ointment without Azone[○!R] or that (12.5±3.6%) after oral administration. About a half of CZP in the ointment with Azone[○!R] was absorbed during a 24 h application. The maximum and minimum plasma concentrations and the area under the plasma concentration-time curve gradually increased during repeated application of the ointment (2% CZP, 0.25 g/d, 2.25cm2), probably due to the accumulation of drug in the skin and body. The efficient absorption and sustained plasma concentration of CZP after application suggest that a once a day p.c. administration regimen is possible by using the ointment with Azone[○!R].抄録全体を表示PDF形式でダウンロード (662K) -
小木曽 太郎, 伊藤 吉将, 岩城 正宏, 山本 裕子1989 年 37 巻 2 号 p. 446-449
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーA trial transdermal dosage form designed to sustain a suitable plasma concentration of clonazepam (CZP) was produced using a porous membrane (Hipore 2100 or 4050) and applied to rabbits and rats for pharmacokinetic and pharmacodynamic evaluations. The release rate constants of the drug through the porous membranes were significantly smaller than that without any membrane. The transdermal system (Hipore 4050 system, ointment 0.25g, 2.25cm2) provided a well sustained plasma concentration of CZP and the therapeutic plasma concentration range was maintained for about 26 h. When the Hipore 4050 system with an increased amount of ointment and enlarged absorption area (0.5 g, 4.0 cm2) was applied, the therapeutic range was sustained for about 40 h, and slightly higher plasma levels over the whole application period and much higher bioavailability (37%) were obtained compared with those after the 2.25 cm2-Hipore 4050 system. The transdermal system exerted an excellent anticonvulsant activity in rats, with the best (3+ or 4+) protective score. The plsasma concentrations of CZP when the activity was estimated were in the therapeutic range. Thus, the transdermal system has the potential to be an efficient drug delivery system.抄録全体を表示PDF形式でダウンロード (643K) -
吉田 久博, 奥村 勝彦, 神谷 晃, 堀 了平1989 年 37 巻 2 号 p. 450-453
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe mechanism of the accumulation of basic drugs was investigated by isolated rat lung perfusion. Treatment with various metabolic inhibitors or non-basic drugs did not affect the accumulation of a basic drug in the lung, but a second basic drug inhibited the accumulation of the first basic drug depending on its lipid solubility. The basic durg already accumulated was rapidly displaced by the second drug except for poorly lipid-soluble basic drugs and non-basic drugs. The ability of a second basic durg ot displace the first basic durg was well correlated with its ability to inhibit accumulation. From the Scatchard plot, at least two independent sets of binding sites for basic drugs were found to be present in the isolated perfused lung. The maximum binding capacity for each basic drug was similar in both sites. These results indicate that specific common binding sites for basic drugs, which do not contribute to the active transport system, exist in the lung tissues and the affinity to the sites depends on the lipid solubility of the basic drugs.抄録全体を表示PDF形式でダウンロード (660K) -
木村 聰城郎, 永原 直樹, 平林 克子, 黒崎 勇二, 中山 太二1989 年 37 巻 2 号 p. 454-457
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe usefulness of lipid disperse systems, containing soybean phosphatidylcholine (PC) and glycosylceramide (GC) as lipid components, to enhance the percutaneous penetration of flufenamic acid (FA) through rat abdominal skin was examined by both in vitro permeation and in vivo absorption studies. The penetration of FA from a simple buffer suspension (pH 3.0) containing no lipid component was poor, but was markedly enhanced when FA was incorporated in PC-dispersion. However, this enhancing effect disappeared when the PC concentration in the preparation exceeded 40 μmol/ml. Enhanced penetration of FA from PC-dispersions could also be recognized when 30% propylene glycol or 30% glycerol was used as the dispersing medium instead of the aqueous buffer solution. Addition of GC to the PC-dispersions brought further enhancement of FA penetration through the skin. The maximal effect was observed when FA was incorporated in a 10%-GC system, and the cumulative amount of FA penetrating through the skin in 24 h from this system was approximately 6-fold larger than that from the simple buffer suspension. Enhanced absorption of FA from lipid disperse systems was also confirmed by in vivo application of these preparations.抄録全体を表示PDF形式でダウンロード (641K) -
杉森 健一, 森 章一, 川島 嘉明1989 年 37 巻 2 号 p. 458-462
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーCapping within a tablet was quantitatively estimated by using the capping ratio, defined as the ratio of the tablet strength to that of the uniformly compacted tablet.Capping index was also newly defined as the ratio of the extrapolated residual die wall pressure to the binding strength of compacted powder. It was found that capping occurred when the capping index exceeded unity. This fact indicated that capping can be regarded as cracking within a tablet caused by high residual die wall presure. The requirements to achieve uniform compaction were clarified from these results.It was found that the extrapolated residual die wall pressures of convex-faced tablets were related to those of flat-faced ones. It was also found that tablets consisting of more elastic powders had a lower ersidual die wall presure.抄録全体を表示PDF形式でダウンロード (753K) -
木村 聰城郎, 武田 和久, 勘解由 昭, 戸田 正文, 黒崎 勇二, 中山 太二1989 年 37 巻 2 号 p. 463-466
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe intestinal absorption of dilichol from various dosage forms was investigated using the intestinal loop and everted sac methods in the rat. The in situ loop experiments showed that the absorption of dolichol from a triglyceride emulsion was dependent on the chain-length of the triglyceride; the absorption from a tri-n-butyring emulsion in 1 h was 18.0% of the dose; and the absorption from an HCO-60 suspension was 4.3%. The liposomal preparation enhanced the absorption up to 39.1% of the dose. In in vitro experiments, 25.0% and 13.2% of dolichol were taken up by everted sacs of the jejunum and the ileum, respectively. On the other hand, phospholipids composing liposomes were not absorbed under these conditions. The above results suggest that the absorption mechanism from liposomal preparations may be as follows : dolichol is released from the liposmes into the aqueous phase adjacement to the surface of the intestine and is subsequently partitioned into the intestinal tissue.抄録全体を表示PDF形式でダウンロード (634K) -
砂田 久一, 篠原 格, 大塚 昭信, 米澤 頼信1989 年 37 巻 2 号 p. 467-470
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe dissolution of n-propyl p-hydroxybenzoate was followed under the sink condition. Experiments were conducted to evaluate the changes of surface area during the dissolution process of sieved crystalline particles. Whole particles were collected at a given time during the dissolution measurements, and the surface areas of the collected particles were estimated by using a LUZEX image analyzer. Hence, changes of surface area and surface area produced during the dissolution were estimated by graphical integration. Then the relationship between the surface producing rate constant and the initial particle size was estimated.Dissolution proceses of mixed samples were simulate on the basis of the changes of surface area and the surface producing rate constant obtained for the component samples. Dissolution measurements of ternary systems mixed to have various values of initial surface area were conducted to estimate the effect of components on the simulation of the dissolution processes, and the validity of the treatment was examined.抄録全体を表示PDF形式でダウンロード (600K) -
高田 寛治, 大橋 衛, 古家 喜弘, 吉川 広志, 村西 昌三1989 年 37 巻 2 号 p. 471-474
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーSolid dispersions composed of three components, ciclosporin A (CiA), surfactant (HCO-60) and a pharmaceutical additive, were prepared. As an additive, cellulose acetate phthalate (CAP), methacrylic acid and methacrylic acid methylester copolymer (Eudragit L-100[○!R]) and hydroxypropylmethylcellulose phthalate (HP-55[○!R]), which are generally used as enteric coating materials, were employed. The dissolution behavior of CiA from these enteric solid-dispersion system was studied according to the paddle method of JP XI in comparison with that of Sandimmun[○!R], an olive oily CiA solution as a reference. Solid dispersion of CiA preparation did not dissolve in the 1st test fluid (pH 1.2) in 2 h. In the 2nd fluid (pH 6.8), about 80% of CiA was dissolved within 12 min, though the dissolution rate was dependent on both the quality and quantity of the additives. An in vivo systemic and lymphatic availability study was performed with rats whose carotid artery and thoracic lymph duct were cannulated. After intrastomach administration of each CiA preparation to rats at a dose of 7 mg/kg, blood and lymph samples were collected for 6 h. One of the HP-55 preparations gave the highest plasma CiA level, Cmax=0.99±0.20 (S.E., n=4) μg/ml, and also showed the highest lymphatic availability, the percentage of dose delivered to the lymphatics in 6 h was 1.98±0.10% and the maximum lymph CiA level was 76.8±12.86 μg/ml. Lymphatic availability of CiA from Sandimmun was 0.78±0.11% and the peak plasma CiA level was 0.46±0.10 μg/ml. These results support the usefulness of the new enteric solid dispersion system for oral delivery of CiA.抄録全体を表示PDF形式でダウンロード (666K) -
宮内 正二, 杉山 雄一, 伊賀 立二, 花野 学1989 年 37 巻 2 号 p. 475-480
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーWe examined the disposition of 4-methylumbelliferone (4-MU) and its conjugative metabolites, glucuronide (4-MUG) and sulfate (4-MUS), using a single-pass rat liver perfusion system. When 4-MU was delivered, the steady-state hepatic extraction ratio for 4-MU was very high (approximately 1.0) and its conjugative metabolites, 4-MUG and 4-MUS, appeared to a large extent in the effluent perfusate, The biliary excretion rate of the 4-MUG conjugated from 4-MU was 44% of the infusion rate at the steady-state, whereas those of 4-MU and 4-MUS were less than 1% of the infusion rate. When 4-MUG was delivered, the steady-state hepatic extraction ratio for 4-MUG was very low (<0.05) and the removal rae of 4-MUG from the perfusate was almost identical to the excretion rate of 4-MUG into the bile, while 4-MU and 4-MUS were slightly excreted into the bile (1% of the total biliary excretion rate), suggesting that a little deconjugation of 4-MUG to 4-MU occurred in the liver. Similarly, 4-MU and 4-MUS were not detectable in the effluent perfusate. The apparent extraction ratio (Eapp) for the intracellularly conjugated 4-MUG was approximately twenty times higher than that for the pre-conjugated 4-MUG. This discrepancy between the values of Eapp for the intracellularly conjugated and pre-conjugated 4-MUG might be attributed mainly to the diffusional barrier for the metaboliet between the blood and hepatocytes, as suggested in the previous simulation (J. Pharmacokin. Biopharm., 15, 399 (1987)). On the other hand, when 4-MUS was delivered, 4-MUG appeared in the effluent perfusate, The biliary excretion rate of 4-MUG was approximately two times higher than that of 4-MUS (30% of the total biliary excretion rate), whereas the biliary excretion rate of 4-MU was negligible, suggesting that the deconjugation of 4-MUS to 4-MU occurred to a large extent in the liver. We also confirmed that the deconjugation of 4-MUG and 4-MUS occurred in the liver, using rat liver homogenate and its 9000×g fraction (pH7.4). On the assumption that the deconjugation was an apparent first-order process, the intrinsic clearance for the sulfatase was approximately eight times higher than that for glucuronidase, being consistent with the results of a single-pass perfusion.抄録全体を表示PDF形式でダウンロード (1029K) -
氷見 敏行, 齋藤 洋, 西山 信好1989 年 37 巻 2 号 p. 481-484
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe effects of nerve growth factor (NGF) and saponins isolated from Panax ginseng C. A. MAYER on the survival of chick and rat embryonic cerebral cortex neurons were examined. Ginsenoside Rg1 (GRg1) exerted a survival-promoting effect on both chick and rat cerebral cortex neurons in cell cultures. Ginsenoside Rb1 (GRb1) also had an effect in the rat and displayed some influence in the chick. NGF alone exerted no effect on both neurons, although it did potentiate the GRb1 effect on chick embryonic cerebral cortex neurons, but did not alter the GRb1 effect on rat embryonic cerebral cortex neurons. NGF did not alter the survival-promoting effect of GRg1 on either chick or rat embryonic cerebral cortex neurons. The other saponins alone or with NGF exertecd no effect on the survival of cerebral cortex neurons in either the chick or rat.抄録全体を表示PDF形式でダウンロード (614K) -
山原 條二, 小林 悟朗, 松田 久司, 岩本 真承, 藤村 一1989 年 37 巻 2 号 p. 485-489
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーFurther experiments were conducted to examine the effect of scoparone (6, 7-dimethoxycoumarin), a coumarin derivative found in the Chinese crude drug "Capillaris Flos", on calcium mobilization, Scoparone does not affect Ca2+ influx through the voltage-dependent channel due to membrane depolarization. Its inhibitory action may be dependent not only on the inhibition of Ca2+ release from sarcoplasmic reticulum but also on the inhibition of extracellular Ca2+ influx through the receptor-operated channel.抄録全体を表示PDF形式でダウンロード (697K) -
松田 玲子, 久保 道徳1989 年 37 巻 2 号 p. 490-492
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーThe effects of extracts of muscles of mackerel (Scomber japonicus; M-ext) on hepatic glycogenolysis were investigated by a rat liver perfusion method. M-ext inhibited glucagon- and cyclic adenosine monophosphate (AMP)-induced glycogenolysis but was ineffective on phenylephrine-induced glycogenolysis.The contents of hepatic glycogen and cyclic AMP, and phosphorylase and glycogen synthase activities in liver were measured after perfusion with glucagon. M-ext inhibited the increase of cyclic AMP and activation of phosphorylase.It is considered that M-ext inhibits hepatic glycogenolysis caused by glucagon through a cyclic AMP-dependent mechanism.抄録全体を表示PDF形式でダウンロード (567K) -
鈴木 悦子, 下村 喜久子, 関口 慶二1989 年 37 巻 2 号 p. 493-497
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーAnhydrous theophylline exhibited polymorphism and two modifications, which were named form I and form II, were isolated. The melting point and the enthalpy of fusion of each polymorph determined by differential scanning calorimetry (DSC) were 273.4±1.0°C and 26.4±0.3 kJ/mol for form I and 269.1±0.4°C and 28.2±1.1 kJ/mol for form II. The higher melting form I had a smaller density. In contrast to caffeine, theophylline formed a monohydrate. The dissociation vapor pressure curves of theophylline hydrate and caffeine hydrate were obtained and the difference in their stabilities was discussed. The enthalpy of dehydration was determined by DSC under closed conditions. The dehydration under isothermal conditions appeared to proceed acoording to the mechanism of random uncleation followed by two-dimensional growth of nuclei as represented by the Avrami-Erofe'ev equation. The solubilities of theophylline and its hydrate were determined as a function of temperature. From the van't Hoff type plot, the transition temperature between the hydrate and the anhydrous form was determined.抄録全体を表示PDF形式でダウンロード (1018K) -
小田切 優樹, 中村 英樹, 丸山 徹, 今村 順茂, 高館 明1989 年 37 巻 2 号 p. 498-501
発行日: 1989/02/25
公開日: 2008/03/31
ジャーナル フリーIn order to gain an understanding of protein binding of sulfadimethoxine (SDM) and its major metabolite, N4-acetylsulfadimethoxine (N4-AcSDM), the binding of SDM and N4-AcSDM to human and rabbit serum albumin (HSA and RSA) was investigated using circular dichroism (CD), fluorescence and dialysis techniques. The CD spectral characteristics of the compounds bound to the albumins suggested that the drug-binding sites on the HSA and RSA had somewhat different asymmetries. The binding constants for SDM-HSA and -RSA interaction were smaller than those for N4-AcSDM. Two specific drug-binding sites were found on RSA, similarly to HSA, from the results of competitive displacement using fluorescence probes. Moreover, SDM AND N4-AcSDM were found to share the same first binding site on the albumins. It can be presumed from the displacement data with a series of p-aminobenzoates that the characteristics of the binding sites (such as depth and width of the hydrophobic cleft) for SDM and N4-AcSDM on RSA may be almost the same, but the characteristics of these drug-binding sites on HSA may be somewhat different.抄録全体を表示PDF形式でダウンロード (597K)