Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
18 巻 , 3 号
選択された号の論文の23件中1~23を表示しています
  • 堂ケ崎 知格, 村上 一, 西島 基弘, 大野 尚仁, 宿前 利郎, 宮崎 利夫
    1995 年 18 巻 3 号 p. 377-381
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    A polysaccharide fraction extracted with cold 0.5M NaOH from the kernels of Prunus mume exhlbited some biological activities. A polysaccharide, P-1, was purified from the 0.5M NaOH extract by ion-exchange chromatography and gel-flltration. The results of the structural analysis of P-1 to determine the relationship between the activities and the structure are described in this paper. In the mild acid hydrolysis of P-1, the nondialyzable hydrolysate (I-3) believed to be its core portion was obtained. The yield of I-3 was 26.0% and contained 59.8% uronic acid as galacturonic acid (GalA). The neutral sugars of I-3 were composed of rhamnose, xylose and galactose in a molar ratio of 1.0 : 3.4 : 0.3 following analysis by gas-liquid chromatography. The molecular weight of I-3 was estimated to be ca. 14000 by gel-filtration on Toyopearl HW55F. I-3 exhibited the mitogenic activity toward spleen cells as well as P-1. These facts appeared to confirm that I-3 was the core part of P-1 and important for its biological activity. I-3 was successfully reduced by the Taylor and Conrad method to avoid so much repetition. Methylation analysis of the reduced hydrolysate by gas-liquid chromatography and gas chromatography-mass spectroscopy showed that the ratio of 1, 4-linked galactopyranosyl and 1, 3, 4-linked galactopyranosyl residues were significantly increased in comparison with native I-3. These results suggested that I-3 was composed of 1, 4- and 1, 3, 4-linked galacturonic acid residues in the main chain.
  • 小林 典裕, 島田 和武, 滝 宏明, 坂本 裕一郎, 蒲池 信一
    1995 年 18 巻 3 号 p. 382-387
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    22-Oxacalcitriol is a synthetic analog of 1α, 25-dihydroxyvitamin D3, which is expected to be a novel agent for the treatment of patients with secondary hyperparathyroidism, psoriasis, and/or breast cancer. A sensitive and practical RIA for 22-oxacalcitriol in rat and human plasma has been developed. A rabbit antiserum raised against 22-oxacalcitriol 3-hemiglutarate conjugated with bovine serum albumin was used in combination with a tritium-labeled 22-oxacalcitriol having high specific radioactivity. A plasma sample was extracted with ethyl ether and the extract was successively purified with Bond Elut[○!■] C18 and a normal-phase HPLC prior to the RIA to remove interfering substances. Accuracy of the RIA was assessed by various studies including serial dilution and recovery tests. Intra- and inter-assay coefficients of variation were lower than 10%, and the quantification limit was low enough for practical use (33 pg/ml plasma). The present RIA will be useful for the pharmacokinetic studies of 22-oxacalcitriol in both preclinical and clinical stages.
  • 木邑 道夫, 鍋倉 智裕, 桂 敏也, 高野 幹久, 堀 了平
    1995 年 18 巻 3 号 p. 388-395
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    As an approach to identification of the organic cation transport system in brush-border membranes, we designed a photoaffinity probe, 1-cyano-2-(4-azido [3, 5-3H] benzoylethyl)-3-[2-[[(5-methyl-4-imidazolyl) methyl] thio] ethyl]-guanidine ([3H] AMC) based on the molecular structure of cimetidine, which is taken up by the organic cation transport system in brush-border membrane vesicles. The effect of nonradioactive 1-cyano-2-(4-azidobenzoylethyl)-3-[2-[[(5-methyl-4-imidazolyl) methyl] thio] ethyl] guanidine (AMC) on tetraethylammonium uptake was investigated in rat renal brush-border membrane vesicles. We examined the photolysis of AMC in which the azido group was converted to an active nitrene group using UV light at a wavelength of 254 nm and established a half-life of 7 s. This half-life duration did not significantly impair brush-border membrane vesicles during the exposure to light for photo-labeling. Photoaffinity labeling of brush-border membrane vesicles from the rat renal cortex with [3H] AMC resulted in the covalent incorporation of radioactivity into membrane polypeptides ; an apparent 36 kDa polypeptide was predominantly labeled. Photolabeling specificity was shown by a reduction in the labeling of the 36 kDa polypeptide in the presence of organic cations, cimetidine, tetraethylammonium and N-methylnicotinamide whereas the organic anion, furosemide, had no effect on labeling patterns. These data demonstrate that AMC, as well as organic cations, cimetidine, tetraethylammonium and N-methylnicotinamide, interact with a common 36 kDa membrane polypeptide, which may be the transport system or one of its brush-border membrane components.
  • 藤本 貞毅, 河上 奈保子, 小原 晃
    1995 年 18 巻 3 号 p. 396-400
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    The total iron-binding capacity (TIBC) and iron contents of diabetic rat serum, as well as the iron-binding capacity of glycated transferrin and oxygen radical production by the glycated proteins were examined. The TIBC and iron content of diabetic rat sera were found to be much lower than those of control rat sera. Incubation of human serum with glucose in vitro resulted in a significant fall of its unsaturated iron-binding capacity (UIBC) with time. When apotransferrin was incubated with glucose, its UIBC significantly decreased. The iron content of holotransferrin was markedly reduced by incubation with bathophenanthroline sulphonic acid (BPSA) in the presence of glucose, although the content was not altered by incubation with BPSA alone. The generation of superoxide radical (O2-) and hydroxyl radical (OH·) by the glycated holotransferrin was much greater than that by glycated apotransferrin. Glycated holotransferrin showed significantly accelerated hydroxyl radical production by the hypoxanthine-xanthine oxidase system, while intact holotransferrin did not. Treatment of holotransferrin with glucose caused the fragmentation of the protein, while the same treatment of apotransferrin did not. These results suggest that iron ions in the glycated transferrin molecule are bound loosely to the protein and are redox-active and the glycated holotransferrin produces oxygen radicals including O2- and OH· efficiently, and that the glycated transferrin does not function as an iron-binding protein.
  • 松村 靖夫, 塚原 八重子, 児島 たか代, 村田 聡, 村上 暁子, 高田 貴美, 高岡 昌徳, 森本 史郎
    1995 年 18 巻 3 号 p. 401-406
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    Using cultured human aortic endothelial cells, we examined the effects of phosphoramidon, an endothelin converting enzyme (ECE) inhibitor, on the release of endogenous endothelin-1 (ET-1) and big endothelin-1 (big ET-1), and on the generation of ET-1 from exogenously applied big ET-1. Phosphoramidon, at concentrations of 10-6 to 2×10-4M, caused a biphasic alteration of the ET-1 release, i.e., at lower concentrations of the drug, there were slight but unexpected increases of the release, whereas higher concentrations led to a decrease which is due to the drug-induced inhibition of ECE. The former effect appears to be based on the inhibition of ET-1 degradation by neutral endopeptidase 24.11 (NEP), since kelatorphan, a specific NEP inhibitor, produced a similar increasing effect on ET-1 release. Phosphoramidon enhanced the big ET-1 release from the cells in a concentration-dependent manner. When high concentrations of phosphoramidon were added, there was a dramatic increase in the release of big ET-1, which cannot be explained only by the drug-induced inhibition of ECE. This increase in big ET-1 release appeared to be partly due to a transient stimulation of the expression of prepro ET-1 mRNA. The amount of ET-1 generated from exogenously applied big ET-1 was markedly decreased by phosphoramidon in a concentrationdependent manner. In a similar fashion, phosphoramidon markedly inhibited ECE activity of the membrane fraction of cultured cells. Thus, ET-1 generation from exogenously applied big ET-1 reflects the functional phosphoramidon-sensitive ECE activities in human aortic endothelial cells. In contrast, the effect of phosphoramidon on the release of endogenous ET-1 appears to be modified by the drug-induced augmentation of big ET-1 production, as well as by an inhibition of ET-1 degradation.
  • 木村 正康, / 柳 誠治, 今野 泰生, 野島 浩史, 木村 郁子, Ikuko KIMURA
    1995 年 18 巻 3 号 p. 407-410
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    β-Eudesmol, a sesquiterpenoid alcohol contained in Atractylodes lancea, potentiates succinylcholine (SuCh)-induced neuromuscular blockade. The potentiating effect is greater in diabetic muscles than in normal ones. As a ligand for affinity chromatography to study the potentiating mechanism, we designed and synthesized newly β-eudesmol-related cyclohexylidene derivatives (2-(3-hydroxy-3-methylbutyl) cyclohexylidene ; KTE-13, 2-(3-hydroxy-3-methylbutyl)-4-cyclohexylidene carboxylic acid ; KTE-32 and 4-tert-butoxycarbonyl-2-(3-hydroxy-3-methylbutyl) cyclohexylidene ; KTE-33). We examined the potentiating effects of those compounds in phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. KTE-33 (100μM) potentiated more greatly SuCh-induced neuromuscular blockade in diabetic muscles than in normal ones (the potentiating ratios in normal and diabetic muscles were 6.7 and 10.6, respectively), while KTE-13 (100 μM) and -32 (200 μM) potentiated weakly. These results suggest that the ester group in KTE-33 rather than a carboxyl group in KTE-32 is important in inducing the potentiation of SuCh-induced neuromuscular blockade in diabetic state.
  • 屋山 勝俊, 松井 貴史, 鷹野 正興, 林 一巳, 永松 正, 鈴木 良雄, 岡本 博
    1995 年 18 巻 3 号 p. 411-415
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    Activity of the reain-angiotensin system in the nephrotic syndrome was investigated in rats with acute nephritis induced by anti-glomerular basement membrane (GBM) antibody. Injection of anti-GBM antibody resulted in a transient 2-fold elevation of both plasma reain and angiotensinogen with a peak at 12 h. Angiotensinogen mRNA levels in the liver also rapidly and transiently increased 4-fold at 3 h. The manifestation of acute nephritis, indicated by proteinuria, hypoalbuminemia, hypercholesterolemia and an increase in serum creatinine, following injection of anti-GBM antibody, was inhibited by a single administration of the selective angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg, p.o.) 2 h before an injection with the antibody, but not by successive administration of this drug for 1 week from 3 d after the injection of antibody. These results suggested that the enhanced generation of angiotensin II by elevated levels of both renin and its substrate in the early phase of anti-GBM nephritis promotes the evolution of acute nephritis via angiotensin II type 1 receptor.
  • 木村 康浩, 木平 健治, 三宅 勝志, 北浦 照明, 福地 坦
    1995 年 18 巻 3 号 p. 416-420
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    The relative changes in the amount of specific [125I] cholecystokinin octapeptide (CCK8) bound to regional brain membrane preparations after 6-hydroxydopamine (6-OHDA) treatment were examined. The specific binding in the frontal cortex and striatum decreased and reached a minimum on the 3rd day after 6-OHDA treatment. Thereafter, the specific binding recovered to 60% and 65% of control values in the frontal cortex and striatum respectively on the 28th day. On the other hand, in the nucleus accumbens, where CCK8 co-exists in the dopamine neuron, the specific binding decreased gradually, and its recovery was delayed compared with that of the frontal cortex and striatum. In the hippocampus, 6-OHDA treatment had no effect on the specific binding throughout the experimental period. The decrease of [125I] CCK8-specific binding could be caused by enhanced release of CCK8 in the frontal cortex, striatum, and nucleus accumbens, and the recovery of specific binding could be induced by depletion of CCK8 in nerve terminals. Particularly in the nucleus accumbens, the delayed recovery of specific binding suggests the loss of the pre-synaptic binding site, which exists in the CCK8/DA co-existing neuron, together with a change in CCK8 release.
  • 陳 戦松, 鷲尾 卓生, 佐藤 益男, 鈴木 康男
    1995 年 18 巻 3 号 p. 421-423
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    The cytotoxic effects of hopanoids, including bacteriohopane-32, 33, 34, 35-tetrol (Tetrol), bacteriohopane-32-ol (Monol), diploptene, diplopterol and acetylated Monol (AcO-Monol) isolated from Acetobacter aceti, were tested against two leukemia cell lines. Tetrol and Monol have been shown to be toxic to mouse L1210 and P388 compared to the other hopanoids. By measuring the ESR spectra of the spin labeled membranes of these cells, it was shown that the incorporation of Monol resulted in a decrease in the fluidity of the membranes. The decrease in membrane fluidity may correlate, in part, with the cytotoxicity of hopanoids against the two cell lines.
  • 幸田 光復, 寺島 勇, 小山 謙一, 渡辺 克夫, 峯浦 一喜
    1995 年 18 巻 3 号 p. 424-430
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    It was reported recently that monomeric O6-benzylguanine (1) acts as an alternative substrate for a DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT), and that therefore pretreatment of cells with 1 induces depletion of AGT resulting in an enhanced cytotoxic response to alkylating antitumor agents. In order to study the interaction of O6-benzylguanine derivatives with AGT and to obtain greater AGT depletion, we synthesized the following O6-arylmethylguanine derivatives and related compounds : O6-(4-, 3- and 2-fluorobenzyl) guanines (2, 3, 4), O6-(4-, 3- and 2-trifluoromethylbenzyl) guanines (5, 6, 7), O6-(4-, 3- and 2-pyridylmethyl) guanines (8, 9, 10), O6-(2- and 1-naphthylmethyl) guanines (11, 12), O6-biphenylmethylguanine (13), S and Se analogues of O6-benzylguanine (14, 15) and O6-phenylguanine (16). Ten of these are new compounds. All these compounds were tested for their potentiation of N'-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-N-(2-chloroethyl)-N-nitrosourea (ACNU) cytotoxicity using HeLa S3 and C6-1 cells. Compounds 2, 3, 5, 8, 9, 11 and 13 were active, as was 1. Compounds 7 and 12, with a substituent at the α position of the benzyl group, and compound 10, the α-nitrogen analogue of 1, were almost completely devoid of potentiating activity. These results suggest that the α-position of the O6-benzyl group plays an important role in the interaction of O6-benzylguanines with AGT. Of the other compounds, 4 and 6 exhibited very weak activity and 14, 15 and 16 were inactive. Possible reasons for these differences in activity are discussed in relation to the biomimetic dealkylation rates of O6-benzylguanine derivatives and the chemical characteristics of their substituents.
  • 宮本 謙一, 坂井 良輔, 栗田 真理子, 大前 真司, 早苗 富士子, 澤西 啓之, 長谷川 高明, 高木 健三
    1995 年 18 巻 3 号 p. 431-434
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    The structure-activity relationships of a series of alkylxanthine derivatives were investigated. The partition coefficient of alkylxanthines enlarged with an elongation of the alkyl chain at the 1-, 3-, or 7-position of xanthine. There was a mild correlation between the apparent partition coefficient and the tracheal relaxant activity or the inhibitory activity on phosphodiesterase (PDE) IV isoenzyme, while the tracheal relaxant activity closely correlated with the PDE IV inhibitory activity. Regarding substituents at different positions, the alkylation at the 3-position increased the inhibitory activity on every PDE isoenzyme. The alkylation at the 1-position potentiated the inhibitory activity on PDE IV with the alkyl chain length, but decreased the activities on other PDE isoenzymes. The alkylation at the 7-position was characteristic in its decrease in inhibitory activity on PDE III. These results suggested that the potency of the inhibitory activity of xanthine derivatives on PDE isoenzymes is not dependent simply upon their hydrophobicity but upon change in the affinity for the active sites on PDE isoenzymes by the introduction of the alkyl group at particular positions of the xanthine skeleton.
  • 高崎 みどり, 木島 孝夫, 小塚 睦夫, 徳田 春邦
    1995 年 18 巻 3 号 p. 435-438
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    To search for possible anti-tumor-promoters (chemopreventive agents), we carried out a primary screening of 21 euglobals (acylphloroglucinol-monoterpene or -sesquiterpene structures) isolated from the juvenile leaves of five species of Eucalyptus plants using an in vitro synergistic assay system. Of these compounds, euglobal-G1-G5 (1-5), -Am-2 (15) and -III (16) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the effects of compounds 1 and 16 on the cell cycle of Raji cells were also examined by a flow cytometer, and both compounds 1 and 16 exhibited strong inhibition on the effect of the cell cycle induced by TPA. These two euglobals (1 and 16) exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.
  • 大原 長夫喜, 高山 幸三, 永井 恒司
    1995 年 18 巻 3 号 p. 439-442
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    The combined effect of d-limonene and temperature on the skin permeation of lipophilic and hydrophilic penetrants has been investigated in rats in vitro. Prednisolone was used as a lipophilic penetrant, and glucose and isoniazid were used as hydrophilic ones, respectively. When the skin was pretreated with 30% ethanol without d-limonene, the steady state permeability coefficient (P) of every penetrant through the skin was difficult to calculate because of very low permeability. On the other hand, the cumulative amount of each penetrant increased with an increase in temperature when the skin was pretreated with 1.5% d-limonene in 30% ethanol. The Arrhenius plots of P values for glucose and isoniazid showed a linear relationship, and the activation energies of skin permeation were estimated to be 87.6 and 66.5 kJ/mol, respectively. When prednisolone was used as penetrant, however, the Arrhenius plot of P values exhibited a convex curvature. This may suggest that the combined use of d-limouene and temperature effectively changes the barrier structure of the non-polar pathway in the stratum corneum, while no synergistic effect was observed on the polar pathway.
  • 渡邊 淳, 浦野 公彦, 村西 廣哉, 巾 正美, 湯浅 博昭
    1995 年 18 巻 3 号 p. 443-446
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    The uptake of low molecular weight fractionated [3H] heparin (LMWFH : 7000 Da) was examined, for comparison with that of high molecular weight fractionated [3H] heparin (HMWFH : 20000 Da), in a primary culture of rat hepatocytes. The uptake of LMWFH increased almost linearly with time up to 60 min (extended uptake), although a faster uptake was observed in the initial 2 min (initial uptake). Both the initial and extended uptake were saturable, and the maximum uptake velocity (Vmax) and the Michaelis constant (Km) were estimated to be 10.7 pmol/min/mg protein and 398 nM, respectively, for the initial uptake and 0.34 pmol/min/mg protein and 116 nM, respectively, for the extended uptake. The Km for the extended uptake was 5 times larger than that of 21 nM for HMWFH, but the other parameters were comparable with those for HMWFH. Thus, an increase in Km, or a decrease in the apparent affinity, with a decrease in molecular weight in the extended uptake may be responsible for the reported lower hepatic uptake of low molecular weight heparin, compared with unfractionated heparin. It was also shown that both the initial and the extended uptake of LMWFH were inhibited by several analogs of heparin, including HMWFH, and anionic compounds such as 4, 4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS), suggesting that LMWFH and HMWFH, in spite of a large difference in the molecular weight, share the same specialized uptake mechanism, in which an anionic moiety and/or heparin-like structure plays an important role.
  • 関川 彬, 八木 直美, 織田 克彦, 剣持 晴美, 高田 昌彦, / / , Emil LIN, Leslie BENET
    1995 年 18 巻 3 号 p. 447-453
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    Furosemide (F) was administered to rabbits intravenously and intraduodenaly and the biliary excretion was studied. The major metabolite excreted in blle was furosemide glucuronide (FG). F and acyl migration isomers of FG (FG-iso) were also excreted in bile. The biliary excretion rates of total F (F+FG+FG-iso) following intraduodenal administration of F were much smaller than those following intravenous administration. The fraction of (F+FG-iso) in bile following intraduodenal administration of F were larger than those following intravenous administration. Stability of FG or FG-iso in bile and supernatant solution of the duodenum homogenate of rabbits was studied. FG was unstable in both media and its degradation followed apparent first-order kinetics in both media. In bile, FG degraded to produce several FG-iso and F, while in the supernatant solution of the duodenum homogenate, it hydrolyzed immediately to F. FG-iso were hardly detected in the supernatant solution. These results indicated that FG excreted in bile degraded easily to FG-iso and F. FG might easily hydrolyze to F enzymatically in the duodenum, and the resultant F might be reabsorbed from the intestinal tract. Unabsorbed FG-iso and F might be excreted in the feces.
  • 山本 重雄, 猪飼 久登, 上杉 寿子, 堀江 あゆみ, 浅川 浩樹
    1995 年 18 巻 3 号 p. 454-456
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    We have previously reported that a novel enzyme, L-2, 4-diaminobutyrate decarboxylase (DABA DC), which is responsible for the formation of 1, 3-diaminopropane, occurs in two Acinetobacter species. The present study extends this observation to additional Acinetobacter species and strains (6 reference strains and 30 clinical isolates). Furthermore, the DABA DC protein was detected in every strain by Western blot analysis with the antiserum against the enzyme purified from A. baumannii ATCC 19606. However, only the DABA DCs in the A. calcoaceticus and Acinetobacter genospecies 3 in addition to A. baumannii strains strongly cross-reacted with the antiserum, suggesting antigenic heterogeneity among the DABA DC proteins in Acinetobacter species. Therefore, immunological testing of the DABA DC protein may provide an additional method for differentiating and identifying Acinetobacter strains.
  • / , 川畑 俊一郎, 倉田 祥一朗, 名取 俊二 /, Shunji NATORI, Bok LEE
    1995 年 18 巻 3 号 p. 457-459
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    We purified and characterized a sapecin homologue, named holotricin 1, from the hemolymph of immunized larvae of a coleopteran insect, Holotrichia diomphalia. We determined its complete amino acid sequence and three disulfide pairs. Holotricin 1 consisted of 43 amino acid residues and showed potent antibacterial activity against gram-positive bacteria, but antibacterial activity against gram-negative bacteria was not obvious.
  • 小泉 利明, 田島 健一, 恵美 伸男, 原 淳, 鈴木 和夫
    1995 年 18 巻 3 号 p. 460-462
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    In order to elucidate the mechanism by which molybdenum prevents the carcinogenesis of N-nitroso compounds, the effects of Na2MoO4-pretreatment on N-nitrosodiethylamine (NDEA)-induced DNA strand breaks, fluctuation in cation contents and lipid peroxidation levels in rat liver were examined. Male Wistar rats weighing 170-190g were pretreated with Na2MoO4 (1.24 mmol/kg body weight, i.p., once a day) for 3 d and on day 4, they were exposed to NDEA (50 mg/kg body weight, once, i.p.). Three days after exposure to NDEA, the nitroso compound caused DNA strand breaks and disrupted potassium (K) and calcium (Ca) metabolism in the liver but did not affect lipid peroxidation levels. Na2MoO4-pretreatment prevented both NDEA-induced DNA damage and disruption of the metabolism of those cations but rather enhanced lipid peroxidation. These results suggest that Mo prevented NDEA-induced DNA damage by preventing disruption of intracellular Ca metabolism while stimulating the metabolism of the nitroso compound via a nontoxic pathway.
  • 松田 秀秋, 蔡 虹, 久保 道徳, 土佐 秀樹, 飯沼 宗和
    1995 年 18 巻 3 号 p. 463-466
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    The inhibitory effects of nine crude drugs were tested on unpurified rat lens aldose reductase, an enzyme involved in the complications of diabetes. Among the crude drugs, a 70% methanolic extract of Buddlejae Flos (flower of Buddleja officinalis) exhibited the highest inhibition. Luteolin, luteolin-7-O-β-D-glucopyranoside, apigenin and acacetin-7-O-α-L-rhamnopyranosyl-(6-1)-β-D-glucopyranoside isolated from Buddlejae Flos showed the inhibitory activity, the IC50 (concentration of 50% inhibitory percentage) values of which were 0.21, 0.28, 0.58 and 0.75 μM, respectively. It is suggested that the inhibitory effect of Buddlejae Flos on aldose reductase is partially attributable to these flavonols or their glycosides.
  • 三巻 祥浩, 指田 豊, 黒田 明平, 西野 敦子, 里見 佳子, 西野 輔翼
    1995 年 18 巻 3 号 p. 467-469
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    Certain Lilium plants contain (25S)-spirost-5-ene-3β, 27-diol glycosides embracing 3-hydroxy-3-methylglutaric acid at the C-27 hydroxy position. One of their derivatives, methyl ester of (25R)-27-O-[(S)-3-hydroxy-3-methylglutaryl]-spirost-5-ene-3β, 27-diol 3-O-{O-α-L-rhamnopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→4)]-β-D-glucopyranoside} was found to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32P-incorporation into the phospholipids of human cervical cancer (HeLa) cells and also to inhibit the proliferation of various kinds of human malignant tumor cells, pancreatic cancer (PANC-1), osteosarcoma (OST), human gastric cancer (HGC-27), pheochromocytoma (PC-12) and HeLa cells, in vitro.
  • SangSoo HAN, KiYoung KIM, SeongHo HAM, DongHwan SOHN, JaeBaek KIM
    1995 年 18 巻 3 号 p. 470-473
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    This experiment was performed to evaluate the usefulness of an experimental fibrosis model by bile duct ligation as a pharmacokinetic model of a disease state. First, experimental liver fibrosis was produced by bile duct ligation. At 4 weeks postoperation, a fibrotic condition was characterized by measurement of the aminoterminal procollagen type III peptide (PIIINP) level in serum, total collagen content in liver and light microscopic histology. Four weeks after bile duct ligation there was an increase in total collagen content of the liver to 430% of the initial values, accompanied by an increase of serum-PIIINP (385%). Secondly, we examined the pharmacokinetics of theophylline in the fibrotic rat induced by bile duct ligation. An i.v. dose of 8 mg of theophylline per kg of body weight was administered, and the levels of theophylline in serum were assayed by high performance liquid chromatography. The area under the serum concentration-time curve of theophylline was increased significantly in fibrotic rats compared with that of the control, and the total clearance of drug in fibrotic rats was low, averaging 22.6 mg/kg/h vs. 36.1 and 60.9 ml/kg/h in the control and the normal rat, respectively. However, the value of distribution during the β-phase was not significantly affected by experimental liver fibrosis.
  • 川口 健夫, 浅川 浩樹, 田代 康壽貴, 從二 和彦, 末石 俊彦
    1995 年 18 巻 3 号 p. 474-476
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    Oligodeoxynucleotide (ODN) composed of 15 nucleotides was modified at 5'-terminal phosphate with hexylamine linker and chemically activated poly (ethylene glycol). This derivative showed improved characteristics in terms of enzymatic stability, binding activity, and in vivo retention in mouse. The data are discussed in comparison with those of corresponding unmodified and phosphorothioate ODNs.
  • 陳 戦松, 佐藤 幸夫, 中澤 亥三, 鈴木 康男
    1995 年 18 巻 3 号 p. 477-480
    発行日: 1995/03/15
    公開日: 2008/04/10
    ジャーナル フリー
    The effects of bacteriohopane-32, 33, 34, 35-tetrol (Tetrol), on liposomal membranes composed of dipalmitoyl-phosphatidylcholine (DPPC) were examined and compared with those of bacteriohopane-32-ol (Monol) and cholesterol (Chol) by means of ESR and NMR techniques. 1H-NMR spectra of Tetrol-incorporated DPPC membranes showed splitting of the signals of the choline N-methyl resonance, whereas Monol-and Chol-incorporated membranes showed no splitting of signals above the transition temperature of DPPC. It was suggested that the incorporation of Tetrol affected only the fluidity near the polar head groups of the DPPC membranes. The characteristics of the interactions between Tetrol and membranes are due to the fact that in DPPC bilayers Tetrol and Monol have an inverted orientation contrary to Chol, and that the hydroxy groups of Tetrol suppress the hydrophobic interaction between DPPC molecules whereas the methyl groups of the hopanoid ring promote this.
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