Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
17 巻 , 8 号
選択された号の論文の35件中1~35を表示しています
  • 若林 広行, 大和 進, 中島 正晴, 嶋田 健次
    1994 年 17 巻 8 号 p. 997-1002
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    A convenient and sensitive high performance liquid chromatographic method with post-column platinum catalyst reduction and electrochemical detection was applied to the simultaneous determination of oxidized and reduced coenzyme Q (CoQ and CoQH2) and α-tocopherol (α-TP) in human and rat samples. After the separation of oxidized and reduced CoQ homologues (CoQ8-CoQ10 and CoQ8H2-CoQ10H2) and α-TP on a reversed-phase column, oxidized CoQ homologues were reduced on a platinum catalyst reduction column, and then all the reduced forms were quantified with an electrochemical detector operated in the oxidation mode (+0.6V vs. Ag/AgCl). The order of elution was α-TP, CoQ8H2, CoQ9H2, CoQ8, CoQ10H2, CoQ9, and CoQ10 and all were well separated within 13min. The detection limits at a signal-to-noise ratio of 3 were 20pg for α-TP, 70pg for CoQ8 and CoQ8H2, and 100pg for CoQ9, CoQ9H2, CoQ10 and CoQ10H2. Quantitative recoveries (93-102%) from serum and tissues were obtained for all the analytes studied. This method was applied satisfactorily to the simultaneous determination of CoQ, CoQH2 and α-TP in biological materials.
  • 加藤 真介, 緑上 淳一, 高須 重人, 藤原 民雄
    1994 年 17 巻 8 号 p. 1003-1007
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    We demonstrated the invagination of transferrin into reticulocyte plasma membrane to learn whether membrane-bound transglutaminase (TGase, a Ca2+-dependent enzyme) is involved in this invagination. The invagination was assessed by acid-resistance assay and antibody-inaccessibility assay. The invagination was blocked in the absence of ATP. [14C] Putrescine, a substrate for TGase, was incorporated into the membrane during the invagination. This incorporation was decreased in the absence of ATP or transferrin and was completely blocked in the presence of monodansylcadaverine or EGTA. The TGase inhibitor and EGTA also decreased the invagination. In the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, the labeling of 43kDa membrane protein with [14C] putrescine and the increase in aggregation of proteins were observed in a transferrin-, ATP-and Ca2+-dependent manner. These results provide the first evidence for modification of protein by TGase accompanying the invagination of transferrin into the membrane, and suggest that membrane-bound TGase is involved in the invagination step of endocytosis.
  • 成冨 洋一, 丹羽 俊朗, 白神 歳文, 岩崎 一秀, 野田 耕世
    1994 年 17 巻 8 号 p. 1008-1011
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    An alicyclic amine N-sulfotransferase sulfonating 4-phenyl-1, 2, 3, 6-tetrahydropyridine (PTHP) was purified from female rat liver cytosol and showed a homogeneous band with a molecular weight of 30500 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme, designated NST-1, catalyzed sulfonation not only of the alicyclic amine but also dehydroepiandrosterone, a typical substrate of hydroxysteroid sulfotransferases (STs), but had little sulfonating activity towards 2-naphthol, a typical substrate of aryl STs. The N-terminal amino acid sequence for the first 24 residues had a high homology with those of rat liver hydroxysteroid STs. Therefore, it is suggested that NST-1 is classified as a member of the hydroxysteroid ST. Immunoblot analysis of male and female rat liver cytosol, carried out by using rabbit antisera raised against NST-1, indicated that the female cytosol contained a higher level of the enzyme than that of male. The marked sex difference in the expression level of NST-1 was in good accordance with the previous demonstration that female rat liver cytosol catalyzed sulfonation of PTHP to a greater extent than that of male.
  • 長岡 正人, 橋本 秀介, 渡辺 常一, 横倉 輝男, 森 陽
    1994 年 17 巻 8 号 p. 1012-1017
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The anti-ulcer effects of bifidobacteria, lactobacilli and streptococci were examined using the acetic acid-induced gastric ulcer and ethanol-induced erosion models in rats. Bifidobacterium breve YIT4014 and 4043, and Bifidobacterium bifidum YIT4007 were administered orally, and anti-ulcer effects were confirmed for not only these organisms but also their polysaccharide fractions (PSFs). The major component of these anti-ulcer polysaccharides was rhamnose. In particular, polysaccharides in which the rhamnose content exceeded 60% were more effective in healing gastric ulcers. After administration of the PSF from B. bifidum YIT4007, the levels of epidermal growth factor and basic fibroblast growth factor increased in gastric tissues. Similar results were observed for the culture supernatant of gastric epithelial cells cultured with PSF. Furthermore, the production of 6-ketoprostaglandin F1a by macrophages was also enhanced by PSF. These results indicated that these bacteria and their polysaccharides induced host repair and protective systems in the gastric ulcer model.
  • 今村(小西) 理佐, 佐藤 誠, 土肥 啓司, 門田 重利, 難波 恒雄, 小橋 恭一
    1994 年 17 巻 8 号 p. 1018-1022
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    A novel type of arylsulfate sulfotransferase (ASST) from a predominant human intestinal bacterium catalyzes the stoichiometric transfer of a sulfate group from phenolic sulfate esters to phenols. We clarified that polyphenols were better substrates of this enzyme than the corresponding glycosides. Additionally, a coumarin derivative, esculetin, was sulfated by ASST at the 6-position to give 6-monosulfate. Therefore, ASST is more useful for the preparation of sulfated polyphenols at their specific hydroxyl groups and would play an important role in the metabolism of phenolic compounds in vegetable food and traditional medicines.
  • 草山 俊之, 岡 淳一郎, 矢花 秀雄, 赤羽 悟美, 長尾 拓
    1994 年 17 巻 8 号 p. 1023-1028
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The affinities for β-adrenoceptors, the subtype-selectivity and the agonistic effectiveness of T-0509 (a catechol derivative of denopamine) and colterol (N-tert-butylnoradrenaline ; Col) were compared with those of other β-agonists using a binding assay method. Specific binding of [3H] dihydroalprenolol (3H-DHA) to guinea pig left ventricular and lung membranes was saturable, and Scatchard and Hill analyses suggested that 3H-DHA bound to both membranes with a single population of binding sites with no binding site cooperativity. Addition of 5'-guanylyl-imidodiphosphate (GppNHp, 30μM) led to a rightward shift of the 3H-DHA binding displacement curves of T-0509 and Col in both membranes, and the degree of shift was similar to that of full agonists such as isoproterenol (Iso), adrenaline (Adr) and noradrenaline (NA). Both T-0509 and Col were thus considered to be full agonists at both β1-and β2-adrenoceptors, respectively, unlike denopamine and procaterol. T-0509 and Col showed considerably high affinity for both β1-and β2-adrenoceptors, and T-0509, like denopamine, was as selective for the β1-subtype as NA (4.5-fold compared with Iso as a non-selective agonist), whereas Col was more selective for the β2-subtype than Adr (4.5-fold compared with Iso).
  • Shivayogi P. HIREMATH, Shrishailappa BADAMI, H.K.S. SWAMY, Sarawati B. ...
    1994 年 17 巻 8 号 p. 1029-1031
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Four successive solvent extracts of the whole plant Striga orobanchioides have been screened for antifertility activity in albino rats. Of these the ethanolic extract was found to be most effective in causing significant anti-implantation activity. The antifertility activity was reversible on withdrawal of treatment with the extract. The ethanolic extract at 200 mg/kg showed estrogenic activity. Histological studies of the uterus were carried out to confirm this estrogenic activity.
  • 南 武志, 中川 裕文, 鍋島 政義, 門田 永治, 並川 清博, 川木 秀子 /, Yuko OKAZAKI
    1994 年 17 巻 8 号 p. 1032-1037
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Twenty-four adenine analogs were administered to mice and the relationship between the structure of analogs and the occurrence of renal injury was examined. Plasma urea nitrogen (UN) and creatinine levels were measured 24h after oral administration of analogs. Both levels increased in the adenine-, 8-azaadenine-, isoguanine-, or 6-dimethyl aminopurine (6-DMAP)-administered group, but did not increase in the other analog groups. From light microscopy, the damages of tubuli, mainly of proximal tubuli, were observed in the kidneys of these four groups. The common property of these compounds is the strong basicity of nitrogen which binds the 6-position of the purine ring. Furthermore, UN and creatinine increas-ed time-dependently with intravenous administration of isoguanine. When adenine was intravenously administered, UN slightly increased at 1 h, but creatinine was unchanged. No changes were observed in the 6-DMAP-or 8-azaadenine-administered group. The basicity of nitrogen which binds to the 6-position of the purine ring is thus considered to be related to the occurrence of renal injury with oral administration, and isoguanine has high affinity with the kidney.
  • 菊地 松夫, 橋村 吉正, 黒葛原 啓, 長澤 正明, 井上 博純, 谷口 友康, 内田 泰典
    1994 年 17 巻 8 号 p. 1038-1046
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Structure-activity relationships in the inhibitory effects of 4-acylaminophenol derivatives on the 5-lipoxygenase (5-LOX) from RBL-1 cells and leukotriene B4 (LTB4) production by guinea pig neutrophils were studied. When the N-acyl group was n-octanoyl or 2-thiophenecarbonyl and the size of the two ortho substituents of phenol was varied, the substituents bulkier than isopropyl, i.e., 2, 6-di-tert-butyl and 2, 6-dicyclohexyl, substantially weakened the inhibitory activity in both enzymatic and cellular systems. Among the 2, 6-dimethyl derivatives with an acyl group of various carbon-chain lengths (C1-13), those with a n-alkyl chain of C5 to C12 showed similarly potent inhibitory activities toward 5-LOX with an IC50 ranging from 0.27 to 0.66μM ; in contrast, maximal inhibitory activities toward LTB4 production were observed in a narrower range of the serial compounds : i.e., those with a n-hexyl, n-heptyl, or n-octyl chain on the carbonyl carbon formed by far the most inhibitory group of the series and the inhibitory activity sharply decreased on either side of the chain length. Nearly all the active compounds also inhibited cyclooxygenase (COX), but the IC50 values for COX inhibition were more than ten times higher than the corresponding IC50 values for 5-LOX inhibition in most cases, indicating that the acylaminophenols are relatively selective 5-LOX inhibitors.
  • 吉川 日出雄, 菅野 賢吉, 池沢 一郎
    1994 年 17 巻 8 号 p. 1047-1052
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Relaxant effects of the β2-selective adrenoceptor agonist TA-2005 on bronchoconstriction in the anesthetized guinea pig and cat were evaluated in comparison with other known β2-adrenoceptor agonists. The ED50 values of intravenously administered TA-2005, procaterol, formoterol, isoproterenol, salbutamol, and salmeterol to inhibit the histamine-induced bronchoconstriction of the guinea pigs were 0.024, 0.053, 0.056, 0.099, 0.23, and 2.00μg/kg, respectively, and those in serotonin-challenged cats were 0.019, 0.037, 0.039, 0.042, 0.13, and 0.52μg/kg, respectively, in the same increasing order. When guinea pigs were passively sensitized with anti-ovalbumin antiserum, the ED50 values of TA-2005, formoterol, procaterol, and isoproterenol to inhibit the antigen-induced bronchoconstriction were 0.09, 0.30, 0.65, and 7.0μg/kg, i.v., respectively, while those of TA-2005, procaterol, formoterol, and salbutamol in actively sensitized animals were 0.24, 0.25, 1.40, and 23.0μg/kg. When TA-2005 was administered by inhalation to guinea pigs or by the intraduodenal route to cats, it exhibited a long-lasting inhibitory effect comparable or superior to the effects of salmeterol and formoterol. These data indicate that, among the known β2-adrenoceptor agonists examined, TA-2005 exerts the most potent bronchodilating effects with a long duration of action in vivo, and its potency ratios to the other reference drugs were greater in antigen-than spasmogen-induced bronchoconstric-tion models.
  • 長谷川 宏之, 村山 俊彦, 高橋 明美, 板倉 智敏, 野村 靖幸
    1994 年 17 巻 8 号 p. 1053-1055
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Changes in neurotransmission are known to take place in a variety of conditions, such as Parkinson's disease, A neurofilament-deficient mutant of the Japanese quail, named the Quiver quail, exhibits generalized quivering as a clinical sign. The content of monoamines (noradrenaline (NA), dopamine and 5-hydroxytryptamine) and the uptake and release of L-[3H]NA were measured in brain of this bird. In Quiver, the NA content in neostriatum and thalamus, and the 5-hydroxytryptamine content in neostriatum, paleostraitum and thalamus were significantly increased, in comparison with the normal quail. The dopamine content and L-[3H]NA uptake and release in the Quiver mutant were similar to those in normal quail.
  • 徳山 尚吾, 中村 文博, 高橋 正克, 金戸 洋
    1994 年 17 巻 8 号 p. 1056-1059
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Using various administration schedules, the physical dependence produced by dihydroetorphine (DHE) was compared with that of morphine in mice. Physical dependence, evaluated by naloxone-precipitated withdrawal signs, did not develop following daily treatment with DHE (10, 20, 100 and 1000μg/kg, i. p. or 30, 100 and 1000 ng/mouse, i. c. v.) for 6d. However, 5 repeated injections of DHE (10μg/kg, i. p.) at 1 or 2 h intervals did produce physical dependence and the dependent state disappeared after 2h. Accordingly, it was demonstrated that a sufficient degree of antinociceptive activity needed to be maintained, longer than several hours, for the development of physical dependence on DHE and that the duration of the dependent state was very short. In the single dose suppression test, a single dose of DHE completely suppressed the natural withdrawal signs that appeared following abstinence in morphine-dependent animals without reappearance of significant withdrawal signs, indicating the suitability of DHE as a substitute for morphine. The characteristic properties of DHE, the extremely potent antinociceptive effect and minimal dependence, indicate the separation of the antinociceptive effect from dependence, and suggest that it may be possible to develop a novel drug which may be safely used in clinical situations.
  • 宍戸 祐之, 松本 常男, 酒井 正士, 兼田 憲昌, 三沢 宏, 志村 喜作, 橋本 秀介, 横倉 輝男
    1994 年 17 巻 8 号 p. 1060-1064
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    We compared the thrombolytic properties of recombinant staphylokinase (SAK) with those of streptokinase (SK), a tissue-type plasminogen activator (t-PA) and a urokinase-type plasminogen activator (u-PA) in the jugular vein thrombosis model in the rabbit in vivo and a circulating human plasma system in vitro. 50% thrombolysis was observed at 360 min after intravenous infusion into rabbits of 150μg/kg of SAK or 500μg/kg of t-PA, respectively. And the fibrinogen level in the blood was not affected by either agent. 50% clot lysis in vitro was observed at 120 min with 1.8μg/ml of SAK, 22.1 μg/ml of SK, 2.1μg/ml of t-PA, or 4.7μg/ml of u-PA, respectively. All the plasminogen activators with the exception of SAK decreased the residual fibrinogen level in the circulating plasma at their moderate concentration for clot lysis. SAK had less influence on the plasminogen and α2-plasmin inhibitor (α2-antiplasmin) levels than the other plasminogen activators. These findings suggest that SAK is a potent fibrin-specific thrombolytic agent.
  • 一木 浩, 桜田 仁, 加茂 直樹, 高橋 恒夫, 関口 定美
    1994 年 17 巻 8 号 p. 1065-1069
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The generation of peroxides (presumably hydrogen peroxide) by UV-B irradiation of human blood cells was detected. Non-fluorescent dihydrorhodamine 123 (DHR) is oxidized to fluorescent rhodamine 123 (R123) by H2O2 or peroxides with a stoichiometry of 1 : 1 in the presence of exogeneous peroxidase, and the fluorescence of R123 within the cells was measured using flow-cytometry. UV irradiation gave rise to changes in the cellular volume and the membrane potential, whose extent and direction were dependent on the type of blood cells. The production of peroxides (H2O2) in polymorphonuclear leukocytes is the largest among blood cells at the lower dose (<0.1J/cm2), and the production decreases with an increase in the dose, while the production in platelets is the smallest at the lower dose, but above 0.4J/cm2 it increases suddently so that at the higher dose (1.2J/cm2) it amounts to 3.3×10-16 mol/cell. For monocytes and lymphocytes, the production increases gradually with the increase in the dose.
  • 水越 貞範, 塚本 正満, 田中 久樹, 中村 恭子, 加藤 文法
    1994 年 17 巻 8 号 p. 1070-1074
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The anti-inflammatory effects of 1, 6-anhydro-3, 4-dideoxy-2-furfuryl-β-D-threo-3-enopyranose (MT2221) were investigated using animal models and compared with the effects of dexamethasone (DEX) and cyclosporin A (CYA). MT2221 inhibited carrageenan-induced acute inflammation and adjuvant arthritis in rats, as well as the delayed-type hypersensitive response and collagen-induced arthritis (CIA) in mice. However, it seemed that this compound was more effective against murine CIA than upon the other inflammation models. The MT2221 mode of action differed from those of conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs (DMARDs). All of these drugs are effective against acute inflammation or adjuvant arthritis models, but not against murine CIA. DEX and CYA did inhibit murine CIA, but in other animal models, their mode of action differed from that of MT2221. Moreover, allograft transplantation in mice showed that MT2221 slightly prolonged the allograft survival time. These results suggest that MT2221 has not only anti-inflammatory but also im-munosuppressive effects based upon a novel mechanism of action that is different from NSAIDs, DMARDs, DEX and CYA.
  • 尾崎 幸紘, 大野 晶子, 斉藤 雄二, 佐竹 元吉
    1994 年 17 巻 8 号 p. 1075-1077
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The present study was carried out to compare the accelerative effect of shikonin (R-type), alkannin (S-type), and acetylshikonin on the proliferation of granulation tissue in rats, and to elucidate the correlation between the potency of the effect and their optical activity. Koushikon mainly contained the R-type of acetylshikonin, and Nanshikon mainly contained the S-type of acetylshikonin. Each compound produced a dose-dependent acceleration of the cotton pellet-induced granuloma formation. In comparing identical doses of shikonin, alkannin and acetylshikonin, the potency of their accelerative effects on the proliferation of granulation tissue was about the same. This result suggests that their absolute configurations (R-type or S-type) and their acetylation on the hydroxy group of the sidechain of shikonin or alkannin may not be important in producing the effect.
  • 松木 洋子, 坂東 理恵, 際田 弘志, 前田 晴美, 五郎丸 毅
    1994 年 17 巻 8 号 p. 1078-1082
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The effects of ascorbic acid (AA) on hepatic injury induced by iproniazid (IPN) in phenobarbital-treated rats were investigated by the evaluation of hepatic function using the clearance of aminopyrine (AM). Either IPN or isopropylhydrazine (IP-Hy), a potent toxic metabolite of IPN, were administered as a pretreatment to rats with or without AA. After i.v. injection of AM, the blood concentration of AM was determined by capillary gas chro-matography by isotope dilution analysis using deuterium-labeled AM (AM-d9) as the internal standard. The kinetic parameters of AM, Vd, kel and total body clearance, were estimated from the time course of blood concentration. Pretreatment with IPN with AA led to a marked increase in the kel and in the clearance compared with pretreatment using IPN alone. A significant increase in the kel and the clearance was also found in the case of combined pretreat-ment using IP-Hy with AA. The effects of AA on the hepatic injury induced by IPN were studied according to its histological aspects. In the speciments obtained following the administration of IPN or IP-Hy with AA, the degree of cell necrosis was remarkably lowed both quantitatively and qualitatively. The present results clearly demonstrate that AA was effective in reducing IPN-induced hepatitis.
  • 田島 武志, 金子 和代, 畑中 朋美, 合葉 哲也, 片山 和憲, 小泉 保
    1994 年 17 巻 8 号 p. 1083-1088
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The degree of twitch depression induced by nondepolarizing neuromuscular blocking drugs is known to be dependent on the stimulation frequency employed. Train-of-four (TOF) stimulations with different frequencies (0.67, 1.33 and 2.0Hz) were delivered to a sciatic nerve of a rat and series of four twitch heights of a tibialis anterior muscle were measured after d-tubocurarine (d-TC) administration. With a decrease of stimulus interval, twitch heights were intensely depressed. We hypothesized that the oservations are due to the changes of released amount of neuromuscular transmitter, acetylcholine, dependent on stimulus interval, and a pharmacokinetic/pharmacodynamic model based on the hypothesis was proposed. The model allowed simultaneous fitting of the twitch height depression after d-TC administration. It also could give a rationale to the fact that TOF stimulation at 2.0 Hz is a more sensitive monitoring method of neuromuscular function than single twitch stimulation (0.1-0.2 Hz).
  • 田島 武志, 加藤 安宏, 畑中 朋美, 合葉 哲也, 片山 和憲, 小泉 保
    1994 年 17 巻 8 号 p. 1089-1093
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The degree of train-of-four (TOF) fade, i.e., the reduction of the fourth to the first twitch height in a train, induced by d-tubocurarine (d-TC) and α-bungarotoxin (α-BX) was investigated. The fade induced by d-TC was pronounced in comparison with that by α-BX, and the difference was analyzed using a kinetic model. Based on the assumptions : (1) Acetylcholine (ACh) binds to the nicotinic receptor and evokes twitch response. (2) The amount of released ACh is dependent on stimulus interval. (3) d-TC interacts competitively with the receptor. (4) α-BX interacts irreversibly with the receptor. It was suggested that the fade by d-TC and α-BX can be explained by the difference of the receptor occupancy by ACh which was caused by different interaction mechanisms of the two muscle relaxants with receptors.
  • 小木曽 太郎, 朴 剛, 岩城 正宏, 谷野 公俊, 西岡 志穂
    1994 年 17 巻 8 号 p. 1094-1100
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    This study was designed to evaluate the percutaneous absorption of physiologically active peptides, ebiratide (a behaviorally potent adrenocorticotropic analog) and elcatonin (a hypocalcemic peptide) in an attempt to develop an efficient transdermal therapeutic system for the treatment of diseases. The [125I] ebiratide penetration through rat skin from gel formulations could be described fairly well by a zero-order kinetic profile. Skin penetration was the greatest when EDTA, n-octyl-β-D-thioglucoside (OTG, 1.5%) and taurocholate (1.0%) were combined in a gel formulation. The order of flux was : EDTA, OTG and taurocholate (formulation 3) > OTG and taurocholate (formulation 2) > glucosyl-β-cyclodextrin and OTG (formulation 4). When the transdermal systems of [125I] ebiratide prepared using a corresponding gel formulation were applied to rat abdomen, the plasma levels of radioactivity after formulations 3 and 2 were much higher than those after formulation 1 without enhancers, and the radioactivity was observed in the brain, although in a very small quantity. The hypocalcemic effect of elcatonin was measured in vivo after application of the transdermal systems. The plasma calcium levels decreased comparatively rapidly and low levels were maintained for a long period, indicating the effectively percutaneous absorption of elcatonin. Formulation 7 containing D-limonen and taurocholate as enhancers and/or inhibitors showed much higher hypocalcemic effect than two other formulations combined with laurocapram or N, N-diethyl-m-toluamide, consequently giving the highest pharmacological availability (8.7±1.0%). These results clearly demonstrated that the peptides were effectively absorbed through rat skin in the presence of enhancers.
  • 佐藤 純, 浜口 直, 道券 一浩, 後藤 和徳, 大津 紘一郎, 岩佐 進, 小川 泰亮, 戸口 始
    1994 年 17 巻 8 号 p. 1101-1105
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    We have investigated the biological properties of an immune complex composed of recombinant interleukin-2 (rIL-2) and an F (ab')2 fragment of a monoclonal antibody against rIL-2 in mice for the induction of killer cells and anti-tumor activity, as well as the pharmacokinetic properties of the immune complex injected subcutaneous-ly into mice. The immune complex demonstrated sustained serum rIL-2 levels, with a 2.4-times longer"mean-residence-time"than free rIL-2. A more significant portion of rIL-2 was detected in lymph nodes after the subcutaneous injection of the immune complex than with rIL-2 alone. Splenic lymphocytes from mice given the immune complex showed higher killer cell activity against YAC-1 and P815 cells than those from mice given rIL-2 alone. The immune complex also exerted a more significant anti-tumor effect in a dose-dependent manner in Meth-A fibrosarcoma-bearing mice than dit rIL-2 alone.
  • 久保 恵子, 青木 久夫, 難波 宏彰
    1994 年 17 巻 8 号 p. 1106-1110
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The fruit body of Grifola frondosa (maitake), Basidiomycetes was confirmed to contain substances with anti-diabetic activity. When 1g/d of powdered fruit body of maitake was given orally to a genetically diabetic mouse (KK-Ay), blood glucose reduction was observed, in contrast to the control group in which the blood glucose increased with ageing. Moreover, levels of insulin and triglyceride in plasma demonstrated a change similar to blood glucose with feeding of maitake. Ether-ethanol-soluble (ES) and hot water-soluble (WS) fractions were prepared from the fruit body and their hypoglycemic activity was examined. Blood glucose-lowering activity was found when ES-fraction or WS-50% ethanol float (X) fraction was administered orally, but other WS-fractions were inactive. These results suggest that the anti-diabetic activity was present not only in the ES-fraction consisting of lipid but also in the X-fraction of peptidoglycan (sugar : protein=65 : 35).
  • 伊吹 裕子, 五島 廉輔
    1994 年 17 巻 8 号 p. 1111-1113
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    This study was undertaken to examine the adaptive response in Chinese hamster V79 cells using the cell survival (colony formation assay) and DNA synthesis ([3H] thymidine incorporation) as endpoints. When V79 cells were preirradiated with an adapting dose (0.05Gy), their survival after irradiation with the challenging dose (4Gy) was about 120% of the control without such preirradiation. Following irradiation with the challenging dose, the DNA synthesis of the preirradiated cells was less reduced than those without it. The adaptive responses were considered to be associated with the signal transduction via protein kinase C from the results that this response was not observed when the cells were preirradiated with the adapting dose in the presence of protein kinase C inhibitor, H-7.
  • 溝口 秀俊, 深沢 弘志, / 矢野 敬一, 山崎 基生, 岩崎 成夫, 橋本 祐一, Yuichi HASHIMOTO
    1994 年 17 巻 8 号 p. 1114-1117
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    12-O-Tetradecanoylphorbol-13-acetate (TPA) binds specifically to histone H1 prepared from HeLa cells and to calf histone H1 with dissociation constants of 4.3×10-7 and 9.3×10-7 M, respectively. The TPA-binding to histone H1 was confirmed immunologically using a monoclonal antibody directed against an evolutionally conserved epitope of histone H1. This binding would influence DNA structure and the basal level of transcription, and may, in turn, account for the cell growth-regulatory activity of TPA.
  • 舟橋 孝之, 島村 真里子, 古茶 友二, 福田 照夫, 青柳 高明
    1994 年 17 巻 8 号 p. 1118-1120
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    It has been suggested that the activities of type IV collagenase and/or ectopeptidases possessed by malignant cells are related to their metastatic potentials. In the present study, we examined the activities of three aminopepti-dases, two serine proteases, as well as type IV collagenase, in three kinds of cell lines of malignant cells. The activities of the aminopeptidases and serine proteases, rather than of type IV collagenase, were found to be proportionate to the metastatic potentials of those cell lines. Such activities of aminopeptidases were effectively suppressed by the addition of low molecular weight inhibitors.
  • 原 清人, 小松 英忠, 堤 直行, 氏家 新生, 池田 滋, 小林 哲幸, 工藤 一郎, 井上 圭三
    1994 年 17 巻 8 号 p. 1121-1123
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Anti-allergic drugs, tranilast and azelastine, were examined for their effects on lysophosphatidylserine (lysoPS)-dependent histamine release from rat mast cells. Although both compounds suppressed the histamine release in a dose-dependent manner, the inhibition was affected by lysoPS concentration differently. In the presence of an increasing concentration of lysoPS, the suppressive effect of tranilast decreased. The inhibition by azelastine, however, was independent of the concentration of lysoPS. The findings suggest that these two drugs inhibit lysoPS-dependent histamine release through essentially different routes.
  • 大島 康一, 森川 忠則, 萩原 正樹
    1994 年 17 巻 8 号 p. 1124-1125
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The degree of platelet aggregation induced by ADP and collagen was examined in platelet-rich plasma from 7-to 90-week-old rats. The aggregation induced by ADP was unchanged at 90 weeks. Collagen-induced aggregation decreased remarkably at 60 and 90 weeks. Therefore, collagen-induced platelet activation is highly age-dependent, with rats of advanced age showing a lower response than younger rats.
  • 丸山 恵子, 大倉 紀子, 八木 優子, 長友 孝文
    1994 年 17 巻 8 号 p. 1126-1129
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The present study was designed to assess displacemental potencies of terazosin and its isomers for α1High and α1Low adrenoceptor subtypes in rat brain, heart, bovine prostate and canine aorta using a radioligand binding assay method. Although no significant difference in pKi values of each terazosin isomer for α1High in canine aorta and rat brain were observed, the displacemental potency of (S-) terazosin for those in rat heart and bovine prostate was stronger than that of (R+) isomer (p<0.01). On the other hand, only in α1Low subtypes of bovine prostate was stronger displacemental potency of (S-) terazosin than (R+) isomer (p<0.05) observed. Thus, these results imply that there is a different affinity between (S-) terazosin and (R+) isomer on the α1High in bovine prostate and rat heart and α1Low in bovine prostate.
  • 平田 道則, 加藤 秀子, 出淵 早巳, 池末 厚俊, 三田村 真理, 中川 秀夫
    1994 年 17 巻 8 号 p. 1130-1131
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The anti-inflammatory effect of 22-oxa-1α, 25-dihydroxyvitamin D3 [22-oxa-1α, 25 (OH)2D3], an analogue of the active form of vitamin D3, was studied regarding carrageenin-induced inflammation in rats. In the early phase of the inflammation, the formation of granulation tissue and the weight of exudate were significantly suppressed by both oral and local administrations of 22-oxa-1α, 25 (OH)2D3 daily for 4d (day 0-3) after carrageenin injection, though the local injection of 22-oxa-1α, 25 (OH)2D3 (7 and 10μg/kg). Similarly, oral and local administrations of 22-oxa-1α, 25 (OH)2D3 from day 4 to 7 significantly suppressed the increase in exudate and the proliferation of granulation tissue in the late phase of carrageenin-induced inflammation in rats. The results suggest that 22-oxa-1α, 25 (OH)2D3 has an anti-inflammatory activity on both the acute and proliferative phases of inflammation in rats.
  • 石原 誠一, 山田 清文, 林 哲夫, 長谷川 高明, 亀山 勉, 盛政 忠臣, 金行 孝雄, 庄盛 敏廉, 鍋島 俊隆
    1994 年 17 巻 8 号 p. 1132-1134
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Using in vitro autoradiography, we investigated the effects of Kamikihito (KKT), a traditional Chinese medicine, on specific [3H] SCH23390 binding to dopamine D1 receptors and [3H] ketanserine binding to serotonin 5-HT2A receptors in the rat brain. Specific binding of both compounds was affected by aging. Long-term administration of KKT resulted in decreases in [3H] SCH23390 binding to the cortex and hippocampus in aged rats, and in decreases in [3H] ketanserine binding to the caudate/putamen in young rats. These results suggest that the changes in dopamine D1 and serotonin 5-HT2A receptor binding may be involved in the central effects of KKT.
  • 関 俊暢, 佐藤 準人, 長谷川 哲也, 川口 健夫, 從二 和彦
    1994 年 17 巻 8 号 p. 1135-1137
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The nasal absorption of zidovudine (AZT) and its subsequent transport to cerebrospinal fluid (CSF) was examined in rats. Both rapid absorption and a high CSF concentration were observed after the nasal application. Plasma and CSF concentrations of AZT increased when probenecid was coadministered with AZT. Thus, this nasal coadministration of AZT and probenecid could be useful for the treatment of AIDS patients with neuropathies.
  • 徳村 忠一, 田中 智英
    1994 年 17 巻 8 号 p. 1138-1140
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    A granule of 2-[4-(p-fluorobenzoyl)-piperidin-1-yl]-2'-acetonaphthone hydrochloride (E2001) with an enhanced dissolution rate (preparation A) prepared by a method previously reported (T. Tokumura, T. Tanaka, Yakuzaigaku, accepted) was evaluated by the dissolution test and its bioavailability in beagle dogs was determined. The dissolution rate of E2001 from preparation A at pH 6.0-6.8 was increased significantly in comparison with that from preparation B (a physical mixture of the same formula). There was no significant difference in Cmax, area under the concentration-time curve (AUC0-6h), or Tmax between preparations A and B when a dose equivalent to 20 mg of E2001 was administered to the beagle dogs. However, a significant difference was observed between the AUC0-6h values after oral administration of the two preparations with NaHCO3. These findings suggest that the bioavailability of E2001 from the oral administration preparation A will be higher than that of preparation B.
  • 坂東 博人, 山下 富義, 高倉 喜信, 橋田 充
    1994 年 17 巻 8 号 p. 1141-1143
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    The effectiveness of prodrug-enhancer combination in skin penetration enhancement was studied using acyclovir and its lipophilic prodrug, acyclovir butyrate, with octanol/water partition coefficient of 0.0123 and 0.402, respectively. In the in vitro diffusion experiment with rat skin, the total amount of acyclovir appearing in the receptor phase after administration of the aqueous suspension of acyclovir butyrate was smaller than that obtained after administration of acyclovir, but their permeability coefficients were almost equal. An enhancer, 1-geranylazacycloheptan-2-one (GACH) did not show a large penetration enhancement of acyclovir (3.37-fold) but demonstrated extensive en-hancement effect on the prodrug (12.3-fold). Most of the prodrug appeared in the form of acyclovir in the receptor phase without GACH, but the appearance ratio of acyclovir to total flux decreased with an increase in pretreatment doses of GACH.
  • 飯島 亮介, 来生 淳, 山崎 正利
    1994 年 17 巻 8 号 p. 1144-1146
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Dolabellanin A (DAA), the antineoplastic and antibacterial glycoprotein purified from the albumen gland of Dolabella auricularia, showed an antifungal activity. DAA suppressed fungal growth completely at a concentration of over 2μg/ml, and the colony forming ability of the fungus was significantly decreased after contact with DAA. These results indicate that DAA is an antifungal protein and its mode of antifungal activity is fungicidal.
  • 遠藤 泰之, 大野 道博, 平野 祐明, 藤原 民雄, 佐藤 彰彦, 日沼 頼夫, 首藤 紘一
    1994 年 17 巻 8 号 p. 1147-1149
    発行日: 1994/08/15
    公開日: 2008/04/10
    ジャーナル フリー
    Teleocidin B-4 and structurally related synthetic benzolactams were found to be potent inhibitors of cell killing by HIV-1. One of the benzolactams, (-)-BL-V8-310, showed a high selectivity index.
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