著者

Muneo Tsukiyama Tatsuhiro Akaishi Takuro Ueki Hidenobu Okumura Kazuho Abe

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.11, pp.2063-2068, 2007-11-01 (Released:2007-11-01)

参考文献数

20

被引用文献数

3 9

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Although the fruit of Nandina domestica THUNBERG (ND) has been used to treat respiratory disorders such as coughing and breathing difficulty in Japan for many years, very little is known about mechanisms underlying its action. In the present study, we investigated effects of the crude extract from ND (NDE) and one of its constituents, nantenine, on contractile responses in isolated guinea pig tracheal ring preparations. In normal experimental condition, guinea pig trachea remained tonically contracted during the resting state, and addition of NDE (1 mg/ml) caused a relaxation of tracheal smooth muscles, but had little effect on the responsiveness of trachea to acetylcholine. The basal, tonic contraction was abolished by the presence of atropine and indomethacin. In this condition, NDE at 0.1—1 mg/ml inhibited histamine-induced contraction in both competitive and non-competitive manners. NDE at 0.01—1 mg/ml inhibited serotonin-induced contraction in a competitive manner. Nantenine (2—20 μM) did not affect histamine-induced contraction, and slightly inhibited serotonin-induced contraction. These results suggest that NDE has inhibitory effects on tracheal smooth muscle contraction, and nantenine cannot account solely for this effect of NDE.

著者

Marina Isshiki Kazuo Umezawa Hiroomi Tamura

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.10, pp.1624-1627, 2011-10-01 (Released:2011-10-01)

参考文献数

25

被引用文献数

13 15

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Coffee is a beverage that is consumed world-wide on a daily basis and is known to induce a series of metabolic and pharmacological effects, especially in the digestive tract. However, little is known concerning the effects of coffee on transporters in the gastrointestinal tract. To elucidate the effect of coffee on intestinal transporters, we investigated its effect on expression of the breast cancer resistance protein (BCRP/ABCG2) in a human colorectal cancer cell line, Caco-2. Coffee induced BCRP gene expression in Caco-2 cells in a coffee-dose dependent manner. Coffee treatment of Caco-2 cells also increased the level of BCRP protein, which corresponded to induction of gene expression, and also increased cellular efflux activity, as judged by Hoechst33342 accumulation. None of the major constituents of coffee tested could induce BCRP gene expression. The constituent of coffee that mediated this induction was extractable with ethyl acetate and was produced during the roasting process. Dehydromethylepoxyquinomicin (DHMEQ), an inhibitor of nuclear factor (NF)-κB, inhibited coffee-mediated induction of BCRP gene expression, suggesting involvement of NF-κB in this induction. Our data suggest that daily consumption of coffee might induce BCRP expression in the gastrointestinal tract and may affect the bioavailability of BCRP substrates.

著者

Masayuki Nadai Miki Kato Kazumasa Yasui Masao Kimura Ying Lan Zhao Jun Ueyama Yoshimi Tsunekawa Hideo Yoshizumi Takaaki Hasegawab

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.3, pp.562-568, 2007 (Released:2007-03-01)

参考文献数

49

被引用文献数

1 2 3

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There is an interesting clinical report indicating that aciclovir, which is mainly excreted into urine, decreases the systemic clearance of theophylline by inhibiting cytochrome P450 (CYP) 1A2-mediated metabolism. In this study, we investigated the effect of aciclovir on the metabolism of theophylline, and on the activity and expression of hepatic CYP1A2 in rats. Theophylline (10 mg/kg) was injected intravenously into rats treated with two different dosages of aciclovir. When theophylline was simultaneously administered with aciclovir (50 mg/kg), the systemic clearance of theophylline and metabolic clearance of its major metabolites, 1-methyluric acid and 1,3-dimethyluric acid, were unchanged. In place of theophylline, when 1-methyl-3-propylxanthine (2.5 mg/kg), which is almost metabolized by CYP1A2 in rats, was coadministered intravenously with aciclovir (50 mg/kg), the pharmacokinetics of 1-methyl-3-propylxanthine was also unchanged. When theophylline was administered to rats pretreated with repeated intraperitoneal injections of aciclovir (25 mg/kg twice daily for 3 d), no significant differences in the systemic clearance of theophylline and its metabolic clearance to 1-methyluric acid and 1,3-dimethyluric acid were observed between the control and aciclovir-treated rats. This dosage of aciclovir did not change the activity of 7-ethoxyresorufin O-dealkylation, which is represented as CYP1A2 activity. In Western blot analysis, no significant change in the protein levels of hepatic CYP1A2 was observed between the control and aciclovir-treated rats. The present study suggests that aciclovir has no effect on the pharmacokinetics and metabolism of theophylline and on the activity and expression of hepatic CYP1A2 in rats.

著者

Xiaoyan Sun Xiaobing Fu Weidong Han Yali Zhao Huiling Liu Zhiyong Sheng

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.7, pp.1037-1045, 2011-07-01 (Released:2011-07-01)

参考文献数

30

被引用文献数

18 27

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Reprogramming differentiated cells toward stem cells may have long-term applications in stem-cell research and regenerative medicine. Here we report on the dedifferentiation of human epidermal keratinocytes into their precursor cells in vitro with basic fibroblast growth factor (bFGF) but not external gene intervention. After incubation of human terminally differentiating keratinocytes, some of the surviving keratinocytes reverted from a differentiated to a dedifferentiated state, as evidenced by re-expression of biological markers of native keratinocyte stem cells (nKSCs), including β1-integrin, CK19 and CK14. Moreover, these dedifferentiation-derived KSCs (dKSCs) showed an ability for high colony formation correlated with cell cycle analysis showing a marked accumulation in S phases, acquired a similar regional distribution of both α6-integrin and CD71 expression at the ultrastructural level, and had a increased proliferative capacity by releasing telomerase from nucleolar sites to nucleoplasmic distribution. However, on comparing dKSCs with nKSCs, 2 points seem noteworthy: (1) the proportion of transit amplifying cells in dKSCs treated with bFGF is much higher than that in nKSCs and (2) regional differences exist in the subcellular localization of telomerase in nKSCs and dKSCs. Most nKSCs showed a prominent nucleolar concentration of human telomerase reverse transcriptase expression, whereas most dKSCs showed a more diffuse intranuclear distribution of telomerase or even signal depletion at nucleoli relative to the general nucleoplasm. These results indicate that bFGF could induce the terminally differentiating epidermal keratinocytes to convert into their precursor cells, which offers a new approach for generating residual healthy stem cells for wound repair and regeneration.

著者

枝野 敏行 新井 晃一 大島 武 古志 朋之 平田 光輝 大口 正夫 岡部 哲郎

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.3, pp.379-382, 1994-03-15

被引用文献数

4

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In order to identify the membrane-bound peptidase that is responsible for the degradation of endothelin (ET), an endothelin-1 (ET-1) degradation enzyme was solubilized from membrane fractions of porcine kidney with 1% Triton X-100,and subsequently purified by column chromatographies, i. e., diethylamino-Sepharose ion exchange, gel permeation, Con A Sepharose and hydroxyapatite chromatography. On DEAE-Toyopearl ion exchange column chromatography, the ET degradation enzyme and aminopeptidase were separated, but ET degradation enkephalinase activities were not separable. In order to separate ET degradation enzyme and enkephalinase, the active fractions were loaded on each of the column chromatographies : sephacryl S-200,Con A Sepharose or hydroxyapatite. The ET degradation activities were co-migrated with enkephalinase activities on all of the three chromatographies. In addition, the ET degradation activities were inhibited by thiorphan, phosphoramidon and EDTA, which are known to inhibit enkephalinase. These results suggest that ET degradation activity in the membrane fractions of the kidney is related to enkephalinase and may be involved in the degradation of ET-1 in vivo.

著者

Masago Ishikawa Ichiro Kawase Fumio Ishii

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.11, pp.2031-2036, 2007-11-01 (Released:2007-11-01)

参考文献数

37

被引用文献数

12 16

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The simplest amino acid, glycine, is important in protein composition and plays a significant role in numerous physiological events in mammals. Despite the inhibitory effect of glycine on spontaneous melanogenesis in B16F0 melanoma cells, the details of the underlying mechanisms remain unknown. The present study was conducted to investigate the further effects and the mechanisms of inhibitory effect of glycine on melanogenesis using B16F0 melanoma cells and hair follicle melanogenesis in C57BL/6J mice. Treatment with glycine (1—16 mM) for 72 h inhibited α-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in a concentration-dependent manner without any effects on cell proliferation in B16F0 melanoma cells. Treatment with kojic acid (2.5 mM) for 72 h also inhibited α-MSH-induced melanogenesis in B16F0 melanoma cells. The highest dose of glycine inhibited the α-MSH-induced increment of tyrosinase protein levels in B16F0 melanoma cells. In hair follicle melanogenesis in C57BL/6J mice, treatment with glycine (1250 or 2500 mg/kg, i.p.) for 5 d prevented the decrement of L* and C* values and inhibited the increment of tyrosinase protein levels and melanin content within the skin. Treatment with hydroquinone (100 mg/kg, i.p.) for 5 d had a similar hypopigmenting effect to that of high dose glycine. These results suggest that glycine has an inhibitory effect on melanogenesis that is mediated by down-regulation of tyrosinase protein levels, leading to a hypopigmenting effect in C57BL/6J mice.

著者

Masago Ishikawa Ichiro Kawase Fumio Ishii

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.4, pp.677-681, 2007 (Released:2007-04-01)

参考文献数

34

被引用文献数

18 23

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Amino acids, the building blocks of proteins, play significant roles in numerous physiological events in mammals. As the effects of amino acids on melanogenesis have yet to be demonstrated, the present study was conducted to identify whether amino acids, in particular alanine, glycine, isoleucine and leucine, influence melanogenesis in B16F0 melanoma cells. Glycine and L-isoleucine, but not D-isoleucine, reduced melanogenesis in a concentration-dependent manner without any morphological changes in B16F0 melanoma cells. L-Alanine and L-leucine, but not D-alanine and D-leucine, also reduced melanogenesis without any morphological changes in B16F0 melanoma cells. However these amino acids did not show a concentration-dependency. Combination of L-alanine and the other amino acids, particularly 4 amino acids combination, had an additive effect on the inhibition of melanogenesis compared with single treatment of L-alanine. None of the amino acids affected the activity of tyrosinase, a key enzyme in melanogenesis. These results suggest that L-alanine, glycine, L-isoleucine and L-leucine, but not the D-form amino acids, have a hypopigmenting effect in B16F0 melanoma cells, and that these effects are not due to the inhibition of tyrosinase activity. Combination of these 4 amino acids had the additive effect on hypopigmentation that was as similar as that of kojic acid.

著者

松本 陽子 今村 主税 伊藤 貴俊 谷口 智穂 上岡 龍一

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.18, no.10, pp.1456-1458, 1995-10-15

被引用文献数

15 31

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The hybrid liposomes (90mol% DMPC/10mol% C_<12> (EO)_8 and 90mol% DMPC/10mol% C_<12> (EO)_<12>) have a highly inhibitory action against the growth of tumor cells. The uniform and stable structure of the hybrid liposomes was revealed on the basis of electron microscopy and dynamic light scattering measurements.

著者

Munehiro Nakagawa Takamasa Ohno Rumi Maruyama Munenori Okubo Akito Nagatsu Makoto Inoue Hiroki Tanabe Genzou Takemura Shinya Minatoguchi Hisayoshi Fujiwara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.9, pp.1754-1757, 2007-09-01 (Released:2007-09-01)

参考文献数

27

被引用文献数

5 12

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Abnormal vascular smooth muscle cell (VSMC) proliferation and migration are involved in restenosis following percutaneous transluminal angioplasty (PTCA) as well as in the development and progression of atherosclerosis. We investigated the mechanisms underlying the inhibitory effect of the sesquiterpene 3-oxo-5αH,8βH-eudesma-1,4(15),7(11)-trien-8,12-olide (1) on rat VSMC proliferation and migration. VSMCs were isolated from rat aorta, and then the effect of 1 on cell proliferation and migration was examined using methylthiazolyldiphenyl-tetrazolium bromide (MTT) and chemotaxis assays, respectively. Compound 1 had a potent inhibitory effect on fetal calf serum-induced VSMC proliferation. This effect correlated with reduced expression of cyclin D1. In addition, 1 also inhibited platelet derived growth factor (PDGF)-induced migration of VSMCs. These results indicate that 1 is a promising candidate for additional biological evaluation to further define its potential as an inhibitory modulator of VSMC responses that contribute to restenosis following PTCA and to the development and progression of atherosclerosis.

著者

Hideki Sasaki Hiroshi Akiyama Yoshifumi Yoshida Kazunari Kondo Yoshiaki Amakura Yoshimasa Kasahara Tamio Maitani

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.29, no.12, pp.2514-2518, 2006 (Released:2006-12-01)

参考文献数

21

被引用文献数

15 20

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In autumn 2004, many Japanese patients with renal failure developed cryptogenic encephalopathy by consuming sugihiratake mushroom, a Japanese delicacy. To elucidate the relationship between the cryptogenic cases and this mushroom, we conducted a multivariate analysis of metabolites in ‘Probably Toxic’ sugihiratake collected from the area of encephalopathy outbreaks, and ‘Probably Safe’ sugihiratake collected from unaffected areas using UPLC/ToF MS. The results indicate that the presence of milligram quantities of vitamin D-like compounds per 10 g of dried sugihiratake from the areas of encephalopathy outbreaks. Two hypotheses to induce the encephalopathy are proposed: the found metabolites are (1) vitamin D agonists, which induce acute and severe hypercalcemia and/or hyperammonemia and/or vitamin D toxicity, or (2) vitamin D antagonists, which induce acute and severe hypocalcemia.

著者

Liu Ke-Xin Kato Yukio Kaku Tai-ichi SUGIYAMA Yuichi

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.21, no.1, pp.44-49, 1998-01-15

被引用文献数

3 50

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The effect of human placental extract (HPE) on liver regenaration in rats was investigated. After intravenous administration of HPE to α-naphthylisothiocyanate (ANIT)-intoxicated rats, the labeling index in hepatocytes was significantly increased to a level 16.5 times higher than that of the control. A 1/500 dilution of HPE directly stimulated DNA synthesis of the hepatocytes in primary culture. HPE heated at 121℃ did not stimulate the labeling index in vivo or hepatocyte DNA synthesis in primary culture, suggesting that HPE contains heatunstable but potent mitogens for hepatocytes. HPE contains hepatocyte growth factor (HGF), but the mitogenic effect of HPE cannot be explained by the effect exerted by HGF alone, since both the labeling index in vivo and hepatocellular DNA synthesis in vitro stimulated by HPE were much higher than those stimulated by HGF alone when the applied doses of HGF were set to be almost the same level between each case. When HPE was fractionated on a heparin-sepharose column, the mitogenic effect of HPE was found to be located mainly in the heparin-bound fraction. Hepatocyte DNA synthesis induced by this fraction was enhanced cooperatively by the heparin-unbound fraction, suggesting that there are some modulators in the heparin-unbound fraction which enhance the proliferative activity of the heparin-bound fraction by a synergetic mechanism. Both HPE and heated HPE completely recovered the biochemical marker activity for liver function (glutamic-pyruvic transaminase, GPT;alkaline phosphatase, ALP; lactate dehydrogenase, LAP; γ-glutamyltransferase, γ-GTP activities and the bilirubin concentration) almost to the control level in the serum of ANIT-intoxicated rats, indicating that HPE also contains a heat-stable fraction which repairs liver function.

著者

白井 寿海 十川 清己 山本 和充 児島 健次 藤岡 弘 牧田 浩和 中村 康彦

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.16, no.2, pp.172-177, 1993

被引用文献数

7 39

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In order to prepare fine granules of sparfloxacin (SPFX), a new quinolone anti-bacterial drug that shows masking of the bitter taste of SPFX and dissolutes at a rapid rate, various film-coated fine granules containing 20% SPFX and 0-52% low-substituted hydroxypropylcellulose(L-HPC) in the cores, were prepared by a spray method. Mixtures of ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC), titanium dioxide and sucrose stearate in weight ratios of X : Y : 2 : 1 (X+Y=6) were used as film materials.The degree of masking of the bitter taste by water-insoluble film, mainly consisting of EC and HPMC, increased by increasing the content ratio of EC to HPMC and the amount of films, but was also slightly affected by the amount of L-HPC in the cores, which were coated with either EC or EC/HPMC (4/2). On the other hand, the dissolution rate increased with an increased amount of L-HPC in the cores and with a decreasing ratio of EC to HPMC in the films. Increasing the amount of L-HPC in the cores, which induced a considerable expansion of the fine granules owing to their taking up of water from the dissolution medium, resulted in burstin of the film after a short lag time. The bioavailability of the film-coated fine granules containing 20% SPFX and 52% L-HPC in the cores and 10% EC/HPMC (4/2) in the coating film, which masked the bitter taste of SPFX and showed the optimal release characteristics, was equivalent to that of conventional tablets containing 100 mg SPFX in beagle dogs.

著者

Minematsu Tsuyoshi Ohtani Hisakazu Sato Hitoshi IGA Tatsuji

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.22, no.12, pp.1341-1346, 1999-12-15

被引用文献数

1 7

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Recently, several reports of clinical cases of QT prolongation and torsades de pointes, associated with the use of tacrolimus (FK506), have come to light. We have previously demonstrated FK506-induced QT prolongation in guinea pigs [Minematsu T., et al., Life Sci., 65,PL197-PL202 (1999)]. We now examined the relationship between QTc prolongation and the pharmacokinetics of FK506 in guinea pigs, in order to evaluate the arrhythmogenicity of FK506 when compared with that of quinidine sulfate (QND). Thus, dose-response relationships for FK506 (0.01 or 0.1 mg/h/kg) or QND (30 mg/h/kg) were investigated during and after intravenous infusion and also following intravenous bolus administration of FK506 (0.2mg/kg). The dose-response relationship between plasma drug concentration and QTc prolongation for FK506 and QND were subsequently analyzed using an effect compartment model. The pharmacodynamic parameters thus obtained were as follows : k_<E0> 2.72×10^<-4> (min^<-1>), E_<max> 27.1 (ms), EC_<50> 0.376 (ng/ml) for FK506; and k_<E0> 0.148 (min^<-1>), K 8.41 (ms・ml/μg) for QND. The anti-clockwise hysteresis observed for FK506-induced QT prolongation was successfully analyzed by the present pharmacokinetic/pharmacodynamic model, which may provide a rational basis for developing a clinical dosing regimen to avoid possible QT prolongation induced by FK506.