詳細検索結果
以下の条件での結果を表示する:
全文: "Mifepristone"
85件中 1-20の結果を表示しています
  • Ning Wang, Hui Zhao, Weitian Han, Bin He, Shucheng Zhang, Jiedong Wang
    The Tohoku Journal of Experimental Medicine
    2010年 220 巻 1 号 77-82
    発行日: 2010年
    公開日: 2009/12/29
    ジャーナル フリー
    Mifepristone is a synthetic steroid compound that has been applied to terminate early pregnancy for many years. However, about 15% of the women undergo failure in termination of early pregnancy, the causes of which remain largely unknown. We herein selected estrogen receptor 1 gene (ESR1) as a candidate gene to determine whether single nuclear polymorphisms (SNPs) in ESR1 were associated with the failure of mifepristone-induce abortion. The subjects recruited were 30 subjects that failed to abort and 60 subjects with a successful medical abortion. Three SNPs, T-397C (rs2234693), C325G (rs1801132), and G2014A (rs2228480), were analyzed by PCR, followed by restriction fragment length polymorphism (RFLP) analysis. The latter two polymorphic sites are located in the protein-coding region, but do not alter the amino acid. Among the three SNPs examined, we found the significant role of the G2014A polymorphism; namely, the distribution of the GG, AG and AA genotypes was different between the failure group and the success group. The frequency of the GG (G2014G) genotype was higher in the failure group (86.7%) than that in the success group (60.0%) (p = 0.030), while the frequency of the G2014A heterozygote was lower in the failure group (6.7%) than in the success group (28.3%) (p = 0.013). Moreover, the frequency of the G allele was higher in the failure group (90%) and lower in the success group (10.0%) (p = 0.013). These results indicate that the GG genotype of the G2014A polymorphism is associated with the risk of failure in the mifepristone-induced abortion.
  • Yoshihiko Nakatani, Taku Amano, Hiroshi Takeda
    Biological and Pharmaceutical Bulletin
    2016年 39 巻 7 号 1121-1129
    発行日: 2016/07/01
    公開日: 2016/07/01
    ジャーナル フリー HTML
    Astroglial cells have been considered to have passive brain function by helping to maintain neurons. However, recent studies have revealed that the dysfunction of such passive functions may be associated with various neuropathological diseases, such as schizophrenia, Alzheimer’s disease, amyotrophic lateral sclerosis and major depression. Corticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the brain. However, it is still obscure how CORT affects astroglial cell function. In this study, we investigated the effects of CORT on the proliferation and survival of astroglial cells using C6 glioma cells. Under treatment with CORT for 24h, the proliferation of C6 glioma cells decreased in a dose-dependent manner. Moreover, this inhibition was diminised by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist, and was independent of GR phosphorylation and other GR-related intracellular signaling cascades. Furthermore, it was observed that the translocation of GR from the cytosol to the nucleus was promoted by the treatment with CORT. These results indicate that CORT decreases the proliferation of C6 glioma cells by modifying the transcription of a particular gene related to cell proliferation independent of GR phosphorylation.
  • Shigekazu Watanabe, Jun Yamakami, Masao Tsuchiya, Tomoko Terajima, Junko Kizu, Seiji Hori
    Journal of Pharmacological Sciences
    2008年 106 巻 4 号 566-570
    発行日: 2008年
    公開日: 2008/04/19
    [早期公開] 公開日: 2008/04/05
    ジャーナル フリー
    Although theophylline has been suggested to have an anti-inflammatory effect, there have been few reports to show the in vivo effect and the mechanism of anti-inflammatory activity of theophylline experimentally. To reveal the anti-inflammatory activity of theophylline, we studied the effect of theophylline and its metabolites on carrageenan-induced edema in rat foot pad. Subcutaneous injection of theophylline (5 – 100 mg/kg) inhibited carrageenan-induced edema dose-dependently. Theophylline metabolites, that is, 1-methylxanthine, 3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid (equimolar dose to 50 mg/kg of theophylline), did not inhibit the edema significantly. The inhibitory effect of theophylline on carrageenan-induced edema disappeared by pretreatment with aminoglutethimide, an inhibitor of glucocorticoid synthesis and with mefepristone, an antagonist of the glucocorticoid receptor. These results suggest that theophylline itself has anti-inflammatory activity and the glucocorticoid–glucocorticoid receptor system is involved in the anti-inflammatory activity of theophylline.
  • Yoshihiko Nakatani, Taku Amano, Hiroshi Takeda
    Biological and Pharmaceutical Bulletin
    2013年 36 巻 4 号 592-601
    発行日: 2013/04/01
    公開日: 2013/04/01
    [早期公開] 公開日: 2013/02/06
    ジャーナル フリー HTML
    Macrophages are white blood cells within tissues that are produced by monocytes and help to protect against infection by bacteria through phagocytosis. Several studies have shown a correlation between the state of depression and abnormalities in the immune response. Corticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the body. However, it is still unclear how CORT regulates macrophage function. In this study, we focused on the effects of CORT on the proliferation and survival of macrophage cells using the macrophage cell line RAW264.7. Under treatment with 10 µm CORT for 24 h, the proliferation of RAW264.7 cells decreased to 73.6% of that in the control. Moreover, this inhibition was blocked by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist. In an lactate dehydrogenase (LDH) assay, CORT did not show any cytotoxic effect on RAW264.7 cells. JC-1 cell staining also showed that CORT did not influence mitochondrial dysfunction in RAW264.7 cells. In an investigation of the modulation of a signaling cascade by CORT, treatment with CORT promoted the translocation of GR, but not MR, from the cytosol to the nucleus in RAW264.7 cells. In conclusion, our findings suggest that CORT suppresses the proliferation of RAW264.7 cells by controlling the transcription of a particular gene, which is related to cell proliferation, through the formation of a CORT–GR complex.
  • Takashi Nakahari, Ayumi Nishimura, Chikao Shimamoto, Akiko Sakai, Hiroko Kuwabara, Takashi Nakano, Saori Tanaka, Yuka Kohda, Hitoshi Matsumura, Hiroshi Mori
    Biomedical Research
    2011年 32 巻 5 号 321-328
    発行日: 2011年
    公開日: 2011/10/28
    ジャーナル フリー
    Ciliary beat frequency (CBF) was measured in slice preparations of the Fallopian tube fimbria, using videomicroscopy with a high-speed (500 Hz) camera in guinea pigs that were treated with β-oestradiol benzoate (βE2B) and medroxy progesterone (mPRG). In non-ovulating guinea pigs at 4 weeks of age, the CBF of the fimbria was high (17.8 Hz). In sexually mature guinea pigs (12- 16 weeks of age) with constant ovulation, the CBF varied from 12 Hz to 16 Hz. The in vivo administration of both ICI-182,780 (a blocker of βE2 receptors) and mifepristone (a blocker of PRG receptors) induced high CBF (17.4 Hz). The administration of βE2B at a low (3.2 mg/kg/day) or high (32 mg/kg/day) dose decreased the CBF to 14.5 Hz or 11 Hz, respectively. ICI-182,780 abolished the βE2B-induced changes in CBF and decreased CBF to 12 Hz. The administration of mPRG (6.4 mg/kg/day) decreased CBF to 12.5 Hz. Mifepristone abolished this mPRG-induced decrease in CBF and maintained the CBF at 15 Hz. However, administering both βE2B and mPRG increased CBF to 17.5 Hz, suggesting that βE2B inhibits mPRG actions and vice versa. To confirm the interactions between &beat;E2B and mPRG, we administered both βE2B and mPRG to guinea pigs that were pretreated for 1.5 days with either mPRG (6.4 mg/kg/day) or βE2B (3.2 mg/kg/day). Prior treatment with βE2B or mPRG prevented the increase in CBF that was otherwise by βE2B plus mPRG, and maintained the CBF at 14.5 Hz or 13 Hz, respectively. The administration of βE2B plus mPRG still induced the expression of PRG receptors, indicating that the highest CBF is not the result of no expression of the receptors. In the beating cilia of the fimbria, the signals that are activated by the βE2 and PRG receptors are proposed to antagonize each other in regulating the frequency.
  • 亀山 貴一, 角田 出
    日本水産学会誌
    2007年 73 巻 5 号 867-871
    発行日: 2007年
    公開日: 2007/10/03
    ジャーナル フリー
    コルチゾルと RU486 の腹腔内(100 mg/kg 体重の割合で隔週 2 回)または経口(100 mg/kg 体重/日で 6 週間)投与が,全長 80~200 mm のヒラメの黒化に及ぼす影響を調べた。黒化率は,対照区に比べ,コルチゾル区で低く,RU486 区で高い傾向にあった。両区の血中コルチゾル濃度は有意に上昇した。本結果は,着色型黒化の発現に HPI 系の活性化(ACTH や αMSH の分泌亢進)が関与することを示唆する。
  • Mitsutoshi Kimura, Hajime Moteki, Masahiko Ogihara
    Biological and Pharmaceutical Bulletin
    2011年 34 巻 5 号 682-687
    発行日: 2011/05/01
    公開日: 2011/05/01
    ジャーナル フリー
    We investigated the effects of dexamethasone on epidermal growth factor (EGF)-induced DNA synthesis and proliferation in serum-free primary cultures of adult rat hepatocytes. Isolated hepatocytes were cultured at a density of 3.3×104 cells/cm2 in Williams' medium E containing 5% bovine calf serum and various concentrations of dexamethasone for 1, 2 and 3 h. After the 3-h attachment period, the medium was changed, and cells were cultured in serum-free and dexamethasone-free Williams' medium E with or without glucocorticoid receptor antagonists. The growth-stimulating effects of EGF (20 ng/ml) on the primary cultured hepatocytes were time- and concentration-dependently inhibited by dexamethasone added to the culture medium. The mineral corticoid aldosterone (10−7 M) did not produce the same growth-inhibitory effects as dexamethasone (10−8 M). The inhibitory effects of dexamethasone were reversed by treatment with the glucocorticoid receptor antagonist mifepristone (RU486, 10−6 M) or a monoclonal antibody against glucocorticoid receptor (100 ng/ml). In addition, the growth-inhibitory effects of dexamethasone did not affect EGF-induced p42 mitogen-activated protein (MAP) kinase phosphorylation. These results indicate that dexamethasone concentration-dependently delays and inhibits the EGF-induced DNA synthesis and proliferation through its own intracellular receptor in primary cultures of adult rat hepatocytes.
  • Tomoyoshi Miyamoto, Yoshinori Funakami, Erika Kawashita, Ai Nomura, Nanako Sugimoto, Haruka Saeki, Maho Tsubota, Seiji Ichida, Atsufumi Kawabata
    Biological and Pharmaceutical Bulletin
    2017年 40 巻 1 号 11-16
    発行日: 2017/01/01
    公開日: 2017/01/01
    ジャーナル フリー HTML

    The rodents exposed to repeated cold stress according to a specific schedule, known as specific alternation of rhythm in temperature (SART), exhibit autonomic imbalance, and is now used as an experimental model of fibromyalgia. To explore the susceptibility of SART-stressed animals to novel acute stress, we tested whether exposure of mice to SART stress for 1 week alters the extent of acute restraint stress-induced hyperthermia. Mice were subjected to 7-d SART stress sessions; i.e., the mice were alternately exposed to 24 and 4°C at 1-h intervals during the daytime (09:00–16:00) and kept at 4°C overnight (16:00–09:00). SART-stressed and unstressed mice were exposed to acute restraint stress for 20–60 min, during which rectal temperature was monitored. Serum corticosterone levels were measured before and after 60-min exposure to restraint stress. SART stress itself did not alter the body temperature or serum corticosterone levels in mice. Acute restraint stress increased the body temperature and serum corticosterone levels, both responses being greater in SART-stressed mice than unstressed mice. The enhanced hyperthermic responses to acute restraint stress in SART-stressed mice were significantly attenuated by SR59230A, a β3 adrenoceptor antagonist, but unaffected by diazepam, an anxiolytic, mifepristone, a glucocorticoid receptor antagonist, or indomethacin, a cyclooxygenase inhibitor. These results suggest that SART stress enhances the susceptibility of mice to acute restraint stress, characterized by increased hyperthermia and corticosterone secretion, and that the increased hyperthermic responses to acute stress might involve accelerated activation of sympathetic β3 adrenoceptors, known to regulate non-shivering thermogenesis in the brown adipose tissue.

  • Bruno Carbonne
    Hypertension Research in Pregnancy
    2014年 2 巻 2 号 59-64
    発行日: 2014年
    公開日: 2015/02/06
    ジャーナル オープンアクセス HTML
    Cervical maturation is one of the key events in the process of labor, either at term or preterm. The mechanisms involved in cervical ripening start early in pregnancy and increase near parturition. The main changes occur in the cervical connective tissue, mainly the extracellular matrix. They include disorganization of collagen network, increase in hyaluronic acid, increased water content and changes in the proteoglycan content, leading to dramatic changes in the consistency of the cervix.
    The pharmacologic control of the cervical ripening process is of major interest, either to allow labor induction in case of an unfavorable cervix, or to prevent preterm delivery in case of premature cervical shortening.
    Many substances are known to play a role in the physiologic and pathologic processes of cervical ripening: prostaglandins, relaxin, nitric oxide and inflammatory cytokines may induce cervical priming whereas progesterone play an inhibitory role in the process of cervical ripening and labor induction.
    Based on these pathophysiological data, several compounds and/or interventions have been proposed to induce or conversely to prevent cervical ripening and labor with uneven success. Data from recent studies on cervical maturation and labor induction in case of unripe cervix are presented in this review.
  • Yoichi NARITOMI, Yuriko TERAMURA, Shigeyuki TERASHITA, Akira KAGAYAMA
    Drug Metabolism and Pharmacokinetics
    2004年 19 巻 1 号 55-61
    発行日: 2004年
    公開日: 2004/10/20
    ジャーナル フリー
      In this study, a simple in vitro method for detecting human P450 (CYP) quasi-irreversible and irreversible inhibitors was evaluated. For the method, cDNA-expressed CYPs were applied to microtiter plate assays, CYP inhibitors were co-incubated with fluorometric substrates, and IC50 were continuously measured (without stopping enzyme reactions). The typical reversible inhibitors (sulfaphenazole, tranylcypromine, quinidine, ketoconazole) showed constant IC50 throughout the reaction. In contrast, the typical quasi-irrversible inhibitors (isosafrole, erythromycin, troleandomycin, diltiazem) and the typical irreversible inhibitors (furafylline, propranolol, mifepristone) showed time-dependent decreases in IC50. For CYP3A4 inhibition studies, two substrates, 7-benzyloxyresorufin (BzRes) and 7-benzyloxy-4-trifluoromethyl-coumarin (BFC), were used. The IC50 of the CYP3A4 inhibitors were dependent on the substrate. However, the quasi-irreversible and irreversible inhibitors could be detected by examining changes in the IC50, regardless of the substrate. Further, the detection method was applied to josamycin and bergamottin. Josamycin did not show definite time-dependent decreases in IC50 for CYP 3A4, suggesting that josamycin is neither a quasi-irrversible nor an irreversible inhibitor of CYP3A4. On the other hand, bergamottin showed time-dependent decreases in IC50 for CYP1A2, CYP 2C9, CYP 2C19, CYP 2D6 and CYP 3A4, suggesting that bergamottin is a quasi-irrversible or an irreversible inhibitor of the 5 CYP isoforms. This method provides more rapid and reliable detection of quasi-irreversible and irreversible inhibitors and may be useful in drug discovery.
  • Shinsuke Suzuki, Tomoko Ohkusa, Takashi Sato, Masaaki Yoshida, Kenji Yasui, Keiko Miwa, Jong-Kook Lee, Masafumi Yano, Itsuo Kodama, Masunori Matsuzaki
    Circulation Journal
    2009年 73 巻 8 号 1504-1512
    発行日: 2009年
    公開日: 2009/07/24
    [早期公開] 公開日: 2009/06/16
    ジャーナル フリー
    Background: The renin-angiotensin-aldosterone system affects cellular morphology and function in the heart under a variety of pathologic conditions. In the present study the effects of aldosterone on the expression of connexin (Cx) 43 gap junctions in cardiomyocytes were investigated. Methods and Results: Cultured rat ventricular myocytes were exposed to aldosterone for 24 h. The protein and mRNA expression of Cx43 was estimated. Propagation of excitation was visualized by a multiple electrode array system. Treatment of the myocytes with 10-8 mol/L aldosterone resulted in a significant upregulation of Cx43 (by ~1.5-fold in protein and by ~1.2-fold in mRNA). The immunoreactive signal of Cx43 was also increased. Conduction velocity (CV) was increased by ~24%. Treatment of the myocytes with aldosterone at higher concentrations (10-6-10-4 mol/L) caused a significant downregulation of Cx43 protein (by ~0.3-fold) without affecting Cx43 mRNA levels, and decreased the CV by ~23%. The Cx43 upregulation and CV acceleration at 10-8 mol/L aldosterone were prevented by pretreatment with eplerenone, but unaffected by mifepristone. Pretreatment of the myocytes with eplerenone or mifepristone did not prevent the Cx43 downregulation by aldosterone at 10-6-10-4 mol/L. Conclusions: Aldosterone may be involved in arrhythmogenic gap junction remodeling through its dual effects on the expression of Cx43. (Circ J 2009; 73: 1504 - 1512)
  • Kotaro YOKOYAMA, Mahoko HAYASHI, Chihiro MOGI, Yoshihiro SASAKAWA, Gen WATANABE, Kazuyoshi TAYA, Sukumar DEVNATH, Kinji INOUE
    Endocrine Journal
    2008年 55 巻 2 号 405-414
    発行日: 2008年
    公開日: 2008/05/10
    [早期公開] 公開日: 2008/04/01
    ジャーナル フリー
    Glucocorticoids are known to stimulate growth hormone (GH) production but to suppress prolactin (PRL) production. However, previous data were obtained with rather high doses of corticosterone. In this study we examined the effects of various doses (10 -12 -10 -7 M) of corticosterone on GH and PRL production in a rat pituitary somatomammotropic cell line, MtT/SM cells, and found that GH mRNA expression was facilitated by high doses (10 -7 and 10 -8 M). In contrast, a biphasic effect of corticosterone on PRL mRNA expression and secretion was observed, i.e., high doses (10 -7 and 10 -8 M) suppressed and low doses (10 -12 -10 -10 M) facilitated them. In an immunofluorescent staining study, the number of PRL immunopositive cells increased with low doses of corticosterone while it decreased with high doses of it, which corresponded to PRL mRNA expression and hormone secretion, respectively. These effects of corticosterone on PRL production were abolished by a glucocorticoid receptor (GR) antagonist, mifepristone. In addition, co-treatment with low doses of corticosterone (10 -12 -10 -10 M) and 17β-estradiol (E2, 10 nM) additively increased the number of PRL immunopositive cells. Moreover, a 24 h BrdU incorporation experiment suggested that the increase in the number of PRL immunopositive cells treated with low dose corticosterone was caused by novel synthesis of PRL while, on the other hand, that of those treated with E2 resulted from PRL cell proliferation. Thus, we concluded that corticosterone biphasically regulates PRL production and the sensitivity of E2 to different degrees.
  • Mitsutoshi Kimura, Hajime Moteki, Masahiko Ogihara
    Journal of Pharmacological Sciences
    2011年 115 巻 3 号 390-398
    発行日: 2011年
    公開日: 2011/03/17
    [早期公開] 公開日: 2011/02/22
    ジャーナル フリー
    We investigated the effects of dexamethasone on hepatocyte growth factor (HGF)-induced DNA synthesis and proliferation in serum-free primary cultures of adult rat hepatocytes. Isolated hepatocytes were cultured at a density of 3.3 × 104 cells/cm2 in Williams’ medium E containing 5% newborn bovine serum and various concentrations of dexamethasone for 1, 2, and 3 h. After a 3-h attachment period, the medium was then changed, and cells were cultured in serum-free dexamethasone (10−10 M)-containing Williams’ medium E with or without glucocorticoid receptor antagonists. After addition of dexamethasone to the culture medium, the growth-stimulating effects of HGF (5 ng/mL) on the primary cultured hepatocytes were time- and dose-dependently inhibited. The mineralcorticoid aldosterone (10−7 M) did not produce the same growth-inhibitory effects as dexamethasone (10−8 M). The inhibitory effects of dexamethasone were reversed by treatment with the glucocorticoid-receptor antagonist mifepristone (RU486, 10−6 M) or a monoclonal antibody against glucocorticoid receptor (100 ng/mL). In addition, the growth-inhibitory dose of dexamethasone did not affect HGF-induced receptor tyrosine kinase and extracellular signal-regulated kinase 2 phosphorylation. These results indicate that dexamethasone dose-dependently delays and inhibits HGF-induced DNA synthesis and proliferation through its own intracellular receptor in primary cultures of adult rat hepatocytes.
  • Jun SHIMIZU, Masayoshi MATSUMOTO, Etsuo YAMAZAKI, Masaharu YASUE
    Neurologia medico-chirurgica
    2008年 48 巻 5 号 227-230
    発行日: 2008年
    公開日: 2008/05/23
    ジャーナル オープンアクセス
    An 80-year-old male visited the hospital as an outpatient with a head injury sustained in a traffic accident. Brain computed tomography incidentally revealed a left frontal lobe tumor measuring 5 cm in a diameter. The patient had a history of taking chlormadinone acetate (a progesterone agonist) prescribed several years previously as treatment for benign prostatic hypertrophy. The tumor was seen as an isointense lesion on T1-weighted magnetic resonance (MR) images with enhancement by gadolinium, and as a heterogeneously hyperintense mass on T2-weighted MR images. The tentative diagnosis was left frontal meningioma attached to the sphenoid ridge or sphenoid plane. The patient was managed conservatively because of his advanced age and no symptoms or progression were observed during a 9-month follow-up period. The medication for benign prostatic hypertrophy was changed from chlormadinone acetate to naftopidil (an alpha-2-blocker) about 9 months after his first presentation. The patient presented again 2 years later complaining of dizziness. Computed tomography and MR imaging performed at this time revealed remarkable regression of the tumor. The signal intensity change with regression of the tumor on T2-weighted images was observed as a hypointense lesion. Thus, we wish to emphasize that treatment of meningiomas, especially those diagnosed incidentally, must be based on a thorough consideration of any history of hormonal therapy with prostate disease.
  • Xiumin Zhang, Mitsuharu Okutsu, Osamu Kanemi, Bahiru Gametchu, Ryoichi Nagatomi
    The Tohoku Journal of Experimental Medicine
    2005年 206 巻 3 号 203-212
    発行日: 2005年
    公開日: 2005/06/07
    ジャーナル フリー
    Intestinal intraepithelial lymphocytes (IEL), one of the major effector components in the mucosal immune system, are phenotypically and functionally distinct from thymic and peripheral T cells. To investigate the effect of repeated stress on the number and function of IEL, we exposed male C3H/HeN mice to mild electric foot shock for 30 min/day for 5 consecutive days. Immediately after the final foot shock stress, the blood, spleen, thymus and small intestine of each of the mice were obtained. As a functional measure, we evaluated interferon (IFN)- γ production by IEL, since IFN-γ is a key immunomodulating cytokine in mucosal immune responses. Serum corticosterone level was elevated immediately after foot shock stress. There were no significant changes in the number of whole IEL and CD3+ IEL subsets after the stress. In contrast, the stress led to a significant decrease in the total number of thymocytes, particularly the reduction in the number of CD4+CD8+ thymocytes. Thymocytes expressed the highest level of intracellular glucocorticoid receptor (GR), followed by splenocytes and IEL. The foot shock stress induced a marked suppression of IFN-γ production by IEL, when stimulated with immobilized anti-CD3 monoclonal antibody. Furthermore, corticosterone suppressed the IFN-γ production by cultured IEL, which was prevented by Mifepristone (RU486), a GR antagonist. In summary, repeated foot shock stress did not alter the numbers of IEL and CD3+ IEL subsets, but suppressed IFN-γ production by IEL, which was probably mediated by the elevated corticosterone. We therefore propose that stress influences host defense by suppressing the production of IFN-γ in IEL.
  • Min LIU, Jiajie HU, Tian MA, Shi WANG, Hong DING
    Analytical Sciences
    2011年 27 巻 8 号 839
    発行日: 2011/08/10
    公開日: 2011/08/10
    ジャーナル フリー
    No exact and digital diagnostic methods for depression have been found. In this study, we prepared a 5-HT biosensor based on screen-printed electrode and applied it to a rat depression model caused by chronic unpredictable mild stress (CUMS). During CUMS, the blood 5-HT and the depression behavior of the depressed rats and the rats treated by antidepressants were recorded. The correlation coefficient of 5-HT was 0.9966 (0 – 4 × 10−6 M) on the sensor. Results demonstrated that 5-HT level of the depressed rats declined while the depression behavior was aggravated. Fluoxetine (20 mg/kg) and lentinan (10, 20 mg/kg) mildly elevated 5-HT level and slowly regulated the behavior. Mifepristone (20 mg/kg) and Rhizoma Coptidis water extract (10, 20, 100 mg/kg) quickly reversed 5-HT level and the depression behavior. This sensor can accurately test blood 5-HT and might be applied to rapid diagnosis for depression and evaluation of antidepressants effect.
  • Kaoru Kubo, Taizo Kita, Takahiro Tsujimura, Toshikatsu Nakashima
    Journal of Pharmacological Sciences
    2004年 94 巻 1 号 31-38
    発行日: 2004年
    公開日: 2004/01/27
    ジャーナル フリー
    To elucidate the anti-inflammatory action of nicotine-induced corticosterone elevation on the passive skin Arthus reaction (PSAR), we investigated the inflammatory process in the PSAR. The polymorphonuclear leukocyte (PMNs) infiltration was observed just before as well as after elicitation by measuring extractable myeloperoxidase. The plasma exudation was significantly inhibited by anti-rat tumor necrosis factor (TNF)-α antibody (5 μg/site, i.d.) at the time of sensitization or by superoxide dismutase (52500 units/kg, i.p.) 1 h before elicitation or NG-nitro-L-arginine-methyl ester (100 mg/kg, i.v.) just at elicitation. Pretreatment with a single injection of nicotine (0.8 mg/kg, i.p.) 30 min before elicitation suppressed the plasma exudation but not the PMNs infiltration. This nicotine-induced decreasing effect was abolished in animals supplemented with L-arginine (300 mg/kg, i.v.) just at elicitation. The production of nitric oxide (NO) in peritoneal PMNs derived from an animal injected peritoneally with oyster glycogen was significantly suppressed by pretreatment with nicotine (0.8 mg/kg, i.v.) 30 min prior to harvesting. This inhibitory action of nicotine was abolished in animals pretreated with mifepristone (30 mg/kg, s.c.), a glucocorticoid receptor antagonist. These findings indicate that a single systematic administration of nicotine may attenuate the plasma exudation in the PSAR by suppressing the production of NO in the PMNs primed with TNF-α via nicotine-induced endogenous glucocorticoid.
  • Makoto Shuto, Kei Higuchi, Chie Sugiyama, Masanori Yoneyama, Nobuyuki Kuramoto, Reiko Nagashima, Koichi Kawada, Kiyokazu Ogita
    Journal of Pharmacological Sciences
    2009年 110 巻 4 号 424-436
    発行日: 2009年
    公開日: 2009/08/11
    [早期公開] 公開日: 2009/07/14
    ジャーナル フリー
    The organotin trimethyltin (TMT) is known to cause neuronal degeneration in the murine brain. Earlier studies indicate that TMT-induced neuronal degeneration is enhanced by adrenalectomy. However, no evaluation has been attempted to determine the mechanism underlying the enhancement of TMT neurotoxicity by adrenalectomy and its implications in neuronal degeneration. To assess the implications and determine the mechanism of adrenalectomy-elicited enhancement of TMT neurotoxicity, we examined neuronal degeneration and associated signaling pathways in adrenalectomized mice. Adrenalectomy dramatically enhanced the TMT-induced neuronal damage in certain brain regions including the dentate gyrus, olfactory bulb, and anterior olfactory nucleus, in addition to exacerbating the behavioral abnormalities. TMT-induced activation of caspase-3 and calpain was also enhanced by adrenalectomy. The above events elicited by TMT were almost entirely prevented by treatment with dexamethasone. In addition to the above events, adrenalectomy clearly enhanced the activation of c-Jun-N-terminal kinases and the formation of 4-hydroxynonenal in the dentate gyrus following TMT treatment. The dentate granule cell damage induced by TMT was exacerbated by mifepristone, a glucocorticoid-receptor antagonist. Taken together, our data suggest that endogenous and exogenous glucocorticoids prevent neurodegeneration induced by TMT in the central nervous system by attenuating intensive oxidative stress and associated signaling pathways.
  • Xuanyu Li, Xuelong Jin
    脳科学誌
    2012年 38 巻 21-34
    発行日: 2012/03/30
    公開日: 2017/06/01
    ジャーナル フリー
    Central nervous system (CNS) injuries lead to severe and permanent neurological deficits. Fortunately, as a result of the rapid progress in biomedical science, particularly the stem cell biology, stem cell transplantation holds promise for promoting anatomical repair and functional recovery after traumatic or ischemic injuries to the CNS. However, the tumorigenic potential of these cells remains a great concern, as reflected in the formation of teratomas by transplanted pluripotent cells. This gap in the field is particularly serious as stem cell tumori-genicity represents the key obstacle to the safe use of stem cell-based therapy for CNS injuries. Although some adult stem cell therapies appear to be safe, they have only a very narrow range of uses in human disease. In this review, the links between pluripotency and tumorigenicity are explored. And new medical imaging modalities for more accurately testing the tumorigenic potential of iPSC and of other stem cells applicable to regenerative medicine are proposed. Finally, the most promising emerging approaches for overcoming the challenges of stem cell tumorigenicity are highlighted.
  • 遠藤 克, 金山 喜一
    Journal of Mammalian Ova Research
    1998年 15 巻 1 号 93-95
    発行日: 1998年
    公開日: 2006/07/08
    ジャーナル フリー
    ハムスターを用いて体外受精の受精成績におよぼすprogesteroneの拮抗物質,RU486(Mifepristone)の影響について検討した.媒精メディウム中にRU486を1,5,10,20,40および60 μMを含む6つの試験区を設けた.RU486を含まない対照区における受精率は97.3%であった.RU486を1 μM添加した試験区の受精率は94.6%で対照区と差は認められなかった.一方,5 μM以上の試験区ではRU486の濃度依存的に受精率は低下し,60 μM添加区では56.3%にまで低下した(P<0.001).以上のように,progesteroneの拮抗物質であるRU486は濃度依存的にハムスターの体外受精を阻害することを明らかにした.
feedback
Top