Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
34 巻 , 2 号
選択された号の論文の22件中1~22を表示しています
Analytical Biochemistry
Note
  • Hirofumi Inoue, Yasuhiko Sakata, Hiroaki Nishio, Kohji Tokumo, Eijiro ...
    原稿種別: Note
    専門分野: Analytical Biochemistry
    2011 年 34 巻 2 号 p. 287-289
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    A simple and highly sensitive high-performance liquid chromatography method for the determination of pipecolic acid in mouse brain areas was developed. After homogenization of brain and pretreatment with o-phthalaldehyde, the pipecolic acid and (2S,3S)-3-methylpyrrolidine-2-carboxylic acid (internal standard) were derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70 °C for 15 min in basic medium (pH 9.0). The fluorescent derivatives of pipecolic acid and internal standard were separated on a reversed-phase column by stepwise elution using acetic acid (30 mM)–acetonitrile at 50 °C and detected by fluorescence measurement at 316 nm (excitation) and 403 nm (emission). The detection limit (signal-to-noise ratio=3) of pipecolic acid was 13 fmol per injection. The recovery was about 106.7%. The precision (relative standard deviation) was 3.2%.
Biochemistry
Regular Articles
  • Chien-Chou Hsiao, Chien-Hsing Lee, Lon-Yen Tsao, Hui-Chen Lo
    原稿種別: Regular Article
    専門分野: Biochemistry
    2011 年 34 巻 2 号 p. 177-182
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Nitric oxide synthase (NOS) inhibitors alleviate the adverse effects of nitric oxide (NO) overproduction that occurs during peritonitis, a clinical condition that is accompanied by arginine deficiency. However, the variations in the disease severity and the dosage, route, and period of NOS inhibitor administration are debatable. Therefore, we investigated the dose effects of chronically infused NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on the anabolism, inflammatory responses, and arginine metabolism in parenterally fed rats with cecal puncture-induced subacute peritonitis. Male Wistar rats were divided into 4 groups and were administered total parenteral nutrition solutions with 0, 5 (low dose), 25 (medium dose), or 50 (high dose) mg·kg−1·d−1 of L-NAME for 7 d. Sham-operated rats administered total parenteral nutrition solution and normal healthy rats fed chow diet were also included. Our results showed that parenteral infusion significantly decreased body weight gain and plasma citrulline concentrations. In rats with subacute peritonitis, the parenteral infusion-induced increases in circulating white blood cells and NO were significantly decreased, whereas the decrease in serum albumin levels was significantly increased. Rats with subacute peritonitis that were administered chronic infusion of L-NAME had a significantly reduced nitrogen balance. In addition, rats administered the medium dose of L-NAME had significantly increased plasma arginine, ornithine, glutamate, and proline. In conclusion, chronic infusion of NOS inhibitors may not alter systemic NO homeostasis and inflammatory response but may facilitate the production of arginine-associated amino acids and nitrogen excretion in cases of subacute peritonitis.
  • Toshihiro Matsuda, Miki Shimada, Akira Sato, Takanori Akase, Kouichi Y ...
    原稿種別: Regular Article
    専門分野: Biochemistry
    2011 年 34 巻 2 号 p. 183-190
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    The mouse cholesterol sulfotransferase St2b2 contributes to epidermal differentiation by biosynthesizing cholesterol sulfate (CS) from cholesterol in the epidermis. 12-O-Tetradecanoylphorbol-13-acetate (TPA) causes epidermal hyperplasia, an abnormal increase in epidermal cell numbers resulting from aberrant cell differentiation and an increase in St2b2 protein levels. The mechanisms underlying enhanced St2b2 expression and the pathophysiologic significance of the increased expression are unclear, however. To verify whether increased St2b2 levels are necessary for TPA-induced epidermal hyperplasia, the effects of St2b2-specific small hairpin RNA (St2b2-shRNA) on hyperplasia were examined in mice. St2b2-shRNA clearly suppressed TPA-induced epidermal hyperplasia and the expression of a marker of epidermal differentiation, involucrin (INV). Interestingly, treating mouse epidermal cells with tumor necrosis factor-alpha (TNFα) increased St2b2 expression. Furthermore, treatment with TNFα-siRNA or anti-TNF receptor antibodies reduced the TPA-induced enhancement of St2b2 expression. Treatment with BAY 11-7082, a specific inhibitor of nuclear factor-kappa B (NF-κB), diminished TPA-induced St2b2 expression. These results suggested that enhancement of St2b2 expression by TPA treatment occurs mainly through the TNFα–NF-κB inflammatory signaling pathway, which in turn leads to increased CS concentrations in epidermal cells and hyperplasia.
  • Keiichi Ishihara, Kengo Tachibana, Asuka Kuroda, Ayano Terakawa, Shins ...
    原稿種別: Regular Article
    専門分野: Biochemistry
    2011 年 34 巻 2 号 p. 191-196
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    The accumulation of hepatocellular triacylglycerol (TG), a major symptom of fatty liver, is associated with the excessive incorporation of exogenous free fatty acids into hepatocytes, the free fatty acids inducing an increase in TG bearing acyl chains derived from not only themselves but also endogenous fatty acids. However, the mechanisms responsible for the supply of endogenous fatty acids, which are mainly esterified into phospholipids, remain unclear. In the present study, we examined the possible involvement of intracellular phospholipase A2 (PLA2)s including group IVA, IVC, VIA, and VIB PLA2s, which catalyze the release of endogenous fatty acids, in the deposition of TG in hepatocytes. Stimulation of human hepatoma Huh-7 cells with oleate or linoleate for 48 h increased TG contents time-dependently. Under the conditions, increased expression of group IVC PLA2 mRNA and protein was observed at 6—12 h and 24—48 h after the stimulation, respectively. However, mRNA levels of group IVA, VIA, or VIB PLA2 did not change. When cells were treated with methyl arachidonyl fluorophosphonate used as an inhibitor of group IVC PLA2, the fatty acid-induced deposition of TG was partially but significantly suppressed at 48 h, although no significant inhibition was observed at 24 h. Overexpression of wild-type group IVC PLA2 but not a catalytically inactive mutant of group IVC PLA2 tended to increase cellular TG levels. The present findings suggest that stimulation of Huh-7 hepatocytes with free fatty acids induces the expression of group IVC PLA2, which is involved in the fatty acid-induced deposition of TG.
Molecular and Cell Biology
Regular Articles
  • Hong Gao, Lei Liu, Zhang-yi Qu, Feng-xiang Wei, Shu-qiu Wang, Guang Ch ...
    原稿種別: Regular Article
    専門分野: Molecular and Cell Biology
    2011 年 34 巻 2 号 p. 197-202
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Radix Lithosperm eyrthrorhizon is a common prescription compound in traditional Chinese medicine. Shikonin is a major component of Radix Lithospermi and has various biological activities. We have investigated the inhibitory effect of shikonin on the growth of adenovirus type 3 (AdV3) in vitro. The antiviral function of shikonin against AdV3 and its virus inhibition ratio were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method (MTT). The expression of hexon protein in AdV3 was determined by immunofluorescence assay using laser scanning confocal microscopy (LSCM) and Western blot analysis. In addition, the rate of apoptosis in cells infected by AdV3 was determined by flow cytometry. Shikonin (0.0156—1 μM) inhibited growth of AdV3 in a concentration-dependent manner with a virus inhibition rate of 23.8—69.1%. Expression of hexon protein in AdV3 was higher in the virus control group than in the shikonin-treated groups as determined by immunofluorescence assay and Western blotting (p<0.05). The rate of shikonin-treated HeLa cell apoptosis had a statistically significant decrease with increasing concentration of drug (p<0.05). Our data demonstrate that shikonin possesses anti-AdV3 capabilities and that the potential antiviral mechanism might involve inhibiting the degree of apoptosis and hexon protein expression of AdV.
  • Sim Namkoong, Tack-Joong Kim, Ik-Soon Jang, Keon-Wook Kang, Won-Keun O ...
    原稿種別: Regular Article
    専門分野: Molecular and Cell Biology
    2011 年 34 巻 2 号 p. 203-208
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    The extracellular signal-regulated kinases/mitogen activated protein kinase (ERK/MAPK) and nuclear factor-κB (NF-κB) pathways are critical for cell survival and proliferation. Alpinumisoflavone (AIF), isolated from the African medicinal plant Erythrina lysistemon, is a member of the isoflavone group. In this report, we demonstrated that AIF treatment induces cell death of human lung tumor cells. Incubation of lung tumor cells with AIF increased the sub-G1 population and caspase 3/7 activity, suggesting that the cell death is caused by apoptosis. To identify the signaling pathway involved in the tumor cell death, we examined the modulation of transcriptional activity using various reporter constructs and found that AIF significantly deregulated both the ERK/MAPK and NF-κB pathways. Western blot analysis with antibodies to MAP/ERK kinase (MEK) and ERK showed that AIF dephosphorylates both MEK and ERK. Alpinumisoflavone also repressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells by inhibiting NF-κB-dependent transcription. Therefore, the cell death induced by AIF may be via repressing both the ERK/MAPK and NF-κB pathways.
  • Mayumi Shimoji, Naoki Imaizumi, Yoko Aniya
    原稿種別: Regular Article
    専門分野: Molecular and Cell Biology
    2011 年 34 巻 2 号 p. 209-213
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Membrane-bound glutathione transferases (MGST1) distributed mostly in liver microsomal and mitochondrial membranes are activated by the thiol modification. In the present study, the effect of phospholipids on MGST1 activity was investigated using purified enzyme. When MGST1 was mixed with liposomes of cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PC), or phosphatidylethanolamine (PE), its activity was increased in a magnitude which was dependent on the anionic property of lipids in the order of CL>PS>PE>PC, indicating that MGST1 activity is enhanced by surrounding anionic lipids. Although MGST1 was activated by the thiol alkylation with N-ethylmaleimide (NEM), the activation was suppressed in the presence of anionic phospholipids as clearly observed in the presence of CL. Similarly, the activation of MGST1 by diamide or diamide plus glutathione through disulfide-bond formation was also disturbed in the presence of CL. Suppression of NEM-derived MGST1 activation by CL was lost when MGST1 was incubated with CL in the presence of the detergent Triton X-100. These results indicate that reactivity (stability) of the thiol in MGST1 is affected by surrounding lipids, namely CL which prevents MGST1 activation by thiol modification. Since CL is a mitochondria specific lipid located in the inner membrane, it was suggested that function of mitochondrial MGST1 could be regulated by interaction with CL.
Note
  • Kazunori Saeki, Yasuyo Nose, Nobukuni Hirao, Ryoko Takasawa, Sei-ichi ...
    原稿種別: Note
    専門分野: Molecular and Cell Biology
    2011 年 34 巻 2 号 p. 290-294
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Caspases cleave several cellular proteins to execute cell death by apoptosis. The identification of novel substrates of caspases could provide an important clue for elucidation of new apoptosis signaling pathways. In this study, we tested whether an amyloid precursor protein (APP) binding protein Fe65 is proteolytically degraded in neuronal cell death by apoptosis, using a neuron-like cell line, human neuroblastoma SH-SY5Y cells. When treated with DNA damaging agents, etoposide (ETP) and camptothecin (CPT), SH-SY5Y cells underwent apoptosis in a dose-dependent manner. Interestingly, Fe65 (97 kDa) was cleaved to a 65 kDa product during DNA damage-induced apoptosis. Furthermore, the cleavage of Fe65 was accompanied by activation of caspases-9 and -3. The restriction cleavage of Fe65 was completely suppressed by the treatment with a pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethylketone (z-VAD-fmk). These results reveal the restriction cleavage of Fe65 by caspases during DNA damage-induced apoptosis. Since Fe65 has been shown to suppress APP processing to amyloid β (Aβ) production, our findings may provide a new insight into the molecular mechanism by which DNA damage induces Aβ production and subsequent neuronal cell death in Alzheimer's disease (AD).
Microbiology
Regular Article
  • ZiJin Fu, Hui Lu, ZhenYu Zhu, Lan Yan, YuanYing Jiang, YingYing Cao
    原稿種別: Regular Article
    専門分野: Microbiology
    2011 年 34 巻 2 号 p. 214-218
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Candida albicans is the most important human fungal pathogen. Amphotericin (AmB) is a gold standard of antifungal treatment for fungi, but the severe side effect of this drug restricts its clinical application. In this study, the interaction of AmB and baicalein (BE) was investigated against thirty clinical isolates of C. albicans. Synergistic activities were determined using the checkerboard microdilution assay based on the fractional inhibitory concentration indices. Combination of BE and AmB accelerated C. albicans apoptosis accompanied with an increase of reactive oxygen species (ROS). Moreover, AmB increased the caspase activity and expression of the corresponding gene CaMCA1 in C. albicans. These effects were enhanced in the presence of BE. Deletion of CaMCA1 clearly attenuated AmB-induced apoptosis, indicating the involvement of CaMCA1-mediated caspase pathway in AmB-induced apoptosis and the synergistic action.
Note
  • Takashi Sato, Hirokazu Kurihara, Noriko Akimoto, Norihisa Noguchi, Mas ...
    原稿種別: Note
    専門分野: Microbiology
    2011 年 34 巻 2 号 p. 295-299
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Aberrant extracellular matrix (ECM) remodeling in sebaceous glands and pilosebaceous units in the skin is associated with scar formation under acne conditions. To investigate the involvement of Propionibacterium acnes (P. acnes), a Gram-positive anaerobic microbial species, in ECM remodeling in sebaceous glands and pilosebaceous units, we examined the effects of P. acnes culture media, formalin-fixed P. acnes, and peptidoglycan (PGN) from Gram-positive bacteria walls on the production of promatrix metalloproteinase 2 (proMMP-2)/progelatinase A in hamster sebocytes and dermal fibroblasts. When hamster sebocytes (1.8×105 cells) and dermal fibroblasts (1×105 cells) were treated with P. acnes culture media and formalin-fixed P. acnes (corresponding to 1×106 and 1×107 bacterial cells), the production of proMMP-2 was augmented. In addition, PGN (5—50 μg/ml) dose-dependently augmented the production of proMMP-2 in both cells. Furthermore, the PGN (50 μg/ml)-augmented proMMP-2 production was resulted from an increase of its transcript. In contrast, there were no changes in cell proliferative activity in either the P. acnes or PGN-treated sebocytes and dermal fibroblasts, indicating that the augmented proMMP-2 production was not due to an increase in cell numbers. Therefore, these results provide novel evidence that PGN transcriptionally up-regulates the production of proMMP-2 in hamster sebocytes and dermal fibroblasts. Given an increase in the quantity of Gram-positive bacteria, including P. acnes in acne lesions, the aberrant ECM degradation may progress in sebaceous glands and pilosebaceous units, which is associated with acne scar formation.
Pharmacology
Regular Articles
  • Guangcheng Wang, Baowen Qi, Hao Zheng, Zhizhi Chen, Xin Wei, Liang Ma, ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 2 号 p. 219-225
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Idiopathic pulmonary fibrosis is regarded as a lethal chronic disease accompanied with excessive collagen disposition. In the early stage, monocyte chemotactic protein-1 (MCP-1) plays a crucial role in the process. Our previously screening with a vitro assay through inhibition of chemotaxis of RAW264.7 cells stimulated by MCP-1 proved that several analogues of thiazolidinediones, especially (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (SKLB010), had potency of protecting acute liver injury in vivo without obvious toxicity. The present study aimed to investigate the preventive effect of SKLB010 in bleomycin-induced pulmonary fibrosis and further explore the underlying mechanisms. Bleomycin (BLM) was injected intratracheally at a single dose of 5 U kg−1 for pulmonary fibrosis induction. SKLB010 (25, 50 mg/kg/d) was respectively administrated by gavages 1 d prior to BLM administration and continued to the end of the study (for 4 weeks). Our results demonstrated that SKLB010 diminished the increase of macrophage, neutrophil and lymphocyte counts as well as the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in bronchoalveolar lavage fluid on day 14 (p<0.05). Moreover, oral gavages of SKLB010 also ameliorated histological changes and significantly suppressed collagen deposition on day 28. The treatment with SKLB010 exerted approximately 34.6% the hydroxyproline content reduction for 25 mg/kg dose and 56.7% reduction for 50 mg/kg dose in contrast to bleomycin-induced group (p<0.05). Meanwhile, SKLB010 inhibited the overexpression of tumor growth factor (TGF)-β1 and Smad3 in a dose-dependent manner. In conclusion, our results showed that SKLB010 could attenuate the BLM-induced pulmonary fibrosis in vivo and therefore be a promising anti-fibrogenic candidate.
  • Fang Zhong, Hui Chen, Lin Han, Yuanmeng Jin, Weiming Wang
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 2 号 p. 226-232
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Renal inflammation is the main pathological change in many acute and chronic kidney diseases. Curcumin, a yellow pigment present in the rhizome of turmeric (Curcuma longa L. Zingiberaceae), was found to be a potential anti-inflammatory agent. The present study aimed to investigate the effects of curcumin on the inflammation of mice kidney and cultured renal tubular epithelial cells (HK-2 cells) induced by lipopolysaccharide (LPS) and to explore the mechanism. Curcumin was injected intraperitoneally before LPS administration. Renal inflammation was assessed by evaluating monocyte chemoattractant protein-1 (MCP-1) expression and macrophage infiltration in renal tissue using immunohistochemical methods, and also by measuring renal MCP-1 mRNA level using Real-Time polymerase chain reaction (PCR). HK-2 cells were cultured to investigate the in vitro effect of curcumin against LPS-induced renal inflammation. The expression of MCP-1 and interleukin-8 (IL-8) mRNA was measured by Real-Time PCR. The expression of MCP-1 and IL-8 protein in supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The activity of nuclear factor (NF)-κB was detected by electrophoretic mobility shift assay (EMSA). The results demonstrated that curcumin could inhibit LPS-induced renal MCP-1 mRNA expression. Curcumin also significantly inhibited the expression of MCP-1 and IL-2 mRNA in HK-2 cells, and partially inhibited the secretion of MCP-1 and IL-8. Furthermore, curcumin was found to inhibit the DNA-binding activity of NF-κB. The present study demonstrated that curcumin has a protective effect on LPS-induced experimental renal inflammation, and this effect might be attributed to its inhibitory effects on MCP-1 mRNA expression and DNA-binding activity of NF-κB. Hence, curcumin might be potentially useful in some kidney diseases by preventing renal inflammation.
  • Yuuki Akagi, Yuta Nio, Shuji Shimada, Takao Aoyama
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 2 号 p. 233-237
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Low-dose aspirin acts by irreversibly acetylating internal cyclooxygenase-1 (COX-1) on platelets, thereby suppressing platelet aggregation. Because nonsteroidal anti-inflammatory drugs (NSAIDs) also inhibit COX-1, the antiplatelet effects of aspirin may be suppressed when it is co-administered with NSAIDs. In this study, the influences of ibuprofen, loxoprofen sodium and etodolac on the antiplatelet effects of aspirin were investigated in male Sprague-Dawley (SD) rats. Aspirin and/or NSAIDs were administered orally at single or multiple daily doses. Platelet aggregation (ADP and collagen were added as stimuli) and serum thromboxane B2 (TXB2) concentrations were measured. The maximum inhibitions of aggregation in the aspirin before ibuprofen group were 41.0±7.8% for ADP and 38.7±5.4% for collagen at 6 h after administration; similar values were seen in the aspirin group; however, percent inhibitions in the aspirin before ibuprofen multiple administration group were lower than those in the aspirin group. Thus, the inhibitory effects of daily low-dose aspirin on platelets are competitively inhibited by the prolonged use of multiple daily doses of ibuprofen. In contrast, serum TXB2 concentrations in all groups were lower than those in the control group (drug-free). This suggests that the relationship between the inhibition of platelet COX-1 and the suppression of platelet aggregation is nonlinear. When aspirin was administered with loxoprofen sodium, similar effects were observed; however, with etodolac, the antiplatelet effects in all groups were equal to those in the aspirin group. Accordingly, if co-administration with NSAIDs is necessary with low-dose aspirin, a selective COX-2 inhibitor, such as etodolac, should be used.
  • Nobutomo Ikarashi, Takashi Ushiki, Toshihide Mochizuki, Takahiro Toda, ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 2 号 p. 238-242
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Aquaporin (AQP) 3 plays an important role in regulating faecal water content in the colon. We investigated the role of AQP3 in the colon in the laxative effect of magnesium sulphate (MgSO4), a widely used osmotic laxative. Rats were administered MgSO4, after which faecal water content, the colon mRNA expression levels of sodium myo-inositol transporter (SMIT) and taurine transporter (TauT), the colon protein expression levels of AQP3 were examined. Faecal water content increased over time after MgSO4 administration, and severe diarrhoea was observed between 4 and 8 h after administration. The mRNA expression levels of SMIT and TauT, which are indicators of variations in osmotic pressure, were highest at 2 h after the administration of MgSO4 and were still elevated at 8 h after administration when compared to immediately after the administration. The immunostaining analysis showed that AQP3 is a dominant AQP in the rat colon. The protein expression levels of AQP3 in the colon increased over time following the administration of MgSO4 and at 8 h after administration were approximately 8 times higher than baseline levels. Previously, osmotic laxatives were believed to induce diarrhoea by elevating the osmotic pressure in the intestinal tract. The results of the present study suggest that the laxative effect of MgSO4 is not simply caused by a change in the osmotic pressure in the intestinal tract, but could be a response to increased expression of AQP3.
  • Soichiro Akashi, Tomonori Kimura, Toshifumi Takeuchi, Kouji Kuramochi, ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 2 号 p. 243-248
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Neoechinulin A, an indole alkaloid from marine fungi, can protect PC12 cells from the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP+), a Parkinson disease-inducing neurotoxin, by ameliorating downstream events resulting from mitochondrial complex I inactivation. However, the cytoprotective mechanisms remained unclear. In this study, by using rotenone, another parkinsonian-inducing neurotoxin targeting mitochondrial complex I, we investigated the cytoprotective mechanism of neoechinulin A. Rotenone-induced cell death was associated with accelerated glucose consumption, and excess glucose supplementation in the culture medium almost completely suppressed cell death, suggesting that glucose deficiency in the medium is critical for triggering cell death in this model. Co-treatment with neoechinulin A, but not neoechinulin A pre-treatment before rotenone exposure, significantly impeded cell death by rotenone. Although the presence of neoechinulin A did not affect the accelerated glycolytic turnover in rotenone-treated cells, it paradoxically decreased ATP levels in the cells, suggesting increased ATP consumption. Although the link between the decreased ATP levels and cytoprotection is not clear at present, it suggests that neoechinulin A may ameliorate rotenone toxicity by activating a cytoprotective machinery that requires ATP.
  • Takayuki Ohtomo, Tomoyuki Kanamatsu, Mariko Fujita, Mitsuhiro Takagi, ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 2 号 p. 249-252
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    YY1AP-related protein (YARP) is a structural homolog of YY1-associated protein (YY1AP), which has a YY1-binding domain. During perinatal development, YARP mRNA expression is increased at a late stage of embryonic neurogenesis. It is not known whether YARP expression is regulated during adult neurogenesis. Electroconvulsive shock (ECS), a model for a highly effective depression treatment, is known to induce hippocampal neurogenesis after repeated treatment, so we employed ECS to measure the expression of YARP mRNA. Northern blots revealed significantly decreased expression of the YARP gene after repeated ECS but not single ECS. In situ hybridization clearly demonstrated a reduction of YARP mRNA expression in the CA (CA1, CA2, and CA3) subfields. Although clonic–tonic seizure was induced not only by ECS but also by injection of kainic acid to the striatum, the regulation of YARP mRNA expression was different between ECS and kainic acid. YARP mRNA was decreased only by the ECS method, suggesting that YARP expression is different at embryonic and adult neurogenic stage.
  • Zhe Xiong, Bo Jiang, Peng-Fei Wu, Jia Tian, Liang-Liang Shi, Jun Gu, Z ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 2 号 p. 253-259
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that baicalein (Bai), one plant-derived active flavonoid, exhibits neuroprotection against ischemic brain injury and stimulates the levels of phosphorylation of extracellular signal-regulated kinase (pERK) and brain-derived neurotrophic factor (BDNF) expression in vivo. In this study, the antidepressant-like effects of baicalein was investigated using acute and chronic animal models of depression. The results showed that acute application of Bai at doses of 1, 2 and 4 mg/kg by intraperitoneal injection (i.p.) significantly reduced the immobility time in the forced swimming test (FST) and tail suspending test (TST) of mice. In addition, the chronic application of Bai by i.p. for 21 d also reduced the immobility time and improved locomotor activity in chronic unpredictable mild stress (CMS) model rats. Furthermore, it was shown that Bai reversed the reduction of extracellular ERKs phosphorylation and the level of BDNF expression in the hippocampus of CMS model rats. These results suggest that Bai produce an antidepressant-like effect and this effect is at least partly mediated by hippocampal ERK-mediated neurotrophic action.
  • Nobuyuki Mochizuki, Yoshiyuki Moriyama, Norio Takagi, Satoshi Takeo, K ...
    原稿種別: Regular Article
    専門分野: Pharmacology
    2011 年 34 巻 2 号 p. 260-265
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    The ability of stem cells to enhance neurological recovery seen after cerebral ischemia has been reported. However, it remains to be clarified whether neural progenitor cells (NPCs) improve cerebral ischemia-induced learning dysfunction. We found in an earlier study that the direct injection of NPCs into the hippocampus prevents spatial learning dysfunction after cerebral ischemia. As the intravascular injection of cells represents a minimally invasive therapeutic approach, we sought to determine whether the intravenous injection of NPCs also would improve ischemia-induced spatial learning dysfunction. Cerebral ischemia was produced by the injection of 700 microspheres into the right hemisphere of rats. The injection of NPCs via a femoral vein on day 7 after the induction of ischemia improved the modified neurological severity score and reduced the prolongation of the escape latency seen in the water maze task on days 12—28 after cerebral ischemia. The intravenous injection of NPCs on day 7 did not affect the viable area of the ipsilateral hemisphere on day 28 compared with that of the non-treated ischemic rats. Furthermore, the NPCs injected via the vein were detected in the ipsilateral hemisphere; and they expressed brain-derived neurotrophic factor (BDNF) on day 28. The decrease in the BDNF level in the ipsilateral hemisphere was also inhibited by the injection of NPCs. These results suggest that the NPCs injected via the vein after cerebral ischemia improved spatial learning dysfunction, but without having any restorative effect on the damaged areas, possibly by acting as a source of neurotrophic factors.
Medicinal Chemistry
Regular Article
  • Ali Shayanfar, Somaieh Soltani, Abolghasem Jouyban
    原稿種別: Regular Article
    専門分野: Medicinal Chemistry
    2011 年 34 巻 2 号 p. 266-271
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Two simple multiple linear regression models were proposed to calculate the logarithm of the blood to brain concentration ratio (log BB) of drugs or drug-like compounds. The drugs were classified into two groups according to their ionization state in blood, and the significant parameters were selected using the train sets for each group. For un-ionizable compounds, the logarithm of distribution coefficient in octanol–water in pH 7.4 (log D7.4) and molecular weight are the significant parameters, whereas for ionizable compounds, log D7.4 and number of hydrogen bond acceptor are significant parameters. The developed models were validated and their prediction capabilities checked using an external dataset of 25 compounds. In addition to the acceptable prediction errors, comparison of the external data analysis results with previously proposed models confirmed superior prediction capability of newly developed models.
Biopharmacy
Note
  • Kenjiro Koga, Yuki Nishimon, Hisashi Ueta, Kenjiro Matsuno, Kanji Taka ...
    原稿種別: Note
    専門分野: Biopharmacy
    2011 年 34 巻 2 号 p. 300-305
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    The aim of this study was to determine the efficiency of nano-sized water-in-oil (w/o) emulsions that encapsulate glycyrrhizin (GZ) (Rp-I) as a sustained release formulation for subcutaneous administration. Four formulations were assessed in rats for 8—72 h: nano-sized water-in-oil (w/o) emulsion encapsulating GZ (Rp-I), GZ aqueous solution (Rp-II), oil-in-water (o/w) emulsion containing GZ (Rp-III), and w/o emulsion containing solid GZ (Rp-IV). All had a GZ concentration of 150 mg/ml. Over an 8-h period, GZ elimination in bile after subcutaneous administration of Rp-I, Rp-II, Rp-III, and Rp-IV (50 mg/kg GZ) was 10.8%, 97.0%, 81.0%, and 7.1%, respectively. The elimination of GZ into bile after the administration of Rp-IV was the lowest (30.5%) at the 72-h endpoint, dropping significantly from 48 to 72 h. On the other hand, the elimination rate of GZ after the administration of Rp-I was sustained at a constant level (1.8—2.1 mg/24 h) over 72 h. GZ concentration in liver at 72 h in Rp-I was highest (19.9 μg/g tissue) among the four formulations, suggesting that the release of GZ from the Rp-I formulation is constant, at least up to 72 h after administration. These results suggest that a nano-sized w/o emulsion is useful as a sustained release formulation for long-term therapy of chronic hepatitis.
Miscellaneous
Regular Articles
  • Mohammad Ahmad, Yasser Elnakady, Muhammad Farooq, Muhammad Wadaan
    原稿種別: Regular Article
    専門分野: Miscellaneous
    2011 年 34 巻 2 号 p. 272-277
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    Lithium is commonly used in treating mental disorders and bipolar diseases. As physicians frequently keep the patients on long-term lithium therapy, awareness of the numerous side effects and pathogenesis of this lightest alkali metal is needed for such treatments. The present study was designed to evaluate the toxic effect of small doses of lithium chloride in male Wistar rats. The oral administration of lithium chloride (15, 30 mg/kg body wt) for 7 weeks through their drinking water elicited a significant alteration in their body weight and blood serum chemistry. The serum enzyme levels of alkaline phosphatase (ALP), high density lipoprotein (HDLP), and creatinine kinase (CK) were diminished, whereas the level of serum urea and glucose were elevated in the lithium treated animals, depicting the disturbed general physiological status. Furthermore, a marked inhibition in the levels of serum alanine and aspartate transaminases (ALT and AST) reflected a stimulating transamination reaction in hepatic and renal tissues. Lithium exposure also reduced the glutathione (GSH) level and stimulated the lipid peroxidation (LPO) level in the rat blood cells, indicating oxidative stress in the red blood cells due to lithium exposures. The histopathological observations of the liver and kidney tissues revealed many deformities and histological alterations due to lithium treatment. The results of present study suggest that small doses of lithium induce toxicity in rat blood as well as in liver and kidney tissues. However, the precise mechanism of lithium toxicity is still incompletely understood.
  • Ying Chen, Chen Chen, Jianling Zheng, Zhiyu Chen, Qiongzhi Shi, Hong L ...
    原稿種別: Regular Article
    専門分野: Miscellaneous
    2011 年 34 巻 2 号 p. 278-286
    発行日: 2011/02/01
    公開日: 2011/02/01
    ジャーナル フリー
    The objective of this study was to prepare a solid supersaturatable self-emulsifying drug delivery system (S-sSEDDS) using docetaxel (DTX). Different from conventional self-emulsifying drug delivery systems (SEDDSs), a solid supersaturatable self-emulsifying drug delivery system of docetaxel (DTX-S-sSEDDS) was prepared by spray drying, using lactose as the solid carrier and hydroxypropyl methylcellulose (HPMC) as the supersaturation promoter. Physicochemical properties and in vitro dissolution was observed while taking into account factors such as formulations, supersaturated promoters, solid carriers, and preparation methods. The bioavailability of the DTX-S-sSEDDS1 compared with other formulations of DTX was evaluated in rats. The results showed that the presence of HPMC effectively sustained the supersaturated state by retarding the precipitation kinetics. Although the total amount of emulsifying excipients in the DTX-S-sSEDDS1 was only 3/5 as much as that of the conventional SEDDS (DTX-SEDDS2), the percent of the accumulated dissolved DTX-S-sSEDDS1 at 2 h reached 90.96%, which was higher than that of the DTX-SEDDS2 (76.26%) and approximately 29.8 times as much as that of the DTX crude powder. The in vivo studies indicated that the area under the concentration–time curve (AUC0—∞) of the DTX-S-sSEDDS1 increased by nearly 8.77-fold, 1.45-fold more than those of the DTX powder and the conventional SEDDS without the presence of HPMC (DTX-SEDDS1) at a dose of 10 mg/kg. In conclusion, the S-sSEDDS provides an effective approach for improving the dissolution and bioavailability of docetaxel with a low level of emulsifying excipients and provides a reference for good stabilization and the safety of SEDDSs.
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