YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
132 巻 , 7 号
選択された号の論文の8件中1~8を表示しています
総説
  • 石田 寿昌
    2012 年 132 巻 7 号 p. 785-816
    発行日: 2012/07/01
    公開日: 2012/07/01
    ジャーナル フリー
      Information on the conformational feature and specific intermolecular interaction of biomolecules is important to understand the biological function and to develop device for treating disorder caused by the abnormal function. Thus the 3D structures of the biologically active molecules and the specific interactions with their target molecules at the atomic level have been investigated by various physicochemical approaches. Herein, the following five subjects are reviewed: (1) function-linked conformations of biomolecules including natural annular products, opioid peptides and neuropeptides; (2) π-π stacking interactions of tryptophan derivatives with coenzymes and nucleic acid bases; (3) mRNA cap recognition of eukaryotic initiation factor 4E and its regulation by 4E-binding protein; (4) conformational feature of histamine H2 receptor antagonists and design of cathepsin B inhibitors; (5) self-aggregation mechanism of tau protein and its inhibition.
  • 中原 広道
    2012 年 132 巻 7 号 p. 817-822
    発行日: 2012/07/01
    公開日: 2012/07/01
    ジャーナル フリー
      Lung surfactants (LS), a complex of ∼90 wt% lipids (mainly dipalmitoylphosphatidylcholine or DPPC) and ∼10 wt% surfactant proteins (SP-A, -B, -C, and -D), adsorb to an air-alveolar fluid interface and then lower its surface tension down to near zero during expiration. Intratracheal instillation of exogenous LS preparations can effectively compensate for surfactant deficiency in premature infants with respiratory distress syndrome (RDS). Surfacten® (Mitsubishi Tanabe Pharma Corporation, Osaka, Japan), a modified bovine lung extract and an effective surfactant replacement in treatment for RDS patients, is supplemented with DPPC, palmitic acid, and tripalmitin. For the premature infants suffering from RDS, instillation of Surfacten® leads to a dramatic improvement in lung function and compliance. Herein, the author reviews potential use of newly designed preparations containing a mimicking peptide of SP-B and also introduces the current research on the preparations incorporated with partially fluorinated amphiphiles to improve their efficacy.
  • 松末 公彦
    2012 年 132 巻 7 号 p. 823-829
    発行日: 2012/07/01
    公開日: 2012/07/01
    ジャーナル フリー
      Fat-specific protein 27 (fsp27) was originally isolated by screening for genes specifically expressed in fully differentiated mouse adipocytes. Fsp27 and cell death-inducing DFF45-like effector (CIDE) C, the human homologue of fsp27, belong to the CIDE family. Fsp27, which is highly expressed in mouse white and brown adipose tissues, was recently reported to be a lipid droplet (LD)-binding protein that promotes lipid accumulation in adipocytes. In contrast, we showed that fsp27 was also expressed in the fatty liver of the ob/ob type II diabetes model mouse. The expression of fsp27 was markedly decreased in livers lacking the nuclear receptor peroxisome proliferator-activated receptor γ(PPARγ). A functional PPAR response element site was identified in the fsp27 promoter region. Forced expression of fsp27 in hepatocytes in vitro or in vivo led to increased LD through increased triglyceride levels. The current status of the physiological roles of the PPARγ-fsp27 signal in fatty liver are discussed along with its significance as a factor involved in the development of metabolic disorders.
一般論文
  • 小松 健一, 田中 寛子, 中川 大輔, 川嶋 恵子
    2012 年 132 巻 7 号 p. 831-836
    発行日: 2012/07/01
    公開日: 2012/07/01
    ジャーナル フリー
      The protective effects of notoginseng against hepatic damage were investigated in mice. To prepare a model animal of hepatitis, a mixture of lipopolysaccharide and galactosamine (LPS/GAlN) was administered intraperitoneally, leading to the impairment of hepatic function. Extracts of notoginseng or its components (ginsenoside Rb1 and ginsenoside Rg1) were orally administered 2 h before LPS/GalN injection. Eight hours after LPS/GalN injection, blood and liver tissue samples were collected. The levels of serum aspartate amino transferase (AST), alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured using commercial assay kits. Histologic changes in the tissue samples were also observed after hematoxylin-eosin staining. LPS/GalN administration increased the serum levels of AST and ALT, and histologic changes were noted, indicating hepatic cell damage. Prior to the increase in ALT, the serum levels of TNF-α and IFN-γ were elevated after LPS/GalN injection. Pretreatment of the mice with either notoginseng extract or gensenoside Rb1 and Rg1 attenuated the LPS/GalN-induced hepatic damage markedly. The protective effects of the components against hepatic damage appeared to be less potent than those of the crude extract and prescription of notoginseng. Notoginseng may be clinically useful in patients with hepatitis.
  • 長井 紀章, 伊藤 吉將, 岡本 紀夫, 下村 嘉一
    2012 年 132 巻 7 号 p. 837-843
    発行日: 2012/07/01
    公開日: 2012/07/01
    ジャーナル フリー
      Benzalkonium chloride (BAC) is known to cause corneal epithelial damage. In this study we investigated the effect of a BAC solution containing a thickening agent, which enhanced residence time in the eyes, on corneal wound healing using in vivo rat model debrided corneal epithelium. 0.5% or 1.0% methylcellulose (MC), carboxymethylcellulose (CMC) and hydroxypropyl-methylcellulose (HPMC) were used as the thickening agent. The levels of corneal wound healing of rat eyes injected with saline were alone approximately 45.0% at 12 h and 93.6% at 24 h after corneal epithelial abrasion, and healing was almost complete at 36 h. The healing rate in the rat eye treated just with MC, CMC and HPMC was higher than that in those injected with saline. In contrast to the treatment result using only this thickening agent, the healing rate in the eye treated with BAC was lower than that in those injected with saline: the corneal wounds in the BAC-treated eye showed approximately 20% healing at 12 h after abrasion. The injection of 0.02% BAC solution containing MC, CMC and HPMC more significantly delayed the healing than did the injection of 0.02% BAC alone. The results show that the in vivo evaluation method for corneal damage using rat debrided corneal epithelium reflects a toxic change depending upon residence time. These findings provide valuable safety and efficacy information for use in the design of eye drops.
ノート
  • 山口 佳津騎, 福岡 憲泰, 木村 純夫, 篠原 尚樹, 立道 貴清, 田井 達也, 小坂 信二, 大西 宏明, 芳地 一
    2012 年 132 巻 7 号 p. 845-848
    発行日: 2012/07/01
    公開日: 2012/07/01
    ジャーナル フリー
      We report a case of encephalopathy seemingly caused by tacrolimus (FK506) in spite of blood concentration near the upper limit of therapeutic range. A 26-year-old man received FK506 to prevent acute graft-versus-host disease after hematopoietic stem cell transplantation. He underwent an intravenous injection of FK506 the day before transplantation (day −1). He developed headache, hypertension, nausea and vomiting from day 2 to day 3. A computed tomography scan showed a low density area with unclear border in the bilateral cerebellar hemispheres. Thereafter, these symptoms improved with discontinuation of FK506, which was strongly suggestive of encephalopathy caused by FK506. The blood concentration of FK506 at the onset of encephalopathy was 21.7 ng/mL. Although this value was slightly higher than the standard therapeutic range (10-20 ng/mL), it was within clinically acceptable range in the early stage after stem cell transplantation. This indicates that even if the blood concentration of FK506 is within the therapeutic range, encephalopathy may develop. In summary, although the blood concentration of FK506 is useful as an indicator for prevention of encephalopathy, we propose careful monitoring not only of the blood concentration but also clinical status for the detection of initial symptoms and prevention of aggravation.
  • 金子 尚文, 中山 智洋, 一川 暢宏
    2012 年 132 巻 7 号 p. 849-853
    発行日: 2012/07/01
    公開日: 2012/07/01
    ジャーナル フリー
      Antimicrobial agents occasionally cause certain adverse effects, such as diarrhea and loose stool, by altering the composition of the intestinal flora. Antibiotic-resistant lactic acid bacteria are used to prevent these adverse effects. Although these bacteria are not resistant to several recently introduced antimicrobial agents, bacterial preparations are still sometimes prescribed concomitantly with these antimicrobial agents. In this study, we investigated whether the administration of the spore-forming butyric acid bacteria Clostridium butyricum improves the adverse clinical effects by preventing diarrhea. Inhibition of C. butyricum growth was observed with 17 of the 20 antimicrobial agents used. However, dilution of 11 of these 17 agents resulted in the regrowth of C. butyricum. These results suggest that C. butyricum may survive exposure to several antibiotic agents by forming spores. Further, a decrease in the antimicrobial agent concentration in the gastrointestinal tract permits the vegetative growth of C. butyricum, which functions as a probiotic.
  • 小林 淳, 池田 啓一, 望月 眞理子
    2012 年 132 巻 7 号 p. 855-860
    発行日: 2012/07/01
    公開日: 2012/07/01
    ジャーナル フリー
      The drinking facilities in some public spaces (such as parks, public baths, etc.) in Japan which many unspecified people often use are useful for taking moisture easily and rapidly. Sometimes it might be also accepted that it is good for the prevention of diseases and for the health. The cleaning of these facilities is sure to be done in regular. However, they have misgivings about dirt in more short time by using of many people. It would be necessary for the public health to research the safety of them. In the present study, the pollution of inorganic components, inorganic anions, general bacteria and total coliforms in the initial getting water to stay near by the faucets, on the knobs and the intakes were examined.
feedback
Top