YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
136 巻, 9 号
選択された号の論文の12件中1~12を表示しています
総説
  • 北中 進
    2016 年 136 巻 9 号 p. 1195-1216
    発行日: 2016/09/01
    公開日: 2016/09/01
    ジャーナル フリー
     Macrophages play major roles in inflammation, immunity and host defense mechanisms. Once activated they produce and release cytokines, oxygen and nitrogen species, and eicosanoids. The best characterized stimuli to induce the transcription of genes encoding pro-inflammatory proteins in macrophages in vitro is bacterial lipopolysaccharide (LPS). LPS could be used alone or in combination with recombinant mouse interferon-γ (IFN-γ). Such stimulation results in cytokine release and the synthesis of enzymes such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). The nitric oxide (NO) radical is known to play a central role in inflammatory and immune reactions for self-protection. However, the excessive production of NO may lead to tissue damage. In inflammatory diseases such as rheumatoid arthritis, excessive NO production by activated macrophages has been observed. Adipose tissue is composed of various cell types such as mature adipocytes, preadipocytes, fibroblasts, endothelial cells, vascular cells, and macrophages. Recent studies indicate that obesity is associated with low-grade chronic inflammation of adipose tissues, and that such inflammation is one of the potential mechanisms leading to the insulin resistance. It has been demonstrated that obese adipose tissue is characterized by the increased infiltration of macrophages. Therefore, we attempted to identify natural anti-inflammatory compounds that not only inhibit the secretion of NO from RAW 264.7 cells, but also inhibit triglyceride accumulation in 3T3-L1 adipocytes. This review describes the NO prpduction inhibitory activity or the TG accumulation inhibitory activity of the compounds obtained from 18 plants and a fungi that have been used as traditional medicines.
  • 米山 弘樹, 山本 大助, 大和谷 厚, 春沢 信哉
    2016 年 136 巻 9 号 p. 1217-1232
    発行日: 2016/09/01
    公開日: 2016/09/01
    ジャーナル フリー
    S-Alkyl-N-alkylisothiourea compounds, which contain various cyclic amines, were synthesized using 3-phenylpropionyl isothiocyanate (PPI) to discover novel non-imidazole histamine H3 receptor (H3R) antagonists. The synthetic route was improved remarkably by using 2-nitrophenylacetyl isothiocyanate (NPAI). Among the synthesized compounds, N-[4-(4-chlorophenyl)butyl]-S-[3-piperidin-1-yl)propyl]isothiourea (1k, OUP-186) exhibited potent and selective antagonism against human H3R but not human H4R, in vitro. Of particular interest, they did not show antagonism for the histamine release in rat brain microdialysis in vivo, suggesting species-selective differences in antagonist affinities. Furthermore, in silico docking studies of OUP-186 and its C2-homolog (OUP-181) in human/rat H3Rs suggested that the structural difference of antagonist-docking sites between human and rat H3Rs was attributable to the Ala122/Val122 mutation.
一般論文
  • 奥西 淳二, 長原 弘毅, 辻谷 久美子, 松瀬 仁, 久川 和之, 曽我 学
    2016 年 136 巻 9 号 p. 1233-1242
    発行日: 2016/09/01
    公開日: 2016/09/01
    [早期公開] 公開日: 2016/06/15
    ジャーナル フリー
     Environmental cleaning and disinfection plays an important role as a part of the standard precautions to prevent healthcare-associated infections, whereas hand hygiene is one of the most important strategies for breaking the chain of transmission. Cleaning and disinfection of high-touch areas in a health-care facility is emphasized. And wiping with an alcohol-saturated cloth which has features such as low corrosion and a wide range of antimicrobial activity is performed commonly for this purpose. Although alcohol provides immediate activity against enveloped viruses, its virucidal activity against certain non-enveloped viruses, including norovirus, is insufficient. We created a novel alcohol-based hand rub, MR06B7, which is safe for the skin, and is active against an extended spectrum of microorganisms including non-enveloped viruses. For environmental surface disinfection, a novel disinfectant MR13B15, which is based on MR06B7, has been developed. In vitro antimicrobial activity against a variety of pathogens, material compatibility, and simulated surface disinfection and decontamination efficacy of MR13B15 were investigated. According to the results, MR13B15 demonstrated potent bactericidal, fungicidal, mycobactericidal, and virucidal activity within a short contact time in addition to superior efficacy against non-enveloped viruses compared to ethanol for disinfection. Moreover, MR13B15 showed better material compatibility. Two simulation tests conducted for evaluating the disinfection and decontamination potency on environmental surfaces against feline calicivirus, a surrogate for norovirus, indicated that MR13B15 had superior efficacy for surface treatment compared to ethanol. These findings suggest that MR13B15, which satisfies most requirements of an environmental surface disinfectant, may contribute to accomplishing advanced standard precautions in preventing infections.
  • 渡邉 文之, 篠原 久仁子, 土橋 朗, 天貝 賢二, 原 和夫, 倉田 香織, 飯嶋 秀郎, 島川 清, 島田 匡彦, 阿部 櫻子, 武井 ...
    2016 年 136 巻 9 号 p. 1243-1254
    発行日: 2016年
    公開日: 2016/09/01
    ジャーナル フリー
     This study built a protocol for drug therapy management (hereinafter “the protocol”) that would enable continuous support from the decision making of smoking cessation therapy to the completion of therapy through the collaboration of physicians and community pharmacists, after which we evaluated whether the use of this protocol would be helpful to smoking cessation therapy. This study utilized the “On the Promotion of Team-Based Medical Care”, a Notification by the Health Policy Bureau as one of the resources for judgment, and referred to collaborative drug therapy management (CDTM) in the United States. After the implementation of this protocol, the success rate of smoking cessation at the participating medical institutions rose to approximately 70%, approximately 28-point improvement compared to the rate before the implementation. In addition to the benefits of the standard smoking cessation program, this result may have been affected by the intervention of pharmacists, who assisted in continuing cessation by advising to reduce drug dosage as necessary approximately one week after the smoking cessation, when side effects and the urge to smoke tend to occur. Additionally, the awareness survey for the intervention group revealed that all respondents, including patients who failed to quit smoking, answered that they were satisfied to the question on general satisfaction. The question about the reason for successful cessation revealed that the support by pharmacists was as important as, or more important than, that by physicians and nurses. This infers that the pharmacists' active engagement in drug therapy for individual patients was favorably acknowledged.
  • 海野 けい子, 野田 誠紀, 川崎 洋平, 井口 和明, 山田 浩
    2016 年 136 巻 9 号 p. 1255-1262
    発行日: 2016年
    公開日: 2016/09/01
    ジャーナル フリー
     Beta-cryptoxanthin [β-CRX, (3R)-β, β-caroten-3-ol] is a provitamin A and a potent antioxidant that is abundant in Satsuma mandarin orange (Citrus unshiu MARC.), which is the most popular fruit in Japan. The anti-stress effect of β-CRX on humans was evaluated in fifth-year university students during both routine daily life at the university and at pharmacy practice. The study design was a double-blind group comparison and participants (n=20; female 12, male 8) were randomly assigned to β-CRX-rich orange juice or placebo (β-CRX was removed from orange juice) groups. β-CRX or placebo juice (125 mL, once a day, after breakfast) were consumed from 10 d prior to the pharmacy practice and continued for 10 d into the practice period. To assess participants' anxiety, the state-trait anxiety inventory test was carried out before the pharmacy practice. Salivary α-amylase activity (sAA) was measured as a marker of sympathetic nervous system activity. In the placebo-group, sAA in the evening (post-practice sAA) tended to be higher than sAA in the morning (pre-practice sAA) during both routine daily life at the university and during pharmacy practice. In the β-CRX-group, the increase of post-practice sAA was suppressed in females. These results suggested that β-CRX has an anti-stress effect, at least, in females.
  • 鹿村 恵明, 真野 泰成, 小茂田 昌代, 根岸 健一, 佐藤 嗣道, 宮崎 智
    2016 年 136 巻 9 号 p. 1263-1273
    発行日: 2016年
    公開日: 2016/09/01
    ジャーナル フリー
     This nationwide survey aimed to evaluate reduction of drug and medical costs due to prevention of serious adverse drug reactions through pharmaceutical inquires by community pharmacist, and investigate relation with iyaku bungyo (separation of dispensing from medical practice) rates. Using the national list of pharmacies, 10% of pharmacies were randomly selected by prefecture and asked to participate in an Internet-based survey. The survey period was 7 days, from July 21 to July 27, 2015. Of the 5575 pharmacies queried, 818 responded to the survey (response rate: 14.7%). The proportion of inquiries to total prescriptions was 2.6%. Among these, the proportion of prescriptions changed in response to inquiry was 74.9%. An estimated 103 million yen was saved by reducing drug costs, and 133 million yen was saved by reducing medical costs due to prevention of serious adverse drug reactions. Comparison of prescription change rates between pharmacies with high and low iyaku bungyo rates indicated that the proportion of prescriptions changed was significantly higher in pharmacies with high iyaku bungyo rates than in those with low iyaku bungyo rates (78.2% vs. 69.9%, p<0.01). The findings suggest that inquiries about prescriptions are useful in ensuring the safety of pharmacotherapy and reducing the cost of healthcare. They also suggest that iyaku bungyo promotes prescription changes through inquiries, leading to proper use of pharmaceutical products.
ノート
  • 小森 浩二, 片岡 誠, 倉本 展行, 辻 琢己, 中谷 尊史, 安原 智久, 三田村 しのぶ, 塙 由美子, 荻田 喜代一
    2016 年 136 巻 9 号 p. 1275-1284
    発行日: 2016/09/01
    公開日: 2016/09/01
    ジャーナル フリー
     At Setsunan University, a debrief session (a poster session) is commonly performed by the students who have completed the long-term students' practice. Since the valuable changes in practical competency of the students cannot be evaluated through this session, we specified items that can help evaluate and methods that can help estimate the students' competency as clinical pharmacists. We subsequently carried out a trial called the “Advanced Clinical Competency Examination”. We evaluated 103 students who had concluded the students' practice for the second period (Sep 1, 2014, to Nov 16, 2014): 70 students (called “All finish students”) who had completed the practice in a hospital and pharmacy, and 33 students (called “Hospital finish students”) who had finished the practice at a hospital only. The trial was executed in four stages. In the first stage, students drew pictures of something impressive they had learned during the practice. In the second stage, students were given patient cases and were asked, ”What is this patient's problem?” and “How would you solve this problem?”. In the third stage, the students discussed their answers in a group. In the fourth stage, each group made a poster presentation in separate rooms. By using a rubric, the teachers evaluated each student individually, the results of which showed that the “All finish students” could identify more problems than the “Hospital finish students”.
  • 中村 仁哉, 羅 鍾煥, 金 柱成
    2016 年 136 巻 9 号 p. 1285-1296
    発行日: 2016年
    公開日: 2016/09/01
    ジャーナル フリー
     The different concentrations of ethanol (20-100%) and distilled water extract for Dendropanax morbifera LEV. leaves were evaluated to induce antioxidant and biological activity employed by variety of assays. The 20%, 80%, and 100% ethanol extract demonstrated the relatively higher activity, whereas distilled water, 40%, and 60% ethanol extracts exhibited the lower antioxidant and biological activity. Especially, 80% ethanol extract showed the remarkably higher radical scavenging activity, reducing power, total phenol and flavonoid content, α-glucosidase, and tyrosinase inhibitory activity, and alcohol dehydrogenases (ADH) and aldehyde dehydrogenase (ALDH) activity. Also, 100% ethanol extract exhibited relatively greater activity, but there did not show significant radical scavenging activity. Furthermore, there were 50% and 30% promotion effect for ADH activity assay and 80% and 40% promotion effect for ALDH activity assay in 80% and 100% ethanol extract, respectively. In addition, in the minimum inhibitory concentration (MIC), all extracts except for distilled water extract inhibited Bacillus cereus, Staphylococcus aureus subsp. aureus, Escherichia coli. For Pichia jadinii, whole extracts effectively inhibited yeast multiplication at concentration of 125 μg/mL for 100% ethanol extract and 250 μg/mL for the rest of extract. These result indicated that D. morbifera LEV. leaves extracted by 80% ethanol would be the ideal extracting solution to maximize inherent antioxidant and biological activity agent.
  • 鈴木 祥菜, 佐藤 陽子, 梅垣 敬三, 千葉 剛
    2016 年 136 巻 9 号 p. 1297-1305
    発行日: 2016/09/01
    公開日: 2016/09/01
    ジャーナル フリー
     We previously reported that a high-fat and high-cholesterol (HFHC) diet for 12 weeks induced non-alcoholic steatohepatitis (NASH) and influenced major CYP subtype gene expression levels and activities in a mouse model. In the present study, we determined the effects of the HFHC diet on CYP expression levels and activities prior to the establishment of NASH. When male C57BL/6J mice were fed the HFHC or a normal chow diet (Control) ad libitum for 4 weeks, body weights were significantly lower, whereas liver weights and hepatic lipid contents were significantly higher in the HFHC group than in the Control group. Under these conditions, hepatic microsomal luciferin-H (human CYP2C9 substrate) hydroxylation activity was significantly lower in the HFHC group than in the Control group. In order to investigate drug efficacy in mice fed the HFHC diet, an intraperitoneal glucose tolerance test was conducted with or without a pretreatment with tolbutamide (a CYP2C substrate) after 4 weeks of feeding. The plasma glucose-lowering effects of tolbutamide were attenuated in the HFHC group even though luciferin-H hydroxylation activity was suppressed in this group. The reason for this discrepancy was attributed to the mRNA expression levels of Cyp2c44 being lower and those of Cyp2c29 and Cyp2c66, which are involved in the metabolism of tolbutamide, being higher in the HFHC group than in the Control group. These results indicate that the expression of Cyp2c in the liver is influenced by the HFHC diet prior to the establishment of NASH and its regulation differed among the subtypes examined.
ケースレポート
  • 山本 千琴, 石田 卓矢, 大澤 隆志, 内藤 隆文, 川上 純一
    2016 年 136 巻 9 号 p. 1307-1312
    発行日: 2016/09/01
    公開日: 2016/09/01
    ジャーナル フリー
     Recalls of non-prescription drugs can contribute to preventing harm to human health, however, they also interrupt the supply of medicines to the market. The aim of the present study was to investigate the trends in non-prescription drug recalls in Japan. Class I, II, and III recalls reported from April 2009 to March 2014 were obtained from the websites of the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency. Each drug recall was classified according to year, dosage form, therapeutic category, and reasons for the recall. The trends over the 5 year period were assessed for each class. A total of 220 recalls were reported in the 5-year study period. The numbers of drug recalls were 21, 16, 80, 58, and 45 in 2009, 2010, 2011, 2012, and 2013, respectively. The drugs recalled consisted of 177 internal medications, 35 topical agents, and 8 others. Drug recalls were observed in 12 therapeutic categories of drug effects. The largest number of recalls was for Chinese herbal medicines and crude drugs. Of all the drug recalls in 2011, Chinese herbal medicines and crude drugs produced by one manufacturer accounted for 84%. Slightly more than half (54%) of drug recalls were due to a violation of the regulations. One manufacturer recalled many drugs because of non-compliance with the standard regulations for manufacturing drugs after 2011. In conclusion, non-prescription drug recalls can occur for any drug regardless of the dosage form and therapeutic category.
  • 潮平 英郎, 仲松 正司, 喜瀬 勇也, 比嘉 太, 健山 正男, 外間 惟夫, 国吉 幸男, 植田 真一郎, 中村 克徳, 藤田 次郎
    2016 年 136 巻 9 号 p. 1313-1317
    発行日: 2016/09/01
    公開日: 2016/09/01
    ジャーナル フリー
     Teicoplanin, a glycopeptide antibiotic for methicillin-resistant Staphylococcus aureus, is recommended for therapeutic drug monitoring during treatment. Maintaining a high trough range of teicoplanin is also recommended for severe infectious disease. However, the optimal dose and interval of treatment for severe renal impairment is unknown. We report a 79-year-old man who received long-term teicoplanin treatment for methicillin-resistant Staphylococcus aureus bacteremia due to postoperative sternal osteomyelitis with renal impairment. Plasma teicoplanin trough levels were maintained at a high range (20-30 μg/mL). Although the patient required long-term teicoplanin treatment, a further decline in renal function was not observed, and blood culture remained negative after the start of treatment. Teicoplanin treatment that is maintained at a high trough level by therapeutic drug monitoring might be beneficial for severe methicillin-resistant Staphylococcus aureus infection accompanied by renal impairment.
  • 渡部 俊彦, 伊藤 邦郎, 米澤 章彦
    2016 年 136 巻 9 号 p. 1319-1323
    発行日: 2016/09/01
    公開日: 2016/09/01
    ジャーナル フリー
     We set students' learning goal of basic life support (BLS) education at “being able to describe all the steps of BLS in an appropriate order”, and objectively analyzed the appropriateness of the learning goal we set and educational effects of lecture contents. Before delivering a lecture, we provided students with an assignment which asked them to “Describe the steps of BLS in an appropriate order”, and investigated students' levels of acquiring knowledge on BLS. As the results, the majority of students failed to perform this assignment. Since many students did not understand the process of BLS correctly, the learning goal was considered appropriate in the sense of promoting students' understanding of BLS. We also investigated whether the contents of BLS education was effective to achieve the learning goal. We provided students with the same assignment after the lecture, and the results showed that most students successfully performed the assignment. Furthermore, the time required for students to recall the whole process of BLS was significantly reduced after receiving the lecture, showing that the BLS lecture was effective in improving students' “ability to act to save lives”.
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