YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
141 巻, 12 号
選択された号の論文の12件中1~12を表示しています
受賞総説
  • 西山 卓志
    2021 年 141 巻 12 号 p. 1281-1288
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    We are developing the synthesis of biologically interesting carbazole compounds, including natural products by tandem cyclic reactions. In this report, we describe the new synthesis of carbazole-1,4-quinones as follows; 1) the synthesis of carbazole-1,4-quinones using a tandem ring closing metathesis (RCM) -dehydrogenation reaction, 2) a novel one-pot synthesis of carbazole-1,4-quinone by consecutive Pd-catalyzed cyclocarbonylation, desilylation, and oxidation reactions. Two new synthetic strategies were applied to the synthesis of carbazole-1,4-quinone alkaloids and ellipticine quinones, and then the antiproliferative activity against HCT-116 and HL-60 cells of the synthesized compounds were evaluated.

  • 石原 慎之
    2021 年 141 巻 12 号 p. 1289-1296
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    In recent years, antimicrobial resistance bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) have become a global problem. One of the countermeasures is to optimize the use of antimicrobial drugs, specifically to optimize the dosage and administration based on the therapeutic drug monitoring (TDM) and pharmacokinetics (PK)/pharmacodynamics (PD) theory. On the other hand, in clinical practice, clinical-pharmacometrics can be used for optimized management of individual patients of pharmaceutical products. Therefore, we aimed at individual optimization of infectious disease treatment for antimicrobial resistant bacteria, and tried a series of flows from model construction to clinical application, that is, practice of clinical pharmacometrics. In the context of individual optimization and optimization management of drug therapy in the medical field, it is considered that hospital pharmacists can contribute to the improvement of infectious disease treatment of antimicrobial resistance bacteria by contributing to the optimization of administration method. In addition, clinical pharmacometrics can be applied not only to antibacterial drugs but also to all drugs, and can be said to be a useful method for quantitatively evaluating the promotion of individualized administration methods for patients.

  • 松岡 悠太
    2021 年 141 巻 12 号 p. 1297-1304
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    Disruption of the redox balance in vivo is closely involved in the development of various diseases associated with oxidative stress. Therefore, methods for the in vivo analysis of antioxidants and free radicals are essential to elucidate the pathogenic mechanisms of such diseases. Although profluorescent nitroxide probes can be used to evaluate redox molecules with high sensitivity, these probes have low selectivity. Recently, we developed two profluorescent nitroxide probes, 15-((9-(ethylimino)-10-methyl-9Hbenzo[a]phenoxazin-5-yl)amino)-3,11-dioxa-7-azadispiro-hexadecan-7-yloxyl (Nile-DiPy) and 2,2,6-trimethyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)-6-pentylpiperidine-1-oxyl (NBD-Pen), which had high sensitivity and selectivity toward ascorbic acid and lipid-derived radicals, respectively. These probes can react sensitively and selectively to each target molecule and can be used in animal experiments. In this paper, we review the design strategies and application of these profluorescent nitroxide probes.

誌上シンポジウム
  • 中澤 洋介, 長井 紀章
    2021 年 141 巻 12 号 p. 1305-1306
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー
    Editor's pick

    Due to aging society of Japan, ophthalmic research is becoming more importance in not only doctor and nurse but pharmacist. This symposium (review) shows the state of the art in “Age-related changes in eye function and preventive ways”, and update ophthalmic studies including senescence, antiaging, immune privilege and drug delivery system. Many members will be interested in the ophthalmic research field when they read this review, and the information will help to improve the “Quality of Vision” in aging society.

  • 中村 信介, 原 英彰
    2021 年 141 巻 12 号 p. 1307-1317
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    The number of patients with exudative age-related macular degeneration, diabetic retinopathy and retinal vein occlusion is expected to rise in proportion with the aging of the population and increasing diabetes patients. Also, they are the most common diseases caused by intraocular neovascularization and are often difficult to treat. Currently, anti-vascular endothelial growth factor (VEGF) therapy has been developed and has demonstrated excellent results in treating macular edema, and many patients have avoided blindness. Unfortunately, there are problems with cases that do not respond to the anti-VEGF drugs and complications of administration. It is necessary to deepen the understanding of the physiological and pathological retinal roles of VEGF and to optimize the anti-VEGF therapy. There are also no drugs indicated for the regression of neovascularization itself. The solution to this problem is to develop novel therapies targeting other than VEGF. In this symposium review, we introduce the roles of VEGF in the ischemic retina and anti-angiogenic factors as promising therapeutic targets.

  • 細谷 健一, 赤沼 伸乙, 久保 義行
    2021 年 141 巻 12 号 p. 1319-1325
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    Since the retina continuously receives light to enable vision, reactive oxygen species (ROS) are easily generated in neural retina. The oxidative stress induced by ROS may be involved in the onset and progression of blinding aging diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Although supply of antioxidants to the retina is important to maintain the redox homeostasis in neural retina, the blood-retinal barrier (BRB) is created by complex tight-junctions of retinal capillary endothelial cells and retinal pigment epithelial cells to prevent the free diffusion of substances. The BRB is equipped with several membrane transporters to supply nutrients and essential molecules including antioxidants and drugs which exhibit antiaging effect to the retina from the circulating blood. In this review, the transporter-mediated retinal distribution of key endogenous compounds and drugs, such as vitamin C, l-cystine and gabapentin, is introduced for antiaging of the retina.

  • 奈邉 健, 松田 将也
    2021 年 141 巻 12 号 p. 1327-1332
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    Particularity of ocular immunity is manifested by “Immune privilege”. For example, it has been generally known that corneal transplantation is a typically successful organ transplantation compared with other organs. This immune privilege can be explained by “immune-suppressive ocular microenvironment” and “anterior chamber-associated immune deviation, ACAID”. This review focused on molecular mechanisms of the “immune-suppressive ocular microenvironment” and “ACAID”, so that possible anti-inflammatory strategies could be raised. Especially, in murine ACAID model, anti-inflammatory actions were induced probably through induction of Treg cells. As an anti-inflammatory strategy, anti-inflammatory Treg cells could be induced in vitro. Treg cells that are specifically responsive for a specific antigen can be induced by culturing spleen cells with the antigen and transforming growth factor-β (TGF-β). The induced Treg cells were activated by stimulation with the specific antigen. When the induced Treg cells were adoptively transferred to recipient mice, antigen-induced inflammation was effectively suppressed. The Treg cells may be able to be efficiently induced by eye-based mechanisms. Further analyses of mechanisms underlying the ocular immune privilege can be useful for development of new anti-inflammatory strategies on the eye basis.

総説
  • 亀井 淳三
    2021 年 141 巻 12 号 p. 1333-1342
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    An increasing number of patients complain to medical institutions about a cough that persists for more than 8 weeks, namely chronic cough. The cough observed in patients with chronic cough is not responsive to conventional antitussive agents such as dihydrocodeine and dextromethorphan, and this is a major clinical problem. The most common pathology of chronic cough in Japan is dry cough. Two causes of dry cough are increased sensitivity of cough receptors (cough hypersensitivity) and increased contraction of bronchial smooth muscle. Among these, the mechanisms of cough hypersensitivity are diverse, and understanding these mechanisms is important for the diagnosis and treatment of chronic cough. In this paper I will review the regulatory mechanisms of cough hypersensitivity, especially the regulation of Aδ fiber excitability by C fibers. Furthermore, the central mechanisms involved cough reflex are discussed in relation to central acting antitussives.

  • 大塚 誠
    2021 年 141 巻 12 号 p. 1343-1357
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    Since entering graduate school 43 years ago, I have been studying physical pharmaceutics with a focus on the effects of environmental factors on pharmaceutical properties of solid oral dosage forms during the manufacturing process. I have reported on changes in the characteristics of pharmaceutical products during manufacturing processes, such as grinding, mixing, granulation, and tableting owing to complicated phenomena based on chemical reactions or the crystalline polymorphic transitions of bulk drugs and excipients. To develop modern pharmaceutical manufacturing processes based on process analysis technology (PAT) as a next generation good manufacturing practice, real-time monitoring was introduced in these processes using a non-destructive analytical method, such as the near-infrared spectroscopy combined with chemometrics. Many case studies related to the mixing, granulation, tableting, and coating processes involving PAT have been reported. In those studies, I focused on clarifying the physical and chemical mechanism through “design space” representation. Additionally, non-destructive analytical methods, including X-ray computed tomography, audible acoustic emission, Raman spectroscopy, terahertz spectroscopy, and infrared thermal imaging analysis were applied as novel candidate analytical methods to the pharmaceutical process to monitor critical quality attributes. To achieve this purpose in various pharmaceutical dosage forms, I have been attempting the assembly of a modern manufacturing process managed through a “design space” paradigm involving in-line monitoring using novel analytical methods, multivariate analyses, and feed-back systems.

  • 安西 和紀
    2021 年 141 巻 12 号 p. 1359-1372
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    In the present paper, generation, detection and protection of reactive oxygen species (ROS)/free radicals in relation to the author's research over about 20 years are reviewed. ROS/free radicals are generally generated physically, chemically and biologically, and they are harmful to living organisms by inducing various disorders and diseases. To prevent the harmful effects of ROS/free radicals, antioxidants are believed to be useful. Among many methods to detect ROS/free radicals, ESR technique is a direct method and is described in detail in this review. Several topics such as the production of ROS/free radicals by low temperature atmospheric pressure plasma, the evaluation of antioxidant activity using hemolysis of erythrocytes and the protective effects of antioxidants against X-ray induced damage to mice, are presented.

一般論文
  • 杉本 幸子, 大原 宏司, 眞島 崇
    2021 年 141 巻 12 号 p. 1373-1387
    発行日: 2021/12/01
    公開日: 2021/12/01
    [早期公開] 公開日: 2021/10/01
    ジャーナル フリー

    The purpose of this study was to clarify the current status of collaboration between nurses and community pharmacists as well as the requests and expectations that community pharmacists have of nurses in community-based comprehensive care systems. Questionnaires requiring open-ended responses were sent to 867 pharmacies throughout Fukushima prefecture (excluding four suspended pharmacies). We asked one pharmacist at each facility to answer the questions. We then analyzed the collected questionnaires using descriptive statistics, including the current status of nurse cooperation and the basic information about the pharmacies. Additionally, the open-ended descriptions of nurses' requests and expectations were analyzed quantitatively and qualitatively. The questionnaire collection rate was 32% (278 cases), and the breakdown of pharmacies that responded was 68.0% for facilities with 1 or 2 full-time pharmacists and 27.0% for facilities with 3 to 5 pharmacists. About 30% of respondents reported contact with the nursing profession at least once a week, while about 50% reported no contact at all or several times a year. The types of nurses collaborating with the pharmacies were clinic nurses (54.6%) and visiting nurses (43.4%). Some pharmacists had expected nurses to work cooperatively and rely on pharmacists. These results indicate that only about half of the pharmacists had opportunities to cooperate with nurses. For trust to be established between nurses and pharmacists, it is necessary for nurses to ask the pharmacists about medication and consult with them about patient medication management.

ノート
  • 廣瀬 正幸, 平川 昭彦, 丹羽 若菜, 東口 貴彦, 田島 康介, 加藤 貴大, 山田 成樹
    2021 年 141 巻 12 号 p. 1389-1392
    発行日: 2021/12/01
    公開日: 2021/12/01
    ジャーナル フリー

    We discuss the current status of, and possible countermeasures for, acute drug poisoning among adolescents using OTC drugs. In the last 10 years, 36 patients aged <20 years who overdosed on OTC drugs were examined for the type of drug ingested, its active ingredients in cases of lethal dose intake, and the relevant place of purchase. Patients aged <20 years accounted for 30% of all the cases. The ingestion of multi-ingredient common-cold medication was the highest at 23%, and no ingestion of any first-class OTC drugs was observed. Caffeine accounted for 54% of the cases of lethal dose intake. At 80%, the most common method of drug purchase was from drugstores and other OTC vendors. In recent years, the number of adolescents patients who take lethal doses of OTC drugs has been increasing, and new measures are needed to avoid such cases. School pharmacists and vendors play a major role in reducing the incidences of drug poisoning. As drugs can be easily purchased over the counter, increasing the vendors' awareness of the problem throughout society may be the quickest way to reduce the incidences of acute drug poisoning among adolescents.

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