YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
最新号
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
  • 夏苅 英昭
    2024 年 144 巻 3 号 p. 243-247
    発行日: 2024/03/01
    公開日: 2024/03/01
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    The Education Award of the Pharmaceutical Society of Japan (PSJ) was conferred for “Contribution to pharmacy/pharmacist education through writing on organic chemistry.” The award-winning activities were described in three parts section 1–3. Section 1 Importance of Research and Education in Organic Chemistry: In this section, it is explained that organic chemistry serves as the fundamental basis for a wide range of natural science disciplines studied in pharmaceutical departments. It emphasizes that having a solid foundation in organic chemistry is essential for pharmacists to understand pharmaceuticals. This knowledge contributes significantly in healthcare settings such as team-based medical care (interprofessional cooperation) with physicians and nurses, as well as in interactions with patients, providing a unique contribution that other professions cannot achieve. Section 2 Two Serial Articles Written on Organic Chemistry: This part mentions two serial articles that are beneficial for pharmacists and pharmaceutical researchers. These articles aimed to broaden specialized knowledge and provide practical information, contributing to pharmaceutical education and professional training for pharmacists. Section 3 Publication of New Organic Chemistry Textbooks: In this section, the introduction of textbooks and reference books in the field of organic chemistry for pharmaceutical education is highlighted. These educational materials were published to offer valuable information to pharmaceutical students and aspiring pharmacists, enhancing their expertise. These three writing activities significantly contributed to pharmaceutical education and the improvement of the professional work of pharmacists.

誌上シンポジウム
  • 諫田 泰成, 黒川 洵子
    2024 年 144 巻 3 号 p. 249-250
    発行日: 2024/03/01
    公開日: 2024/03/01
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  • 黒川 洵子, 清水 聡史, 坂本 多穗
    2024 年 144 巻 3 号 p. 251-255
    発行日: 2024/03/01
    公開日: 2024/03/01
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    Cardiotoxicity induced by anti-cancer drugs is a significant concern for patients undergoing cancer treatment. Some anti-cancer drugs can damage cardiac muscle cells directly or indirectly, potentially leading to severe heart failure. Various risk factors, including the type and dosage of chemotherapy agents as well as patient background, contribute to the development of cardiotoxicity. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which enable patient-specific toxicity prediction, hold great promise in this regard. However, the practical implementation of hiPSC-CMs-based prediction of anti-cancer drug-induced cardiotoxicity still faces hurdles. One major challenge involves establishing and optimizing experimental systems for evaluating contractile dysfunction, the ultimate output of heart failure, using hiPSC-CMs. Such efforts are currently underway globally, focusing on tailoring functional evaluation systems to the characteristics of hiPSC-CMs. In this paper, we provide an overview of the contraction mechanisms of cardiac cells and introduce a method of measuring contraction that we have developed, and discuss the current status of contractile function evaluation methods using hiPSC-CMs.

  • 濱野 裕章, 座間味 義人, 牛尾 聡一郎, 新村 貴博, 合田 光寛, 石澤 有紀, 石澤 啓介
    2024 年 144 巻 3 号 p. 257-264
    発行日: 2024/03/01
    公開日: 2024/03/01
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    Cancer therapies have evolved considerably thereby substantially improving the survival of patients with cancer. However, cardiotoxicity, such as myocarditis and heart failure, induced by anticancer drugs, including immune checkpoint inhibitor(ICI)s and doxorubicin, present serious challenges. Numerous observations have indicated increased risks of cardiotoxicity- and cancer-related mortality in patients with drug-induced cardiotoxicity. Therefore, the prevention and management of drug-induced cardiotoxicity should be prioritized to enable sustainable long-term treatment while preserving patients’ quality of life. Recently, medical research has been primarily focused on elucidation of therapeutic benefits and adverse events using medical big data, including worldwide databases of adverse events. The aim of the present study was to establish prevention strategies for drug-induced cardiotoxicity and advance data analytics. A data-driven approach was adopted to comprehensively analyze patient data and drug-induced cardiotoxicity. These data analytics revealed numerous risk factors, leading to the development of drugs that mitigate these factors. Furthermore, many unknown adverse events with molecularly targeted drugs were brought to light. Consequently, the importance of managing adverse events, guided by insights from data science, is predicted to increase. In this symposium review, we introduce our research exemplifying pharmaceutical studies utilizing medical big data. In particular, we discuss in detail the risk factors associated with myocarditis induced by immune checkpoint inhibitors along with prophylactic agents to mitigate doxorubicin-induced cardiotoxicity.

  • 柳田 翔太, 諫田 泰成
    2024 年 144 巻 3 号 p. 265-271
    発行日: 2024/03/01
    公開日: 2024/03/01
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    Recent advances in cancer therapy have significantly improved the survival rate of patients with cancer. In contrast, anti-cancer drug-induced adverse effects, especially cardiotoxicity, have come to affect patients’ prognosis and quality of life. Therefore, there is a growing need to understand the anti-cancer drug-induced cardiotoxicity. Human induced pluripotent stem (iPS) cell-derived cardiomyocytes (hiPSC-CMs) have been used to assess drug-induced cardiotoxicity by improving the predictability of clinical cardiotoxicity and the principles of the 3Rs (replacement, reduction and refinement). To predict the anti-cancer drug-induced cardiotoxicity, we developed a novel method to assess drug-induced proarrhythmia risk using hiPSC-CMs by participating in the international validation. In addition, we established the chronic contractility toxicity assessment by image-based motion analysis. The compound BMS-986094, which was withdrawn from clinical trials, inhibited contractility velocity and relaxation velocity in hiPSC-CMs. Currently, we are trying to investigate the predictability of the contractility assay by comparing the hiPSC-CM data with adverse events reports from real-world database. In this review, we would like to introduce the novel imaging-based contractility method using hiPSC-CMs and future perspectives in anti-cancer drug-induced cardiotoxicity.

  • 藤川 雄太, 浅沼 大祐
    2024 年 144 巻 3 号 p. 273-274
    発行日: 2024/03/01
    公開日: 2024/03/01
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  • 吉原 利忠
    2024 年 144 巻 3 号 p. 275-283
    発行日: 2024/03/01
    公開日: 2024/03/01
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    Molecular oxygen plays essential roles in aerobic organisms as a terminal electron acceptor in the electron transport chain in mitochondria. The intracellular oxygen concentration of the entire body is strictly regulated by a balance between the supply of oxygen from blood vessels and the consumption of oxygen in mitochondria. The disruption of oxygen homeostasis in the body often results in serious pathologies such as cancer, cerebral infarction, and chronic kidney disease, and thus considerable effort has been devoted to the development of suitable techniques allowing the qualitative and quantitative detection of tissue oxygen levels. This review focuses on recent advances in the visualization of oxygen levels in tissue based on phosphorescence lifetime measurements using exogenously small molecular oxygen probes. Specially, I introduce the principle of oxygen sensing by means of phosphorescence quenching, recent advances in intracellular and intravascular oxygen probes based on iridium(III) complexes, a system for measuring phosphorescence lifetime combined with confocal scanning microscopy, and the applications of these technologies to in vivo oxygen measurements, emphasizing the usefulness of iridium(III) complexes as biological oxygen probes.

  • 上原 知也
    2024 年 144 巻 3 号 p. 285-290
    発行日: 2024/03/01
    公開日: 2024/03/01
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    Many useful radionuclides exist among the halogen elements. Fluorine-18 (18F) is used for positron emission tomography (PET) diagnosis, iodine-123 and iodine-131 (131I) for single photon emission computed tomography (SPECT) diagnosis, 131I for nuclear medicine therapy, and iodine-125 (125I) for research. Astatine-211 (211At), which can be produced by a cyclotron and is attracting attention as a versatile α-ray emitting radionuclide, also belongs to the halogen family. Therefore, if a labeling agent that can stably hold radio-halogens can be developed, it would be useful for the development of radiotheranostic agents that can be expanded from nuclear medicine diagnosis using PET and SPECT to nuclear medicine therapy using β-rays and even α-rays. Currently, benzoic acid derivatives are widely used as labeling agents for radio-halogens. The compounds labeled with 18F or radioiodine using this structure retain the radionuclide stably in vivo, but when 211At is labeled using this structure, 211At is rapidly released from the structure in vivo. Therefore, it is desirable to develop labeling agents that can stably hold 18F to 211At. Under these circumstances, we have found that a neopentyl structure with diol can stably retain 211At and 125I in vivo. Furthermore, this structure can also stably retain 18F in vivo. In this review, I would like to introduce the characteristics of neopentyl diol as a radio-halogens labeling agent and the development of radiotheranositc agents using neopentyl diol.

  • 小野 正博
    2024 年 144 巻 3 号 p. 291-297
    発行日: 2024/03/01
    公開日: 2024/03/01
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    Recently, radiotheranostics, which systematically combines diagnosis by nuclear medicine imaging and treatment by internal radiotherapy, constitutes a new modality in cancer treatment, with some clinical reports showing marked effects on cancer. We have been developing multifunctional chelates containing a target recognition unit, a radiation release unit, and a radioactivity pharmacokinetics control unit in the same molecule to develop efficient agents for cancer radiotheranostics based on chemical control of radioactivity pharmacokinetics. Using these compounds, we have achieved improved cancer accumulation and reduced renal accumulation in tumor-bearing mice, and have developed novel hybrid radiotheranostic agents that can be applied to simultaneously perform target-specific molecular imaging using γ-ray emitting radionuclides and internal radiotherapy using α-particle-emitting radionuclides. For example, 111In/225Ac-labeled PSMA-DA1, which targets prostate-specific membrane antigen (PSMA) for radiotheranostics, achieved clear in vivo imaging of PSMA in tumor-bearing mice and showed marked tumor growth inhibition. In addition to PSMA, this platform for radiotheranostics has also shown efficacy against various cancer target molecules, including carbonic anhydrase IX (CA-IX), which is highly expressed in hypoxic regions of cancer, and glucagon-like peptide-1 receptor (GLP-1R), which is highly expressed in insulinomas. This review presents these recent results of our studies on radiotheranostics for cancer.

総説
  • 植田 正
    2024 年 144 巻 3 号 p. 299-310
    発行日: 2024/03/01
    公開日: 2024/03/01
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    This study focuses on the modulation of protein aggregation and immunogenicity. As a starting point for investigating long-range interactions within a non-native protein, the effects of perturbing denatured protein states on their aggregation, including the formation of amyloid fibrils, were evaluated. The effects of adducts, sugar modifications, and stabilization on protein aggregation were then examined. We also investigated how protein immunogenicity was affected by enhancing protein conformational stability and other factors.

  • 寺町 ひとみ
    2024 年 144 巻 3 号 p. 311-328
    発行日: 2024/03/01
    公開日: 2024/03/01
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    When I graduated from university, my aim was to become a pharmacist capable of recommending prescription medicines to doctors and teaching others to do the same. To achieve this goal, I developed comprehensive curricula incorporating progressive educational tools such as problem-based learning and small group discussions. Subsequently, the effectiveness of these tools and curricula was evaluated, and the findings of these assessments were published in various peer-reviewed journal articles. Consequently, a body of evidence on the most effective ways to recommend prescription medicines to doctors was gradually established. This paper aims to summarize this comprehensive body of research spanning over 43 years, with the objective of highlighting the valuable insights gained thus far, identifying the best practice techniques, and exploring potential avenues for future research.

    Editor's pick

    著者は、大学卒業時に医師に処方提案ができ、患者などに服薬指導ができる薬剤師を目指していた。その目的を達成するために、新しい教育手法であるPBL・SGDなどの教育ツールを組み込みこんだカリキュラムを作成し、その有効性について評価した。また、処方提案に必要なエビデンスのための論文を多数公表した。本総説は、著者の43年間にわたる研究について述べている。

ノート
  • 横幕 香織, 安原 智久, 永田 実沙, 上田 昌宏, 串畑 太郎, 曽根 知道
    2024 年 144 巻 3 号 p. 329-338
    発行日: 2024/03/01
    公開日: 2024/03/01
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    Although the issue of home medical care and pharmacists remains widespread, much of the discussion has concentrated on its state in urban areas. We believe that it is necessary to consider the state of home health care in medium-sized regions, that is separate from its urban form, with a population of approximately 100000. Thus, we conducted a qualitative study in Hikone City, Shiga Prefecture, to identify factors that impede pharmacists involved in home medical care. We conducted a questionnaire-based survey in an area of the same size to verify the generality of the concepts obtained from the qualitative study and validate the concepts using quantitative analyses. Two questionnaires on the role of community health care and home health care practice based on the concepts obtained from the qualitative study was sent to 342 pharmacies located in five regions. The number of valid responses was 170, and the data collection rate was 49.4%. We identified nine factors from the former and five from the latter. The current status of pharmacists in home health care in a medium-sized region, as identified by the quantitative study, was similar to that of the conceptual picture obtained from the qualitative study. Furthermore, the high versatility of the extracted concepts was verified.

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