著者

田中 啓祥

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.141, no.5, pp.647-653, 2021-05-01 (Released:2021-05-01)

参考文献数

35

被引用文献数

3

---

Remarkable progress in our ability to analyze diseased tissue has revolutionized our understanding of disease. From a simplistic understanding of abnormalities in bulk tissue, there is now increasing recognition that the heterogeneous and dynamically evolving disease microenvironment plays a crucial role in disease pathogenesis and progression as well as in the determination of therapeutic response. The disease microenvironment consists of multiple cell types as well as the various factors that these cells secrete. There is now immense interest in treatment strategies that target or modify the abnormal disease microenvironment, and a deeper understanding of the mechanisms that drive the formation, maintenance, and progression of the disease microenvironment is thus necessary. The advent of 3-dimensional (3D) cell culture technology has made possible the reconstitution of the disease microenvironment to a previously unimaginable extent in vitro. As an intermediate between traditional in vitro models based on 2-dimensional (2D) cell culture and in vivo models, 3D models of disease enable the in vitro reconstitution of complex interactions within the disease microenvironment which were unamenable in 2D while simultaneously allowing the mechanistic analysis of these interactions that would be difficult to perform in vivo. This symposium review aims to highlight the promise of using 3D cell culture technology to model and analyze the disease microenvironment using pancreatic cancer as an example.

著者

野瀬 清

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.122, no.10, pp.773-780, 2002-10-01 (Released:2003-02-18)

参考文献数

54

被引用文献数

5 5

---

Reactive oxygen species (ROS) are generated from cells stimulated by various cytokines, hormones, and stresses, and regulate celluar functions such as gene expression and cell growth. They affect activities of many types of molecular targets, including signaling molecules and transcription factors. Early-respons genes (c-fos, egr-1 and JE) that encode transcription factors are induced by ROS, and activities of their products are modulated by ROS through redox-based mechanisms. We isolated a novel gene, hic-5, that was induced by hydrogen peroxide and encodes a focal adhesion protein. hic-5 was found to translocate to the nucleus in cells treated with ROS and regulates several cellular genes. We propose that hic-5 is a key element in the transduction of signals from the cell surface to the nucleus under oxidative stress.

著者

倉田 祥一朗

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.126, no.12, pp.1213-1218, 2006-12-01 (Released:2006-12-01)

参考文献数

37

被引用文献数

1 3

---

One of the fundamental questions in innate immunity is how a large battery of invading pathogens is recognized by a limited number of germ line-encoding receptors. In Drosophila, peptidoglycan recognition protein (PGRP) family members have a crucial role in recognizing invading bacterial pathogens and in inducing immune reactions. PGRP-SA, -SD, and -SC1a are involved in recognizing gram-positive bacteria and in activating the Toll pathway to produce antimicrobial peptides. PGRP-LC and -LE recognize diaminopimelic acid (DAP)-containing peptidoglycans, which are cell wall components of many gram-negative bacteria and some gram-positive bacteria, and activate the imd pathway to produce antibacterial peptides. In addition to the extracellular function of PGRP-LE to activate immune reactions in the hemolymph, PGRP-LE acts as an intracellular receptor for monomeric DAP-type peptidoglycans. Moreover, a version of PGRP-LE containing only the PGRP domain functions extracellularly as a CD14-like accessory factor, capable of enhancing PGRP-LC-mediated peptidoglycan recognition. Subsequent intracellular signaling is transduced through the RHIM-like motif found in PGRP-LC and -LE.

著者

北澤 京子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.4, pp.575-578, 2019-04-01 (Released:2019-04-01)

参考文献数

18

被引用文献数

1

---

“Choosing Wisely” is a campaign activity promoting awareness of the dangers of providing medical tests, drugs, and procedures that are not supported by firm scientific evidence and that may harm patients. The American Society of Health-System Pharmacists has released a recommendation on polypharmacy. Stakeholders such as patients, health professionals, hospital executives, industry, and mass media may all contribute to treatment decision making. The patient-centric “five questions you need to ask your doctor” are a useful trigger for better dialogue between patients and health professionals and could contribute to appropriate drug prescription in which benefit always exceeds the potential for harm.

著者

元屋地 孝士

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.141, no.4, pp.511-515, 2021-04-01 (Released:2021-04-01)

参考文献数

16

被引用文献数

1

---

The first step in small-molecule drug discovery is the identification of hit compounds via high-throughput screening (HTS). In transporter drug discovery, most HTS assays are based on the uptake of labeled substrates, but such functional assays cannot be developed for many transporters, such as intracellular organelle transporters. These transporters remain unexplored in drug discovery despite their promise as drug targets. Affinity selection-mass spectrometry (AS-MS) is a label-free binding assay technology that has been developed as an HTS technology for analyzing interactions between targets and compounds. The use of AS-MS technology enables HTS against every type of drug target, in contrast to functional assays. AS-MS technology is usually used for soluble proteins, but we have developed this technology for application to membrane proteins as well. So far, we have used AS-MS for HTS of approximately 400000 compounds. In this review, the principles and application of AS-MS technology are introduced and an HTS campaign for solute carrier type 17A8 (SLC17A8) (vesicular glutamate transporter 3) is presented as an example.

著者

平山 恵津子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.124, no.7, pp.437-442, 2004-07-01 (Released:2004-07-01)

参考文献数

18

被引用文献数

2 2

---

The influenza virus copies its genomic RNA in the nuclei of host cells, but the viral particles are formed at the plasma membrane. Thus the export of a new genome from the nucleus into the cytoplasm is essential for viral production. Several viral proteins, such as nucleoprotein (NP), RNA polymerases, and matrix protein 1 (M1), synthesized in the cytoplasm are imported into the nucleus and form a viral ribonucleoprotein complex (vRNP) with new genomic RNA. vRNP is then exported into the cytoplasm from the nucleus. It was found unexpectedly that the production of influenza virus was suppressed in Madin-Darby canine kidney cells at 41°C, although viral proteins were synthesized, because nuclear export of vRNP is blocked by the dissociation of M1 from vRNP. It was also suggested that a certain protein(s) synthesized only at 41°C inhibited the association of M1 with vRNP. The potential of heat-shock protein 70 (HSP70) as a candidate obstructive protein was investigated. Induction of HSP70 by prostaglandin A1 (PGA1) at 37°C caused the suppression of virus production. The nuclear export of viral proteins was inhibited by PGA1, and M1 was not associated with vRNP, indicating that HSP70 prevents M1 from binding to vRNP. An immunoprecipitation assay showed that HSP70 was bound to vRNP, suggesting that the interaction of HSP70 with vRNP is the reason for the dissociation of M1.

著者

佐藤 政男 鈴木 真也

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.127, no.4, pp.703-708, 2007-04-01 (Released:2007-04-01)

参考文献数

16

被引用文献数

6 6

---

Much attention has been paid to lifestyle-related diseases including type 2 diabetes mellitus, cardiovascular disease, hypertension, and hyperlipidemia because the incidence rates of these diseases are increasing in developed countries. Elucidation of factors contributing to the development of obesity and insulin resistance is needed. Metallothionein (MT), a ubiquitous metal-binding protein, is induced not only by heavy metals but also by various kinds of stresses. Endoplasmic reticulum (ER) stress is caused by accumulation of misfolded proteins in ER. Recently, increased ER stress by obesity and impairment of insulin action by ER stress have been reported. Exposure to ER stress increased induction of MT synthesis, and an enhanced response to ER stress evaluated as expression of Bip/GRP78mRNA was observed in the liver of MT-null mice, suggesting that MT attenuates expression of ER stress. MT may prevent ER stress and thereby modulate the development of obesity and insulin resistance. A possible role of metallothionein in response reaction for ER stress is discussed.

著者

山本 美智子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.141, no.3, pp.393-402, 2021-03-01 (Released:2021-03-01)

参考文献数

21

---

With the progress of medical treatment, information on drugs, etc. is overflowing on the media and the Internet, and some of them are leading to uncertain information for the purpose of profit, and some of them are wrong information or inaccurate information, and the effect on the patient is regarded as a problem. In Japan, information on public pharmaceuticals for patients and consumers is provided on the Internet, but its utilization is not sufficient. In the Pharmaceuticals and Medical Devices Act, it is stated that “Citizens shall endeavor to use pharmaceuticals, etc., properly and deepen their knowledge and understanding of their efficacy and safety”. On the other hand, there is a variety of information available on the Internet, and simply searching does not necessarily lead to reliable information. It is necessary to provide information with a mechanism to ensure that the information is reliable so that it can lead to appropriate medical care. Overseas, medical information infrastructure systems, including highly reliable public pharmaceuticals based on evidence, have been developed. Examples include National Health Service (NHS) in the United Kingdom, MedlinePlus in the United States, and National Prescribing Service (NPS) MedicineWise in Australia. In the era of digital health, it is necessary to discuss issues and prospects for the construction and dissemination of information provision infrastructure that meets the needs of patients and consumers from the perspective of industry, government, academia, and patients.

著者

元井 玲子 矢野 育子 尾崎 淳子 鋒山 香苗 山本 崇 深津 祥央 石塚 良子 松村 由美 谷口 正洋 東村 享治 松原 和夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.10, pp.1177-1184, 2015-10-01 (Released:2015-10-01)

参考文献数

13

被引用文献数

2 2

---

The use of iodine contrast agents occasionally causes serious allergic symptoms including anaphylaxis. At Kyoto University Hospital to prevent nephropathy we began recommending water intake before and after administration of iodine contrast agents in September 2012. In the present study we investigated the effect of water intake on the incidence of allergy-like events after the use of non-ionic iodine contrast agents. We extracted the occurrence of allergy-like events from the incident report system in our hospital from January 2011 to September 2014, and classified these events into the following 3 grades: 1+ (follow-up); 2+ (medication treatment); and 3+ (hospitalization). The allergy-like incidence rate was calculated for subsequent evaluation according to season and water intake. Allergy-like events significantly decreased from 0.49% before the recommendation of water intake to 0.26% at 1 year and 0.20% at 2 years after implementing the recommendation. The incidence of allergy-like events was significantly higher in summer than in winter before water intake was recommended. After implementing the recommendation, the value for summer significantly decreased to an incidence similar to that of winter. Respiratory and gastrointestinal allergy-like symptoms were dramatically decreased after implementing the recommendation. Water intake may be useful for preventing allergy-like events associated with non-ionic iodine contrast agents, especially during the summer.

著者

松尾 洋介

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.3, pp.347-354, 2017-03-01 (Released:2017-03-01)

参考文献数

32

被引用文献数

1

---

In recent years, plant polyphenols have attracted great attention due to their wide range of biological activities. Certain kinds of polyphenols have complex structures; therefore, it is difficult to elucidate their total structure, including stereochemistry. In this study, we reinvestigated the stereostructures of two major C-glycosidic ellagitannins contained in Quercus plants, vescalagin and castalagin, and revised their stereostructures based on theoretical calculations of spectroscopic data. We also determined the structures of quercusnins A and B, isolated from the sapwood of Quercus crispula, based on theoretical calculations of NMR data. The oxidation mechanism of polyphenols has not been entirely elucidated. Therefore, we have also studied the oxidation mechanism of tea catechins during black tea production. Our investigation of the oxidation mechanism of black tea pigment theaflavins revealed that the difference in the position of the galloyl ester affords different oxidation products of theaflavins. In addition, oxidation products of pyrogallol-type catechins could be classified into three types—dehydrotheasinensins, theacitrins, and proepitheaflagallins; their detailed production and degradation mechanisms were also examined.

著者

深井 良祐 鄭 暁霞 本島 和典 加来田 博貴

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.131, no.3, pp.347-351, 2011-03-01 (Released:2011-03-01)

参考文献数

27

被引用文献数

3 4

---

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve physical and mental pain, and to improve patients' quality of life. However, stomach irritation is a major side effect. Most NSAIDs inhibit cyclooxygenases (COXs), and inhibition of COX-1 on the stomach mucous membrane is thought to be responsible for the gastric disturb- ance. Consequently, development efforts have focused on COX-2-selective inhibitors, while COX-1-selective inhibitors have been rather neglected. Subsequently, however, it was shown that inhibition of either COX-1 or COX-2 alone does not induce gastric damage. Therefore, we have developed the COX-1-selective inhibitor N-(4-aminophenyl)-4-trifluoromethylbenzamide (TFAP), which shows analgesic activity without causing gastric damage. However, metabolism of TFAP generates a colored metabolite, resulting in red-purple coloration of urine after administration. In addition, the analgesic activity of TFAP is weaker than that of indomethacin. Thus, we designed a series of new COX-1-selective inhibitors, the 5-amino-2-ethoxy-N-(substituted)benzamide (ABEX) series, in order to avoid formation of the colored metabolite by modifying the diaminopyridine skeleton. As a result of structural modification and in vitro and in vivo testing of compounds in the ABEX series, we found a novel COX-1-selective inhibitor, 5-amino-2-ethoxy-N-(3-trifluoromethylphenyl)benzamide (ABEX-3TF), which shows better analgesic activity than indomethacin, and does not cause coloration of urine.

著者

寺田 智祐

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.5, pp.663-666, 2020-05-01 (Released:2020-05-01)

参考文献数

3

被引用文献数

1

---

The development of cancer genomic medicine has been embraced as an important new policy issue in “The 3rd Basic Plan to Promote Cancer Control Programs” formulated by the Japanese government. Cancer-associated gene panel testing has been recognized by the public health insurance system since July 2019, and is a critical component of the clinical implementation of genomic science. Because of this dynamic change in cancer medicine, pharmacists are now expected to acquire knowledge about genomic science, and to apply it to individualized and appropriate pharmacotherapies. This review outlines the roles of pharmacists in cancer genomic medicine.

著者

山本 美智子 中山 健夫 入江 徹美

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.141, no.3, pp.375-376, 2021-03-01 (Released:2021-03-01)

著者

藤川 康浩

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.6, pp.881-885, 2019-06-01 (Released:2019-06-01)

被引用文献数

1 1

---

Many nonclinical and clinical studies are conducted to submit new drug applications for chemical entities. Nonclinical studies cover pharmacology, pharmacokinetic, and toxicology aspects and provide pharmacologic evidence as well as kinetic and toxicologic profiles of the compounds. The risks and benefits of compounds are evaluated based on these nonclinical studies, especially before initiation of the first human trials. Therefore, using adequate procedures, highly controlled, quality nonclinical data should be obtained. This section shares and discusses items required of good laboratory practice (GLP)-compliant organizations and management systems in GLP facilities in the pharmaceutical industry as well as those required for GLP inspections by the Japanese Pharmaceuticals and Medical Devices Agency. In addition, it explains standard operating procedures for conducting quality, non-GLP, pharmacology, and pharmacokinetic studies.

著者

吉川 友章 岡田 直貴 中川 晋作

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.127, no.5, pp.789-796, 2007-05-01 (Released:2007-05-01)

参考文献数

39

被引用文献数

3 4

---

Drug delivery system (DDS) research has contributed greatly toward improving chemotherapy efficacy and reducing its adverse effects through the development of approaches to optimize pharmacokinetics, such as controlled release and targeting. On the other hand, the remarkable progress of this latest life science research has altered the concept of what constitutes medical supplies. A change in this concept would allow for the consideration of medical materials that use not only conventional low molecular-weight organic compounds, but also biomacromolecules, including nucleic acids and proteins, that constitute living organisms. Although these biomacromolecular drugs are expected to demonstrate excellent efficacy based on their intrinsic bioactivity, they quickly degrade when administered in vivo and only a limited number have therefore been developed into medicines. In addition, most biomacromolecular drugs are ineffective until they are delivered to particular cells within a tissue or to particular organelles within a cell. To develop effective biomacromolecular medicines, it is necessary to introduce a DDS that is capable of ensuring internal stability as well as precise control of internal and intracellular dynamics, and to establish a new fundamental technology for DDS that can accommodate the material properties and mechanisms of action of the biomacromolecular drugs. In this context, this review introduces our approach to the design and creation of “Intracellular DDS” using fusogenic liposomes for application to gene therapy and tumor peptide vaccines. We suggest that this technology is very important for controlling the intracellular pharmacokinetics of biomacromolecular drugs.

著者

酒井 隆全

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.141, no.2, pp.165-168, 2021-02-01 (Released:2021-02-01)

参考文献数

12

被引用文献数

3

---

In recent years, a variety of medical information has been digitized, and hence, various medical big data have become available. Spontaneous reporting databases are a part of the medical big data. In Japan, the Pharmaceuticals and Medical Devices Agency has developed the “Japanese Adverse Drug Event Report (JADER) database” which has been available since 2012. Thus, everyone can publish safety signal information based on the results of disproportionality analysis using the spontaneous reporting database. Since the release of JADER, many researchers and healthcare professionals are interested in it, and many reports have been prepared using JADER. Although we tend to focus on the fact that it is a publicly available database with many cases, it also has various limitations such as lack of the denominator information, under-reporting, and reporting biases. Detected signals do not necessarily imply a causal relationship between the drug and adverse event. In the “Guideline on good pharmacovigilance practices (GVP) Module IX by European Medicines Agency”, signal detection is the first step in the signal management process. Signal detection alone does not complete pharmacovigilance activities. It is important to understand that spontaneous reporting databases are not only for researchers but also for those who are considering to apply them to clinical work by referring to research using these databases. In this symposium review, I will discuss the role and applicability of spontaneous reporting databases in medical big data.

著者

武隈 洋 百 賢二

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.141, no.2, pp.163-164, 2021-02-01 (Released:2021-02-01)

著者

平塚 祥子 熊野 宏昭 片山 潤 岸川 幸生 菱沼 隆則 山内 祐一 水柿 道直

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.120, no.2, pp.224-229, 2000-02-01 (Released:2008-05-30)

参考文献数

11

被引用文献数

5 7

---

The failure of patients to comply with treatment regimens recommended by their physicians is a significant clinical problem. Researches on the assessment of compliance have, however, been precluded by methodological difficulties such as lack of adequate measures. The purpose of this study was to develop a self-administered questionnaire to evaluate drug compliance. First, questionnaire containing a 52-items complied by two doctors, a pharmacist and a nurse, was tested on 81 outpatients, all volunteers, attending the departments of psychosomatic medicine and internal medicine. Four items were temporarily removed for later analysis because they directly inquired about drug compliance (drug compliance items). The other 48 items were analyzed and three factors consisting of 26 items were further studied : expectation on taking medicine, rejection to taking medicine and seeking knowledge of drugs. Chronback's alpha coefficients representing internal consistency of the three factors were sufficiently high (ranging from .75 to .84). Furthermore, we preformed a simplified pill count to validate the 4 drug compliance items. There was a weak to moderate correlation between the result of pill count and each of 4 drug compliance items. A new self-administered questionnaire of 30 items was thus developed and named the Drug Compliance Scale.

著者

原田 利一 水野 瑞夫 加藤 智雄

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.72, no.4, pp.591-593, 1952-04-25 (Released:2010-02-19)

参考文献数

4

被引用文献数

1 1

---

The alcoholic extracts of 53 kinds of shelf-fungi were tested for their antibacterial action against Staphylococcus aureus (Friedlender) and E. coli by the dilution method. Digests of Grifola sp. and Fomes sp. were found to have the most strong action against Staphylococus aureus.

著者

堤 広之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.8, pp.925-931, 2012-08-01 (Released:2012-08-01)

参考文献数

24

被引用文献数

3 4

---

Two crystals of a complex of (−)-gallocatechin-3-O-gallate (GCg) with caffeine and crystals of the complexes of (+)-catechin (CA) and (−)-catechin-3-O-gallate (Cg) with caffeine were prepared, and their stereochemical structures and intermolecular interactions were determined in X-ray crystallographic analysis. GCg formed 1:2 and 2:2 complexes with caffeine, and π-π interactions formed between the aromatic rings of GCg and caffeine in both complexes. In addition, CA of nongalloylated catechins formed a 1:1 complex with caffeine through intermolecular hydrogen bonds, whereas Cg of galloylated catechins formed a 1:2 complex with caffeine, which was formed by face-to-face and offset π-π interactions and intermolecular hydrogen bonds.