著者

江口 里加 加藤 正久 金子 絵里奈 草場 健司 吉川 学 山野 徹 瀬尾 隆 萩原 明人

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.3, pp.501-506, 2015 (Released:2015-03-01)

参考文献数

26

被引用文献数

1

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Much of the damage to health caused by drugs could be prevented by appropriate care. A well-defined duty of care and further information are required for healthcare professionals. Although there are many litigation cases to use as references, neither the extent of the duty of care nor the obligation to explain medication according to the type of drug prescribed has yet been fully established. Thus, we systematically collected decided cases of adverse drug events, and assessed the degree of the duties of care and information. Specifically, we collected decided cases in which physicians, dentists, pharmacists, nurses, or hospitals had been sued. Data were derived from Bessatsu Jurist Iryo-kago Hanrei Hyakusen, Hanrei Jihou, and Hanrei Times from 1989 to November 2013, and information on precedents in the records of the Supreme Court of Japan from 2001 to November 2013. We analyzed the cases, and assessed the following according to the type of drug: (1) standards and explanations when dealing with drugs that were critical issues in litigation, and (2) the degree of the physician's or pharmacist's duties of care and information. In total, 126 cases were collected. The number of drug categories classified was 27, and 9 were considered of practical importance. After this systematic review, we found a trend in the degree of the required level of care and information on several drugs. With respect to duties of care and information, the gap between the required level and actual practice suggests that healthcare professionals must improve their care and explanations.

著者

大石 和徳 佐藤 弘 多屋 馨子

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.140, no.7, pp.901-904, 2020-07-01 (Released:2020-07-01)

参考文献数

4

被引用文献数

6

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Although rubella is usually a mild, febrile illness, and up to 50% of rubella infections are asymptomatic, congenital rubella syndrome (CRS) can occur in the developing fetus of a pregnant woman infected with rubella virus (RV) in early pregnancy. After a rubella outbreak from early 2012 to late 2013 in Japan, another outbreak re-emerged from mid-2018 in the Tokyo metropolitan area and other large cities. In 2018, and up to epidemiological week (EW) 25 in 2019, more than 4000 rubella cases had been reported. Three CRS cases were also reported up to EW 24. Seroepidemiological surveys among Japanese residents indicated that the susceptible pocket to RV in male adults aged 30-50 years, as determined in 2013, remained unchanged in 2018. To reduce the number of male adults sensitive to RV, in early 2019, Japan's Ministry of Health, Labour and Welfare decided to implement routine immunization of male adults aged 40-57 years between 2019 and 2021. These male adults have been determined to have low anti-RV antibodies, and were therefore designated as the target population for this routine immunization (as category A). Although one-third of male patients with rubella reported in 2018 were in their 20 s and 30 s, these younger generations were not included in the target population for routine immunization against rubella, because they had already received a routine vaccination. Rubella vaccination is also required for male adults aged 20-40 years to diminish the susceptible pocket.

著者

田中 理恵 河村 麻衣子 袴塚 高志 花尻(木倉) 瑠理

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.739-750, 2020-05-01 (Released:2020-05-01)

参考文献数

21

被引用文献数

8

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To prevent the abuse of new psychoactive substances (NPS), a total of 2372 substances and two plants are controlled as “Designated Substances” in Japan as of September 2019. Although the distribution of these substances has decreased for the past three years, newly-emerged NPS are still being found. In this study, we detected four lysergic acid diethylamide (LSD) derivatives as designer drugs from four paper sheet products, which were obtained from 2014 to 2017 in Japan. The compounds were identified as 4-Acetyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ALD-52), N,N,7-triethyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ETH-LAD), 7-Allyl-N,N-diethyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (AL-LAD), N,N-diethyl-7-methyl-4-propionyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1P-LSD), by GC-MS, LC-MS, LC-Q-TOF-MS and NMR analyses. Further, we studied the extraction methods of LSD derivatives from paper sheet, and the analytical conditions of GC-MS, LC-MS and LC-FL(fluorescence). Among LSD derivatives, 1P-LSD have been controlled as designated substances (Shitei Yakubutsu) under the Pharmaceutical and Medical Device Act in Japan since April 2016. For the legislation of the other derivatives identified in this study, the evaluation of their pharmacological properties are now in progress.

著者

大井 一弥

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.12, pp.1553-1556, 2019-12-01 (Released:2019-12-01)

参考文献数

10

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The skin is the largest human organ, comprising the epidermis that is composed of epithelial tissue, the dermis composed of connective tissue, and the innermost subcutaneous tissue. Generally, skin conditions are due to aging and the influence of the external environment, but empirically patients with gastrointestinal diseases are more prone to pruritus and inflammation caused by dry skin. A decrease in the skin barrier function, involving immunocompetent mast cells and oxidative stress, was noted in indomethacin-induced small intestine inflammation, dextran sodium sulfate (DSS)-induced ulcerative colitis, and azoxymethane+DSS-induced colorectal cancer. A possible correlation was found to exist between inflammatory gastrointestinal diseases and the skin, and this correlation was investigated using a rheumatoid arthritis model as representative of inflammatory diseases. Similar to previously reported results, deterioration of the skin barrier function was observed, and new information was obtained by analyzing changes in inflammatory markers in the blood and skin tissues. Understanding the underlying mechanism of decreased skin barrier function will help in establishing effective prophylaxis and treatment methods and clarify the importance of crosstalk between organs. It will also help accelerate drug development.

著者

小田切 優樹

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.129, no.4, pp.413-425, 2009-04-01 (Released:2009-04-01)

参考文献数

103

被引用文献数

21 35

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After being distributed in the circulating blood, drugs bind to serum proteins varying degrees. In general, such binding is reversible, and a dynamic equilibrium exists between the bound and unbound molecular species. It is believed that unless there is a specific transport system (e.g. receptor-mediated endocytosis, protein-mediated transport), only unbound drugs are able to penetrate through biomembranes, are distributed to tissues, and undergo metabolism and glomerular filtration. It is also believed that only unbound molecules present in target tissues can exert their pharmacological effects, and that the concentration of unbound molecules in tissues is in proportion to the drug serum concentration. Therefore, drug-serum protein binding is critically involved in the manifestation of the pharmacological effects of a drug as well as its pharmacokinetics. Among serum proteins, human serum albumin (HSA) and α1-acid glycoprotein (AGP) play important roles in protein binding for many drugs, which is of key importance to drug distribution in the body. In addition, they are widely used in clinical settings as blood preparations and drug delivery system carriers. It is thus of great importance from the viewpoint of pharmaceutical science to clarify the structure, function, and pharmaceutical properties of HSA and AGP. Accordingly, since starting my laboratory, the focus of my research has involved molecular pharmaceutical studies on the interactions of drugs and HSA and AGP for the purpose of applying these findings to clinical fields, such as drug treatment, diagnosis and drug discovery. In this review, the molecular properties of HSA and AGP will be briefly outlined. The static and dynamic topology of drug binding sites on these proteins, investigated by various spectroscopic techniques, X-ray crystallography, quantitative structure-activity relationships, molecular modeling, photo affinity labeling, site-directed mutagenesis etc., changes in the serum protein binding of drugs in pathological conditions, such as liver and kidney failure and various inflammation diseases and factors contributing to the changes will then be summarized. Finally, cases in which protein binding displacement can be applied to medical fields will also be introduced.

著者

田中 大輔

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.130, no.3, pp.315-323, 2010 (Released:2010-03-01)

参考文献数

19

被引用文献数

4 5

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Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically <300 Da), have not been employed in conventional high-throughput screening (HTS), the recent significant progress in the biophysical screening methods enables fragment screening at a practical level. The intention of FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to “undruggable targets” (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.

著者

髙栗 郷

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.138, no.11, pp.1329-1334, 2018-11-01 (Released:2018-11-01)

参考文献数

30

被引用文献数

8

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Impaired insulin signaling in adipose tissue and skeletal muscle causes insulin resistance associated with the development of type 2 diabetes. However, the molecular mechanisms underlying insulin resistance remain to be elucidated. In this review, we describe the current understanding of the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and tumor necrosis factor (TNF)-α on insulin signal transduction in adipocytes. First, we determined that atorvastatin inhibits the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 through a decrease in the RhoA-Rho-kinase pathway, resulting in the inhibition of glucose uptake. Second, we found that TNF-α induces IRS-1 phosphorylation at serine residues 636/639 and inhibits the tyrosine phosphorylation of IRS-1 through the increase in both extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation. Interestingly, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMP-activated protein kinase activator, suppresses TNF-α-induced IRS-1 serine phosphorylation at 636/639 and the phosphorylation of ERK by enhancing interactions between ERK and dual-specificity phosphatase-9. These results may be helpful in understanding the mechanisms underlying insulin resistance.

著者

岡本 佳男

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.50, no.2, pp.105-107, 2014 (Released:2016-04-05)

参考文献数

15

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生体が光学異性体に対して高い識別を示すために,キラルな医薬品については,より有効な片方の異性体からなる光学活性な医薬品の開発が非常に重要であることは,今日ではごく当たり前のこととして知られている.しかし,今から20年前はキラルな合成医薬品の多くは,光学異性体の等量混合物であるラセミ体として用いられていた.その理由の1つは,キラル化合物の純度(鏡像体過剰率,ee)を微量で正確に決める手段がなかったためである.本稿では,今日,光学異性体の分離,分析に最もよく利用されている高速液体クロマトグラフィー(high-performance liquid chromatography;HPLC)用のらせん高分子からなるキラル固定相(カラム)の開発について,筆者が行った研究を紹介したい.

著者

山本 由似 塩田 倫史 大和田 祐二 福永 浩司

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.4, pp.497-501, 2011-04-01 (Released:2011-04-01)

参考文献数

23

被引用文献数

1 2

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Haloperidol as a potent dopamine D2 receptor (D2R) antagonist was a major tranquilizer to treat schizophrenia patients. However, the D2R blocking action in dorsal striatum is thought to cause extrapyramidal symptoms as adverse effects. However, the pathophysiological mechanism underlying extrapramidal symptoms induced by chronic treatment of haloperidol remains unclear. We recently found that lacking of heart-type fatty acid binding protein (H-FABP) in the brain aggravate catalepsy behavior induced by haloperidol. Here, we examined neuronal mechanism of augmentation of haloperidol-induced catalepsy in H-FABP null mice. Notably, catalepsy induced by haloperidol, a D2 antagonist, is augmented, whereas catalepsy induced by SCH23390, a D1 antagonist, was not affected in H-FABP null mice. Interestingly, haloperidol-induced acetylcholine (ACh) release in the dorsal striatum was markedly enhanced in H-FABP null mice compared to wild mice. We also defined the co-localization of D2R with H-FABP in the ACh interneurons in the striatum. Taken together, H-FABP regulates dopaminergic neuronal activity through interaction with D2R in rodent brain. The increased ACh release in the striatum accounts for haloperidol-induced catalepsy.

著者

斎藤 嘉朗 中村 亮介

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.139, no.12, pp.1557-1562, 2019-12-01 (Released:2019-12-01)

参考文献数

15

被引用文献数

2

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Severe cutaneous adverse reactions (SCARs) are important in postmarketing drug safety because SCAR patients were highest in the adverse drug reaction relief system of Japan. The SCAR symptoms of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) include high fever, severe mucosal impairment, and epidermal necrosis-induced erosions and blisters. Approximately 600 cases of SJS and 300 cases of TEN are reported annually in Japan. Many suspected drugs such as acetaminophen, lamotrigine, allopurinol, and carbamazepine have been reported. Over the last 15 years, an association between human leukocyte antigen and SJS/TEN onset has been reported with several drugs. Pathophysiological examinations in those reports revealed marked CD8-positive T cell infiltration into epidermal lesions, and the presence of cytotoxic granulysin, soluble Fas ligand, and tumor necrosis factor (TNF)-α in blister fluid. Therefore, SJS and TEN are immunological disorders that lead to epidermal necrosis and are consequently treated with the systemic administration of corticosteroids and with high-dose intravenous immunoglobulin therapy and plasma exchange in severe cases. Additionally, because the epidermal necrosis has characteristics similar to those of organ rejection after transplantation, the administration of cyclosporine, an immunosuppressant that inhibits helper T cell activation, has been attempted. Further, the administration of the TNF-α inhibitor etanercept has also been reported. This review summarizes current knowledge on the mechanisms of onset of SJS/TEN and their treatments.

著者

今野 良

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.49, no.3, pp.217-222, 2013-03-01 (Released:2016-09-26)

著者

緒方 章

出版者

公益社団法人 日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.1919, no.451, pp.751-765, 1919-09-26 (Released:2018-08-30)

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著者はフェニールイソプロビールメチルアミンを合成して是れを左右兩旋光性體に分離し其右旋性體をエフェドリン還元成績體なるデスオキシエフェドリンと比較して兩者の同一物なることを證明し從てエフェドリンの構造式が[chemical formula]なることの證明となせり

著者

和田 直樹 藤田 誠

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.55, no.7, pp.668-670, 2019 (Released:2019-07-01)

参考文献数

5

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分子の化学構造を決定する強力な手段は単結晶X線回折(SXRD)法だが,「単結晶を形成しない化合物に適用できない」「単結晶作製条件の最適化に多量の試料を必要とする」等の原理的な問題を抱えていた.しかし,結晶スポンジ(CS)法では,細孔性の金属錯体を鋳型として試料溶液を流し込めば化合物のSXRD解析が可能となる.われわれは本手法を用いて,従来の常識を覆す天然物の構造解析スタイルを確立した.

著者

山本 郁男 吉村 英敏

出版者

公益社団法人 日本薬学会

雑誌

衛生化学 (ISSN:0013273X)

巻号頁・発行日

vol.28, no.5, pp.233-248, 1982-10-30 (Released:2008-05-30)

参考文献数

117

被引用文献数

2 1

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This review is concerned primarily with our recent papers which have been published or presented since 1978. Especially, metabolic conversion of Δ8-THC to Δ8-THC-11-oic acid and to 8α, 9α-epoxyhexahydrocannabinol (8α, 9α-EHHC) and their pharmacological implications are described. Liver microsomes catalyze formation of 11-OH-Δ8-THC from Δ8-THC, 11-oxo-Δ8-THC from 11-OH-Δ8-THC, and 8α, 9α-EHHC from Δ8-THC. The involvement of cytochrome P-450 in these reactions were suggested in vivo as well as in vitro. 11-OH-Δ8-THC was detected and determined as a metabolite in vivo of Δ8-THC in the liver and brain of mice. 11-OH-Δ8-THC, when administered to mice, showed higher distribution in the brain as compared with Δ8-THC. Pharmacological activities of 11-OH-Δ8-THC, 11-oxo-Δ8-THC, Δ8-THC-11-oic acid, 8α, 9α-EHHC, 8β, 9β-EHHC, 9α, 10α-EHHC and 8β, 9α-di OH-HHC were compared with that of Δ8-THC using mice. Pharmacological effect of 11-OH-Δ8-THC, 11-oxo-Δ8-THC, 8β, 9β-EHHC and 9α, 10α-EHHC were more potent than that of Δ8-THC in the cataleptogenic, hypothermic, pentobarbital-induced sleep prolonging, and anticonvulsant effects. Daily administration of 11-OH-Δ8-THC or 11-oxo-Δ8-THC as well as Δ8-THC quickly induced tolerance to their hypothermic and pentobarbital-induced sleep-prolonging effects. The LD50s of 11-OH-Δ8-THC, 11-oxo-Δ8-THC and Δ8-THC-11-oic acid are larger than that of Δ8-THC.

著者

池田 幸弘

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.53, no.11, pp.1106-1107, 2017

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戸越銀座を歩き、星薬科大学へと向かう。正門を入ってすぐ右手の建物の1階に資料館があった。本資料館には、創立者星一ゆかりの資料を中心に、本学にかかわる多様な歴史資料が展示されている。星薬科大学の歴史を辿ると、明治44(1911)年、星製薬株式会社が創立された際、社内に設置された教育部に遡る。会社創立と同時に教育部門を設けることは珍しいと思われるが、これは、建学の精神である「世界に奉仕する人材育成の揺籃である」に由来するのであろう。この根底には、座右の銘である「親切第一」 -「親切第一を主義として、自己に親切なれ、何人にも親切なれ、物品に親切なれ、時間に親切なれ、学問に親切なれ、金銭に親切なれ、親切は平和なり、繁栄なり、向上なり、親切の前には敵なし、親切は世界を征服す」の信念が礎となっている。ちなみに、星薬科大学と聞くと、つい創立者の長男である作家星新一を頭に浮かべてしまうが、本名は親一で、この言葉から名づけられたという。さらに余談を述べると、次男は協力第一の銘から、協一と名づけられたらしい。

著者

吉山 友二

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.54, no.2, pp.151-153, 2018 (Released:2018-02-01)

参考文献数

5

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「在宅医療推進における薬剤師のかかわり」のシリーズで多くの実践的な事例紹介がなされてきた。初回の「地域医療行政の立場からの薬剤師への期待」では、地域医療と在宅医療の全体像について総説されている。続いて、各領域の先生方から、在宅医療推進における薬剤師のかかわりについて最新の事例紹介がなされた。本コラムで提供された有用な情報を、在宅医療の推進に活用することが薬剤師の腕の見せ所と確信している。

著者

本橋 秀之 藤本 敦子 坂根 稔康 山本 昌 矢野 義孝

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.133, no.11, pp.1235-1241, 2013 (Released:2013-11-01)

参考文献数

9

被引用文献数

1 1

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In recent years there have been over 30000 suicides annually in Japan. This is one of the most serious problems for Japanese society. Because mental disorder is closely associated with suicide, factors related to the increase in mental disorders and suicides should be clarified. In this study, various data regarding social factors were evaluated to assess the correlation of the number of patients with mental disorders and suicides among the 47 prefectures of Japan. Various data regarding social factors, such as income, savings, or rate of divorce, were obtained from the database of the Ministry of Health, Labour and Welfare of Japan. Among the factors, the annual income and the amount of savings were significantly correlated with the number of patients with mental disorder. On the other hand, while the annual income did not have a significant correlation with suicides, the amount of savings had a significant correlation with suicides. In conclusion, the annual income and amount of savings may both be one of the important factors involved in mental disorders, and the savings may also be a factor affecting suicides. These analyses are valuable in helping to clarify the causes of mental disease, and can hopefully contribute to the health and welfare of Japanese.

著者

杉林 堅次

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.37, no.5, pp.385-387, 2001

参考文献数

21

被引用文献数

1

著者

武富 芳隆 村上 誠

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.5, pp.503-515, 2017-05-01 (Released:2017-05-01)

参考文献数

56

被引用文献数

2 3

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Mast cells originate from hematopoietic stem cells and undergo terminal maturation in the extravascular tissues, in which they are ultimately resident. Mast maturation, phenotype, and function are dictated by the local microenvironment, which has a significant influence on the ability of mast cells to recognize and respond to stimuli. Activation of mast cells can lead to the release of three distinct classes of mediators, including preformed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo-synthesized bioactive lipid mediators. It is currently recognized that bioactive lipids such as arachidonic acid metabolites (prostaglandins and leukotrienes) released from mast cells modulate innate and adaptive immune responses both directly and indirectly through communication with other microenvironmental immune cells or stroma cells. Moreover, mast cells express a variety of lipid receptors and, if activated by bioactive lipids such as arachidonic acid, ω3 fatty acids, lysophospholipids, and their metabolites, can alter the release and production of other mediators including histamine, cytokines, and chemokines, and thereby alter homeostatic or pathophysiological responses. This review focuses on newly identified functional aspects of bioactive lipids with regard to their immune regulation and functional outcomes in both homeostasis and allergic disease.

著者

日下部 哲也

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.54, no.11, pp.1098_1, 2018 (Released:2018-11-01)