著者

寺澤 捷年

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.26, no.9, pp.924-926, 1990-09-01 (Released:2018-08-26)

著者

近藤 邦生

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.8, pp.985-992, 2020-08-01 (Released:2020-08-01)

参考文献数

49

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Central neural circuits in the brain receive and integrate environmental and internal information to enable the animals to execute appropriate behaviors and physiological responses. Communication between the brain and peripheral organs via peripheral neural circuits maintains energy homeostasis in the body. Therefore it is important to investigate the anatomical organization of central and peripheral neural circuits for elucidating the mechanisms of energy homeostasis. Transsynaptic viral tracers can travel through connected neurons via synaptic connections and have been used to delineate the anatomical organization of neural circuits with specific functions. Herein, I review our recent studies investigating neural circuits and their involvement in physiological changes using transsynaptic tracers.

著者

渡邊 博志

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.8, pp.889-895, 2013-08-01 (Released:2013-08-01)

参考文献数

28

被引用文献数

4 6

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Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

著者

四柳 宏

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.56, no.12, pp.1071-1075, 2020 (Released:2020-12-01)

参考文献数

10

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B型肝炎治療の最終目標は、治癒、すなわちウイルスの肝細胞からの排除にあるが、その達成はこれまでのインターフェロンや核酸アナログだけでは難しい。最近、新たな抗ウイルス薬や宿主免疫に作動する薬物が数多く開発され、それらの臨床試験が開始されており、今後の進歩が期待される。

著者

松木 則夫

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.42, no.3, pp.231-235, 2006-03-01 (Released:2018-08-26)

被引用文献数

1

著者

小野田 稔久 木下 雅子 田中 博之 井澤 香 浦野 敦 佐藤 直子 増田 雅行 石井 敏浩

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.142, no.11, pp.1267-1276, 2022-11-01 (Released:2022-11-01)

参考文献数

19

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During the treatment of cardiogenic shock, various continuous infusion drugs are used simultaneously. However, administration from the same route may result in stability changes due to mixing of drugs. In addition, stability tests after mixing more than three types of drugs have hardly been conducted. In this study, noradrenaline, milrinone, dobutamine hydrochloride, and landiolol hydrochloride were used to evaluate the chemical stability of the mixture. Chemical stability was evaluated by measuring the change in each drug concentration over time and calculating the content. The concentration of each drug was measured using an optimized gradient elution method by HPLC. In a four-drug mixed sample, noradrenaline, milrinone, dobutamine hydrochloride, and landiolol hydrochloride had retention times of 2.1 min, 5.2 min, 9.3 min, and 11.9 min, respectively. The concentration immediately after mixing each drug was almost the same as the theoretical concentration at the time of mixing each drug. Furthermore, noradrenaline, milrinone, and dobutamine hydrochloride concentrations were maintained up to 99% in each drug mixture until 24 h after mixing all the samples. However, the content of landiolol hydrochloride was 90% or less 24 h after mixing, except for two types of mixed solutions with dobutamine hydrochloride. This result suggested that landiolol hydrochloride was being degraded owing to acidic conditions. The results of this study suggest that noradrenaline, milrinone, and dobutamine hydrochloride can be administered from one route, while it is recommended that landiolol hydrochloride be administered from another route.

著者

五十嵐 中

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.142, no.12, pp.1379-1390, 2022-12-01 (Released:2022-12-01)

参考文献数

35

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Development of a formulary is an important issue to achieve rational use of medicines in each local medical area in Japan. The purpose of developing the formulary is to secure the access for safe, effective, and affordable medications based on evidence for patients, families, healthcare professionals as well as for general publics. The economic aspect plays an important role for the establishment of the formulary, while the word “economic” is often misread as simple “cost reduction”, which only aims to generic/biosimilar substitutions. Both health outcomes and costs, should be taken into account under the true “health economic analysis”, or the cost-effectiveness analyses (CEA). Information provided via the CEA could be useful for establishment of the formulary. Moreover, various value assessment of medicines in health technology assessments (HTA) field beyond the current approach of safety, effectiveness, and economics evaluations should be considered. In this review, we discuss comprehensive assessment of various value components of medicines to establish the most suitable formulary which would contribute to whole society, as well as healthcare facilities/patients.

著者

川上 亘作

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.52, no.5, pp.402-406, 2016 (Released:2016-05-01)

参考文献数

23

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経口製剤の溶解性問題を克服する製剤技術として、可溶化製剤、非晶質固体分散体、ナノ結晶製剤が代表的であるが、これら各々には一長一短がある。固体分散体は製造に特殊技術が必要となることに加え、物理的安定性に関する理解が十分とは言えない。しかし通常製剤と同様のカプセル化、錠剤化が可能であるため、患者視点においては製剤が大きくなりがちな可溶化製剤より利便性に優れることが多い。本稿では製剤化手段としての非晶質の特徴について解説する。

著者

桑山 健次

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.8, pp.1063-1070, 2019-08-01 (Released:2019-08-01)

参考文献数

39

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The abuse of drugs has become a serious social problem worldwide. Amphetamine-type stimulants such as methamphetamine are recreationally abused and can cause toxic effects in the body. Unfortunately, death from drug poisoning can occur due to careless intake. In postmortem examinations, the distribution of drugs in an entire organ gives valuable information for evaluating their toxicity. We developed methods to measure the distribution of drugs in organs using LC/MS and matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). The complementary use of the two methods provides more detailed information on the distribution and concentration of drugs in organs because the accurate quantification in LC/MS and small spatial resolution in MALDI-IMS are combined. On the other hand, it is important to elucidate the drug intake history of suspects and victims in drug-facilitated crimes (DFCs). Hair and nail samples are often used to confirm chronic drug intake because ingested drugs can stably remain in these specimens over several months. However, it is impossible to determine the day of drug ingestion in conventional segmental analysis of bulk samples. Therefore, we developed methods to cut hair strands at 0.4-mm intervals and nails at 0.2-mm intervals, which correspond to their respective growth rates over 1-2 d, to analyze the drugs in each segment efficiently using LC/MS. The microsegmental hair analysis method is applied to estimate the day of drug ingestion in DFC investigations. These methods could be applied to measure the distribution of compounds in various solid samples.

著者

三島 和夫

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.51, no.2, pp.104-108, 2015 (Released:2018-08-26)

参考文献数

10

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睡眠障害は臨床場面で最もよく遭遇する疾患の1つであり,なかでも不眠症はその代表格である.不眠症状の大部分は一過性で自然消退する.ただし1か月以上持続する慢性不眠症は難治性である. 慢性不眠症患者の70%では1年後も不眠が持続し,約半数では3~20年後も不眠が持続するといわれる.また慢性不眠症患者は,薬物療法などで一旦寛解してもその半数は再発する.必然的に睡眠薬は長期使用かつ高用量となりがちである.実際,国内で睡眠薬を長期服用する患者は増加しており,1日当たりの服用量も増加傾向にある.それだけに,中長期的な治療ビジョンを持ち,治療開始当初からリスク・ベネフィットバランス比を考慮しながら慎重に処方すべき薬剤である.特に,治療途中で薬効や副作用を適宜評価することなしに漫然と睡眠薬の長期処方をすることは,厳に戒められるべきである.

著者

角田 慎一

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.142, no.12, pp.1297-1305, 2022-12-01 (Released:2022-12-01)

参考文献数

25

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Tumor necrosis factor-α (TNF), a proinflammatory cytokine, is critical to the pathogenesis of various inflammatory diseases. There are two subtypes of receptors for TNF, namely type I TNF receptor (TNFR1) and type II TNF receptor (TNFR2). Previous studies using animal models of diseases have demonstrated the predominant role of TNFR1 in the pathogenesis of inflammation. It has recently been proposed that TNFR2 is associated with anti-inflammatory function. This intriguing function of TNFR2 has implications from an immunological and pharmacological perspective. However, the mechanism of the TNFR2-mediated anti-inflammatory effect is not fully understood. In this context, we attempted to elucidate the TNFR2-mediated anti-inflammatory effect and other unknown biological functions of TNFR2 by utilizing our protein engineering technology to generate functional mutant cytokines. Our findings reveal the following. (1) TNFR2 is expressed on regulatory T cells (Tregs) but not conventional T cells (Tconvs) and TNFR2-mediated signals promote proliferation and activation of Tregs. (2) The crystal structure of TNF/TNFR2 complex was solved, which suggests a possible signal initiation mechanism via TNF/TNFR2 cluster formation on the cellular membrane. (3) A novel TNFR2-mediated signal molecule, aminopeptidase P3 (APP3/XPNPEP3), was identified that interacts with TNFR2 as an intracellular adaptor protein. APP3 is required for c-Jun N-terminal kinase (JNK) phosphorylation, the downstream molecule of TNFR2 signal transduction. These results are key to understanding the mechanism of immune regulation and will assist in the identification of immunomodulatory drugs targeting the TNFR2 signaling cascade as well as the function of Tregs.

著者

山田 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.142, no.12, pp.1371-1377, 2022-12-01 (Released:2022-12-01)

参考文献数

30

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Green tea components, such as catechins have been reported to provide several benefits including anti-oxidative, anti-viral/bacterial, and anti-inflammatory effects in vitro and in vivo. Catechins effectively inhibited the adsorption and replication of the influenza virus. Additionally, green tea contains theanine and vitamin C, which enhance the immunity against viral/bacterial infections. Based on these, green tea is hypothesized to have potential benefits in the prevention of influenza and other respiratory tract infections in the clinical setting. However, its specific effects in patients remain unclear. To determine the clinical significance of green tea in the prevention of respiratory tract infections, we conducted an observational study and eight interventional studies. Based on the results of three studies, consuming or gargling green tea or its components significantly aided in the prevention of influenza. Meanwhile, one study showed that green tea successfully prevented common colds. Catechin inhalation was also reported to decrease the bacterial load of methicillin-resistant Staphylococcus aureus in the sputum. Although the anti-viral/anti-bacterial effects of green tea components have been demonstrated in experimental studies, the clinical evidence remains limited. Further studies are required to confirm the clinical efficacy of green tea and its components in preventing respiratory tract infections.

著者

淡川 孝義

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.58, no.12, pp.1125-1129, 2022 (Released:2022-12-01)

参考文献数

14

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NADは生体内での酸化反応の補酵素として広く用いられている。それ以外に、sirtuinなど重要な生理作用に関わるタンパク質の基質として受け入れられ、多様な生理学的機能を担う。近年、我々は、NADが医薬品活性天然物生合成反応の基質となることを明らかにし、その新たな役割を示すことに成功した。本稿では、その生合成研究の内容と意義、生物活性、生理活性化合物合成への応用の可能性など、今後の展望について記述する。

著者

宮田(古谷) 聡美 河野 惠三 森元 崇史 原島 哲 岩田 裕子 有安 利夫

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

pp.21-00219, (Released:2022-02-28)

参考文献数

29

被引用文献数

1

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Transient receptor potential vanilloid 2 (TRPV2) channels are expressed and play functional roles in various immune cells. Physical stimuli leading to TRPV2 activation causes mast cell degranulation. Besides their roles in immune cells, it has been shown that TRPV2 channels are pathophysiologically relevant to degenerative muscular diseases such as dilated cardiomyopathy and muscular dystrophy. Hence, development of drug candidates that inhibit human TRPV2 activation is an urgent matter. NK-4, a cryptocyanine dye, inhibited agonist-induced TRPV2 activity in mouse TRPV2-transfected HEK293 cells. However, it remains unclear whether NK-4 exerts regulatory effects on the activation of human TRPV2 channels. In this study, we show that NK-4 inhibits intracellular Ca2+ increase in human TRPV2-transfected HEK293 cells preactivated with a TRPV2 agonist. The inhibitory effect of NK-4 (IC50 = 0.27 μM) on human TRPV2 activation was 74-fold stronger than that on mouse TRPV2 activation (IC50 = 20 μM). NK-4 also inhibited the agonist-induced TRPV2 expression at the plasma membrane, when the human TRPV2-expressing cells were stimulated with the agonist in the presence of NK-4. These results suggest that NK-4 abrogates the agonist-induced signaling events leading to human TRPV2 activation. Furthermore, TRPV2 agonist caused degranulation of RBL-2H3 cells, which represents a phenomenon related to physical urticarias. NK-4 suppressed the release of β-hexosaminidases upon degradation with IC50 of 1.9 μM, 35-fold lower than that determined with an anti-allergic drug, Epinastine. Our results suggest that NK-4 would be a potential therapeutic strategy to resolve dilated cardiomyopathy and its associated heart failure as well as physical urticarias.

著者

柳 奈津代 佐藤 宏樹 澤田 康文

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.9, pp.1095-1107, 2021-09-01 (Released:2021-09-01)

参考文献数

24

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The difficulty and anxiety of nursery staff in administering medication to children at nursery schools has been reported, and its reduction is desired. However, the attitudes of mothers in requesting medication and the factors related to a high frequency of requests are not clear. We conducted an online survey of 600 mothers from April to May 2019 regarding the administration of medication at nursery school, and 301 mothers who had previously made such requests were analyzed. The results showed that 100.0% and 76.4% of the mothers felt gratitude and were apologetic for requesting medicine administration, respectively. In total, 47.5% of mothers expected pharmacists to support nursery staff in administering medication. Mothers' attitude of “I think the nursery staff should administer medication to my child more often” was significantly positively associated with a high frequency of the request in adjusted Model [adjusted odds ratio (AOR) 2.75, 95% confidence interval (CI) 1.36-5.55, p=0.005], while “I think the parents should manage so that the children do not have to take medicine in the nursery school so often” showed a negative association (AOR 0.33, 95% CI 0.17-0.66, p=0.002). Factors related to the involvement of community pharmacists were not significant. It is suggested that a change in mothers' attitudes could decrease the frequency of requests and consequently reduce the burden on nursery staff. Community pharmacists may support nursery staff to contribute to changing mothers' attitudes through medication consultations at the pharmacy.

著者

進藤 直哉 王子田 彰夫

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.10, pp.939-943, 2019 (Released:2019-10-01)

参考文献数

10

被引用文献数

1

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標的タンパク質と特異的に反応して、その機能を阻害するコバレントドラッグ(共有結合性医薬品)は、強力で持続する薬効を発揮できる。非特異反応を起こさない安全なコバレントドラッグを生み出すためには、標的タンパク質と特異的かつ効率的に共有結合を形成するための反応化学が重要である。近年、標的タンパク質特異性の高いコバレントドラッグであるtargeted covalent inhibitor (TCI )の創出に向けた反応基(warhead)の開拓が世界中で取り組まれている。

著者

寒川 賢治 児島 将康

出版者

公益社団法人 日本薬学会

雑誌

MEDCHEM NEWS (ISSN:24328618)

巻号頁・発行日

vol.10, no.4, pp.12-17, 2000-11-01 (Released:2021-06-19)

参考文献数

16

著者

辻 尚孝

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.42, no.3, pp.269-270, 2006-03-01 (Released:2018-08-26)

参考文献数

4

著者

内野 正 竹澤 俊明 五十嵐 良明 徳永 裕司

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.128, no.1, pp.45-50, 2008-01-01 (Released:2008-01-01)

参考文献数

21

被引用文献数

7 8

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Recently, to study an in vitro evaluation method of skin irritation and acute toxicity, many three-dimensional human skin models consisting of normal human keratinocytes and fibroblasts have been used. However, these skin models did not have any dendritic cells so were difficult to apply to an in vitro skin sensitization test. On the other hand, a single cell-culture model using normal human dendritic cells was recently studied for an in vitro evaluation method of immune-sensitizing compounds. However, these models have various problems: 1) the life span of dendritic cells is short(within 1 week) and 2) it is difficult to apply water-insoluble samples to these models. To study an alternative to animal testing using immune-sensitizing compounds, we therefore constructed a three-dimensional human skin model consisting of three different cells, dendritic cells (keratinocytes, and fibroblasts) then exposed immune-sensitizing compounds and non-sensitizers to the new skin model for 1 h and investigated the effect of these compounds on cytokine release and expression of CD86. Due to immune-sensitizing compounds, the new skin model significantly released cytokine and significantly expressed CD86. On the other hand, non-sensitizers did not induce IL-1α, IL-2, and IL- 4 release and expression of CD86. These results suggest that the new skin model is suitable for study as an alternative to animal testing using immune-sensitizing compounds.

著者

中澤 洋介

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.58, no.11, pp.1051-1055, 2022 (Released:2022-11-01)

参考文献数

21

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白内障が発症すると外科的に混濁水晶体を摘出し、人口眼内レンズを挿入する水晶体再建術が行われ、その満足度は非常に高い。一方で手術が受けられない国や地域がいまだに多く存在し、予防薬の探索が求められる。筆者らは日常食生活から白内障発症予防をすることを目的とし検討してきた結果、コーヒー愛飲によって白内障発症が有意に抑制されることを報告してきた。またみかん果皮に多く含まれるヘスペリジンに白内障予防効果や老眼予防効果を持つことを明らかにした。