著者
酒井 弘憲
出版者
公益社団法人 日本薬学会
雑誌
ファルマシア
巻号頁・発行日
vol.50, no.10, pp.1002-1003, 2014

少し暑さも納まり,過ごしやすい季節になってきた.サマージャンボに続き,オータムジャンボ宝くじが発売される.当たらないとは分かっていても先日のサマージャンボのように1等前後賞合わせて6億円などと言われると,ついつい買ってしまうのが人情である.銀座数寄屋橋の宝くじ売り場などは毎回,長蛇の列である.しかし宝くじは,言ってみれば某銀行や地方自治体が胴元の公認/公営ギャンブルみたいなものである.<br>皆さんはそのテラ銭,つまり胴元の取り分の割合をご存じだろうか? 競馬などの公営ギャンブルで25%くらい,パチンコでもせいぜい12%程度なのである.ところが,宝くじのテラ銭は何と54%にも上るのである.売り上げの半分以上が懐に入る仕組みで,胴元の某銀行は笑いが止まらないであろうと思われるかも知れないが,このお金はご存じのように公益事業に使われるので,公共団体などへの寄付のようなものとも考えられなくもない.4月に消費税が8%に上がって不平不満たらたらのはずだが,宝くじなら炎天下に2,3時間並んでも買おうというのであるから,著者も含め,まったくみんなおめでたくできている.<br>統計の連載なので少しそれらしい話に戻ると,皆さんは,宝くじの当選確率はいったいどのくらいになると思われるだろうか? 確率の世界では,「期待値」という考え方がある.取らぬ狸の何とやらで,宝くじ1枚あたりでいくら自分の手元に戻ってくるかという金額である.ジャンボ宝くじの場合,1ユニットあたり1,000万本が発行され,その中で1等はわずかに1本のみ.つまり1等を手にする確率は,1,000万分の1の確率なのである.当選金の期待値は,当選金額×当選確率で計算されるので,1等3億円の期待値はわずかに30円ということになる.この計算を1等から6等まですべてに当てはめて合算すると,ジャンボ宝くじ1枚の期待値は140~150円程度なのである.1枚300円なのでその半分以下しか期待できないというのが現実なのである.<br>その事実を知ったうえでも,なお,宝くじをお買いになるかどうかは皆さんの判断次第であるが,あまりにも分の悪い勝負というよりほかはない(と偉そうに講釈しながらも著者自身,まずは買わなければ当たらないと,毎回購入しているのだが…).<br>勝負というと,医薬品の開発も勝負には違いない.1つの医薬品を開発するのに,いまや1,000億円以上の経費を費やし10年もの歳月を重ねることになるが,最後の最後で安全性で問題が見つかり開発中止になるなどといった事例は枚挙に暇がない.製薬企業にとっては,まさに真剣勝負なのである.
著者
佐々木 均
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.9, pp.835-840, 2015 (Released:2018-08-26)
参考文献数
5

フィジカルアセスメントとは,問診・視診・聴診・触診などを通して,患者の症状の把握や異常の早期発見を行うことである.チーム医療のなかで薬剤師は「薬の専門家」として医薬品適正使用や副作用の早期発見に貢献することが望まれている.そのための技能の1つがフィジカルアセスメントである.長崎大学病院では,早くから体系的なフィジカルアセスメント研修体制を構築し,施設や他職種による承認を受け,薬剤師によるフィジカルアセスメントを展開している.その概略と意義を本稿で紹介したい.
著者
天ヶ瀬 紀久子
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.57, no.8, pp.775, 2021 (Released:2021-08-01)
参考文献数
5

自己免疫疾患の1つである多発性硬化症(multiple sclerosis: MS)は,脳および脊髄における散在性の脱髄斑を特徴とし,脱髄による神経伝達障害が視力障害,運動障害,感覚障害,認知症,排尿障害などさまざまな神経症状を引き起こすが,その発症原因は明らかでない.近年,腸内細菌叢の宿主に対する生理学および病理学的役割が注目されており,炎症性腸疾患,精神・神経疾患,免疫および代謝内分泌疾患などさまざまな疾患での研究が進められている.MSにおいても,2011年に健常人の糞便微生物移植によりMS患者の症状改善が報告され,患者の腸内細菌叢とMS発症および増悪との関係性が明らかになりつつある.現在,腸内細菌によるMSの増悪にはヘルパーT細胞のサブセットTh17細胞の分化誘導が関与すると考えられているが,その詳細は明らかでない.今回紹介する論文では,MSモデルであるマウス実験的自己免疫性脳脊髄炎(experimental autoimmune encephalomyelitis: EAE)を用い,2種の腸内細菌が協調して疾患の発症と増悪を促進することを報告している.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Borody T. J. et al., Am. J. Gastroenterol., 106, S352(2011).2) Cosorich I. et al., Sci. Adv., 3, e1700492(2017).3) Miyauchi E. et al., Nature, 585, 102-106(2020).4) Jangi S. et al., Nat. Commun., 7, 12015 (2016).5) Mangalam A. et al., Cell Rep., 20, 1269-1277(2017).
著者
小埜 栄一郎 村田 純 堀川 学
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.57, no.8, pp.715-720, 2021 (Released:2021-08-01)
参考文献数
25

ゴマ(シソ目ゴマ科ゴマ属 Sesamum spp.)は種子にフェニルプロパノイドの二量体のリグナンと呼ばれる植物特化代謝物を蓄積している。セサミンに代表されるリグナンは多様な生物活性を有しているものの、同じフェニルプロパノイドから生合成されるフラボノイド類に比べると医薬や食品分野では認知度は低い。それらの多岐に渡る薬理活性については優れた先行文献に譲り、本稿ではリグナン代謝物の多様性がどのようにして生じているか、つまり特化代謝の進化をゴマの栽培種と野生種の酵素活性の比較を通じて論じたい。
著者
矢﨑 一史
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.57, no.8, pp.705-709, 2021 (Released:2021-08-01)
参考文献数
19

脂溶性のナフトキノン系赤色色素であるシコニンは、ムラサキ科の6属内の限られた種だけが生産する化合物である。その化学構造は比較的単純であるが、特殊な化学特性を持つため、供給はもっぱら天然資源に依存している。その代表が絶滅危惧植物に指定されている薬用草本のムラサキで、新たな薬理活性が次々と報告される一方、供給には潜在リスクがある。今、世界的に新たな潮流を生み出しているこのシコニンをめぐる研究を紹介する。
著者
堤 きく江 土屋 千佳子 花輪 和己 鈴木 正彦 花輪 剛久 小口 敏夫
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.128, no.6, pp.965-970, 2008-06-01 (Released:2008-06-01)
参考文献数
18
被引用文献数
1 1

Beraprost sodium (BPS) is often used for pediatric patients with pulmonary hypertension. The purpose of this study was to determine the expiration date of the powdered medicine prepared by grinding tablets. In the present study, the hygroscopicity and stability of the beraprost tablet (DORNER® tablet), ground Dorner tablet and powder formulation (Doener powder) consisting of the ground DORNER® tablet and lactose (EFC® lactose) were investigated after storage at various relative humidities (RHs) and light exposures. While the DORNER® tablets and ground DORNER® tablets were found to adsorb significant amounts of water vapor at an RHs of greater than 51.0%, Dorner powder scarcely adsorbed water. The stability of BPS in the Dorner powder decreased after storage under 3000 lux for 90 days. From these results, the expiration date and storage conditions of Dorner powder were determined to “90 days without exposure to light.” We also investigated the stability of BPS in solutions of various pH values on the assumption that Dorner powder may be given to pediatric patients after dissolving in soft drinks. Because BPS degraded significantly below pH 2, pharmacists should alert patients not to take Dorner powder with acidic soft drinks.
著者
山下 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.53, no.12, pp.1171-1176, 2017 (Released:2017-12-01)

・僅かなメンバーで起業し、加速するIT進化を駆使して未知の製品やサービスを生み出し、猛烈な速度で成長して世界を変えてゆく企業をスタートアップと呼ぶ。一見あり得ないと思えるアイデアを実現し、未来の当たり前を生み出すイノベーターである彼らについて、そのあらましを紹介する
著者
鈴木 勉
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.121, no.12, pp.909-914, 2001-12-01 (Released:2002-09-27)
参考文献数
25
被引用文献数
10 10

Clinical studies have demonstrated that when opiates are used to control cancer pain, psychological dependence and analgesic tolerance are not a major concern. The present study was, therefore, designed to investigate the modulation of rewarding effects of opiates under inflammatory chronic pain in SD rats. Formalin (2.5%, 50 μl) or carrageenan (1%, 100 μl) was injected into the plantar surface of the rat paw. Formalin and carrageenan reduced the paw pressure threshold. The hyperalgesia lasted for 9 to 13 days. Rewarding effect of morphine was evaluated by conditioned place preference paradigm. Morphine produced a significant place preference. This effect was significantly attenuated in inflamed groups as compared with the respective non-inflamed groups. Furthermore, the morphine-induced place preference in the inflamed group gradually recovered to the respective control level as the inflammation healed. On the other hand, we found that κ-opioid receptor agonists markedly inhibit rewarding effect of μ-opioid receptor agonists. Therefore, to elucidate the mechanism of this attenuation, the effects of pretreatment with κ- and δ-opioid receptor antagonists, nor-binaltorphimine (nor-BNI) and naltrindole (NTI), on the development of the morphine-induced place preference under inflammation were examined. Nor-BNI, but not NTI, eliminated the suppression of the morphine-induced place preference in inflamed groups. The morphine-induced increase in dopamine turnover in the limbic forebrain was suppressed under inflammation, and the suppression was abolished by the pretreatment with nor-BNI. These results suggest that endogenous κ-opioid systems may be activated by chronic inflammatory nociception, resulting in the suppression of the development of rewarding effects produced by morphine.
著者
税所 篤行 高砂 美和子 若林 和貴 秋山 真里 幸田 恭治 髙崎 彰久 松永 和人 石田 博 北原 隆志
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.141, no.7, pp.971-978, 2021-07-01 (Released:2021-07-01)
参考文献数
14

To reduce the number of falls caused by hypnotic agents, the standardization of insomnia treatment was carried out at Yamaguchi University Hospital from April 2019. There were concerns that medical costs would increase due to the selected medicines―suvorexant and eszopiclone―being more expensive than conventional benzodiazepines. In this study, the standardization of insomnia treatment was evaluated by pharmacoeconomics. The costs of the hypnotic agents was considered, as was the cost of examination/treatment following falls. Effectiveness was evaluated as the incidence of falls within 24 hours of taking hypnotic agents. This analysis took the public healthcare payer's perspective. Propensity score matching based on patient background, showed that, per hospitalization the medicine costs of the recommended group increased by 1,020 yen, however, the examination/treatment costs following falls decreased by 487 yen when compared with the non-recommended group. Overall, the recommended group incurred costs of 533 yen more per hospitalization for patients prescribed hypnotic agents compared to the non-recommended group, but the incidence of falls for the recommended group was significantly lower than that in the non-recommended group (1.9% vs. 6.3%; p<0.01). These results suggest that in order to prevent the incidence of falls by 1 case, it is necessary to increase costs by 12,086 yen which is the subthreshold cost for switching to the recommended medicine as standardization. The selection of recommended medicines may be a cost-effectiveness option compared with non-recommended medicines.
著者
宮村 充彦 横田 淳子 西原 利治
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.136, no.4, pp.579-582, 2016-04-01 (Released:2016-04-01)
参考文献数
9
被引用文献数
2 5

Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease characterized by intense liver steatosis accompanied by hepatocyte destruction, inflammation and fibrous, despite little or no history of alcoholic consumption. There are also cases of drug-induced secondary steatohepatitis. Drug-induced steatohepatitis is a relatively rare type of drug-induced liver disease, but close attention to the possible onset of steatohepatitis is needed when drugs with the potential to induce fatty liver are prescribed for long term use. Estrogen is a factor indispensable to smooth fatty acid β-oxidation in hepatocytes. However, treatment with Tamoxifen markedly suppresses fatty acid β-oxidation in the liver. As free fatty acids are toxic, their accumulation results in the activation of alternative fatty acid oxidation pathways mediated by CYP2E1 in cytosol and lipid peroxidases in peroxisomes in hepatocytes. CYP2E1 enhances lipid peroxidation and dicarboxylic acid synthesis via the activation of fatty acid ω-oxidation that injures mitochondria and results in the emergence of ballooned hepatocytes. In such cases, the attenuation of alternative fatty acid oxidation pathways could have some beneficial effects on mitochondrial injury, since fibrates (PPAR-α ligands) are potent enough to stimulate neutral fat consumption through the activation of peroxisomal fatty acid β-oxidation. Fortunately, fibrates attenuate serum estrogen levels by affecting estrogen receptor expression, so the co-administration of fibrates with Tamoxifen is expected to exert higher efficacy in breast cancer patients with Tamoxifen-induced hepatic steatosis.
著者
小田 真隆
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.10, pp.1233-1238, 2009-10-01 (Released:2009-10-01)
参考文献数
11
被引用文献数
1 1

Bacillus cereus is one that causes of opportunistic human infections. Sphingomyelinase produced by B. cereus is assumed a virulence factor for the infection. Sphingomyelinase from Bacillus cereus (Bc-SMase) is Mg2+-containing metalloenzyme. Bc-SMase is a family of neutral SMase (nSMase) and mimics the actions of the endogenous mammalian nSMase in causing differentiation, development, and apoptosis. Bc-SMase may be a good model for the poorly characterized mammalian nSMase. Activation of Bc-SMase by divalent metal ions was in the order Co2+>Mn2+>Mg2+≫Ca2+>Sr2+. Crystal structure analysis of Bc-SMase bound to Co2+, Mg2+, or Ca2+ revealed that the water-bridged double divalent metal ions at the center of the cleft in both the Co2+- and Mg2+-bound forms is the catalytic architecture required for sphingomyelinase activity. In contrast, the architecture of Ca2+ binding at the site showed only one binding site. A further single metal-binding site existed at one side edge of the cleft. Based on the highly conserved nature of amino acid residues of the binding sites, the crystal structure of Bc-SMase with Mg2+ or Co2+ provided a common structural framework applicable to phosphohydrolases belonging to the DNase I-like folding superfamily. In addition, our analysis provided evidence that β-hairpin containing the aromatic amino acid residues and the metal ion of the side-edge participate in binding to sphinogmyelin and membranes containing sphingomyelin. This article summarized current knowledge of characteristics and mode of action of Bc-SMase.
著者
髙鳥 悠記
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.6, pp.851-856, 2021-06-01 (Released:2021-06-01)
参考文献数
33
被引用文献数
2

Donepezil, the most widely used drug for the treatment of Alzheimer's disease (AD), is an acetylcholinesterase (AChE) inhibitor and is thought to improve cognition by stimulating cholinergic neurotransmission. However, no correlation has yet been established between the inhibitory role of AChE inhibitors and their therapeutic effects when used in AD patients. The cleavage pathway of amyloid precursor protein (APP) includes amyloidgenic (β, γ-cleavage) and non-amyloidgenic (α-cleavage) pathways. The intracellular transportation of APP is important in determining these cleavage pathways. It has been suggested that sorting nexin (SNX) family proteins regulates the intracellular transport of APP, thereby enhancing α-cleavage. In this study, we examined the effects of donepezil on SNX33 expression changes and APP processing in primary cultures of fetal rat cortical neurons. While donepezil treatment increased the levels of SNX33 expression and soluble APPα (sAPPα) in culture media, no changes were observed regarding full-length APP expression in the cell lysate. Donepezil also reduced the release of amyloid β (Aβ) into culture media in a concentration- and time-dependent manner. This reduction was not affected by acetylcholine receptor antagonists. The membrane surface expression of APP was elevated by donepezil. Furthermore, SNX knockdown by antisense morpholino oligos prevented the effects of donepezil. These results indicated that donepezil increased APP expression at the surface of the plasma membrane by decreasing APP endocytosis through upregulation of SNX33, suggesting donepezil might stimulate the non-amyloidogenic pathway. This new mechanism of action for the currently used anti-AD drug may provide a valuable basis for future drug discovery.
著者
山田 大輔
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.4, pp.347, 2016 (Released:2016-04-01)
参考文献数
3

恐怖と食欲はともに生存に必須な本能である.動物が餌を探すなか天敵に遭遇した場合,恐怖を感じて危機回避行動が生じなければ捕食されてしまう.そして,この恐怖は記憶しておく必要がある(恐怖記憶).しかし,恐怖が強すぎて餌にありつけなければ餓死してしまう.つまり,動物の生存には恐怖と食欲のバランスを保つことが必要であり,それを実現するような神経機構が存在する可能性が考えられていた.この点についてVermaらは,空腹感が恐怖を司る神経回路をシナプス伝達レベルで修飾し,恐怖記憶を変化させること,その変化に摂食制御ペプチド受容体が関与することを報告したので紹介する.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Verma D. et al., Neuropsychopharmacology, 41, 431-439 (2016).2) Holzer P. et al., Neuropeptides, 46, 261-274 (2012).3) Pape H. C., Pare D., Physiol. Rev., 90, 419-463 (2010).
著者
中原 雄二
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.36, no.2, pp.100-108, 1990-04-28 (Released:2008-05-30)
参考文献数
10
被引用文献数
1 1

World trends and problems of amphetamine and methamphetamine abuse, were described. Since the world seizures of the controlled drugs such as opiates, heroin, cocaine, cannabis and other psychotropic substances have rapidly increased in recent years, the author focused on the world-wide spread of amphetamine abuse. The world seizure of stimulant including amphetamines in 1987 has increased by 5-6 fold over in 1982. The trends of amphetamine abuse in many countries were summarized and this report pointed out the past and present problems of amphetamine abuse in U.S.A., Sweden, and Japan. In west coast regions of U.S.A., methamphetamine abuse has surprisingly spread in recent years. The increases of clandestine laboratory have become a big problem in US western states. The trends of amphetamine abuse patterns were introduced. Because of the great risk of acquired immunodeficiency syndrome with intravenous injection drug use, abuse patterns have been changing from injection to inhalation of amphetamines. About a new smokable methamphetamine, so-called "ice", its chemical and pharmacological characters were discussed and its toxicity also described. Additionally, concerning psychotropic drugs chemically and pharmacologically similar to amphetamines, their histories and hallucinogenic activities were described. In paticular, the epidemiologic topics of 3, 4-methylenedioxymethamphetamine (MDMA) called the rivival of LSD was described.
著者
内田 英二
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.129, no.2, pp.213-221, 2009-02-01 (Released:2009-02-01)
参考文献数
8
被引用文献数
3 4

This paper describes the history of discussions on ethnic differences at the International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use (ICH). The first part of this paper gives a short outline of the purpose, organization, history, decision making process of the ICH. The ICH process consists of five steps. Step 1: Consensus building by Expert Working Group (EWG); Step 2: Confirmation of six-party consensus; Step 3: Regulatory consultation and discussion; Step 4: Adoption of an ICH harmonized tripartite guideline and Step 5: Implementation. Ethnic factors in the acceptability of foreign clinical data (“Ethnic Difference”) was one of the 14 topics on Efficacy. The author being one of the members of ICH-E5 EWG took part in the discussion of Ethnic Difference. The second part of this paper, describes the history of the discussion on this topic (from its inception to the finalization of the guideline) focusing on Step 2. A retrospective survey on individual pharmacokinetic data of around 80 drugs approved or under development in the 3 regions was conducted. In drafts 2 and 3, acceptance of phase 1 study only was discussed. But the proposal was opposed by industry members from US and EU. In drafts 4 and 5, the concept of “triage” was introduced and several algorithms were proposed, but finally a consensus could not be reached because the proposal was not so pragmatic. In drafts 7 and 8, the concept of “bridging study” was discussed to solve the problem of conducting phase II and III studies. Again, a consensus could not be reached. After the discussion of the “complete clinical data package” as proposed in drafts 9-12, the bridging study was once again discussed in drafts 13-19. Finally, draft 20 was confirmed and the discussion then moved to Step 3.
著者
高石 清和
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.88, no.11, pp.1467-1471, 1968-11-25 (Released:2008-05-30)
参考文献数
12
被引用文献数
7 7

Coumarin (1) and coumaric acid glucoside (2) were isolated from the leaves of Prunus yedoensis MATSUM. (cherry tree). The structure of (2) was proved as o-coumaric acid β-D-glucoside which had been isolated from Melilotus altissima TEUIL. and named melilotoside by C. Charaux. Comparative determination of (1) and (2) in the leaves of cherry tree was made, and it was thereby found that red leaves in autumn contained much more o-coumaric acid glucoside than green leaves in spring, with a very small amount of coumarin in free state throughout the year. It is noteworthy that the deeper the red color of the leaves, the higher the content of o-coumaric acid glucoside. It is also interesting from biosynthetic point of view that both coumarin and anthocyan are synthesized through shikimic acid pathway. It was suggested that the leaves of cherry tree contain a fairly high amount of coumarin in the form of o-coumaric acid glucoside with a very small amount of free coumarin, although Kosuge, Brown, and Soine, have reported that o-coumaric acid glucoside in Melilotus spp. is finally converted into free coumarin.