著者
小原 拓
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.463-471, 2021-04-01 (Released:2021-04-01)
参考文献数
31

We have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarified that prescriptions of antihypertensive drugs for pregnant women increased during the second half of pregnancy, while prescriptions of anti-epileptic and anti-anxiety drugs decreased after pregnancy using a claims database. A survey of pharmacists and pharmacy students revealed a lack of awareness of effective folic acid intake to reduce the risk of neural tube defects in infants. The percentage of pre-pregnancy folic acid supplementation among pregnant women participating in the Babies and their Parents' Longitudinal Observation in Suzuki Memorial Hospital on Intrauterine Period (BOSHI) study, the JECS, and the Tohoku Medical Megabank (TMM) Birth and Three-Generation (BirThree) cohort study was 6.3-18.0%. As a result of close examination of the records of inquiries to the Drug Information Office of our hospital, and of cases in which our lactation plan sheet was applied, it was found that there were discrepancies between the information on the drug package insert and the information on Medications & Mother's Milk, etc. in Japan. The results obtained have been clinically applied in daily practice and we are continuing our research while taking measures.
著者
小前 憲久 日比野 康英 菅野 延彦
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.119, no.10, pp.763-772, 1999-10-01
被引用文献数
2

The spectral karyotyping (SKY) method is a novel molecular cytogenetic technique which simultaneously discerns entire chromosomes. In order to elucidate the origins of micronuclei induced under hyperthermic conditions in human lymphocyte culture, peripheral blood cells were cultured at 40℃ or 42℃ for 3-24 h, using the cytokinesis-block method with cytochalasin B. The induced micronuclei were identified by the fluorescence in situ hybridization (FISH) and SKY methods. At 42℃ for more than 6 h, the frequency of occurrence of micronuclei in binucleated cells rose with increasing incubation time. By the FISH method, 83.3% of micronuclei induced in 24 h culture at 42℃ were shown to be positive for the human centromeric probes. By the SKY method, each micronucleus induced under the hyperthermic conditions was identified unequivocally and shown to contain a specific chromosome. These results suggest that the micronuclei induced under the hyperthermic conditions in human lymphocyte culture contain chromosomes which do not migrate to the poles at the anaphase of the cell cycle because of the breakdown of the spindle apparatus.
著者
猪又 明子 小縣 昭夫 多田 幸恵 長澤 明道 湯澤 勝廣 安藤 弘 久保 喜一 高橋 博 海鉾 藤文 田中 和良 中嶋 順一 鈴木 淳子 植村 望美 守安 貴子 渡辺 大介 石原 恵 宇佐美 孝 亀井 学 河野 安昭
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.8, pp.1005-1015, 2017-08-01 (Released:2017-08-01)
参考文献数
18
被引用文献数
1 1

We developed a new inhalation exposure method to evaluate effects of synthetic cannabimimetics that are being distributed as new, unregulated drugs in the Tokyo area. We selected the commercial product “SOUTOU” containing AB-CHMINACA and 5F-AMB as the test drug and dried marshmallow (Althaea officinalis) leaves as the negative control. A half cigarette packed with dried marshmallow leaves or SOUTOU was ignited, then mainstream smoke from each was delivered to five mice in an exposure box. After the cigarettes were fully consumed, neurobehavioral observations and a catalepsy test were performed at 15, 30 and 60 min after exposure. The effluent air from the exposure box was poured into impingers containing acetonitrile (first impinger) and dimethyl sulfoxide (second impinger). The resulting solutions were analyzed to assess decomposition of the synthetic cannabimimetics. Mice exposed to SOUTOU smoke showed many excitement behaviors and some suppressive behaviors at 15, 30 and 60 min. These clearly included cannabimimetic specific pharmacological actions. Negative control mice also showed some suppressive behaviors at 15 min but these were attenuated at later times, nearly disappearing at 60 min. In addition, the behavioral effects observed in controls were less pronounced than those in SOUTOU exposed mice. The inhalation exposure method developed in our study would be effective for determining cannabinoid specific pharmacological effects of illegal drugs, as well as for assessing the presence of active compound(s) by comparing the test substance with a negative control.
著者
石井 正和 加藤 大貴 今若 楽明 笠井 英世 石橋 正祥
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.139, no.1, pp.107-111, 2019-01-01 (Released:2019-01-01)
参考文献数
22

To clarify the associated factors for negative response to sumatriptan nasal spray in patients with cluster headache, we investigated the involvement of clinical information, such as the characteristics of headaches, before commencing sumatriptan nasal spray treatment. There were 18 male patients and 4 female patients. A total of 17 responders and 5 non-responders to sumatriptan nasal spray participated in the present study. Three factors for negative response to sumatriptan nasal spray, “young age of onset”, “psychiatric disorder”, and “the headache is not in the orbit,” were found. Oxygen inhalation and/or subcutaneous injection were effective for nonresponsive cases. Therefore, these factors are considered to be useful for predicting therapy before applying sumatriptan nasal spray.
著者
虎谷 哲夫
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.130, no.11, pp.1453-1462, 2010-11-01 (Released:2010-11-01)
参考文献数
28
被引用文献数
1 1

Vitamin B12 is produced only by prokaryotes and utilized by animals as an essential micronutrient. Genetic complementation analysis of cell lines from patients indicated that at least eight gene products are involved in intracellular B12 metabolism and utilization. We have investigated bacterial adenosylcobalamin-dependent enzymes and elucidated their structure-based fine mechanisms. They tend to undergo mechanism-based inactivation during catalysis, because they use highly reactive radicals for catalyzing chemically difficult reactions. We have discovered molecular chaperone-like reactivating factors for these enzymes that release a damaged cofactor forming apoenzyme. Methylcobalamin-dependent methionine synthase also undergoes inactivation, because it utilizes cob(I)alamin, a super nucleophile, for catalysis. Methionine synthase reductase is a reactivating partner for this enzyme. Recent studies suggested that activity-maintaining systems for B12 enzymes are present in animal cells as well, and thus hints for designing therapeutic agents for B12-related metabolic disorders might be obtained from the investigations of microbial B12 metabolism.
著者
菊山 史博 鈴木 小夜 地引 綾 横山 雄太 河添 仁 中村 智徳
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.6, pp.799-808, 2020-06-01 (Released:2020-06-01)
参考文献数
28

Pharmacy practice experience (PPE) is essential in the six-year course of pharmaceutical education in Japan. We previously found that PPE reinforced students' self-efficacy for curriculums (SECs), leading robust acquisition and reconstruction of pharmaceutical expertise. In this study, we aimed to clarify whether students' SECs affect successful experiences as enactive attainments in PPE. We distributed survey questionnaires to the fifth-year students in Keio University in 2016-2017 before and after PPE. The students made a self-assessment of their psychological state “expect to do well” on a seven-point Likert scale for each curriculum (C1 to C18), and their successful experiences were also collected from free description type questionnaire. We could follow up 139 students. The SEC scores increased from pre-PPE to post I (p<0.001) and II terms (p<0.01). The increase in SEC scores during PPE was associated with the rate of students' successful experiences in the first-term PPE (p=0.04). The path analysis revealed the following as significant predictive factors of SECs for successful experiences: basic sciences (C1, C2, C3, C4, C5, and C6) with stand-ardizing coefficient 0.35, health and environmental sciences (C11 and C12) with 0.39, and pharmaceutical sciences (C7, C8, C9, C10, C13, and C14) with −0.51. Students in the first-term PPE tended to experience successful performance in medical professions by using their pharmaceutical expertise that they had learned. In this study, for the first time, we demonstrated that Japanese students' SECs for pharmaceutical expertise affected successful experiences, leading better outcomes of PPE.
著者
大久保 正人 増田 和司 小林 由佳 中村 貴子 鈴木 貴明 石井 伊都子
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.5, pp.731-742, 2021-05-01 (Released:2021-05-01)
参考文献数
18

In 2010, the in-hospital practical training period for pharmacy students was extended from 4 to 11 weeks. We have conducted questionnaire surveys of these students every year with the aim of reviewing the quality of training by conduction of surveys and evaluations. However, it was not clear whether reviewing based on the questionnaire results improved student satisfaction with the in-hospital practical training. Therefore, the aim of this study was to verify the validity of reviewing based on the questionnaire results by analyzing the data accumulated during the long-term practical training. A questionnaire survey was conducted of 333 5th-year students upon completion of practical training at Chiba University Hospital from 2010 to 2017. Students self-evaluated their attitude toward practical training on a 6-point scale and their satisfaction level for each component of the practical training on a 5-point scale. The students were also allowed to share their feelings about hospital pharmacy work. Repeated review of the training content can facilitate communication with patients, which was lacking at the beginning of the training period. Improved communication led to higher-quality pharmacy practice and increased student satisfaction. Meanwhile, changes to work procedures may reduce student satisfaction unless the training strategy is reviewed accordingly. Because the work of hospital pharmacists is constantly changing, it is considered that the content of the practical training should be revised accordingly through continuous conduction of surveys and evaluations, thereby enabling optimal practical training.
著者
澤間 善成
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.2, pp.139-144, 2022-02-01 (Released:2022-02-01)
参考文献数
24

Deuterium (2H, D) is a stable isotope of hydrogen (1H). Deuterium-incorporated (labelled) compounds are widely utilized in various scientific fields such as mechanistic studies of organic reactions, elucidation of drug metabolism, application as tracers for microanalysis. Recently, development of heavy drugs and molecular imaging using techniques such as neutron scattering and Raman spectroscopy are spotlighted. We have developed various deuterium-incorporated compounds using D2O as an inexpensive deuterium source to construct novel functional materials. The use of platinum group metals on carbon as catalysts could result in the multi-deuteration of compounds in the mixed solvents of 2-propanol and D2O, and site-selectively deuterated compounds can be synthesized by organocatalytic methods. In this review, the latter deuteration methods using organocatalysts and their applications are summarized. Terminal alkynes smoothly underwent deuterium incorporation by using triethylamine as an organic base or a solid resin possessing the tertiary amine moiety in the same molecule to give mono-deuterated alkynes. These compounds were partially reduced over our prepared specific palladium catalyst under atmospheric D2 gas to produce tri-deuterated alkenes. Achiral or chiral di-deuterated β-nitro alcohols were also prepared by the organic-base-catalyzed deuteration of nitromethane, followed by nitroaldol reactions in a one pot manner. The mono-deuteration of aromatic aldehyde could be effectively catalyzed by N-heterocyclic carbene. Furthermore, the α-deuteration of aliphatic aldehydes using a basic resin catalyst and the subsequent Knoevenagel condensation with malononitrile could provide γ-deuterium-incorporated α,β-unsaturated nitrile derivatives. The deuterated compounds thus obtained can be important synthetic precursors to construct the deuterium-incorporated target functional materials.
著者
丹羽 俊朗 白神 歳文 高木 明
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.125, no.10, pp.795-805, 2005-10-01 (Released:2005-10-01)
参考文献数
81
被引用文献数
22 25

This article reviews the in vitro metabolic and the in vivo pharmacokinetic drug-drug interactions with antifungal drugs, including fluconazole, itraconazole, micafungin, miconazole, and voriconazole. In the in vitro interaction studies, the effects of antifungal drugs on specific activities of cytochrome P450s (CYPs), including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, in human liver microsomes are compared to predict the possibility of drug interactions in vivo. Fluconazole, micafungin, and voriconazole have lower inhibitory effects on CYP3A4 activities than itraconazole and miconazole, and IC50 and/or Ki values against CYP2C9 and CYP2C19 activities are the lowest for miconazole, followed by voriconazole and fluconazole. In in vivo pharmacokinetic studies, it is well known that itraconazole is a potent clinically important inhibitor of the clearance of CYP3A4 substrates, and fluconazole and voriconazole are reported to increase the blood or plasma concentrations of not only midazolam and cyclosporine (CYP3A4 substrates) but also of phenytoin (CYP2C9 substrate) and/or omeprazole (CYP2C19/CYP3A4 substrate). On the other hand, no inhibition of CYP activities except for CYP3A4 activity by micafungin is observed in vitro, and the blood concentrations of cyclosporine and tacrolimus are not affected by coadministration of micafungin in vivo, suggesting that micafungin would not cause clinically significant interactions with drugs that are metabolized by CYPs via the inhibition of metabolism. Miconazole is a potent inhibitor of all CYPs investigated in vitro, although there are few detailed studies on the clinical significance of this except for CYP2C9. Therefore the differential effects of these antifungal drugs on CYP activities must be considered in the choice of antifungal drugs in patients receiving other drugs.
著者
新見 伸吾
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.4, pp.431-437, 2017-04-01 (Released:2017-04-01)
参考文献数
7
被引用文献数
1 2

Prototypes of medical devices are made in accordance with the needs of clinical practice, and for systems required during the initial process of medical device development for new surgical practices. Verification of whether these prototypes produce the intended performance specifications is conducted using basic tests such as mechanical and animal tests. The prototypes are then improved and modified until satisfactory results are obtained. After a prototype passes through a clinical trial process similar to that for new drugs, application for approval is made. In the approval application process, medical devices are divided into new, improved, and generic types. Reviewers judge the validity of intended use, indications, operation procedures, and precautions, and in addition evaluate the balance between risk and benefit in terms of efficacy and safety. Other characteristics of medical devices are the need for the user to attain proficiency in usage techniques to ensure efficacy and safety, and the existence of a variety of medical devices for which assessment strategies differ, including differences in impact on the body in cases in which a physical burden to the body or failure of a medical device develops. Regulatory science of medical devices involves prediction, judgment, and evaluation of efficacy, safety, and quality, from which data result which can become indices in the development stages from design to application for approval. A reduction in the number of animals used for testing, improvement in efficiency, reduction of the necessity for clinical trials, etc. are expected through rational setting of evaluation items.
著者
石館 守三 田村 善藏
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.70, no.5, pp.239-241, 1950-05-25 (Released:2010-02-19)
参考文献数
7
被引用文献数
2 4

A study was made on cardiac glycosides in the methanolic extract of the leaves of Nerium odorum cultivated in Japan. From the chloroform-soluble fraction, oleandrin, one of the components of Nerium Oleander, was isolated and identified.
著者
岡 希太郎
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.100, no.3, pp.227-240, 1980
被引用文献数
1

Synthetic studies on salamander alkaloids isolated from animal venom in the skin gland of Salamandra maculosa LAURENTI were performed. Syntheses of three groups of alkaloids, one with a bicyclo-oxazolidine, one with a carbinolamine, and another with a pure 3-aza-A-homo steroid, are discussed. Regio- and stereospecific syntheses of the alkaloids are discussed in connection with the construction of the bicyclo-oxazolidine system of the major alkaloids and in connection with Beckmann rearrangement of steroid 3-ketoximes for the syntheses of the other alkaloids. A theoretical approach to the resolution of the geometrical isomers of oximes by adsorption chromatography is also discussed.
著者
武田 美雄 藤多 哲朗 佐藤 利夫 掛川 寿夫
出版者
公益社団法人日本薬学会
雑誌
薬学雑誌 (ISSN:00316903)
巻号頁・発行日
vol.105, no.10, pp.p955-959, 1985-10
被引用文献数
2

From the aerial part of Stachys sieboldi MIQ. (Labiatae), three glycosides were isolated and characterized as isoscutellarein. 4'-methyl ether 7-O-β-(6'''-O-acetyl-2"-allosyl) glucoside (1), isoscutellarein 7-O-β-(6'''-O-acetyl-2"-allosyl) glucoside (2), and acteoside (8). The effects of these glycosides on the activity of hyarulonidase were also examined.
著者
山原 条二 木谷 哲也 小林 弘美 河原 有三
出版者
公益社団法人日本薬学会
雑誌
薬学雑誌 (ISSN:00316903)
巻号頁・発行日
vol.110, no.12, pp.p932-935, 1990-12
被引用文献数
6

During screening for the development of drugs from natural products, methanolic extract of tuber of Stachys sieboldii MIQ. (Labiatae) significantly inhibited the lethal induced by KCN in mice. The methanolic extract was fractionated by column chromatography to identify the active constituents. Acteoside and stachysoside C, phenylethanoid glycoside, have a significant effect on the KCN-induced anoxia model.
著者
郡山 恵樹
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.133, no.8, pp.843-848, 2013 (Released:2013-08-01)
参考文献数
12
被引用文献数
3 4

The retina has been regarded as 'an approachable part of the brain' for investigating central nervous system (CNS). The optic nerve injury is a well-accepted model to study the mechanisms of neural degeneration and/or axonal regeneration after trauma in the CNS. Nitric oxide (NO) is a gaseous messenger molecule biosynthesized from L-arginine and molecular oxygen by NO synthase. Many reports suggest that excess production of NO plays a crucial role in neuronal cell death including in death of retinal ganglion cells (RGCs). In contrast, several lines of evidence indicate that NO can prevent neuronal death. In general, NO mediates neuroprotection through two main signaling pathways: the NO/cyclic guanosine monophosphate (cGMP) pathway and the S-nitrosylation pathway. Especially, whether S-nitrosylation of proteins promotes RGCs survival and its axonal regeneration after injury is unclear. Thus, we focused on the S-nitrosylation-dependent mechanism of RGCs survival and axonal regeneration by NO after nerve injury.
著者
安茂 寿夫 和志 武三徳 漆崎 文男 野田 国男
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.88, no.11, pp.1404-1411, 1968

2, 2-Diphenyl-2-propargyloxyacetic acid (2-dimethylaminoethyl) ester hydrochloride (DPDM) is decomposed in aqueous solution. It was confirmed by thin-layer chromatography and gas chromatography that the decomposition of DPDM occurs as consecutive reactions. In the first step, DPDM is hydrolysed to propargyloxy-benzilic acid (BPE) and &beta;-dimethylaminoethanol hydrochloride and next, BPE is decomposed to benzilic acid (BA) and propargyl alcohol. As BPE is extremely slightly soluble in water, BPE precipitates in aqueous solution in proportion to decomposition of DPDM. In the present investigation, the hydrolytic decomposition of DPDM and BPE was studied in order to obtain more stable aqueous preparations, and DPDM was found to be stable at pH 2.5 to 3.5. Variations in the concentration of DPDM, BPE, and BA in aqueous solution were calculated by an analog computer. Data observed in the experiment corresponded with those calculated by the computer.
著者
石原 慎之
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.141, no.12, pp.1289-1296, 2021-12-01 (Released:2021-12-01)
参考文献数
23

In recent years, antimicrobial resistance bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) have become a global problem. One of the countermeasures is to optimize the use of antimicrobial drugs, specifically to optimize the dosage and administration based on the therapeutic drug monitoring (TDM) and pharmacokinetics (PK)/pharmacodynamics (PD) theory. On the other hand, in clinical practice, clinical-pharmacometrics can be used for optimized management of individual patients of pharmaceutical products. Therefore, we aimed at individual optimization of infectious disease treatment for antimicrobial resistant bacteria, and tried a series of flows from model construction to clinical application, that is, practice of clinical pharmacometrics. In the context of individual optimization and optimization management of drug therapy in the medical field, it is considered that hospital pharmacists can contribute to the improvement of infectious disease treatment of antimicrobial resistance bacteria by contributing to the optimization of administration method. In addition, clinical pharmacometrics can be applied not only to antibacterial drugs but also to all drugs, and can be said to be a useful method for quantitatively evaluating the promotion of individualized administration methods for patients.
著者
竹本 常松 草野 源次郎 ヒキノ ヒロシ
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.86, no.12, pp.1160-1161, 1966-12-25

From the herbs of Youngia denticulata (Japanese name "Yakushi-so")(Compositae), germanicyl acetate (I), taraxasteryl acetate (II), germanicol (III), taraxasterol (IV), β-sitosterol (V), and 1-hexacosanol (VI) were isolated.