著者

内藤 結花 前田 真之 長友 安弘 宇賀神 和久 秋間 悦子 田中 道子 時松 一成 佐々木 忠徳

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.142, no.5, pp.527-534, 2022-05-01 (Released:2022-05-01)

参考文献数

18

被引用文献数

2

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Antimicrobial stewardship (AS) intervention strategy is a critical process in promoting appropriate antibiotic use, thus preventing unnecessarily prolonged therapy and reducing antimicrobial resistance (AMR). Although limiting unnecessary carbapenem use by AS intervention is speculated to reduce AMR, there is a lack of specific data on the efficacy of AS team (AST) intervention regarding carbapenem-resistant Pseudomonas aeruginosa (CRPA). Consequently, this study aimed to evaluate the impact of our AS strategy on carbapenem use and CRPA. The AS intervention strategy was launched in July 2017 and consisted of daily audits and feedback on carbapenem use. We evaluated the 4-year prescription trend, including the rate of switching to other antimicrobials, and the rate of CRPA and the days of therapy required prior to and after the beginning of the AST intervention. The rate of switching to narrow-spectrum antibiotics and the discontinuation of carbapenem treatment were significantly higher in the pre-intervention period compared with the post-intervention period. (7.0% vs. 14.5%; p<0.001; 54.1% vs. 50.9%; p=0.027). However, there were no significant differences in the rate of CRPA prior to and after the beginning of the AST intervention. Furthermore, there was no correlation found between consumption and resistance rate (Pearson's r=0.123). Our results suggest that it is extremely important for AST to promote de-escalation and reduce unnecessary use, while the combination of process and outcome indicators other than antimicrobial consumption and resistance rate are required for the evaluation of the AS programs.

著者

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.142, no.4, pp.327-330, 2022-04-01 (Released:2022-04-01)

参考文献数

7

---

Medical big data are accumulated daily by medical staff in clinical settings. We developed a formulary in 2016 using medical big data from eight hospitals affiliated with Showa University, Japan (3200 beds). In 2019, we revised the procedure from the perspective of authenticity, reproducibility, and clarity to develop a medicine formulary with unbiased data. Briefly, we organized two teams of expert physicians. Team 1 was a systematic review team that conducted a literature search using systematic review. Team 2 was a medical big data team that conducted the analysis using medical big data. Both teams developed a bisphosphonate formulary. First and second team recommendations were alendronic acid and minodronic acid, and alendronic acid and risedronic acid, respectively. Discussion between the two teams yielded alendronic acid only in the bisphosphonate formulary. We developed reports for the bisphosphonate formulary that included conflicts of interest, the role of each staff member in developing the formulary, and the process for determining the formulary. To use our formulary in a community context, we updated the formulary on our website. We tried to substantiate our bisphosphonate formulary and make a recommendation to change the bisphosphonates according to our formulary. The formulary is focused on controlling the economic burden of medical expenses. We believe that the formulary needs to represent authenticity, reproducibility, and clarity in the procedure and conflicts of interest, with unbiased data to preclude context (hospital)-convenient decisions.

著者

柴田 ゆうか

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.1, pp.25-31, 2021-01-01 (Released:2021-01-01)

参考文献数

32

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Various issues related to clinical use of medicines remain unclear, and pharmacists are expected to establish evidence for appropriate use of medicines. The present review summarizes our findings from three areas of research regarding the use of medicines in the operating room: 1) We evaluated the extent of extravasation injury due to thiopental (2.5 mg/100 μL) and propofol (1.0 mg/100 μL) at the macroscopic and histopathologic levels in a rat model. Thiopental, which causes tissue necrosis, can be classified as a “vesicant”, and propofol can be classified as an “irritant”. Moreover, warming strongly exacerbated the degeneration or necrosis induced by extravasation of thiopental. 2) The cytotoxicity of povidone-iodine solution (PVP-I) for ophthalmic use and that of polyvinyl alcohol-iodine solution (PAI) was compared using a human corneal epithelial cell line. Despite exhibiting equivalent antiseptic effects, the cytotoxicity of PVP-I diluted 16-fold was greater than that of PAI diluted 6-fold. After inactivation of iodine, the cytotoxicity of PVP-I persisted; therefore, to avoid corneal damage, antisepsis should be achieved with PAI. 3) The stability of 1 μg/mL adrenaline when used as an intraocular irrigating solution to maintain pupil dilation was evaluated. After mixing for 6 h, the adrenaline concentration was 65.2% (pH 8.0) of the initial concentration. Moreover, the low concentration of sodium bisulfite in the irrigating solution could have caused adrenaline reduction. Our results strongly suggest that intraocular irrigation solution containing adrenaline should be prepared just prior to use in surgery.

著者

若槻 壮市 山田 悠介 Leonard M. G. CHAVAS 五十嵐 教之 川崎 政人 加藤 龍一 平木 雅彦 松垣 直宏

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.5, pp.631-640, 2010-05-01 (Released:2010-05-01)

参考文献数

10

被引用文献数

2 2

---

The Targeted Protein Research Program (TPRP) started in 2007 as a sequel of the Protein 3000 Project which lasted from 2002 to 2007. In the new project, four cores, Protein Production, Structure Analysis, Control of Protein Functions with Compounds, and Informatics, have been established as focus of methodology developments critical for functional and structural studies by the target protein research teams. Within the “Analysis Core” synchrotron radiation plays a pivotal role providing X-ray beams for structural analyses of the target proteins. The two large Japanese synchrotron radiation facilities, SPring-8 and Photon Factory (PF), along with three protein crystallography groups from Hokkaido, Kyoto and Osaka Universities have teamed up to develop two complementary micro-beam beamlines, one on each synchrotron site, and associated technologies for cutting edge structural biology research. At the PF, there are 5 operational beamlines which are equipped with state-of-the-art instrumentation for high-throughput protein crystallography experiments. Within the TPRP framework, the PF is developing a micro-focus beamline optimized for a lower energy single anomalous diffraction (SAD) experiment. This will be particularly useful for structure determination of difficult protein targets for which heavy atom derivatives or selenomethionine substitution does not work and other standard phasing methods fail to give structure solutions. This will augment the capabilities of the PF structural biology beamlines with similar look-and-feel experimental environments.

著者

森本 健幹 長島 裕樹 森本 泰子 徳山 尚吾

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.9, pp.1129-1136, 2017-09-01 (Released:2017-09-01)

参考文献数

20

被引用文献数

7

---

Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function. We studied a cohort of 57 patients with impaired renal function hospitalized with pneumonia and treated with TAZ/PIPC between January 2015 and November 2016. Patients were classified into four groups according to TAZ/PIPC dose: 2.25 g three times daily (Group A); 2.25 g four times daily (B); 4.5 g twice daily (C) and 4.5 g three times daily (D). We examined the frequency of acute kidney injury (AKI) and treatment effectiveness. In Groups A, B, C and D, AKI occurred in 5.6%, 0.0%, 25.0% and 38.5% of patient. In groups C and D, hydration and dose reduction were required to address early signs of impending AKI. Our findings suggest that the higher TAZ/PIPC dose of 4.5 g was responsible for the decline in renal function, even if the dose frequency was reduced.

著者

吉松 嘉代 北澤 尚 河野 徳昭 飯田 修 川原 信夫

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.2, pp.237-246, 2010-02-01 (Released:2010-02-01)

参考文献数

10

被引用文献数

2 2

---

Illegal cannabis (Cannabis sativa L.) cultivation is still a social problem worldwide. Fifty inquiries on cannabis that Research Center for Medicinal Plant Resources (Tsukuba Division) received between January 1, 2000 and March 31, 2009 were itemized in to 8 categories; 1: seed identification, 2: plant identification, 3: indoor cultivation, 4: outdoor cultivation, 5: germination and growth characteristics, 6: expected amount of cannabis products derived from illegal cannabis plant, 7: non-narcotic cannabis and 8: usage of medicinal cannabis. Top three inquiries were 1: seed identification (16 cases), 3: indoor cultivation (10 cases) and 4: outdoor cultivation (6 cases). Characteristics of cannabis, namely seed morphology, germination and growth characteristics, and distinction from kenaf (Hibiscus cannabinus L.) that is frequently misjudged as cannabis, were studied to contribute for prevention of illegal cannabis cultivation.

著者

鈴木 亮 丸山 一雄

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.138, no.7, pp.919-922, 2018-07-01 (Released:2018-07-01)

参考文献数

6

被引用文献数

1 5

---

Theranostics is a term used to describe the combination of diagnostic and therapeutic functions in a single agent. Ultrasound, for example, is a good tool for theranostics due to its multi-potency as both a diagnostic tool using sonography, and as a therapeutic, i.e., by high intensity focused ultrasound (HIFU). Likewise, microbubbles and nanobubbles are not only used as contrast imaging agents, but also as enhancers of drug delivery. Recently, the combination of these bubbles with low intensity ultrasound has been utilized as an effective drug delivery system. We have implemented a similar technique by combining bubbles and ultrasound to study cancer gene therapy and chemotherapy. In addition, we have used high intensity ultrasound as a method for directly damaging tumor cells, thus serving as a cancer therapy. For effective cancer treatment, however, the properties of the bubbles are of utmost importance. Currently, we are applying these bubbles to various therapeutic strategies in cancer treatment. In this session, we would like to introduce the feasibility study of our use of these bubbles in cancer treatment.

著者

清野 慧至 髙田 幸尚 雑賀 司珠也

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.141, no.1, pp.35-39, 2021-01-01 (Released:2021-01-01)

参考文献数

25

被引用文献数

3

---

Eyedrops often contain additives other than active pharmaceutical ingredients, such as preservatives. The most frequently used preservative is benzalkonium chloride (BAC). When the ocular surface is exposed to eyedrops, the active pharmaceutical ingredients and additives can cause corneal epithelial disorder. Particularly in clinical settings, there is great interest in corneal epithelial disorders resulting from the use of glaucoma eyedrops, which is inevitable when instilled for a long period of time after the onset of disease. At the authors' institute, glaucoma is treated with consideration of reducing corneal epithelial disorder while ensuring the effect of lowering intraocular pressure by the appropriate choice of eyedrops. In this review, we show the examples of the retrospective studies. Sodium hyaluronate eyedrops are prescribed for corneal epithelial disorders such as superficial punctate keratitis associated with dry eye. Prescribable concentrations of sodium hyaluronate in Japan are 0.1% or 0.3%, and the 0.3% formulation does not contain BAC. The authors' study showed that 0.3% sodium hyaluronate pretreatment reduced the cytotoxicity of BAC in cultured corneal epithelial cells, whereas an in vivo study in mice showed that a 0.3% sodium hyaluronate instillation was suggested and that the drug may enhance the cytotoxicity of separately administered BAC. It is suggested that sodium hyaluronate prolonged the retention of BAC on the ocular surface. However, there have been no reports of this problem in the clinical setting. It is important for ophthalmologists to understand the properties of additives other than the active pharmaceutical ingredients in eyedrops.

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.11, pp.1405-1413, 2020-11-01 (Released:2020-11-01)

参考文献数

15

被引用文献数

8

---

Lysergic acid diethylamide (LSD) is a hallucinogen, synthesized from ergot alkaloid, and controlled as a narcotic in Japan. Recently, LSD derivatives have appeared as designer drugs, all over the world. In previous study, we reported identification and analysis of four LSD derivatives in four paper sheet products. In this study, we detected three additional LSD derivatives from three paper sheet products, which were obtained from September 2019 to March 2020 in Japan. We extracted the compounds from paper sheet products with methanol for LC-MS, high-resolution MS and GC-MS analyses. The compounds were identified as 4-cyclopropionyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1cP-LSD), N-methyl-N-isopropyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3-fg]quinoline-9-carboxamide (MIPLA), 4-butyryl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1B-LSD), by GC-MS, LC-MS, LC-Q-TOF-MS and NMR analyses. As well as other N1-acylated LSD derivatives, 1cP-LSD and 1B-LSD were easily deacylated to LSD during GC-MS analysis, we have to be careful to analyze these compounds.

著者

大野 雅恵

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.3, pp.343-355, 2008-03-01 (Released:2008-03-01)

参考文献数

62

被引用文献数

4 4

---

Nuclear receptors function as ligand-inducible transcription factors that regulate various physiological functions such as development, reproduction, and metabolism. Dysregulation of the metabolism of cholesterol, triglyceride, and glucose leads to the metabolic syndrome including type 2 diabetes mellitus, obesity, dyslipidemia, and atherosclerosis. Studies of nuclear receptors promise to provide discoveries of therapeutic agents against the metabolic syndrome. Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and is activated by bile acids. FXR regulates the metabolism of not only bile acid but also cholesterol, lipoprotein, triglyceride, and glucose, and is considered a potential therapeutic target for the metabolic syndrome because of these functions. Nuclear receptors have two regions for transactivation, a constitutive activation function (AF-1) and a ligand-dependent activation function (AF-2). AF-1 and AF-2 seem to require interactions with coactivators for the activation function and both work synergistically to give full transactivation of nuclear receptors. However, coactivators for AF-1 activity are poorly understood, whereas coactivators required for AF-2 activity have been well studied. To understand the molecular mechanism of AF-1 in FXR, we isolated proteins associated with AF-1 by GST pull-down assay using the N-terminal region of FXR and nuclear extracts from HeLa cells. This review focuses on the roles of FXR and our new findings regarding FXR-associated factors.

著者

望月 眞弓 初谷 真咲 六條 恵美子 有田 悦子 橋口 正行 清水 直容 竹内 正弘 山本 信夫 秋葉 保次

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.124, no.12, pp.989-995, 2004 (Released:2004-12-01)

参考文献数

24

被引用文献数

7 18

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We conducted a randomized, controlled study to evaluate whether pharmacists' advice on smoking cessation would result in a higher smoking cessation rate using Nicorette (nicotine gum preparation). Fourteen pharmacies in Tokyo, Kanagawa, and Nagano participated. Smokers who visited pharmacies to buy Nicorette from March 1, 2002, through August 31, 2002, were recruited and randomly assigned to two groups. For the intervention group (A), pharmacists provided both regular instructions on Nicorette use and smoking cessation advice at the first sale and then gave follow-up advice just before starting a cessation and 1, 3, and 8 weeks and 3 months thereafter. For the control group (B), pharmacists provided regular instructions alone. The primary outcome measure was the self-reported smoking cessation rate and the secondary outcome measure was the relationship between the smoker's egogram and effectiveness of intervention. Twenty-eight smokers were enrolled and randomized into group A (n=11) or group B (n=17). The absolute abstinence rate in groups A and B at 3 months was 45.5% and 31.2%, respectively. The odds ratio was 1.83, which was not statistically significant. There was no difference in egogram score between absolute abstinence subjects and nonabstinence subjects in group A. The egogram scores in Adapted Child of absolute abstinence subjects in group B were significantly higher than in nonabstinence subjects. In conclusion, instructions and advice given by pharmacists may improve the smoking cessation rate in smokers receiving nicotine replacement therapy.

著者

馬来 秀行 朴 恵林 三木 晶子 佐藤 宏樹 小西 ゆかり 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.140, no.10, pp.1285-1294, 2020-10-01 (Released:2020-10-01)

参考文献数

3

被引用文献数

3

---

Care workers at care facilities play an important role in providing medication-administration assistance, and in medication risk management. Nevertheless, research has not made clear the specific concerns that care workers have at work sites, as well as the extent of their burdens. Thus, we conducted a questionnaire survey from October 1 through October 31, 2014 for staff who provide medication-administration assistance at for-pay elderly person homes about the concrete concerns and burdens with regards to the assistance. A total of 1677 respondents were analyzed: 228 nurses and 1449 care workers. Results showed that the care workers had a variety of problems and issues. These included the fact that, since care workers are not medical profession, they were unable to answer questions that the facility residents asked about their medications; they had concerns regarding their own lack of awareness of the efficacies of medications, and as to whether certain drugs were inappropriate for certain patients with swallowing dysfunctions; they wondered whether drugs in tablet forms had to be crushed before administration. They also encountered pharmacological-related issues, including whether administration times and numbers failed to match the lifestyle patterns of facility residents, and so forth. It is presumed that, with active intervention of pharmacists within facilities, these issues could be resolved. Study results, thus, suggested the need for system creation whereby pharmacists can become deeply involved in medication-administration assistance along with the care workers within facilities.

著者

瀬筒 秀樹 笠嶋(炭谷) めぐみ 近藤 まり 小林 功 高須 陽子 鈴木 誉保 米村 真之 飯塚 哲也 内野 恵郎 田村 俊樹 坪田 拓也 立松 謙一郎

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.7, pp.863-874, 2018-07-01 (Released:2018-07-01)

参考文献数

33

被引用文献数

6

---

We have been constructing a platform for the development of pharmaceutical and medical applications using the domesticated silkworm, Bombyx mori, as a new animal model for drug development and evaluation. Because silkworm larvae originally have the capacity to synthesize up to 0.5 g of silk proteins, genetically modified silkworms (transgenic silkworms) are expected to have high potential in the production of recombinant silks/proteins. An innovative method for generating transgenic silkworms was established in 2000, and ever since this epoch-defining technological development, longstanding efforts have succeeded in developing novel silks that enable the manufacture of new textile materials for regenerative medical uses. Furthermore, we have succeeded in developing a new system of recombinant protein production. This recombinant protein production system is currently capable of producing a maximum of approximately 15 mg recombinant protein per silkworm larva. Transgenic silkworms have also been shown to produce a wide variety of useful proteins, including antibodies and membrane proteins. Some of these recombinant proteins have been in commercial use since 2011. In addition, we have been developing transgenic silkworms as a novel animal model for testing medicines based on metabolic similarities between silkworms and mammals. These applications show the suitability and potential of transgenic silkworms for medical use. Here, we will describe the challenges faced in creating a transgenic silkworm-based platform for pharmaceutical and medical applications.

著者

川本 庸太 田山 剛崇 佐和 章弘 門出 孝美 佐島 進 吉岡 真理 三宅 勝志 森田 修之 木平 健治

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.128, no.8, pp.1221-1226, 2008-08-01 (Released:2008-08-01)

参考文献数

12

被引用文献数

2 3

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Impetigo contagiosa staphylogenes is commonly treated by administering a combination of nadifloxacin and tetracycline ointments. However, it is not clear whether nadifloxacin and tetracycline are stable after mixing. The purpose of this study was to evaluate the stability of these agents in combination. We also evaluated changes in antibacterial activity after mixing. Mixing the two ointments caused tetracycline to change from yellow to brown in the admixture. Furthermore, the tetracycline content in the ointment decreased in a time-dependent manner, to about 40% at 288 h after mixing. In addition, the nadifloxacin content in the ointment did not change 288 h after mixing. In an alkaline environment (pH 9.0 and 11.0), the tetracycline content decreased and the color of tetracycline changed to brown. These results suggest that sodium hydroxide, which is an additive in nadifloxacin ointment, influences the content of tetracycline. We evaluated the chemical sensitivity of Staphylococcus aureus using disk tests. Nadifloxacin and tetracycline ointment showed the largest radius of inhibition circle, followed by the admixture 0 h after mixing and the admixture 72 h after mixing. These results suggest that the antibacterial activity is inhibited by the admixture. We propose that pharmacists should avoid mixing nadifloxacin with tetracycline ointment in the treatment of impetigo contagiosa staphylogenes and should take care to avoid interactions caused by additives in the ointments.

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

---

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

---

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.