著者
田中 真吾 朝比奈 泰子 佐藤 宏樹 三木 晶子 堀 里子 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.134, no.6, pp.757-766, 2014-06-01 (Released:2014-06-01)
参考文献数
30
被引用文献数
1 1

It has been reported the use of nonsteroid anti-inflammatory drugs (NSAIDs) in late pregnancy was associated with potentially fetal toxicity (contraction of fetal ductus areteriosus). According to the package inserts in Japan, many oral NSAIDs are contraindicated to women in late pregnancy, but several oral and topical NSAIDs with case reports of fetal toxicity are not. In the present study, a web-based questionnaire survey was conducted in pharmacists/physicians to determine their awareness of fetal toxicity caused by NSAIDs, as well as their attitudes regarding the use of NSAIDs in late pregnancy. Responses were obtained from 427 pharmacists, 22 obstetricians, and 160 non-obstetric physicians. Of the non-obstetric respondents, more than 40% had no knowledge of fetal ductus arteriosus contraction caused by oral ibuprofen, and most of them were not aware of the relevant warning statement on the package insert. In contrast, these were familiar to nearly 100% of the obstetricians. As for ketoprofen tape, only 20-40% of the pharmacists/physicians were aware of the warning statement, and nearly all respondents did not confirm whether the patient was in late pregnancy. The majority of the respondents answered that oral ibuprofen, ketoprofen tape and NSAID-containing OTC drugs should not be used in late pregnancy after they knew the warning statements in late pregnancy. This survey suggests that the fetal toxicity of NSAIDs is not well recognized by pharmacists/physicians. It would be necessary to make it thoroughly known to them through such as enrichment of safety information on the package inserts, accompanying with the evidence.
著者
Ambara R. Pradipta 田中 克典
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.3, pp.301-306, 2017-03-01 (Released:2017-03-01)
参考文献数
20
被引用文献数
1

Acrolein, a highly toxic α, β-unsaturated aldehyde, occurs as pollutant in the environment (e.g., tobacco smoke and exhaust gas) and is ubiquitously generated in biosystems (e.g., the lipid peroxidation process and metabolism of polyamine or amino acids). High accumulation of acrolein in biosystems is often linked pathologically with several oxidative stress-related diseases, including cancer and Alzheimer's disease. Accordingly, acrolein holds great potential as a key biomarker in oxidative stress-related diseases, and direct measurement of acrolein in biological samples is important to provide information for diagnostic and therapeutic purposes. Recently, we have serendipitously discovered the unrecognized reactivity of phenyl azide to acrolein. Phenyl azide can rapidly and selectively react with acrolein in a “click” manner to provide 4-formyl-1,2,3-triazoline through 1,3-dipolar cycloaddition. We have successfully utilized the acrolein-azide click reaction as a simple but robust method for detecting and visualizing acrolein generated by live cells in the context of oxidative stress processes. In addition, we also serendipitously discovered novel cycloaddition reactions of N-alkyl-α,β-unsaturated imines derived from acrolein and biogenic amines (e.g., polyamines, norepinephrine, and sphingosine), to yield 8-membered cyclic compounds. We then examined the biological functions of the cyclic products and revealed for the first time their roles in the oxidative stress mechanism and inhibition of amyloid β(1-40) fibrillization.
著者
F. W. FOONG
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.8, pp.795-798, 2015 (Released:2018-08-26)
参考文献数
1
被引用文献数
1

科学的研究において広く使用されるラテン語とギリシャ語およびそれらの使用法を理解し,習得することはとても大切である.ラテン語およびギリシャ語の基本を知ることが,科学的な報告を理解したり,論文原稿を読み書きする際の効率アップにつながるからである.また,冗長で扱いにくい文章も,ラテン語の術語を用いると簡潔に表現できることがある.さらに,研究発表の資料作成の際にも大変有用である.今回は,以下の3項目に焦点を当てて簡潔に説明する.すなわち,1.論文等で汎用されるラテン(略)語,2.ラテン語およびギリシャ語の単数形と複数形,ならびに,3.ラテン語やギリシャ語から造り出された新術語である.なお最近,米語論文誌の中には,特定のラテン(略)語(例えば,i.e.,viz.など)の使用を制限する傾向があるが,英欧系英語論文誌では今後もラテン(略)語が使用されると考えられる.
著者
春田 純一
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.25, no.3, pp.128-131, 2015-08-01 (Released:2018-11-01)
参考文献数
11
被引用文献数
2

JTオリジナル新薬、抗HIV薬elvitegravirと抗腫瘍薬trametinibの開発ストーリーをエピソードを交えながら紹介する。創薬には化学、生物、医学、物理(分析機器の発展)等の最先端のサイエンスが必須であることは論を待たない。創薬には時間がかかり、数々の困難に出会い、それらを解決して次へと進め、そしてほんの一握りのプロジェクトが成功する。そんな長くて遠い創薬の道を乗り切るには理論だけではどうにもならない時がある。その時、理論以外の「何か」が必要である。それを浮き彫りにしたい。
著者
三星 知 山田 仁志 山崎 修治 小林 真理子 上野 和行 長井 一彦
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.943-947, 2020-07-01 (Released:2020-07-01)
参考文献数
19
被引用文献数
1

Concomitant therapy with acetaminophen (APAP) and low-dose aspirin is often used in clinical settings; however, it is unclear whether this combination is involved in the progression of chronic kidney disease (CKD). We hypothesized that concomitant therapy with APAP and low-dose aspirin may cause CKD progression. We carried out a retrospective 6-year cohort study that included all patients who received low-dose aspirin from January 2011 to December 2016 at Kaetsu Hospital. Primary outcome was defined as CKD progression at the end of the study compared with baseline. Among the 441 patients treated during the study period, we identified 89 cases of CKD progression. Multivariate regression analysis showed that exposure to APAP>50 g [odds ratio (OR), 2.68, 95% confidence interval (CI), 1.08-6.70], age increase by 1 year (OR, 1.05, 95% CI, 1.02-1.08), and diabetes mellitus (OR, 2.40, 95% CI, 1.41-4.08) had positive associations with CKD progression. Our findings suggested that concomitant therapy with APAP and low-dose aspirin increased the risk of CKD progression. Therefore, we recommend more thorough monitoring of serum creatinine when patients are on such concomitant therapy. Moreover, it is important to advise users of low-dose aspirin to avoid unnecessary use of APAP, in order to reduce the risk of CKD progression.
著者
小野嵜 菊夫
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.133, no.6, pp.645-660, 2013-06-01 (Released:2013-06-01)
参考文献数
96
被引用文献数
1 2

Interleukin 1 (IL-1) was initially defined as a factor which is produced by macrophages and exhibits proliferative activity on thymocytes and fibroblasts, B cell activation and endogenous pyrogen activity. Now IL-1 is known to exhibit pleiotropic activities on various cell types and play important roles in the regulation of immune, nervous and endocrine systems, progression of tumor cells, hematopoietic cell proliferation/differentiation and especially in inflammatory diseases. In 1985 I found that IL-1 exhibits cytocidal activity against human melanoma cells. Since then I have been engaged in the research of various aspects of IL-1. This review summarizes current knowledge of IL-1, including our research and beneficial effect of IL-1 blocking on inflammatory diseases.
著者
白坂 善之
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.140, no.5, pp.599-608, 2020-05-01 (Released:2020-05-01)
参考文献数
20
被引用文献数
2

Although oral drugs account for 80% of the world drug market, many difficulties arise in their development. The drug absorption profile after oral administration may be influenced by multiple factors, including dosing conditions and physiological state of the gastrointestinal (GI) tract. Variability in GI fluid volume may influence the absorption characteristics. Indeed, the contributions of passive diffusion, transporters, and metabolic enzymes depend on GI drug concentration, which is influenced by changes in GI fluid volume. However, this important variable has been neglected in many prediction methods for oral drug absorption and drug interactions, and for convenience it is often assumed that the GI water volume is fixed at a constant value. Major global regulatory agencies such as the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) recommend using a constant fluid volume of 250 mL (the fluid volume of a glass of water) to estimate the theoretical GI concentration of drugs after oral administration. However, the actual volume of water in the GI tract is both time- and site-dependent as a result of water intake, absorption, secretion, and GI transit. This review article summarizes our data showing that luminal water volume is influenced by the osmolality of the applied solution, and illustrates how this effect may contribute to changes in GI drug concentration, resulting in altered drug absorption.
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.131, no.2, pp.203-207, 2011-02-01 (Released:2011-02-01)
参考文献数
7
被引用文献数
4 7

Recently, the number of applications of nanomaterials in medicine, cosmetics and food to which we are directly exposed has been expanding rapidly. The safety of such nanomaterials has not been well assessed, because nanomaterials have been considered as safe as common larger sized materials which are known not to be absorbed by the body. Therefore, WHO and OECD are collecting safety information on nanomaterials with a view to regulation of their use. Although assessment of in vivo behaviors of nanomaterials, (i.e., absorption and distribution, and correlation analysis with hazard information) is urgently needed, such research has not yet been undertaken. In this regard, using amorphous silica particles as model nanomaterials, we are starting to study safety, in vivo behavior and their correlation; silica particles are often used in cosmetics and foods and also, downsized particles are rapidly becoming available. In our study, we have found that silica particles below 100 nm in diameter show significantly different characteristics in in vivo behavior and biological effects i.e., penetration through skin and distribution to brain. Here, I addressed the importance of studies in physicochemical characteristics, kinetic behaviors, and biological effects of nanomaterials below 100 nm in size, to ensure their safety.
著者
林 利光
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.61-79, 2008-01-01 (Released:2008-01-01)
参考文献数
42
被引用文献数
4 11

In the search for novel antiviral molecules from natural products, we have discovered various antiviral molecules with characteristic mechanisms of action. Scopadulciol (SDC), isolated from the tropical medicinal plant Scoparia dulcis L., showed stimulatory effects on the antiviral potency of acyclovir (ACV) or ganciclovir (GCV). This effect of SDC was exerted via the activation of viral thymidine kinase (HSV-1 TK) and, as a result, an increase in the cellular concentration of the active form of ACV/GCV, i.e., the triphosphate of ACV or GCV. On the basis of these experimental results, cancer gene therapy using the HSV-1 tk gene and ACV/GCV together with SDC was found to be effective in suppressing the growth of cancer cells in animals. Acidic polysaccharides such as calcium spirulan (Ca-SP) from Spirulina platensis, nostoflan from Nostoc flagelliforme, and a fucoidan from the sporophyll of Undaria pinnatifida (mekabu fucoidan) were also found to be potent inhibitors against several enveloped viruses. Their antiviral potency was dependent on molecular weight and content of the sulfate or carboxyl group as well as counterion species chelating with sulfate groups, indicating the importance of the three-dimensional structure of the molecules. In addition, unlike dextran sulfate, Ca-SP was shown to target not only viral absorption/penetration stages but also some replication stages of progeny viruses after penetration into cells. When mekabu fucoidan or nostoflan was administered with oseltamivir phosphate, their synergistic antiviral effects on influenza A virus were confirmed in vitro as well as in vivo.
著者
江角 悟 河崎 陽一 猪田 宏美 北村 佳久 千堂 年昭
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.138, no.5, pp.649-653, 2018-05-01 (Released:2018-05-01)
参考文献数
5
被引用文献数
1

Pharmacists are required to contribute to evidence-based medicine (EBM) by providing drug information, which can be collected from various sources such as books, websites, and original articles. In particular, information from original articles is needed in some situations. For example, original articles by international researchers are used to aid the management of novel in-hospital preparations on which little knowledge is available. We introduced an information evaluation program, the Okayama University Hospital EBM Model, into the clinical training of 5th-year pharmacy students. It aims to enable students to evaluate the validity of novel in-hospital preparations using original articles. This program has improved students' knowledge of EBM, and the satisfaction level of those enrolled was high. In addition, customer satisfaction analysis revealed that the overall degree of student satisfaction was related to their understanding of the necessity for EBM and the difficulty of practical training. In addition, students' achievements were evaluated using rubrics, and that method allowed the achievements of each student to be assessed appropriately. We hope to revise this program with the aim of improving students' understanding of EBM.
著者
和久 敬蔵
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.126, no.2, pp.67-81, 2006-02-01 (Released:2006-02-01)
参考文献数
63
被引用文献数
4 3

Marijuana has been used as a traditional medicine and a pleasure-inducing drug for thousands of years around the world, especially in Asia. Δ9-Tetrahydrocannabinol, major psychoactive component of marijuana, has been shown to interact with specific cannabinoid receptors, thereby eliciting a variety of pharmacological responses in experimental animals and human. In 1990, the gene encoding a cannabinoid receptor (CB1) was cloned. This prompted the search for endogenous ligands. In 1992, N-arachidonoylethanolamine (anandamide) was isolated from pig brain as an endogenous ligand, and in 1995, 2-arachidonoylglycerol was isolated from rat brain and canine gut as another endogenous ligand. Both anandamide and 2-arachidonoylglycerol exhibit various cannabimimetic activities. The results of structure-activity relationship experiments, however, revealed that 2-arachidonoylglycerol, but not anandamide, is the intrinsic natural ligand for the cannabinoid receptor. 2-Arachidonoylglycerol is a degradation product of inositol phospholipids that links the function of the cannabinoid receptors with the enhanced inositol phospholipid turnover in stimulated tissues and cells. The possible physiological roles of cannabinoid receptors and 2-arachidonoylglycerol in various mammalian tissues such as those of the nervous and inflammatory cells are demonstrated. Furthermore, the future development of therapeutic drugs coming from this endocannabinoid system are discussed.
著者
小田原 真希 山科 卓也 入江 健司 山下 克也 鶴田 南奈子 塚田 寛子 鶴山 萌子 金内 弘志 原 利宝 児玉 真由子 久保 徳彦 平木 洋一
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.140, no.2, pp.319-328, 2020-02-01 (Released:2020-02-01)
参考文献数
31
被引用文献数
1

In this study, antimicrobial stewardship team (AST) intervention was evaluated by comparing patient outcomes and consumption of broad-spectrum antibiotics [carbapenem antibiotics and tazobactam/piperacillin (TAZ/PIPC)] before and after the intervention. There was no fluctuation in the consumption rate of carbapenem, TAZ/PIPC and other antibiotics, but there was a decreased annual consumption of antibiotics after AST intervention compared to before intervention. For the carbapenems, antimicrobial use density (AUD) of meropenem (MEPM) was highest in both periods, at 20.1 and 20.4 before and after AST intervention, respectively, with no significant change after AST intervention. However, the days of therapy (DOT) for MEPM were 27.4 and 24.8 d, respectively, with a decreasing trend after AST intervention. AUD and DOT for TAZ/PIPC after AST intervention were 6.5 and 8.1 d, respectively, which were lower than the pre-intervention values. Rapid identification of the causative strain enables early de-escalation and may improve the economics of antibiotic use, but there was no difference from before to after AST intervention. Compared with before and after strain identification, the carbapenem administration rate after AST intervention was significantly lower than the pre-intervention rate (p<0.01). There was no difference in 28-day mortality and treatment period before and after AST intervention, and there were no differences in outcomes such as resolution of bacteremia, mortality, exacerbation and no change from before to after AST intervention. Based on these results, we suggest that AST intervention can reduce consumption of antibiotics without altering patient outcomes.
著者
小島 周二
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.134, no.6, pp.743-749, 2014-06-01 (Released:2014-06-01)
参考文献数
28
被引用文献数
1 4

We previously reported that low doses (0.25-0.5 Gy) of γ-rays induce intracellular antioxidant, radioresistant, DNA damage repair, and so on. Meanwhile, we have recently reported that ATP is released from the cells exposed to low-dose γ-rays. Here, it was investigated whether or not γ-radiation-induced release of extracellular ATP contributes to various radiation effects, in paricular, focusing on the inductions of intracellular antioxidant and DNA damage repair. Irradiation with γ-rays or exogenously added ATP increased expression of intracellular antioxidants such as thioredoxin and the increases were blocked by pretreatment with an ecto-nucleotidase in both cases. Moreover, release of ATP and autocrine/paracrine positive feedback through P2Y receptors serve to amplify the cellular repair response to radiation-induced DNA damage. To sum up, it would be suggested that ATP signaling is important for the effective induction of radiation stress response, such as protection of the body from the radiation and DNA damage repair. In addition, the possibility that this signaling is involved in the radiation resistance of cancer cells and beneficial effect on the organism of low-dose radiation and radiation adaptive response, would be further suggested.
著者
日下 英司
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.136, no.2, pp.237-242, 2016-02-01 (Released:2016-02-01)
参考文献数
4

In developing countries, many people are unable to access basic healthcare services, resulting in many avoidable deaths and/or disabilities. The United Nations adopted the Millennium Development Goals in order to resolve this problem, and Japan has been contributing greatly to the achievement of these goals. In this context, in 2013 the Government of Japan proposed its Strategy on Global Health Diplomacy, and since then has been promoting Universal Health Coverage. Since the beginning of the 21st century, the particular importance of addressing neglected tropical diseases (NTDs) has been stressed by the international community. Nevertheless, of the 1 billion people world-wide who are currently living with NTDs, about three-fourths of these are living in poverty, and of these, nearly 65% are unable to acquire or access drugs for the prevention and treatment of these diseases. Under these circumstances, Japan decided to support the Global Health Innovative Technology (GHIT) Fund in order to support the research and development of drugs for people in developing countries, as well as the manufacture, supply and administration of these drugs. Over the last two years, the GHIT Fund has been supporting the research and development of five new candidate drugs for three NTDs (Chagas disease, leishmaniasis and malaria). Japan also hopes to stimulate domestic pharmaceutical industries in developing countries, as well as to increase international cooperation through various activities such the utilization of our capacity to research and develop new drugs.