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

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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

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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

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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

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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.

著者

髙栗 郷

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.11, pp.1329-1334, 2018-11-01 (Released:2018-11-01)

参考文献数

30

被引用文献数

8

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Impaired insulin signaling in adipose tissue and skeletal muscle causes insulin resistance associated with the development of type 2 diabetes. However, the molecular mechanisms underlying insulin resistance remain to be elucidated. In this review, we describe the current understanding of the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and tumor necrosis factor (TNF)-α on insulin signal transduction in adipocytes. First, we determined that atorvastatin inhibits the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 through a decrease in the RhoA-Rho-kinase pathway, resulting in the inhibition of glucose uptake. Second, we found that TNF-α induces IRS-1 phosphorylation at serine residues 636/639 and inhibits the tyrosine phosphorylation of IRS-1 through the increase in both extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation. Interestingly, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMP-activated protein kinase activator, suppresses TNF-α-induced IRS-1 serine phosphorylation at 636/639 and the phosphorylation of ERK by enhancing interactions between ERK and dual-specificity phosphatase-9. These results may be helpful in understanding the mechanisms underlying insulin resistance.

著者

山本 由似 塩田 倫史 大和田 祐二 福永 浩司

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.131, no.4, pp.497-501, 2011-04-01 (Released:2011-04-01)

参考文献数

23

被引用文献数

1 2

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Haloperidol as a potent dopamine D2 receptor (D2R) antagonist was a major tranquilizer to treat schizophrenia patients. However, the D2R blocking action in dorsal striatum is thought to cause extrapyramidal symptoms as adverse effects. However, the pathophysiological mechanism underlying extrapramidal symptoms induced by chronic treatment of haloperidol remains unclear. We recently found that lacking of heart-type fatty acid binding protein (H-FABP) in the brain aggravate catalepsy behavior induced by haloperidol. Here, we examined neuronal mechanism of augmentation of haloperidol-induced catalepsy in H-FABP null mice. Notably, catalepsy induced by haloperidol, a D2 antagonist, is augmented, whereas catalepsy induced by SCH23390, a D1 antagonist, was not affected in H-FABP null mice. Interestingly, haloperidol-induced acetylcholine (ACh) release in the dorsal striatum was markedly enhanced in H-FABP null mice compared to wild mice. We also defined the co-localization of D2R with H-FABP in the ACh interneurons in the striatum. Taken together, H-FABP regulates dopaminergic neuronal activity through interaction with D2R in rodent brain. The increased ACh release in the striatum accounts for haloperidol-induced catalepsy.

著者

斎藤 嘉朗 中村 亮介

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.1557-1562, 2019-12-01 (Released:2019-12-01)

参考文献数

15

被引用文献数

2

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Severe cutaneous adverse reactions (SCARs) are important in postmarketing drug safety because SCAR patients were highest in the adverse drug reaction relief system of Japan. The SCAR symptoms of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) include high fever, severe mucosal impairment, and epidermal necrosis-induced erosions and blisters. Approximately 600 cases of SJS and 300 cases of TEN are reported annually in Japan. Many suspected drugs such as acetaminophen, lamotrigine, allopurinol, and carbamazepine have been reported. Over the last 15 years, an association between human leukocyte antigen and SJS/TEN onset has been reported with several drugs. Pathophysiological examinations in those reports revealed marked CD8-positive T cell infiltration into epidermal lesions, and the presence of cytotoxic granulysin, soluble Fas ligand, and tumor necrosis factor (TNF)-α in blister fluid. Therefore, SJS and TEN are immunological disorders that lead to epidermal necrosis and are consequently treated with the systemic administration of corticosteroids and with high-dose intravenous immunoglobulin therapy and plasma exchange in severe cases. Additionally, because the epidermal necrosis has characteristics similar to those of organ rejection after transplantation, the administration of cyclosporine, an immunosuppressant that inhibits helper T cell activation, has been attempted. Further, the administration of the TNF-α inhibitor etanercept has also been reported. This review summarizes current knowledge on the mechanisms of onset of SJS/TEN and their treatments.

著者

緒方 章

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.1919, no.451, pp.751-765, 1919-09-26 (Released:2018-08-30)

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著者はフェニールイソプロビールメチルアミンを合成して是れを左右兩旋光性體に分離し其右旋性體をエフェドリン還元成績體なるデスオキシエフェドリンと比較して兩者の同一物なることを證明し從てエフェドリンの構造式が[chemical formula]なることの證明となせり

著者

本橋 秀之 藤本 敦子 坂根 稔康 山本 昌 矢野 義孝

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.11, pp.1235-1241, 2013 (Released:2013-11-01)

参考文献数

9

被引用文献数

1 1

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In recent years there have been over 30000 suicides annually in Japan. This is one of the most serious problems for Japanese society. Because mental disorder is closely associated with suicide, factors related to the increase in mental disorders and suicides should be clarified. In this study, various data regarding social factors were evaluated to assess the correlation of the number of patients with mental disorders and suicides among the 47 prefectures of Japan. Various data regarding social factors, such as income, savings, or rate of divorce, were obtained from the database of the Ministry of Health, Labour and Welfare of Japan. Among the factors, the annual income and the amount of savings were significantly correlated with the number of patients with mental disorder. On the other hand, while the annual income did not have a significant correlation with suicides, the amount of savings had a significant correlation with suicides. In conclusion, the annual income and amount of savings may both be one of the important factors involved in mental disorders, and the savings may also be a factor affecting suicides. These analyses are valuable in helping to clarify the causes of mental disease, and can hopefully contribute to the health and welfare of Japanese.

著者

武富 芳隆 村上 誠

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.5, pp.503-515, 2017-05-01 (Released:2017-05-01)

参考文献数

56

被引用文献数

2 3

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Mast cells originate from hematopoietic stem cells and undergo terminal maturation in the extravascular tissues, in which they are ultimately resident. Mast maturation, phenotype, and function are dictated by the local microenvironment, which has a significant influence on the ability of mast cells to recognize and respond to stimuli. Activation of mast cells can lead to the release of three distinct classes of mediators, including preformed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo-synthesized bioactive lipid mediators. It is currently recognized that bioactive lipids such as arachidonic acid metabolites (prostaglandins and leukotrienes) released from mast cells modulate innate and adaptive immune responses both directly and indirectly through communication with other microenvironmental immune cells or stroma cells. Moreover, mast cells express a variety of lipid receptors and, if activated by bioactive lipids such as arachidonic acid, ω3 fatty acids, lysophospholipids, and their metabolites, can alter the release and production of other mediators including histamine, cytokines, and chemokines, and thereby alter homeostatic or pathophysiological responses. This review focuses on newly identified functional aspects of bioactive lipids with regard to their immune regulation and functional outcomes in both homeostasis and allergic disease.

著者

奥西 淳二 長原 弘毅 辻谷 久美子 松瀬 仁 久川 和之 曽我 学

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.9, pp.1233-1242, 2016 (Released:2016-09-01)

参考文献数

26

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Environmental cleaning and disinfection plays an important role as a part of the standard precautions to prevent healthcare-associated infections, whereas hand hygiene is one of the most important strategies for breaking the chain of transmission. Cleaning and disinfection of high-touch areas in a health-care facility is emphasized. And wiping with an alcohol-saturated cloth which has features such as low corrosion and a wide range of antimicrobial activity is performed commonly for this purpose. Although alcohol provides immediate activity against enveloped viruses, its virucidal activity against certain non-enveloped viruses, including norovirus, is insufficient. We created a novel alcohol-based hand rub, MR06B7, which is safe for the skin, and is active against an extended spectrum of microorganisms including non-enveloped viruses. For environmental surface disinfection, a novel disinfectant MR13B15, which is based on MR06B7, has been developed. In vitro antimicrobial activity against a variety of pathogens, material compatibility, and simulated surface disinfection and decontamination efficacy of MR13B15 were investigated. According to the results, MR13B15 demonstrated potent bactericidal, fungicidal, mycobactericidal, and virucidal activity within a short contact time in addition to superior efficacy against non-enveloped viruses compared to ethanol for disinfection. Moreover, MR13B15 showed better material compatibility. Two simulation tests conducted for evaluating the disinfection and decontamination potency on environmental surfaces against feline calicivirus, a surrogate for norovirus, indicated that MR13B15 had superior efficacy for surface treatment compared to ethanol. These findings suggest that MR13B15, which satisfies most requirements of an environmental surface disinfectant, may contribute to accomplishing advanced standard precautions in preventing infections.

著者

齊藤 和季

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.1, pp.1-18, 2018 (Released:2018-01-01)

参考文献数

245

被引用文献数

7

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A variety of chemicals produced by plants, often referred to as ‘phytochemicals’, have been used as medicines, food, fuels and industrial raw materials. Recent advances in the study of genomics and metabolomics in plant science have accelerated our understanding of the mechanisms, regulation and evolution of the biosynthesis of specialized plant products. We can now address such questions as how the metabolomic diversity of plants is originated at the levels of genome, and how we should apply this knowledge to drug discovery, industry and agriculture. Our research group has focused on metabolomics-based functional genomics over the last 15 years and we have developed a new research area called ‘Phytochemical Genomics’. In this review, the development of a research platform for plant metabolomics is discussed first, to provide a better understanding of the chemical diversity of plants. Then, representative applications of metabolomics to functional genomics in a model plant, Arabidopsis thaliana, are described. The extension of integrated multi-omics analyses to non-model specialized plants, e.g., medicinal plants, is presented, including the identification of novel genes, metabolites and networks for the biosynthesis of flavonoids, alkaloids, sulfur-containing metabolites and terpenoids. Further, functional genomics studies on a variety of medicinal plants is presented. I also discuss future trends in pharmacognosy and related sciences.

著者

入口 慎史 今井 徹 田中 昌代 田沼 道也 折井 孝男 加藤 敏明

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.137, no.9, pp.1117-1127, 2017 (Released:2017-09-01)

参考文献数

32

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We conducted a meta-analysis to investigate the influence of antifungal spectrum on the effectiveness and adverse events of empirical antifungal therapy for febrile neutropenia. We searched PubMed and Cochrane Central Register of Controlled Trials (Central), and identified randomized controlled trials reporting mortality, efficacy, adverse events, and hepatic and renal dysfunction. Five trials assessed the efficacy and adverse events of agents with antifungal spectrum covering and those not covering Aspergillus. There were no differences in mortality [risk ratio (RR); 0.79, 95% confidence interval (Cl); 0.60-1.02], efficacy ratio (RR; 1.01, 95%Cl; 0.91-1.12), adverse event ratio (RR; 0.23, 95%Cl; 0.04-1.23), and hepatic dysfunction ratio (RR; 0.81, 95%Cl; 0.59-1.12) between two groups. Antifungals with no activity against Aspergillus were associated with lower renal dysfunction ratio (RR; 0.27, 95%Cl; 0.10-0.71). Five trials compared agents with antifungal spectrum covering versus those not covering Mucor. There were no difference in mortality (RR; 1.24, 95%Cl; 0.98-1.57), efficacy ratio (RR; 1.09, 95%Cl; 0.91-1.30), and hepatic dysfunction ratio (RR; 0.98, 95%Cl; 0.66-1.45) between two groups. Antifungals with no activity against Mucor were associated with lower adverse event ratio (RR; 0.60, 95%Cl; 0.47-0.77) and renal dysfunction ratio (RR; 0.25, 95%Cl; 0.13-0.49). Presence or absence of activity against Aspergillus or Mucor is not associated with mortality or efficacy ratio. Amphotericin B with activity against Aspergillus and Mucor has a higher adverse event ratio. Depending on the case, selection of antifungal drugs considering efficacy and side effects is necessary.