著者

渡邊 博志

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.133, no.8, pp.889-895, 2013-08-01 (Released:2013-08-01)

参考文献数

28

被引用文献数

4 6

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Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

著者

小野田 稔久 木下 雅子 田中 博之 井澤 香 浦野 敦 佐藤 直子 増田 雅行 石井 敏浩

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.11, pp.1267-1276, 2022-11-01 (Released:2022-11-01)

参考文献数

19

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During the treatment of cardiogenic shock, various continuous infusion drugs are used simultaneously. However, administration from the same route may result in stability changes due to mixing of drugs. In addition, stability tests after mixing more than three types of drugs have hardly been conducted. In this study, noradrenaline, milrinone, dobutamine hydrochloride, and landiolol hydrochloride were used to evaluate the chemical stability of the mixture. Chemical stability was evaluated by measuring the change in each drug concentration over time and calculating the content. The concentration of each drug was measured using an optimized gradient elution method by HPLC. In a four-drug mixed sample, noradrenaline, milrinone, dobutamine hydrochloride, and landiolol hydrochloride had retention times of 2.1 min, 5.2 min, 9.3 min, and 11.9 min, respectively. The concentration immediately after mixing each drug was almost the same as the theoretical concentration at the time of mixing each drug. Furthermore, noradrenaline, milrinone, and dobutamine hydrochloride concentrations were maintained up to 99% in each drug mixture until 24 h after mixing all the samples. However, the content of landiolol hydrochloride was 90% or less 24 h after mixing, except for two types of mixed solutions with dobutamine hydrochloride. This result suggested that landiolol hydrochloride was being degraded owing to acidic conditions. The results of this study suggest that noradrenaline, milrinone, and dobutamine hydrochloride can be administered from one route, while it is recommended that landiolol hydrochloride be administered from another route.

著者

五十嵐 中

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.12, pp.1379-1390, 2022-12-01 (Released:2022-12-01)

参考文献数

35

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Development of a formulary is an important issue to achieve rational use of medicines in each local medical area in Japan. The purpose of developing the formulary is to secure the access for safe, effective, and affordable medications based on evidence for patients, families, healthcare professionals as well as for general publics. The economic aspect plays an important role for the establishment of the formulary, while the word “economic” is often misread as simple “cost reduction”, which only aims to generic/biosimilar substitutions. Both health outcomes and costs, should be taken into account under the true “health economic analysis”, or the cost-effectiveness analyses (CEA). Information provided via the CEA could be useful for establishment of the formulary. Moreover, various value assessment of medicines in health technology assessments (HTA) field beyond the current approach of safety, effectiveness, and economics evaluations should be considered. In this review, we discuss comprehensive assessment of various value components of medicines to establish the most suitable formulary which would contribute to whole society, as well as healthcare facilities/patients.

著者

桑山 健次

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.139, no.8, pp.1063-1070, 2019-08-01 (Released:2019-08-01)

参考文献数

39

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The abuse of drugs has become a serious social problem worldwide. Amphetamine-type stimulants such as methamphetamine are recreationally abused and can cause toxic effects in the body. Unfortunately, death from drug poisoning can occur due to careless intake. In postmortem examinations, the distribution of drugs in an entire organ gives valuable information for evaluating their toxicity. We developed methods to measure the distribution of drugs in organs using LC/MS and matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). The complementary use of the two methods provides more detailed information on the distribution and concentration of drugs in organs because the accurate quantification in LC/MS and small spatial resolution in MALDI-IMS are combined. On the other hand, it is important to elucidate the drug intake history of suspects and victims in drug-facilitated crimes (DFCs). Hair and nail samples are often used to confirm chronic drug intake because ingested drugs can stably remain in these specimens over several months. However, it is impossible to determine the day of drug ingestion in conventional segmental analysis of bulk samples. Therefore, we developed methods to cut hair strands at 0.4-mm intervals and nails at 0.2-mm intervals, which correspond to their respective growth rates over 1-2 d, to analyze the drugs in each segment efficiently using LC/MS. The microsegmental hair analysis method is applied to estimate the day of drug ingestion in DFC investigations. These methods could be applied to measure the distribution of compounds in various solid samples.

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.142, no.12, pp.1297-1305, 2022-12-01 (Released:2022-12-01)

参考文献数

25

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Tumor necrosis factor-α (TNF), a proinflammatory cytokine, is critical to the pathogenesis of various inflammatory diseases. There are two subtypes of receptors for TNF, namely type I TNF receptor (TNFR1) and type II TNF receptor (TNFR2). Previous studies using animal models of diseases have demonstrated the predominant role of TNFR1 in the pathogenesis of inflammation. It has recently been proposed that TNFR2 is associated with anti-inflammatory function. This intriguing function of TNFR2 has implications from an immunological and pharmacological perspective. However, the mechanism of the TNFR2-mediated anti-inflammatory effect is not fully understood. In this context, we attempted to elucidate the TNFR2-mediated anti-inflammatory effect and other unknown biological functions of TNFR2 by utilizing our protein engineering technology to generate functional mutant cytokines. Our findings reveal the following. (1) TNFR2 is expressed on regulatory T cells (Tregs) but not conventional T cells (Tconvs) and TNFR2-mediated signals promote proliferation and activation of Tregs. (2) The crystal structure of TNF/TNFR2 complex was solved, which suggests a possible signal initiation mechanism via TNF/TNFR2 cluster formation on the cellular membrane. (3) A novel TNFR2-mediated signal molecule, aminopeptidase P3 (APP3/XPNPEP3), was identified that interacts with TNFR2 as an intracellular adaptor protein. APP3 is required for c-Jun N-terminal kinase (JNK) phosphorylation, the downstream molecule of TNFR2 signal transduction. These results are key to understanding the mechanism of immune regulation and will assist in the identification of immunomodulatory drugs targeting the TNFR2 signaling cascade as well as the function of Tregs.

著者

山田 浩

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.12, pp.1371-1377, 2022-12-01 (Released:2022-12-01)

参考文献数

30

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Green tea components, such as catechins have been reported to provide several benefits including anti-oxidative, anti-viral/bacterial, and anti-inflammatory effects in vitro and in vivo. Catechins effectively inhibited the adsorption and replication of the influenza virus. Additionally, green tea contains theanine and vitamin C, which enhance the immunity against viral/bacterial infections. Based on these, green tea is hypothesized to have potential benefits in the prevention of influenza and other respiratory tract infections in the clinical setting. However, its specific effects in patients remain unclear. To determine the clinical significance of green tea in the prevention of respiratory tract infections, we conducted an observational study and eight interventional studies. Based on the results of three studies, consuming or gargling green tea or its components significantly aided in the prevention of influenza. Meanwhile, one study showed that green tea successfully prevented common colds. Catechin inhalation was also reported to decrease the bacterial load of methicillin-resistant Staphylococcus aureus in the sputum. Although the anti-viral/anti-bacterial effects of green tea components have been demonstrated in experimental studies, the clinical evidence remains limited. Further studies are required to confirm the clinical efficacy of green tea and its components in preventing respiratory tract infections.

著者

宮田(古谷) 聡美 河野 惠三 森元 崇史 原島 哲 岩田 裕子 有安 利夫

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

pp.21-00219, (Released:2022-02-28)

参考文献数

29

被引用文献数

1

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Transient receptor potential vanilloid 2 (TRPV2) channels are expressed and play functional roles in various immune cells. Physical stimuli leading to TRPV2 activation causes mast cell degranulation. Besides their roles in immune cells, it has been shown that TRPV2 channels are pathophysiologically relevant to degenerative muscular diseases such as dilated cardiomyopathy and muscular dystrophy. Hence, development of drug candidates that inhibit human TRPV2 activation is an urgent matter. NK-4, a cryptocyanine dye, inhibited agonist-induced TRPV2 activity in mouse TRPV2-transfected HEK293 cells. However, it remains unclear whether NK-4 exerts regulatory effects on the activation of human TRPV2 channels. In this study, we show that NK-4 inhibits intracellular Ca2+ increase in human TRPV2-transfected HEK293 cells preactivated with a TRPV2 agonist. The inhibitory effect of NK-4 (IC50 = 0.27 μM) on human TRPV2 activation was 74-fold stronger than that on mouse TRPV2 activation (IC50 = 20 μM). NK-4 also inhibited the agonist-induced TRPV2 expression at the plasma membrane, when the human TRPV2-expressing cells were stimulated with the agonist in the presence of NK-4. These results suggest that NK-4 abrogates the agonist-induced signaling events leading to human TRPV2 activation. Furthermore, TRPV2 agonist caused degranulation of RBL-2H3 cells, which represents a phenomenon related to physical urticarias. NK-4 suppressed the release of β-hexosaminidases upon degradation with IC50 of 1.9 μM, 35-fold lower than that determined with an anti-allergic drug, Epinastine. Our results suggest that NK-4 would be a potential therapeutic strategy to resolve dilated cardiomyopathy and its associated heart failure as well as physical urticarias.

著者

柳 奈津代 佐藤 宏樹 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.141, no.9, pp.1095-1107, 2021-09-01 (Released:2021-09-01)

参考文献数

24

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The difficulty and anxiety of nursery staff in administering medication to children at nursery schools has been reported, and its reduction is desired. However, the attitudes of mothers in requesting medication and the factors related to a high frequency of requests are not clear. We conducted an online survey of 600 mothers from April to May 2019 regarding the administration of medication at nursery school, and 301 mothers who had previously made such requests were analyzed. The results showed that 100.0% and 76.4% of the mothers felt gratitude and were apologetic for requesting medicine administration, respectively. In total, 47.5% of mothers expected pharmacists to support nursery staff in administering medication. Mothers' attitude of “I think the nursery staff should administer medication to my child more often” was significantly positively associated with a high frequency of the request in adjusted Model [adjusted odds ratio (AOR) 2.75, 95% confidence interval (CI) 1.36-5.55, p=0.005], while “I think the parents should manage so that the children do not have to take medicine in the nursery school so often” showed a negative association (AOR 0.33, 95% CI 0.17-0.66, p=0.002). Factors related to the involvement of community pharmacists were not significant. It is suggested that a change in mothers' attitudes could decrease the frequency of requests and consequently reduce the burden on nursery staff. Community pharmacists may support nursery staff to contribute to changing mothers' attitudes through medication consultations at the pharmacy.

著者

内野 正 竹澤 俊明 五十嵐 良明 徳永 裕司

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.128, no.1, pp.45-50, 2008-01-01 (Released:2008-01-01)

参考文献数

21

被引用文献数

7 8

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Recently, to study an in vitro evaluation method of skin irritation and acute toxicity, many three-dimensional human skin models consisting of normal human keratinocytes and fibroblasts have been used. However, these skin models did not have any dendritic cells so were difficult to apply to an in vitro skin sensitization test. On the other hand, a single cell-culture model using normal human dendritic cells was recently studied for an in vitro evaluation method of immune-sensitizing compounds. However, these models have various problems: 1) the life span of dendritic cells is short(within 1 week) and 2) it is difficult to apply water-insoluble samples to these models. To study an alternative to animal testing using immune-sensitizing compounds, we therefore constructed a three-dimensional human skin model consisting of three different cells, dendritic cells (keratinocytes, and fibroblasts) then exposed immune-sensitizing compounds and non-sensitizers to the new skin model for 1 h and investigated the effect of these compounds on cytokine release and expression of CD86. Due to immune-sensitizing compounds, the new skin model significantly released cytokine and significantly expressed CD86. On the other hand, non-sensitizers did not induce IL-1α, IL-2, and IL- 4 release and expression of CD86. These results suggest that the new skin model is suitable for study as an alternative to animal testing using immune-sensitizing compounds.

著者

緒方 文彦 東 剛志

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.3, pp.269-270, 2018 (Released:2018-03-01)

著者

比留間 航 駿河 康平 門倉 一成 富田 剛 関野 芳弘 小松 靖弘 木村 公彦 小野 信文

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.133, no.5, pp.487-491, 2013-05-01 (Released:2013-05-01)

参考文献数

14

被引用文献数

5 5

---

Cancer is the most common cause of death in Japan. Fundamental and clinical studies on cancer were conducted from the viewpoint of Western medicine so far. However, a sustained complete remission has not been achieved yet. In order to alleviate the side effects of anticancer drugs, some traditional herbal medicines (Kampo medicines) have been prescribed to cancer patients. We have been studying on antitumor substances in medicinal herbs and found an antitumor medicinal herb named Rhus verniciflua (lacquer, Urushi in Japanese). To investigate the antitumor effect in vitro, a plant extract mixture was prepared from six medicinal herbs containing lacquer. The plant extract mixture containing lacquer (Rv-PEM) inhibited the proliferation of several mouse and human tumor cell lines. Rv-PEM had more potent inhibitory effect on the proliferation of human leukemia cell lines (MOLT-3, KG-1) than on other tumor cell lines. The IC50 values of Rv-PEM on MOLT-3 and KG-1 cells were 0.208 and 0.293 mg/mL, respectively. After treating Rv-PEM to the tumor cells, DNA fragmentation and Caspase-3 and -9 activity increased in the treated cells. The mechanisms of the inhibitory proliferation activity of Rv-PEM would involve apoptosis of human leukemia cells (MOLT-3, KG-1, K-562) by the mitochondrial pathway.

著者

石黒 武雄 古賀 直文 高村 恭治 丸山 哲生

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.75, no.7, pp.781-785, 1955-07-25 (Released:2010-02-19)

参考文献数

9

被引用文献数

8 8

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The flowers of Osmanthus fragrans Lour. var. aurantiacus Makino were soaked in petroleum ether immediately after collection, digested for one week, and filtered with pressing. The aqueous layer of the filtrate was extracted with ether. The residual flowers were then digested with warm dehydrated ethanol for 16 hours.1) The portion soluble in petroleum ether is composed of concretes amounting to 0.214% of the original flowers and its treatment with cold dehydrated ethanol separates it into 0.163% of absolutes and 0.043% of flower wax, which is chiefly composed of triacontane, C30H62.2) The ether solution was chromatographically purified and p-hydroxyphenethyl alcohol C8H10O2, was isolated.3) The ethanol-soluble portion yielded D-mannitol.4) The water-soluble portion was fractionated with lead acetate and basic lead acetate. D-Mannitol was isolated from the filtrate and the presence of D-glucose and D-fructose was detected by paper chromatography. The precipitate obtained by lead acetate and the portion soluble in ethanol, yielded succinic acid.

著者

内山 奈穂子 宮澤 法政 河村 麻衣子 花尻(木倉) 瑠理 合田 幸広

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.263-270, 2010-02-01 (Released:2010-02-01)

参考文献数

18

被引用文献数

14 16

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Thirty-two psychotropic substances were listed as designated substances (Shitei-Yakubutsu, 31 compounds and 1 plant) in Japan by the Pharmaceutical Affairs Law in April 2007 for preventing the abuse of these substances. Subsequently, other psychoactive compounds were also added to this category, 40 substances (classified as 12 tryptamines, 17 phenethylamines, 3 piperazines, 6 alkyl nitrites, 1 diterpene and 1 plant) are controlled as designated substances as of July 2009. However, new designer drugs are still distributed in illegal drug market according to the results of our annual survey. This study presents the analysis of four newly distributed designer drugs detected from two products, which were purchased from October 2008 to February 2009 in Japan. As the results of NMR, GC-MS and LC-MS analyses, three phenethylamine derivertives, 1-(2-fluorophenyl)-N-methylpropan-2-amine (N-Me-2-FMP), 1-(2,5-dimethoxy-4-isopropylsulfanylphenyl)propan-2-amine (ALEPH-4) and 1-(2,5-dimethoxy-4-nitrophenyl)propan-2-amine (DON) and a tryptamine derivative, N-ethyl-5-methoxy-N-propyltryptamine (5-MeO-EPT), were detected. N-Me-2-FMP and 5-MeO-EPT were newly identified in this study. Additionally, ALEPH-4 and DON were found as novel illegal drugs distributed in Japan.

著者

水野 忠快

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.10, pp.1077-1082, 2022-10-01 (Released:2022-10-01)

参考文献数

12

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As the term polypharmacology suggests, there are multiple actions of small-molecule compounds. We proposed a decomposition and understanding concept that sheds light on the small effects in comparison to the large effects by decomposing these multiple effects. This concept was embodied by describing the effects of the compounds in a transcriptome profile, followed by factor analysis to extract latent variables as decomposed effects. Application of this approach to public datasets resulted in the inferences of compound effects consistent with existing knowledge such as gene ontologies and pathways. In one experimental validation, the potential inducibility of endoplasmic reticulum stress of several commercial drugs was detected by decomposition. Another study successfully discriminated the effects of a natural product and its derivatives despite their structural similarity. In the era of big data, it is important to infer conceptual elements composed of measurable elements as a higher layer than the given data of a specimen, which can expand our perception and understanding of the specimen. This review introduces an example of such a philosophy by applying it to the multiple effects of drugs to contribute to the understanding.

著者

山崎 真巳

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.122, no.1, pp.47-56, 2002-01-01 (Released:2003-02-13)

参考文献数

36

被引用文献数

2 2

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A molecular biological approach was applied to the study of diversity and regulation of secondary metabolism in medicinal plants at various levels. For the inter-species diversity, RFLP (restriction fragment length polymorphysm) and RAPD (random amplified polymorphic DNA) analyses of genomic DNA were performed on the plants, belonging to the same genus or family and containing related compounds. Phylogenetic trees of lupin alkaloid containing plants and other medicinal plants, based on RFLP and/or RAPD profiles, showed the relationship between the diversities in genomes and secondary metabolisms. The chemotypes regarding anthocyanin production in Perilla frutescens var. crispa, were subjected to the study on intra-species diversity. The structural genes and the regulatory genes involved in anthocyanin biosynthesis were isolated and their expression in red and green forms was determined by Northern blot analysis. The expression of all structural genes examined was co-ordinately regulated in form-specific manner and by light illumination. The anthocyanin production was enhanced in transgenic plants over-expressing Myc homologue genes from perilla. These results suggested that a protein complex including bHLH factors might regulate the expression of a series of structural genes. Additionally, cDNAs coding anthocyanin 5-O-glucosyltransferase and anthocyanidin synthase were isolated and characterized using recombinant proteins for the first time. In conclusion, it was indicated that the molecular biological techniques are powerful tools for the investigation of diversity and regulation of and for the genetic engineering of secondary metabolism in medicinal plants.

著者

本庄 美喜男

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.73, no.4, pp.368-371, 1953-04-25 (Released:2010-02-19)

参考文献数

21

被引用文献数

1 2

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D-threo-β-Phenylserine was derived to 1-p-nitrophenyl-2-amino-1, 3-propanediol (I) which was found to be an optical antipode of (I) obtained by the hydrolysis of natural chloramphenicol. This confirms the fact that the steric configuration of natural chloramphenicol is the same as that of l-nor-φ-ephedrine.

著者

平野 光河 田頭 秀章 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.134, no.6, pp.707-713, 2014 (Released:2014-06-01)

参考文献数

55

被引用文献数

7 10

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We previously reported that the sigma-1 receptor is down-regulated in cardiomyocytes following heart failure in transverse aortic constriction (TAC) mice. In this review, we summarized the anti-hypertrophic action of selective sigma-1 receptor agonist, SA4503 in the hypertrophied cultured cardiomyocytes and discussed its possible mechanism of cardioprotection. Treatment with SA4503 (0.1-1 μM) dose-dependently inhibited hypertrophy in cultured cardiomyocytes induced by angiotensin II (Ang II). We also found that α1 receptor stimulation by phenylephrine (PE) promotes ATP production through IP3 receptor-mediated Ca2+ mobilization into mitochondria in cultured cardiomyocytes. Interestingly, the PE-induced ATP production was impaired after Ang II-induced hypertrophy and SA4503 treatment largely restored PE-induced ATP production. The impaired PE-induced ATP production was associated with reduced mitochondrial size. The SA4503 treatment completely restored mitochondrial size concomitant with restored ATP production. These effects were blocked by sigma-1 receptor antagonist, NE-100 and sigma-1 receptor siRNA. We also confirmed that chronic SA4503 administration also significantly attenuates myocardial hypertrophy and restores ATP production in transverse aortic constriction mice. Taken together, sigma-1 receptor stimulation with selective agonist SA4503 ameliorates cardiac hypertrophy and dysfunction by restoring both mitochondrial Ca2+ mobilization and ATP production via sigma-1 receptor stimulation. Sigma-1 receptor stimulation represents a new therapeutic strategy to rescue heart from hypertrophic dysfunction in heart failure.

著者

五十嵐 勝秀 大塚(出田) まき 成田 年

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.265-271, 2017-03-01 (Released:2017-03-01)

参考文献数

25

被引用文献数

4 3

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Epigenetics has drawn much attention as a mechanism of transcriptional regulation involving modifications to genomic DNA and histone, without changes to nucleotide sequences. Epigenetics is related to various biological phenomena. We defined one of these phenomena as “epigenetic toxicity”, in which chemicals affect epigenetic regulation and result in undesirable effects on living organisms. We then detailed the importance of epigenetics and the need for intensive research. Epigenetics is a mechanism that might explain the long-lasting effects of chemicals in an organism, and the formation of a predisposition to various diseases. Recent significant technological advancement in the study of epigenetics could break through the barrier of the mysterious black box of epigenetic toxicity. However, at present it is difficult to say whether the epigenetic point of view is being fully utilized in the evaluation of chemical safety. In this review, we will first summarize the epigenetic toxicity research field, with examples of epigenetic toxicities and technologies for epigenetic analysis. Following that, we will point out some challenges in which an epigenetic viewpoint may be essential for the evaluation of chemical safety, and we will show some current approaches. We hope this review will trigger a discussion about epigenetic toxicity that will lead to encouraging research advancements.

著者

江角 浩安

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.3, pp.419-421, 2020-03-01 (Released:2020-03-01)

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Pharmacists at National Cancer Center Hospital East play important roles in designing, conducting new protocol for clinical trials for developing new regimens and even new drugs. They are also key staffs in treating cancer patients in both in- and out-patient clinics by conducting chemotherapy and monitoring adverse effects. In addition, they educate patients and families before and during treatment by operating independent pharmacists' out-patient clinics. Pharmacists are in front-line of cancer chemotherapy. I was in National Cancer Center but am now in a small city hospital where most of the patients are age over 70 or 80 and frequently live alone. They are suffered from cancer, cardiovascular diseases, and mental diseases. Because most of the patients are elderly, their renal function is more or less disturbed. In this area, medical social workers, nurses, care workers and medical doctors together with visiting nurse system, care worker station try to let the patients enjoy life out of hospital. Japan is a leading country to overcome many problems in an elderly society and try to establish comprehensive community system. The position of pharmacists in this system is not fully clear in our city and probably in other city. Here is another frontier for pharmacists.

著者

長井 紀章

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.47-53, 2021-01-01 (Released:2021-01-01)

参考文献数

19

被引用文献数

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The use of eye drops is a well-established practice in the treatment of ophthalmic diseases, although the bioavailability of traditional eye drops, which are either solutions or suspensions, is insufficient, as the corneal barrier and dilution by lacrimation prevent the transcorneal penetration of drugs. Additionally, frequent instillation may cause undesirable systemic side effects and local corneal toxicity. To overcome these problems, micro- and nanoparticles, hydrogels, and viscous solutions have been tested, and solid nanoparticles are also expected to be applied. This review examines the usefulness of ophthalmic formulations based on solid nanoparticles, by using the specific example of indomethacin (IMC). Ophthalmic formulations based on solid IMC nanoparticles (IMC-NP dispersions) have been prepared using various additives (benzalkonium chloride, mannitol, methylcellulose, and cyclodextrin) and a rotation/revolution pulverizer (NP-100), to produce particles of 50-220 nm in size. The solubility of IMC in IMC-NP dispersions was 4.18-fold higher than that in the suspensions containing IMC microparticles (IMC-MP suspensions), and IMC-NP dispersions were better tolerated than commercially available NSAIDs eye drops, such as IMC, pranoprofen, diclofenac, bromfenac, and nepafenac eyedrops, in human corneal epithelial cells. Moreover, the corneal penetration in IMC-NP dispersions was higher than that in commercially available IMC and IMC-MP suspensions, and three energy-dependent endocytosis pathways (clathrin-dependent endocytosis, caveolae-dependent endocytosis, and macropinocytosis) were related to the high ophthalmic bioavailability of IMC-NP dispersions. This information can be used to support future studies aimed at designing novel ophthalmic formulations.