KINDAI UNIVERSITY


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YOKOYAMA Satoshi

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FacultyDepartment of Pharmacy
PositionLecturer
DegreePh.D. in Pharmaceutical Science
Commentator Guidehttps://www.kindai.ac.jp/meikan/2174-yokoyama-satoshi.html
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Last Updated :2020/09/30

Research Activities

Research Areas

  • Life sciences, Clinical pharmacy

Published Papers

  • Influence of co-initiation of antiulcer drugs on persistence and adherence to low-dose aspirin: A retrospective cohort study using a Japanese claims database ., Makiko Iwasawa, Keiko Sagami, Satoshi Yokoyama, Kouichi Hosomi, Mitsutaka Takada, International journal of clinical pharmacology and therapeutics, International journal of clinical pharmacology and therapeutics, 58(4), 214 - 222, Apr. 2020 , Refereed
    Summary:OBJECTIVE: The purpose of this study was to examine whether co-initiation of antiulcer drugs (AUDs) and low-dose aspirin (LDA) therapy is beneficial for good adherence to LDA therapy. MATERIALS AND METHODS: A retrospective cohort study was conducted using the JMDC claims database. Patients for whom LDA therapy was newly initiated between January 2005 and April 2016 were selected from the JMDC database. The selected patients were divided into LDA and LDA+AUD groups and were followed up from the first prescription of LDA or LDA+AUD until the earliest of the following events: discontinuation or the end of the observation period. Unadjusted and multivariable Cox proportional hazards models controlling for all demographic and clinical characteristics were applied to examine whether the addition of an AUD to LDA improved adherence. A 1 : 1 propensity score matching analysis was conducted to balance confounders between the two groups. RESULTS: After the propensity score matching analysis, 4,089 patients were matched in each therapy group. The Kaplan-Meier curves for the rate of LDA continuation showed a sharp decline just after the initiation of LDA therapy. A significant difference was observed in the incidence of LDA therapy discontinuation between the LDA+AUD and LDA groups (HR: 0.87, 95% CI: 0.82 - 0.92), and the median duration of LDA therapy in the LDA+AUD and LDA groups were 18 and 11 months (log-rank test: p < 0.0001), respectively. CONCLUSION: The therapy persistence rate in the LDA+AUD group was significantly higher than that in the LDA group.
  • Adherence to guidelines for antiulcer drug prescription in patients receiving low-dose aspirin therapy in Japan., Makiko Iwasawa, Keiko Sagami, Satoshi Yokoyama, Kouichi Hosomi, Mitsutaka Takada, International journal of clinical pharmacology and therapeutics, International journal of clinical pharmacology and therapeutics, 57(4), 197 - 206, Apr. 2019 , Refereed
    Summary:OBJECTIVE: Prevalence of guideline adherence for antiulcer drug prescription in patients receiving low-dose aspirin (LDA) therapy was examined and the association of risk factors with the adherence was assessed. MATERIALS AND METHODS: A retrospective cohort study using a population-based longitudinal healthcare database was conducted. Claims data between January 2005 and April 2016 were analyzed. A total of 3,079 patients were included in the study. The selected patients taking LDA were divided into two categories: those taking and those not taking antiulcer drugs in an inpatient setting. Additionally, they were classified into four groups according to the time antiulcer therapy was initiated. The risk factors for ulcer, such as history of gastrointestinal injuries; age ≥ 65 years; and concomitant use of anticoagulants, antiplatelets, oral corticosteroids, and nonsteroidal anti-inflammatory drugs except aspirin, were assessed. RESULTS: A total of 3,079 patients were included in the study. The rate of LDA patients using antiulcer drugs was 65.2%, with the strongest single factor associated with the use of antiulcer drugs being the concomitant use of corticosteroids. Among the LDA patients not taking antiulcer drugs, 66.8% had more than one risk factor. Irrespective of the use of concomitant treatment with antiulcer drug prior to hospital admission, 78.3% of the LDA patients continued their home regimen after hospital admission. CONCLUSION: Our results showed that the requirement of antiulcer therapy is not routinely evaluated at hospital admission, and antiulcer drugs for patients with ulcer risks are under-prescribed. Developing strategies to screen gastrointestinal risk factors at hospital admission is required to improve the guideline adherence for LDA-induced ulcer.
  • 悪性リンパ腫患者に対するCHOP療法に伴う悪心・嘔吐におけるアプレピタントの有用性に関する検討, 日本病院薬剤師会雑誌, 日本病院薬剤師会雑誌, 55(3), 279‐285, Mar. 01 2019
  • Voriconazole trough concentration and hepatotoxicity in patients with low serum albumin ., Atsushi Hirata, Keisuke Noto, Ryosuke Ota, Satoshi Yokoyama, Kouichi Hosomi, Mitsutaka Takada, Hiroshi Matsuoka, International journal of clinical pharmacology and therapeutics, International journal of clinical pharmacology and therapeutics, 57(3), 135 - 143, Mar. 2019 , Refereed
    Summary:OBJECTIVE: We aimed to investigate the relationship between voriconazole (VRCZ) trough concentrations and hepatotoxicity and to evaluate whether the recommended trough concentration is adequate in our clinical setting. MATERIALS AND METHODS: A retrospective study was performed to investigate the relationship between serum VRCZ concentrations and the development of hepatotoxicity at the Kindai University Nara Hospital. Patients treated with VRCZ from March 2010 to January 2018 were identified from the medical records. A total of 42 patients (mean age of 61.9 ± 16.9 years; 33 males and 9 females) were enrolled in this study. RESULTS: Hepatotoxicity developed in 28.6% (12/42) of patients treated with VRCZ, and 91.7% (11/12) of these patients developed hepatotoxicity within 3 weeks after initiating the treatment. Significantly increased aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.001), and alanine aminotransferase (p = 0.001) levels were observed after the initiation of VRCZ therapy. In addition, significant positive correlations between AST and VRCZ trough concentrations (p = 0.017) and between ALP and VRCZ trough concentrations (p = 0.012) were observed. VRCZ trough concentration was identified as a significant independent risk factor for hepatotoxicity (adjusted odds ratio: 1.611, 95% confidence interval: 1.131 - 2.579, p = 0.006), and the cutoff serum trough concentration was calculated to be 4.2 μg/mL. CONCLUSION: VRCZ-induced hepatotoxicity should be noted in the early stages of therapy. A sustained VRCZ trough concentration of ~ < 4.2 μg/mL is recommended to prevent hepatotoxicity in patients with low serum albumin levels.
  • Risk of malignant lymphoma in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs and methotrexate ., Ryo Inose, Kouichi Hosomi, Katsuyuki Takahashi, Satoshi Yokoyama, Mitsutaka Takada, International journal of clinical pharmacology and therapeutics, International journal of clinical pharmacology and therapeutics, 57(2), 63 - 72, Feb. 2019 , Refereed
    Summary:OBJECTIVE: This study investigated whether using biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignant lymphoma in patients with rheumatoid arthritis undergoing methotrexate therapy using spontaneous adverse reaction databases in different countries. MATERIALS AND METHODS: Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Report (JADER), and the Canada Vigilance Adverse Reaction Online Database (CVARD) from the first quarter of 2004 to the end of 2015. Data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignant lymphoma in patients receiving methotrexate therapy. RESULTS: The FAERS subset data indicated a significant association between Hodgkin lymphoma and methotrexate with infliximab (reporting odds ratio (ROR): 8.28. 95% CI: 5.70 - 12.02; information component (IC): 2.04, 95% CI: 1.59 - 2.49). In addition, signal scores suggested that methotrexate with infliximab (ROR: 3.26. 95% CI: 2.68 - 3.98; IC: 1.31, 95% CI: 1.04 - 1.58) was significantly associated with non-Hodgkin lymphoma (NHL). The CVARD subset data also indicated a significant association between NHL and methotrexate with infliximab (ROR: 22.82. 95% CI: 5.02 - 103.78; IC: 1.77, 95% CI: 0.13 - 3.41). However, the JADER subset data revealed no significant associations. CONCLUSION: The present study shows that using infliximab further increases the risk of malignant lymphoma in patients receiving methotrexate therapy.
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  • Effects of clotrimazole on tacrolimus pharmacokinetics in patients with heart transplants with different CYP3A5 genotypes., Takaya Uno, Kyoichi Wada, Sachi Matsuda, Yuka Terada, Nobue Terakawa, Akira Oita, Satoshi Yokoyama, Atsushi Kawase, Kouichi Hosomi, Mitsutaka Takada, European journal of clinical pharmacology, European journal of clinical pharmacology, 75(1), 67 - 75, Jan. 2019 , Refereed
    Summary:PURPOSE: This study aimed to investigate the effects of clotrimazole on the pharmacokinetics of tacrolimus in Japanese patients with heart transplants with different CYP3A5 genotypes. METHODS: Twenty-six patients who underwent heart transplantation between June 2012 and July 2017 were enrolled in this retrospective study. The CYP3A5 (rs776746; CYP3A5*3) genotype was determined after monitoring and analysing tacrolimus blood concentrations. The pharmacokinetic profile of tacrolimus was examined before and after the discontinuation of clotrimazole and in patients with different CYP3A5 genotypes. RESULTS: The CYP3A5*1/*1, *1/*3 and *3/*3 genotypes were detected in 2, 8 and 16 patients, respectively. After clotrimazole was discontinued, the CYP3A5 expresser (CYP3A5*1/*1 or *1/*3) group had a 3.3-fold median increase in apparent oral clearance of tacrolimus (0.27 vs. 0.89 L/h/kg, P = 0.002) compared with the CYP3A5 non-expresser (CYP3A5*3/*3) group with a 2.2-fold median increase (0.18 vs. 0.39 L/h/kg, P < 0.0001). Significant correlations were observed between C0 and area under the concentration-time curve (AUC0-12) of tacrolimus after the discontinuation of clotrimazole in the CYP3A5 expresser and non-expresser groups, respectively (R2 = 0.49 and 0.42, all P < 0.05), but not before the discontinuation of clotrimazole. CONCLUSION: The effects of clotrimazole on tacrolimus pharmacokinetics in the CYP3A5 expresser patients were significantly greater than those in the CYP3A5 non-expresser patients. In addition, clotrimazole disturbed the correlation between C0 and AUC0-12 of tacrolimus. Careful dose adjustment of tacrolimus based on CYP3A5 genotypes may be beneficial for the patients with heart transplants who are concomitantly treated with clotrimazole.
  • CapeOX療法の完遂率に影響を与える要因の調査および適切な介入方法を目指した多施設共同研究, 片山広美, 三島江津子, 佐々木俊則, 伴晶子, 横山聡, 桂川健司, 高取裕司, 宮崎雅之, 佐藤由美子, 築山郁人, 久田達也, 板倉由縁, 片山広美, 三島江津子, 佐々木俊則, 伴晶子, 横山聡, 桂川健司, 高取裕司, 宮崎雅之, 佐藤由美子, 築山郁人, 久田達也, 板倉由縁, 日本病院薬剤師会雑誌, 日本病院薬剤師会雑誌, 55(1), 47‐52, Jan. 01 2019
  • Color change in Perlodel® tablets induced by LED lighting – photolysis of bromocriptine mesylate, Yamashita S, Iguchi K, Noguchi Y, Sakai C, Yokoyama S, Ino Y, Hayashi T, Teramachi H, Sako M, Sugiyama T, Pharmazie, Pharmazie, 74, 286 - 289, 2019 , Refereed
  • Oncology pharmacist contributions to treatment with oral anticancer agents in a Japanese community pharmacy setting, Yokoyama S, Yajima S, Shimauchi A, Sakai C, Yamashita S, Noguchi Y, Ino Y, Iguchi K, Teramachi H, Canadian Pharmacists Journal, Canadian Pharmacists Journal, 151(6), 377 - 382, Nov. 2018 , Refereed
  • 政府統計データを用いた薬局に従事する薬剤師の分布に関する調査, 矢島 聖子, 島内 あかり, 堺 千紘, 横山 聡, 伊野 陽子, 松永 俊之, 寺町 ひとみ, 中村 光浩, 井口 和弘, 薬学雑誌, 薬学雑誌, 138(7), 991 - 1000, Jul. 2018
  • Ultraviolet B eye irradiation aggravates atopic dermatitis via adrenocorticotropic hormone and NLRP3 inflammasome in NC/Nga mice., Keiichi Hiramoto, Yurika Yamate, Satoshi Yokoyama, Photodermatology, photoimmunology & photomedicine, Photodermatology, photoimmunology & photomedicine, 34(3), 200 - 210, May 2018 , Refereed
    Summary:BACKGROUND: Ultraviolet (UV) B irradiation has been shown to improve atopic dermatitis (AD). However, the relationship between UVB eye irradiation and AD is not known. This issue was addressed using a mouse model of AD. METHODS: The eyes of NC/Nga mice were irradiated with UVB at a dose of 1.0 kJ/m2 using a 20SE sunlamp for the duration of the experimental period. RESULTS: AD symptoms deteriorated upon UVB eye irradiation. The levels of adrenocorticotropic hormone (ACTH) in the plasma and nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing (NLRP)3 and neutrophil markers in the skin were increased in UVB-irradiated mice. Treatment with inhibitors of ACTH, caspase-1, interleukin-18, and thymic stromal lymphopoietin (TSLP) partly reversed the effects of irradiation, with the greatest improvement observed upon ACTH inhibition. The NLRP3 inflammasome was implicated in the effects of UVB irradiation. CONCLUSIONS: UVB eye irradiation causes AD symptom deterioration, which is likely mediated by ACTH and the activity of the inflammasome.
  • Genetic Risk Factors Associated With Antiemetic Efficacy of Palonosetron, Aprepitant, and Dexamethasone in Japanese Breast Cancer Patients Treated With Anthracycline-based Chemotherapy., Satoshi Yokoyama, Satoshi Tamaru, Shinya Tamaki, Daisuke Nakanishi, Akiya Mori, Tomokazu Yamakawa, Takaaki Ao, Yasuhiko Sakata, Toshiro Mizuno, Takuya Iwamoto, Kenichi Watanabe, Makoto Simomura, Keiki Kawakami, Naomi Konishi, Shinichi Kageyama, Shoichiro Ohtani, Tomomi Yamada, Susumu Ban, Kazuya Ooi, Clinical breast cancer, Clinical breast cancer, 18(2), e157-e165 - e165, Apr. 2018 , Refereed
    Summary:INTRODUCTION: Breast cancer patients often receive anthracycline-based chemotherapy, and chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse reactions. Poor control of CINV reduces the relative dose intensity of chemotherapy agents, which has been associated with poor clinical outcomes and shorter survival. The aim of the present study was to identify genetic risk factors associated with anthracycline-based CINV. PATIENTS AND METHODS: We evaluated CINV attributable to anthracycline-based chemotherapy in Japanese breast cancer patients treated with an antiemetic regimen that included palonosetron, aprepitant, and dexamethasone. Furthermore, we investigated the associations between CINV and single nucleotide polymorphisms in 6 candidate genes. RESULTS: Emesis episodes were rarely observed in the 125 patients included in the present survey (7.2%; n = 9); however, significant nausea occurred in more than one half of the patients (52.8%; n = 66). In particular, acute significant nausea was not effectively controlled. Multivariate logistic regression analysis revealed that the ABCG2 (rs2231142) AA genotype is significantly associated with acute significant nausea (odds ratio, 4.87; 95% confidence interval, 1.01-23.60; P = .049). CONCLUSION: The findings of the present study provide significant insights for developing personalized antiemetic strategies for breast cancer patients receiving anthracycline-based chemotherapy.
  • Ultraviolet A Eye Irradiation Ameliorates Atopic Dermatitis via p53 and Clock Gene Proteins in NC/Nga Mice., Keiichi Hiramoto, Yurika Yamate, Satoshi Yokoyama, Photochemistry and photobiology, Photochemistry and photobiology, 94(2), 378 - 383, Mar. 2018 , Refereed
    Summary:Atopic dermatitis (AD) is a widespread chronic skin condition that severely affects quality of life and can lead to more serious complications. Although ultraviolet (UV)A eye irradiation can exert various effects on the skin, it is unknown whether UVA can affect AD. To investigate potential associations, we used an NC/Nga mouse model of AD to study the effects of UVA eye irradiation. The eyes of mice were irradiated with a UVA dose of 100 kJ m-2 using a FL20SBLB-A lamp. Our histological data demonstrated that AD symptoms could be ameliorated by UVA eye irradiation. We also observed an increase in the levels of adrenocorticotropic hormone (ACTH), p53 and retinoid X receptor α (RXRα) in mice with UVA-irradiated eyes. In contrast, the levels of thymic stromal lymphopoietin (TSLP), period 2 (PER2) and differentiated embryo chondrocytes 1 (DEC1) protein were decreased in mice treated with UVA irradiation. Furthermore, UVA eye-irradiated mice exhibited reduced DEC1 and RXRα colocalization compared with nonirradiated mice. These results suggested that p53 and various clock gene proteins played important roles in the amelioration of AD symptoms observed after UVA eye irradiation; this technique may have therapeutic applications in AD.
  • The Clock Genes Are Involved in The Deterioration of Atopic Dermatitis after Day-and-Night Reversed Physical Stress in NC/Nga Mice., Keiichi Hiramoto, Kumi Orita, Yurika Yamate, Emiko Kasahara, Satoshi Yokoyama, Eisuke F Sato, The open biochemistry journal, The open biochemistry journal, 12, 87 - 102, 2018 , Refereed
    Summary:Background: In modern society, irregular lifestyles are a problem. It is well known that Atopic Dermatitis (AD) occurs during physical stress in people with an irregular lifestyle. We evaluated the influence that day-and-night reversal physical stress has on AD. Methods: Six-week-old specific-pathogen-free and conventional NC/Nga male mice were used. For the day-and-night reversal procedure, the mice ran on a treadmill at a slow speed of 10 m/min for 12 h (between 8:00 and 20:00). Then, between 20:00 and 8:00, we put the mice in a dark place. This treatment was repeated every day for two weeks. The behavioral circadian rhythm of the mice was evaluated with the open field test. Then, the mice were sacrificed and histological examinations of the tissues, the expression of peptide hormones, corticosterone, Immunoglobulin E, histamine, and cytokines was performed using an enzyme-linked immunosorbent assay. Results: In the treadmill-treated conventional NC/Nga mice, AD symptoms were deteriorated compared with the non-treated conventional NC/Nga mice. The levels of Period (Per) 2, Clock, and brain and muscle arnt-like protein 1 (Bmal1) in the skin were increased constantly in the treadmill-treated conventional mice. Furthermore, the expression of Retinoic Acid-related Orphan Receptor (ROR)α, which activates Bmal1, was increased in the treadmill-treated conventional mice compared with the non-treated conventional mice. In addition, when non-treated conventional mice were administrated by the agonist of RORα, AD symptoms were deteriorated similar to treadmill-treated conventional mice. Conclusion: In the day-and-night reversal mice, the clock genes were increased constantly, indicating that this is a factor that deteriorated AD.
  • [Survey of the Distribution of Community Pharmacists Using Government Statistics]., Satoko Yajima, Akari Shimauchi, Chihiro Sakai, Satoshi Yokoyama, Yoko Ino, Toshiyuki Matsunaga, Hitomi Teramachi, Mitsuhiro Nakamura, Kazuhiro Iguchi, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 138(7), 991 - 1000, 2018 , Refereed
    Summary:In Japan, within the background of a progressively aging society, a community general support system is gradually being established. Under this system, community pharmacists are expected to expand their activities in local communities. Here, we surveyed the distribution of community pharmacists in Japan by using government statistics. We found that there are 153 towns/villages without community pharmacists, which is about six times the number of towns without physicians (26 towns/villages). The number of community pharmacists per 100000 population was correlated with the population of the municipality. There was a significant difference in the number of community pharmacists per 100000 population between depopulated and non-depopulated areas. A multiple regression analysis revealed that population, financial capability index, and number of physicians per 100000 population were positively associated with the number of community pharmacists per 100000 population in a given municipality. We hope that the survey provides useful information about future issues facing community pharmacy in a community general support system.
  • Changes in the quality of medicines during storage under LED lighting and consideration of countermeasures., Shuuji Yamashita, Kazuhiro Iguchi, Yoshihiro Noguchi, Chihiro Sakai, Satoshi Yokoyama, Yoko Ino, Hideki Hayashi, Hitomi Teramachi, Magoichi Sako, Tadashi Sugiyama, Journal of pharmaceutical health care and sciences, Journal of pharmaceutical health care and sciences, 4, 12 - 12, 2018 , Refereed
    Summary:Background: In recent years, the popularity of LED lighting has rapidly increased, owing to its many advantages, including economic benefits. We examined the change in the quality of drugs during storage under LED and fluorescent lighting and found that some medicines exhibited a different degree of color change depending on the light source. The purpose of this study was to investigate the effects of different plastic storage bags on the color change over time when various medicines were stored under LED and fluorescent lighting conditions. Methods: Photostability tests were conducted on several types of target drugs. Subsequently, subjective evaluation by ten evaluators and objective evaluation by image analysis software were carried out regarding color change. Results: A similar change in color tone was observed after all types of illumination. Subjective evaluation by 10 evaluators revealed that "change in color tone" occurred in the order of bulb-color LED lighting < daylight-color LED lighting < fluorescent lighting, regardless of the type of plastic bags. A similar tendency was observed also in objective evaluation. In this study, it was considered that a brown light-shielding plastic bag was more effective than a normal plastic bag for the prevention of the color change of medicines stored under LED lighting. Conclusions: The above results suggested that the most appropriate combination of plastic bag and light source for medicine storage was a brown light-shielding plastic bag and bulb-color LED lighting.
  • [Survey of Description on Package Inserts of OTC Drugs]., Akari Shimauchi, Misa Naganuma, Sayaka Sasaoka, Haruna Hatahira, Yumi Motooka, Shiori Hasegawa, Akiho Fukuda, Satoshi Nakao, Chihiro Sakai, Satoshi Yokoyama, Yoko Ino, Mitsuhiro Nakamura, Kazuhiro Iguchi, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 138(2), 259 - 267, 2018 , Refereed
    Summary:The "self-medication tax deduction" system began in Japan in January 2017, allowing people to encourage the use of OTC drugs. Package inserts contain important information for consumers regarding their use. In this study, we first checked whether the items, as required in the notifications of the Japanese Ministry of Health, Labour and Welfare, are described in the package inserts of cold remedies and analgesic antipyretics in OTC drugs. The descriptions of almost all packages checked in this study were based on the notifications, but those of a small number of them were not. Next, we examined the description of the items, unrequired in the notification, but worthy for proper use of drugs; e.g., the description of prohibition for use by "patients with severe hypertension" in case of ibuprofen-containing products, and the description was found in only seven of 180 products. Manufactures should make package inserts along with notifications, including the description for proper use of drugs.
  • Analysis of Pre-avoid Cases at Community Pharmacy, 堺 千紘, 横山 聡, 伊野 陽子, 山下 修司, 野口 義紘, 井口 和弘, 寺町 ひとみ, 薬局薬学 = The journal of community pharmacy and pharmaceutical sciences, 薬局薬学 = The journal of community pharmacy and pharmaceutical sciences, 10(1), 201 - 207, 2018
  • Influence of Repeated Senna Laxative Use on Skin Barrier Function in Mice., Satoshi Yokoyama, Keiichi Hiramoto, Yurika Yamate, Kazuya Ooi, Annals of dermatology, Annals of dermatology, 29(4), 414 - 421, Aug. 2017 , Refereed
    Summary:BACKGROUND: Senna, one of the major stimulant laxatives, is widely used for treating constipation. Chronic senna use has been reported to be associated with colonic disorders such as melanosis coli and/or epithelial hyperplasia. However, there is no obvious information on the influence of chronic senna use on organs except for the intestine. OBJECTIVE: To clarify the influence of senna laxative use on skin barrier function by repeated senna administration. METHODS: Eight-week-old male hairless mice received senna (10 mg/kg/day) for 21 days. After administration, we evaluated transepidermal water loss (TEWL), and investigated the biomarkers in plasma and skin using protein analysis methods. RESULTS: Fecal water content on day seven was significantly increased; however, on day 21, it was significantly decreased after repeated senna administration. In the senna-administered group, TEWL was significantly higher compared to the control on days seven and 21. Plasma acetylcholine concentration and NO2-/NO3- were increased on days seven and 21, respectively. In skin, tryptase-positive mast cells and inducible nitric oxide synthase (iNOS)-positive cells were increased on days seven and 21, respectively. The increase of TEWL on days seven and 21 was suppressed by the administration of atropine and N(G)-nitro-L-arginine methyl ester, respectively. CONCLUSION: It was suggested that diarrhea or constipation induced by repeated senna administration caused the impairment of skin barrier function. There is a possibility that this impaired skin barrier function occurred due to degranulation of mast cells via cholinergic signals or oxidative stress derived from iNOS.
  • 処方箋への検査値表示と薬局薬剤師の役割 岐阜薬科大学附属薬局の取り組み, 寺町 ひとみ, 堺 千紘, 野口 義紘, 山下 修司, 横山 聡, 伊野 陽子, 井口 和弘, 日本地域薬局薬学会誌, 日本地域薬局薬学会誌, 5(1), 要33 - 要33, Jul. 2017 , Refereed
  • Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin., Keiichi Hiramoto, Satoshi Yokoyama, Yurika Yamate, Photodermatology, photoimmunology & photomedicine, Photodermatology, photoimmunology & photomedicine, 33(2), 84 - 91, Mar. 2017 , Refereed
    Summary:BACKGROUND: We previously reported that ultraviolet (UV) A eye irradiation reduces the ulcerative colitis induced by dextran sodium sulfate (DSS). This study examined the effects of UVA on colon carcinoma induced by azoxymethane (AOM) and DSS. METHODS: We irradiated the eyes of ICR mice with UVA at a dose of 110 kJ/m2 using an FL20SBLB-A lamp for the experimental period. RESULTS: In mice treated with these drugs, the symptom of colon carcinoma was reduced by UVA eye irradiation. The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the blood were increased in AOM + DSS-treated mice; however, those levels were reduced by UVA eye irradiation. The expression of β-endorphin, methionine-enkephalin (OGF), μ-opioid receptor, and opioid growth factor receptor (OGFR) of the colon was increased in the AOM + DSS-treated mice, and these levels were increased further following UVA eye irradiation. When β-endorphin inhibitor was administered, the ameliorative effect of UVA eye irradiation was reduced, and the effect of eye irradiation disappeared entirely following the administration of naltrexone (inhibitor of both opioid receptor and OGFR). CONCLUSIONS: These results suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma.
  • 岐阜薬科大学附属薬局における薬局間分割販売業務の状況調査, 井口 和弘, 堺 千紘, 横山 聡, 伊野 陽子, 山下 修司, 野口 義紘, 松永 俊之, 中村 光浩, 杉山 正, 寺町 ひとみ, 薬局薬学, 薬局薬学, 8(2), 149 - 154, Oct. 17 2016
    Summary:医薬分業の進展やかかりつけ薬剤師の普及施策により、薬局での在庫負担は今後も増加することが予想される。各地域の薬剤師会を柱とした薬局間分割販売事業は、薬局の在庫負担の軽減において重要な位置づけにある。岐阜薬科大学附属薬局は、岐阜市薬剤師会の備蓄センター協力薬局として、薬局間分割販売業務を行っている。今回は、岐阜薬科大学附属薬局における分割販売事業の状況について現状を調べた。その結果、分割販売の実績は、地理的要因および価格的要因に規則性が観察された。また、抗生剤や後発医薬品、散剤の分割販売が多い傾向であった。本調査より、分割販売を利用する薬局に対し利便性の高い運用を考えるうえでの知見を得ることができた。(著者抄録)
  • Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha., Satoshi Yokoyama, Keiichi Hiramoto, Mayu Koyama, Kazuya Ooi, Cutaneous and ocular toxicology, Cutaneous and ocular toxicology, 35(3), 194 - 203, Sep. 2016 , Refereed
    Summary:CONTEXT: Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. OBJECTIVE: The purpose of this study was to evaluate skin barrier function during chronic liver injury. MATERIALS AND METHODS: Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma. RESULTS: After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody. CONCLUSIONS: We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.
  • 医療機関での医療品保管における最適な照明器具の選択に関する検討, 山下 修司, 井口 和弘, 野口 義紘, 堺 千紘, 横山 聡, 伊野 陽子, 林 秀樹, 寺町 ひとみ, 酒向 孫市, 杉山 正, 医療薬学, 医療薬学, 42(7), 512 - 517, Jul. 2016
    Summary:医療機関での医薬品保管における最適な照明器具の選択について検討した。対象医薬品はラシックス錠20mg、パーロデル錠2.5mg、フルイトラン錠2mg、ニポラジン錠3mg、カロナール錠200mgとした。照明は昼光色LED電球、昼白色LED電球、電球色LED電球および電球型蛍光灯を使用した。各照明器具の色温度は、それぞれ6700K、5000K、2700Kおよび5000Kである。LED照明の方が色調変化の程度が少ない傾向にある医薬品が存在した。各タイプのLED照明間の比較では、ラシックス錠20mgおよびパーロデル錠2.5mgにおいて色調変化の程度に違いが見られ、最も変化の小さかったのは電球色LED照明であった。
  • 実務実習生の実習調剤時における数量間違い対策導入効果, 井口 和弘, 大久保 沙知, 岩本 理央, 堺 千紘, 横山 聡, 伊野 陽子, 山下 修司, 野口 義紘, 松永 俊之, 中村 光浩, 杉山 正, 寺町 ひとみ, 日本地域薬局薬学会誌, 日本地域薬局薬学会誌, 4(1), 1 - 8, Jun. 25 2016
    Summary:著者等は以前、岐阜薬科大学附属薬局で実習を受け入れた学生の調剤ミスについて調査し、「数量間違い」が全ミスの51%を占めていたことを報告した。今回、数量間違い防止対策として、「調剤開始前に各薬剤の必要総数を計算し、調剤指示箋もしくは処方箋のコピーに記載した後、実際の調剤作業に入る」ことを定めた。その効果を検証するため、対策導入後2年間のインシデントレポートを分析し、導入前2年間と比較した。結果、処方箋枚数あたりの数量間違い発生率は導入前2.95%、導入後1.99%で有意に減少していた。
  • Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium-induced colitis mouse model., Satoshi Yokoyama, Keiichi Hiramoto, Mayu Koyama, Kazuya Ooi, Experimental dermatology, Experimental dermatology, 24(10), 779 - 84, Oct. 2015 , Refereed
    Summary:Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease-induced skin disruption, we used a dextran sulphate sodium (DSS)-induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS-treated mice compared to controls. Tumor necrosis factor-alpha (TNF-α), interleukin 6 and NO2-/NO3- levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS-treated mice. However, when administered TNF-α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase-expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion-blocking agent) was administered to DSS-treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon-to-skin signal transduction, as DSS-induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS-induced colitis, and the activation of mast cells via mAChRs is critical to this association.
  • Immunological changes in the intestines and skin after senna administration., Yurika Yamate, Keiichi Hiramoto, Satoshi Yokoyama, Kazuya Ooi, Pharmaceutical biology, Pharmaceutical biology, 53(6), 913 - 20, Jun. 2015 , Refereed
    Summary:CONTEXT: It has been reported that chronic sennoside use is associated with the development of melanosis coli, colonic adenoma, and/or carcinomas. OBJECTIVES: In this study, we investigated the immunological changes in the colon and skin after the administration of senna. MATERIALS AND METHODS: In this study, we investigated the colon and epidermis of C57/BL6j mice after a single administration of 10 mg/kg of senna [Cassia angustifolia (Caesalpiniaceae); 3, 6, 12, and 24 h after administration] and after repeated once per week administrations (on days 3, 5, 7, 14, and 21 of administration). The LD50 and ED50 of senna used in this experiment were 165 mg/kg and 13 g/kg, respectively. RESULTS: We demonstrated that the DOPA-positive cells in the colon increased at 12 h after single administration and were further increased from at 5-28 d after repeated administration. We also studied the physiological changes of the small intestine using the charcoal meal test. We found that there was a tendency for peristalsis to be inhibited after repeated senna administration. In the epidermis, we investigated the number of Langerhans cells, because they are important immune cells of the skin. The number of these cells decreased, especially after repeated administration. DISCUSSION AND CONCLUSION: The present findings suggested that it is necessary to pay attention to not only the intestine but also the skin, during long-term senna treatment.
  • Impaired skin barrier function in mice with colon carcinoma induced by azoxymethane and dextran sodium sulfate., Satoshi Yokoyama, Keiichi Hiramoto, Mayu Koyama, Kazuya Ooi, Biological & pharmaceutical bulletin, Biological & pharmaceutical bulletin, 38(6), 947 - 50, 2015 , Refereed
    Summary:We have previously reported that impaired skin barrier function was induced by small intestinal injury in mice. Therefore, we postulated that other intestinal diseases might also influence skin barrier function. In this study, we evaluated the skin barrier function of hairless mice with colon carcinoma that was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). In mice treated with these drugs, we observed elevated transepidermal water loss and reduced skin hydration levels, compared to those in the control mice. In addition, plasma nitrogen di/trioxide (NO2(-)/NO3(-)) levels were significantly elevated, and expression of type I collagen was significantly reduced in the treated mice, compared to those in control. These results suggest that impaired skin barrier function occurs in mice when colon carcinoma is present.
  • Skin disruption is associated with indomethacin-induced small intestinal injury in mice., Satoshi Yokoyama, Keiichi Hiramoto, Mayu Koyama, Kazuya Ooi, Experimental dermatology, Experimental dermatology, 23(9), 659 - 63, Sep. 2014 , Refereed
    Summary:One mechanism by which non-steroidal anti-inflammatory drugs (NSAIDs) cause intestinal injury is by inducing matrix metalloproteinases (MMPs) that degrade and remodel the extracellular matrix. In addition to the intestinal mucosa, MMPs are expressed in the skin and can be activated by mast cell-secreted tryptase. We therefore investigated whether intestinal injury resulting from treatment with the NSAID indomethacin induced MMPs in the skin of mice and caused an associated disruption of skin function. Hairless mice and mast cell-deficient mice were administered indomethacin, after which damage to the jejuna and skin was assessed with immunohistochemistry and Western blotting. The plasma concentration of inflammatory mediators was assessed to evaluate potential pathways for signalling skin disruption in response to intestinal injury. In hairless mice with intestinal injury, transepidermal water loss (TEWL) was higher and skin hydration was lower than in control mice. The expression levels of mast cells, tryptase, MMP-1 and MMP-9 were also increased, with concurrent degradation of types I and IV collagen. In contrast, no changes in skin TEWL or skin hydration were observed in mast cell-deficient mice with indomethacin-induced intestinal injury. In all mice evaluated, the plasma concentrations of IgE, IgA, histamine and TNF-α were increased in response to indomethacin treatment. Skin disruption was strongly associated with indomethacin-induced small intestinal injury, and the activation of mast cells and induction of tryptase, MMP-1 and MMP-9 are critical to this association.
  • 経皮吸収型鎮痛・抗炎症剤の皮膚障害性に関する研究 ロキソプロフェンナトリウムを中心として, 大井 一弥, 横山 聡, 平本 恵一, 薬理と治療, 薬理と治療, 42(2), 107 - 113, Feb. 2014
    Summary:経皮吸収型鎮痛・抗炎症剤の皮膚障害性について、マウスを用いて24時間貼付後の変化を調べた。試験薬剤はサージカルテープ優肌絆スキンカラー、高含水シート、ロキソニンテープおよびパップ、ロキソプロフェンナトリウムテープおよびパップ、モーラステープの7剤とした。貼付剤除去1時間後および24時間後の皮膚反応はモーラステープ以外は認めず、掻爬の回数は1時間後で対照群(脱脂綿固定)に比較して各試験薬剤で有意に増加したが、モーラステープで最も高値であった。経表皮水分喪失はスキンカラー以外のテープ剤は対照群より高値で、ロキソニンテープ剤の製剤間に差はなかった。角質水分量は除去1時間にモーラステープで有意な減少を認めた。角質剥離量は、パップ剤に比較してテープ剤が高値であった。表皮の肥厚は、組織学的検討でテープ剤の除去1時間後に認めた。サブスタンスPの発現増加はモーラステープでのみ認めた。
  • Quantitative evaluation of tacrolimus permeation in skin based on the sequential application of both tacrolimus ointment and heparinoid external preparation, Kazuya Ooi, Satoshi Yokoyama, Yuki Awa, Aki Kawai, Keiichi Hiramoto, Nishinihon Journal of Dermatology, Nishinihon Journal of Dermatology, 76(2), 127 - 130, 2014
    Summary:Sequential application of both tacrolimus ointment and heparinoid external preparation has been performed for atopic dermatitis treatment. There are, however, no data about the application order of these two preparations. The aim of this study was to examine the influence of application order of tacrolimus ointment and heparinoid external preparation on the tacrolims concentrations in skin. We applied the tacrolimus ointment (Protopic® ointment 0.1%) followed to heparinoid external preparation (Hirudoid® ointment, Hirudoid® cream or Hirudoid® lotion) on the dorsal skin of NOA/Jcl mice as an atopic dermatitis model, and vice versa. After 3 hours application, we measured the tacrolimus concentration in skin by LC-MS/MS. No significant differences in tacrolimus concentrations were observed between tacrolims ointment application followed to heparinoid external preparation group and heparinoid external preparation application followed to tacrolims ointment group. This finding suggests that application order of tacrolimus ointment and heparinoid external preparation has no influence on the clinical efficacy of tacrolimus.
  • パクリタキセル注射液「NP」のマウス白血病L1210細胞に対する抗腫瘍効果, 大井 一弥, 横山 聡, 河井 亜希, 阿波 勇樹, 平本 恵一, 薬理と治療, 薬理と治療, 41(6), 573 - 576, Jun. 2013
    Summary:L1210細胞をマウスの腹腔内に移植し、パクリタキセル注射液「NP」とタキソール注射液(いずれもパクリタキセルとして6および12mg/kg/day)または媒体を移植後5日間腹腔内投与し、移植28日後まで生死の確認および体重測定を実施した。媒体対照群は8日目までに全例が死亡し、平均生存日数は7.3日であった。パクリタキセル6mg/kg/dayにおける平均生存日数と延命率は「NP」が8.8日および20.5%、タキソールが9.4日および28.8%であり、パクリタキセル12mg/kg/dayにおける平均生存日数と延命率はNP」が10.9日および49.3%、タキソールが9.5日および30.1%であった。媒体対照群と比較していずれの製剤においても有意な延命を認め、同一用量において製剤間に有意差は認めなかった。「NP」の抗腫瘍作用はタキソールと同等の有効性を示すと考えられた。
  • シスプラチン投与時の制吐療法におけるパロノセトロンとアプレピタントの効果, 横山 聡, 藪田 ゆみ, 埋橋 賢吾, 坂 晋, 大田 博子, 藤川 隆彦, 大井 一弥, 薬理と治療, 薬理と治療, 40(12), 1073 - 1078, Dec. 2012
    Summary:シスプラチンを含む高度催吐性化学療法を受けた患者を対象として、GD(グラニセトロン+デキサメタゾン)レジメン、GAD(グラニセトロン+アプレピタント+デキサメタゾン)レジメンおよびPAD(パロノセトロン+アプレピタント+デキサメタゾン)レジメンの悪心・嘔吐抑制効果を後方視的に比較検討し、制吐レジメンにおけるパロノセトロンおよびアプレピタントの有効性を検討した。GAD群ならびにPAD群の全期間CR率はそれぞれ83.8%、82.9%で、GD群の55.3%に比して有意に高くなった。PAD群の全期間「有意な悪心なし」の割合は80.0%で、GD群の29.8%に対して有意に高値を示した。女性におけるCR率はGD群よりもGAD群やPAD群のほうが有意に高かった。男性におけるPAD群の「有意な悪心なし」の割合は、GD群とくらべて有意に高値を示し、女性におけるPAD群では、GD群やGAD群と比べて有意に高値を示した。
  • 薬学部におけるバイタルサイン教育を取り入れた早期体験学習の評価, 林 雅彦, 西村 嘉洋, 横山 聡, 垣東 英史, 大井 一弥, 医療薬学, 医療薬学, 38(6), 339 - 349, Jun. 2012
    Summary:模擬体験型のバイタルサイン実習を組み込んだ早期体験学習を1年次前期に行った。バイタルサイン教育を取り入れた早期体験学習の教育効果を評価する目的でアンケート調査を実施した。また、改善項目抽出のための統計処理方法として用いられている顧客満足度(CS)分析を用いて、早期体験学習における改善項目の抽出を試みた。最優先で取り組むべき項目は、「医療人としての自覚を培う必要性を理解できる」そして「薬剤師の仕事にやりがいを感じる」であることが、事前アンケートのCS分析から明らかとなった。次に取り組むべき課題は、「患者を治したい気持ちになること」、「卒業後のイメージを形成すること」であった。早期体験学習後に卒業後の希望職種を調査した結果では、25.3%の学生が卒業後の進路を明確に示さなかった。
  • [A case of an advanced gastric cancer patient on hemodialysis achieving long-term progression-free survival after CPT-11+CDDP therapy]., Satoshi Yokoyama, Mohei Kouyama, Masatoshi Kuratsune, Yuji Imamura, Atsushi Nakamitsu, Yasuhiko Fukuda, Hiroko Ohta, Gan to kagaku ryoho. Cancer & chemotherapy, Gan to kagaku ryoho. Cancer & chemotherapy, 39(5), 817 - 20, May 2012 , Refereed
    Summary:A 59-year-old male with chronic kidney disease was diagnosed as having advanced gastric cancer(cT2N1P0H1M0), and CPT-11+CDDP therapy was started for him simultaneously with hemodialysis(HD). Serum CDDP concentrations were measured in the 1st course, and free-platinum(f-Pt)showing the anti-tumor effect was found to be eliminated by HD. Serum f-Pt levels, however, re-elevated until 24 hours after HD completion. Serum concentrations measured in the 15th course showed that f-Pt levels became higher than those observed in the 1st course, suggesting that CDDP was not completely removed by HD. Medical treatment was continued until the liver metastases were judged to be a progression disease at completion of the 18th course. When CDDP was administered to patients on HD, it was necessary to pay attention to various CDDP serum concentrations, and to tailor the dose to a tolerable level in each patient. Such an individual therapy might enable CPT-11+CDDP therapy to be one of the medical treatments of choice for advanced gastric cancer patients on HD.
  • [A case of synchronous multiple liver metastasis of sigmoid colon cancer with a pathological complete response to combination chemotherapy of 5-FU/LV and bevacizumab]., Shinnosuke Uegami, Yuji Imamura, Yutaka Daimaru, Atsushi Nakamitsu, Mohei Kouyama, Aki Kuwada, Kunio Toge, Hiroyuki Taogoshi, Satoshi Yokoyama, Yasuhiko Fukuda, Gan to kagaku ryoho. Cancer & chemotherapy, Gan to kagaku ryoho. Cancer & chemotherapy, 38(2), 321 - 4, Feb. 2011 , Refereed
    Summary:A 73-year-old man was referred to our hospital with sigmoid colon cancer in July 2009. CT and MRI showed synchronous multiple liver metastasis. After a sigmoid colon resection in August, he received convergent chemotherapy in combination with 5-fluorouracil(5-FU)/Leucovorin(LV)(RPMI regimen)and bevacizumab for liver metastasis. After two courses without any major adverse effects, liver metastasis remarkably reduced on CT and MRI examination. We thus performed a liver resection, and pathological examination revealed a complete response in liver. Combination chemotherapy of 5-FU/LV and bevacizumab can be expected to provide safe and effective treatment for liver metastasis of colon cancer.
  • [Two cases of advanced colorectal cancer with UGT1A1*28 homozygosity treated by FOLFIRI]., Satoshi Yokoyama, Yuuji Imamura, Naoto Hatano, Tatsuhito Fukuoka, Hirofumi Usui, Yasushi Morita, Gan to kagaku ryoho. Cancer & chemotherapy, Gan to kagaku ryoho. Cancer & chemotherapy, 36(7), 1159 - 61, Jul. 2009 , Refereed
    Summary:Severe neutropenia attributable to irinotecan hydrochloride (CPT-11) is reportedly associated with gene polymorphism of UGT1A1 related to its metabolism. Case 1 is a 70-year-old male patient with rectal cancer that had spread to the liver. Although he received six courses of mFOLFOX6, his hepatic metastasis recurred. Therefore, the regimen was switched to FOLFIRI. The CPT-11 dosage was 150 mg/m(2). Twelve days after the first course was attempted, neutropenia at grade 4 and a fever of 39 degrees C were found. Case 2 is a 65-year-old male whose sigmoid colon cancer had spread to the liver. We started FOLFIRI with a CPT-11 dosage of 120 mg/m(2). Nine days following administration of the first course, we found neutropenia of grade 3 and a fever of 38 degrees C. Analysis of the UGT1A1 gene polymorphism after symptom improvement revealed UGT1A1(*)28 homozygosity in both cases, which suggests that when FOLFIRI is conducted on a patient with homozygous UGT1A1(*)28, it is necessary to pay attention to neutropenia even with a CPT-11 dosage of 120 mg/m(2).
  • Delayed reactivation of p53 in the progeny of cells surviving ionizing radiation., Keiji Suzuki, Satoshi Yokoyama, Satomi Waseda, Seiji Kodama, Masami Watanabe, Cancer research, Cancer research, 63(5), 936 - 41, Mar. 01 2003 , Refereed
    Summary:Ionizing radiation induces genomic instability, which is transmitted through many generations after irradiation in the progeny of surviving cells. To detect delayed activation of p53, we constructed a reporter plasmid containing the p53-responsible promoter and the bacterial beta-galactosidase (beta-gal) gene and introduced it into human fibrosarcoma (HT1080) cells, which retain wild-type p53 function. The resultant clones induce beta-gal protein after X-irradiation, and the induction kinetics were similar to those of p21(WAF1/CIP1) protein. More than 90% of the cells were stained blue when the cells were incubated with X-gal 4 h after 6 Gy of X-rays, whereas very few control cells were beta-gal positive. The primary colonies formed after 6 Gy of X-rays were collected, and they were subjected to secondary colony formation. We observed that a significant number of surviving colonies contained beta-gal-positive cells, suggesting that delayed activation of p53 occurred in the progeny of irradiated cells. We also found higher frequency of phosphorylation of p53, NBS1, and CHK2/Cds1 in the progeny of surviving cells. Furthermore, foci formation of phosphorylated histone H2AX was detected in the progeny of surviving cells. These findings provide the possibility that the observed instability results from these DNA breaks, i.e., the breaks lead to delayed chromosome rearrangements, delayed cell death, and so forth, many generations after irradiation and that activation of p53 function may eliminate cells that have potentially accumulated genomic alterations.
  • Association Between Antipsychotics and Osteoporosis Based on Real-World Data., Satoshi Yokoyama, Shoki Wakamoto, Yuki Tanaka, Chihiro Nakagawa, Kouichi Hosomi, Mitsutaka Takada, The Annals of pharmacotherapy, The Annals of pharmacotherapy, 54(10), 988 - 995, Oct. 2020 , Refereed
    Summary:BACKGROUND: Osteoporosis, which is a major public health concern, has been known to reduce health-related quality of life. Some studies have suggested that antipsychotics could perhaps cause osteoporosis by increasing serum prolactin levels. However, the association between antipsychotics and the risk for developing osteoporosis has been controversial. OBJECTIVE: The present study aimed to assess the association between antipsychotic use and onset of osteoporosis in real-world settings. METHODS: A multimethod data-mining approach using different algorithms and databases was used. First, disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2017) with reporting odds ratio (ROR) and information component (IC) being used to indicate a signal. Furthermore, a sequence symmetry analysis using data from a large Japanese administrative claims database (2005-2017; JMDC Inc, Japan) was conducted. Short-term intervals (ie, 12, 24, and 36 months) were set to investigate the association between antipsychotic use and onset of osteoporosis using the adjusted sequence ratio (SR) to indicate a signal. RESULTS: No potential association between osteoporosis and all antipsychotics was observed in the FAERS database, except for perphenazine, which exhibited significant signals using both ROR and IC. Moreover, no potential association between osteoporosis and antipsychotics was observed in the JMDC claims database, except for sulpiride and aripiprazole. None of the antipsychotics indicated significant signals using all analyzed items (ROR, IC, and adjusted SR). CONCLUSION AND RELEVANCE: Real-world data show no association between antipsychotic use and the onset of osteoporosis. Further pharmacoepidemiological studies are needed for causality assessment.
  • Polypharmacy in three different spontaneous adverse drug event databases ., Takayuki Mabuchi, Kouichi Hosomi, Satoshi Yokoyama, Mitsutaka Takada, International journal of clinical pharmacology and therapeutics, International journal of clinical pharmacology and therapeutics, Jul. 30 2020 , Refereed
    Summary:OBJECTIVE: Polypharmacy has become a major problem in medical care worldwide, including in Japan. The purpose of this study was to investigate the current situation of polypharmacy using different spontaneous adverse drug event report databases. MATERIALS AND METHODS: A retrospective data analysis was performed using reports from 2007 to 2015 from three different spontaneous adverse drug event report databases: the Japanese Adverse Drug Event Report (JADER) constructed by the Pharmaceuticals and Medical Devices Agency in Japan, the US Food and Drug Administration (FDA) Adverse Drug Event Reporting System (FAERS) constructed by the FDA in the United States, and the Canada Vigilance Adverse Reaction Online Database (CVARD) constructed by the government of Canada. Polypharmacy trends during the study period were investigated. RESULTS: The mean numbers of drugs per report in the JADER, FAERS, and CVARD databases during the study period were 6.62, 3.76, and 3.44, respectively. The mean number of drugs per report increased with age in all three databases, with a peak at ages 70 - 79 years in all three databases (7.0 drugs for JADER, 4.7 drugs for FAERS, and 4.2 drugs for CVARD). CONCLUSION: Adverse event reports were more likely to develop in the patients treated through polypharmacy. Polypharmacy in Japan should be improved to prevent adverse events. Additionally, the patients aged ≥ 80 years tended to develop adverse events even if the number of prescribed drugs was relatively small. Therefore, polypharmacy should be noted in these patients to prevent adverse events.
  • Relationship between serum calcium and creatinine in hematopoietic stem cell transplantation patients treated with foscarnet ., Ryosuke Ota, Atsushi Hirata, Keisuke Noto, Satoshi Yokoyama, Kouichi Hosomi, Mitsutaka Takada, Hiroshi Matsuoka, International journal of clinical pharmacology and therapeutics, International journal of clinical pharmacology and therapeutics, 58(5), 274 - 281, May 2020 , Refereed
    Summary:OBJECTIVE: The relationship between serum creatinine and calcium (Ca) was investigated in hematopoietic stem cell transplantation (HSCT) patients treated with foscarnet. MATERIALS AND METHODS: A retrospective study was performed to investigate the development of foscarnet-induced renal dysfunction in patients who received HSCT from April 2010 to November 2018 at the Kindai University Nara Hospital. A total of 80 patients were identified from the medical records, and 42 patients who met the inclusion criteria were enrolled in this study. Renal dysfunction was classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. RESULTS: A significant inverse relationship was observed between serum creatinine and Ca levels (r = -0.372; p < 0.0001; y = -0.537x + 9.268). A separate analysis divided into renal dysfunction and non-renal dysfunction groups showed that there was a significant relationship between serum creatinine and Ca levels in the renal dysfunction group (r = -0.531; p < 0.0001; y = -0.617x + 9.239) but not in the non-renal dysfunction group (r = -0.011; p = 0.561; y = -0.023x + 8.934). The optimal cutoff for the minimum Ca level was calculated to be 8.1 mg/mL. CONCLUSION: A significant inverse relationship was observed between serum creatinine and Ca levels in HSCT patients with foscarnet-induced renal dysfunction. Foscarnet-induced renal dysfunction should be noted if Ca levels fall below 8.1 mg/dL. Monitoring Ca levels may be useful for detecting renal dysfunction at early stages in patients treated with foscarnet.
  • Association between malignancy and methotrexate and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis ., Ryo Inose, Natsue Hashimoto, Kouichi Hosomi, Satoshi Yokoyama, Mitsutaka Takada, International journal of clinical pharmacology and therapeutics, International journal of clinical pharmacology and therapeutics, 58(3), 131 - 138, Mar. 2020 , Refereed
    Summary:OBJECTIVE: This study was aimed at investigating the risk of malignancies in rheumatoid arthritis patients treated with methotrexate (MTX), and whether the addition of biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignancies in patients receiving MTX therapy, by using data from a spontaneous adverse reaction database. MATERIALS: Patient data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2015 were analyzed. METHODS: A data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignancies in patients receiving MTX therapy. RESULTS: MTX showed significant associations with all malignancies except liver cancer. bDMARDs showed significant associations with stomach cancer, colorectal cancer, prostate cancer, ovarian cancer, malignant melanoma, and lung cancer. In addition, bDMARD use increased the risk of breast, ovarian, and lung cancers in rheumatoid arthritis patients receiving MTX therapy. CONCLUSION: MTX use was significantly associated with various malignancies. Moreover, concomitant use of bDMARDs further increased the risk of breast, ovarian, and lung cancers in MTX-treated patients with rheumatoid arthritis.
  • Time-to-onset analysis of amiodarone-associated thyroid dysfunction., Sayoko Kinoshita, Kouichi Hosomi, Satoshi Yokoyama, Mitsutaka Takada, Journal of clinical pharmacy and therapeutics, Journal of clinical pharmacy and therapeutics, 45(1), 65 - 71, Feb. 2020 , Refereed
    Summary:WHAT IS KNOWN AND OBJECTIVE: Amiodarone (AMD) treatment is associated with a number of significant adverse effects including thyroid dysfunction. However, the relationship between the development of thyroid dysfunction and the dosage and treatment duration of AMD remains unclear. The purpose of this study was to examine the onset profiles of amiodarone-associated thyroid dysfunction using a spontaneous adverse drug reaction (ADR) reporting database. METHODS: Data were obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS). For signal detection of spontaneous ADRs, the reporting odds ratio (ROR) and information component (IC) were calculated. Cumulative incidences of hyperthyroidism and hypothyroidism were assessed using the Kaplan-Meier method, and time-to-onset profiles were analysed using the Weibull shape parameter (WSP) test. RESULTS AND DISCUSSION: The median time-to-onset of hyperthyroidism associated with AMD and other drugs was 720.0 (range: 225.5-1145.0) and 101.5 (range: 14.0-468.8) days, respectively. Patients treated with AMD showed a significantly longer time-to-onset of hyperthyroidism than those treated with other drugs (P < .001). The median time-to-onset of hypothyroidism associated with AMD and other drugs was 183.0 (range: 35.0-727.8) and 153.0 (range: 19.0-608.0) days, respectively. There was no significant difference in the time-to-onset of hypothyroidism between patients treated with AMD and those treated with other drugs (P = .13). For hyperthyroidism, the WSP test showed that AMD had a wear-out failure-type profile and other drugs had early failure-type profiles. For hypothyroidism, the WSP test showed that both AMD and other drugs had early failure-type profiles. WHAT IS NEW AND CONCLUSIONS: Amiodarone-associated hyperthyroidism had a different onset profile than hyperthyroidism associated with other drugs. Because the time-to-onset of AMD-associated hyperthyroidism is widely distributed, sustained and continuous attention is required to detect and treat hyperthyroidism during AMD treatment. In contrast, AMD-associated hypothyroidism had an onset profile that was similar to that of other drugs, suggesting that attention should be focused on the earlier stages of treatment.
  • Polypharmacy in elderly patients in Japan: Analysis of Japanese real-world databases., Takayuki Mabuchi, Kouichi Hosomi, Satoshi Yokoyama, Mitsutaka Takada, Journal of clinical pharmacy and therapeutics, Journal of clinical pharmacy and therapeutics, Jan. 27 2020 , Refereed
    Summary:WHAT IS KNOWN AND OBJECTIVE: Polypharmacy is associated with an increased risk of adverse drug reactions (ADRs) and drug interactions, decreased adherence to medication and increased medical cost. Recently, polypharmacy has become a major problem in medical care in Japan as a result of the increase in the ageing population. The purpose of this study was to investigate the current situation of polypharmacy and the association between polypharmacy and adverse events. METHODS: A retrospective data analysis was performed using two different real-world data from 2007 to 2015 in Japan. The Japanese Adverse Drug Event Report (JADER), a public spontaneous adverse drug reaction database constructed by the Pharmaceuticals and Medical Devices Agency (PMDA), and a large prescription database constructed by a database vendor (Japan Medical Information Research Institute, Inc Japan [JMIRI]) were analysed. Trends of polypharmacy during the study period were investigated. RESULTS AND DISCUSSION: The mean number of drugs per report in the JADER database and per prescription in the JMIRI databases during the study period ranged from 4.8 to 5.6 and 3.5 to 3.7, respectively. The mean number of drugs increased with age in both the JADER and JMIRI databases, and the peak of the mean number of drugs was at 80-89 years (5.74 drugs) in the JADER database and at 90-99 years (4.97 drugs) in the JMIRI database. WHAT IS NEW AND CONCLUSIONS: The number of drugs increased until age 90 years or more, even though adverse events are more likely to occur after the age of 80 in Japan. Therefore, polypharmacy in the elderly should be focused on the patients aged ≥80 years rather than patients aged ≥65 years from the viewpoint of the prevention of adverse events.
  • Drug interactions between tacrolimus and clotrimazole troche: a data mining approach followed by a pharmacokinetic study., Takaya Uno, Kyoichi Wada, Kouichi Hosomi, Sachi Matsuda, Megumi Morii Ikura, Hiromi Takenaka, Nobue Terakawa, Akira Oita, Satoshi Yokoyama, Atsushi Kawase, Mitsutaka Takada, European journal of clinical pharmacology, European journal of clinical pharmacology, 76(1), 117 - 125, Jan. 2020 , Refereed
    Summary:PURPOSE: This study investigated the effects of clotrimazole troche on the risk of transplant rejection and the pharmacokinetics of tacrolimus. METHODS: The data mining approach was used to investigate whether the use of clotrimazole increased the risk of transplant rejection in patients receiving tacrolimus therapy. Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2017. Next, we retrospectively investigated the effect of clotrimazole troche on tacrolimus pharmacokinetics in seven patients who underwent heart transplantation between March and December 2017. RESULTS: The FAERS subset data indicated a significant association between transplant rejection and tacrolimus with clotrimazole [reporting odds ratio 1.92, 95% two-sided confidence interval (95% CI) 1.43-2.58, information component 0.81, 95% CI 0.40-1.23]. The pharmacokinetic study demonstrated a significant correlation between trough concentration (C0) and area under the concentration-time curve of tacrolimus after discontinuation of clotrimazole (R2 = 0.60, P < 0.05) but not before its discontinuation. Furthermore, the median clearance/bioavailability of tacrolimus after discontinuation of clotrimazole was 2.2-fold greater than that before its discontinuation (0.27 vs. 0.59 L/h/kg, P < 0.05). The median C0 decreased from 10.7 ng/mL on the day after discontinuation of clotrimazole to 6.5 ng/mL at 1 day and 5.3 ng/mL at 2 days after its discontinuation. CONCLUSION: Immediate dose adjustments of tacrolimus may be beneficial to avoid transplant rejection when clotrimazole troche is added or discontinued.
  • Inverse Association between Metformin and Amiodarone-Associated Extracardiac Adverse Events., Sayoko Kinoshita, Kouichi Hosomi, Satoshi Yokoyama, Mitsutaka Takada, International journal of medical sciences, International journal of medical sciences, 17(3), 302 - 309, 2020 , Refereed
    Summary:Background: The association between metformin and amiodarone-induced adverse events was examined using spontaneous adverse event database. Additionally, the association between other antidiabetic drugs and amiodarone-induced adverse events were also examined. Methods: A total of 6,153,696 reports from the first quarter of 2004 through the fourth quarter of 2015 were downloaded from the US Food and Drug Administration adverse event reporting system. Reporting odds ratio (ROR) and information component (IC) were used to detect associations between antidiabetic drugs and amiodarone-associated adverse events. Additionally, subset data analysis was performed to investigate whether the use of antidiabetic drugs further increased or decreased the risk of adverse events in patients receiving amiodarone therapy. Next, the RORs were adjusted for coadministered antidiabetic drugs using logistic regression analysis. Results: By whole dataset analysis, significant inverse associations were found between metformin and interstitial lung disease (ROR 0.84, 95% confidence interval [CI] 0.79-0.90; IC -0.24, 95% CI -0.33 to -0.15). In the subset data analysis, metformin (ROR 0.62, 95%CI 0.43-0.89; IC -0.63, 95%CI -1.14 to -0.11), sulfonylureas (ROR 0.53, 95%CI 0.32-0.85; IC -0.85, 95%CI -1.53 to -0.17), and dipeptidyl peptidase-4 (DPP-4) inhibitors (ROR 0.25, 95%CI 0.08-0.78; IC -1.66, 95%CI -3.08 to -0.23) were inversely associated with hyperthyroidism. Additionally, metformin (ROR 0.43, 95%CI 0.33-0.57; IC -1.09, 95%CI -1.49 to -0.69), sulfonylureas (ROR 0.64, 95%CI 0.48-0.86; IC -0.59, 95%CI -1.00 to -0.17), and DPP-4 inhibitors (ROR 0.47, 95%CI 0.27-0.81; IC -0.99, 95%CI -1.76 to -0.22) were inversely associated with interstitial lung disease. In the logistic regression analyses, DPP-4 inhibitors (adjusted ROR 0.32, 95% CI 0.10-1.00) and metformin (adjusted ROR 0.46, 95% CI 0.34-0.62) were inversely associated with amiodarone-associated hyperthyroidism and interstitial lung disease, respectively. Conclusion: Metformin is a candidate drug to reduce the risk of amiodarone-induced hyperthyroidism and interstitial lung disease.
  • Association between oral anticoagulants and osteoporosis: Real-world data mining using a multi-methodological approach., Satoshi Yokoyama, Shoko Ieda, Mirai Nagano, Chihiro Nakagawa, Makoto Iwase, Kouichi Hosomi, Mitsutaka Takada, International journal of medical sciences, International journal of medical sciences, 17(4), 471 - 479, 2020 , Refereed
    Summary:Introduction: Warfarin and direct oral anticoagulants (DOACs) have been widely used in antithrombotic therapy. Although warfarin use has been suspected to be associated with osteoporosis risk, several studies have shown otherwise. Conversely, a few reports have found an association between DOACs and osteoporosis. This study therefore clarifies the association between oral anticoagulants and osteoporosis by analyzing real-world data using different methodologies, algorithms, and databases. Methods: Real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS; 2004-2016) and Japanese administrative claims database (2005-2017; JMDC Inc., Tokyo) were used. Reporting odds ratio (ROR) and information component (IC) were calculated through disproportionality analysis (DPA) using reports recorded in the FAERS. Sequence symmetry analysis (SSA) was employed to calculate the adjusted sequence ratio (SR) using the JMDC Claims Database. For the adjusted SR and ROR, a significant signal was detected when the lower limit of the two-sided 95% confidence interval (CI) was more than 1. For the IC, a significant signal was detected when the lower limit of the 95% CI was more than 0. Results: DPA for warfarin found significant signals for osteoporosis in ROR (1.43, 95% CI: 1.32-1.54) and IC (0.50, 95% CI: 0.39-0.61). SSA showed a significant association between warfarin use and osteoporosis or bisphosphonate use. Moreover, a significant association was observed in males and females, albeit only for warfarin. Conclusion: Multi-methodological data mining revealed that warfarin use, not DOACs, is significantly associated with osteoporosis regardless of sex difference.
  • Impaired skin barrier function caused by reactive oxygen species in mice with colonic tumours., Satoshi Yokoyama, Keiichi Hiramoto, Yurika Yamate, Cutaneous and ocular toxicology, Cutaneous and ocular toxicology, 38(4), 349 - 355, Dec. 2019 , Refereed
    Summary:Purpose: We have previously reported that skin barrier function is disrupted in mice with colonic tumours induced by azoxymethane (AOM) and dextran sodium sulphate (DSS). We postulated that the impaired skin barrier function was associated with reactive oxygen species derived from gp91phox. In this study, we investigated the mechanisms underlying the impaired skin barrier function using gp91phox-/- mice. Materials and methods: We induced colonic tumorigenesis in C57BL/6j mice by AOM + DSS administration and evaluated the influence of reactive oxygen species on skin barrier function by using the hydroxyl radical scavenger N-acetyl-l-cysteine (NAC) or gp91phox-/- mice. Damage to the colon and skin following treatment with AOM + DSS was monitored using protein analysis methods and by detection of inflammatory mediators in the plasma. Results: NAC could not prevent the increase in transepidermal water loss (TEWL) and decrease in skin hydration level caused by AOM + DSS in gp91phox+/+ mice. However, gp91phox-/- mice showed no change in TEWL and skin hydration level. The dermal expression levels of nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 (NLRP3), and caspase-1 were reduced in gp91phox-/- mice. Moreover, the plasma concentrations of interleukin-18 and thymic stromal lymphopoietin (TSLP) were lower in gp91phox-/- mice than those in gp91phox+/+ mice. Inhibition of hydrogen peroxide production from superoxide anions in the gp91phox-/- status prevented the increased TEWL and decreased skin hydration level noted with degradation of NLRP3 and caspase-1. Conclusions: Superoxide anions may play an important role in the onset of the impaired skin barrier function in mice with colonic tumours.
  • Integrative analysis of clinical and bioinformatics databases to identify anticancer properties of digoxin., Satoshi Yokoyama, Yasuhiro Sugimoto, Chihiro Nakagawa, Kouichi Hosomi, Mitsutaka Takada, Scientific reports, Scientific reports, 9(1), 16597 - 16597, Nov. 12 2019 , Refereed
    Summary:Cardiac glycosides, such as digoxin, inhibit Na+/K+-ATPases and cause secondary activation of Na+/Ca2+ exchangers. Preclinical investigations have suggested that digoxin may have anticancer properties. In order to clarify the functional mechanisms of digoxin in cancer, we performed an integrative analysis of clinical and bioinformatics databases. The US Food and Drug Administration Adverse Event Reporting System and the Japan Medical Data Center claims database were used as clinical databases to evaluate reporting odds ratios and adjusted sequence ratios, respectively. The BaseSpace Correlation Engine and Connectivity Map bioinformatics databases were used to investigate molecular pathways related to digoxin anticancer mechanisms. Clinical database analyses suggested an inverse association between digoxin and four cancers: gastric, colon, prostate and haematological malignancy. The bioinformatics database analysis suggested digoxin may exert an anticancer effect via peroxisome proliferator-activated receptor α and apoptotic caspase cascade pathways. Our integrative analysis revealed the possibility of digoxin as a drug repositioning candidate for cancers.
  • Relationship between the blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplant recipients ., Ryosuke Ota, Atsushi Hirata, Keisuke Noto, Satoshi Yokoyama, Kouichi Hosomi, Mitsutaka Takada, Hiroshi Matsuoka, International journal of clinical pharmacology and therapeutics, International journal of clinical pharmacology and therapeutics, 57(11), 561 - 566, Nov. 2019 , Refereed
    Summary:OBJECTIVE: We aimed to clarify the drug interaction between tacrolimus and voriconazole and investigate the relationship between blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplantation (HSCT) patients. MATERIALS AND METHODS: A retrospective study was conducted to investigate the relationship between blood concentration of tacrolimus and that of voriconazole at the Kindai University Nara Hospital. Patients who received HSCT and tacrolimus and were prescribed voriconazole for the prevention or treatment of aspergillosis from April 2010 to July 2018 were identified from the medical records. A total of 13 patients (administration route of tacrolimus: intravenously in 6 patients, orally in 7 patients) were enrolled in the present study. RESULTS: No significant correlation was observed between the blood concentration/dose (C/D) ratio of tacrolimus and the blood concentration of voriconazole (r = 0.38; p = 0.402; y = 102.8x + 928.1). However, a significant correlation was observed between the C/D ratio of tacrolimus and the blood concentration of voriconazole in the intravenous-administration group (r = 0.94; p = 0.0048; y = 421.9x + 810.5). Meanwhile, no significant correlation was observed in the oral-administration group (r = 0.43; p = 0.34; y = 7.9x + 719). CONCLUSION: The C/D ratio of tacrolimus was significantly correlated with the blood concentration of voriconazole when tacrolimus was intravenously administered. There was a difference in the mechanism of drug interaction between tacrolimus and voriconazole depending on the administration routes.
  • Clotrimazole troches can alter everolimus pharmacokinetics in post-transplant patients: A case report., Takaya Uno, Kyoichi Wada, Sachi Matsuda, Megumi Ikura, Hiromi Takenaka, Nobue Terakawa, Akira Oita, Satoshi Yokoyama, Atsushi Kawase, Kouichi Hosomi, Mitsutaka Takada, British journal of clinical pharmacology, British journal of clinical pharmacology, 85(9), 2176 - 2178, Sep. 2019 , Refereed
  • Bleeding Risk of Warfarin and Direct Oral Anticoagulants in Younger Population: A Historical Cohort Study Using a Japanese Claims Database., Satoshi Yokoyama, Yuki Tanaka, Kazuki Nakagita, Kouichi Hosomi, Mitsutaka Takada, International journal of medical sciences, International journal of medical sciences, 15(14), 1686 - 1693, 2018 , Refereed
    Summary:A historical cohort analysis of the Japan medical data center (JMDC) claims databases was performed to compare the incidence rates of bleeding events with warfarin (WF) versus direct oral anticoagulant (DOAC) treatment in patients with non-valvular atrial fibrillation. The aim of this study is to clarify the risk factors for bleeding events in younger patients newly treated with WF or DOAC in clinical practice setting. Patients who newly initiated WF or DOAC treatment from April 2012 to March 2015 were selected from the JMDC claims database. A 1:1 propensity score matching analysis was used for new users of WF or DOAC. Kaplan-Meier curves were generated to depict the time to bleeding event (total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage) during the follow-up period. Cox proportional regression models were used to estimate the hazard ratios for total bleeding events caused by oral anticoagulants. Overall, 2,046 patients (503 WF and 1,543 DOAC) were included. After applying propensity score matching, Kaplan-Meier analysis of the WF and DOAC groups displayed comparable incidences of total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage. Cox proportional hazards modeling showed that the use of WF was not associated with total bleeding events compared with DOAC (hazard ratio: 1.21, 95% confidence interval: 0.93-1.54, p = 0.15). This historical cohort study using a claims database indicates that the bleeding risk of DOAC was comparable to that of WF in Japanese younger population.
  • Community pharmacist–led telephone follow-up enabled close management of everolimus-induced adverse events in an outpatient with metastatic breast cancer, Satoshi Yokoyama, Satoko Yajima, Chihiro Sakai, Shuji Yamashita, Yoshihiro Noguchi, Yoko Ino, Kazuhiro Iguchi, Hitomi Teramachi, Canadian Pharmacists Journal, Canadian Pharmacists Journal, 150(6), 362 - 365, Nov. 01 2017 , Refereed
  • Atopic dermatitis deteriorates dextran sodium sulfate-induced ulcerative colitis via thymic stromal lymphopoietin in mice, Hiramoto K, Orita K, Yamate Y, Yokoyama S, J Bio Med, J Bio Med, 5, 85 - 98, May 2017 , Refereed
  • Skin hydrating effects of Corchorus olitorius extract in a mouse model of atopic dermatitis, Yokoyama S, Hiramoto K, Fujikawa T, Kondo N, Konishi N, Sudo S, Iwashima M, Ooi K, J Cosme Dermatol Sci. Appl, J Cosme Dermatol Sci. Appl, 4(1), 1 - 6, Apr. 2014 , Refereed
  • Topical application of Corchorus olitorius leaf extract ameliorates atopic dermatitis in NC/Nga mice, Yokoyama S, Hiramoto K, Fujikawa T, Kondo H, Konishi N, Sudo S, Iwashima M, Ooi K, Dermatol Aspects, Dermatol Aspects, 2, 3, Feb. 2014 , Refereed
  • Mild exercise suppresses exacerbation of dermatitis in NC/Nga mice: correlation with β-endorphin Levels, Hiramoto K, Sato EF, Kobayashi H, Yokoyama S, Ooi K, J Clin Exp Dermatol Res, J Clin Exp Dermatol Res, 4, 180, Mar. 2013 , Refereed
  • The optimal conditions for use of the hydration patch, Win Back®, on human skin, Kazuya Ooi, Satoshi Yokoyama, Masahiko Hayashi, Takahiko Fujikawa, Norihiro Shinkai, Noriko Nakagima, Hitoshi Yamauchi, Jpn Pharmacol Ther, Jpn Pharmacol Ther, 40(11), 1005 - 1010, Nov. 2012 , Refereed

Conference Activities & Talks

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  • 改訂モデル・コアカリキュラムに基づく実務実習トライアルについての岐阜薬科大学附属薬局の取り組み, 寺町 ひとみ, 野口 義紘, 舘 知也, 伊野 陽子, 山下 修司, 堺 千紘, 横山 聡, 井口 和弘, 日本薬剤師会学術大会講演要旨集,   2017 10
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  • 難消化性デキストリン継続摂取の肥満に関する指標への影響, 矢島 聖子, 井口 和弘, 葛城 大介, 松永 俊之, 宮崎 孝, 堺 千紘, 横山 聡, 伊野 陽子, 寺町 ひとみ, 日本地域薬局薬学会誌,   2017 07
  • 処方箋への検査値表示と薬局薬剤師の役割 岐阜薬科大学附属薬局の取り組み, 寺町 ひとみ, 堺 千紘, 野口 義紘, 山下 修司, 横山 聡, 伊野 陽子, 井口 和弘, 日本地域薬局薬学会誌,   2017 07
  • かかりつけ薬局・薬剤師のための研修会の実施とその評価, 伊野 陽子, 舘 知也, 堺 千紘, 大久保 沙知, 山下 修司, 野口 義紘, 横山 聡, 井口 和弘, 寺町 ひとみ, 日本薬学会年会要旨集,   2017 03
  • 岐阜薬科大学附属薬局の薬学部教員を対象とした在宅医療に関する研修の効果, 横山 聡, 小林 篤史, 渡辺 康介, 井口 和弘, 山下 修司, 堺 千紘, 野口 義紘, 伊野 陽子, 山脇 正永, 寺町 ひとみ, 日本薬学会年会要旨集,   2017 03
  • LED照明下での保管における医薬品の品質変化と対応策の検討, 山下 修司, 井口 和弘, 野口 義紘, 堺 千紘, 横山 聡, 伊野 陽子, 林 秀樹, 寺町 ひとみ, 酒向 孫市, 杉山 正, 日本薬剤師会学術大会講演要旨集,   2016 10
  • ビソプロロール貼付による皮膚障害性に関する研究, 大井 一弥, 横山 聡, 小川 文歌, 平本 恵一, 日本薬学会年会要旨集,   2015 03
  • DSS腸炎マウスにおけるアセチルコリン受容体を介した皮膚障害の発現, 横山 聡, 平本 恵一, 小山 真由, 大井 一弥, 日本薬学会年会要旨集,   2015 03
  • センノサイド投与マウスにおける脳・皮膚・腸の相互関係, 平本 恵一, 山手 百合香, 横山 聡, 大井 一弥, 日本薬剤学会年会講演要旨集,   2014 05
  • モロヘイヤ抽出物のアトピー性皮膚炎モデルマウスにおける保湿効果, 横山 聡, 平本 恵一, 藤川 隆彦, 近藤 宏哉, 小西 信幸, 須藤 秀, 岩島 誠, 大井 一弥, 日本薬剤学会年会講演要旨集,   2014 05
  • タクロリムス軟膏とヘパリン類似物質製剤併用時の塗布順序に関する研究, 大井 一弥, 横山 聡, 平本 恵一, 日本皮膚科学会雑誌,   2014 04
  • 雄幼若期ラットにおける有機フッ素化合物N-EtFOSE曝露による血清テストステロン濃度変化, 坂 晋, 松岡 道美, 横山 聡, 黒田 祐, 里見 佳子, 原田 均, 井上 純子, 大西 志保, 川西 正祐, 日本薬学会年会要旨集,   2014 03
  • Crush syndromeにおける腎障害に対するオルメサルタンメドキソミルの影響に関する研究, 河井 亜希, 阿波 勇樹, 小川 文歌, 小山 真由, 横山 聡, 平本 恵一, 大井 一弥, 日本腎臓病薬物療法学会誌,   2013 09
  • 有機フッ素化合物N-EtFOSE胎児期曝露による雌雄胎仔の胎盤遺伝子発現量変化, 坂 晋, 松岡 道美, 横山 聡, 里見 佳子, 原田 均, 井上 純子, 大西 志保, 川西 正祐, 日本薬学会年会要旨集,   2013 03
  • 外来化学療法の現状とあり方 地域がん診療連携拠点病院において薬剤部が担う役割とは, 中島 恵子, 礒貝 明彦, 井向 幹栄, 小川 智恵子, 只佐 正嗣, 藤堂 未来, 横山 聡, 大田 博子, 福田 康彦, 日本農村医学会雑誌,   2009 09
  • 抗がん剤(塩酸イリノテカン)による重篤な副作用回避を目的とした遺伝子多型解析法の検討, 横山 聡, 福岡 達仁, 碓井 裕史, 森田 保司, 日本農村医学会雑誌,   2008 09
  • 遺伝子検査を併用した禁煙支援のあり方に関する研究, 久保 知子, 川村 洋子, 野村 恵美, 鎌田 恭子, 碓井 裕史, 福岡 達仁, 横山 聡, 日本禁煙学会学術総会プログラム・抄録集,   2008 08
  • 薬物治療モニタリング(TDM)による抗MRSA薬の適正使用への取り組み, 前田 奈穂, 知念 聖子, 胡 由希子, 角井 碧, 正畠 和美, 横山 聡, 大田 博子, 森田 保司, 日本農村医学会雑誌,   2008 07
  • 消化器癌治療のキードラッグである塩酸イリノテカンの重篤な副作用回避を目的とした遺伝子検査法, 横山 聡, 森田 保司, 福岡 達仁, 碓井 裕史, 日本農村医学会雑誌,   2007 07
  • 遺伝子検査を併用した個別禁煙支援, 碓井 裕史, 鎌田 恭子, 野村 恵美, 久保 知子, 福岡 達仁, 横山 聡, 共済エグザミナー通信,   2007 01
    Summary:広島市周辺の農協関連職員の喫煙者を対象とし、あらかじめ健康に対する喫煙の害、遺伝子検査を併用した禁煙支援を行う旨の文書を配布した。その後、事業所に医師、保健師が出向き、説明会を開催した。事業所の定期健診受診者は318例で、喫煙者は92例であった。これらのうち遺伝子検査を希望する者は46例で、すべて男性であった。禁煙プログラムを開始した11例中4例が、遺伝子検査の結果が禁煙のきっかけになったと回答した。ニコチン代替療法としてニコチンガムを無償で供与し、禁煙指導を行った11例中7例が使用した。禁煙指導グループで喫煙を再開した8例中3例は喫煙本数が減った。回答のあった44例中15例が行動変容を示し、禁煙あるいは節煙を行った。現在まで禁煙プログラム参加の3例が禁煙を継続している。
  • 遺伝子検査を併用した個別禁煙支援, 碓井 裕史, 鎌田 恭子, 野村 恵美, 久保 知子, 福岡 達仁, 横山 聡, 日本農村医学会雑誌,   2006 09
  • Inverse association between digoxin and cancers derived from real world data, Yokoyama, Satoshi, Sugimoto, Yasuhiro, Nakagawa, Chihiro, Hosomi, Kouichi, Takada, Mitsutaka, PHARMACOEPIDEMIOLOGY AND DRUG SAFETY,   2019 08 , WILEY

Misc

  • 医療データベースと遺伝子発現データベースの統合解析によるジゴキシンの新規薬効探索, 横山聡, 杉本泰浩, 中川千拓, 細見光一, 高田充隆, 日本薬学会年会要旨集(CD-ROM), 139th, ROMBUNNO.21PO‐am362,   2019 , https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201902224901705996
  • 米国有害事象自発報告(FAERS)を用いた,タクロリムスとアゾール系抗真菌薬併用時における,拒絶反応のリスクに関する研究, 宇野貴哉, 宇野貴哉, 細見光一, 横山聡, 和田恭一, 寺川伸江, 老田章, 高田充隆, 日本薬学会年会要旨集(CD-ROM), 139th, ROMBUNNO.21PO‐pm331S,   2019 , https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201902275407508438
  • アントラサイクリン系抗がん薬によって誘発された悪心が摂食量に及ぼす影響, 玉木慎也, 渡邊健一, 田丸智巳, 水野聡朗, 岩本卓也, 中西大介, 下村誠, 森章哉, 川上恵基, 山川智一, 小西尚巳, 青孝明, 影山慎一, 阪田安彦, 大谷彰一郎, 山田知美, 横山聡, 坂晋, 大井一弥, 日本乳癌学会学術総会プログラム・抄録集, 25th, 264,   2017 , http://jglobal.jst.go.jp/public/201702250384050676