研究者詳細 - 座間味　義人

論文 - 座間味　義人

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The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease. 査読国際誌

Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 33 ( 4 ) 586 - 597 2018年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Hepcidin secreted by hepatocytes is a key regulator of iron metabolism throughout the body. Hepcidin concentrations are increased in chronic kidney disease (CKD), contributing to abnormalities in iron metabolism. Levels of indoxyl sulfate (IS), a uremic toxin, are also elevated in CKD. However, the effect of IS accumulation on iron metabolism remains unclear. Methods: We used HepG2 cells to determine the mechanism by which IS regulates hepcidin concentrations. We also used a mouse model of adenine-induced CKD. The CKD mice were divided into two groups: one was treated using AST-120 and the other received no treatment. We examined control mice, CKD mice, CKD mice treated using AST-120 and mice treated with IS via drinking water. Results: In the in vitro experiments using HepG2 cells, IS increased hepcidin expression in a dose-dependent manner. Silencing of the aryl hydrocarbon receptor (AhR) inhibited IS-induced hepcidin expression. Furthermore, IS induced oxidative stress and antioxidant drugs diminished IS-induced hepcidin expression. Adenine-induced CKD mice demonstrated an increase in hepcidin concentrations; this increase was reduced by AST-120, an oral adsorbent of the uremic toxin. CKD mice showed renal anemia, decreased plasma iron concentration, increased plasma ferritin and increased iron content in the spleen. Ferroportin was decreased in the duodenum and increased in the spleen. These changes were ameliorated by AST-120 treatment. Mice treated by direct IS administration showed hepatic hepcidin upregulation. Conclusions: IS affects iron metabolism in CKD by participating in hepcidin regulation via pathways that depend on AhR and oxidative stress.

DOI： 10.1093/ndt/gfx252

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大規模医療情報データベース解析と基礎研究の融合による新規腎保護薬の探索査読

堀ノ内裕也, 池田康将, 石澤有紀, 玉置俊晃, 福島圭穣, 藤野裕道, 濱野裕章, 今西正樹, 座間味義人, 石澤啓介, 土屋浩一郎

四国医学雑誌 74 ( 1-2 ) 82 - 83 2018年4月

Potential Usefulness of Early Potassium Supplementation for Preventing Severe Hypokalemia Induced by Liposomal Amphotericin B in Hematologic Patients: A Retrospective Study. 査読国際誌

Naoto Okada, Momoyo Azuma, Masaki Imanishi, Yoshito Zamami, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka, Masahiro Abe, Keisuke Ishizawa

Clinical therapeutics 40 ( 2 ) 252 - 260 2018年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Liposomal amphotericin B (L-AMB) is an essential antifungal agent for patients with hematologic diseases; however, the drug causes severe hypokalemia at a high frequency. Meanwhile, there is little evidence regarding the risk factors for L-AMB-induced severe hypokalemia, and the prevention protocol has not been established. The goal of this study was to identify the risk factors related to severe hypokalemia induced by L-AMB in hematologic patients. METHODS: Seventy-eight hematologic patients with a first administration of L-AMB were enrolled in the study. Eleven patients who had serum potassium levels <3.0 mmol/L before L-AMB administration and 12 patients who received L-AMB administration within 3 days were excluded. Patients who had a serum potassium level <3.0 mmol/L during L-AMB administration were classified into a hypokalemia group (n = 26), and those who had a serum potassium level ≥3.0 mmol/L were classified into a non-hypokalemia group (n = 29). The patient characteristics were analyzed retrospectively. In addition, the usefulness of potassium supplementation was analyzed for those patients who received potassium formulations (non-hypokalemia group, n = 15; hypokalemia group, n = 24). FINDINGS: Twenty-six patients had hypolalemia after L-AMB administration. Hypokalemia with serum potassium levels <3.0 mmol/L was observed ~7 days after starting L-AMB administration. The patient characteristics, L-AMB dose, and L-AMB administration period did not differ between the 2 groups. In the patients who received potassium formulations, the period between starting L-AMB administration and starting potassium supplementation was significantly shorter in the non-hypokalemia group than in the hypokalemia group (median, 0 vs 4 days, respectively; P < 0.01); the potassium dose was not different between the 2 groups. A receiver-operating characteristic curve revealed that the cutoff time for the start of potassium supplementation to reduce the incidence of L-AMB-induced hypokalemia was 3 days. Multivariate logistic regression analysis revealed that beginning potassium supplementation within 2 days from the start of L-AMB administration was an independent factor reducing the risk of L-AMB-induced hypokalemia (odds ratio, 0.094 [95% CI, 0.019-0.47]). IMPLICATIONS: This study showed that starting administration of a potassium formulation within 2 days from the start of L-AMB administration was a risk reduction factor for L-AMB-induced hypokalemia. This finding indicates that early potassium supplementation should be incorporated into the regimen of hypokalemia management when L-AMB is used.

DOI： 10.1016/j.clinthera.2017.12.006

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Trends in the medication reviews of community pharmacies in Japan: a nationwide retrospective study. 査読国際誌

Toshihiro Koyama, Hiroshi Onoue, Ayako Ohshima, Yuri Tanaka, Yasuhisa Tatebe, Yoshito Zamami, Kazuaki Shinomiya, Yoshihisa Kitamura

International journal of clinical pharmacy 40 ( 1 ) 101 - 108 2018年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background The trends in medication reviews made by community pharmacies in Japan are currently unknown. Objective We aimed to comprehensively describe the national trends in medication reviews in Japan's community pharmacies in the backdrop of the country's ageing population. Setting Community pharmacies in Japan. Methods We analysed national health insurance claims data for 2010-2015. These data were provided by the Ministry of Health, Labour and Welfare as part of the Survey of Medical Care Activities in Public Health Insurance. Main outcome measures The national trends in community pharmacy visits involving medicine dispensing and medication reviews that involve consultations with a physician. Results Among the 365 million pharmacy visits for 2010-2015, we identified 373,429 medication reviews accompanied by consultations with a physician. The pharmacy visit rate per 1000 population increased from 427.2 in 2010 to 483.7 in 2015. Medication reviews also increased from 407 per million pharmacy visits in 2010 to 1445 in 2015. Among the 373,429 medication reviews during the study period, the prescription was changed through collaboration with a physician 338,982 times (90.4%). The proportion of medication review acceptance increased from 80.6% in 2010 to 94.8% in 2015. The prescription change rate was higher among older patients than among younger ones. Conclusions Medication reviews by community pharmacists involving consultations with a physician increased in Japan from 2010 to 2015, as did prescription changes following these reviews.

DOI： 10.1007/s11096-017-0559-7

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Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit. 査読

Niimura T, Zamami Y, Imai T, Nagao K, Kayano M, Sagara H, Goda M, Okada N, Chuma M, Takechi K, Imanishi M, Koyama T, Koga T, Nakura H, Sendo T, Ishizawa K

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 21 ( 1 ) 54 - 59 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

The findings of this study suggest that sepsis treatment de-escalation is beneficial for treatment efficacy and appropriate use of antibiotics. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

DOI： 10.18433/jpps29737

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Relationship between the administration of nicardipine hydrochloride and the development of delirium in patients on mechanical ventilation 査読

Zamami Y, Kouno Y, Niimura T, Chuma M, Imai T, Mitsui M, Koyama T, Kayano M, Okada N, Hamano H, Goda M, Imanishi M, Takechi K, Horinouchi Y, Kondo Y, Yanagawa H, Kitamura Y, Sendo T, Ujike Y, Ishizawa K

Pharmazie 73 ( 12 ) 740 - 743 2018年

Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses. 査読

石澤有紀, 今西正樹, 座間味義人, 戸谷紘基, 長尾朋子, Marin Morishita, 常山幸一, 堀ノ内裕也, 木平孝高, 武智研志, 池田康将, 土屋浩一郎, 吉栖正典, 玉置俊晃, 石澤啓介

Journal of Hypertension 2018年

Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation. 査読国際誌

Masaki Imanishi, Yuki Izawa-Ishizawa, Takumi Sakurada, Yusuke Kohara, Yuya Horinouchi, Eriko Sairyo, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Keijo Fukushima, Yasumasa Ikeda, Hiromichi Fujino, Masanori Yoshizumi, Koichiro Tsuchiya, Toshiaki Tamaki, Keisuke Ishizawa

Pharmacology 102 ( 5-6 ) 287 - 299 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. METHODS: The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. RESULTS: NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. CONCLUSION: NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation.

DOI： 10.1159/000492577

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Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit. 査読国際誌

Takahiro Niimura, Yoshito Zamami, Toru Imai, Kanako Nagao, Masafumi Kayano, Hidenori Sagara, Mitsuhiro Goda, Naoto Okada, Masayuki Chuma, Kenshi Takechi, Masaki Imanishi, Toshihiro Koyama, Tadashi Koga, Hironori Nakura, Toshiaki Sendo, Keisuke Ishizawa

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 21 ( 1 ) 54 - 59 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Although the 2016 Japanese guidelines for the management of sepsis recommend de-escalation of treatment after identification of the causative pathogen, adherence to this practice remain unknown. The objective of this study was to evaluate the benefits of de-escalating treatment for sepsis patients at an advanced critical care and emergency medical centre. METHODS: Based on electronic patient information, 85 patients who were transported to the centre by ambulance, and diagnosed with sepsis between January 2008 and September 2013 were enrolled and evaluated. Patients were divided into two groups with and without de-escalation, and comparisons were conducted for several variables, including length of hospital stay, and length of antibiotic administration. Two types of subgroup analysis were conducted between patients with septic shock or positive blood cultures. Statistical analysis was conducted using chi-square and Mann-Whitney U tests. RESULTS: The length of hospital stay after diagnosis was significantly shorter for the de-escalation group than for the non-de-escalation group. In the subgroup analysis, de-escalation for blood culture-positive patients was beneficial in terms of the length of hospital stay and length of antibiotic administration. CONCLUSIONS: The findings of this study suggest that sepsis treatment de-escalation is beneficial for treatment efficacy and appropriate use of antibiotics. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

DOI： 10.29173/jpps29737

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Administration of Kampo medicine through a tube at an advanced critical care center. 査読

Takahiro Niimura, Yoshito Zamami, Toru Imai, Tsuyoshi Ito, Hidenori Sagara, Hichiya Hiroyuki, Satoru Esumi, Kenshi Takechi, Masaki Imanishi, Toshihiro Koyama, Manabu Amano, Naomi Kurata, Yoshihisa Kitamura, Hironori Nakura, Toshiaki Sendo, Keisuke Ishizawa

The journal of medical investigation : JMI 65 ( 1.2 ) 32 - 36 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

n emergency and critical care medical centers, tube administration is employed for patients who have difficulty swallowing oral drugs owing to decreased consciousness or mechanical ventilation. However, tube clogging due to drug injection is a concern. We compared the crushing method with the simple suspension method for the passage of amlodipine, an antihypertensive drug, in combination with rikkunshito, which has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux in emergency and critical care medical centers, to ascertain the effect of Kampo products on the passage of other drugs during tube administration. When the crushing method was employed, poorly water-soluble solid products were formed, while a uniformly dispersed suspension was obtained using the simple suspension method. In addition, the passage rate of amlodipine through the tube was 64% and 93% in the crushing and simple suspension methods, respectively, thereby indicating that the simple suspension method provided more favorable than the crushing method. The results of this study suggested that the passage rate of amlodipine for patients who received Kampo products concurrently was higher when the simple suspension method was used, and an appropriate drug amount might well be able to administered to patients using this method. J. Med. Invest. 65:32-36, February, 2018.

DOI： 10.2152/jmi.65.32

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Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest. 査読国際誌

Takahiro Niimura, Yoshito Zamami, Toshihiro Koyama, Yuki Izawa-Ishizawa, Masashi Miyake, Tadashi Koga, Keisaku Harada, Ayako Ohshima, Toru Imai, Yutaka Kondo, Masaki Imanishi, Kenshi Takechi, Keijo Fukushima, Yuya Horinouchi, Yasumasa Ikeda, Hiromichi Fujino, Koichiro Tsuchiya, Toshiaki Tamaki, Shiro Hinotsu, Mitsunobu R Kano, Keisuke Ishizawa

Scientific reports 7 ( 1 ) 17919 - 17919 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

There are few reports on hydrocortisone administration after cardiac arrest, and those that have been published included few subjects. This study aimed to evaluate the effect of hydrocortisone administration on the outcomes of patients who experienced cardiac arrest. We investigated the survival discharge rates and the length of hospital stay from cardiac arrest to discharge, stratified by use of hydrocortisone, using a Japanese health-insurance claims dataset that covers approximately 2% of the Japanese population. The study included the data of 2233 subjects who experienced either in-hospital or out-of-hospital cardiac arrest between January 2005 and May 2014. These patients were divided into two groups, based on the administration of hydrocortisone. We adjusted the baseline characteristics, medical treatment, and drug administration data of the two groups using propensity scores obtained via the inverse probability of treatment weighted method. The hydrocortisone group had a significantly higher survival discharge rate (13/61 [21.1%] vs. 240/2172 [11.0%], adjusted odds ratio: 4.2, 95% CI: 1.60-10.98, p = 0.004). In addition, the administration of hydrocortisone was independent predictor of survival to discharge (hazard ratio: 4.6, p < 0.001). The results demonstrate a correlation between hydrocortisone administration and the high rates of survival to discharge.

DOI： 10.1038/s41598-017-17686-3

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Patterns of CT use in Japan, 2014: A nationwide cross-sectional study. 査読国際誌

Toshihiro Koyama, Yoshito Zamami, Ayako Ohshima, Yusuke Teratani, Kazuaki Shinomiya, Yoshihisa Kitamura

European journal of radiology 97 96 - 100 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: To describe CT usage in Japan by age, gender, and region and to clarify the relationship between aging and CT examination rate. MATERIALS AND METHODS: We conducted a cross-sectional study using openly accessible data from the National Database, which includes all Japanese health insurance claim data from 2014. These data are anonymized and publicly available as spreadsheets. Therefore, this study did not require institutional review board approval. We calculated the rate of CT examinations per 1000 population by age, sex, and region with 99% confidence intervals. Pearson correlation coefficients were calculated between CT rate and aging in each region. RESULTS: We analyzed 28.1 million CT scans, and the rate per 1000 population was 221.5 (99% CI, 221.4-221.6). By age, the corresponding rate for age 0-9 years was 28.9, that for age 10-9 years was 48.6, that for 20-29 years was 52.2, that for 30-39 years was 69.0, that for 40-49 years was 105.9, that for 50-59 years was 177.6, that for 60-69 years was 303.3, that for 70-79 years was 532.5 and that for ≥80 years was 801.5. The rate for male individuals was 233.6 and that for females was 210.0. The CT examination rate was 171.7 and 296.0 in the lowest- and highest-frequency regions, respectively. The average correlation coefficient between the aging rate in each region and the CT examination rate was 0.58 (0.35-0.74, p=0.00002). CONCLUSION: In Japan, the CT examination rate per 1000 population was high (third highest in the world). Age may be a factor that increases CT use. Furthermore, because variation in CT examination rates by age, gender, and region were observed, it is necessary to standardize CT utilization.

DOI： 10.1016/j.ejrad.2017.10.023

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Meta-analysis of the efficacies of amiodarone and nifekalant in shock-resistant ventricular fibrillation and pulseless ventricular tachycardia. 査読国際誌

Shiho Sato, Yoshito Zamami, Toru Imai, Satoshi Tanaka, Toshihiro Koyama, Takahiro Niimura, Masayuki Chuma, Tadashi Koga, Kenshi Takechi, Yasuko Kurata, Yutaka Kondo, Yuki Izawa-Ishizawa, Toshiaki Sendo, Hironori Nakura, Keisuke Ishizawa

Scientific reports 7 ( 1 ) 12683 - 12683 2017年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Amiodarone (AMD) and nifekalant (NIF) are used in the treatment of ventricular fibrillation or tachycardia; however, only few studies have been conducted on their efficacies. Therefore, a meta-analysis was conducted. Relevant sources were identified from PubMed, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi. The outcomes were short-term and long-term survival in patients with shock-resistant ventricular fibrillation /pulseless ventricular tachycardia. Thirty-three studies were analysed. The results showed that, compared to the control treatment, AMD did not improve short-term survival (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.91-1.71) or long-term survival (OR: 1.00, 95% CI: 0.63-1.57). However, compared to the control treatment, NIF significantly improved short-term survival (OR: 3.23, 95% CI: 2.21-4.72) and long-term survival (OR: 1.88, 95% CI: 1.36-2.59). No significant difference was observed in short-term survival (OR: 0.85, 95% CI: 0.63-1.15) or long-term survival (OR: 1.25, 95% CI: 0.67-2.31) between AMD- and NIF-treated patients. The results suggest that NIF is beneficial for short-term and long-term survival in shock-resistant ventricular fibrillation/pulseless ventricular tachycardia; however, the efficacy of AMD in either outcome is not clear.

DOI： 10.1038/s41598-017-13073-0

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Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice. 査読国際誌

Yasumasa Ikeda, Yuya Horinouchi, Hirofumi Hamano, Tasuku Hirayama, Seiji Kishi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Ken-Ichi Aihara, Hideko Nagasawa, Koichiro Tsuchiya, Toshiaki Tamaki

Scientific reports 7 ( 1 ) 10621 - 10621 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22phox expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury.

DOI： 10.1038/s41598-017-11089-0

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Evaluation of factors associated with the achievement of an optimal teicoplanin trough concentration . 査読国際誌

Kenshi Takechi, Hiroaki Yanagawa, Yoshito Zamami, Keisuke Ishizawa, Akihiro Tanaka, Hiroaki Araki

International journal of clinical pharmacology and therapeutics 55 ( 8 ) 672 - 677 2017年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Because teicoplanin has a long serum half-life, a longer period of time is needed to achieve a steady-state concentration compared with vancomycin. The administration of an initial loading dose has been recommended to reach an effective teicoplanin serum concentration for the treatment of methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA). However, little is known regarding factors that affect teicoplanin concentration. This study aimed to retrospectively determine which factors are associated with achieving an optimal teicoplanin trough level. METHODS: We analyzed patients with MRSA infections who were treated with teicoplanin intravenously between January 2010 and July 2014. The effect of loading dose administration was evaluated in patients treated with 1,200 mg or 1,600 mg of teicoplanin, respectively. RESULTS: Approximately 32% (31/97) of patients achieved the trough concentration target (≥ 15 µg/mL) on the 3^rd or 4^th day. Multivariate analysis showed that loading doses and body surface area (BSA) were associated with trough concentration > 15 µg/mL on the 3^rd or 4^th day. Moreover, patients treated with the 2-day loading dose (1,600 mg group: 800 mg/day on 2 days) promptly achieved a trough concentration > 15 µg/mL on the 3^rd or 4^th day compared with those receiving a 1-day loading dose (1,200 mg group: 800 mg/day on only 1 day). The receiver operating characteristic curve showed that the optimal cut-off point of estimated glomerular filtration rate (eGFR) was 56 mL/min with 1-day loading dose to achieve a trough concentration target > 15 µg/mL. CONCLUSION: These results suggested that patients with decreased renal function (eGFR < 56 mL/min) can safely achieve an optimal trough level with the 1-day loading dose. In patients with normal renal function (eGFR ≥ 56 mL/min), administration of a 2-day loading dose may be needed to rapidly achieve a trough concentration ≥ 15 µg/mL. .

DOI： 10.5414/CP203009

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HSP105 prevents depression-like behavior by increasing hippocampal brain-derived neurotrophic factor levels in mice. 査読国際誌

Naoya Hashikawa, Yuta Utaka, Takumi Ogawa, Ryo Tanoue, Yuna Morita, Sayumi Yamamoto, Satoru Yamaguchi, Masafumi Kayano, Yoshito Zamami, Narumi Hashikawa-Hobara

Science advances 3 ( 5 ) e1603014 - e1603014 2017年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Heat shock proteins (HSPs) are stress-induced chaperones that are involved in neurological disease. Although increasingly implicated in behavioral disorders, the mechanisms of HSP action, and the relevant functional pathways, are still unclear. We examined whether oral administration of geranylgeranylacetone (GGA), a known HSP inducer, produced an antidepressant effect in a social defeat stress model of depression in mice. We also investigated the possible molecular mechanisms involved, particularly focusing on hippocampal neurogenesis and neurotrophic factor expression. In stressed mice, hippocampal HSP105 expression decreased. However, administration of GGA increased HSP105 expression and improved depression-like behavior, induced hippocampal cell proliferation, and elevated brain-derived neurotrophic factor (BDNF) levels in mouse hippocampus. Co-treatment with GGA and the BDNF receptor inhibitor K252a suppressed the antidepressant effects of GGA. HSP105 knockdown decreased BDNF mRNA levels in HT22 hippocampal cell lines and hippocampal tissue and inhibited the GGA-mediated antidepressant effect. These observations suggest that GGA administration is a therapeutic candidate for depressive diseases by increasing hippocampal BDNF levels via HSP105 expression.

DOI： 10.1126/sciadv.1603014

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Effects of endogenous nitric oxide on adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide-containing nerve mediated vasodilation in pithed rats 査読

Kousuke Yamawaki, Yoshito Zamami, Hiromu Kawasaki, Shingo Takatori

EUROPEAN JOURNAL OF PHARMACOLOGY 802 69 - 75 2017年5月

Effect of Nerve Growth Factor on Innervation of Perivascular Nerves in Neovasculatures of Mouse Cornea 査読

Akiko Matsuyama, Shingo Takatori, Yoko Sone, Eiko Ochi, Mitsuhiro Goda, Yoshito Zamami, Narumi Hashikawa-Hobara, Yoshihisa Kitamura, Hiromu Kawasaki

BIOLOGICAL & PHARMACEUTICAL BULLETIN 40 ( 4 ) 396 - 401 2017年4月

電気的除細動抵抗性心室細動/無脈性心室頻拍に対するニフェカラントの有効性評価メタ解析アミオダロンとの効果比較

佐藤志帆, 今井徹, 田中敏, 座間味義人, 名倉弘哲

日本薬学会年会要旨集 137年会 ( 4 ) 75 - 75 2017年3月

Psychiatric Patients with Antipsychotic Drug-Induced Hyperprolactinemia and Menstruation Disorders. 査読

Kenshi Takechi, Yurika Yoshioka, Hitoshi Kawazoe, Mamoru Tanaka, Shingo Takatori, Miwako Kobayashi, Ichiro Matsuoka, Hiroaki Yanagawa, Yoshito Zamami, Masaki Imanishi, Keisuke Ishizawa, Akihiro Tanaka, Hiroaki Araki

Biological & pharmaceutical bulletin 40 ( 10 ) 1775 - 1778 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）

Treatment with antipsychotic drugs has been associated with hyperprolactinemia. The same antipsychotic drugs have also been associated with side effects such as menstruation disorders. The aim of this study was to evaluate the prevalence of hyperprolactinemia and menstruation disorders in women undergoing antipsychotic treatment. We performed a retrospective chart review study of psychiatric patients who underwent laboratory testing for serum prolactin (PRL) level between March 2011 and March 2015 in Ehime University Hospital. Patients presenting with and without menstruation disorders were evaluated to determine if they presented concomitant hyperprolactinemia. Patients with menstrual disorders had a significant increase in serum PRL level with a mean of approximately 90 ng/mL. Those with menstrual disorders presented increased PRL levels by 2-fold that of patients without menstrual disorder. However, there was no significant difference in the equivalent dose of chlorpromazine between these two groups. Additionally, about 70% of patients with menstrual disorders received risperidone treatment. The receiver operating characteristic curve showed that the optimal cutoff point of serum PRL level associated with the development of menstrual disorders was 60 ng/mL. Based on these results, we concluded that patients with menstrual disorders presented increased serum PRL, and that most of them underwent treatment with risperidone.

DOI： 10.1248/bpb.b17-00053

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