Faculty Profiles - UEYAMA, Jun

Papers - UEYAMA, Jun

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Panipenem does not alter the pharmacokinetics of the active metabolite of irinotecan SN-38 and inactive metabolite SN-38 glucuronide (SN-38G) in rats Reviewed

KATO Ayako, UEYAMA Jun, ABE Fumie, HOTTA Kazuo, TSUKIYAMA Ikuo, OSHIMA Taeyuki, KONDO F, SAITO Hiroko, HASEGAWA Takaaki.

Anticancer Res. Vol. 31 ( 9 ) page： 2915-2922 2011.9

Language：English Publishing type：Research paper (scientific journal)

PubMed ID21868538
The present study has investigated the effect of panipenem, a widely used antibiotic, on the pharmacokinetics of an active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide (SN-38G) produced by uridine-diphosphate glucuronosyltransferase (UGT) 1A isoform-mediated glucuronidation in rats. Rats received a 1 h infusion with panipenem at a loading dose of 10 mg/kg and a maintenance dose of 15 mg/min/kg once a day for 5 days. When the effect of pretreatment with panipenem on glucuronidation activities of substrates for hepatic UGT1A isoforms was investigated using substrates 4-methylumbelliferone (4MU), estradiol and SN-38, the rate of 4MU glucuronide formation was significantly increased, but that of estradiol glucuronide formation was unchanged. However, the rate of SN-38G formation showed a tendency to increase. One hour after the final infusion of panipenem or saline, SN-38 (2 mg/kg) was administered intravenously in rats with or without bile duct cannulation. Pretreatment with panipenem had no effect on the plasma concentration-time curves and biliary excretion of SN-38 and SN-38G in rats with and without bile duct cannulation. There were also no significant differences in the relative extent of glucuronidation of SN-38 to SN-38G (AUC(2 h, SN-38G)/AUC(2 h, SN-38)) between panipenem-treated and untreated rats. These findings suggest that pretreatment with panipenem does not alter the pharmacokinetics of SN-38 and SN-38G, suggesting the possibility that panipenem can be used safely for cancer patients undergoing irinotecan chemotherapy.

Study Profile on Baseline Survey of Daiko Study in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) Reviewed

MORITA Emi, HAMAJIMA Nobuyuki, HISHIDA Asahi, AOYAMA Kyoko, OKADA Rieko, KAWAI Sayo, TOMITA Koutaro, KURIKI Sayaka, TAMURA Takashi, NAITO Mariko, KONDO Takaaki, UEYAMA Jun, KIMATA Akiko, YAMAMOTO Kanami, HORI Yoko, HOSHINO Junko, HAMAMOTO Ritsuko, TSUKAMOTO Sanae, ONISHI Johji, HAGIKURA Shoichi, NAITO Hisao, HIBI Satoshi, ITO Yoshinori and WAKAI Kenji

Nagoya Journal of Medical Science Vol. 73 page： 187-195 2011.8

Effect of DDVP on urinary excretion levels of pyrethroid metabolite 3-phenoxybenzoic acid in rats Reviewed

HIROSAWA Naoko, UEYAMA Jun, KONDO Takaaki, KAMIJIMA Michihiro, TAKAGI Kenji, FUJINAKA Sanae, HIRATE Ayaka, HASEGAWA Takaaki, WAKUSAWA Shinya.

Toxicol Lett. Vol. 203 ( 1 ) page： 28-32 2011.4

Language：English Publishing type：Research paper (scientific journal)

PubMed ID:21471973
Pyrethroid insecticide (PYR) is used worldwide in agriculture and for indoor extermination of harmful insects. Urinary PYR metabolites (e.g. 3-phenoxybenzoic acid, 3PBA) have been used as the most sensitive biomarker for environmental PYR exposure since the late 1990's. In this study, we examined the effect of organophosphorus insecticide (OP) dichlorvos (DDVP) on excretion levels of urinary cis-permethrin-derived 3PBA in rats. Concentration of urinary 3PBA and cis-permethrin in plasma were monitored using gas chromatography-mass spectrometry and high-performance liquid chromatography after cis-permethrin injection (20mg/kg) via the tail vein of rats pretreatmented intraperitoneally with DDVP (low dose, 0.3mg/kg; high dose, 1.5mg/kg). The amount of urinary 3PBA excretion over 48h after cis-permethrin administration in control was 21.5±5.1μg (mean±S.D.). In the low- and high-dose DDVP groups, the amounts of urinary 3PBA excretion were decreased to 81.1% (17.4±2.7μg) and 70.3% (15.1±2.6μg) of control, respectively. The plasma concentrations of cis-permethrin-derived 3-phenoxybenzyl alcohol (3PBAlc), which is a metabolite derived following hydrolysis of cis-permethrin, in high-dose DDVP group (0.18±0.01μg) were significantly lower than in control (0.23±0.03μg) 1h after cis-permethrin injection. Both in the control and high-dose DDVP group, no differences were observed in the excretion levels of urinary 3PBA after injection of 3PBAlc (25mg/kg, i.v). These results suggested that the effect of DDVP on the amount of urinary 3PBA excretion was caused by the DDVP-induced modification of the cis-permethrin metabolic pathway. In conclusion, the possible decrease in urinary excretion level of 3PBA due to co-exposure to OPs should be considered in the biological monitoring of PYR exposure.

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension. Reviewed

YAMADA Yuichiro, TSUBOI Koji, HATTORI Takuya, MURATE Takashi, OHTAKE Masafumi, FRUKAWA Mayuko, UEYAMA Jun, NISHIYAMA Akira, MUROHARA Toyoaki, NAGATA Kohzo.

Hypertens Res Vol. 34 ( 7 ) page： 809-816 2011.4

Language：English Publishing type：Research paper (scientific journal)

PubMed ID21471973
Although thiazide diuretics are commonly used to supplement angiotensin receptor blockers for treatment of hypertension, the mechanism underlying the therapeutic effects of this drug combination remains unclear. We investigated the antihypertensive and cardioprotective effects of combination therapy with losartan (LOS) and hydrochlorothiazide (HCTZ), in comparison with those of either drug alone, in Dahl salt-sensitive hypertensive rats. Rats fed a high-salt diet from 6 weeks of age were treated with LOS, HCTZ, both drugs (COMB) and vehicle from 6 to 11 weeks. The salt-induced increase in systolic blood pressure was attenuated moderately by LOS and to a greater extent by HCTZ and COMB. Left ventricular (LV) hypertrophy and fibrosis, diastolic dysfunction, as well as angiotensin-converting enzyme and angiotensin II type 1A (AT(1A)) receptor gene expression were attenuated similarly by LOS and HCTZ and more so by COMB. LOS downregulated expression of the AT(1A) receptor gene, without affecting that of the AT(2) receptor gene, in the aorta. In contrast, neither HCTZ nor COMB affected aortic expression of the AT(1A) receptor gene, but both markedly upregulated that of the AT(2) receptor gene. The salt-induced decrease in the plasma concentration of nitric oxide metabolites was attenuated substantially by LOS and abolished by both HCTZ and COMB. In conclusion, the combination of LOS and HCTZ attenuated hypertension, as well as LV remodeling and diastolic dysfunction, more effectively than did LOS or HCTZ alone in rats with salt-sensitive hypertension. Modulation of the cardiac and vascular renin-angiotensin system may have contributed to these beneficial effects of the drug combination.

Association of UGT1A1 Gly71Arg with urine urobilinogen Reviewed

KATAOKA Ryuji, KIMATA Akiko, YAMAMOTO Kanami, HIROSAWA Naoko, UEYAMA Jun, KONDO Takaaki, OKADA Rieko, KAWAI Sayo, HISHIDA Asahi, NAITO Mariko, MORITA Emi, WAKITA Kenji, HAMAJIMA Nobuyuki

Nagoya Journal of Medical Science Vol. 73 ( 1-2 ) page： 33-40 2011.4

Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (MRP2) in sex-related differences in the pharmacokinetics of garenoxacin in rats Reviewed

HAYASHI Tamon, ABE Fumie, KATO Miki, SAITO Hiroko, UEYAMA Jun, KONDO Yuya, IMAI Kuniyuki, KATOH Miki, NADAI Masayuki, HASEGAWA Takaaki

J Infect Chemother Vol. 17 ( 1 ) page： 24-29 2011.2

Beta-glucuronidase activity is a more sensitive biomarker than cholinesterase inhibition for organophosphorus insecticide exposure Reviewed

UEYAMA Jun, SATOH Tetsuo, KONDO Takaaki, TAKAGI Kenji, SHIBATA Eiji, GOTO Masahiro, KIMATA Akiko, SAITO Isao, HASEGAWA Takaaki, WAKUSAWA Shinya, KAMIJIMA Michihiro.

Toxicol Lett Vol. 193 ( 1 ) page： 115-119 2010.12

Endotoxin does not alter the pharmacokinetics of micafungin,but it impairs biliary excretion of micafungin via multidrugresistance-associated protein 2 (ABCC2/Mrp2) in rats Reviewed

NODA Takayuki, ABE Fumie, UEYAMA Jun, KATO Miki, KATOH Miki, NADAI Masayuki, SAITO Hiroko, HASEGAWA Takaaki

J Infect Chemother 2010.9

Language：English Publishing type：Research paper (scientific journal)

PubMed ID:20835743
Micafungin, a newly developed echinocandin-type antifungal agent, is widely used for the treatment of deep-seated fungal infections including those of Candida species and Aspergillus species. In the present study, the possible alterations in the pharmacokinetics and biliary excretion of micafungin were investigated in endotoxemic rats induced by Klebsiella pneumoniae endotoxin. Endotoxin (2 mg/kg) was injected intraperitoneally 24 h before an intravenous injection of micafungin (1 mg/kg). No significant differences in the plasma concentration-time curves and pharmacokinetic parameters of micafungin were observed between endotoxin-treated and endotoxin-untreated rats. When endotoxin-treated rats received a constant-rate infusion of micafungin, the biliary clearance of micafungin was significantly decreased, whereas the steady-state plasma concentration did not change. By protein immunoblot analysis, a significant decrease in the expression of hepatic multidrug resistance-associated protein 2 (ABCC2/Mrp2), which is an efflux protein for micafungin, was observed in endotoxin-treated rats. These results suggest that endotoxin-induced decrease in the hepatobiliary excretion of micafungin is caused, at least in part, by the reduction of Mrp2-mediated hepatobiliary transport ability. The present study may provide information suggesting that micafungin can be used for patients with endotoxemia without the need for dosage adjustment.

DOI： 10.1007/s10156-010-0118-9

Preliminary study on spontaneous hepatitis in long-evans cinnamon rats: a blood echange may improve the fetal hepatitis Reviewed

UEYAMA Jun, WAKUSAWA Shinya, TATSUMI Yasuyuki, HATTOEI Ai, YANO Motoyoshi, HAYASHI Hisao

Nagoya J Med Sci Vol. 72 ( 3-4 ) page： 173-177 2010.8

Toxicokinetics of pyrethroid metabolites in male and female rats Reviewed

UEYAMA Jun, HIROSAWA Naoko, MOCHIZUKI Aiko, KIMATA Akiko, KAMIJIMA Michihiro, KONDO Takaaki, TAKAGI Kenji, WAKUSAWA Shinya, HASEGAWA Takaaki

Environmental Toxicology and Pharmacology Vol. 30 ( 1 ) page： 88-91 2010.7

Revised method for routine determination of urinary dialkyl phosphates using gas chromatography-mass spectrometry Invited Reviewed

UEYAMA Jun, KAMIJIMA Michihiro, KONDO Takaaki, TAKAGI Kenji, SHIBATA Eiji, HASEGAWA Takaaki, WAKUSAWA Shinya, TAKI Tomoko, GOTO Masahiro, SAITO Isao

J Chromatogra B Vol. 878 ( 17-18 ) page： 1257-1263 2010.5

Analysis and evaluation of pyrethroid exposure in human population based on biological monitoring of urinary pyrethroid metabolites Reviewed

UEYAMA Jun, SAITO Isao, KAMIJIMA Michihiro

Journal of Pesticide Science Vol. 35 ( 2 ) page： 87-98 2010.4

健常成人における成熟にんにくの血管内皮機能へ及ぼす影響 Reviewed

宮田聖子、野田明子、永井万由佳、大嶽正文、上山純、古池保雄

日本臨床生理学会雑誌 Vol. 40 ( 2 ) page： 103-108 2010.4

Measurement of forearm blood flow of healthy young men and women using strain-gauge plethysmography Reviewed

KONDO Takaaki, YAMADA Chie, FURUTA Takako, YOSHITAKE Junko, SHIROTORI AYA, OKADA Yoshiko, KIMATA Akiko, YAMAMOTO Kanami, UEYAMA Jun, SAKAKIBARA Hisataka, FUKAYA Yukio

Bull Aichi Bunkyo Women's Coll Vol. 31 page： 27-34 2010.3

Comparison of urinary concentrations of 3-phenoxybenzoic acid among general residents in rural and suburban areas and employees of pest control firms Reviewed

KIMATA Akiko, KONDO Takaaki, UEYAMA Jun, YAMAMOTO K, YOSHITAKE Junko, TAKAGI Kenji, SUZUKI Koji, INOUE Takashi, ITO Yoshinori, HAMAJIMA Nobuyuki, KAMIJIMA Michihiro, GOTOH Masahiro, SHIBATA Eiji.

Int Arch Occup Environ Health Vol. 82 ( 10 ) page： 1173-1178 2009.11

Broken sperm, cytoplasmic droplets and reduced sperm motility are principal markers of decreased sperm quality due to organophosphorus pesticides in rats Reviewed

OKAMURA Ai, KAMIJIMA Michihiro, OHTANI Katsumi, YAMANOSHITA Osamu, NAKAMURA Daichi, ITO Yuki, MIYATA Maiko, UEYAMA Jun, SUZUKI Takayoshi, IMAI Ryota, TAKAGI Kenji, NAKAJIMA Tamie.

J Occup Health Vol. 51 ( 6 ) page： 478-487 2009.9

Relationship between dietary habits and urinary concentrations of 3-phenoxybonzoic acid in a middle-aged and elderly general population in Japan Reviewed

KIMATA Akiko, KONDO Takaaki, UEYAMA Jun, YAMAMOTO Kanami, KAMIJIMA Michihiro, SUZUKI Koji INOUE Takashi, ITO Yoshinori, HAMAJIMA Nobuyuki.

Environ Health Prev Med Vol. 14 ( 3 ) page： 173-179 2009.5

Possible involvement of interleukin-6 (IL-6) in down-regulation of hepatic breast cancer resistance protein (Bcrp/ABCG2) in endotoxemic mice Reviewed

ZHAO Ying Lan, CEN X, ABE Fumie, UEYAMA Jun, HOTTA K, KATO S, ITO S, SAGA S, FUKAYA Yukio, WANG L, WEI Y, HASEGAWA Takaaki

Bull Aichi Bunkyo Women's Coll Vol. 30 page： 27-42 2009.3

Multilevel analyses of effects of variation in body mass index on serum lipid concentrations in middle-aged Japanese men Reviewed

KONDO Takaaki, KIMATA Akiko, YAMAMOTO Kanami, UEYAMA Sayoko, UEYAMA Jun, Yatsuya H, TAMAKOSHI K, HORI Yoko

Nagoya J Med Sci. Vol. 71 ( 1-2 ) page： 19-28 2009.2

Urinary excretion of 3-phenoxybenzoic acid in middle-aged and elderly general population of Japan Reviewed

UEYAMA Jun, KIMATA Akiko, KAMIJIMA Michihiro, HAMAJIMA Nobuyuki, ITO Yuki, SUZUKI Koji, INOUE Takashi, YAMAMOTO Kanami, TAKAGI Kenji, SAITO Isao, MIYAMOTO K, HASEGAWA Takaaki, KONDO Takaaki

Environ Res Vol. 109 ( 2 ) page： 175-180 2009.2

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Limited data are available on the background levels of exposure to synthetic pyrethroid (PYR) in Japan, despite their frequent application for agriculture and indoor extermination and possible effects of chronic and/or low-dose PYR exposure on human health. This study was conducted to describe the level and distribution of one of the major PYR metabolites, 3-phenoxybenzoic acid (3-PBA), in urine samples collected from a general population in Japan. The subjects were 535 individuals (184 men and 351 women; 61.5+/-9.8 years of age, mean+/-S.D.) residing in a town in Hokkaido, a dairy and agricultural area. Urinary 3-PBA was found detectable in 98% of samples above the limit of detection of 0.02 microg/l. The geometric mean values of urinary 3-PBA in occupationally exposed farmers (n=87) and the remaining general group without occupational exposure (n=448) were 0.38 and 0.29 microg/l, respectively, ranging from <LOD to 17.09 microg/l. No significant differences in urinary 3-PBA concentrations were shown between these two groups. Moreover, 3-PBA concentrations were found comparable to those reported in some countries. The present study is, to our knowledge, the first report of a biological monitoring study of urinary 3-PBA, which elucidated the background environmental exposure level of PYR in the Japanese general population without occupational exposure. Further nationwide studies covering different seasons and age distribution are needed to monitor the urinary 3-PBA levels in Japan.

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Papers - UEYAMA, Jun